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JPH11106371A - Acylhydrazone derivative - Google Patents

Acylhydrazone derivative

Info

Publication number
JPH11106371A
JPH11106371A JP10177222A JP17722298A JPH11106371A JP H11106371 A JPH11106371 A JP H11106371A JP 10177222 A JP10177222 A JP 10177222A JP 17722298 A JP17722298 A JP 17722298A JP H11106371 A JPH11106371 A JP H11106371A
Authority
JP
Japan
Prior art keywords
group
hydroxy
following formula
butyl
pmr
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
JP10177222A
Other languages
Japanese (ja)
Inventor
Hitoshi Inoue
仁志 井上
Masato Horigome
正人 堀米
Nobusuke Kinoshita
宣祐 木下
Rie Shibayama
利恵 柴山
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nisshin Seifun Group Inc
Original Assignee
Nisshin Seifun Group Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nisshin Seifun Group Inc filed Critical Nisshin Seifun Group Inc
Priority to JP10177222A priority Critical patent/JPH11106371A/en
Publication of JPH11106371A publication Critical patent/JPH11106371A/en
Withdrawn legal-status Critical Current

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  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Furan Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Quinoline Compounds (AREA)
  • Pyrane Compounds (AREA)

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new compound useful as a Maillard reaction inhibitor, an active oxygen-resistant medicine, a medicine for various kinds of diabetic complications, a medicine for senile diseases and the like. SOLUTION: A compound of the formula: X-W-Y X is a group of formula I [R<1> and R<2> are each a 1-4C alkyl; R<3> is H or a 1-4C alkyl; (n<1> ) is 0-2] or the like; Y is furyl, thienyl, pyrrolyl or the like; W is formula II (R<25> and R<26> are each H or a 1-4C alkyl; Z<1> is O or S) or the like}, e.g. benzaldehyde-3,5-di-t- butyl-4-hydroxybenzoyl hydrazone. The compound of the formula is obtained e.g. by reacting 3,5-ti-t-butyl-4-hydroxybenzhydrazide with benzaldehyde in ethanol at room temperature for 24 hr with agitation, distilling off the solvent, adding isopropyl ether, depositing the crystals, and subsequently filtering off the crystals, while using a column chromatography using silica gel or the like as a carrier, methanol and the like complication.

Description

【発明の詳細な説明】DETAILED DESCRIPTION OF THE INVENTION

【0001】[0001]

【発明の属する技術分野】本発明は、アシルヒドラゾン
誘導体及びその類縁体並びに医薬組成物、特にメイラー
ド反応阻害薬及び抗活性酸素薬(過酸化脂質生成抑制
薬)に関するものである。
TECHNICAL FIELD The present invention relates to an acylhydrazone derivative and an analog thereof, and a pharmaceutical composition, particularly to a Maillard reaction inhibitor and an antireactive oxygen agent (lipid peroxide production inhibitor).

【0002】[0002]

【従来の技術】近年、糖尿病合併症の発症要因の一つと
してグルコースによる蛋白質の変性が大きくクローズア
ップされている。これは、生体内で生じるメイラード反
応に起因するものと考えられている。メイラード反応
は、その初期段階として蛋白質のアミノ基がグルコース
で非酵素的に糖化(グリケーション)され、アマドリ(A
madori) 化合物が形成される。更にアマドリ化合物は他
の蛋白質と反応して架橋を形成して、不溶性でプロテア
ーゼによる分解が困難な、蛍光を発する褐変物質である
後期段階生成物(AGE: Advanced Glycation End produc
ts)に至る(Science,232, 1629(1986))。メイラード
反応は、健常者においてもみられる現象であるが、特に
糖尿病患者において顕著におこる現象であり、例えばヘ
モグロビン、血清アルブミン、また、代謝速度が遅いか
あるいは代謝されない蛋白質、結合組織のコラーゲンや
エラスチン、ミエリン、眼球レンズクリスタリン等の蛋
白質の変性をもたらす。この蛋白質の変性により、器官
の機能低下や異常をもたらし、網膜症、腎症、心臓血管
系障害、神経障害や白内障等の糖尿病の合併症を引き起
こす原因の一つとなっていると考えられている。また、
生体内メイラード反応は、老化の機序の一つと考えられ
ており、加齢による疾患とも密接に関連するものと推測
されている。従って、メイラード反応を阻害すること
は、糖尿病の各種合併症や老人性疾患等の疾患の治療に
極めて有用であると考えられている。また、最近の研究
では、メイラード反応にフリーラジカルが関与している
可能性があるということが報告されている(J. Biol. Ch
em.,262(35), 16969-16972 (1987))。
2. Description of the Related Art In recent years, denaturation of proteins due to glucose has been greatly highlighted as one of the causes of diabetic complications. This is thought to be due to the Maillard reaction occurring in vivo. In the Maillard reaction, the amino acid of a protein is non-enzymatically saccharified (glycated) with glucose as an initial step, and Amadori (A
madori) The compound is formed. In addition, Amadori compounds react with other proteins to form crosslinks, and are late-stage products (AGE: Advanced Glycation End produc), which are insoluble, difficult to decompose by proteases, and are fluorescent browning substances.
ts) (Science, 232 , 1629 (1986)). The Maillard reaction is a phenomenon that is also observed in healthy subjects, but is a phenomenon that occurs particularly in diabetic patients, for example, hemoglobin, serum albumin, or a protein that is slow or not metabolized, collagen or elastin in connective tissue, It causes denaturation of proteins such as myelin and ocular lens crystallin. This protein alteration is thought to be one of the causes of diabetic complications such as retinopathy, nephropathy, cardiovascular disorders, neuropathy and cataracts, resulting in functional and abnormal organs. . Also,
The in vivo Maillard reaction is considered to be one of the mechanisms of aging, and is presumed to be closely related to aging-related diseases. Therefore, inhibiting the Maillard reaction is considered to be extremely useful for treating various complications of diabetes and senile diseases. Recent studies have also reported that free radicals may be involved in the Maillard reaction (J. Biol. Ch.
em., 262 (35), 16969-16972 (1987)).

【0003】以上のような背景のもとに、最近メイラー
ド反応を阻害する物質の検索が行われている。従来、メ
イラード反応阻害活性を有する化合物としては、種々の
ものが報告されている。例えば、特開昭62−1421
14号公報では、アマドリ転位生成物中の活性カルボニ
ル基と反応しうる活性窒素含有基(ヒドラジン基)を有
する化合物からなる二次グリコシル化最終生成物の生成
を抑制する組成物が示唆されており、当該化合物として
アミノグアニジン、α−ヒドラジノヒスチジン及びリジ
ンが開示されている。
[0003] Against this background, substances that inhibit the Maillard reaction have recently been searched for. Conventionally, various compounds have been reported as compounds having Maillard reaction inhibitory activity. For example, Japanese Unexamined Patent Publication No. 62-1421
Japanese Patent No. 14 suggests a composition for suppressing the production of a secondary glycosylation end product comprising a compound having an active nitrogen-containing group (hydrazine group) capable of reacting with an active carbonyl group in an Amadori rearrangement product. As such compounds, aminoguanidine, α-hydrazinohistidine and lysine are disclosed.

【0004】一方、アシルヒドラゾン誘導体及びその類
縁体としては、次式(Ia):
On the other hand, acyl hydrazone derivatives and their analogs are represented by the following formula (Ia):

【0005】[0005]

【化31】 Phe−CO−NH−N=CH−Phe−OH−2 (Ia) (式中、Pheはフェニル基を表し、Phe−OH−2
は2−ヒドロキシフェニル基を表す。)で示されるアシ
ルヒドラゾン誘導体が抗結核剤イソニコチン酸ヒドラジ
ドの関連化合物として記載され(薬学雑誌,87
(1),27−32(1967))、次式(Ib):
Embedded image Phe—CO—NH—N = CH—Phe—OH-2 (Ia) (wherein Phe represents a phenyl group, and Phe—OH-2
Represents a 2-hydroxyphenyl group. Reeds shown with)
Luhydrazone derivative is an antituberculous agent hydrazi isonicotinic acid
Is described as a related compound of87
(1), 27-32 (1967)), and the following formula (Ib):

【0006】[0006]

【化32】 Ar1 −CO−NH−NH−CO−Ar2 (Ib) (式中、Ar1 は3,5−ジ−t−ブチル−4−ヒドロ
キシフェニル基を表し、Ar2 はフェニル基又は2−ヒ
ドロキシフェニル基を表す。)で示されるアシルヒドラ
ジン誘導体が有機材料の安定化剤として有用であること
が報告されている(米国特許第3,773,830号明
細書、特開昭49−35281号公報、特開昭51−1
4885号公報)。しかしながら、前記の化合物がメイ
ラード反応阻害活性又は抗活性酸素活性を有するとの報
告はない。
Embedded image Ar 1 —CO—NH—NH—CO—Ar 2 (Ib) (wherein, Ar 1 represents a 3,5-di-t-butyl-4-hydroxyphenyl group, and Ar 2 represents a phenyl group Or a 2-hydroxyphenyl group) has been reported to be useful as a stabilizer for organic materials (U.S. Pat. No. 3,773,830; -35281, JP-A-51-1
No. 4885). However, there is no report that the compound has Maillard reaction inhibitory activity or anti-reactive oxygen activity.

【0007】[0007]

【発明が解決しようとする課題】本発明は、新規なアシ
ルヒドラゾン誘導体及びその類縁体、並びに公知又は新
規なアシルヒドラゾン誘導体又はその類縁体を有効成分
とする医薬組成物、特にメイラード反応阻害薬及び抗活
性酸素薬を提供することを目的とする。
DISCLOSURE OF THE INVENTION The present invention relates to a novel acylhydrazone derivative and an analog thereof, and a pharmaceutical composition containing a known or novel acylhydrazone derivative or an analog thereof as an active ingredient, particularly a Maillard reaction inhibitor and It is intended to provide an antireactive oxygen drug.

【0008】[0008]

【課題を解決するための手段】本発明は、以下の発明を
包含する。 (1)次式(I): X−W−Y [式中、Xは、次式(A):
The present invention includes the following inventions. (1) The following formula (I): X-W-Y [where X is the following formula (A):

【0009】[0009]

【化33】 Embedded image

【0010】(式中、R1 及びR2 は、同一又は異なっ
て、C1-4 −アルキル基を表し、Rは水素原子又はC
1−4 −アルキル基を表し、n1 は0〜2を表す。)
で示される基、次式(B):
(Wherein R 1 and R 2 are the same or different and each represents a C 1-4 -alkyl group, and R 3 is a hydrogen atom or a C
Represents an 1-4 -alkyl group, and n 1 represents 0 to 2. )
A group represented by the following formula (B):

【0011】[0011]

【化34】 Embedded image

【0012】(式中、R4 及びR5 は、同一又は異なっ
て、C1-4 −アルキル基を表し、R6は水素原子又はC
1-4 −アルキル基を表す。)で示される基、次式
(C):
(Wherein R 4 and R 5 are the same or different and each represents a C 1-4 -alkyl group, and R 6 is a hydrogen atom or C
1-4 represents an alkyl group. A group represented by the following formula (C):

【0013】[0013]

【化35】 Embedded image

【0014】(式中、R7 、R8 、R9 、及びR10は、
同一又は異なって、C1-4 −アルキル基を表し、R11
水素原子又はC1-4 −アルキル基を表し、n2 は0〜3
を表す。)で示される基、又は次式(D):
(Wherein R 7 , R 8 , R 9 and R 10 are
Identical or different, represents a C 1-4 -alkyl group, R 11 represents a hydrogen atom or a C 1-4 -alkyl group, and n 2 represents 0 to 3
Represents Or a group represented by the following formula (D):

【0015】[0015]

【化36】 Embedded image

【0016】(式中、R27はC1-4 −アルキル基を表
し、R28は水素原子、ハロゲン原子、水酸基又はC1-4
−アルコキシ基を表す。)で示される基を表し;Yは、
フリル基、チエニル基、ピロリル基、ピリジル基、2−
ヒドロキシ−6−メチルピリジン−3−イル基、C1-4
−アルキル基、次式(E):
(Wherein R 27 represents a C 1-4 -alkyl group, and R 28 represents a hydrogen atom, a halogen atom, a hydroxyl group or a C 1-4
-Represents an alkoxy group. ) Represents a group represented by;
Furyl, thienyl, pyrrolyl, pyridyl, 2-
Hydroxy-6-methylpyridin-3-yl group, C 1-4
An alkyl group of the following formula (E):

【0017】[0017]

【化37】 Embedded image

【0018】(式中、R12、R13、R14、R15及びR16
は、同一又は異なって、水素原子、ハロゲン原子、水酸
基、C1-4 −アルコキシ基、C1-4 −アルキル−カルボ
ニルオキシ基、ニトロ基、シアノ基、フェニル基、モル
ホリノ基、ピロリジノ基、ピペリジノ基、ピペラジノ基
もしくはアミノ基(当該ピペラジノ基又はアミノ基中の
窒素原子はC1-4 −アルキル基、C5-8 −シクロアルキ
ル基及びC1-4 −アルコキシ−カルボニルメチル基から
選ばれる1又は2個の基で置換されていてもよい。)又
は含窒素複素環置換−メチル基を表し、また、R12とR
13、又はR15とR16は共同して縮合6員環を形成しても
よい。)で示される基、次式(F):
(Wherein R 12 , R 13 , R 14 , R 15 and R 16
Are the same or different and are a hydrogen atom, a halogen atom, a hydroxyl group, a C 1-4 -alkoxy group, a C 1-4 -alkyl-carbonyloxy group, a nitro group, a cyano group, a phenyl group, a morpholino group, a pyrrolidino group, a piperidino group Group, piperazino group or amino group (the nitrogen atom in the piperazino group or amino group is selected from C 1-4 -alkyl, C 5-8 -cycloalkyl and C 1-4 -alkoxy-carbonylmethyl) or two groups may be substituted) or a nitrogen-containing heterocyclic ring-substituted -. represents a methyl group, also, R 12 and R
13 or R 15 and R 16 may together form a fused 6-membered ring. A group represented by the following formula (F):

【0019】[0019]

【化38】 Embedded image

【0020】(式中、R17、R18及びR19は、同一又は
異なって、水素原子又はC1-4 −アルキル基を表す。)
で示される基、次式(G):
(Wherein, R 17 , R 18 and R 19 are the same or different and each represent a hydrogen atom or a C 1-4 -alkyl group)
A group represented by the following formula (G):

【0021】[0021]

【化39】 Embedded image

【0022】(式中、R20及びR21は、同一又は異なっ
て、水素原子又はC1-4 −アルキル基を表す。)で示さ
れる基、又は次式(H):
Wherein R 20 and R 21 are the same or different and each represent a hydrogen atom or a C 1-4 -alkyl group, or the following formula (H):

【0023】[0023]

【化40】 Embedded image

【0024】(式中、R22、R23及びR24は、同一又は
異なって、水素原子又はC1-4 −アルキル基を表す。)
で示される基を表し;Wは、次式(J):
Wherein R 22 , R 23 and R 24 are the same or different and each represents a hydrogen atom or a C 1-4 -alkyl group.
W represents the following formula (J):

【0025】[0025]

【化41】 Embedded image

【0026】(式中、R25及びR26は、同一又は異なっ
て、水素原子又はC1-4 −アルキル基を表し、また、R
26は、前記式(E)中のR16と共同してトリメチレン基
を形成してもよく、Z1 は酸素原子又は硫黄原子を表
す。)で示される基、次式(K):
(Wherein R 25 and R 26 are the same or different and each represent a hydrogen atom or a C 1-4 -alkyl group;
26 may form a trimethylene group in cooperation with R 16 in the formula (E), and Z 1 represents an oxygen atom or a sulfur atom. A group represented by the following formula (K):

【0027】[0027]

【化42】 Embedded image

【0028】(式中、Z2 は酸素原子又は硫黄原子を表
す。)で示される基、次式(L):
(Wherein Z 2 represents an oxygen atom or a sulfur atom), a group represented by the following formula (L):

【0029】[0029]

【化43】 Embedded image

【0030】(式中、Z3 及びZ4 は、同一又は異なっ
て、酸素原子又は硫黄原子を表す。)で示される基、次
式(M):
Wherein Z 3 and Z 4 are the same or different and each represent an oxygen atom or a sulfur atom, and a group represented by the following formula (M):

【0031】[0031]

【化44】 Embedded image

【0032】(式中、Z5 は酸素原子又は硫黄原子を表
す。)で示される基、次式(N):
(Wherein Z 5 represents an oxygen atom or a sulfur atom), a group represented by the following formula (N):

【0033】[0033]

【化45】 Embedded image

【0034】(式中、Z6 及びZ7 は、同一又は異なっ
て、酸素原子又は硫黄原子を表す。)で示される基、次
式(O):
Wherein Z 6 and Z 7 are the same or different and each represent an oxygen atom or a sulfur atom, and a group represented by the following formula (O):

【0035】[0035]

【化46】 Embedded image

【0036】(式中、Z8 及びZ9 は、同一又は異なっ
て、酸素原子又は硫黄原子を表す。)で示される基、次
式(P): −CH=N−N=CH− (P) で示される基、又は次式(Q):
Wherein Z 8 and Z 9 are the same or different and each represent an oxygen atom or a sulfur atom, and a group represented by the following formula (P): -CH = NN-CH = (P Or a group represented by the following formula (Q):

【0037】[0037]

【化47】 Embedded image

【0038】(式中、Z10は酸素原子又は硫黄原子を表
す。)で示される基を表す。]で示される化合物又はそ
の薬学的に許容される塩を有効成分として含有する医薬
組成物。
(Wherein, Z 10 represents an oxygen atom or a sulfur atom). Or a pharmaceutically acceptable salt thereof as an active ingredient.

【0039】(2)メイラード反応阻害薬である前記
(1)に記載の医薬組成物。 (3)抗活性酸素薬である前記(1)に記載の医薬組成
物。 (4)次式(I’): X−W−Y [式中、Xは、次式(A):
(2) The pharmaceutical composition according to the above (1), which is a Maillard reaction inhibitor. (3) The pharmaceutical composition according to the above (1), which is an antireactive oxygen drug. (4) The following formula (I ′): X—W—Y wherein X is the following formula (A):

【0040】[0040]

【化48】 Embedded image

【0041】(式中、R1 及びR2 は、同一又は異なっ
て、C1-4 −アルキル基を表し、R3は水素原子又はC
1-4 −アルキル基を表し、n1 は0〜2を表す。)で示
される基、次式(B):
(Wherein R 1 and R 2 are the same or different and each represents a C 1-4 -alkyl group, and R 3 is a hydrogen atom or a C
Represents an 1-4 -alkyl group, and n 1 represents 0 to 2. A group represented by the following formula (B):

【0042】[0042]

【化49】 Embedded image

【0043】(式中、R4 及びR5 は、同一又は異なっ
て、C1-4 −アルキル基を表し、R6は水素原子又はC
1-4 −アルキル基を表す。)で示される基、次式
(C):
(Wherein R 4 and R 5 are the same or different and each represents a C 1-4 -alkyl group, and R 6 is a hydrogen atom or a C
1-4 represents an alkyl group. A group represented by the following formula (C):

【0044】[0044]

【化50】 Embedded image

【0045】(式中、R7 、R8 、R9 、及びR10は、
同一又は異なって、C1-4 −アルキル基を表し、R11
水素原子又はC1-4 −アルキル基を表し、n2 は0〜3
を表す。)で示される基、又は次式(D):
(Wherein R 7 , R 8 , R 9 , and R 10 are
Identical or different, represents a C 1-4 -alkyl group, R 11 represents a hydrogen atom or a C 1-4 -alkyl group, and n 2 represents 0 to 3
Represents Or a group represented by the following formula (D):

【0046】[0046]

【化51】 Embedded image

【0047】(式中、R27はC1-4 −アルキル基を表
し、R28は水素原子、ハロゲン原子、水酸基又はC1-4
−アルコキシ基を表す。)で示される基を表し;Yは、
フリル基、チエニル基、ピロリル基、ピリジル基、2−
ヒドロキシ−6−メチルピリジン−3−イル基、C1-4
−アルキル基、次式(E):
(Wherein R 27 represents a C 1-4 -alkyl group, and R 28 represents a hydrogen atom, a halogen atom, a hydroxyl group or a C 1-4
-Represents an alkoxy group. ) Represents a group represented by;
Furyl, thienyl, pyrrolyl, pyridyl, 2-
Hydroxy-6-methylpyridin-3-yl group, C 1-4
An alkyl group of the following formula (E):

【0048】[0048]

【化52】 Embedded image

【0049】(式中、R12、R13、R14、R15及びR16
は、同一又は異なって、水素原子、ハロゲン原子、水酸
基、C1-4 −アルコキシ基、C1-4 −アルキル−カルボ
ニルオキシ基、ニトロ基、シアノ基、フェニル基、モル
ホリノ基、ピロリジノ基、ピペリジノ基、ピペラジノ基
もしくはアミノ基(当該ピペラジノ基又はアミノ基中の
窒素原子はC1-4 −アルキル基、C5-8 −シクロアルキ
ル基及びC1-4 −アルコキシ−カルボニルメチル基から
選ばれる1又は2個の基で置換されていてもよい。)又
は含窒素複素環置換−メチル基を表し、また、R12とR
13、又はR15とR16は共同して縮合6員環を形成しても
よい。)で示される基、次式(F):
Wherein R 12 , R 13 , R 14 , R 15 and R 16
Are the same or different and are a hydrogen atom, a halogen atom, a hydroxyl group, a C 1-4 -alkoxy group, a C 1-4 -alkyl-carbonyloxy group, a nitro group, a cyano group, a phenyl group, a morpholino group, a pyrrolidino group, a piperidino group Group, piperazino group or amino group (the nitrogen atom in the piperazino group or amino group is selected from C 1-4 -alkyl, C 5-8 -cycloalkyl and C 1-4 -alkoxy-carbonylmethyl) or two groups may be substituted) or a nitrogen-containing heterocyclic ring-substituted -. represents a methyl group, also, R 12 and R
13 or R 15 and R 16 may together form a fused 6-membered ring. A group represented by the following formula (F):

【0050】[0050]

【化53】 Embedded image

【0051】(式中、R17、R18及びR19は、同一又は
異なって、水素原子又はC1-4 −アルキル基を表す。)
で示される基、次式(G):
(Wherein, R 17 , R 18 and R 19 are the same or different and each represent a hydrogen atom or a C 1-4 -alkyl group)
A group represented by the following formula (G):

【0052】[0052]

【化54】 Embedded image

【0053】(式中、R20及びR21は、同一又は異なっ
て、水素原子又はC1-4 −アルキル基を表す。)で示さ
れる基、又は次式(H):
Wherein R 20 and R 21 are the same or different and each represent a hydrogen atom or a C 1-4 -alkyl group, or the following formula (H):

【0054】[0054]

【化55】 Embedded image

【0055】(式中、R22、R23及びR24は、同一又は
異なって、水素原子又はC1-4 −アルキル基を表す。)
で示される基を表し;Wは、次式(J):
(Wherein, R 22 , R 23 and R 24 are the same or different and each represent a hydrogen atom or a C 1-4 -alkyl group).
W represents the following formula (J):

【0056】[0056]

【化56】 Embedded image

【0057】(式中、R25及びR26は、同一又は異なっ
て、水素原子又はC1-4 −アルキル基を表し、Z1 は酸
素原子又は硫黄原子を表す。)で示される基、次式
(K):
Wherein R 25 and R 26 are the same or different and each represent a hydrogen atom or a C 1-4 -alkyl group, and Z 1 represents an oxygen atom or a sulfur atom. Equation (K):

【0058】[0058]

【化57】 Embedded image

【0059】(式中、Z2 は酸素原子又は硫黄原子を表
す。)で示される基、次式(L):
(Wherein Z 2 represents an oxygen atom or a sulfur atom), a group represented by the following formula (L):

【0060】[0060]

【化58】 Embedded image

【0061】(式中、Z3 及びZ4 は、同一又は異なっ
て、酸素原子又は硫黄原子を表す。)で示される基、次
式(M):
Wherein Z 3 and Z 4 are the same or different and each represent an oxygen atom or a sulfur atom, and a group represented by the following formula (M):

【0062】[0062]

【化59】 Embedded image

【0063】(式中、Z5 は酸素原子又は硫黄原子を表
す。)で示される基、次式(N):
(Wherein Z 5 represents an oxygen atom or a sulfur atom), a group represented by the following formula (N):

【0064】[0064]

【化60】 Embedded image

【0065】(式中、Z6 及びZ7 は、同一又は異なっ
て、酸素原子又は硫黄原子を表す。)で示される基、次
式(O):
(Wherein Z 6 and Z 7 are the same or different and each represent an oxygen atom or a sulfur atom), a group represented by the following formula (O):

【0066】[0066]

【化61】 Embedded image

【0067】(式中、Z8 及びZ9 は、同一又は異なっ
て、酸素原子又は硫黄原子を表す。)で示される基、次
式(P): −CH=N−N=CH− (P) で示される基、又は次式(Q):
(Wherein Z 8 and Z 9 are the same or different and each represent an oxygen atom or a sulfur atom), a group represented by the following formula (P): -CH = NN-CH = (P Or a group represented by the following formula (Q):

【0068】[0068]

【化62】 Embedded image

【0069】(式中、Z10は酸素原子又は硫黄原子を表
す。)で示される基を表す。但し、Xが3,5−ジ−t
−ブチル−4−ヒドロキシフェニル基であり、Yがフェ
ニル基又は2−ヒドロキシフェニル基であり、かつ、W
が−CONHNHCO−である場合を除く。]で示され
る化合物又はその薬学的に許容される塩。
(In the formula, Z 10 represents an oxygen atom or a sulfur atom.) Provided that X is 3,5-di-t
-Butyl-4-hydroxyphenyl group, Y is a phenyl group or a 2-hydroxyphenyl group, and W
Is -CONHNHCO-. Or a pharmaceutically acceptable salt thereof.

【0070】(5)前記式(I’)において、Wが前記
式(J)で示される基である前記(4)に記載の化合物
又はその薬学的に許容される塩。 (6)前記式(I’)において、Wが前記式(K)で示
される基である前記(4)に記載の化合物又はその薬学
的に許容される塩。 (7)前記式(I’)において、Xが前記式(A)で示
される基である前記(4)に記載の化合物又はその薬学
的に許容される塩。 (8)前記式(I’)において、Xが前記式(C)で示
される基である前記(4)に記載の化合物又はその薬学
的に許容される塩。
(5) The compound or a pharmaceutically acceptable salt thereof according to the above (4), wherein in the above formula (I '), W is a group represented by the above formula (J). (6) The compound according to (4) or a pharmaceutically acceptable salt thereof, wherein W in the formula (I ′) is a group represented by the formula (K). (7) The compound or a pharmaceutically acceptable salt thereof according to the above (4), wherein in the formula (I ′), X is a group represented by the above formula (A). (8) The compound according to (4) or a pharmaceutically acceptable salt thereof, wherein in the formula (I ′), X is a group represented by the formula (C).

【0071】本明細書において、C1-4 −アルキル基、
及び各置換基中の「C1-4 −アルキル」としては、例え
ばメチル基、エチル基、プロピル基、イソプロピル基、
ブチル基、イソブチル基、 sec−ブチル基、tert−ブチ
ル基が挙げられる。ハロゲン原子としては、例えばフッ
素原子、塩素原子、臭素原子、ヨウ素原子が挙げられ
る。
In the present specification, a C 1-4 -alkyl group,
And "C 1-4 -alkyl" in each substituent includes, for example, methyl group, ethyl group, propyl group, isopropyl group,
Butyl group, isobutyl group, sec-butyl group and tert-butyl group. Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

【0072】C1-4 −アルコキシ基、及び各置換基中の
「C1-4 −アルコキシ」としては、例えばメトキシ基、
エトキシ基、プロポキシ基、イソプロポキシ基、ブトキ
シ基、イソブトキシ基、 sec−ブトキシ基、tert−ブト
キシ基が挙げられる。C5-8 −シクロアルキル基として
は、例えばシクロペンチル基、シクロヘキシル基、シク
ロペプチル基、シクロオクチル基が挙げられる。本明細
書において、含窒素複素環置換−メチル基とは、ピペリ
ジノ基、ピペラジノ基、モルホリノ基、ピロリジノ基、
パーヒドロ−1,4−ジアゼピノ基、イミダゾリジノ
基、ピラゾリジノ基等の含窒素複素環基で置換されたメ
チル基を意味し、当該含窒素複素環基は、C1-4 −アル
キル基等の置換基で置換されていてもよい。
The C 1-4 alkoxy group and “C 1-4 alkoxy” in each substituent include, for example, methoxy group,
An ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group, and a tert-butoxy group are exemplified. C 5-8 - cycloalkyl group such as cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group. In the present specification, a nitrogen-containing heterocyclic-substituted -methyl group refers to a piperidino group, a piperazino group, a morpholino group, a pyrrolidino group,
Means a methyl group substituted with a nitrogen-containing heterocyclic group such as a perhydro-1,4-diazepino group, an imidazolidino group, or a pyrazolidino group, and the nitrogen-containing heterocyclic group is a substituent such as a C 1-4 -alkyl group. May be substituted.

【0073】R12とR13、又はR15とR16が共同して形
成し得る縮合6員環としては、例えばベンゼン環、含窒
素複素環(例えばピペリジン環)が挙げられる。前記式
(I)においてWで表されるスペーサー基としては、前
記式(J)又は(K)で示される基が好ましく、Xで表
される基としては、前記式(A)又は(C)で示される
基が好ましい。
Examples of the fused 6-membered ring which R 12 and R 13 or R 15 and R 16 can form together include a benzene ring and a nitrogen-containing heterocyclic ring (eg, a piperidine ring). In the formula (I), the spacer group represented by W is preferably a group represented by the formula (J) or (K), and a group represented by X is a group represented by the formula (A) or (C) Are preferred.

【0074】前記式(I)で示される化合物のうち、X
が3,5−ジ−t−ブチル−4−ヒドロキシフェニル基
であり、Yがフェニル基又は2−ヒドロキシフェニル基
であり、かつ、Wが−CONHNHCO−である化合物
以外は新規化合物である。前記式(I)で示される化合
物は、その有する官能基の種類によって、薬学的に許容
される塩として用いることができるが、そのような塩と
しては、例えば、塩酸塩、リン酸塩、硫酸塩、フマル酸
塩、マレイン酸塩等の酸付加塩、ナトリウム塩等のアル
カリ金属塩が挙げられる。
Among the compounds represented by the above formula (I), X
Is a 3,5-di-t-butyl-4-hydroxyphenyl group, Y is a phenyl group or a 2-hydroxyphenyl group, and W is -CONHNHCO-. The compound represented by the formula (I) can be used as a pharmaceutically acceptable salt depending on the type of the functional group, and examples of such a salt include hydrochloride, phosphate, and sulfate. Examples thereof include salts, acid addition salts such as fumarate and maleate, and alkali metal salts such as sodium salt.

【0075】[0075]

【発明の実施の形態】前記式(I)で示される化合物
は、例えば、次の反応式で示される方法に従って製造す
ることができる。
BEST MODE FOR CARRYING OUT THE INVENTION The compound represented by the above formula (I) can be produced, for example, according to the method represented by the following reaction formula.

【0076】[0076]

【化63】 Embedded image

【0077】(式中、X、Y、R25及びR26は前記と同
義であり、Zは酸素原子又は硫黄原子を表し、Vはメチ
レン基、酸素原子、硫黄原子又はNHを表し、DCCは
ジシクロヘキシルカルボジイミドを表す。)
(Wherein X, Y, R 25 and R 26 are as defined above, Z represents an oxygen atom or a sulfur atom, V represents a methylene group, an oxygen atom, a sulfur atom or NH, and DCC represents Represents dicyclohexylcarbodiimide.)

【0078】各反応で得られる生成物を精製するには、
通常用いられる手法、例えばシリカゲル等を担体として
用いたカラムクロマトグラフィーやメタノール、エタノ
ール、クロロホルム、ジメチルスルホキシド、水等を用
いた再結晶法によればよい。カラムクロマトグラフィー
の溶出溶媒としては、メタノール、エタノール、クロロ
ホルム、アセトン、ヘキサン、ジクロロメタン、酢酸エ
チル、及びこれらの混合溶媒等が挙げられる。
To purify the product obtained in each reaction,
A commonly used method such as column chromatography using silica gel or the like as a carrier or a recrystallization method using methanol, ethanol, chloroform, dimethyl sulfoxide, water, or the like may be used. Examples of the elution solvent for column chromatography include methanol, ethanol, chloroform, acetone, hexane, dichloromethane, ethyl acetate, and a mixed solvent thereof.

【0079】前記式(I)で示される化合物及びその薬
学的に許容される塩(以下「アシルヒドラゾン誘導体
(I)」という。)は、医薬、特にメイラード反応阻害
薬及び抗活性酸素薬として有用であり、特に、冠動脈性
心疾患、末梢循環障害、脳血管障害、糖尿病性神経障
害、糖尿病性腎症、動脈硬化症、関節硬化症、白内障、
網膜症、凝固障害症、糖尿病性骨減少症等の糖尿病性合
併症;アテローム性動脈硬化症、糸球体腎炎、白内障、
骨関節症、関節周囲硬直症、関節硬化症、老人性骨粗鬆
症、アルツハイマー病等の老人性疾患;動脈硬化、冠動
脈性心疾患、脳血管障害、肝不全、腎不全、白内障、網
膜症、自己免疫疾患(例えばベーチェット病)等の活性
酸素の生成が原因となる種々の疾患の治療に有用であ
る。
The compound represented by the above formula (I) and a pharmaceutically acceptable salt thereof (hereinafter, referred to as “acylhydrazone derivative (I)”) are useful as a drug, particularly as a Maillard reaction inhibitor and an antireactive oxygen drug. In particular, coronary heart disease, peripheral circulatory disorders, cerebrovascular disorders, diabetic neuropathy, diabetic nephropathy, arteriosclerosis, arthrosclerosis, cataract,
Diabetic complications such as retinopathy, coagulopathy, and diabetic osteopenia; atherosclerosis, glomerulonephritis, cataract,
Senile diseases such as osteoarthritis, periarticular stiffness, arthrosclerosis, senile osteoporosis, Alzheimer's disease; arteriosclerosis, coronary heart disease, cerebrovascular disease, liver failure, renal failure, cataract, retinopathy, autoimmunity It is useful for treating various diseases caused by the production of active oxygen such as diseases (eg, Behcet's disease).

【0080】また、アシルヒドラゾン誘導体(I)の経
口投与での急性毒性試験をSD系マラットを用いて行っ
たところ、2000mg/kg の経口投与で死亡例はなかった。
このように、アシルヒドラゾン誘導体(I)は極めて毒
性が低く、安全性の高いものである。以下、アシルヒド
ラゾン誘導体(I)の投与量及び製剤化について説明す
る。
An acute toxicity test of the oral administration of the acylhydrazone derivative (I) was carried out using an SD type marat, and no death occurred at an oral administration of 2000 mg / kg.
Thus, the acylhydrazone derivative (I) has extremely low toxicity and high safety. Hereinafter, the dosage and formulation of the acylhydrazone derivative (I) will be described.

【0081】アシルヒドラゾン誘導体(I)はそのま
ま、あるいは慣用の製剤担体と共に動物及びヒトに投与
することができる。投与形態としては、特に限定がな
く、必要に応じ適宜選択して使用され、錠剤、カプセル
剤、顆粒剤、細粒剤、散剤等の経口剤、注射剤、坐剤等
の非経口剤が挙げられる。経口剤として所期の効果を発
揮するためには、患者の年令、体重、疾患の程度により
異なるが、通常成人でアシルヒドラゾン誘導体(I)の
重量として1mg〜2000mgを、1日数回に分けての服用が
適当である。
The acylhydrazone derivative (I) can be administered to animals and humans as it is or together with a conventional pharmaceutical carrier. The administration form is not particularly limited and may be appropriately selected and used as needed. Examples thereof include oral preparations such as tablets, capsules, granules, fine granules and powders, and parenteral preparations such as injections and suppositories. Can be In order to achieve the intended effect as an oral preparation, the dosage of the acylhydrazone derivative (I) is usually 1 mg to 2000 mg divided into several times a day for an adult, although it depends on the age, weight and degree of the disease of the patient. All doses are appropriate.

【0082】経口剤は、例えばデンプン、乳糖、白糖、
マンニット、カルボキシメチルセルロース、コーンスタ
ーチ、無機塩類等を用いて常法に従って製造される。こ
の種の製剤には、適宜前記賦形剤の他に、結合剤、崩壊
剤、界面活性剤、滑沢剤、流動性促進剤、矯味剤、着色
剤、香料等を使用することができる。結合剤としては、
例えばデンプン、デキストリン、アラビアゴム末、ゼラ
チン、ヒドロキシプロピルスターチ、メチルセルロー
ス、カルボキシメチルセルロースナトリウム、ヒドロキ
シプロピルセルロース、結晶セルロース、エチルセルロ
ース、ポリビニルピロリドン、マクロゴールが挙げられ
る。
Oral preparations include, for example, starch, lactose, sucrose,
Manufactured according to a conventional method using mannitol, carboxymethyl cellulose, corn starch, inorganic salts and the like. In this type of preparation, a binder, a disintegrating agent, a surfactant, a lubricant, a fluidity promoter, a flavoring agent, a coloring agent, a flavor, and the like can be used as appropriate in addition to the excipients. As a binder,
Examples include starch, dextrin, gum arabic powder, gelatin, hydroxypropyl starch, methylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, crystalline cellulose, ethylcellulose, polyvinylpyrrolidone, and macrogol.

【0083】崩壊剤としては、例えばデンプン、ヒドロ
キシプロピルスターチ、カルボキシメチルセルロースナ
トリウム、カルボキシメチルセルロースカルシウム、カ
ルボキシメチルセルロース、低置換ヒドロキシプロピル
セルロースが挙げられる。界面活性剤としては、例えば
ラウリル硫酸ナトリウム、大豆レシチン、ショ糖脂肪酸
エステル、ポリソルベート80が挙げられる。滑沢剤とし
ては、例えばタルク、ロウ類、水素添加植物油、ショ糖
脂肪酸エステル、ステアリン酸マグネシウム、ステアリ
ン酸カルシウム、ステアリン酸アルミニウム、ポリエチ
レングリコールが挙げられる。
Examples of the disintegrant include starch, hydroxypropyl starch, sodium carboxymethylcellulose, calcium carboxymethylcellulose, carboxymethylcellulose and low-substituted hydroxypropylcellulose. Examples of the surfactant include sodium lauryl sulfate, soybean lecithin, sucrose fatty acid ester, and polysorbate 80. Examples of the lubricant include talc, waxes, hydrogenated vegetable oil, sucrose fatty acid ester, magnesium stearate, calcium stearate, aluminum stearate, and polyethylene glycol.

【0084】流動性促進剤としては、例えば軽質無水ケ
イ酸、乾燥水酸化アルミニウムゲル、合成ケイ酸アルミ
ニウム、ケイ酸マグネシウムが挙げられる。また、アシ
ルヒドラゾン誘導体(I)は、懸濁液、エマルジョン
剤、シロップ剤、エリキシル剤としても投与することが
でき、これらの各種剤形には、矯味矯臭剤、着色剤を含
有してもよい。非経口剤として所期の効果を発揮するた
めには、患者の年令、体重、疾患の程度により異なる
が、通常成人でアシルヒドラゾン誘導体(I)の重量と
して1日0.1〜600mg までの静注、点滴静注、皮下注
射、筋肉注射が適当である。
Examples of the fluidity promoter include light anhydrous silicic acid, dried aluminum hydroxide gel, synthetic aluminum silicate and magnesium silicate. The acylhydrazone derivative (I) can also be administered as a suspension, emulsion, syrup, and elixir, and these various dosage forms may contain a flavoring agent and a coloring agent. . In order to achieve the desired effect as a parenteral drug, it depends on the age, weight and degree of the disease of the patient, but it is usually 0.1% to 600 mg per day as the weight of acylhydrazone derivative (I) for adults in adults. Intravenous, subcutaneous and intramuscular injections are suitable.

【0085】この非経口剤は常法に従って製造され、希
釈剤として一般に注射用蒸留水、生理食塩水、ブドウ糖
水溶液、オリブ油、ゴマ油、ラッカセイ油、ダイズ油、
トウモロコシ油、プロピレングリコール、ポリエチレン
グリコール等を用いることができる。更に必要に応じ
て、殺菌剤、防腐剤、安定剤を加えてもよい。また、こ
の非経口剤は安定性の点から、バイアル等に充填後冷凍
し、通常の凍結乾燥技術により水分を除去し、使用直前
に凍結乾燥物から液剤を再調製することもできる。更
に、必要に応じて適宜、等張化剤、安定剤、防腐剤、無
痛化剤等を加えてもよい。その他の非経口剤としては、
外用液剤、軟膏等の塗布剤、直腸内投与のための坐剤等
が挙げられ、常法に従って製造される。
This parenteral preparation is produced according to a conventional method, and is generally used as a diluent in distilled water for injection, physiological saline, aqueous glucose solution, olive oil, sesame oil, peanut oil, soybean oil,
Corn oil, propylene glycol, polyethylene glycol and the like can be used. Further, if necessary, a bactericide, a preservative and a stabilizer may be added. Further, from the viewpoint of stability, this parenteral preparation can be frozen after filling into a vial or the like, water can be removed by a usual freeze-drying technique, and a liquid preparation can be prepared from the freeze-dried product immediately before use. Further, if necessary, an isotonic agent, a stabilizer, a preservative, a soothing agent and the like may be added as appropriate. Other parenteral agents include
Examples thereof include liquid preparations for external use, ointments and other suppositories, suppositories for rectal administration, and the like.

【0086】[0086]

【実施例】以下、参考例、実施例及び試験例により本発
明を更に具体的に説明するが、本発明の範囲はこれらに
限定されるものではない。 参考例1 3,5−ジ−t−ブチル−4−ヒドロキシベ
ンゾヒドラジド(3,5-di-t-butyl-4-hydroxybenzohydraz
ide) 3,5−ジ−t−ブチル−4−ヒドロキシ安息香酸メチ
ル(methyl 3,5-di-t-butyl-4-hydroxybenzoate) 25.04g
(95mmol)及びヒドラジン水和物(hydrazine hydrate) 4
5.95ml(950mmol)を1−プロパノール 190mlに懸濁し,
バス温140 ℃で加熱還流した。溶媒を留去し、酢酸エチ
ル 300mlを加えて、飽和塩化アンモニウム水溶液、水、
飽和食塩水で順次洗浄し、硫酸ナトリウムで乾燥し、溶
媒留去した。析出した結晶をろ取し、減圧下で乾燥し、
標記化合物 18.44g(収率73%)を得た。 (物性) 無色結晶(mp.190-193 ℃) PMR(CDCl3,δ ppm) :7.57(2H,s),7.37(1H,brs),5.59(1
H,s),4.09(2H,brs),1.45(18H,s)
EXAMPLES Hereinafter, the present invention will be described in more detail by reference examples, examples, and test examples, but the scope of the present invention is not limited thereto. Reference Example 1 3,5-di-t-butyl-4-hydroxybenzohydrazide
ide) 25.04 g of methyl 3,5-di-t-butyl-4-hydroxybenzoate
(95 mmol) and hydrazine hydrate 4
5.95 ml (950 mmol) is suspended in 190 ml of 1-propanol,
The mixture was heated to reflux at a bath temperature of 140 ° C. The solvent was distilled off, 300 ml of ethyl acetate was added, and a saturated aqueous solution of ammonium chloride, water,
The extract was washed successively with saturated saline, dried over sodium sulfate, and the solvent was distilled off. The precipitated crystals are collected by filtration and dried under reduced pressure.
18.44 g (73% yield) of the title compound were obtained. (Physical properties) Colorless crystal (mp.190-193 ° C) PMR (CDCl 3 , δ ppm): 7.57 (2H, s), 7.37 (1H, brs), 5.59 (1
H, s), 4.09 (2H, brs), 1.45 (18H, s)

【0087】参考例2 6−ヒドロキシ−2,5,7,
8−テトラメチルクロマン−2−アセトヒドラジド(6-h
ydroxy-2,5,7,8-tetramethylchroman-2-acetohydrazid
e)6−アセトキシ−2,5,7,8−テトラメチルクロ
マン−2−酢酸メチル(methyl 6-acetoxy-2,5,7,8-tetr
amethylchroman-2-acetate) 32.68g(102mmol) 及びヒド
ラジン水和物49.48ml(1020mmol) を1−プロパノール 2
04mlに溶かし、バス温110 ℃で4 時間加熱還流した。溶
媒を留去し、結晶を析出させ、その結晶をろ取した。ろ
取した結晶を減圧下で乾燥し、標記化合物 14.95g(収率
53%)を得た。ろ液をシリカゲルカラムクロマトグラフィ
ーに付し、メタノール:クロロホルム=1:20溶出部を
溶媒留去し、酢酸エチルを加えて結晶化し、減圧下で乾
燥した。標記化合物4.34g(収率15%)を得た。 (物性) 無色結晶(mp.155-157 ℃) PMR(DMSO-d6,δ ppm) :8.96(1H,brs),7.36(1H,s),4.18
(2H,brs),2.62-2.44(2H,m),2.35(1H,d,J=13.2Hz),2.24
(1H,d,J=13.2Hz),2.05(3H,s),2.02(3H,s),1.97-1.90(4
H,m),1.80-1.72(1H,m),1.29(3H,s) IR(KBr, cm-1):3274,1650,1539,1458,1243,1101,1023,9
23
Reference Example 2 6-hydroxy-2,5,7,
8-tetramethylchroman-2-acetohydrazide (6-h
ydroxy-2,5,7,8-tetramethylchroman-2-acetohydrazid
e) methyl 6-acetoxy-2,5,7,8-tetr
amethylchroman-2-acetate) 32.68 g (102 mmol) and hydrazine hydrate 49.48 ml (1020 mmol) in 1-propanol 2
It was dissolved in 04 ml and heated under reflux at a bath temperature of 110 ° C. for 4 hours. The solvent was distilled off to precipitate crystals, and the crystals were collected by filtration. The crystals collected by filtration were dried under reduced pressure to give 14.95 g of the title compound (yield
53%). The filtrate was subjected to silica gel column chromatography. The solvent eluted with methanol: chloroform = 1: 20 was evaporated, ethyl acetate was added for crystallization, and the crystal was dried under reduced pressure. 4.34 g (yield 15%) of the title compound was obtained. (Physical properties) Colorless crystal (mp.155-157 ° C) PMR (DMSO-d 6 , δ ppm): 8.96 (1H, brs), 7.36 (1H, s), 4.18
(2H, brs), 2.62-2.44 (2H, m), 2.35 (1H, d, J = 13.2Hz), 2.24
(1H, d, J = 13.2Hz), 2.05 (3H, s), 2.02 (3H, s), 1.97-1.90 (4
(H, m), 1.80-1.72 (1H, m), 1.29 (3H, s) IR (KBr, cm- 1 ): 3274,1650,1539,1458,1243,1101,1023,9
twenty three

【0088】参考例3 6−ヒドロキシ−2,5,7,
8−テトラメチルクロマン−2−カルボヒドラジド(6-h
ydroxy-2,5,7,8-tetramethylchroman-2-carbohydrazid
e) 6−ヒドロキシ−2,5,7,8−テトラメチルクロマ
ン−2−カルボン酸メチル(methyl 6-hydroxy-2,5,7,8-
tetramethylchroman-2-carboxylate) 3.06g(11.6mmol)
及びヒドラジン水和物2.81ml(57.9mmol)を1−プロパノ
ール 25ml に溶かし、バス温110 ℃で4 時間加熱還流し
た。溶媒を留去し、結晶を析出させ、その結晶をろ取し
た。ろ取した結晶を減圧下で乾燥し、標記化合物 2.63g
(収率86%)を得た。 (物性) 無色結晶 PMR(DMSO-d6,δ ppm) :8.45(1H,brs),7.43(1H,s),4.22
(2H,brs),2.56-2.38(2H,m),2.26-2.19(1H, m),2.09(3H,
s),2.07(3H,s),1.99(3H,s),1.74-1.66(1H,m),1.40(3H,
s)
Reference Example 3 6-hydroxy-2,5,7,
8-tetramethylchroman-2-carbohydrazide (6-h
ydroxy-2,5,7,8-tetramethylchroman-2-carbohydrazid
e) methyl 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylate (methyl 6-hydroxy-2,5,7,8-
tetramethylchroman-2-carboxylate) 3.06 g (11.6 mmol)
Then, 2.81 ml (57.9 mmol) of hydrazine hydrate were dissolved in 25 ml of 1-propanol, and the mixture was refluxed for 4 hours at a bath temperature of 110 ° C. The solvent was distilled off to precipitate crystals, and the crystals were collected by filtration. The crystals collected by filtration were dried under reduced pressure to give the title compound (2.63 g).
(86% yield). (Physical properties) Colorless crystal PMR (DMSO-d 6 , δ ppm): 8.45 (1H, brs), 7.43 (1H, s), 4.22
(2H, brs), 2.56-2.38 (2H, m), 2.26-2.19 (1H, m), 2.09 (3H,
s), 2.07 (3H, s), 1.99 (3H, s), 1.74-1.66 (1H, m), 1.40 (3H,
s)

【0089】参考例4 6−ヒドロキシ−2,5,7,
8−テトラメチルクロマン−2−ブチロヒドラジド(6-h
ydroxy-2,5,7,8-tetramethylchroman-2-butyrohydrazid
e) 6−ヒドロキシ−2,5,7,8−テトラメチルクロマ
ン−2−酪酸メチル(methyl 6-hydroxy-2,5,7,8-tetram
ethylchroman-2-butyrate)3.06g(10mmol) 及びヒドラジ
ン水和物2.43ml(50mmol)を1−プロパノール 10ml に溶
かし、バス温80℃で5 時間加熱還流した。溶媒を留去
し、酢酸エチルを加え、飽和塩化アンモニウム水溶液、
飽和食塩水で順次洗浄し、硫酸マグネシウムで乾燥し、
溶媒留去した。残渣をシリカゲルカラムクロマトグラフ
ィーに付した。メタノール:クロロホルム=1:20溶出
部を溶媒留去し、酢酸エチルを加えて結晶化し、減圧下
で乾燥した。標記化合物 2.83g (収率92%)を得た。 (物性) 無色結晶(mp.112-113 ℃) PMR(DMSO-d6,δ ppm) :8.90(1H,brs),7.31(1H,s),4.11
(2H,brs),2.53-2.51(2H,m),2.05-1.98(11H,m),1.76-1.4
3(6H,m),1.16(3H,s)
Reference Example 4 6-hydroxy-2,5,7,
8-tetramethylchroman-2-butyrohydrazide (6-h
ydroxy-2,5,7,8-tetramethylchroman-2-butyrohydrazid
e) methyl 6-hydroxy-2,5,7,8-tetramethylchroman-2-butyrate (methyl 6-hydroxy-2,5,7,8-tetram
3.06 g (10 mmol) of ethylchroman-2-butyrate) and 2.43 ml (50 mmol) of hydrazine hydrate were dissolved in 10 ml of 1-propanol, and the mixture was heated and refluxed at a bath temperature of 80 ° C. for 5 hours. The solvent was distilled off, and ethyl acetate was added.
Wash sequentially with saturated saline, dry over magnesium sulfate,
The solvent was distilled off. The residue was subjected to silica gel column chromatography. The solvent was distilled off from the eluted portion of methanol: chloroform = 1: 20, crystallized by adding ethyl acetate, and dried under reduced pressure. 2.83 g (yield 92%) of the title compound was obtained. (Physical properties) Colorless crystal (mp.112-113 ° C) PMR (DMSO-d 6 , δ ppm): 8.90 (1H, brs), 7.31 (1H, s), 4.11
(2H, brs), 2.53-2.51 (2H, m), 2.05-1.98 (11H, m), 1.76-1.4
3 (6H, m), 1.16 (3H, s)

【0090】参考例5 6−ヒドロキシ−2,5,7,
8−テトラメチルクロマン−2−プロピオノヒドラジド
(6-hydroxy-2,5,7,8-tetramethylchroman-2-propionohy
drazide) 参考例4と同様に処理して、標記化合物を得た (収率10
0%) 。 (物性) 無色結晶(mp.89-91 ℃) PMR(DMSO-d6,δ ppm) :8.97(1H,br
s),7.33(1H,s),4.08(2H,br
s),2.54−2.51(2H,m),2.23−
1.98(11H,m),1.83−1.66(4H,
m),1.15(3H,s)
Reference Example 5 6-hydroxy-2,5,7,
8-tetramethylchroman-2-propionohydrazide
(6-hydroxy-2,5,7,8-tetramethylchroman-2-propionohy
drazide) The title compound was obtained in the same manner as in Reference Example 4 (yield: 10
0%). (Physical properties) Colorless crystal (mp. 89-91 ° C.) PMR (DMSO-d 6 , δ ppm): 8.97 (1H, br)
s), 7.33 (1H, s), 4.08 (2H, br)
s), 2.54-2.51 (2H, m), 2.23-
1.98 (11H, m), 1.83-1.66 (4H,
m), 1.15 (3H, s)

【0091】参考例6 ベンズアルデヒドメチルヒドラ
ゾン(benzaldehyde methylhyd
razone) ベンズアルデヒド 1.02ml(10mmol) 及びメチルヒドラジ
ン 0.53ml(10mmol) をエタノール 20ml に加え、室温で
3 時間攪拌した。溶媒を留去し、残渣をシリカゲルカラ
ムクロマトグラフィーに付した。酢酸エチル:n−ヘキ
サン=1:3溶出部を溶媒留去し、標記化合物 1.21g
(収率90%)を得た。 (物性) 無色油状物
Reference Example 6 Benzaldehyde methylhydrazone
razone) 1.02 ml (10 mmol) of benzaldehyde and 0.53 ml (10 mmol) of methylhydrazine are added to 20 ml of ethanol, and the mixture is added at room temperature.
Stir for 3 hours. The solvent was distilled off, and the residue was subjected to silica gel column chromatography. The solvent was distilled off from the eluted portion of ethyl acetate: n-hexane = 1: 3 to give the title compound (1.21 g)
(90% yield). (Physical properties) Colorless oil

【0092】参考例7 サリチルアルデヒドメチルヒド
ラゾン(salicylaldehyde methylhydrazone) サリチルアルデヒド 1.07ml(10mmol) 及びメチルヒドラ
ジン 0.53ml(10mmol)をエタノール 20ml に加え、室温
で24時間攪拌した。溶媒を留去し、標記化合物1.44g
(収率96%)を得た。 (物性) 黄色油状物 PMR(CDCl3,δ ppm) :7.67(1H,s),7.17(1H,td,J=7.8,1.5
Hz),7.12(1H,dd,J=7.8,1.5Hz),6.93(1H,d,J =8.3Hz),6.
86(1H,td,J=7.3,1.0Hz),2.98(3H,s)
Reference Example 7 Salicylaldehyde methylhydrazone 1.07 ml (10 mmol) of salicylaldehyde and 0.53 ml (10 mmol) of methylhydrazine were added to 20 ml of ethanol, and the mixture was stirred at room temperature for 24 hours. The solvent was distilled off to give the title compound (1.44 g).
(96% yield). (Physical properties) Yellow oil PMR (CDCl 3 , δ ppm): 7.67 (1H, s), 7.17 (1H, td, J = 7.8,1.5
Hz), 7.12 (1H, dd, J = 7.8,1.5Hz), 6.93 (1H, d, J = 8.3Hz), 6.
86 (1H, td, J = 7.3,1.0Hz), 2.98 (3H, s)

【0093】参考例8 2,4−ジヒドロキシベンズア
ルデヒドメチルヒドラゾン(2,4-dihydroxybenzaldehyde
methylhydrazone) 参考例7と同様に処理して、標記化合物を得た (収率54
%)。 (物性) 褐色結晶 PMR(DMSO-d6,δ ppm) :11.58(1H,
s),9.47(1H,brs),7.63(1H,
s),7.02(1H,d,J=8.3Hz),6.9
9(1H,q,J=4.9Hz),6.25(1H,d
d,J=8.3,2.4Hz),6.20(1H,d,
J=2.4Hz),2.76(3H,d,J=4.9H
z)
Reference Example 8 2,4-dihydroxybenzaldehyde methylhydrazone (2,4-dihydroxybenzaldehyde
methylhydrazone) The title compound was obtained in the same manner as in Reference Example 7 (yield: 54
%). (Physical properties) Brown crystal PMR (DMSO-d 6 , δ ppm): 11.58 (1H,
s), 9.47 (1H, brs), 7.63 (1H,
s), 7.02 (1H, d, J = 8.3 Hz), 6.9
9 (1H, q, J = 4.9 Hz), 6.25 (1H, d
d, J = 8.3, 2.4 Hz), 6.20 (1H, d,
J = 2.4 Hz), 2.76 (3H, d, J = 4.9 H)
z)

【0094】参考例9 o−バニリンメチルヒドラゾン
(o−vanillin methylhydrazo
ne) o−バニリン(2−ヒドロキシ−3−メトキシベンズア
ルデヒド) 1.52g(10mmol)及びメチルヒドラジン0.53ml
(10mmol)をエタノール 20ml に加え、室温で24時間攪拌
した。溶媒を留去し、残渣をシリカゲルカラムクロマト
グラフィーに付し、酢酸エチル:n−ヘキサン=1:1
溶出部を溶媒留去し、結晶化させ、ろ取した。減圧下で
乾燥し、標記化合物 1.39g (収率77%)を得た。 (物性) 淡黄色結晶 PMR(DMSO-d6,δ ppm) :11.33(1H,s),7.64(1H,s),7.45(1
H,brs),6.87(1H,dd,J=7.8,1.0Hz),6.82(1H,dd,J=6.4H
z),6.75(1H,t,J=7.8Hz),3.77(3H,s),2.81(3H,s)
Reference Example 9 o-Vanillin methylhydrazo
ne) 1.52 g (10 mmol) of o-vanillin (2-hydroxy-3-methoxybenzaldehyde) and 0.53 ml of methylhydrazine
(10 mmol) was added to 20 ml of ethanol, and the mixture was stirred at room temperature for 24 hours. The solvent was distilled off, and the residue was subjected to silica gel column chromatography, and ethyl acetate: n-hexane = 1: 1.
The solvent was distilled off from the eluted portion to crystallize and was collected by filtration. Drying under reduced pressure gave 1.39 g (yield 77%) of the title compound. (Physical properties) Pale yellow crystal PMR (DMSO-d 6 , δ ppm): 11.33 (1H, s), 7.64 (1H, s), 7.45 (1
H, brs), 6.87 (1H, dd, J = 7.8,1.0Hz), 6.82 (1H, dd, J = 6.4H
z), 6.75 (1H, t, J = 7.8Hz), 3.77 (3H, s), 2.81 (3H, s)

【0095】参考例10 4−(ジエチルアミノ)サリ
チルアルデヒドメチルヒドラゾン(4-(diethylamino)sal
icylaldehyde methylhydrazone) 4−(ジエチルアミノ)サリチルアルデヒド 1.93g(10m
mol)及びメチルヒドラジン 0.53ml(10mmol) をエタノー
ル 20ml 及びメタノール 10ml の混合溶媒に加え、室温
で24時間攪拌した。溶媒を留去し、残渣をシリカゲルカ
ラムクロマトグラフィーに付し、酢酸エチル:n−ヘキ
サン=1:2溶出部を溶媒留去し、標記化合物 1.40g
(収率77%)を得た。 (物性) 褐色油状物 PMR(CDCl3,δ ppm) :11.40(1H,brs),7.67(1H,s),6.93(1
H,d,J=8.3Hz),6.21(1H,d,J=2.4Hz),6.19(1H,dd,J=8.3,
2.4Hz),3.35(4H,q,J=7.2Hz),2.92(3H,s),1.17(6H,t,J=
7.1Hz)
Reference Example 10 4- (Diethylamino) salicylaldehyde methylhydrazone (4- (diethylamino) sal
icylaldehyde methylhydrazone) 4- (diethylamino) salicylaldehyde 1.93g (10m
mol) and 0.53 ml (10 mmol) of methylhydrazine were added to a mixed solvent of 20 ml of ethanol and 10 ml of methanol, and the mixture was stirred at room temperature for 24 hours. The solvent was distilled off, the residue was subjected to silica gel column chromatography, and the eluted portion of ethyl acetate: n-hexane = 1: 2 was evaporated to remove the solvent.
(77% yield). (Physical properties) Brown oil PMR (CDCl 3 , δ ppm): 11.40 (1H, brs), 7.67 (1H, s), 6.93 (1
H, d, J = 8.3Hz), 6.21 (1H, d, J = 2.4Hz), 6.19 (1H, dd, J = 8.3,
2.4Hz), 3.35 (4H, q, J = 7.2Hz), 2.92 (3H, s), 1.17 (6H, t, J =
(7.1Hz)

【0096】参考例11 5−ニトロサリチルアルデヒ
ドメチルヒドラゾン(5-nitrosalicylaldehyde methylhy
drazone) 5−ニトロサリチルアルデヒド 1.67g(10mmol)及びメチ
ルヒドラジン 0.53ml(10mmol) をエタノール 20ml 及び
メタノール 10ml の混合溶媒に加え、室温で24時間攪
拌した。生じた結晶をろ取した。減圧下で乾燥し、標記
化合物 1.72g (収率88%)を得た。 (物性) 黄色結晶 PMR(DMSO-d6,δ ppm) :12.42(1H,brs),8.30(1H,d,J=2.0
Hz),7.97(1H,dd,J=8.8,2.0Hz),7.86(1H,brq,J=3.9Hz),
7.73(1H,s),6.98(1H,d,J=8.8Hz),2.86(3H,d,J=4.4Hz)
Reference Example 11 5-nitrosalicylaldehyde methyl hydrazone
(Drazone) 1.67 g (10 mmol) of 5-nitrosalicylaldehyde and 0.53 ml (10 mmol) of methylhydrazine were added to a mixed solvent of 20 ml of ethanol and 10 ml of methanol, and the mixture was stirred at room temperature for 24 hours. The resulting crystals were collected by filtration. Drying under reduced pressure gave 1.72 g (88% yield) of the title compound. (Physical properties) Yellow crystal PMR (DMSO-d 6 , δ ppm): 12.42 (1H, brs), 8.30 (1H, d, J = 2.0
Hz), 7.97 (1H, dd, J = 8.8,2.0Hz), 7.86 (1H, brq, J = 3.9Hz),
7.73 (1H, s), 6.98 (1H, d, J = 8.8Hz), 2.86 (3H, d, J = 4.4Hz)

【0097】参考例12 2,4−ジヒドロキシベンズ
アルデヒドオキシム(2,4-dihydroxybenzaldehyde oxim
e) 2,4−ジヒドロキシベンズアルデヒド 1.38g(10mmo
l)、塩酸ヒドロキシルアミン 0.69g(10mmol)及び炭酸ナ
トリウム 1.06g(10mmol)をメタノール 20ml に加え、室
温下で24時間攪拌した。溶媒を留去し、酢酸エチル100m
l を加え、水、飽和食塩水で順次洗浄し、有機層を硫酸
マグネシウムで乾燥した。溶媒留去し、生じた結晶をろ
取した。減圧下で乾燥し、標記化合物1.14g(収率74%)を
得た。 (物性) 淡褐色結晶 PMR(DMSO-d6,δ ppm) :10.92(1H,s),10.09(1H,s),9.67
(1H,s),8.18(1H,s),7.20(1H,d,J=9.3Hz),6.31-6.28(2H,
m)
Reference Example 12 2,4-dihydroxybenzaldehyde oxime
e) 1,38 g of 2,4-dihydroxybenzaldehyde (10 mmo
l), 0.69 g (10 mmol) of hydroxylamine hydrochloride and 1.06 g (10 mmol) of sodium carbonate were added to 20 ml of methanol, followed by stirring at room temperature for 24 hours. The solvent was distilled off and ethyl acetate 100m
The organic layer was washed with water and saturated saline in this order, and the organic layer was dried over magnesium sulfate. The solvent was distilled off, and the resulting crystals were collected by filtration. Drying under reduced pressure gave 1.14 g (74% yield) of the title compound. (Physical properties) Light brown crystal PMR (DMSO-d 6 , δ ppm): 10.92 (1H, s), 10.09 (1H, s), 9.67
(1H, s), 8.18 (1H, s), 7.20 (1H, d, J = 9.3Hz), 6.31-6.28 (2H,
m)

【0098】参考例13 o−バニリンオキシム(o-van
illin oxime) 参考例12と同様に処理して、標記化合物を得た (収率
77%)。 (物性) 無色結晶 PMR(DMSO-d6,δ ppm) :11.31(1H,brs),9.69(1H,brs),8.
32(1H,s),7.06(1H,d,J=7.8Hz),6.95(1H,d,J=7.8Hz),6.8
0(1H,t,J=7.8Hz),3.80(3H,s)
Reference Example 13 o-vanillin oxime (o-van
illin oxime) The title compound was obtained in the same manner as in Reference Example 12 (yield
77%). (Physical properties) Colorless crystal PMR (DMSO-d 6 , δ ppm): 11.31 (1H, brs), 9.69 (1H, brs), 8.
32 (1H, s), 7.06 (1H, d, J = 7.8Hz), 6.95 (1H, d, J = 7.8Hz), 6.8
0 (1H, t, J = 7.8Hz), 3.80 (3H, s)

【0099】参考例14 4−(ジエチルアミノ)サリ
チルアルデヒドオキシム(4-(diethylamino)salicylalde
hyde oxime) 4-(シ゛エチルアミノ)サリチルアルテ゛ヒト゛ 3.87g(20mmol)、塩酸ヒドロキシ
ルアミン1.39g(20mmol) 及び炭酸ナトリウム 2.12g(20m
mol)をメタノール 40mlに加え、室温下で20時間攪拌し
た。溶媒を留去し、酢酸エチル100ml を加え、水、飽和
食塩水で順次洗浄し、酢酸エチル層を硫酸マグネシウム
で乾燥した。溶媒留去し、残渣をシリカゲルカラムクロ
マトグラフィーに付し、メタノール:クロロホルム=
1:50溶出部を溶媒留去し、生じた結晶をろ取した。減
圧下で乾燥し、標記化合物 1.34g (収率32%)を得た。 (物性) 無色結晶 PMR(DMSO-d6,δ ppm) :10.74(1H,s),10.00(1H,s),8.13
(1H,s),7.13(1H,d,J=8.8Hz),6.20(1H,dd,J=8.8,2.4Hz),
6.09(1H,d,J=2.0Hz),3.32(4H,q,J=6.8Hz),1.09(6H,t,J=
7.1Hz)
Reference Example 14 4- (diethylamino) salicylalde oxime
hyde oxime) 4- (diethylamino) salicylartifice 3.87 g (20 mmol), hydroxylamine hydrochloride 1.39 g (20 mmol) and sodium carbonate 2.12 g (20 m
mol) was added to 40 ml of methanol, and the mixture was stirred at room temperature for 20 hours. The solvent was distilled off, 100 ml of ethyl acetate was added, and the mixture was washed sequentially with water and saturated saline, and the ethyl acetate layer was dried over magnesium sulfate. The solvent was distilled off, the residue was subjected to silica gel column chromatography, and methanol: chloroform =
The solvent was distilled off from the 1:50 elution part, and the resulting crystals were collected by filtration. Drying under reduced pressure gave 1.34 g (yield 32%) of the title compound. (Physical properties) Colorless crystal PMR (DMSO-d 6 , δ ppm): 10.74 (1H, s), 10.00 (1H, s), 8.13
(1H, s), 7.13 (1H, d, J = 8.8Hz), 6.20 (1H, dd, J = 8.8,2.4Hz),
6.09 (1H, d, J = 2.0Hz), 3.32 (4H, q, J = 6.8Hz), 1.09 (6H, t, J =
(7.1Hz)

【0100】参考例15 5−ニトロサリチルアルデヒ
ドオキシム(5-nitrosalicylaldehyde oxime) 5−ニトロサリチルアルデヒド 3.34g(20mmol)、塩酸ヒ
ドロキシルアミン1.39g(20mmol) 及び炭酸ナトリウム
2.12g(20mmol)をメタノール 40ml に加え、室温下で20
時間攪拌した。溶媒を留去し、酢酸エチル100ml を加
え、水洗し、不溶物をろ取した。メタノールに溶かし、
溶媒留去し、生じた結晶をろ取した。減圧下で乾燥し、
標記化合物 2.19g (収率60%)を得た。 (物性) 黄色結晶 PMR(DMSO-d6,δ ppm) :10.54(1H,s),8.22(1H,d,J=3.4H
z),8.21(1H,s),7.73(1H,dd,J=9.3,3.5Hz),6.06(1H,d,J=
9.3Hz)
Reference Example 15 5-nitrosalicylaldehyde oxime 3.34 g (20 mmol) of 5-nitrosalicylaldehyde, 1.39 g (20 mmol) of hydroxylamine hydrochloride and sodium carbonate
2.12 g (20 mmol) was added to 40 ml of methanol, and
Stirred for hours. The solvent was distilled off, 100 ml of ethyl acetate was added, the mixture was washed with water, and the insoluble matter was collected by filtration. Dissolve in methanol,
The solvent was distilled off, and the resulting crystals were collected by filtration. Dried under reduced pressure,
2.19 g (yield 60%) of the title compound were obtained. (Physical properties) Yellow crystal PMR (DMSO-d 6 , δ ppm): 10.54 (1H, s), 8.22 (1H, d, J = 3.4H
z), 8.21 (1H, s), 7.73 (1H, dd, J = 9.3,3.5Hz), 6.06 (1H, d, J =
(9.3Hz)

【0101】参考例16 3,5−ジイソプロピル−4
−ヒドロキシベンゾヒドラジド(3,5-diisopropyl-4-hyd
roxybenzohydrazide) 3,5−ジイソプロピル−4−ヒドロキシ安息香酸メチ
ル(methyl 3,5-diisopropyl-4-hydroxybenzoate) 6.91g
(29mmol)及びヒドラジン水和物10.0ml及び1−プロパノ
ール 100mlの混合液を10時間加熱還流した。溶媒を留去
し、析出した結晶を酢酸エチルで洗浄し、標記化合物6.
73g(収率97%)を得た。 (物性) 無色結晶(mp.240-243 ℃) PMR(DMSO-d6,δ ppm) :9.53(1H,brs),8.40(1H,brs),7.5
1(2H,s),4.35(2H,brs),3.30(2H,sept,J=7.0Hz),1.16(12
H,d,J=7.0Hz)
Reference Example 16 3,5-diisopropyl-4
-Hydroxybenzohydrazide (3,5-diisopropyl-4-hyd
roxybenzohydrazide) methyl 3,5-diisopropyl-4-hydroxybenzoate 6.91 g
(29 mmol), a mixture of 10.0 ml of hydrazine hydrate and 100 ml of 1-propanol was heated under reflux for 10 hours. The solvent was distilled off, and the precipitated crystals were washed with ethyl acetate to give the title compound 6.
73 g (97% yield) was obtained. (Physical Properties) colorless crystals (mp.240-243 ℃) PMR (DMSO- d 6, δ ppm): 9.53 (1H, brs), 8.40 (1H, brs), 7.5
1 (2H, s), 4.35 (2H, brs), 3.30 (2H, sept, J = 7.0Hz), 1.16 (12
(H, d, J = 7.0Hz)

【0102】参考例17 3−(3,5−ジ−t−ブチ
ル−4−ヒドロキシフェニル)プロピオノヒドラジド(3
-(3,5-di-t-butyl-4-hydroxyphenyl)propionohydrazid
e) 3−(3,5−ジ−t−ブチル−4−ヒドロキシフェニ
ル)プロピオン酸メチル(methyl 3-(3,5-di-t-butyl-4-
hydroxyphenyl)propionate) 10.46g(36mmol)及びヒドラ
ジン水和物10.0ml及び1−プロパノール 100mlの混合液
を10時間加熱還流した。溶媒を留去し、析出した結晶を
イソプロピルエーテルで洗浄し、標記化合物9.66g(収率
92%)を得た。 (物性) 無色結晶(mp.154-158 ℃) PMR(DMSO-d6,δ ppm) :8.97(1H,brs),6.90(2H,s),6.69
(1H,s),4.14(2H,brs),2.71-2.65(2H,m),2.28-2.23(2H,
m),1.36(18H,s)
Reference Example 17 3- (3,5-di-t-butyl-4-hydroxyphenyl) propionohydrazide (3
-(3,5-di-t-butyl-4-hydroxyphenyl) propionohydrazid
e) methyl 3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate
A mixture of 10.46 g (36 mmol) of hydroxyphenyl) propionate, 10.0 ml of hydrazine hydrate and 100 ml of 1-propanol was heated under reflux for 10 hours. The solvent was distilled off, and the precipitated crystals were washed with isopropyl ether to give 9.66 g of the title compound (yield
92%). (Physical properties) Colorless crystal (mp.154-158 ° C) PMR (DMSO-d 6 , δ ppm): 8.97 (1H, brs), 6.90 (2H, s), 6.69
(1H, s), 4.14 (2H, brs), 2.71-2.65 (2H, m), 2.28-2.23 (2H,
m), 1.36 (18H, s)

【0103】参考例18 3−(3,5−ジイソプロピ
ル−4−ヒドロキシフェニル)プロピオノヒドラジド(3
-(3,5-diisopropyl-4-hydroxyphenyl)propionohydrazid
e) 参考例17と同様に処理して、標記化合物を得た (収率
100%) 。 (物性) 無色結晶(mp.101-104 ℃) PMR(DMSO-d6,δ ppm) :8.95(1H,brs),7.77(1H,brs),6.7
7(2H,s),4.13(2H,brs),3.25(2H,sept,J=7.0 Hz),2.71-
2.65(2H,m),2.29-2.21(2H,m),1.13(12H,d,J=7.0Hz)
Reference Example 18 3- (3,5-diisopropyl-4-hydroxyphenyl) propionohydrazide (3
-(3,5-diisopropyl-4-hydroxyphenyl) propionohydrazid
e) The title compound was obtained by treating in the same manner as in Reference Example 17 (yield
100%). (Physical Properties) colorless crystals (mp.101-104 ℃) PMR (DMSO- d 6, δ ppm): 8.95 (1H, brs), 7.77 (1H, brs), 6.7
7 (2H, s), 4.13 (2H, brs), 3.25 (2H, sept, J = 7.0 Hz), 2.71-
2.65 (2H, m), 2.29-2.21 (2H, m), 1.13 (12H, d, J = 7.0Hz)

【0104】実施例1 ベンズアルデヒド3,5−ジ−
t−ブチル−4−ヒドロキシベンゾイルヒドラゾン(ben
zaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazon
e) 参考例1で合成した化合物3,5−ジ−t−ブチル−4
−ヒドロキシベンゾヒドラジド 1.32g(5mmol) 及びベン
ズアルデヒド 0.51ml(5mmol)をエタノール 10ml に溶か
し、室温下で24時間攪拌した。溶媒を留去し、イソプロ
ピルエーテルを加え、結晶を析出させ、その結晶をろ取
した。減圧下で乾燥し、標記化合物 1.09g (収率62%)を
得た。 (物性) 無色結晶(mp.223 ℃) PMR(CDCl3,δ ppm) :9.09(1H,brs),8.36(1H,brs),7.74
(4H,m),7.41-7.38(3H,m),5.63(1H,s),1.48(18H,s) IR(KBr, cm-1):3620,3412,3200,2958,1643,1555,1437,1
364,1308,1239,696
Example 1 Benzaldehyde 3,5-di-
t-butyl-4-hydroxybenzoylhydrazone (ben
zaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazon
e) Compound 3,5-di-t-butyl-4 synthesized in Reference Example 1
1.32 g (5 mmol) of -hydroxybenzohydrazide and 0.51 ml (5 mmol) of benzaldehyde were dissolved in 10 ml of ethanol, and the mixture was stirred at room temperature for 24 hours. The solvent was distilled off, isopropyl ether was added to precipitate crystals, and the crystals were collected by filtration. Drying under reduced pressure gave 1.09 g (yield 62%) of the title compound. (Physical properties) Colorless crystal (mp.223 ° C) PMR (CDCl 3 , δ ppm): 9.09 (1H, brs), 8.36 (1H, brs), 7.74
(4H, m), 7.41-7.38 (3H, m), 5.63 (1H, s), 1.48 (18H, s) IR (KBr, cm- 1 ): 3620,3412,3200,2958,1643,1555,1437 , 1
364,1308,1239,696

【0105】実施例2 4−フルオロベンズアルデヒド
3,5−ジ−t−ブチル−4−ヒドロキシベンゾイルヒ
ドラゾン(p-fluorobenzaldehyde 3,5-di-t-butyl-4-hyd
roxybenzoylhydrazone) 参考例1で合成した化合物3,5−ジ−t−ブチル−4
−ヒドロキシベンゾヒドラジド 0.53g(2mmol) 及び4−
フルオロベンズアルデヒド 0.22ml(2mmol)をエタノール
5mlに溶かし、室温下で5 時間攪拌した。析出した結晶
をろ取し、エタノールで洗浄した。減圧下で乾燥し、標
記化合物 0.63g (収率85%)を得た。 (物性) 無色結晶(mp.220 ℃) PMR(DMSO-d6,δ ppm) :11.60(1H,brs),8.46(1H,brs),7.
77(2H,m),7.65(2H,s),7.49(1H,s),7.26(2H,t,J=8.8Hz),
1.43(18H,s) IR(KBr, cm-1):3620,3510,3230,2956,1646,1606,1558,1
510,1306,1237,1156,1068,834
Example 2 4-Fluorobenzaldehyde 3,5-di-t-butyl-4-hydroxybenzoyl hydrazone
roxybenzoylhydrazone) Compound 3,5-di-t-butyl-4 synthesized in Reference Example 1.
-Hydroxybenzohydrazide 0.53 g (2 mmol) and 4-
0.22 ml (2 mmol) of fluorobenzaldehyde in ethanol
It was dissolved in 5 ml and stirred at room temperature for 5 hours. The precipitated crystals were collected by filtration and washed with ethanol. Drying under reduced pressure gave 0.63 g (yield 85%) of the title compound. (Physical properties) Colorless crystals (mp. 220 ° C) PMR (DMSO-d 6 , δ ppm): 11.60 (1H, brs), 8.46 (1H, brs), 7.
77 (2H, m), 7.65 (2H, s), 7.49 (1H, s), 7.26 (2H, t, J = 8.8Hz),
1.43 (18H, s) IR (KBr, cm -1 ): 3620,3510,3230,2956,1646,1606,1558,1
510,1306,1237,1156,1068,834

【0106】実施例3〜49 ベンズアルデヒド又は4−フルオロベンズアルデヒドを
他のアルデヒド化合物又はケトン化合物に代える以外は
実施例1又は2と実質的に同様に処理して、以下の化合
物を製造した。
Examples 3-49 The following compounds were prepared by treating substantially the same as in Examples 1 or 2 except that benzaldehyde or 4-fluorobenzaldehyde was replaced with another aldehyde compound or ketone compound.

【0107】実施例3 4−クロロベンズアルデヒド
3,5−ジ−t−ブチル−4−ヒドロキシベンゾイルヒ
ドラゾン(4-chlorobenzaldehyde 3,5-di-t-butyl-4-hyd
roxybenzoylhydrazone) 収率:72% (物性) 無色結晶(mp.260-261 ℃) PMR(DMSO-d6,δ ppm) :11.65(1H,brs),8.45(1H,brs),7.
73(2H,d,J=7.3Hz),7.65(2H,s),7.50-7.48(3H,m),1.43(1
8H,s) IR(KBr, cm-1):3618,3216,2958,1642,1539,1241
Example 3 4-chlorobenzaldehyde 3,5-di-t-butyl-4-hyd hydrazone
Roxybenzoylhydrazone) Yield: 72% (Physical Properties) colorless crystals (mp.260-261 ℃) PMR (DMSO- d 6, δ ppm): 11.65 (1H, brs), 8.45 (1H, brs), 7.
73 (2H, d, J = 7.3Hz), 7.65 (2H, s), 7.50-7.48 (3H, m), 1.43 (1
8H, s) IR (KBr, cm -1 ): 3618,3216,2958,1642,1539,1241

【0108】実施例4 4−ブロモベンズアルデヒド
3,5−ジ−t−ブチル−4−ヒドロキシベンゾイルヒ
ドラゾン(4-bromobenzaldehyde 3,5-di-t-butyl-4-hydr
oxybenzoylhydrazone) 収率:75% (物性) 無色結晶(mp.264-265 ℃) PMR(DMSO-d6,δ ppm) :11.66(1H,s),8.43(1H,s),7.65-
7.62(6H,m),7.50(1H,s),1.43(18H,s) IR(KBr, cm-1):3612,3450,3216,2956,1642,1601,1544,1
303,1240,1071
Example 4 4-bromobenzaldehyde 3,5-di-t-butyl-4-hydr
Oxybenzoylhydrazone) Yield: 75% (Physical Properties) colorless crystals (mp.264-265 ℃) PMR (DMSO- d 6, δ ppm): 11.66 (1H, s), 8.43 (1H, s), 7.65-
7.62 (6H, m), 7.50 (1H, s), 1.43 (18H, s) IR (KBr, cm -1 ): 3612,3450,3216,2956,1642,1601,1544,1
303,1240,1071

【0109】実施例5 4−ヒドロキシベンズアルデヒ
ド3,5−ジ−t−ブチル−4−ヒドロキシベンゾイル
ヒドラゾン(p-hydroxybenzaldehyde 3,5-di-t-butyl-4-
hydroxybenzoylhydrazone) 収率:92% (物性) 無色結晶(mp.290-295 ℃(dec.)) PMR(DMSO-d6,δ ppm) :11.39(1H,brs),9.85(1H,brs),8.
34(1H,brs),7.62(2H,s),7.54(2H,d,J=7.8Hz),7.46(1H,
s),6.83(2H,d,J=7.8Hz),1.43(18H,s) IR(KBr, cm-1):3620,3380,2960,1636,1604,1558,1518,1
436,1313,1275,1239,1170
Example 5 4-Hydroxybenzaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone
hydroxybenzoylhydrazone) Yield: 92% (physical properties) Colorless crystals (mp. 290-295 ° C (dec.)) PMR (DMSO-d 6 , δ ppm): 11.39 (1H, brs), 9.85 (1H, brs), 8 .
34 (1H, brs), 7.62 (2H, s), 7.54 (2H, d, J = 7.8Hz), 7.46 (1H,
s), 6.83 (2H, d, J = 7.8Hz), 1.43 (18H, s) IR (KBr, cm -1 ): 3620,3380,2960,1636,1604,1558,1518,1
436,1313,1275,1239,1170

【0110】実施例6 p−アニスアルデヒド3,5−
ジ−t−ブチル−4−ヒドロキシベンゾイルヒドラゾン
(p-anisaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhyd
razone) 収率:81% (物性) 無色結晶(mp.244-246 ℃) PMR(DMSO-d6,δ ppm) :11.46(1H,brs),8.40(1H,s),7.67
(2H,s),7.64(2H,d,J=6.8Hz),7.46(1H,s),7. 00(2H,d,J=
8.3Hz),3.81(3H,s),1.43(18H,s) IR(KBr, cm-1):3590,3200,2958,1651,1514,1306,1248,1
180,1023,840
Example 6 p-anisaldehyde 3,5-
Di-t-butyl-4-hydroxybenzoylhydrazone
(p-anisaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhyd
Razone) Yield: 81% (Physical Properties) colorless crystals (mp.244-246 ℃) PMR (DMSO- d 6, δ ppm): 11.46 (1H, brs), 8.40 (1H, s), 7.67
(2H, s), 7.64 (2H, d, J = 6.8Hz), 7.46 (1H, s), 7.00 (2H, d, J =
(8.3Hz), 3.81 (3H, s), 1.43 (18H, s) IR (KBr, cm -1 ): 3590,3200,2958,1651,1514,1306,1248,1
180,1023,840

【0111】実施例7 4−ジメチルアミノベンズアル
デヒド3,5−ジ−t−ブチル−4−ヒドロキシベンゾ
イルヒドラゾン(4-dimethylaminobenzaldehyde 3,5-di-
t-butyl-4-hydroxybenzoylhydrazone) 収率:94% (物性) 淡黄色結晶(mp.225-227 ℃) PMR(DMSO-d6,δ ppm) :11.30(1H,s),8.30(1H,s),7.61(2
H,s),7.53(2H,d,J=8.8Hz),7.44(1H,s),6.75 (2H,d,J=8.
8Hz),2.98(6H,s),1.43(18H,s) IR(KBr, cm-1):3598,3450,3230,2954,1647,1602,1525,,
1436,1364,1303,1237,1184
Example 7 4-dimethylaminobenzaldehyde 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone
t-butyl-4-hydroxybenzoylhydrazone) Yield: 94% (physical properties) pale yellow crystal (mp.225-227 ° C) PMR (DMSO-d 6 , δ ppm): 11.30 (1H, s), 8.30 (1H, s ), 7.61 (2
H, s), 7.53 (2H, d, J = 8.8Hz), 7.44 (1H, s), 6.75 (2H, d, J = 8.
8Hz), 2.98 (6H, s), 1.43 (18H, s) IR (KBr, cm -1 ): 3598,3450,3230,2954,1647,1602,1525 ,,
1436,1364,1303,1237,1184

【0112】実施例8 4−ニトロベンズアルデヒド
3,5−ジ−t−ブチル−4−ヒドロキシベンゾイルヒ
ドラゾン(4-nitrobenzaldehyde 3,5-di-t-butyl-4-hydr
oxybenzoylhydrazone) 収率:75% (物性) 淡黄色結晶(mp.284−287 ℃) PMR(DMSO-d6,δ ppm) :11.91(1H,brs),8.56(1H,brs),8.
29(2H,d,J=8.3Hz),7.98(2H,brd,J=7.3Hz),7.68(2H,s),
7.57(1H,s),1.44(18H,s) IR(KBr, cm-1):3618,3425,3214,2958,1645,1520,1344,1
239,1155
Example 8 4-nitrobenzaldehyde 3,5-di-t-butyl-4-hydr
(oxybenzoylhydrazone) Yield: 75% (physical properties) pale yellow crystal (mp. 284-287 ° C) PMR (DMSO-d 6 , δ ppm): 11.91 (1H, brs), 8.56 (1H, brs), 8.
29 (2H, d, J = 8.3Hz), 7.98 (2H, brd, J = 7.3Hz), 7.68 (2H, s),
7.57 (1H, s), 1.44 (18H, s) IR (KBr, cm -1 ): 3618,3425,3214,2958,1645,1520,1344,1
239,1155

【0113】実施例9 4−シアノベンズアルデヒド
3,5−ジ−t−ブチル−4−ヒドロキシベンゾイルヒ
ドラゾン(4-cyanobenzaldehyde 3,5-di-t-butyl-4-hydr
oxybenzoylhydrazone) 収率:85% (物性) 無色結晶(mp.274-275 ℃) PMR(CDCl3,δ ppm) :9.30(1H,brs),8.45(1H,brs),7.82
(2H,d,J=6.8Hz),7.73(2H,brs),7.68(2H,d,J= 8.3Hz),5.
68(1H,s),1.48(18H,s) IR(KBr, cm-1):3450,3214,2956,1643,1540,1437,1361,1
303,1242
Example 9 4-cyanobenzaldehyde 3,5-di-t-butyl-4-hydr
(oxybenzoylhydrazone) Yield: 85% (physical properties) Colorless crystals (mp.274-275 ° C) PMR (CDCl 3 , δ ppm): 9.30 (1H, brs), 8.45 (1H, brs), 7.82
(2H, d, J = 6.8Hz), 7.73 (2H, brs), 7.68 (2H, d, J = 8.3Hz), 5.
68 (1H, s), 1.48 (18H, s) IR (KBr, cm -1 ): 3450,3214,2956,1643,1540,1437,1361,1
303,1242

【0114】実施例10 4−フェニルベンズアルデヒ
ド3,5−ジ−t−ブチル−4−ヒドロキシベンゾイル
ヒドラゾン(4-phenylbenzaldehyde 3,5-di-t-butyl-4-h
ydroxybenzoylhydrazone) 収率:82% (物性) 無色結晶(mp.268 ℃) PMR(CDCl3,δ ppm) :9.04(1H,brs),8.40(1H,brs),7.82
(2H,brs),7.69(2H,brs),7.66-7.61(4H,m),7.46(2H,t,J=
7.8Hz),7.37(1H,t,J=7.3Hz),5.64(1H,s),1.49(18H,s) IR(KBr, cm-1):3450,1649,1556,1308,1254,1238,1073,7
70
Example 10 4-phenylbenzaldehyde 3,5-di-t-butyl-4-h
ydroxybenzoylhydrazone) Yield: 82% (physical properties) Colorless crystal (mp.268 ° C) PMR (CDCl 3 , δ ppm): 9.04 (1H, brs), 8.40 (1H, brs), 7.82
(2H, brs), 7.69 (2H, brs), 7.66-7.61 (4H, m), 7.46 (2H, t, J =
7.8Hz), 7.37 (1H, t, J = 7.3Hz), 5.64 (1H, s), 1.49 (18H, s) IR (KBr, cm -1 ): 3450,1649,1556,1308,1254,1238, 1073,7
70

【0115】実施例11 アセトフェノン3,5−ジ−
t−ブチル−4−ヒドロキシベンゾイルヒドラゾン(a
cetophenone 3,5−di−t−buty
l−4−hydroxybenzoylhydrazo
ne) 収率:63% (物性) 無色結晶(mp.208 ℃) PMR(DMSO-d6,δ ppm) :10.60(1H,s),7.81(2H,brs),7.62
(2H,s),7.47(1H,s),7.40(3H,brs),2.34(3H,s),1.43(18
H,s) IR(KBr, cm-1):3616,3168,2960,1642,1373,1235,760
Example 11 Acetophenone 3,5-di-
t-butyl-4-hydroxybenzoylhydrazone (a
cetophenone 3,5-di-t-butyl
l-4-hydroxybenzoylhydrazo
ne) Yield: 63% (Physical Properties) colorless crystals (mp.208 ℃) PMR (DMSO- d 6, δ ppm): 10.60 (1H, s), 7.81 (2H, brs), 7.62
(2H, s), 7.47 (1H, s), 7.40 (3H, brs), 2.34 (3H, s), 1.43 (18
H, s) IR (KBr, cm -1 ): 3616,3168,2960,1642,1373,1235,760

【0116】実施例12 プロピオフェノン3,5−ジ
−t−ブチル−4−ヒドロキシベンゾイルヒドラゾン(p
ropiophenone 3,5-di-t-butyl-4-hydroxybenzoylhydraz
one) 収率:72% (物性) 無色結晶(mp.181-182 ℃) PMR(DMSO-d6,δ ppm) :10.65(1H,brs),7.78(2H,brs),7.
59(2H,s),7.46(1H,s),7.39(3H,brs),2.90(2H,q,J=7.3H
z),1.43(18H,s),1.10(3H,t,J=7.3Hz) IR(KBr, cm-1):3616,2956,1642,1375,1233,768
Example 12 Propiophenone 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone (p
ropiophenone 3,5-di-t-butyl-4-hydroxybenzoylhydraz
one) Yield: 72% (Physical Properties) colorless crystals (mp.181-182 ℃) PMR (DMSO- d 6, δ ppm): 10.65 (1H, brs), 7.78 (2H, brs), 7.
59 (2H, s), 7.46 (1H, s), 7.39 (3H, brs), 2.90 (2H, q, J = 7.3H
z), 1.43 (18H, s), 1.10 (3H, t, J = 7.3Hz) IR (KBr, cm -1 ): 3616,2956,1642,1375,1233,768

【0117】実施例13 n−ブチロフェノン3,5−
ジ−t−ブチル−4−ヒドロキシベンゾイルヒドラゾン
(n-butyrophenone 3,5-di-t-butyl-4-hydroxybenzoylhy
drazone) 収率:75% (物性) 無色結晶(mp.174-176 ℃) PMR(DMSO-d6,δ ppm) :10.65(1H,brs),7.78(2H,brs),7.
58(2H,s),7.48(1H,s),7.39(3H,brs),2.89(2H,brt,J=7.8
Hz),1.54(2H,q,J=7.5Hz),1.42(18H,s),0.98(3H,t,J=7.3
Hz) IR(KBr, cm-1):3614,3450,3174,2962,1640,1448,1377,1
314,1234,1120,767,693
Example 13 n-butyrophenone 3,5-
Di-t-butyl-4-hydroxybenzoylhydrazone
(n-butyrophenone 3,5-di-t-butyl-4-hydroxybenzoylhy
(drazone) Yield: 75% (physical properties) Colorless crystals (mp. 174-176 ° C) PMR (DMSO-d 6 , δ ppm): 10.65 (1H, brs), 7.78 (2H, brs), 7.
58 (2H, s), 7.48 (1H, s), 7.39 (3H, brs), 2.89 (2H, brt, J = 7.8
Hz), 1.54 (2H, q, J = 7.5 Hz), 1.42 (18H, s), 0.98 (3H, t, J = 7.3
Hz) IR (KBr, cm -1 ): 3614,3450,3174,2962,1640,1448,1377,1
314,1234,1120,767,693

【0118】実施例14 イソブチロフェノン3,5−
ジ−t−ブチル−4−ヒドロキシベンゾイルヒドラゾン
(isobutyrophenone 3,5-di-t-butyl-4-hydroxybenzoylh
ydrazone) 収率:49% (物性) 無色結晶(mp.124-125 ℃) PMR(DMSO-d6,δ ppm) :9.06(1H,brs),7.55(2H,t,J=7.3H
z),7.51-7.48(2H,m),7.34(2H,d,J=7.3Hz),7.22(2H,br
s),2.92-2.88(1H,m),1.31(18H,s),1.12(6H,d,J=6.8Hz) IR(KBr, cm-1):3368,2958,1666,1506,1434,1238,773,70
8
Example 14 Isobutyrophenone 3,5-
Di-t-butyl-4-hydroxybenzoylhydrazone
(isobutyrophenone 3,5-di-t-butyl-4-hydroxybenzoylh
ydrazone) Yield: 49% (Physical properties) Colorless crystals (mp. 124-125 ° C) PMR (DMSO-d 6 , δ ppm): 9.06 (1H, brs), 7.55 (2H, t, J = 7.3H)
z), 7.51-7.48 (2H, m), 7.34 (2H, d, J = 7.3Hz), 7.22 (2H, br
s), 2.92-2.88 (1H, m), 1.31 (18H, s), 1.12 (6H, d, J = 6.8Hz) IR (KBr, cm -1 ): 3368,2958,1666,1506,1434,1238 , 773,70
8

【0119】実施例15 サリチルアルデヒド3,5−
ジ−t−ブチル−4−ヒドロキシベンゾイルヒドラゾン
(salicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhy
drazone) 収率:50% (物性) 無色結晶(mp.275-276 ℃) PMR(DMSO-d6,δ ppm) :11.85(1H,s),11.46(1H,s),8.63
(1H,s),7.69(2H,s),7.55(1H,s),7.49(1H,d,J=6.8Hz),7.
28(1H,d,J=7.6Hz),6.94-6.89(2H,m),1.44(18H,s) IR(KBr, cm-1):3600,3222,2962,1645,1550,1361,1307,1
275,1238,1152,753
Example 15 Salicylaldehyde 3,5-
Di-t-butyl-4-hydroxybenzoylhydrazone
(salicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhy
(drazone) Yield: 50% (physical properties) Colorless crystals (mp. 275-276 ° C) PMR (DMSO-d 6 , δ ppm): 11.85 (1H, s), 11.46 (1H, s), 8.63
(1H, s), 7.69 (2H, s), 7.55 (1H, s), 7.49 (1H, d, J = 6.8Hz), 7.
28 (1H, d, J = 7.6Hz), 6.94-6.89 (2H, m), 1.44 (18H, s) IR (KBr, cm -1 ): 3600,3222,2962,1645,1550,1361,1307, 1
275,1238,1152,753

【0120】実施例16 3−ヒドロキシベンズアルデ
ヒド3,5−ジ−t−ブチル−4−ヒドロキシベンゾイ
ルヒドラゾン(3-hydroxybenzaldehyde 3,5-di-t-butyl-
4-hydroxybenzoylhydrazone) 収率:100% (物性) 無色結晶(mp.265-266 ℃) PMR(DMSO-d6,δ ppm) :11.52(1H,br
s),9.56(1H,brs),8.36(1H,
s),7.64(2H,s),7.48(1H,s),
7.25−7.19(2H,m),7.08(1H,
d,J=7.8Hz),6.81(1H,d,J=7.
3Hz),1.43(18H,s) IR(KBr, cm−1):3592,3400,3
230,2968,1646,1557,1242
Example 16 3-hydroxybenzaldehyde 3,5-di-t-butyl-hydroxybenzoyl hydrazone
4-hydroxybenzoylhydrazone) Yield: 100% (physical properties) of colorless crystals (mp.265-266 ℃) PMR (DMSO- d 6, δ ppm): 11.52 (1H, br
s), 9.56 (1H, brs), 8.36 (1H,
s), 7.64 (2H, s), 7.48 (1H, s),
7.25-7.19 (2H, m), 7.08 (1H,
d, J = 7.8 Hz), 6.81 (1H, d, J = 7.
3Hz), 1.43 (18H, s) IR (KBr, cm -1 ): 3592, 3400, 3
230, 2968, 1646, 1557, 1242

【0121】実施例17 o−アニスアルデヒド3,5
−ジ−t−ブチル−4−ヒドロキシベンゾイルヒドラゾ
ン(o−anisaldehyde 3,5−di−t
−butyl−4−hydroxybenzoylhy
drazone) 収率:35% (物性) 無色結晶(mp.250-251 ℃) PMR(DMSO-d6,δ ppm) :11.59(1H,brs),8.80(1H,brs),7.
89(1H,d,J=7.3Hz),7.66(2H,s),7.46(1H,s), 7.40(1H,t,
J=7.6Hz),7.09(1H,d,J=8.3Hz),7.01(1H,brt),3.88(3H,
s),1.43(18H,s) IR(KBr, cm-1):3594,3450,3246,2958,1656,1607,1553,1
436,1366,1304,1253,752
Example 17 o-anisaldehyde 3,5
-Di-t-butyl-4-hydroxybenzoylhydrazone (o-anisaldehyde 3,5-di-t
-Butyl-4-hydroxybenzoylhy
Drazone) Yield: 35% (Physical Properties) colorless crystals (mp.250-251 ℃) PMR (DMSO- d 6, δ ppm): 11.59 (1H, brs), 8.80 (1H, brs), 7.
89 (1H, d, J = 7.3Hz), 7.66 (2H, s), 7.46 (1H, s), 7.40 (1H, t,
J = 7.6Hz), 7.09 (1H, d, J = 8.3Hz), 7.01 (1H, brt), 3.88 (3H,
s), 1.43 (18H, s) IR (KBr, cm -1 ): 3594,3450,3246,2958,1656,1607,1553,1
436,1366,1304,1253,752

【0122】実施例18 o−アセチルサリチルアルデ
ヒド3,5−ジ−t−ブチル−4−ヒドロキシベンゾイ
ルヒドラゾン(o-acetylsalicylaldehyde 3,5-di-t-buty
l-4-hydroxybenzoylhydrazone) 収率:79% (物性) 無色結晶(mp.246-248 ℃) PMR(DMSO-d6,δ ppm) :11.61(1H,brs),8.43(1H,brs),7.
83(1H,d,J=7.8Hz),7.64(2H,s),7.52(1H,s), 7.46(1H,t,
J=7.3Hz),7.35(1H,t,J=6.8Hz),7.18(1H,d,J=7.8Hz),2.4
1(3H,s),1.43(18H,s) IR(KBr, cm-1):3582,3192,2956,1754,1652,1553,1363,1
306,1243
Example 18 o-acetylsalicylaldehyde 3,5-di-t-buty
l-4-hydroxybenzoylhydrazone) Yield: 79% (Physical properties) Colorless crystals (mp.246-248 ° C) PMR (DMSO-d 6 , δ ppm): 11.61 (1H, brs), 8.43 (1H, brs), 7 .
83 (1H, d, J = 7.8Hz), 7.64 (2H, s), 7.52 (1H, s), 7.46 (1H, t,
J = 7.3Hz), 7.35 (1H, t, J = 6.8Hz), 7.18 (1H, d, J = 7.8Hz), 2.4
1 (3H, s), 1.43 (18H, s) IR (KBr, cm -1 ): 3582,3192,2956,1754,1652,1553,1363,1
306,1243

【0123】実施例19 o−トルアルデヒド3,5−
ジ−t−ブチル−4−ヒドロキシベンゾイルヒドラゾン
(o-tolualdehyde 3,5-di-t-butyl-4-hydroxybenzoylhyd
razone) 収率:86% (物性) 無色結晶(mp.257-258 ℃) PMR(DMSO-d6,δ ppm) :11.58(1H,s),8.72(1H,s),7.84(1
H,brd),7.65(2H,s),7.50(1H,s),7.30-7.23(3H,m),2.46
(3H,s),1.44(18H,s) IR(KBr, cm-1):3620,3430,3224,2958,1647,1554,1437,1
366,1306,1241,758
Example 19 o-Tolualdehyde 3,5-
Di-t-butyl-4-hydroxybenzoylhydrazone
(o-tolualdehyde 3,5-di-t-butyl-4-hydroxybenzoylhyd
razone) Yield: 86% (physical properties) Colorless crystals (mp. 257-258 ° C) PMR (DMSO-d 6 , δ ppm): 11.58 (1H, s), 8.72 (1H, s), 7.84 (1
H, brd), 7.65 (2H, s), 7.50 (1H, s), 7.30-7.23 (3H, m), 2.46
(3H, s), 1.44 (18H, s) IR (KBr, cm -1 ): 3620,3430,3224,2958,1647,1554,1437,1
366,1306,1241,758

【0124】実施例20 2−ニトロベンズアルデヒド
3,5−ジ−t−ブチル−4−ヒドロキシベンゾイルヒ
ドラゾン(2-nitrobenzaldehyde 3,5-di-t-butyl-4-hydr
oxybenzoylhydrazone) 収率:79% (物性) 無色結晶(mp.218-219 ℃) PMR(DMSO-d6,δ ppm) :11.95(1H,s),8.86(1H,s),8.15(1
H,brd),8.06(1H,d,J=8.3Hz),7.80(1H,brt), 7.67-7.64
(3H,m),7.54(1H,s),1.44(18H,s) IR(KBr, cm-1):3626,3250,2956,1651,1527,1346,1302,1
238,1160
Example 20 2-nitrobenzaldehyde 3,5-di-t-butyl-4-hydr-4-hydroxybenzoylhydrazone
(oxybenzoylhydrazone) Yield: 79% (physical properties) Colorless crystals (mp. 218-219 ° C) PMR (DMSO-d 6 , δ ppm): 11.95 (1H, s), 8.86 (1H, s), 8.15 (1
H, brd), 8.06 (1H, d, J = 8.3Hz), 7.80 (1H, brt), 7.67-7.64
(3H, m), 7.54 (1H, s), 1.44 (18H, s) IR (KBr, cm -1 ): 3626,3250,2956,1651,1527,1346,1302,1
238,1160

【0125】実施例21 2−フルオロベンズアルデヒ
ド3,5−ジ−t−ブチル−4−ヒドロキシベンゾイル
ヒドラゾン(2-fluorobenzaldehyde 3,5-di-t-butyl-4-h
ydroxybenzoylhydrazone) 収率:22% (物性) 無色結晶(mp.192-193 ℃) PMR(DMSO-d6,δ ppm) :11.71(1H,s),8.71(1H,s),7.96(1
H,brs),7.67(2H,s),7.51(1H,s),7.48-7.44(1H,m),7.30-
7.24(2H,m),1.44(18H,s) IR(KBr, cm-1):3622,3228,2956,1646,1543,1438,1363,1
303,1238,759
Example 21 2-fluorobenzaldehyde 3,5-di-t-butyl-4-h
Ydroxybenzoylhydrazone) Yield: 22% (Physical Properties) colorless crystals (mp.192-193 ℃) PMR (DMSO- d 6, δ ppm): 11.71 (1H, s), 8.71 (1H, s), 7.96 (1
H, brs), 7.67 (2H, s), 7.51 (1H, s), 7.48-7.44 (1H, m), 7.30-
7.24 (2H, m), 1.44 (18H, s) IR (KBr, cm -1 ): 3622,3228,2956,1646,1543,1438,1363,1
303,1238,759

【0126】実施例22 2−シアノベンズアルデヒド
3,5−ジ−t−ブチル−4−ヒドロキシベンゾイルヒ
ドラゾン(2-cyanobenzaldehyde 3,5-di-t-butyl-4-hydr
oxybenzoylhydrazone) 収率:42% (物性) 淡黄色結晶(mp.200-201 ℃) PMR(DMSO-d6,δ ppm) :11.98(1H,s),8.83(1H,s),8.14(1
H,s),7.88(1H,d,J=7.8Hz),7.77(1H,t,J=7.6Hz),7.68(2
H,s),7.59(1H,t,J=7.6Hz),7.54(1H,s),1.44(18H,s) IR(KBr, cm-1):3624,3214,2958,2226,1653,1541,1437,1
364,1302,1239,1160,766
Example 22 2-cyanobenzaldehyde 3,5-di-t-butyl-4-hydr
(oxybenzoylhydrazone) Yield: 42% (Physical properties) Pale yellow crystal (mp.200-201 ° C) PMR (DMSO-d 6 , δ ppm): 11.98 (1H, s), 8.83 (1H, s), 8.14 (1
H, s), 7.88 (1H, d, J = 7.8Hz), 7.77 (1H, t, J = 7.6Hz), 7.68 (2
H, s), 7.59 (1H, t, J = 7.6Hz), 7.54 (1H, s), 1.44 (18H, s) IR (KBr, cm -1 ): 3624,3214,2958,2226,1653,1541 , 1437,1
364,1302,1239,1160,766

【0127】実施例23 α−テトラロン3,5−ジ−
t−ブチル−4−ヒドロキシベンゾイルヒドラゾン(α
-tetralone 3,5-di-t-butyl-4-hydroxybenzoylhydrazon
e) 収率:75% (物性) 無色結晶(mp.235-237 ℃) PMR(DMSO-d6,δ ppm) :10.52(1H,s),8.06(1H,brs),7.62
(2H,s),7.45(1H,s),7.29-7.18(3H,m),2.79-2.73(4H,m),
1.89-1.85(2H,m),1.43(18H,s) IR(KBr, cm-1):3624,3170,2954,1641,1376,1314,1242,1
133,762
Example 23 α-tetralone 3,5-di-
t-butyl-4-hydroxybenzoylhydrazone (α
-tetralone 3,5-di-t-butyl-4-hydroxybenzoylhydrazon
e) Yield: 75% (Physical Properties) colorless crystals (mp.235-237 ℃) PMR (DMSO- d 6, δ ppm): 10.52 (1H, s), 8.06 (1H, brs), 7.62
(2H, s), 7.45 (1H, s), 7.29-7.18 (3H, m), 2.79-2.73 (4H, m),
1.89-1.85 (2H, m), 1.43 (18H, s) IR (KBr, cm- 1 ): 3624,3170,2954,1641,1376,1314,1242,1
133,762

【0128】実施例24 o−ヒドロキシアセトフェノ
ン3,5−ジ−t−ブチル−4−ヒドロキシベンゾイル
ヒドラゾン(o-hydroxyacetophenone 3,5-di-t-butyl-4-
hydroxybenzoylhydrazone) 収率:80% (物性) 無色結晶(mp.218-219 ℃) PMR(DMSO-d6,δ ppm) :13.42(1H,brs),11.14(1H,brs),
7.65(2H,s),7.61(1H,d,J=7.3Hz),7.56(1H,s),7.31-7.26
(2H,m),2.46(3H,s),1.44(18H,s) IR(KBr, cm-1):3600,3250,2956,1640,1603,1522,1435,1
302,1154,755
Example 24 o-Hydroxyacetophenone 3,5-di-t-butyl-4-o-hydroxyacetophenone 3,5-di-t-butyl-4-
hydroxybenzoylhydrazone) Yield: 80% (physical properties) Colorless crystals (mp. 218-219 ° C) PMR (DMSO-d 6 , δ ppm): 13.42 (1H, brs), 11.14 (1H, brs),
7.65 (2H, s), 7.61 (1H, d, J = 7.3Hz), 7.56 (1H, s), 7.31-7.26
(2H, m), 2.46 (3H, s), 1.44 (18H, s) IR (KBr, cm -1 ): 3600,3250,2956,1640,1603,1522,1435,1
302,1154,755

【0129】実施例25 2,4−ジヒドロキシベンズ
アルデヒド3,5−ジ−t−ブチル−4−ヒドロキシベ
ンゾイルヒドラゾン(2,4-dihydroxybenzaldehyde 3,5-d
i-t-butyl-4-hydroxybenzoylhydrazone) 収率:87% (物性) 無色結晶(mp.261−264 ℃) PMR(DMSO-d6,δ ppm) :11.64(1H,s),11.63(1H,s),9.87
(1H,s),8.48(1H,s),7.66(2H,s),7.49(1H,s),7. 24(1H,
d,J=8.3Hz),6.35(1H,d,J=8.8Hz),6.31(1H,s),1.43(18H,
s) IR(KBr, cm-1):3600,3214,2958,1634,1515,1436,1305,1
244
Example 25 2,4-Dihydroxybenzaldehyde 3,5-d-tert-butyl-4-hydroxybenzoylhydrazone
it-butyl-4-hydroxybenzoylhydrazone) Yield: 87% (physical properties) Colorless crystal (mp. 261-264 ° C) PMR (DMSO-d 6 , δ ppm): 11.64 (1H, s), 11.63 (1H, s) , 9.87
(1H, s), 8.48 (1H, s), 7.66 (2H, s), 7.49 (1H, s), 7.24 (1H, s
d, J = 8.3Hz), 6.35 (1H, d, J = 8.8Hz), 6.31 (1H, s), 1.43 (18H,
s) IR (KBr, cm -1 ): 3600,3214,2958,1634,1515,1436,1305,1
244

【0130】実施例26 2,3−ジヒドロキシベンズ
アルデヒド3,5−ジ−t−ブチル−4−ヒドロキシベ
ンゾイルヒドラゾン(2,3-dihydroxybenzaldehyde 3,5-d
i-t-butyl-4-hydroxybenzoylhydrazone) 収率:61% (物性) 無色結晶(mp.273-275 ℃) PMR(DMSO-d6,δ ppm) :11.83(1H,s),11.37(1H,s),9.11
(1H,s),8.58(1H,s),7.68(2H,s),7.54(1H,s),6. 91(1H,
d,J=7.8Hz),6.84(1H,d,J=7.8Hz),6.73(1H,t,J=7.8Hz),
1.44(18H,s) IR(KBr, cm-1):3610,3222,2962,1643,1549,1361,1307,1
263,1239,732
Example 26 2,3-dihydroxybenzaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone
it-butyl-4-hydroxybenzoylhydrazone) Yield: 61% (Physical Properties) colorless crystals (mp.273-275 ℃) PMR (DMSO- d 6, δ ppm): 11.83 (1H, s), 11.37 (1H, s) , 9.11
(1H, s), 8.58 (1H, s), 7.68 (2H, s), 7.54 (1H, s), 6.91 (1H,
d, J = 7.8Hz), 6.84 (1H, d, J = 7.8Hz), 6.73 (1H, t, J = 7.8Hz),
1.44 (18H, s) IR (KBr, cm -1 ): 3610,3222,2962,1643,1549,1361,1307,1
263,1239,732

【0131】実施例27 5−ニトロサリチルアルデヒ
ド3,5−ジ−t−ブチル−4−ヒドロキシベンゾイル
ヒドラゾン(5-nitrosalicylaldehyde 3,5-di-t-butyl-4
-hydroxybenzoylhydrazone) 収率:74% (物性) 無色結晶(mp.265-267 ℃) PMR(DMSO-d6,δ ppm) :12.47(1H,brs),12.04(1H,s),8.7
3(1H,s),8.56(1H,s),8.16(1H,d,J=8.8Hz),7.70(2H,s),
7.57(1H,s),7.11(1H,d,J=8.8Hz),1.44(18H,s) IR(KBr, cm-1):3598,2958,1646,1522,1481,1342,1307,1
241
Example 27 5-nitrosalicylaldehyde 3,5-di-t-butyl-4
-Hydroxybenzoylhydrazone) Yield: 74% (Physical properties) Colorless crystal (mp.265-267 ° C) PMR (DMSO-d 6 , δ ppm): 12.47 (1H, brs), 12.04 (1H, s), 8.7
3 (1H, s), 8.56 (1H, s), 8.16 (1H, d, J = 8.8Hz), 7.70 (2H, s),
7.57 (1H, s), 7.11 (1H, d, J = 8.8Hz), 1.44 (18H, s) IR (KBr, cm -1 ): 3598,2958,1646,1522,1481,1342,1307,1
241

【0132】実施例28 2−ヒドロキシ−5−メトキ
シベンズアルデヒド3,5−ジ−t−ブチル−4−ヒド
ロキシベンゾイルヒドラゾン(2-hydroxy-5-methoxybenz
aldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone) 収率:84% (物性) 無色結晶(mp.283-284 ℃) PMR(DMSO-d6,δ ppm) :11.83(1H,s),10.83(1H,s),8.60
(1H,s),7.68(2H,s),7.53(1H,s),7.07(1H,d,J=2.5Hz),6.
91-6.83(2H,m),3.74(3H,s),1.44(18H,s) IR(KBr, cm-1):3614,3238,2962,1644,1551,1496,1268,1
240,1159,1039
Example 28 2-Hydroxy-5-methoxybenzaldehyde 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone
aldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone) Yield: 84% (physical properties) colorless crystal (mp.283-284 ° C) PMR (DMSO-d 6 , δ ppm): 11.83 (1H, s) , 10.83 (1H, s), 8.60
(1H, s), 7.68 (2H, s), 7.53 (1H, s), 7.07 (1H, d, J = 2.5Hz), 6.
91-6.83 (2H, m), 3.74 (3H, s), 1.44 (18H, s) IR (KBr, cm -1 ): 3614,3238,2962,1644,1551,1496,1268,1
240,1159,1039

【0133】実施例29 5−クロロサリチルアルデヒ
ド3,5−ジ−t−ブチル−4−ヒドロキシベンゾイル
ヒドラゾン(5-chlorosalicylaldehyde 3,5-di-t-butyl-
4-hydroxybenzoylhydrazone) 収率:78% (物性) 無色結晶(mp.276-277 ℃) PMR(DMSO-d6,δ ppm) :11.95(1H,s),11.43(1H,s),8.60
(1H,s),7.68(2H,s),7.61(1H,s),7.56(1H,s),7.28(1H,d,
J=6.8Hz),6.94(1H,d,J=8.8Hz),1.44(18H,s) IR(KBr, cm-1):3616,3210,2960,1642,1544,1481,1343,1
310,1273,1239
Example 29 5-chlorosalicylaldehyde 3,5-di-t-butyl-
4-hydroxybenzoylhydrazone) Yield: 78% (Physical Properties) colorless crystals (mp.276-277 ℃) PMR (DMSO- d 6, δ ppm): 11.95 (1H, s), 11.43 (1H, s), 8.60
(1H, s), 7.68 (2H, s), 7.61 (1H, s), 7.56 (1H, s), 7.28 (1H, d,
J = 6.8Hz), 6.94 (1H, d, J = 8.8Hz), 1.44 (18H, s) IR (KBr, cm -1 ): 3616,3210,2960,1642,1544,1481,1343,1
310,1273,1239

【0134】実施例30 5−ブロモサリチルアルデヒ
ド3,5−ジ−t−ブチル−4−ヒドロキシベンゾイル
ヒドラゾン(5-bromosalicylaldehyde 3,5-di-t-butyl-4
-hydroxybenzoylhydrazone) 収率:72% (物性) 無色結晶(mp.279-280 ℃) PMR(DMSO-d6,δ ppm) :11.94(1H,
s),11.43(1H,s),8.59(1H,
s),7.74(1H,d,J=1.5Hz),7.6
8(2H,s),7.57(1H,s),7.40(1
H,d,J=8.3Hz),6.89(1H,d,J=
8.8Hz),1.44(18H,s) IR(KBr, cm−1):3614,3206,2
958,1639,1543,1477,1340,1
300,1237,1241
Example 30 5-bromosalicylaldehyde 3,5-di-t-butyl-4
-Hydroxybenzoylhydrazone) Yield: 72% (Physical Properties) colorless crystals (mp.279-280 ℃) PMR (DMSO- d 6, δ ppm): 11.94 (1H,
s), 11.43 (1H, s), 8.59 (1H,
s), 7.74 (1H, d, J = 1.5 Hz), 7.6
8 (2H, s), 7.57 (1H, s), 7.40 (1
H, d, J = 8.3 Hz), 6.89 (1H, d, J =
8.8 Hz), 1.44 (18 H, s) IR (KBr, cm -1 ): 3614, 3206,2
958, 1639, 1543, 1477, 1340, 1
300, 1237, 1241

【0135】実施例31 2−ヒドロキシ−4−メトキ
シベンズアルデヒド3,5−ジ−t−ブチル−4−ヒド
ロキシベンゾイルヒドラゾン(2−hydroxy−4
−methoxybenzaldehyde 3,5−
di−t−butyl−4−hydroxybenzo
ylhydrazone) 収率:98% (物性) 無色結晶(mp.280-281 ℃) PMR(DMSO-d6,δ ppm) :11.78(1H,s),11.73(1H,s),8.53
(1H,s),7.67(2H,s),7.52(1H,s),7.37(1H,d,J=8.3Hz),6.
52-6.49(2H,m),3.78(3H,m),1.43(18H,s) IR(KBr, cm-1):3586,3230,2964,1649,1638,1609,1576,1
511,1436,1362,1292,1240,1164,1143,1029
Example 31 2-hydroxy-4-methoxybenzaldehyde 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone (2-hydroxy-4
-Methoxybenzaldehyde 3,5-
di-t-butyl-4-hydroxybenzo
ylhydrazine) Yield: 98% (physical properties) Colorless crystals (mp. 280-281 ° C) PMR (DMSO-d 6 , δ ppm): 11.78 (1H, s), 11.73 (1H, s), 8.53
(1H, s), 7.67 (2H, s), 7.52 (1H, s), 7.37 (1H, d, J = 8.3Hz), 6.
52-6.49 (2H, m), 3.78 (3H, m), 1.43 (18H, s) IR (KBr, cm -1 ): 3586,3230,2964,1649,1638,1609,1576,1
511,1436,1362,1292,1240,1164,1143,1029

【0136】実施例32 2,5−ジヒドロキシベンズ
アルデヒド3,5−ジ−t−ブチル−4−ヒドロキシベ
ンゾイルヒドラゾン(2,5-dihydroxybenzaldehyde 3,5-d
i-t-butyl-4-hydroxybenzoylhydrazone) 収率:62% (物性) 無色結晶(mp.229-232 ℃) PMR(DMSO-d6,δ ppm) :11.74(1H,s),10.57(1H,s),8.92
(1H,s),8.54(1H,s),7.67(2H,s),7.52(1H,s),6.91(1H,
s),6.76-6.72(2H,m),1.44(18H,s) IR(KBr, cm-1):3610,3222,2958,1644,1550,1492,1438,1
366,1309,1240,1156
Example 32 2,5-Dihydroxybenzaldehyde 3,5-d-t-butyl-4-hydroxybenzoylhydrazone
it-butyl-4-hydroxybenzoylhydrazone) Yield: 62% (physical properties) Colorless crystal (mp.229-232 ° C) PMR (DMSO-d 6 , δ ppm): 11.74 (1H, s), 10.57 (1H, s) , 8.92
(1H, s), 8.54 (1H, s), 7.67 (2H, s), 7.52 (1H, s), 6.91 (1H,
s), 6.76-6.72 (2H, m), 1.44 (18H, s) IR (KBr, cm -1 ): 3610,3222,2958,1644,1550,1492,1438,1
366,1309,1240,1156

【0137】実施例33 o−バニリン3,5−ジ−t
−ブチル−4−ヒドロキシベンゾイルヒドラゾン(o-van
illin 3,5-di-t-butyl-4-hydroxybenzoylhydrazone) 収率:95% (物性) 無色結晶(mp.282-283 ℃) PMR(DMSO-d6,δ ppm) :11.83(1H,s),11.22(1H,s),8.63
(1H,s),7.68(2H,s),7.54(1H,s),7.10(1H,d,J=7.8Hz),7.
01(1H,d,J=7.8Hz),6.86(1H,t,J=8.1Hz),3.82(3H,s),1.4
4(18H,s) IR(KBr, cm-1):3578,3236,2964,1646,1540,1461,1246,7
35
Example 33: o-Vaniline 3,5-di-t
-Butyl-4-hydroxybenzoylhydrazone (o-van
illin 3,5-di-t-butyl -4-hydroxybenzoylhydrazone) Yield: 95% (Physical Properties) colorless crystals (mp.282-283 ℃) PMR (DMSO- d 6, δ ppm): 11.83 (1H, s) , 11.22 (1H, s), 8.63
(1H, s), 7.68 (2H, s), 7.54 (1H, s), 7.10 (1H, d, J = 7.8Hz), 7.
01 (1H, d, J = 7.8Hz), 6.86 (1H, t, J = 8.1Hz), 3.82 (3H, s), 1.4
4 (18H, s) IR (KBr, cm -1 ): 3578,3236,2964,1646,1540,1461,1246,7
35

【0138】実施例34 4−(ジエチルアミノ)サリ
チルアルデヒド3,5−ジ−t−ブチル−4−ヒドロキ
シベンゾイルヒドラゾン(4-(diethylamino)salicylalde
hyde3,5-di-t-butyl-4-hydroxybenzoylhydrazone) 収率:81% (物性) 淡褐色結晶(mp.235-236 ℃) PMR(DMSO-d6,δ ppm) :11.59(1H,s),11.53(1H,s),8.41
(1H,s),7.65(2H,s),7.48(1H,s),7.15(1H,d,J=8.8Hz),6.
25(1H,d,J=8.3Hz),6.12(1H,s),3.36(4H,q,J=6.4Hz),1.4
4(18H,s),1.12(6H,t,J=6.8Hz) IR(KBr, cm-1):3620,3228,1632,1599,1521,1355,1303,1
245,1135
Example 34 4- (Diethylamino) salicylaldehyde 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone (4- (diethylamino) salicylalde)
hyde3,5-di-t-butyl-4-hydroxybenzoylhydrazone) Yield: 81% (Physical properties) Light brown crystal (mp.235-236 ° C) PMR (DMSO-d 6 , δ ppm): 11.59 (1H, s) , 11.53 (1H, s), 8.41
(1H, s), 7.65 (2H, s), 7.48 (1H, s), 7.15 (1H, d, J = 8.8Hz), 6.
25 (1H, d, J = 8.3Hz), 6.12 (1H, s), 3.36 (4H, q, J = 6.4Hz), 1.4
4 (18H, s), 1.12 (6H, t, J = 6.8Hz) IR (KBr, cm -1 ): 3620,3228,1632,1599,1521,1355,1303,1
245,1135

【0139】実施例35 3,5−ジクロロサリチルア
ルデヒド3,5−ジ−t−ブチル−4−ヒドロキシベン
ゾイルヒドラゾン(3,5-dichlorosalicylaldehyde 3,5-d
i-t-butyl-4-hydroxybenzoylhydrazone) 収率:62% (物性) 無色結晶(mp.298 ℃) PMR(DMSO-d6,δ ppm) :12.66(1H,s),12.23(1H,s),8.56
(1H,s),7.70(2H,s),7.62(1H,s),7.59(1H,d,J=2.0Hz),7.
56(1H,d,J=2.0Hz),1.44(18H,s) IR(KBr, cm-1):3616,3418,3218,2960,1641,1539,1452,1
306,1239
Example 35 3,5-Dichlorosalicylaldehyde 3,5-dichlorosalicylaldehyde 3,5-d
it-butyl-4-hydroxybenzoylhydrazone) Yield: 62% (Physical properties) Colorless crystal (mp.298 ° C) PMR (DMSO-d 6 , δ ppm): 12.66 (1H, s), 12.23 (1H, s), 8.56
(1H, s), 7.70 (2H, s), 7.62 (1H, s), 7.59 (1H, d, J = 2.0Hz), 7.
56 (1H, d, J = 2.0Hz), 1.44 (18H, s) IR (KBr, cm -1 ): 3616,3418,3218,2960,1641,1539,1452,1
306,1239

【0140】実施例36 3,5−ジニトロサリチルア
ルデヒド3,5−ジ−t−ブチル−4−ヒドロキシベン
ゾイルヒドラゾン(3,5-dinitrosalicylaldehyde 3,5-di
-t-butyl-4-hydroxybenzoylhydrazone) 収率:88% (物性) 黄色結晶(mp.269-270 ℃) PMR(DMSO-d6,δ ppm) :12.44(1H,brs),8.79(2H,brs),8.
76(1H,s),7.72(2H,s),7.65(1H,s),1.44(18H,s) IR(KBr, cm-1):3565,2965,1680,1620,1535,1345,1225
Example 36 3,5-Dinitrosalicylaldehyde 3,5-di-nitrobutyl-4-hydroxybenzoylhydrazone
-t-butyl-4-hydroxybenzoylhydrazone) Yield: 88% (physical properties) Yellow crystal (mp.269-270 ° C) PMR (DMSO-d 6 , δ ppm): 12.44 (1H, brs), 8.79 (2H, brs ), 8.
76 (1H, s), 7.72 (2H, s), 7.65 (1H, s), 1.44 (18H, s) IR (KBr, cm -1 ): 3565,2965,1680,1620,1535,1345,1225

【0141】実施例37 2−ヒドロキシ−1−ナフト
アルデヒド3,5−ジ−t−ブチル−4−ヒドロキシベ
ンゾイルヒドラゾン(2-hydroxy-1-naphthaldehyde 3,5-
di-t-butyl-4-hydroxybenzoylhydrazone) 収率:85% (物性) 淡褐色結晶(mp.>300℃) PMR(DMSO-d6,δ ppm) :12.96(1H,s),11.94(1H,s),9.48
(1H,s),8.22(1H,d,J=8.8Hz),7.90(1H,t,J=9.0Hz),7.74
(2H,s),7.61-7.56(2H,m),7.40(1H,t,J=7.6Hz),7.23(1H,
d,J=8.8Hz),1.46(18H,s) IR(KBr, cm-1):3612,3188,2958,1640,1602,1329,1242
Example 37 2-hydroxy-1-naphthaldehyde 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone
di-t-butyl-4-hydroxybenzoylhydrazone) Yield: 85% (Physical properties) Light brown crystal (mp.> 300 ℃) PMR (DMSO-d 6 , δ ppm): 12.96 (1H, s), 11.94 (1H, s), 9.48
(1H, s), 8.22 (1H, d, J = 8.8Hz), 7.90 (1H, t, J = 9.0Hz), 7.74
(2H, s), 7.61-7.56 (2H, m), 7.40 (1H, t, J = 7.6Hz), 7.23 (1H,
d, J = 8.8Hz), 1.46 (18H, s) IR (KBr, cm -1 ): 3612,3188,2958,1640,1602,1329,1242

【0142】実施例38 2,4,6−トリヒドロキシ
ベンズアルデヒド3,5−ジ−t−ブチル−4−ヒドロ
キシベンゾイルヒドラゾン(2,4,6-trihydroxybenzaldeh
yde3,5-di-t-butyl-4-hydroxybenzoylhydrazone) 収率:39% (物性) 淡褐色結晶(mp.200 ℃(dec.)) PMR(DMSO-d6,δ ppm) :11.60(1H,s),11.11(2H,brs),9.7
2(1H,brs),8.80(1H,s),7.67(2H,s),7.50(1H,brs),5.84
(2H,s),1.43(18H,s) IR(KBr, cm-1):3616,3225,2962,1640,1614,1525,1463,1
239,1156,1045,828
Example 38 2,4,6-Trihydroxybenzaldehyde 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone (2,4,6-trihydroxybenzaldeh)
yde3,5-di-t-butyl-4-hydroxybenzoylhydrazone) Yield: 39% (physical properties) Light brown crystal (mp. 200 ° C (dec.)) PMR (DMSO-d 6 , δ ppm): 11.60 (1H, s), 11.11 (2H, brs), 9.7
2 (1H, brs), 8.80 (1H, s), 7.67 (2H, s), 7.50 (1H, brs), 5.84
(2H, s), 1.43 (18H, s) IR (KBr, cm -1 ): 3616,3225,2962,1640,1614,1525,1463,1
239,1156,1045,828

【0143】実施例39 4,6−ジメトキシサリチル
アルデヒド3,5−ジ−t−ブチル−4−ヒドロキシベ
ンゾイルヒドラゾン(4,6−dimethoxysa
licylaldehyde 3,5−di−t−bu
tyl−4−hydroxybenzoylhydra
zone) 収率:90% (物性) 淡褐色結晶(mp.303 ℃) PMR(DMSO-d6,δ ppm) :12.55(1H,s),11.75(1H,s),8.83
(1H,s),7.68(2H,s),7.53(1H,s),6.13(2H,s),3. 84(3H,
s),3.79(3H,s),1.43(18H,s) IR(KBr, cm-1):3600,2960,1634,1604,1437,1343,1241,1
213,1156
Example 39 4,6-Dimethoxysalicylaldehyde 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone (4,6-dimethyoxysa)
lycyldehyde 3,5-di-t-bu
tyl-4-hydroxybenzoylhydra
zone) Yield: 90% (physical properties) Light brown crystal (mp. 303 ° C.) PMR (DMSO-d 6 , δ ppm): 12.55 (1H, s), 11.75 (1H, s), 8.83
(1H, s), 7.68 (2H, s), 7.53 (1H, s), 6.13 (2H, s), 3.84 (3H,
s), 3.79 (3H, s), 1.43 (18H, s) IR (KBr, cm -1 ): 3600,2960,1634,1604,1437,1343,1241,1
213,1156

【0144】実施例40 2−メチルアミノベンズアル
デヒド3,5−ジ−t−ブチル−4−ヒドロキシベンゾ
イルヒドラゾン(2-methylaminobenzaldehyde 3,5-di-t-
butyl-4-hydroxybenzoylhydrazone) 収率:28% (物性) 淡黄色結晶(mp.303 ℃) PMR(DMSO-d6,δ ppm) :11.56(1H,s),8.51(1H,s),8.41(1
H,brq,J=4.4Hz),7.68(2H,s),7.50(1H,s),7.26-7.20(2H,
m),6.69(1H,d,J=8.3Hz),6.63(1H,t,J=7.8Hz),2.93(3H,
d,J=4.4Hz),1.44(18H,s) IR(KBr, cm-1):3618,3425,3208,2964,1640,1599,1555,1
418,1370,1304,1241,1117,706
Example 40 2-Methylaminobenzaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone
butyl-4-hydroxybenzoylhydrazone) Yield: 28% (property) pale yellow crystals (mp.303 ℃) PMR (DMSO- d 6, δ ppm): 11.56 (1H, s), 8.51 (1H, s), 8.41 ( 1
H, brq, J = 4.4Hz), 7.68 (2H, s), 7.50 (1H, s), 7.26-7.20 (2H,
m), 6.69 (1H, d, J = 8.3Hz), 6.63 (1H, t, J = 7.8Hz), 2.93 (3H,
d, J = 4.4Hz), 1.44 (18H, s) IR (KBr, cm -1 ): 3618,3425,3208,2964,1640,1599,1555,1
418,1370,1304,1241,1117,706

【0145】実施例41 8−ホルミル−1,2,3,
4−テトラヒドロキノリン3,5−ジ−t−ブチル−4
−ヒドロキシベンゾイルヒドラゾン(8-formyl-1,2,3,4-
tetrahydroquinoline 3,5-di-t-butyl-4-hydroxybenzoy
lhydrazone) 収率:69% (物性) 淡黄色結晶(mp.301-302 ℃) PMR(DMSO-d6,δ ppm) :11.50(1H,s),8.47(1H,s),8.45(1
H,brs),7.67(2H,s),7.48(1H,s),7.00(1H,d,J=7.3Hz),6.
90(1H,d,J=7.3Hz),6.47(1H,t,J=7.6Hz),3.45(2H,m),2.7
7(2H,m),1.87(2H,m),1.43(18H,s) IR(KBr, cm-1):3612,3425,3222,2954,1637,1607,1556,1
518,1429,1366,1303,1240
Example 41 8-Formyl-1,2,3
4-tetrahydroquinoline 3,5-di-t-butyl-4
-Hydroxybenzoylhydrazone (8-formyl-1,2,3,4-
tetrahydroquinoline 3,5-di-t-butyl-4-hydroxybenzoy
Lhydrazone) Yield: 69% (property) pale yellow crystals (mp.301-302 ℃) PMR (DMSO- d 6, δ ppm): 11.50 (1H, s), 8.47 (1H, s), 8.45 (1
H, brs), 7.67 (2H, s), 7.48 (1H, s), 7.00 (1H, d, J = 7.3Hz), 6.
90 (1H, d, J = 7.3Hz), 6.47 (1H, t, J = 7.6Hz), 3.45 (2H, m), 2.7
7 (2H, m), 1.87 (2H, m), 1.43 (18H, s) IR (KBr, cm -1 ): 3612,3425,3222,2954,1637,1607,1556,1
518,1429,1366,1303,1240

【0146】実施例42 2,3−ジメトキシ−6−ホ
ルミル−5−メチルヒドロキノン3,5−ジ−t−ブチ
ル−4−ヒドロキシベンゾイルヒドラゾン(2,3-dimetho
xy-6-formyl-5-methylhydroquinone 3,5-di-t-butyl-4-
hydroxybenzoylhydrazone) 収率:71% (物性) 淡黄色結晶(mp.272-275 ℃(dec.)) PMR(DMSO-d6,δ ppm) :12.17(1H,s),11.80(1H,s),8.80
(1H,s),8.21(1H,s),7.68(2H,s),7.54(1H,s),3.83(3H,
s),3.81(3H,s),2.23(3H,s),1.44(18H,s) IR(KBr, cm-1):3541,3221,2954,1639,1602,1552,1425,1
392,1285,1239,1197,1140,1108,1059,1024
Example 42 2,3-Dimethoxy-6-formyl-5-methylhydroquinone 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone (2,3-dimetho
xy-6-formyl-5-methylhydroquinone 3,5-di-t-butyl-4-
hydroxybenzoylhydrazone) Yield: 71% (physical properties) pale yellow crystal (mp.272-275 ° C (dec.)) PMR (DMSO-d 6 , δ ppm): 12.17 (1H, s), 11.80 (1H, s), 8.80
(1H, s), 8.21 (1H, s), 7.68 (2H, s), 7.54 (1H, s), 3.83 (3H,
s), 3.81 (3H, s), 2.23 (3H, s), 1.44 (18H, s) IR (KBr, cm -1 ): 3541,3221,2954,1639,1602,1552,1425,1
392,1285,1239,1197,1140,1108,1059,1024

【0147】実施例43 ピリドキサール3,5−ジ−
t−ブチル−4−ヒドロキシベンゾイルヒドラゾン(pyr
idoxal 3,5-di-t-butyl-4-hydroxybenzoylhydrazone) 収率:86% (物性) 無色結晶(mp.>300℃) PMR(DMSO-d6,δ ppm) :12.82(1H,brs),12.51(1H,s),8.9
5(1H,s),8.05(1H,s),7.75(2H,s),7.67(1H,s),5.57(1H,b
rs),4.69(2H,s),2.51(3H,s),1.45(18H,s) IR(KBr, cm-1):3433,3211,2968,1645,1600,1539,1435,1
402,1361,1303,1260,1237,1218,1163,1121,1017,703
Example 43 Pyridoxal 3,5-di-
t-butyl-4-hydroxybenzoylhydrazone (pyr
idoxal 3,5-di-t-butyl-4-hydroxybenzoylhydrazone) Yield: 86% (physical properties) colorless crystal (mp.> 300 ℃) PMR (DMSO-d 6 , δ ppm): 12.82 (1H, brs), 12.51 (1H, s), 8.9
5 (1H, s), 8.05 (1H, s), 7.75 (2H, s), 7.67 (1H, s), 5.57 (1H, b
(rs), 4.69 (2H, s), 2.51 (3H, s), 1.45 (18H, s) IR (KBr, cm -1 ): 3433,3211,2968,1645,1600,1539,1435,1
402,1361,1303,1260,1237,1218,1163,1121,1017,703

【0148】実施例44 2−ピコリンアルデヒド3,
5−ジ−t−ブチル−4−ヒドロキシベンゾイルヒドラ
ゾン(2-picolinaldehyde 3,5-di-t-butyl-4-hydroxyben
zoylhydrazone) 収率:92% (物性) 淡褐色結晶(mp.209-210 ℃) PMR(DMSO-d6,δ ppm) :11.80(1H,brs),8.61(1H,d,J=4.9
Hz),8.49(1H,brs),7.97(1H,brs),7.86(1H,t,J=7.1Hz),
7.67(2H,s),7.54(1H,s),7.39(1H,t,J=6.1Hz),1.44(18H,
s) IR(KBr, cm-1):3620,3450,3220,2958,1651,1553,1437,1
307,1240,1164,1079,778
Example 44 2-Picolinaldehyde 3,
5-di-t-butyl-4-hydroxybenzoylhydrazone (2-picolinaldehyde 3,5-di-t-butyl-4-hydroxyben
Zoylhydrazone) Yield: 92% (property) pale brown crystals (mp.209-210 ℃) PMR (DMSO- d 6, δ ppm): 11.80 (1H, brs), 8.61 (1H, d, J = 4.9
Hz), 8.49 (1H, brs), 7.97 (1H, brs), 7.86 (1H, t, J = 7.1Hz),
7.67 (2H, s), 7.54 (1H, s), 7.39 (1H, t, J = 6.1Hz), 1.44 (18H,
s) IR (KBr, cm -1 ): 3620,3450,3220,2958,1651,1553,1437,1
307,1240,1164,1079,778

【0149】実施例45 ニコチンアルデヒド3,5−
ジ−t−ブチル−4−ヒドロキシベンゾイルヒドラゾン
(nicotinaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhy
drazone) 収率:96% (物性) 無色結晶(mp.224 ℃) PMR(DMSO-d6,δ ppm) :11.76(1H,brs),8.84(1H,brs),8.
59(1H,d,J=3.9Hz),8.52(1H,brs),8.12(1H,brs),7.66(2
H,s),7.53(1H,s),7.47(1H,t,J=6.1Hz),1.43(18H,s) IR(KBr, cm-1):3618,3425,3208,2964,1640,1599,1555,1
418,1370,1304,1241,1117,706
Example 45 Nicotinaldehyde 3,5-
Di-t-butyl-4-hydroxybenzoylhydrazone
(nicotinaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhy
Drazone) Yield: 96% (Physical Properties) colorless crystals (mp.224 ℃) PMR (DMSO- d 6, δ ppm): 11.76 (1H, brs), 8.84 (1H, brs), 8.
59 (1H, d, J = 3.9Hz), 8.52 (1H, brs), 8.12 (1H, brs), 7.66 (2
H, s), 7.53 (1H, s), 7.47 (1H, t, J = 6.1Hz), 1.43 (18H, s) IR (KBr, cm -1 ): 3618,3425,3208,2964,1640,1599 , 1555,1
418,1370,1304,1241,1117,706

【0150】実施例46 イソニコチンアルデヒド3,
5−ジ−t−ブチル−4−ヒドロキシベンゾイルヒドラ
ゾン(isonicotinaldehyde 3,5-di-t-butyl-4-hydroxybe
nzoylhydrazone) 収率:96% (物性) 無色結晶(mp.>300℃) PMR(DMSO-d6,δ ppm) :11.85(1H,brs),8.63(2H,d,J=5.4
Hz),8.45(1H,brs),7.67(2H,s),7.64(2H,brs),7.54(1H,
s),1.44(18H,s) IR(KBr, cm-1):3622,3400,3194,2954,1640,1599,1550,1
361,1307,1244
Example 46 Isonicotinaldehyde 3,
5-di-t-butyl-4-hydroxybenzoylhydrazone (isonicotinaldehyde 3,5-di-t-butyl-4-hydroxybe
Nzoylhydrazone) Yield: 96% (Physical Properties) colorless crystals (mp> 300 ℃) PMR ( DMSO-d 6, δ ppm):. 11.85 (1H, brs), 8.63 (2H, d, J = 5.4
Hz), 8.45 (1H, brs), 7.67 (2H, s), 7.64 (2H, brs), 7.54 (1H,
s), 1.44 (18H, s) IR (KBr, cm -1 ): 3622,3400,3194,2954,1640,1599,1550,1
361,1307,1244

【0151】実施例47 2−フルアルデヒド3,5−
ジ−t−ブチル−4−ヒドロキシベンゾイルヒドラゾン
(2-furaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydr
azone) 収率:100% (物性) 無色結晶(mp.233-235 ℃) PMR(DMSO-d6,δ ppm) :11.52(1H,brs),8.36(1H,brs),7.
79(1H,brs),7.63(2H,brs),7.47(1H,brs),6.87(1H,brs),
6.61(1H,brs),1.43(18H,s) IR(KBr, cm-1):3607,3204,2958,1633,1549,1436,1335,1
304,1238,1162,1063,1015,941,743,700
Example 47 2-furaldehyde 3,5-
Di-t-butyl-4-hydroxybenzoylhydrazone
(2-furaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydr
Azone) Yield: 100% (physical properties) of colorless crystals (mp.233-235 ℃) PMR (DMSO- d 6, δ ppm): 11.52 (1H, brs), 8.36 (1H, brs), 7.
79 (1H, brs), 7.63 (2H, brs), 7.47 (1H, brs), 6.87 (1H, brs),
6.61 (1H, brs), 1.43 (18H, s) IR (KBr, cm -1 ): 3607,3204,2958,1633,1549,1436,1335,1
304,1238,1162,1063,1015,941,743,700

【0152】実施例48 ピロール−2−カルバルデヒ
ド3,5−ジ−t−ブチル−4−ヒドロキシベンゾイル
ヒドラゾン(pyrrole-2-carbaldehyde 3,5-di-t-butyl-4
-hydroxybenzoylhydrazone) 収率:37% (物性) 無色結晶(mp.275-280 ℃(dec.)) PMR(DMSO-d6,δ ppm) :11.48(1H,brs),11.25(1H,brs),
8.27(1H,d,J=2.0Hz),7.61(2H,s),7.42(1H,s),6.88(1H,
s),6.44(1H,s),6.12(1H,d,J=2.4Hz),1.43(18H,s) IR(KBr, cm-1):3631,3441,3212,2955,1634,1606,1551,1
437,1357,1307,1238,1141,1065,890,729
Example 48 Pyrrole-2-carbaldehyde 3,5-di-t-butyl-4
-Hydroxybenzoylhydrazone) Yield: 37% (Physical Properties) colorless crystals (mp.275-280 ℃ (dec.)) PMR (DMSO-d 6, δ ppm): 11.48 (1H, brs), 11.25 (1H, brs),
8.27 (1H, d, J = 2.0Hz), 7.61 (2H, s), 7.42 (1H, s), 6.88 (1H,
s), 6.44 (1H, s), 6.12 (1H, d, J = 2.4Hz), 1.43 (18H, s) IR (KBr, cm -1 ): 3631,3441,3212,2955,1634,1606,1551 , 1
437,1357,1307,1238,1141,1065,890,729

【0153】実施例49 2−チオフェンアルデヒド
3,5−ジ−t−ブチル−4−ヒドロキシベンゾイルヒ
ドラゾン(2-thiophenaldehyde 3,5-di-t-butyl-4-hydro
xybenzoylhydrazone) 収率:85% (物性) 無色結晶(mp.237-238 ℃) PMR(DMSO-d6,δ ppm) :11.52(1H,br
s),8.70(1H,brs),7.63(3H,b
rs),7.47(1H,brs),7.40(1H,
brs),7.12(1H,brs),1.43(18
H,s) IR(KBr, cm−1):3610,3239,2
958,1647,1556,1437,1366,1
325,1303,1234,700
Example 49 2-thiophenaldehyde 3,5-di-t-butyl-4-hydro-4-hydroxybenzoylhydrazone
Xybenzoylhydrazone) Yield: 85% (Physical Properties) colorless crystals (mp.237-238 ℃) PMR (DMSO- d 6, δ ppm): 11.52 (1H, br
s), 8.70 (1H, brs), 7.63 (3H, b
rs), 7.47 (1H, brs), 7.40 (1H,
brs), 7.12 (1H, brs), 1.43 (18
H, s) IR (KBr, cm -1 ): 3610,3239,2
958, 1647, 1556, 1437, 1366, 1
325,1303,1234,700

【0154】実施例50 ベンズアルデヒドN−メチル
−3,5−ジ−t−ブチル−4−ヒドロキシベンゾイル
ヒドラゾン(benzaldehyde N−meth
yl−3,5−di−t−butyl−4−hydro
xybenzoylhydrazone) 参考例6で合成した化合物ベンズアルデヒドメチルヒド
ラゾン 1.21g(9.0mmol) 及び3,5−ジ−t−ブチル−
4−ヒドロキシ安息香酸 2.26g(9.0mmol) を塩化メチレ
ン 20ml に加え、攪拌した。この溶液に、ジシクロヘキ
シルカルボジイミド(DCC)2.23g(10.8mmol) を加
え、24時間攪拌した。析出物をろ去し、溶媒を留去し
た。残渣をシリカゲルカラムクロマトグラフィーに付
し、クロロホルム溶出部を溶媒留去し、生じた結晶をろ
取した。減圧下で乾燥し、標記化合物 2.02g(収率61%)
を得た。
Example 50 Benzaldehyde N-methyl-3,5-di-tert-butyl-4-hydroxybenzoylhydrazone
yl-3,5-di-t-butyl-4-hydro
Xybenzoylhydrazone) 1.21 g (9.0 mmol) of benzaldehyde methylhydrazone synthesized in Reference Example 6 and 3,5-di-t-butyl-
2.26 g (9.0 mmol) of 4-hydroxybenzoic acid was added to 20 ml of methylene chloride and stirred. 2.23 g (10.8 mmol) of dicyclohexylcarbodiimide (DCC) was added to this solution, and the mixture was stirred for 24 hours. The precipitate was removed by filtration, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, the solvent eluted from the chloroform-eluting portion, and the resulting crystals were collected by filtration. Dry under reduced pressure to give the title compound (2.02 g, 61% yield)
I got

【0155】(物性) 無色結晶(mp.245-246 ℃) PMR(DMSO-d6,δ ppm) :7.98(1H,s),7.61-7.57(2H,m),7.
51(2H,s),7.42(1H,s),7.37-7.34(3H,m),3.48(3H,s),1.4
1(18H,s) IR(KBr, cm-1):3585,2954,1643,1608,1471,1408,1345,1
314,1238,1069,958,883,756,685
(Physical properties) Colorless crystal (mp.245-246 ° C.) PMR (DMSO-d 6 , δ ppm): 7.98 (1H, s), 7.61-7.57 (2H, m), 7.
51 (2H, s), 7.42 (1H, s), 7.37-7.34 (3H, m), 3.48 (3H, s), 1.4
1 (18H, s) IR (KBr, cm -1 ): 3585,2954,1643,1608,1471,1408,1345,1
314,1238,1069,958,883,756,685

【0156】実施例51 サリチルアルデヒドN−メチ
ル−3,5−ジ−t−ブチル−4−ヒドロキシベンゾイ
ルヒドラゾン(salicylaldehyde N-methyl-3,5-di-t-but
yl-4-hydroxybenzoylhydrazone) 参考例7で合成した化合物サリチルアルデヒドメチルヒ
ドラゾン 1.44g(9.6mmol) 及び3,5−ジ−t−ブチル
−4−ヒドロキシ安息香酸 2.40g(9.6mmol) を塩化メチ
レン 20ml に加え、攪拌した。この溶液に、DCC 2.3
7g(11.5mmol)を加え、24時間攪拌した。析出物をろ去
し、溶媒を留去した。残渣をシリカゲルカラムクロマト
グラフィーに付し、クロロホルム溶出部を溶媒留去し、
n−ヘキサンを加えて結晶化させ、ろ取した。減圧下で
乾燥し、標記化合物 2.36g(収率:64%)を得た。
Example 51 Salicylaldehyde N-methyl-3,5-di-t-but
yl-4-hydroxybenzoylhydrazone) 1.44 g (9.6 mmol) of the compound synthesized in Reference Example 7 and 2.40 g (9.6 mmol) of 3,5-di-t-butyl-4-hydroxybenzoic acid were added to 20 ml of methylene chloride. Addition and stirring. To this solution was added DCC 2.3
7 g (11.5 mmol) was added, and the mixture was stirred for 24 hours. The precipitate was removed by filtration, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the chloroform eluted portion was evaporated to remove the solvent.
Crystallization was performed by adding n-hexane, and the crystals were collected by filtration. Drying under reduced pressure gave 2.36 g (yield: 64%) of the title compound.

【0157】(物性) 無色結晶(mp.242-243 ℃) PMR(DMSO-d6,δ ppm) :10.04(1H,brs),8.16(1H,s),7.47
(1H,d,J=7.3Hz),7.42(3H,s),7.20(1H,t,J=7.8Hz),6.84-
6.79(2H,m),3.48(3H,s),1.40(18H,s) IR(KBr, cm-1):3585,2954,1645,1619,1600,1475,1409,1
343,1312,1229,1072,961,891,760,702,685
(Physical properties) Colorless crystal (mp. 242-243 ° C.) PMR (DMSO-d 6 , δ ppm): 10.04 (1H, brs), 8.16 (1H, s), 7.47
(1H, d, J = 7.3Hz), 7.42 (3H, s), 7.20 (1H, t, J = 7.8Hz), 6.84-
6.79 (2H, m), 3.48 (3H, s), 1.40 (18H, s) IR (KBr, cm -1 ): 3585,2954,1645,1619,1600,1475,1409,1
343,1312,1229,1072,961,891,760,702,685

【0158】実施例52 2,4−ジヒドロキシベンズ
アルデヒドN−メチル−3,5−ジ−t−ブチル−4−
ヒドロキシベンゾイルヒドラゾン(2,4-dihydroxybenzal
dehyde N-methyl-3,5-di-t-butyl-4-hydroxybenzoylhyd
razone) 参考例8で合成した化合物2,4−ジヒドロキシベンズ
アルデヒドメチルヒドラゾン 0.83g(5mmol) 及び3,5
−ジ−t−ブチル−4−ヒドロキシ安息香酸 1.25g(5mm
ol) をジオキサン20ml及び塩化メチレン20mlの混合溶媒
に加え、攪拌した。この溶液に、DCC 1.24g(6mmol)
を加え、24時間攪拌した。析出物をメタノールに懸濁
し、ろ取した。減圧下で乾燥し、標記化合物 1.14g(収
率57%)を得た。
Example 52 2,4-Dihydroxybenzaldehyde N-methyl-3,5-di-tert-butyl-4-
Hydroxybenzoyl hydrazone (2,4-dihydroxybenzal
dehyde N-methyl-3,5-di-t-butyl-4-hydroxybenzoylhyd
razone) 0.83 g (5 mmol) of compound 2,4-dihydroxybenzaldehyde methylhydrazone synthesized in Reference Example 8 and 3,5
-Di-t-butyl-4-hydroxybenzoic acid 1.25 g (5 mm
ol) was added to a mixed solvent of 20 ml of dioxane and 20 ml of methylene chloride and stirred. To this solution, 1.24 g (6 mmol) of DCC was added.
Was added and stirred for 24 hours. The precipitate was suspended in methanol and collected by filtration. Drying under reduced pressure gave 1.14 g (57% yield) of the title compound.

【0159】(物性) 淡褐色結晶(mp.299-301 ℃(dec.)) PMR(DMSO-d6,δ ppm) :10.07(1H,brs),9.76(1H,s),8.06
(1H,s),7.38(3H,s),7.26(1H,d,J=8.8Hz),6.26(1H,dd,J=
8.3,2.0Hz),6.18(1H,d,J=2.0Hz),3.44(3H,s),1.39(18H,
s) IR(KBr, cm-1):3579,3142,2967,1614,1587,1479,1411,1
399,1342,1311,1244,1174,1076,986,800
(Physical properties) Light brown crystal (mp. 299-301 ° C. (dec.)) PMR (DMSO-d 6 , δ ppm): 10.07 (1H, brs), 9.76 (1H, s), 8.06
(1H, s), 7.38 (3H, s), 7.26 (1H, d, J = 8.8Hz), 6.26 (1H, dd, J =
8.3,2.0Hz), 6.18 (1H, d, J = 2.0Hz), 3.44 (3H, s), 1.39 (18H,
s) IR (KBr, cm -1 ): 3579,3142,2967,1614,1587,1479,1411,1
399,1342,1311,1244,1174,1076,986,800

【0160】実施例53 o−バニリンN−メチル−
3,5−ジ−t−ブチル−4−ヒドロキシベンゾイルヒ
ドラゾン(o−vanillin N−methyl−
3,5−di−t−butyl−4−hydroxyb
enzoylhydrazone) 参考例9で合成した化合物o−バニリンメチルヒドラゾ
ン1.39g(7.7mmol)及び3,5−ジ−t−
ブチル−4−ヒドロキシ安息香酸 1.93g(7.7mmol) を塩
化メチレン 20ml に加え、攪拌した。この溶液に、DC
C 1.91g(9.2mmol) を加え、24時間攪拌した。析出物を
ろ去し、溶媒を留去した。残渣をシリカゲルカラムクロ
マトグラフィーに付し、クロロホルム溶出部を溶媒留去
し、イソプロピルエーテルを加えて結晶化させ、ろ取し
た。減圧下で乾燥し、標記化合物 1.91g(収率60%)を得
た。
Example 53: o-Vaniline N-methyl-
3,5-di-t-butyl-4-hydroxybenzoylhydrazone (o-vanillin N-methyl-
3,5-di-t-butyl-4-hydroxyb
Enzyhydrazine 1.39 g (7.7 mmol) of compound o-vanillin methylhydrazone synthesized in Reference Example 9 and 3,5-di-t-
1.93 g (7.7 mmol) of butyl-4-hydroxybenzoic acid was added to 20 ml of methylene chloride and stirred. In this solution, DC
1.91 g (9.2 mmol) of C was added and stirred for 24 hours. The precipitate was removed by filtration, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the solvent eluted with chloroform was distilled off. The residue was crystallized with isopropyl ether and collected by filtration. Drying under reduced pressure gave 1.91 g (yield 60%) of the title compound.

【0161】(物性) 無色結晶(mp.154-155 ℃) PMR(DMSO-d6,δ ppm) :9.66(1H,brs),8.14(1H,s),7.43
(2H,s),7.42(1H,s),7.08(1H,d,J=7.8Hz),6.93(1H,dd,J=
8.3,1.0Hz),6.74(1H,t,J=7.8Hz),3.77(3H,s),3.48(3H,
s),1.40(18H,s) IR(KBr, cm-1):3543,2955,2911,1650,1574,1470,1406,1
332,1249,1115,1095,1069,974,727
(Physical properties) Colorless crystal (mp.154-155 ° C.) PMR (DMSO-d 6 , δ ppm): 9.66 (1H, brs), 8.14 (1H, s), 7.43
(2H, s), 7.42 (1H, s), 7.08 (1H, d, J = 7.8Hz), 6.93 (1H, dd, J =
8.3,1.0Hz), 6.74 (1H, t, J = 7.8Hz), 3.77 (3H, s), 3.48 (3H,
s), 1.40 (18H, s) IR (KBr, cm -1 ): 3543,2955,2911,1650,1574,1470,1406,1
332,1249,1115,1095,1069,974,727

【0162】実施例54 4−(ジエチルアミノ)サリ
チルアルデヒドN−メチル−3,5−ジ−t−ブチル−
4−ヒドロキシベンゾイルヒドラゾン(4-(diethylamin
o)salicylaldehyde N-methyl-3,5-di-t-butyl-4-hydrox
ybenzoylhydrazone) 参考例10で合成した化合物4−(ジエチルアミノ)サ
リチルアルデヒドメチルヒドラゾン 1.40g(6.3mmol) 及
び3,5−ジ−t−ブチル−4−ヒドロキシ安息香酸
1.58g(6.3mmol) を塩化メチレン 20ml に加え、攪拌し
た。この溶液に、DCC 1.57g(7.6mmol) を加え、24時
間攪拌した。析出物をろ去し、溶媒を留去した。残渣を
シリカゲルカラムクロマトグラフィーに付し、クロロホ
ルム溶出部を溶媒留去し、酢酸エチル及びn−ヘキサン
を加えて結晶化させ、ろ取した。減圧下で乾燥し、標記
化合物 1.29g(収率45%)を得た。
Example 54 4- (Diethylamino) salicylaldehyde N-methyl-3,5-di-tert-butyl-
4-hydroxybenzoylhydrazone (4- (diethylamin
o) salicylaldehyde N-methyl-3,5-di-t-butyl-4-hydrox
ybenzoylhydrazone) 1.40 g (6.3 mmol) of compound 4- (diethylamino) salicylaldehyde methylhydrazone synthesized in Reference Example 10 and 3,5-di-t-butyl-4-hydroxybenzoic acid
1.58 g (6.3 mmol) was added to 20 ml of methylene chloride and stirred. 1.57 g (7.6 mmol) of DCC was added to this solution, and the mixture was stirred for 24 hours. The precipitate was removed by filtration, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, the chloroform eluted portion was evaporated, and ethyl acetate and n-hexane were added for crystallization, followed by filtration. Drying under reduced pressure gave 1.29 g (yield 45%) of the title compound.

【0163】(物性) 淡褐色結晶(mp.110 ℃) PMR(DMSO-d6,δ ppm) :9.96(1H,brs),8.02(1H,s),7.36
(2H,s),7.34(1H,s),7.20(1H,d,J=8.3Hz),6.19(1H,d,J=
8.3Hz),5.95(1H,s),3.44(3H,s),3.31(4H,q,J=6.8Hz),1.
40(18H,s),1.08(6H,t,J=6.8Hz) IR(KBr, cm-1):3553,2966,1624,1522,1474,1402,1338,1
239,1131,1072,667
(Physical properties) Light brown crystal (mp. 110 ° C.) PMR (DMSO-d 6 , δ ppm): 9.96 (1H, brs), 8.02 (1H, s), 7.36
(2H, s), 7.34 (1H, s), 7.20 (1H, d, J = 8.3Hz), 6.19 (1H, d, J =
(8.3Hz), 5.95 (1H, s), 3.44 (3H, s), 3.31 (4H, q, J = 6.8Hz), 1.
40 (18H, s), 1.08 (6H, t, J = 6.8Hz) IR (KBr, cm -1 ): 3553,2966,1624,1522,1474,1402,1338,1
239,1131,1072,667

【0164】実施例55 5−ニトロサリチルアルデヒ
ドN−メチル−3,5−ジ−t−ブチル−4−ヒドロキ
シベンゾイルヒドラゾン(5-nitrosalicylaldehyde N-me
thyl-3,5-di-t-butyl-4-hydroxybenzone) 参考例11で合成した化合物5−ニトロサリチルアルデ
ヒドメチルヒドラゾン1.72g(8.8mmol)及び3,5−ジ−
t−ブチル−4−ヒドロキシ安息香酸 2.21g(8.8mmol)
を塩化メチレン20ml、ジオキサン10ml及びジメチルホル
ムアミド10mlの混合溶媒に加え、攪拌した。この溶液
に、DCC 2.18g(10.6mmol)を加え、24時間攪拌した。
析出物をろ去し、溶媒を留去した。残渣をシリカゲルカ
ラムクロマトグラフィーに付し、クロロホルム溶出部を
溶媒留去し、イソプロピルエーテルを加えて結晶化さ
せ、ろ取した。減圧下で乾燥し、標記化合物 1.05g(収
率28%)を得た。
Example 55 5-nitrosalicylaldehyde N-methyl-3,5-di-tert-butyl-4-hydroxybenzoylhydrazone
(Thyl-3,5-di-t-butyl-4-hydroxybenzone) 1.72 g (8.8 mmol) of the compound 5-nitrosalicylaldehyde methylhydrazone synthesized in Reference Example 11 and 3,5-di-
2.21 g (8.8 mmol) of t-butyl-4-hydroxybenzoic acid
Was added to a mixed solvent of 20 ml of methylene chloride, 10 ml of dioxane and 10 ml of dimethylformamide, followed by stirring. 2.18 g (10.6 mmol) of DCC was added to this solution, and the mixture was stirred for 24 hours.
The precipitate was removed by filtration, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the solvent eluted with chloroform was distilled off. The residue was crystallized with isopropyl ether and collected by filtration. Drying under reduced pressure gave 1.05 g (yield 28%) of the title compound.

【0165】(物性) 淡黄色結晶(mp.257-259 ℃) PMR(DMSO-d6,δ ppm) :11.50(1H,brs),8.38(1H,d,J=2.9
Hz),8.21(1H,s),8.10(1H,dd,J=9.3,2.9Hz),7.48(2H,s),
7.46(1H,s),7.04(1H,d,J=8.8Hz),3.50(3H,s),1.40(18H,
s) IR(KBr, cm-1):3586,3090,2955,1662,1627,1524,1467,1
340,1309,1073,645
(Physical properties) Light yellow crystal (mp. 257-259 ° C.) PMR (DMSO-d 6 , δ ppm): 11.50 (1H, brs), 8.38 (1H, d, J = 2.9)
Hz), 8.21 (1H, s), 8.10 (1H, dd, J = 9.3,2.9Hz), 7.48 (2H, s),
7.46 (1H, s), 7.04 (1H, d, J = 8.8Hz), 3.50 (3H, s), 1.40 (18H,
s) IR (KBr, cm -1 ): 3586,3090,2955,1662,1627,1524,1467,1
340,1309,1073,645

【0166】実施例56 N’−(2−ヒドロキシベン
ジル)−3,5−ジ−t−ブチル−4−ヒドロキシベン
ゾヒドラジド(N'-(2-hydroxybenzyl)-3,5-di-t-butyl-4
-hydroxybenzohydrazide) 実施例15で合成した化合物サリチルアルデヒド3,5
−ジ−t−ブチル−4−ヒドロキシベンゾイルヒドラゾ
ン 1.47g(4mmol) 及び 5%Pd/C 0.15g をメタノール 20m
l に加え、18時間接触還元した。触媒をセライトろ去
し、溶媒を留去した。残渣をシリカゲルカラムクロマト
グラフィーに付した。メタノール:クロロホルム=1:
33溶出部を溶媒留去し、結晶を析出させ、その結晶をろ
取した。ろ取した結晶を減圧下で乾燥し、標記化合物
0.95g(収率64%)を得た。
Example 56 N '-(2-hydroxybenzyl) -3,5-di-t-butyl-4-hydroxybenzohydrazide (N'-(2-hydroxybenzyl) -3,5-di-t-butyl) -Four
-hydroxybenzohydrazide) The compound synthesized in Example 15 salicylaldehyde 3,5
1.47 g (4 mmol) of di-t-butyl-4-hydroxybenzoylhydrazone and 0.15 g of 5% Pd / C in methanol 20m
and catalytic reduction for 18 hours. The catalyst was removed by filtration through Celite, and the solvent was distilled off. The residue was subjected to silica gel column chromatography. Methanol: chloroform = 1:
The solvent was distilled off from the 33 elution portion to precipitate crystals, and the crystals were collected by filtration. The crystals collected by filtration were dried under reduced pressure to give the title compound.
0.95 g (64% yield) was obtained.

【0167】(物性) 無色結晶(mp.185-186 ℃) PMR(DMSO-d6,δ ppm) :10.00(1H,d,J=5.4Hz),9.73(1H,
s),7.58(2H,s),7.37(1H,s),7.18(1H,d,J=7.3Hz),7.09(1
H,t,J=7.3Hz),6.79(1H,d,J=8.3Hz),6.74(1H,t,J=7.6H
z),5.42 (1H,q,J=6.2Hz),3.93(2H,d,J=6.4Hz),1.40(18
H,s) IR(KBr, cm-1):3633,3274,3206,2956,1635,1542,1485,1
433,1319,1262,1161,761,699
(Physical properties) Colorless crystals (mp. 185-186 ° C.) PMR (DMSO-d 6 , δ ppm): 10.00 (1H, d, J = 5.4 Hz), 9.73 (1H,
s), 7.58 (2H, s), 7.37 (1H, s), 7.18 (1H, d, J = 7.3Hz), 7.09 (1H
H, t, J = 7.3Hz), 6.79 (1H, d, J = 8.3Hz), 6.74 (1H, t, J = 7.6H)
z), 5.42 (1H, q, J = 6.2Hz), 3.93 (2H, d, J = 6.4Hz), 1.40 (18
H, s) IR (KBr, cm -1 ): 3633,3274,3206,2956,1635,1542,1485,1
433,1319,1262,1161,761,699

【0168】実施例57 N’−(2,4−ジヒドロキ
シベンジル)−3,5−ジ−t−ブチル−4−ヒドロキ
シベンゾヒドラジド(N'-(2,4-dihydroxybenzyl)-3,5-di
-t-butyl-4-hydroxybenzohydrazide) 実施例25で合成した化合物2,4−ジヒドロキシベン
ズアルデヒド3,5−ジ−t−ブチル−4−ヒドロキシ
ベンゾイルヒドラゾン 1.54g(4mmol) 及び 5%Pd/C 0.15
g をメタノール 20ml に加え、24時間接触還元した。触
媒をセライトろ去し、溶媒を留去し、結晶を析出させ、
その結晶をろ取した。ろ取した結晶を減圧下で乾燥し、
標記化合物 0.44g(収率28%)を得た。
Example 57 N '-(2,4-dihydroxybenzyl) -3,5-di-t-butyl-4-hydroxybenzohydrazide (N'-(2,4-dihydroxybenzyl) -3,5-di
-t-butyl-4-hydroxybenzohydrazide) 1.54 g (4 mmol) of compound 2,4-dihydroxybenzaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone synthesized in Example 25 and 5% Pd / C 0.15
g was added to 20 ml of methanol and subjected to catalytic reduction for 24 hours. The catalyst was removed by filtration through Celite, the solvent was distilled off, and crystals were precipitated.
The crystals were collected by filtration. The filtered crystals are dried under reduced pressure,
0.44 g (yield 28%) of the title compound was obtained.

【0169】(物性) 無色結晶(mp.226-229 ℃(dec.)) PMR(DMSO-d6,δ ppm) :9.97(1H,d,J
=3.9Hz),9.56(1H,s),9.09(1
H,s),7.58(2H,s),7.36(1H,
s),6.92(1H,d,J=8.3Hz),6.2
6(1H,d,J=2.5Hz),6.15(1H,d
d,J=8.3,2.5Hz),5.25 (1H,b
rd),3.80(1H,d,J=4.9Hz),1.
40(18H,s) IR(KBr, cm−1):3627,3264,3
066,2955,2345,1633,1612,1
551,1430,1320,1238,1180,1
123,978,848
(Physical properties) Colorless crystal (mp.226-229 ° C. (dec.)) PMR (DMSO-d 6 , δ ppm): 9.97 (1H, d, J)
= 3.9 Hz), 9.56 (1H, s), 9.09 (1
H, s), 7.58 (2H, s), 7.36 (1H,
s), 6.92 (1H, d, J = 8.3 Hz), 6.2
6 (1H, d, J = 2.5 Hz), 6.15 (1H, d
d, J = 8.3, 2.5 Hz), 5.25 (1H, b
rd), 3.80 (1H, d, J = 4.9 Hz), 1.
40 (18H, s) IR (KBr, cm- 1 ): 3627, 3264, 3
066,2955,2345,1633,1612,1
551, 1430, 1320, 1238, 1180, 1
123,978,848

【0170】実施例58 N−フェネチル−3,5−ジ
−t−ブチル−4−ヒドロキシベンズアミド(N−ph
enethyl−3,5−di−t−butyl−4−
hydroxybenzamide) 3,5−ジ−t−ブチル−4−ヒドロキシ安息香酸 1.2
5g(5mmol) 及びフェネチルアミン 0.63ml(5mmol)を塩化
メチレン 10ml に加え、攪拌した。この溶液に、DCC
1.24g(6mmol) を加え、12時間攪拌した。析出物をろ去
し、溶媒を留去した。残渣をシリカゲルカラムクロマト
グラフィーに付し、クロロホルム溶出部を溶媒留去し、
生じた結晶をろ取した。減圧下で乾燥し、標記化合物
0.30g(収率17%)を得た。 (物性) 無色結晶(mp.198-202 ℃) PMR(DMSO-d6,δ ppm) :8.31(1H,brt,J=5.4Hz),7.56(2H,
s),7.32-7.17(6H,m),3.44(2H,dt,J=6.8,6.8Hz),2.83(2
H,t,J=7.3Hz),1.40(18H,s) IR(KBr, cm-1):3616,3435,3250,2956,1629,1542,1434,1
329,1238,700
Example 58 N-phenethyl-3,5-di-tert-butyl-4-hydroxybenzamide (N-ph
ethyl-3,5-di-t-butyl-4-
hydroxybenzamide) 3,5-di-t-butyl-4-hydroxybenzoic acid 1.2
5 g (5 mmol) and 0.63 ml (5 mmol) of phenethylamine were added to 10 ml of methylene chloride and stirred. In this solution, DCC
1.24 g (6 mmol) was added and the mixture was stirred for 12 hours. The precipitate was removed by filtration, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the chloroform eluted portion was evaporated to remove the solvent.
The resulting crystals were collected by filtration. Dry under reduced pressure to give the title compound
0.30 g (17% yield) was obtained. (Physical Properties) colorless crystals (mp.198-202 ℃) PMR (DMSO- d 6, δ ppm): 8.31 (1H, brt, J = 5.4Hz), 7.56 (2H,
s), 7.32-7.17 (6H, m), 3.44 (2H, dt, J = 6.8,6.8Hz), 2.83 (2H
H, t, J = 7.3Hz), 1.40 (18H, s) IR (KBr, cm -1 ): 3616,3435,3250,2956,1629,1542,1434,1
329,1238,700

【0171】実施例59 N−(2−ヒドロキシフェネ
チル)−3,5−ジ−t−ブチル−4−ヒドロキシベン
ズアミド(N-(2-hydroxyphenethyl)-3,5-di-t-butyl-4-h
ydroxybenzamide) 3,5−ジ−t−ブチル−4−ヒドロキシ安息香酸 1.1
3g(4.5mmol) 及び2−ヒドロキシフェネチルアミン 0.6
2g(4.5mmol) をジメチルホルムアミド 9mlに加え、攪拌
した。この溶液に、DCC 0.93g(4.5mmol) を加え、24
時間攪拌した。析出物をろ去し、溶媒を留去した。残渣
をシリカゲルカラムクロマトグラフィーに付し、クロロ
ホルム溶出部を溶媒留去し、減圧下で乾燥し、標記化合
物0.76g(収率46%)を得た。
Example 59 N- (2-hydroxyphenethyl) -3,5-di-tert-butyl-4-hydroxybenzamide (N- (2-hydroxyphenethyl) -3,5-di-t-butyl-4-) h
ydroxybenzamide) 3,5-di-t-butyl-4-hydroxybenzoic acid 1.1
3 g (4.5 mmol) and 2-hydroxyphenethylamine 0.6
2 g (4.5 mmol) was added to 9 ml of dimethylformamide and stirred. To this solution, 0.93 g (4.5 mmol) of DCC was added, and 24
Stirred for hours. The precipitate was removed by filtration, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the solvent eluted with chloroform was distilled off, followed by drying under reduced pressure to obtain 0.76 g (yield 46%) of the title compound.

【0172】(物性) 無色不定形固体 PMR(DMSO-d6,δ ppm) :9.33(1H,s),8.30(1H,brt,J=4.9H
z),7.58(2H,s),7.28(1H,s),7.07(1H,d,J=7.3Hz),7.01(1
H,t,J=7.6Hz),6.80(1H,d,J=7.8Hz),6.71(1H,t,J=7.3H
z),3.41(2H,brq,J=6.8Hz),2.78(2H,brt,J=7.3Hz),1.41
(18H,s) IR(KBr, cm-1):3627,3381,2957,1634,1538,1456,1434,1
361,1316,1239,753
(Physical properties) Colorless amorphous solid PMR (DMSO-d 6 , δ ppm): 9.33 (1H, s), 8.30 (1H, brt, J = 4.9H)
z), 7.58 (2H, s), 7.28 (1H, s), 7.07 (1H, d, J = 7.3Hz), 7.01 (1
H, t, J = 7.6Hz), 6.80 (1H, d, J = 7.8Hz), 6.71 (1H, t, J = 7.3H)
z), 3.41 (2H, brq, J = 6.8Hz), 2.78 (2H, brt, J = 7.3Hz), 1.41
(18H, s) IR (KBr, cm -1 ): 3627,3381,2957,1634,1538,1456,1434,1
361,1316,1239,753

【0173】実施例60 ベンズアルデヒド O−3,
5−ジ−t−ブチル−4−ヒドロキシベンゾイルオキシ
ム(benzaldehyde O-3,5-di-t-butyl-4-hydroxybenzoylo
xime) 3,5−ジ−t−ブチル−4−ヒドロキシベンゾイルク
ロリド 0.54g(2mmol)、α−ベンズアルドキシム 0.24g
(2mmol) 及びピリジン 0.16ml(2mmol)をエーテル 4mlに
加え、3 時間攪拌した。溶媒を留去した。残渣をシリカ
ゲルカラムクロマトグラフィーに付し、酢酸エチル:n
−ヘキサン=1:3溶出部を溶媒留去し、酢酸エチル及
びn−ヘキサンを加えて結晶化させ、ろ取した。減圧下
で乾燥し、標記化合物 0.04g(収率6%) を得た。 (物性) 無色結晶(mp.159-161 ℃) PMR(DMSO-d6,δ ppm) :8.86(1H,s),7.88(1H,s),7.86(2
H,s),7.82(2H,d,J=7.8Hz),7.56-7.50(3H,m),1.44(18H,
s) IR(KBr, cm-1):3566,2959,1739,1598,1428,1308,1216,1
093,919,890,749,683
Example 60 Benzaldehyde O-3,
5-di-t-butyl-4-hydroxybenzoyloxime (benzaldehyde O-3,5-di-t-butyl-4-hydroxybenzoylo
xime) 3,5-di-t-butyl-4-hydroxybenzoyl chloride 0.54 g (2 mmol), α-benzaldoxime 0.24 g
(2 mmol) and 0.16 ml (2 mmol) of pyridine were added to 4 ml of ether and stirred for 3 hours. The solvent was distilled off. The residue was subjected to silica gel column chromatography, and ethyl acetate: n
The solvent was distilled off from the eluted portion of -hexane = 1: 3, and ethyl acetate and n-hexane were added for crystallization, followed by filtration. Drying under reduced pressure gave 0.04 g (yield 6%) of the title compound. (Physical properties) Colorless crystal (mp.159-161 ° C) PMR (DMSO-d 6 , δ ppm): 8.86 (1H, s), 7.88 (1H, s), 7.86 (2
H, s), 7.82 (2H, d, J = 7.8Hz), 7.56-7.50 (3H, m), 1.44 (18H,
s) IR (KBr, cm -1 ): 3566,2959,1739,1598,1428,1308,1216,1
093,919,890,749,683

【0174】実施例61〜65 α−ベンズアルドキシムを他のアルドキシム化合物に代
える以外は実施例60と実質的に同様に処理して、以下
の化合物を製造した。 実施例61 サリチルアルデヒド O−3,5−ジ−t
−ブチル−4−ヒドロキシベンゾイルオキシム(salicyl
aldehyde O-3,5-di-t-butyl-4-hydroxybenzoyloxime) 収率:46% (物性) 無色結晶(mp.167-168 ℃) PMR(DMSO-d6,δ ppm) :10.30(1H,s),8.93(1H,s),7.88(1
H,s),7.86(2H,s),7.73(1H,d,J=7.8Hz),7.37(1H,t,J=7.6
Hz),6.98(1H,d,J=8.3Hz),6.93(1H,t,J=7.3Hz),1.44(18
H,s) IR(KBr, cm-1):3588,2960,1738,1611,1432,1301,1269,1
213,1109,1086,951,892,747,706
Examples 61 to 65 The following compounds were prepared in substantially the same manner as in Example 60 except that α-benzaldoxime was replaced with another aldoxime compound. Example 61 Salicylaldehyde O-3,5-di-t
-Butyl-4-hydroxybenzoyl oxime (salicyl
aldehyde O-3,5-di-t-butyl-4-hydroxybenzoyloxime) Yield: 46% (physical properties) colorless crystal (mp.167-168 ° C) PMR (DMSO-d 6 , δ ppm): 10.30 (1H, s), 8.93 (1H, s), 7.88 (1
H, s), 7.86 (2H, s), 7.73 (1H, d, J = 7.8Hz), 7.37 (1H, t, J = 7.6
Hz), 6.98 (1H, d, J = 8.3Hz), 6.93 (1H, t, J = 7.3Hz), 1.44 (18
H, s) IR (KBr, cm -1 ): 3588,2960,1738,1611,1432,1301,1269,1
213,1109,1086,951,892,747,706

【0175】実施例62 2,4−ジヒドロキシベンズ
アルデヒド O−3,5−ジ−t−ブチル−4−ヒドロ
キシベンゾイルオキシム(2,4-dihydroxybenzaldehyde O
-3,5-di-t-butyl-4-hydroxybenzoyloxime) 収率:45% (物性) 無色結晶(mp.167-170 ℃) PMR(DMSO-d6,δ ppm) :10.16(1H,s),10.05(1H,s),8.78
(1H,s),7.83(3H,s),7.53(1H,d,J=8.3Hz),6.38(1H,s),6.
37(1H,d,J=8.3Hz),1.43(18H,s) IR(KBr, cm-1):3579,3383,2955,1717,1630,1609,1519,1
428,1301,1207,1116,946,848,703
Example 62 2,4-Dihydroxybenzaldehyde O-3,5-di-t-butyl-4-hydroxybenzoyl oxime
-3,5-di-t-butyl- 4-hydroxybenzoyloxime) Yield: 45% (Physical Properties) colorless crystals (mp.167-170 ℃) PMR (DMSO- d 6, δ ppm): 10.16 (1H, s) , 10.05 (1H, s), 8.78
(1H, s), 7.83 (3H, s), 7.53 (1H, d, J = 8.3Hz), 6.38 (1H, s), 6.
37 (1H, d, J = 8.3Hz), 1.43 (18H, s) IR (KBr, cm -1 ): 3579,3383,2955,1717,1630,1609,1519,1
428,1301,1207,1116,946,848,703

【0176】実施例63 o−バニリン O−3,5−
ジ−t−ブチル−4−ヒドロキシベンゾイルオキシム(o
-vanillin O-3,5-di-t-butyl-4-hydroxybenzoyloxime) 収率:19% (物性) 無色不定形固体 PMR(DMSO-d6,δ ppm) :11.44(1H,s),8.03(1H,s),7.94(1
H,s),7.93(2H,s),7.38(1H,d,J=7.8Hz),7.27(1H,t,J=7.8
Hz),7.15(1H,d,J=7.8Hz),3.77(3H,s),1.44(18H,s) IR(KBr, cm-1):3610,3428,2959,1731,1713,1479,1438,1
303,1279,1228,1190,1169,1110,976,783
Example 63 o-Vaniline O-3,5-
Di-t-butyl-4-hydroxybenzoyl oxime (o
-vanillin O-3,5-di-t-butyl-4-hydroxybenzoyloxime) Yield: 19% (physical properties) Colorless amorphous solid PMR (DMSO-d 6 , δ ppm): 11.44 (1H, s), 8.03 ( 1H, s), 7.94 (1
H, s), 7.93 (2H, s), 7.38 (1H, d, J = 7.8Hz), 7.27 (1H, t, J = 7.8
Hz), 7.15 (1H, d, J = 7.8Hz), 3.77 (3H, s), 1.44 (18H, s) IR (KBr, cm- 1 ): 3610,3428,2959,1731,1713,1479,1438 , 1
303,1279,1228,1190,1169,1110,976,783

【0177】実施例64 4−(ジエチルアミノ)サリ
チルアルデヒド O−3,5−ジ−t−ブチル−4−ヒ
ドロキシベンゾイルオキシム(4−(diethyla
mino)salicylaldehyde O−3,
5−di−t−butyl−4−hydroxyben
zoyloxime) 収率:75% (物性) 黄色不定形固体 PMR(DMSO-d6,δ ppm) :9.90(1H,s),8.72(1H,s),7.83(2
H,s),7.80(1H,s),7.43(1H,d,J=9.3Hz),6.29(1H,dd,J=9.
3,2.0Hz),6.16(1H,d,J=2.0Hz),3.37(4H,q,J=6.8Hz),1.4
3(18H,s),1.14(6H,t,J=7.1Hz) IR(KBr, cm-1):3619,3400,2970,1735,1634,1593,1518,1
297,1219,1133,1099,942
Example 64 4- (Diethylamino) salicylaldehyde O-3,5-di-tert-butyl-4-hydroxybenzoyloxime (4- (diethyla)
mino) salicylaldehyde O-3,
5-di-t-butyl-4-hydroxyben
zoloxime) Yield: 75% (physical properties) Yellow amorphous solid PMR (DMSO-d 6 , δ ppm): 9.90 (1H, s), 8.72 (1H, s), 7.83 (2
H, s), 7.80 (1H, s), 7.43 (1H, d, J = 9.3Hz), 6.29 (1H, dd, J = 9.
3,2.0Hz), 6.16 (1H, d, J = 2.0Hz), 3.37 (4H, q, J = 6.8Hz), 1.4
3 (18H, s), 1.14 (6H, t, J = 7.1Hz) IR (KBr, cm -1 ): 3619,3400,2970,1735,1634,1593,1518,1
297,1219,1133,1099,942

【0178】実施例65 5−ニトロサリチルアルデヒ
ド O−3,5−ジ−t−ブチル−4−ヒドロキシベン
ゾイルオキシム(5-nitrosalicylaldehyde O-3,5-di-t-b
utyl-4-hydroxybenzoyloxime) 収率:16% (物性) 無色結晶(mp.152-154 ℃) PMR(DMSO-d6,δ ppm) :11.86(1H,s),8.60(1H,d,J=2.9H
z),8.30(1H,dd,J=8.8,2.9Hz),8.18(1H,s),8.05(1H,s),
7.95(2H,s),7.62(1H,d,J=8.8Hz),1.44(18H,s) IR(KBr, cm-1):3577,3430,2966,1721,1533,1413,1352,1
305,1216,1095,979,839
Example 65 5-Nitrosalicylaldehyde O-3,5-di-t-butyl-4-hydroxybenzoyl oxime
utyl-4-hydroxybenzoyloxime) Yield: 16% (physical properties) Colorless crystals (mp. 152-154 ° C) PMR (DMSO-d 6 , δ ppm): 11.86 (1H, s), 8.60 (1H, d, J = 2.9H
z), 8.30 (1H, dd, J = 8.8,2.9Hz), 8.18 (1H, s), 8.05 (1H, s),
7.95 (2H, s), 7.62 (1H, d, J = 8.8Hz), 1.44 (18H, s) IR (KBr, cm -1 ): 3577,3430,2966,1721,1533,1413,1352,1
305,1216,1095,979,839

【0179】実施例66 N−ベンジルオキシ−3,5
−ジ−t−ブチル−4−ヒドロキシベンズアミド(N-ben
zyloxy-3,5-di-t-butyl-4-hydroxybenzamide) 3,5−ジ−t−ブチル−4−ヒドロキシ安息香酸 2.5
0g(10mmol)及びO−ベンジルヒドロキシルアミン 1.23g
(10mmol)を塩化メチレン 20ml に加え、攪拌した。この
溶液に、DCC 2.48g(12mmol)を加え、4 時間攪拌し
た。析出物をろ去し、溶媒を留去した。残渣をシリカゲ
ルカラムクロマトグラフィーに付し、メタノール:クロ
ロホルム=1:50溶出部を溶媒留去し、生じた結晶をろ
取した。減圧下で乾燥し、標記化合物 2.00g(収率56%)
を得た。 (物性) 無色結晶(mp.158-159 ℃) PMR(DMSO-d6,δ ppm) :11.54(1H,brs),7.53(2H,s),7.47
-7.33(6H,m),4.90(2H,s),1.39(18H,s) IR(KBr, cm-1):3619,3443,3146,2955,1635,1524,1434,1
332,1238,1163,1045,954,744,703
Example 66 N-benzyloxy-3,5
-Di-t-butyl-4-hydroxybenzamide (N-ben
zyloxy-3,5-di-t-butyl-4-hydroxybenzamide) 3,5-di-t-butyl-4-hydroxybenzoic acid 2.5
0 g (10 mmol) and O-benzylhydroxylamine 1.23 g
(10 mmol) was added to 20 ml of methylene chloride and stirred. To this solution, 2.48 g (12 mmol) of DCC was added and stirred for 4 hours. The precipitate was removed by filtration, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the solvent was distilled off from the eluted portion of methanol: chloroform = 1: 50, and the resulting crystals were collected by filtration. Dry under reduced pressure to give the title compound (2.00 g, 56% yield)
I got (Physical properties) Colorless crystal (mp.158-159 ° C) PMR (DMSO-d 6 , δ ppm): 11.54 (1H, brs), 7.53 (2H, s), 7.47
-7.33 (6H, m), 4.90 (2H, s), 1.39 (18H, s) IR (KBr, cm -1 ): 3619,3443,3146,2955,1635,1524,1434,1
332,1238,1163,1045,954,744,703

【0180】実施例67 3,5−ジ−t−ブチル−4
−ヒドロキシベンズアルデヒドサリチリデンヒドラゾン
(3,5-di-t-butyl-4-hydroxybenzaldehyde salicylidene
hydrazone) 3,5−ジ−t−ブチル−4−ヒドロキシベンズアルデ
ヒド 1.17g(5mmol) 及びサリチルアルデヒドヒドラゾン
0.68g(5mmol) をジメチルホルムアミド 10mlに溶か
し、室温下で15時間攪拌した。溶媒を留去し、酢酸エチ
ルを加え、飽和食塩水で洗浄し、硫酸マグネシウムで乾
燥し、溶媒を留去した。残渣をシリカゲルカラムクロマ
トグラフィーに付した。酢酸エチル:n−ヘキサン=
1:9溶出部を溶媒留去し、酢酸エチル及びn−ヘキサ
ンを加えて結晶化させ、ろ取した。減圧下で乾燥し、標
記化合物0.79g(収率45%)を得た。 (物性) 無色結晶(mp.145-147 ℃) PMR(DMSO-d6,δ ppm) :11.54(1H,s),8.92(1H,s),8.69(1
H,s),7.69(2H,s),7.62-7.58(2H,m),7.36(1H,td,J=7.8,
2.0Hz),6.97-6.93(2H,m),1.43(18H,s) IR(KBr, cm-1):3620,2953,1625,1419,1369,1317,1271,1
234,1209,1152,754
Example 67 3,5-Di-t-butyl-4
-Hydroxybenzaldehyde salicylidenehydrazone
(3,5-di-t-butyl-4-hydroxybenzaldehyde salicylidene
1.17 g (5 mmol) of 3,5-di-t-butyl-4-hydroxybenzaldehyde and salicylaldehyde hydrazone
0.68 g (5 mmol) was dissolved in 10 ml of dimethylformamide, and the mixture was stirred at room temperature for 15 hours. The solvent was distilled off, ethyl acetate was added, the mixture was washed with saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography. Ethyl acetate: n-hexane =
The solvent eluted from the 1: 9 eluted portion was crystallized by adding ethyl acetate and n-hexane, and collected by filtration. Drying under reduced pressure gave 0.79 g (yield 45%) of the title compound. (Physical Properties) colorless crystals (mp.145-147 ℃) PMR (DMSO- d 6, δ ppm): 11.54 (1H, s), 8.92 (1H, s), 8.69 (1
H, s), 7.69 (2H, s), 7.62-7.58 (2H, m), 7.36 (1H, td, J = 7.8,
2.0Hz), 6.97-6.93 (2H, m), 1.43 (18H, s) IR (KBr, cm- 1 ): 3620,2953,1625,1419,1369,1317,1271,1
234,1209,1152,754

【0181】実施例68 プロピオンアルデヒド3,5
−ジ−t−ブチル−4−ヒドロキシベンゾイルヒドラゾ
ン(propionaldehyde 3,5-di-t-butyl-4-hydroxybenzoyl
hydrazone) 参考例1で合成した化合物3,5−ジ−t−ブチル−4
−ヒドロキシベンゾヒドラジド 0.53g(2mmol) 及びプロ
ピオンアルデヒド 0.15ml(2mmol)をエタノール10ml に
溶かし、室温下で24時間攪拌した。溶媒を留去し、イソ
プロピルエーテルを加え、結晶をろ取した。減圧下で乾
燥し、標記化合物0.42g(収率69%)を得た。 (物性) 無色結晶(mp.190-192 ℃) PMR(DMSO-d6,δ ppm) :11.17(1H,brs),7.73(1H,brs),7.
56(2H,s),7.42(1H,s),2.30-2.26(2H,m),1.41(18H,s),1.
06(3H,t,J=7.1Hz) IR(KBr, cm-1):3630,3356,3212,3075,2964,1624,1555,1
435,1361,1313,1240,1159,1053,770,699
Example 68 Propionaldehyde 3,5
-Di-t-butyl-4-hydroxybenzoylhydrazone (propionaldehyde 3,5-di-t-butyl-4-hydroxybenzoyl
hydrazone) Compound 3,5-di-t-butyl-4 synthesized in Reference Example 1.
0.53 g (2 mmol) of -hydroxybenzohydrazide and 0.15 ml (2 mmol) of propionaldehyde were dissolved in 10 ml of ethanol, and the mixture was stirred at room temperature for 24 hours. The solvent was distilled off, isopropyl ether was added, and the crystals were collected by filtration. Drying under reduced pressure gave 0.42 g (69% yield) of the title compound. (Physical Properties) colorless crystals (mp.190-192 ℃) PMR (DMSO- d 6, δ ppm): 11.17 (1H, brs), 7.73 (1H, brs), 7.
56 (2H, s), 7.42 (1H, s), 2.30-2.26 (2H, m), 1.41 (18H, s), 1.
06 (3H, t, J = 7.1Hz) IR (KBr, cm -1 ): 3630,3356,3212,3075,2964,1624,1555,1
435,1361,1313,1240,1159,1053,770,699

【0182】実施例69〜70 プロピオンアルデヒドを他のアルデヒド化合物に代える
以外は実施例68と実質的に同様に処理して、以下の化
合物を製造した。 実施例69 グリセルアルデヒド3,5−ジ−t−ブチ
ル−4−ヒドロキシベンゾイルヒドラゾン(glyceraldeh
yde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone) 収率:82% (物性) 無色結晶(mp.227-229 ℃(dec.)) PMR(DMSO-d6,δ ppm) :11.33(1H,brs),7.66(1H,brd,J=
5.6Hz),7.59(2H,s),7.47(1H,s),5.26(1H,brd,J=4.4Hz),
4.75(1H,brt,J=5.4Hz),4.10(1H,m),3.51(2H,brt,J=5.6H
z),1.41(18H,s) IR(KBr, cm-1):3402,3205,3066,2961,2360,2344,1616,1
546,1435,1340,1316,1252,1106
Examples 69 to 70 The following compounds were prepared in substantially the same manner as in Example 68 except that propionaldehyde was replaced with another aldehyde compound. Example 69 Glyceraldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone (glyceraldeh
yde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone) Yield: 82% (physical properties) colorless crystal (mp.227-229 ° C (dec.)) PMR (DMSO-d 6 , δ ppm): 11.33 ( 1H, brs), 7.66 (1H, brd, J =
5.6Hz), 7.59 (2H, s), 7.47 (1H, s), 5.26 (1H, brd, J = 4.4Hz),
4.75 (1H, brt, J = 5.4Hz), 4.10 (1H, m), 3.51 (2H, brt, J = 5.6H
z), 1.41 (18H, s) IR (KBr, cm -1 ): 3402,3205,3066,2961,2360,2344,1616,1
546,1435,1340,1316,1252,1106

【0183】実施例70 2,2−ジメチル−3−ヒド
ロキシプロピオンアルデヒド3,5−ジ−t−ブチル−
4−ヒドロキシベンゾイルヒドラゾン(2,2-dimethyl-3-
hydroxypropionaldehyde 3,5-di-t-butyl-4-hydroxyben
zoylhydrazone) 収率:72% (物性) 無色結晶(mp.229-231 ℃) PMR(DMSO-d6,δ ppm) :11.15(1H,brs),7.73(1H,s),7.56
(2H,s),7.41(1H,s),4.77(1H,brs),3.30(2H,s),1.41(18
H,s),1.05(6H,s) IR(KBr, cm-1):3635,3422,3224,2950,1645,1550,1436,1
360,1311,1240,1047
Example 70 2,2-Dimethyl-3-hydroxypropionaldehyde 3,5-di-tert-butyl-
4-hydroxybenzoylhydrazone (2,2-dimethyl-3-
hydroxypropionaldehyde 3,5-di-t-butyl-4-hydroxyben
Zoylhydrazone) Yield: 72% (Physical Properties) colorless crystals (mp.229-231 ℃) PMR (DMSO- d 6, δ ppm): 11.15 (1H, brs), 7.73 (1H, s), 7.56
(2H, s), 7.41 (1H, s), 4.77 (1H, brs), 3.30 (2H, s), 1.41 (18
H, s), 1.05 (6H, s) IR (KBr, cm -1 ): 3635,3422,3224,2950,1645,1550,1436,1
360,1311,1240,1047

【0184】実施例71 ベンズアルデヒド6−ヒドロ
キシ−2,5,7,8−テトラメチルクロマン−2−ア
セチルヒドラゾン(benzaldehyde 6-hydroxy-2,5,7,8-te
tramethylchroman-2-acetylhydrazone) 参考例2で合成した化合物6−ヒドロキシ−2,5,
7,8−テトラメチルクロマン−2−アセトヒドラジド
(6-hydroxy-2,5,7,8-tetramethylchroman-2-acetohydra
zide) 0.56g(2mmol)及びベンズアルデヒド 0.22ml(2mmo
l)をエタノール10ml及びメタノール 5mlに溶かし、室温
下で12時間攪拌した。溶媒を留去し、残渣をシリカゲル
カラムクロマトグラフィーに付した。酢酸エチル:n−
ヘキサン=1:1溶出部を溶媒留去し、クロロホルムを
加えて結晶化させ、ろ取した。減圧下で乾燥し、標記化
合物 0.71g(収率.97%) を得た。 (物性) 無色結晶(mp.121-123 ℃) PMR(DMSO-d6,δ ppm) :11.33,11.29(1H,each-s),8.15,
7.94(1H,each-s),7.69,7.67(1H,each-s),7.45-7.32(5H,
m),3.01-2.46(4H,m),2.06-1.81(11H,m),1.39,1.35(3H,e
ach-s) IR(KBr, cm-1):3390,2930,1667,1558,1460,1373,1254,7
57,693
Example 71 Benzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
tramethylchroman-2-acetylhydrazone) Compound 6-hydroxy-2,5,5 synthesized in Reference Example 2.
7,8-tetramethylchroman-2-acetohydrazide
(6-hydroxy-2,5,7,8-tetramethylchroman-2-acetohydra
zide) 0.56 g (2 mmol) and benzaldehyde 0.22 ml (2 mmo
l) was dissolved in ethanol (10 ml) and methanol (5 ml), and the mixture was stirred at room temperature for 12 hours. The solvent was distilled off, and the residue was subjected to silica gel column chromatography. Ethyl acetate: n-
The solvent was distilled off from the eluted portion of hexane = 1: 1, chloroform was added for crystallization, and the crystal was collected by filtration. Drying under reduced pressure gave 0.71 g (yield .97%) of the title compound. (Physical Properties) colorless crystals (mp.121-123 ℃) PMR (DMSO- d 6, δ ppm): 11.33,11.29 (1H, each-s), 8.15,
7.94 (1H, each-s), 7.69,7.67 (1H, each-s), 7.45-7.32 (5H,
m), 3.01-2.46 (4H, m), 2.06-1.81 (11H, m), 1.39,1.35 (3H, e
ach-s) IR (KBr, cm -1 ): 3390,2930,1667,1558,1460,1373,1254,7
57,693

【0185】実施例72〜107 ベンズアルデヒドを他のアルデヒド化合物又はケトン化
合物に代える以外は実施例71と実質的に同様に処理し
て、以下の化合物を製造した。 実施例72 サリチルアルデヒド6−ヒドロキシ−2,
5,7,8−テトラメチルクロマン−2−アセチルヒド
ラゾン(salicylaldehyde 6-hydroxy-2,5,7,8-tetrameth
ylchroman-2-acetylhydrazone) 収率:100% (物性) 淡黄色結晶(mp.116-118 ℃) PMR(DMSO-d6,δ ppm) :11.58,11.28(1H,each-s),11.19,
10.05(1H,each-s),8.33,8.24(1H,each-s),7.47,7.40(1
H,each-dd,J=7.8,1.5Hz),7.39,7.33(1H,each-s),7.27,
7.19(1H,each-td,J=7.8,1.5Hz),6.92,6.77(2H,m),2.95-
2.45(4H,m),2.06-1.82(11H,m),1.36,1.25(3H,each-s) IR(KBr, cm-1):3160,3040,2928,1651,1614,1571,1460,1
358,1329,1250,1159,755
Examples 72 to 107 The following compounds were prepared in substantially the same manner as in Example 71 except that benzaldehyde was replaced with another aldehyde compound or ketone compound. Example 72 Salicylaldehyde 6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetylhydrazone (salicylaldehyde 6-hydroxy-2,5,7,8-tetrameth
ylchroman-2-acetylhydrazone) Yield: 100% (physical properties) pale yellow crystals (mp.116-118 ℃) PMR (DMSO- d 6, δ ppm): 11.58,11.28 (1H, each-s), 11.19,
10.05 (1H, each-s), 8.33,8.24 (1H, each-s), 7.47,7.40 (1
H, each-dd, J = 7.8,1.5Hz), 7.39,7.33 (1H, each-s), 7.27,
7.19 (1H, each-td, J = 7.8,1.5Hz), 6.92,6.77 (2H, m), 2.95-
2.45 (4H, m), 2.06-1.82 (11H, m), 1.36,1.25 (3H, each-s) IR (KBr, cm -1 ): 3160,3040,2928,1651,1614,1571,1460,1
358,1329,1250,1159,755

【0186】実施例73 3−ヒドロキシベンズアルデ
ヒド6−ヒドロキシ−2,5,7,8−テトラメチルク
ロマン−2−アセチルヒドラゾン(3-hydroxybenzaldehy
de 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhy
drazone) 収率:55% (物性) 無色結晶(mp.207-210 ℃) PMR(DMSO-d6,δ ppm) :11.27,11.24(1H,each-s),9.54,
9.51(1H,each-s),8.04,7.87(1H,each-s),7.39,7.33(1H,
each-s),7.23-7.14(1H,m),7.13,7.00(1H,each-s),7.04,
6.92(1H,each-d,J=7.8Hz),6.81-6.76(1H,m),2.94-2.42
(4H,m),2.05-1.81(11H,m),1.36,1.34(3H,each-s) IR(KBr, cm-1):3560,1674,1538,1462,1366,1260,1166,1
079
Example 73 3-Hydroxybenzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
de 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhy
drazone) Yield: 55% (Physical properties) Colorless crystals (mp. 207-210 ° C) PMR (DMSO-d 6 , δ ppm): 11.27, 11.24 (1H, each-s), 9.54,
9.51 (1H, each-s), 8.04,7.87 (1H, each-s), 7.39,7.33 (1H,
each-s), 7.23-7.14 (1H, m), 7.13,7.00 (1H, each-s), 7.04,
6.92 (1H, each-d, J = 7.8Hz), 6.81-6.76 (1H, m), 2.94-2.42
(4H, m), 2.05-1.81 (11H, m), 1.36,1.34 (3H, each-s) IR (KBr, cm -1 ): 3560,1674,1538,1462,1366,1260,1166,1
079

【0187】実施例74 4−ヒドロキシベンズアルデ
ヒド6−ヒドロキシ−2,5,7,8−テトラメチルク
ロマン−2−アセチルヒドラゾン(4-hydroxybenzaldehy
de 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhy
drazone) 収率:76% (物性) 無色結晶(mp.168-170 ℃) PMR(DMSO-d6,δ ppm) :11.11,11.08
(1H,each−s),9.82,9.76(1H,
each−s),8.03,7.85(1H,each
−s),7.49,7.31(2H,each−d,J
=8.3Hz),7.38,7.34(1H,each
−s),6.80,6.75(2H,each−d,J
=8.3Hz),2.91−2.39 (4H,m),
2.05−1.82(11H,m),1.38,1.3
4(3H,each−s) IR(KBr, cm−1):3430,3396,1
675,1609,1515,1449,1371,1
238,1170,1089
Example 74 4-Hydroxybenzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
de 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhy
(drazone) Yield: 76% (physical properties) Colorless crystals (mp. 168-170 ° C) PMR (DMSO-d 6 , δ ppm): 11.11, 11.08
(1H, etch-s), 9.82, 9.76 (1H,
each-s), 8.03, 7.85 (1H, each
-S), 7.49, 7.31 (2H, reach-d, J
= 8.3 Hz), 7.38, 7.34 (1H, each)
-S), 6.80, 6.75 (2H, reach-d, J
= 8.3 Hz), 2.91-2.39 (4H, m),
2.05-1.82 (11H, m), 1.38, 1.3
4 (3H, each-s) IR (KBr, cm- 1 ): 3430,3396,1
675,1609,1515,1449,1371,1
238, 1170, 1089

【0188】実施例75 o−アニスアルデヒド6−ヒ
ドロキシ−2,5,7,8−テトラメチルクロマン−2
−アセチルヒドラゾン(o−anisaldehyde
6−hydroxy−2,5,7,8−tetram
ethylchroman−2− acetylhyd
razone) 収率:69% (物性) 無色結晶(mp.166-167 ℃) PMR(DMSO-d6,δ ppm) :11.30,11.25(1H,each-s),8.48,
8.29(1H,each-s),7.80,7.47(1H,each-dd,J=7.8,1.5Hz),
7.41-7.32(2H,m),7.07,7.03(1H,each-d,J=8.8Hz),6.99,
6.90(1H,each-t,J=7.6Hz),3.85,3.82(3H,each-s),2.99-
2.40(4H,m),2.06-1.78(11H,m),1.38,1.34(3H,each-s) IR(KBr, cm-1):3380,2936,1675,1604,1569,1467,1376,1
254,1161,1097,753
Example 75 o-Anisaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2
-Acetylhydrazone (o-anisaldehyde
6-hydroxy-2,5,7,8-tetram
ethylchroman-2-acetylhyd
razone) Yield: 69% (physical properties) Colorless crystals (mp. 166-167 ° C) PMR (DMSO-d 6 , δ ppm): 11.30, 11.25 (1H, each-s), 8.48,
8.29 (1H, each-s), 7.80,7.47 (1H, each-dd, J = 7.8,1.5Hz),
7.41-7.32 (2H, m), 7.07,7.03 (1H, each-d, J = 8.8Hz), 6.99,
6.90 (1H, each-t, J = 7.6Hz), 3.85,3.82 (3H, each-s), 2.99-
2.40 (4H, m), 2.06-1.78 (11H, m), 1.38,1.34 (3H, each-s) IR (KBr, cm -1 ): 3380,2936,1675,1604,1569,1467,1376,1
254,1161,1097,753

【0189】実施例76 o−アセチルサリチルアルデ
ヒド6−ヒドロキシ−2,5,7,8−テトラメチルク
ロマン−2−アセチルヒドラゾン(o-acetylsalicylalde
hyde6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylh
ydrazone) 収率:47% (物性) 無色結晶(mp.170-171 ℃) PMR(DMSO-d6,δ ppm) :11.34,11.25(1H,each-s),8.15,
8.02(1H,each-s),7.80,7.50(1H,each-d,J=7.8Hz),7.46,
7.41(1H,each-d,J=7.8Hz),7.38,7.32(1H,each-s),7.32,
7.23(1H,each-t,J=7.6Hz),7.16,7.12(1H,each-d,J=7.8H
z),3.31-2.81(2H,m),2.62-2.42(2H,m),2.37,2.30(3H,ea
ch-s),2.09-1.80(11H,m),1.38,1.34(3H,each-s) IR(KBr, cm-1):3374,1773,1682,1557,1452,1366,1201,1
176,1091,1008,908,756
Example 76 o-acetylsalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
hyde6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylh
Ydrazone) Yield: 47% (Physical properties) Colorless crystals (mp. 170-171 ° C) PMR (DMSO-d 6 , δ ppm): 11.34, 11.25 (1H, each-s), 8.15,
8.02 (1H, each-s), 7.80,7.50 (1H, each-d, J = 7.8Hz), 7.46,
7.41 (1H, each-d, J = 7.8Hz), 7.38,7.32 (1H, each-s), 7.32,
7.23 (1H, each-t, J = 7.6Hz), 7.16,7.12 (1H, each-d, J = 7.8H
z), 3.31-2.81 (2H, m), 2.62-2.42 (2H, m), 2.37,2.30 (3H, ea
ch-s), 2.09-1.80 (11H, m), 1.38,1.34 (3H, each-s) IR (KBr, cm -1 ): 3374,1773,1682,1557,1452,1366,1201,1
176,1091,1008,908,756

【0190】実施例77 o−トルアルデヒド6−ヒド
ロキシ−2,5,7,8−テトラメチルクロマン−2−
アセチルヒドラゾン(o−tolualdehyde
6−hydroxy−2,5,7,8−tetrame
thylchroman−2−acetylhydra
zone) 収率:91% (物性) 無色結晶(mp.150 ℃) PMR(DMSO-d6,δ ppm) :11.31,11.22(1H,each-s),8.42,
8.23(1H,each-s),7.78,7.47(1H,each-d,J=7.3Hz),7.39,
7.33(1H,each-s),7.31-7.14(3H,m),3.00-2.43(4H,m),2.
41,2.36(3H,each-s),2.06-1.79(11H,m),1.38,1.35(3H,e
ach-s) IR(KBr, cm-1):3400,3200,2926,1662,1564,1458,1373,1
258,1087,757
Example 77 o-Tolualdehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-
Acetylhydrazone (o-toludehyde)
6-hydroxy-2,5,7,8-tetrame
thylchroman-2-acetylhydra
zone) Yield: 91% (physical properties) Colorless crystals (mp. 150 ° C.) PMR (DMSO-d 6 , δ ppm): 11.31, 11.22 (1H, each-s), 8.42,
8.23 (1H, each-s), 7.78,7.47 (1H, each-d, J = 7.3Hz), 7.39,
7.33 (1H, each-s), 7.31-7.14 (3H, m), 3.00-2.43 (4H, m), 2.
41,2.36 (3H, each-s), 2.06-1.79 (11H, m), 1.38,1.35 (3H, e
ach-s) IR (KBr, cm -1 ): 3400,3200,2926,1662,1564,1458,1373,1
258,1087,757

【0191】実施例78 2−ニトロベンズアルデヒド
6−ヒドロキシ−2,5,7,8−テトラメチルクロマ
ン−2−アセチルヒドラゾン(2-nitrobenzaldehyde 6-h
ydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazon
e) 収率:36% (物性) 無色結晶(mp.160 ℃) PMR(DMSO-d6,δ ppm) :11.67,11.56(1H,each-s),8.57,
8.31(1H,each-s),8.10-7.53(4H,m),7.38,7.30(1H,each-
s),3.29-2.46(4H,m),2.06-1.78(11H,m),1.40,1.35(3H,e
ach-s) IR(KBr, cm-1):3450,2932,1658,1526,1338,1259,1088
Example 78 2-Nitrobenzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
ydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazon
e) Yield: 36% (Physical Properties) colorless crystals (mp.160 ℃) PMR (DMSO- d 6, δ ppm): 11.67,11.56 (1H, each-s), 8.57,
8.31 (1H, each-s), 8.10-7.53 (4H, m), 7.38,7.30 (1H, each-s)
s), 3.29-2.46 (4H, m), 2.06-1.78 (11H, m), 1.40,1.35 (3H, e
ach-s) IR (KBr, cm -1 ): 3450,2932,1658,1526,1338,1259,1088

【0192】実施例79 2−フルオロベンズアルデヒ
ド6−ヒドロキシ−2,5,7,8−テトラメチルクロ
マン−2−アセチルヒドラゾン(2-fluorobenzaldehyde
6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydra
zone) 収率:79% (物性) 無色結晶(mp.131-133 ℃) PMR(DMSO-d6,δ ppm) :11.47,11.41
(1H,each−s),8.38,8.14(1H,
each−s),7.91−7.13(5H,m),
3.08−2.4 3(4H,m),2.05−1.7
8(11H,m),1.39,1.35(3H,eac
h−s) IR(KBr, cm−1):3420,2930,1
666,1559,1460,1370,1256,1
087,759
Example 79 2-fluorobenzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydra
zone) Yield: 79% (physical properties) Colorless crystals (mp. 131-133 ° C.) PMR (DMSO-d 6 , δ ppm): 11.47, 11.41
(1H, each-s), 8.38,8.14 (1H,
each-s), 7.91-7.13 (5H, m),
3.08-2.4 3 (4H, m), 2.05-1.7
8 (11H, m), 1.39, 1.35 (3H, eac
h-s) IR (KBr, cm- 1 ): 3420, 2930, 1
666, 1559, 1460, 1370, 1256, 1
087,759

【0193】実施例80 2−シアノベンズアルデヒド
6−ヒドロキシ−2,5,7,8−テトラメチルクロマ
ン−2−アセチルヒドラゾン(2−cyanobenz
aldehyde 6−hydroxy−2,5,7,
8−tetramethylchroman−2−ac
etylhydrazone) 収率:27% (物性) 淡黄色結晶(mp.163-164 ℃) PMR(DMSO-d6,δ ppm) :11.73,11.56(1H,each-s),8.52,
8.18(1H,each-s),8.08,7.87(1H,each-d,J=7.8Hz),7.81-
7.49(3H,m),7.39,7.24(1H,each-s),3.25-2.46(4H,m),2.
06-1.78(11H,m),1.39,1.36(3H,each-s) IR(KBr, cm-1):3440,2934,2224,1657,1451,1378,1259,1
088,762
Example 80 2-cyanobenzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (2-cyanobenz)
aldehyde 6-hydroxy-2,5,7,
8-tetramethylchroman-2-ac
Etylhydrazone) Yield: 27% (property) pale yellow crystals (mp.163-164 ℃) PMR (DMSO- d 6, δ ppm): 11.73,11.56 (1H, each-s), 8.52,
8.18 (1H, each-s), 8.08,7.87 (1H, each-d, J = 7.8Hz), 7.81-
7.49 (3H, m), 7.39,7.24 (1H, each-s), 3.25-2.46 (4H, m), 2.
06-1.78 (11H, m), 1.39,1.36 (3H, each-s) IR (KBr, cm -1 ): 3440,2934,2224,1657,1451,1378,1259,1
088,762

【0194】実施例81 α−テトラロン6−ヒドロキ
シ−2,5,7,8−テトラメチルクロマン−2−アセ
チルヒドラゾンN-5398α-tetralone 6-hydroxy-2,5,7,8
-tetramethylchroman-2-acetylhydrazone) 収率:54% (物性) 淡黄色結晶(mp.153-155 ℃) PMR(DMSO-d6,δ ppm) :10.37,10.15(1H,each-s),8.03,
7.67(1H,each-d,J=7.8Hz),7.40-7.09(4H,m),3.06-2.50
(8H,m),2.06-1.81(13H,m),1.40,1.36(3H,each-s) IR(KBr, cm-1):3400,3222,2930,1662,1540,1454,1344,1
252,1087,762
Example 81 α-tetralone 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone N-5398α-tetralone 6-hydroxy-2,5,7,8
-tetramethylchroman-2-acetylhydrazone) Yield: 54% (property) pale yellow crystals (mp.153-155 ℃) PMR (DMSO- d 6, δ ppm): 10.37,10.15 (1H, each-s), 8.03,
7.67 (1H, each-d, J = 7.8Hz), 7.40-7.09 (4H, m), 3.06-2.50
(8H, m), 2.06-1.81 (13H, m), 1.40,1.36 (3H, each-s) IR (KBr, cm -1 ): 3400,3222,2930,1662,1540,1454,1344,1
252,1087,762

【0195】実施例82 o−ヒドロキシアセトフェノ
ン6−ヒドロキシ−2,5,7,8−テトラメチルクロ
マン−2−アセチルヒドラゾン(o-hydroxyacetophenone
6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydr
azone) 収率:52% (物性) 無色結晶(mp.174-176 ℃) PMR(DMSO-d6,δ ppm) :13.23(1H,s),10.85(1H,s),7.56
(1H,d,J=6.8Hz),7.41(1H,s),7.26(1H,t,J=7.1Hz),6.89-
6.85(2H,m),2.67(2H,s),2.64-2.50(2H,m),2.33(3H,s),
2.05-1.80(11H,m),1.37(3H,s) IR(KBr, cm-1):3350,3248,1663,1612,1525,1250,1231,1
173,1089,756
Example 82: o-Hydroxyacetophenone 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (o-hydroxyacetophenone)
6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydr
Azone) Yield: 52% (Physical Properties) colorless crystals (mp.174-176 ℃) PMR (DMSO- d 6, δ ppm): 13.23 (1H, s), 10.85 (1H, s), 7.56
(1H, d, J = 6.8Hz), 7.41 (1H, s), 7.26 (1H, t, J = 7.1Hz), 6.89-
6.85 (2H, m), 2.67 (2H, s), 2.64-2.50 (2H, m), 2.33 (3H, s),
2.05-1.80 (11H, m), 1.37 (3H, s) IR (KBr, cm -1 ): 3350,3248,1663,1612,1525,1250,1231,1
173,1089,756

【0196】実施例83 2,4−ジヒドロキシベンズ
アルデヒド6−ヒドロキシ−2,5,7,8−テトラメ
チルクロマン−2−アセチルヒドラゾン(2,4-dihydroxy
benzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-
2-acetylhydrazone) 収率:90% (物性) 淡黄色結晶(mp.153 ℃) PMR(DMSO-d6,δ ppm) :11.38(1H,s),11.36(1H,s),9.87
(1H,s),8.19(1H,s),7.39(1H,s),7.23(1H,d,J=8.8Hz),6.
34(1H,d,J=8.4Hz),6.29(1H,s),2.70-2.40(4H,m),2.10-
1.70(11H,m),1.34(3H,s) IR(KBr, cm-1):3222,2932,1653,1633,1610,1521,1240,1
216,1177,1163,1083,759
Example 83 2,4-Dihydroxybenzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (2,4-dihydroxy
benzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-
2-acetylhydrazone) Yield: 90% (property) pale yellow crystals (mp.153 ℃) PMR (DMSO- d 6, δ ppm): 11.38 (1H, s), 11.36 (1H, s), 9.87
(1H, s), 8.19 (1H, s), 7.39 (1H, s), 7.23 (1H, d, J = 8.8Hz), 6.
34 (1H, d, J = 8.4Hz), 6.29 (1H, s), 2.70-2.40 (4H, m), 2.10-
1.70 (11H, m), 1.34 (3H, s) IR (KBr, cm -1 ): 3222,2932,1653,1633,1610,1521,1240,1
216,1177,1163,1083,759

【0197】実施例84 2,3−ジヒドロキシベンズ
アルデヒド6−ヒドロキシ−2,5,7,8−テトラメ
チルクロマン−2−アセチルヒドラゾン(2,3-dihydroxy
benzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-
2-acetylhydrazone) 収率:75% (物性) 淡黄色結晶(mp.184-186 ℃) PMR(DMSO-d6,δ ppm) :11.58(1H,brs),11.05(1H,brs),
9.12(1H,brs),8.28(1H,s),7.39(1H,brs),6.90(1H,d,J=
7.8Hz),6.83(1H,d,J=7.8Hz),6.71(1H,t,J=7.8Hz),2.70-
2.40(4H,m),2.10-1.80(11H,m),1.35(3H,s) IR(KBr, cm-1):3266,1663,1562,1370,1275,1162,1088
Example 84 2,3-Dihydroxybenzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (2,3-dihydroxy
benzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-
2-acetylhydrazone) Yield: 75% (property) pale yellow crystals (mp.184-186 ℃) PMR (DMSO- d 6, δ ppm): 11.58 (1H, brs), 11.05 (1H, brs),
9.12 (1H, brs), 8.28 (1H, s), 7.39 (1H, brs), 6.90 (1H, d, J =
7.8Hz), 6.83 (1H, d, J = 7.8Hz), 6.71 (1H, t, J = 7.8Hz), 2.70-
2.40 (4H, m), 2.10-1.80 (11H, m), 1.35 (3H, s) IR (KBr, cm -1 ): 3266,1663,1562,1370,1275,1162,1088

【0198】実施例85 5−ニトロサリチルアルデヒ
ド6−ヒドロキシ−2,5,7,8−テトラメチルクロ
マン−2−アセチルヒドラゾン(5−nitrosal
icylaldehyde 6−hydroxy−2,
5,7,8−tetramethylchroman−
2−acetylhydrazone) 収率:75% (物性) 黄色結晶(mp.230-231 ℃) PMR(DMSO-d6,δ ppm) :12.27,11.50(1H,each-brs),11.7
8,11.43(1H,each-s),8.55,8.23(1H,each-d,J=2.9Hz),8.
45,8.20(1H,each-s),8.15,8.07(1H,each-dd,J=8.8,2.9H
z),7.40,7.18(1H,each-s),7.09,7.02(1H,each-d,J=8.8H
z),3.25-2.50(4H,m),2.10-1.75(11H,m),1.37,1.35(3H,e
ach-s) IR(KBr, cm-1):3600,3208,3062,2926,1667,1613,1528,1
482,1339,1284,1253,1197,1086
Example 85 5-Nitrosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (5-nitrosalal)
icylaldehyde 6-hydroxy-2,
5,7,8-tetramethylchroman-
2-acetylhydrazine) Yield: 75% (physical properties) Yellow crystal (mp. 230-231 ° C) PMR (DMSO-d 6 , δ ppm): 12.27, 11.50 (1H, each-brs), 11.7
8,11.43 (1H, each-s), 8.55,8.23 (1H, each-d, J = 2.9Hz), 8.
45,8.20 (1H, each-s), 8.15,8.07 (1H, each-dd, J = 8.8,2.9H
z), 7.40,7.18 (1H, each-s), 7.09,7.02 (1H, each-d, J = 8.8H
z), 3.25-2.50 (4H, m), 2.10-1.75 (11H, m), 1.37,1.35 (3H, e
ach-s) IR (KBr, cm -1 ): 3600,3208,3062,2926,1667,1613,1528,1
482,1339,1284,1253,1197,1086

【0199】実施例86 2−ヒドロキシ−5−メトキ
シベンズアルデヒド6−ヒドロキシ−2,5,7,8−
テトラメチルクロマン−2−アセチルヒドラゾン(2-hyd
roxy-5-methoxybenzaldehyde 6-hydroxy-2,5,7,8-tetra
methylchroman-2-acetylhydrazone) 収率:90% (物性) 淡黄色結晶(mp.153-154 ℃) PMR(DMSO-d6,δ ppm) :11.57,11.33(1H,each-s),10.60,
9.62(1H,each-s),8.32,8.22(1H,each-s),7.40,7.33(1H,
each-s),7.07,7.03(1H,each-d,J=2.9Hz),6.89-6.77(2H,
m),3.72,3.64(3H,s),2.93-2.44(4H,m),2.06-1.80(11H,
m),1.35(3H,s) IR(KBr, cm-1):3384,3292,3210,3056,2934,1669,1628,1
493,1269,1164,1084,1038
Example 86 2-hydroxy-5-methoxybenzaldehyde 6-hydroxy-2,5,7,8-
Tetramethylchroman-2-acetylhydrazone (2-hyd
roxy-5-methoxybenzaldehyde 6-hydroxy-2,5,7,8-tetra
methylchroman-2-acetylhydrazone) Yield: 90% (property) pale yellow crystals (mp.153-154 ℃) PMR (DMSO- d 6, δ ppm): 11.57,11.33 (1H, each-s), 10.60,
9.62 (1H, each-s), 8.32,8.22 (1H, each-s), 7.40,7.33 (1H, each-s)
each-s), 7.07,7.03 (1H, each-d, J = 2.9Hz), 6.89-6.77 (2H,
m), 3.72,3.64 (3H, s), 2.93-2.44 (4H, m), 2.06-1.80 (11H,
m), 1.35 (3H, s) IR (KBr, cm -1 ): 3384,3292,3210,3056,2934,1669,1628,1
493,1269,1164,1084,1038

【0200】実施例87 5−クロロサリチルアルデヒ
ド6−ヒドロキシ−2,5,7,8−テトラメチルクロ
マン−2−アセチルヒドラゾン(5-chlorosalicylaldehy
de 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhy
drazone) 収率:85% (物性) 無色結晶(mp.159-160 ℃) PMR(DMSO-d6,δ ppm) :11.67,11.37(1H,each-s),11.19,
10.30(1H,each-brs),8.32,8.20(1H,each-s),7.61,7.45
(1H,each-d,J=2.4Hz),7.40,7.30(1H,each-s),7.26,7.19
(1H,each-dd,J=8.8,2.9Hz),6.89(1H,d,J=8.8Hz),2.93-
2.44(4H,m),2.06-1.79(11H,m),1.35(3H,s) IR(KBr, cm-1):3238,3060,2926,1668,1549,1481,1346,1
271,1182,1088
Example 87 5-chlorosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
de 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhy
drazone) Yield: 85% (physical properties) Colorless crystals (mp. 159-160 ° C) PMR (DMSO-d 6 , δ ppm): 11.67, 11.37 (1H, each-s), 11.19,
10.30 (1H, each-brs), 8.32,8.20 (1H, each-s), 7.61,7.45
(1H, each-d, J = 2.4Hz), 7.40,7.30 (1H, each-s), 7.26,7.19
(1H, each-dd, J = 8.8,2.9Hz), 6.89 (1H, d, J = 8.8Hz), 2.93-
2.44 (4H, m), 2.06-1.79 (11H, m), 1.35 (3H, s) IR (KBr, cm -1 ): 3238,3060,2926,1668,1549,1481,1346,1
271,1182,1088

【0201】実施例88 5−ブロモサリチルアルデヒ
ド6−ヒドロキシ−2,5,7,8−テトラメチルクロ
マン−2−アセチルヒドラゾン(5-bromosalicylaldehyd
e 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhyd
razone) 収率:35% (物性) 淡黄色結晶(mp.168-170 ℃) PMR(DMSO-d6,δ ppm) :11.67,11.37(1H,each-s),11.20,
10.32(1H,each-brs),7.74,7.60(1H,each-d,J=2.4Hz),7.
41-7.31(2H,m),6.87,6.83(1H,each-d,J=8.8Hz),2.93-2.
44(4H,m),2.09-1.79(11H,m),1.35(3H,s) IR(KBr, cm-1):3240,2926,1669,1547,1477,1344,1270,1
182,1085
Example 88 5-bromosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
e 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhyd
razone) Yield: 35% (physical properties) pale yellow crystal (mp.168-170 ° C) PMR (DMSO-d 6 , δ ppm): 11.67, 11.37 (1H, each-s), 11.20,
10.32 (1H, each-brs), 7.74,7.60 (1H, each-d, J = 2.4Hz), 7.
41-7.31 (2H, m), 6.87,6.83 (1H, each-d, J = 8.8Hz), 2.93-2.
44 (4H, m), 2.09-1.79 (11H, m), 1.35 (3H, s) IR (KBr, cm -1 ): 3240,2926,1669,1547,1477,1344,1270,1
182,1085

【0202】実施例89 2−ヒドロキシ−4−メトキ
シベンズアルデヒド6−ヒドロキシ−2,5,7,8−
テトラメチルクロマン−2−アセチルヒドラゾン(2-hyd
roxy-4-methoxybenzaldehyde 6-hydroxy-2,5,7,8-tetra
methylchroman-2-acetylhydrazone) 収率:85% (物性) 無色結晶(mp.140-142 ℃) PMR(DMSO-d6,δ ppm) :11.51,11.18
(1H,each−s),11.47,10.25(1
H,each−s),8.24,8.14(1H,ea
ch−s),7.40−7.28(2H,m),6.5
0−6.40(2H,m),3.77,3.73(3
H,each−s),2.88−2.41(4H,
m),2.05−1.79(11H, m),1.35
(3H,s) IR(KBr, cm−1):3350,3042,2
932,1666,1633,1617,1510,1
456,1360,1245,1167
Example 89 2-Hydroxy-4-methoxybenzaldehyde 6-hydroxy-2,5,7,8-
Tetramethylchroman-2-acetylhydrazone (2-hyd
roxy-4-methoxybenzaldehyde 6-hydroxy-2,5,7,8-tetra
methylchroman-2-acetylhydrazone) Yield: 85% (Physical Properties) colorless crystals (mp.140-142 ℃) PMR (DMSO- d 6, δ ppm): 11.51,11.18
(1H, each-s), 11.47, 10.25 (1
H, each-s), 8.24,8.14 (1H, ea
ch-s), 7.40-7.28 (2H, m), 6.5.
0-6.40 (2H, m), 3.77, 3.73 (3
H, each-s), 2.88-2.41 (4H,
m), 2.05-1.79 (11H, m), 1.35
(3H, s) IR (KBr, cm -1 ): 3350, 3042, 2
932, 1666, 1633, 1617, 1510, 1
456,1360,1245,1167

【0203】実施例90 2,5−ジヒドロキシベンズ
アルデヒド6−ヒドロキシ−2,5,7,8−テトラメ
チルクロマン−2−アセチルヒドラゾン(2,5−di
hydroxybenzaldehyde 6−hyd
roxy−2,5,7,8−tetramethylc
hroman−2−acetylhydrazone) 収率:88% (物性) 淡黄色結晶(mp.229-232 ℃) PMR(DMSO-d6,δ ppm) :11.47,11.24(1H,each-s),10.31,
9.37(1H,each-s),8.90,8.84(1H,each-s),8.24,8.19(1H,
each-s),7.39,7.34(1H,each-s),6.95,6.89(1H,each-d,J
=2.0Hz),6.73-6.62(2H,m),2.91-2.42(4H,m),2.05-1.79
(11H,m),1.35,1.33(3H,each-s) IR(KBr, cm-1):3430,3248,1675,1549,1455,1375,1259,1
162,794
Example 90 2,5-Dihydroxybenzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (2,5-di
hydroxybenzaldehyde 6-hyd
roxy-2,5,7,8-tetramethylc
roman-2-acetylhydrazine yield: 88% (physical properties) pale yellow crystal (mp. 229-232 ° C.) PMR (DMSO-d 6 , δ ppm): 11.47, 11.24 (1H, each-s), 10.31,
9.37 (1H, each-s), 8.90,8.84 (1H, each-s), 8.24,8.19 (1H, each-s)
each-s), 7.39,7.34 (1H, each-s), 6.95,6.89 (1H, each-d, J
= 2.0Hz), 6.73-6.62 (2H, m), 2.91-2.42 (4H, m), 2.05-1.79
(11H, m), 1.35,1.33 (3H, each-s) IR (KBr, cm -1 ): 3430,3248,1675,1549,1455,1375,1259,1
162,794

【0204】実施例91 o−バニリン6−ヒドロキシ
−2,5,7,8−テトラメチルクロマン−2−アセチ
ルヒドラゾン(o-vanillin 6-hydroxy-2,5,7,8-tetramet
hylchroman-2-acetylhydrazone) 収率:69% (物性) 淡褐色無定形固体 PMR(DMSO-d6,δ ppm) :11.53,11.27(1H,each-s),10.88,
9.41(1H,each-s),8.30,8.24(1H,each-s),7.36,7.30(1H,
each-s),7.04,7.00(1H,each-d,J=6.8Hz),6.95,6.90(1H,
each-d,J=7.8Hz),6.79,6.71(1H,each-t,J=8.1Hz),3.77
(3H,s),2.87-2.40(4H,m),2.02-1.76(11H,m),1.32(3H,s) IR(KBr, cm-1):3412,3222,2934,1667,1466,1366,1254,1
083,732
Example 91 o-vanillin 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
hylchroman-2-acetylhydrazone) Yield: 69% (physical properties) Light brown amorphous solid PMR (DMSO-d 6 , δ ppm): 11.53, 11.27 (1H, each-s), 10.88,
9.41 (1H, each-s), 8.30,8.24 (1H, each-s), 7.36,7.30 (1H, each-s)
each-s), 7.04,7.00 (1H, each-d, J = 6.8Hz), 6.95,6.90 (1H,
each-d, J = 7.8Hz), 6.79,6.71 (1H, each-t, J = 8.1Hz), 3.77
(3H, s), 2.87-2.40 (4H, m), 2.02-1.76 (11H, m), 1.32 (3H, s) IR (KBr, cm -1 ): 3412,3222,2934,1667,1466,1366 , 1254,1
083,732

【0205】実施例92 4−(ジエチルアミノ)サリ
チルアルデヒド6−ヒドロキシ−2,5,7,8−テト
ラメチルクロマン−2−アセチルヒドラゾン(4−(d
iethylamino)salicylaldehy
de 6−hydroxy−2,5,7,8−tetr
amethylchroman−2−acetylhy
drazone) 収率:35% (物性) 紫色結晶(mp.210-214 ℃) PMR(DMSO-d6,δ ppm) :11.33(1H,s),11.26(1H,s),8.11
(1H,s),7.39(1H,s),7.13(1H,d,J=8.8Hz),6.23(1H,dd,J=
8.3,2.0Hz),6.09(1H,d,J=2.4Hz),3.35(4H,q,J=6.8Hz),
2.83-2.39(4H,m),2.06-1.79(11H,m),1.35(3H,s),1.11(6
H,t,J=6.8Hz) IR(KBr, cm-1):3418,3266,2970,1669,1599,1554,1522,1
420,1356,1250,1135,1079,792
Example 92 4- (Diethylamino) salicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (4- (d
ielamino) salicylaldehy
de 6-hydroxy-2,5,7,8-tetra
amethylchroman-2-acetylhy
Drazone) Yield: 35% (Physical properties) Purple crystal (mp. 210-214 ° C) PMR (DMSO-d 6 , δ ppm): 11.33 (1H, s), 11.26 (1H, s), 8.11
(1H, s), 7.39 (1H, s), 7.13 (1H, d, J = 8.8Hz), 6.23 (1H, dd, J =
8.3,2.0Hz), 6.09 (1H, d, J = 2.4Hz), 3.35 (4H, q, J = 6.8Hz),
2.83-2.39 (4H, m), 2.06-1.79 (11H, m), 1.35 (3H, s), 1.11 (6
(H, t, J = 6.8Hz) IR (KBr, cm -1 ): 3418,3266,2970,1669,1599,1554,1522,1
420,1356,1250,1135,1079,792

【0206】実施例93 3,5−ジクロロサリチルア
ルデヒド6−ヒドロキシ−2,5,7,8−テトラメチ
ルクロマン−2−アセチルヒドラゾン(3,5-dichlorosal
icylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-
2-acetylhydrazone) 収率:55% (物性) 無色結晶(mp.210-212 ℃) PMR(DMSO-d6,δ ppm) :12.38,11.56(1H,each-s),11.97,
10.51(1H,each-s),8.30,8.17(1H,each-s),7.62,7.48(1
H,each-d,J=2.4Hz),7.55,7.42(1H,each-d,J=2.4Hz),7.4
0,7.27(1H,each-s),3.00-2.48(4H,m),2.05-1.80(11H,
m),1.35(3H,s) IR(KBr, cm-1):3586,3206,3064,2928,1666,1555,1453,1
378,1253,1221,1184,1087
Example 93 3,5-Dichlorosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (3,5-dichlorosal
icylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-
2-acetylhydrazone) Yield: 55% (Physical Properties) colorless crystals (mp.210-212 ℃) PMR (DMSO- d 6, δ ppm): 12.38,11.56 (1H, each-s), 11.97,
10.51 (1H, each-s), 8.30,8.17 (1H, each-s), 7.62,7.48 (1
H, each-d, J = 2.4Hz), 7.55,7.42 (1H, each-d, J = 2.4Hz), 7.4
0,7.27 (1H, each-s), 3.00-2.48 (4H, m), 2.05-1.80 (11H,
m), 1.35 (3H, s) IR (KBr, cm -1 ): 3586,3206,3064,2928,1666,1555,1453,1
378,1253,1221,1184,1087

【0207】実施例94 3,5−ジニトロサリチルア
ルデヒド6−ヒドロキシ−2,5,7,8−テトラメチ
ルクロマン−2−アセチルヒドラゾン(3,5-dinitrosali
cylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2
-acetylhydrazone) 収率:86% (物性) 無色結晶(mp.270 ℃(dec.)) PMR(DMSO-d6,δ ppm) :12.13,11.55(1H,each-s),8.80,
8.65(1H,each-d,J=2.9Hz),8.74,8.27(1H,each-d,J=2.9H
z),8.55,8.21(1H,each-s),2.61-2.50(4H,m),2.05-1.77
(11H,m),1.40,1.36(3H,ea ch-s) IR(KBr, cm-1):3586,3202,3062,1691,1669,1618,1551,1
465,1339,1267,1085,741
Example 94 3,5-Dinitrosalicylic aldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (3,5-dinitrosali
cylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2
-Acetylhydrazone) Yield: 86% (Physical Properties) colorless crystals (mp.270 ℃ (dec.)) PMR (DMSO-d 6, δ ppm): 12.13,11.55 (1H, each-s), 8.80,
8.65 (1H, each-d, J = 2.9Hz), 8.74,8.27 (1H, each-d, J = 2.9H
z), 8.55,8.21 (1H, each-s), 2.61-2.50 (4H, m), 2.05-1.77
(11H, m), 1.40,1.36 (3H, each-s) IR (KBr, cm -1 ): 3586,3202,3062,1691,1669,1618,1551,1
465,1339,1267,1085,741

【0208】実施例95 2−ヒドロキシ−1−ナフト
アルデヒド6−ヒドロキシ−2,5,7,8−テトラメ
チルクロマン−2−アセチルヒドラゾン(2-hydroxy-1-n
aphthaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman
-2-acetylhydrazone) 収率:59% (物性) 淡褐色結晶(mp.190 ℃) PMR(DMSO-d6,δ ppm) :12.63,11.38(1H,each-s),11.69,
11.07(1H,each-s),9.17,8.93(1H,each-s),8.49,8.16(1
H,each-d,J=8.8Hz),7.88(2H,t,J=9.0Hz),7.58(1H,t,J=
7.3Hz),7.42-7.31(2H,m),7.20,7.17(1H,each-d,J=8.8H
z),3.00-2.50(4H,m),2.09-1.83(11H,m),1.39,1.38(3H,e
ach-s) IR(KBr, cm-1):3372,3200,2932,1669,1626,1468,1245,1
177,1084,818,744
Example 95 2-hydroxy-1-naphthaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (2-hydroxy-1-n
aphthaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman
-2-acetylhydrazone) Yield: 59% (property) pale brown crystals (mp.190 ℃) PMR (DMSO- d 6, δ ppm): 12.63,11.38 (1H, each-s), 11.69,
11.07 (1H, each-s), 9.17,8.93 (1H, each-s), 8.49,8.16 (1
H, each-d, J = 8.8Hz), 7.88 (2H, t, J = 9.0Hz), 7.58 (1H, t, J =
7.3Hz), 7.42-7.31 (2H, m), 7.20,7.17 (1H, each-d, J = 8.8H
z), 3.00-2.50 (4H, m), 2.09-1.83 (11H, m), 1.39,1.38 (3H, e
ach-s) IR (KBr, cm -1 ): 3372,3200,2932,1669,1626,1468,1245,1
177,1084,818,744

【0209】実施例96 2,4,6−トリヒドロキシ
ベンズアルデヒド6−ヒドロキシ−2,5,7,8−テ
トラメチルクロマン−2−アセチルヒドラゾン(2,4,6-t
rihydroxybenzaldehyde 6-hydroxy-2,5,7,8-tetramethy
lchroman-2-acetylhydrazone) 収率:43% (物性) 無色結晶(mp.170 ℃(dec.)) PMR(DMSO-d6,δ ppm) :11.33(1H,s),10.93(1H,s),9.73
(1H,s),8.48(1H,s),7.40(1H,s),5.81(2H,s),2.58-2.38
(4H,m),2.05-1.80(11H,m),1.34(3H,s) IRIR(KBr, cm-1):3234,2970,2930,1638,1616,1463,138
3,1332,1257,1161,1086,1051
Example 96 2,4,6-Trihydroxybenzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (2,4,6-t
rihydroxybenzaldehyde 6-hydroxy-2,5,7,8-tetramethy
lchroman-2-acetylhydrazone) Yield: 43% (Physical Properties) colorless crystals (mp.170 ℃ (dec.)) PMR (DMSO-d 6, δ ppm): 11.33 (1H, s), 10.93 (1H, s) , 9.73
(1H, s), 8.48 (1H, s), 7.40 (1H, s), 5.81 (2H, s), 2.58-2.38
(4H, m), 2.05-1.80 (11H, m), 1.34 (3H, s) IRIR (KBr, cm -1 ): 3234,2970,2930,1638,1616,1463,138
3,1332,1257,1161,1086,1051

【0210】実施例97 4,6−ジメトキシサリチル
アルデヒド6−ヒドロキシ−2,5,7,8−テトラメ
チルクロマン−2−アセチルヒドラゾン(4,6-dimethoxy
salicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchrom
an-2-acetylhydrazone) 収率:75% (物性) 無色結晶(mp.115-117 ℃) PMR(DMSO-d6,δ ppm) :12.23(1H,s),11.49(1H,s),8.52
(1H,s),7.40(1H,s),6.11(2H,s),3.81(3H,s),3. 77(3H,
s),2.58-2.39(4H,m),2.05-1.80(11H,m),1.34(3H,s) IR(KBr, cm-1):3400,2932,1636,1606,1460,1342,1218,1
163,1095
Example 97 4,6-Dimethoxysalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (4,6-dimethoxy
salicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchrom
an-2-acetylhydrazone) Yield: 75% (Physical Properties) colorless crystals (mp.115-117 ℃) PMR (DMSO- d 6, δ ppm): 12.23 (1H, s), 11.49 (1H, s), 8.52
(1H, s), 7.40 (1H, s), 6.11 (2H, s), 3.81 (3H, s), 3.77 (3H,
s), 2.58-2.39 (4H, m), 2.05-1.80 (11H, m), 1.34 (3H, s) IR (KBr, cm -1 ): 3400,2932,1636,1606,1460,1342,1218, 1
163,1095

【0211】実施例98 2−メチルアミノベンズアル
デヒド6−ヒドロキシ−2,5,7,8−テトラメチル
クロマン−2−アセチルヒドラゾン(2-methylaminobenz
aldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-ac
etylhydrazone) 収率:19% (物性) 黄色結晶(mp.209-210 ℃) PMR(DMSO-d6,δ ppm) :11.28,11.17(1H,each-s),8.19,
8.07(1H,each-s),8.18,7.43(1H,each-m),7.39,7.35(1H,
each-s),7.25-7.11(2H,m),6.68-6.59(2H,m),2.89,2.65
(3H,each-d,J=4.9Hz),2.88-2.42(4H,m),2.05-1.81(11H,
m),1.38,1.36(3H,each-s) IR(KBr, cm-1):3332,3210,3064,2934,1632,1613,1570,1
517,1379,1326,1236,1176,1157,1089,752
Example 98 2-Methylaminobenzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
aldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-ac
etylhydrazone) Yield: 19% (physical properties) Yellow crystals (mp. 209-210 ° C) PMR (DMSO-d 6 , δ ppm): 11.28, 11.17 (1H, each-s), 8.19,
8.07 (1H, each-s), 8.18,7.43 (1H, each-m), 7.39,7.35 (1H, each-s)
each-s), 7.25-7.11 (2H, m), 6.68-6.59 (2H, m), 2.89,2.65
(3H, each-d, J = 4.9Hz), 2.88-2.42 (4H, m), 2.05-1.81 (11H,
m), 1.38,1.36 (3H, each-s) IR (KBr, cm -1 ): 3332,3210,3064,2934,1632,1613,1570,1
517,1379,1326,1236,1176,1157,1089,752

【0212】実施例99 8−ホルミル−1,2,3,
4−テトラヒドロキノリン6−ヒドロキシ−2,5,
7,8−テトラメチルクロマン−2−アセチルヒドラゾ
ン(8-formyl-1,2,3,4-tetrahydroquinoline 6-hydroxy-
2,5,7,8-tetramethylchroman-2-acetylhydrazone) 収率:21% (物性) 淡黄色結晶(mp.117-120 ℃) PMR(DMSO-d6,δ ppm) :11.22,11.12(1H,each-s),8.22,
7.53(1H,each-m),8.15,8.03(1H,each-s),7.40,7.36(1H,
each-s),6.99-6.85(2H,m),6.45,6.44(1H,each-t,J=7.6H
z),3.42,3.12(2H,each-m),2.87-2.40(6H,m),2.06-1.75
(13H,m),1.36,1.35(3H,each-s) IR(KBr, cm-1):3358,2930,1657,1609,1579,1519,1463,1
426,1237,1085,741
Example 99 8-Formyl-1,2,3
4-tetrahydroquinoline 6-hydroxy-2,5,
7,8-tetramethylchroman-2-acetylhydrazone (8-formyl-1,2,3,4-tetrahydroquinoline 6-hydroxy-
2,5,7,8-tetramethylchroman-2-acetylhydrazone) Yield: 21% (property) pale yellow crystals (mp.117-120 ℃) PMR (DMSO- d 6, δ ppm): 11.22,11.12 (1H, each-s), 8.22,
7.53 (1H, each-m), 8.15,8.03 (1H, each-s), 7.40,7.36 (1H, each-s)
each-s), 6.99-6.85 (2H, m), 6.45,6.44 (1H, each-t, J = 7.6H
z), 3.42,3.12 (2H, each-m), 2.87-2.40 (6H, m), 2.06-1.75
(13H, m), 1.36,1.35 (3H, each-s) IR (KBr, cm -1 ): 3358,2930,1657,1609,1579,1519,1463,1
426,1237,1085,741

【0213】実施例100 2,3−ジメトキシ−6−
ホルミル−5−メチルヒドロキノン6−ヒドロキシ−
2,5,7,8−テトラメチルクロマン−2−アセチル
ヒドラゾン(2,3-dimethoxy-6-formyl-5-methylhydroqui
none 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetyl
hydrazone) 収率:59% (物性) 淡黄色結晶(mp.180-184 ℃) PMR(DMSO-d6,δ ppm) :11.85(1H,s),11.55(1H,s),8.52
(1H,s),8.22(1H,s),7.39(1H,s),3.82(3H,s),3.79(3H,
s),2.59-2.43(3H,m),2.17(3H,s),2.06-1.83(12H,m),1.3
3(3H,s) IR(KBr, cm-1):3455,3255,2924,1662,1455,1421,1390,1
290,1252,1193,1141,1114,1062,921
Example 100 2,3-Dimethoxy-6
Formyl-5-methylhydroquinone 6-hydroxy-
2,5,7,8-tetramethylchroman-2-acetylhydrazone (2,3-dimethoxy-6-formyl-5-methylhydroqui
none 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetyl
Hydrazone) Yield: 59% (property) pale yellow crystals (mp.180-184 ℃) PMR (DMSO- d 6, δ ppm): 11.85 (1H, s), 11.55 (1H, s), 8.52
(1H, s), 8.22 (1H, s), 7.39 (1H, s), 3.82 (3H, s), 3.79 (3H,
s), 2.59-2.43 (3H, m), 2.17 (3H, s), 2.06-1.83 (12H, m), 1.3
3 (3H, s) IR (KBr, cm -1 ): 3455,3255,2924,1662,1455,1421,1390,1
290,1252,1193,1141,1114,1062,921

【0214】実施例101 ピリドキサール6−ヒドロ
キシ−2,5,7,8−テトラメチルクロマン−2−ア
セチルヒドラゾン(pyridoxal 6-hydroxy-2,5,7,8-tetra
methylchroman-2-acetylhydrazone) 収率:26% (物性) 淡黄色結晶(mp.221-224 ℃) PMR(DMSO-d6,δ ppm) :12.11(1H,
s),12.04(1H,s),8.66(1H,
s),7.92(1H,s),7.39(1H,s),
5.35(1H,t,J=5.1Hz),4.58(1
H,d,J=5.4Hz),2.64−2.50(3
H,m),2.40(3H,s),2.05−1.81
(12H,m),1.36(3H,s) IR(KBr, cm−1):3345,3095,2
926,1673,1409,1364,1277,1
248,1166,1132,1090,1029,1
101
Example 101 Pyridoxal 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
methylchroman-2-acetylhydrazone) Yield: 26% (property) pale yellow crystals (mp.221-224 ℃) PMR (DMSO- d 6, δ ppm): 12.11 (1H,
s), 12.04 (1H, s), 8.66 (1H,
s), 7.92 (1H, s), 7.39 (1H, s),
5.35 (1H, t, J = 5.1 Hz), 4.58 (1
H, d, J = 5.4 Hz), 2.64-2.50 (3
H, m), 2.40 (3H, s), 2.05-1.81.
(12H, m), 1.36 (3H, s) IR (KBr, cm -1 ): 3345, 3095, 2
926, 1673, 1409, 1364, 1277, 1
248, 1166, 1132, 1090, 1029, 1
101

【0215】実施例102 2−ピコリンアルデヒド6
−ヒドロキシ−2,5,7,8−テトラメチルクロマン
−2−アセチルヒドラゾン(2−picolinald
ehyde 6−hydroxy−2,5,7,8−t
etramethylchroman−2−acety
lhydrazone) 収率:76% (物性) 無色結晶(mp.178-180 ℃) PMR(DMSO-d6,δ ppm) :11.56,11.50(1H,each-s),8.58,
8.52(1H,each-d,J=4.9Hz),8.17,7.96(1H,each-s),7.92,
7.41-7.30(3H,m),7.84,7.70(1H,each-t,J=7.6Hz),3.15-
2.46(4H,m),2.05-1.76(11H,m),1.40,1.35(3H,each-s) IR(KBr, cm-1):3174,3060,2930,1669,1589,1381,1257,1
089,1002,943,781
Example 102 2-picolinaldehyde 6
-Hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (2-picolinald
ehydro 6-hydroxy-2,5,7,8-t
Etramethylchroman-2-acety
Lhydrazone) Yield: 76% (Physical Properties) colorless crystals (mp.178-180 ℃) PMR (DMSO- d 6, δ ppm): 11.56,11.50 (1H, each-s), 8.58,
8.52 (1H, each-d, J = 4.9Hz), 8.17,7.96 (1H, each-s), 7.92,
7.41-7.30 (3H, m), 7.84,7.70 (1H, each-t, J = 7.6Hz), 3.15-
2.46 (4H, m), 2.05-1.76 (11H, m), 1.40,1.35 (3H, each-s) IR (KBr, cm -1 ): 3174,3060,2930,1669,1589,1381,1257,1
089,1002,943,781

【0216】実施例103 ニコチンアルデヒド6−ヒ
ドロキシ−2,5,7,8−テトラメチルクロマン−2
−アセチルヒドラゾン(nicotinaldehyde 6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetylhydrazone) 収率:95% (物性) 無色結晶(mp.186-188 ℃) PMR(DMSO-d6,δ ppm) :11.51,11.45(1H,each-s),8.81,
8.64(1H,each-d,J=1.5Hz),8.58,8.52(1H,each-dd,J=4.
9,1.5Hz),8.21,7.95(1H,each-s),8.08,7.67(1H,each-d
t,J=8.3,1.5Hz),7.45,7.33(1 H,each-dd,J=7.8,4.9Hz),
7.40,7.31(1H,each-s),3.13-2.44(4H,m),2.06-1.76(11
H,m),1.39,1.35(3H,each-s) IR(KBr, cm-1):3176,3068,2930,1667,1397,1374,1252,1
090,1033,921,806,703
Example 103 Nicotinaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2
-Acetylhydrazone (nicotinaldehyde 6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetylhydrazone) Yield: 95% (Physical Properties) colorless crystals (mp.186-188 ℃) PMR (DMSO- d 6, δ ppm): 11.51,11.45 (1H, each-s ), 8.81,
8.64 (1H, each-dd, J = 1.5Hz), 8.58,8.52 (1H, each-dd, J = 4.
9,1.5Hz), 8.21,7.95 (1H, each-s), 8.08,7.67 (1H, each-d
t, J = 8.3,1.5Hz), 7.45,7.33 (1H, each-dd, J = 7.8,4.9Hz),
7.40,7.31 (1H, each-s), 3.13-2.44 (4H, m), 2.06-1.76 (11
(H, m), 1.39,1.35 (3H, each-s) IR (KBr, cm -1 ): 3176,3068,2930,1667,1397,1374,1252,1
090,1033,921,806,703

【0217】実施例104 イソニコチンアルデヒド6
−ヒドロキシ−2,5,7,8−テトラメチルクロマン
−2−アセチルヒドラゾン(isonicotinaldehyde 6-hydr
oxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone) 収率:88% (物性) 淡黄色結晶(mp.224-225 ℃) PMR(DMSO-d6,δ ppm) :11.62,11.56(1H,each-s),8.62,
8.51(2H,each-d,J=5.9Hz),8.15,7.88(1H,each-s),7.61,
7.27(2H,each-d,J=5.9Hz),7.40,7.33(1H,each-s),3.17-
2.46(4H,m),2.05-1.77(11H,m),1.40,1.35(3H,each-s) IR(KBr, cm-1):3166,3082,2938,1679,1607,1452,1378,1
274,1185,1145,1092,924
Example 104 Isonicotinaldehyde 6
-Hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (isonicotinaldehyde 6-hydr
oxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone) Yield: 88% (Physical properties) Light yellow crystal (mp.224-225 ° C) PMR (DMSO-d 6 , δ ppm): 11.62, 11.56 ( 1H, each-s), 8.62,
8.51 (2H, each-d, J = 5.9Hz), 8.15,7.88 (1H, each-s), 7.61,
7.27 (2H, each-d, J = 5.9Hz), 7.40,7.33 (1H, each-s), 3.17-
2.46 (4H, m), 2.05-1.77 (11H, m), 1.40,1.35 (3H, each-s) IR (KBr, cm -1 ): 3166,3082,2938,1679,1607,1452,1378,1
274,1185,1145,1092,924

【0218】実施例105 2−フルアルデヒド6−ヒ
ドロキシ−2,5,7,8−テトラメチルクロマン−2
−アセチルヒドラゾン(2-furaldehyde 6-hydroxy-2,5,
7,8-tetramethylchroman-2-acetylhydrazone) 収率:79% (物性) 無色不定形固体 PMR(DMSO-d6,δ ppm) :11.28,11,25(1H,each-s),8.05,
7.85(1H,each-s),7.78,7.72(1H,each-s),7.38,7.34(1H,
each-s),6.85,6.72(1H,each-d,J=3.0Hz),6.59,6.55(1H,
each-dd,J=3.0,1.5Hz),2.93-2.40(3H,m),2.05-1.77(12
H,m),1.36,1.33(3H,each-s) IR(KBr, cm-1):3425,3238,2926,1661,1456,1378,1346,1
158,1086,1006,931
Example 105 2-Furaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2
-Acetylhydrazone (2-furaldehyde 6-hydroxy-2,5,
7,8-tetramethylchroman-2-acetylhydrazone) Yield: 79% (physical properties) Colorless amorphous solid PMR (DMSO-d 6 , δ ppm): 11.28,11,25 (1H, each-s), 8.05,
7.85 (1H, each-s), 7.78,7.72 (1H, each-s), 7.38,7.34 (1H, each-s)
each-s), 6.85,6.72 (1H, each-d, J = 3.0Hz), 6.59,6.55 (1H,
each-dd, J = 3.0,1.5Hz), 2.93-2.40 (3H, m), 2.05-1.77 (12
H, m), 1.36,1.33 (3H, each-s) IR (KBr, cm -1 ): 3425,3238,2926,1661,1456,1378,1346,1
158,1086,1006,931

【0219】実施例106 ピロール−2−カルバルデ
ヒド6−ヒドロキシ−2,5,7,8−テトラメチルク
ロマン−2−アセチルヒドラゾン(pyrrole-2-carbaldeh
yde6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhy
drazone) 収率:49% (物性) 無色結晶(mp.200-201 ℃) PMR(DMSO-d6,δ ppm) :11.41,11.08
(1H,each−brs),10.98,10.97
(1H,each−s),7.99,7.81(1H,
each−s),7.38,7.34(1H,each
−s),6.86(1H,s),6.41,6.33
(1H,each−d,J=1.5Hz),6.10,
6.08(1H,each−dd,J=5.4,2.4
Hz),2.93−2.38(4H,m),2.08−
1.79(11H,m),1.34(3H,s) IR(KBr, cm−1):3359,3083,1
638,1610,1545,1420,1269,1
238,1166,1128,1090,741
Example 106 Pyrrole-2-carbaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
yde6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhy
Drazone) Yield: 49% (Physical Properties) colorless crystals (mp.200-201 ℃) PMR (DMSO- d 6, δ ppm): 11.41,11.08
(1H, each-brs), 10.98, 10.97
(1H, each-s), 7.99,7.81 (1H,
each-s), 7.38, 7.34 (1H, each
-S), 6.86 (1H, s), 6.41, 6.33
(1H, reach-d, J = 1.5 Hz), 6.10,
6.08 (1H, each-dd, J = 5.4,2.4
Hz), 2.93-2.38 (4H, m), 2.08-
1.79 (11H, m), 1.34 (3H, s) IR (KBr, cm -1 ): 3359, 3083,1
638, 1610, 1545, 1420, 1269, 1
238, 1166, 1128, 1090, 741

【0220】実施例107 2−チオフェンアルデヒド
6−ヒドロキシ−2,5,7,8−テトラメチルクロマ
ン−2−アセチルヒドラゾン(2−thiophena
ldehyde 6−hydroxy−2,5,7,8
−tetramethylchroman−2−ace
tylhydrazone) 収率:78% (物性) 無色無定型固体 PMR(DMSO-d6,δ ppm) :11.29(1H,s),8.38,8.14(1H,each
-s),7.61,7.54(1H,each-d,J=4.9Hz),7.41-7.31(2H,m),
7.10,7.07(1H,each-dd,J=4.9,3.4Hz),2.93-2.40(3H,m),
2.09-1.77(12H,m),1.34(3H,s) IR(KBr, cm-1):3411,3214,2925,1659,1597,1564,1454,1
429,1372,1256,1160,1086,1003,921,707
Example 107 2-thiophenaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (2-thiophena)
Idehyde 6-hydroxy-2,5,7,8
-Tetramethylchroman-2-ace
Tylhydrazine) Yield: 78% (physical properties) Colorless amorphous solid PMR (DMSO-d 6 , δ ppm): 11.29 (1H, s), 8.38, 8.14 (1H, each
-s), 7.61,7.54 (1H, each-d, J = 4.9Hz), 7.41-7.31 (2H, m),
7.10,7.07 (1H, each-dd, J = 4.9,3.4Hz), 2.93-2.40 (3H, m),
2.09-1.77 (12H, m), 1.34 (3H, s) IR (KBr, cm -1 ): 3411,3214,2925,1659,1597,1564,1454,1
429,1372,1256,1160,1086,1003,921,707

【0221】実施例108 ベンズアルデヒドN−メチ
ル−6−ヒドロキシ−2,5,7,8−テトラメチルク
ロマン−2−アセチルヒドラゾン(benzaldehyde N-meth
yl-6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhy
drazone) 6−ヒドロキシ−2,5,7,8−テトラメチルクロマ
ン−2−酢酸(6-hydroxy-2,5,7,8-tetramethylchroman-
2-acetic acid) 0.79g(3mmol) 及び参考例6で合成した
化合物ベンズアルデヒドメチルヒドラゾン 0.40g(3mmo
l) をジオキサン6mlに加え、攪拌した。この溶液に、D
CC 0.74g(3.6mmol) を加え、24時間攪拌した。析出物
をろ去し、溶媒を留去した。残渣をシリカゲルカラムク
ロマトグラフィーに付し、酢酸エチル:n−ヘキサン=
1:2溶出部を溶媒留去し、酢酸エチル及びn−ヘキサ
ンを加えて結晶化させ、ろ取した。減圧下で乾燥し、標
記化合物 0.80g(収率70%)を得た。 (物性) 無色結晶(mp.140-145 ℃) PMR(DMSO-d6,δ ppm) :7.88(1H,s),7.56-7.53(2H,m),7.
39-7.34(4H,m),3.33(3H,s),3.20(1H,d,J=13.2Hz),3.13
(1H,d,J=13.2Hz),2.59-2.50(1H,m),2.04-1.90(12H,m),
1.33(3H,s) IR(KBr, cm-1):3522,3289,2933,2851,1701,1635,1528,1
451,1237,1088,919
Example 108 Benzaldehyde N-methyl-6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
yl-6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhy
drazone) 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetic acid (6-hydroxy-2,5,7,8-tetramethylchroman-
2-acetic acid) 0.79 g (3 mmol) and the compound synthesized in Reference Example 6 benzaldehyde methylhydrazone 0.40 g (3 mmo
l) was added to 6 ml of dioxane and stirred. In this solution, D
0.74 g (3.6 mmol) of CC was added, and the mixture was stirred for 24 hours. The precipitate was removed by filtration, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and ethyl acetate: n-hexane =
The solvent eluted from the 1: 2 eluted portion was crystallized by adding ethyl acetate and n-hexane, and collected by filtration. Drying under reduced pressure gave 0.80 g (yield 70%) of the title compound. (Physical Properties) colorless crystals (mp.140-145 ℃) PMR (DMSO- d 6, δ ppm): 7.88 (1H, s), 7.56-7.53 (2H, m), 7.
39-7.34 (4H, m), 3.33 (3H, s), 3.20 (1H, d, J = 13.2Hz), 3.13
(1H, d, J = 13.2Hz), 2.59-2.50 (1H, m), 2.04-1.90 (12H, m),
1.33 (3H, s) IR (KBr, cm -1 ): 3522,3289,2933,2851,1701,1635,1528,1
451,1237,1088,919

【0222】実施例109〜112 ベンズアルデヒドメチルヒドラゾンを他のメチルヒドラ
ゾン化合物に代える以外は実施例108と実質的に同様
に処理して、以下の化合物を製造した。 実施例109 サリチルアルデヒドN−メチル−6−ヒ
ドロキシ−2,5,7,8−テトラメチルクロマン−2
−アセチルヒドラゾン(salicylaldehyde N-methyl-6-hy
droxy-2,5,7,8-tetramethylchroman-2-acetylhydrazon
e) 収率:20% (物性) 無色結晶(mp.105-110 ℃) PMR(DMSO-d6,δ ppm) :10.14(1H,s),8.07(1H,s),7.47(1
H,dd,J=7.8,1.0Hz),7.34(1H,s),7.20(1H,td,J=7.6,1.5H
z),6.87(1H,d,J=8.3Hz),6.82(1H,t,J=7.3Hz),3.34(3H,
s),3.13(1H,d,J=13.7Hz),3.09(1H,d,J=13.7Hz),2.59-2.
50(1H,m),2.00-1.82(12H,m),1.34(3H,s) IR(KBr, cm-1):3501,2925,1671,1480,1416,1347,1273,1
259,1166,1125,1069,764
Examples 109 to 112 The following compounds were prepared in substantially the same manner as in Example 108 except that benzaldehyde methylhydrazone was replaced with another methylhydrazone compound. Example 109: Salicylaldehyde N-methyl-6-hydroxy-2,5,7,8-tetramethylchroman-2
-Acetylhydrazone (salicylaldehyde N-methyl-6-hy
droxy-2,5,7,8-tetramethylchroman-2-acetylhydrazon
e) Yield: 20% (Physical Properties) colorless crystals (mp.105-110 ℃) PMR (DMSO- d 6, δ ppm): 10.14 (1H, s), 8.07 (1H, s), 7.47 (1
H, dd, J = 7.8,1.0Hz), 7.34 (1H, s), 7.20 (1H, td, J = 7.6,1.5H
z), 6.87 (1H, d, J = 8.3Hz), 6.82 (1H, t, J = 7.3Hz), 3.34 (3H,
s), 3.13 (1H, d, J = 13.7Hz), 3.09 (1H, d, J = 13.7Hz), 2.59-2.
50 (1H, m), 2.00-1.82 (12H, m), 1.34 (3H, s) IR (KBr, cm -1 ): 3501,2925,1671,1480,1416,1347,1273,1
259,1166,1125,1069,764

【0223】実施例110 2,4−ジヒドロキシベン
ズアルデヒドN−メチル−6−ヒドロキシ−2,5,
7,8−テトラメチルクロマン−2−アセチルヒドラゾ
ン(2,4-dihydroxybenzaldehyde N-methyl-6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetylhydrazone) 収率:31% (物性) 無色結晶(mp.175-185 ℃(dec.)) PMR(DMSO-d6,δ ppm) :10.21(1H,
s),9.75(1H,s),7.99(1H,s),
7.36(1H,s),7.30(1H,d,J=8.
8Hz),6.29(1H,s),6.28(1H,d
d,J=7.3,2.5Hz),3.30(3H,
s),3.05(2H,s),2.59−2.50(1
H,m),2.06−1.82(12H,m),1.3
2(3H,s) IR(KBr, cm−1):3486,3133,2
924,1626,1600,1484,1423,1
336,1257,1165,1118,1077
Example 110 2,4-Dihydroxybenzaldehyde N-methyl-6-hydroxy-2,5
7,8-tetramethylchroman-2-acetylhydrazone (2,4-dihydroxybenzaldehyde N-methyl-6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetylhydrazone) Yield: 31% (physical properties) Colorless crystals (mp. 175-185 ° C (dec.)) PMR (DMSO-d 6 , δ ppm): 10.21 (1H ,
s), 9.75 (1H, s), 7.99 (1H, s),
7.36 (1H, s), 7.30 (1H, d, J = 8.
8Hz), 6.29 (1H, s), 6.28 (1H, d
d, J = 7.3, 2.5 Hz), 3.30 (3H,
s), 3.05 (2H, s), 2.59-2.50 (1
H, m), 2.06-1.82 (12H, m), 1.3.
2 (3H, s) IR (KBr, cm -1 ): 3486, 3133, 2
924, 1626, 1600, 1484, 1423, 1
336,1257,1165,1118,1077

【0224】実施例111 o−バニリンN−メチル−
6−ヒドロキシ−2,5,7,8−テトラメチルクロマ
ン−2−アセチルヒドラゾン(o−vanillin
N−methyl−6−hydroxy−2,5,7,
8−tetramethylchroman−2−ac
etohydorazone) 収率:28% (物性) 無色結晶(mp.173-175 ℃) PMR(DMSO-d6,δ ppm) :9.59(1H,s),8.08(1H,s),7.34(1
H,s),7.10(1H,d,J=7.8Hz),6.95(1H,d,J=7.8Hz),6.77(1
H,t,J=8.1Hz),3.81(3H,s),3.33(3H,s),3.11(2H,brs),2.
59-2.50(2H,m),2.00-1.80(11H,m),1.33(3H,s) IR(KBr, cm-1):3515,2929,2851,1669,1626,1572,1475,1
416,1349,1252,1128,1082,1070,784,731
Example 111 o-Vaniline N-methyl-
6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (o-vanillin)
N-methyl-6-hydroxy-2,5,7,
8-tetramethylchroman-2-ac
Etohydorazone) Yield: 28% (Physical Properties) colorless crystals (mp.173-175 ℃) PMR (DMSO- d 6, δ ppm): 9.59 (1H, s), 8.08 (1H, s), 7.34 (1
H, s), 7.10 (1H, d, J = 7.8Hz), 6.95 (1H, d, J = 7.8Hz), 6.77 (1
(H, t, J = 8.1Hz), 3.81 (3H, s), 3.33 (3H, s), 3.11 (2H, brs), 2.
59-2.50 (2H, m), 2.00-1.80 (11H, m), 1.33 (3H, s) IR (KBr, cm -1 ): 3515,2929,2851,1669,1626,1572,1475,1
416,1349,1252,1128,1082,1070,784,731

【0225】実施例112 4−(ジエチルアミノ)サ
リチルアルデヒドN−メチル−6−ヒドロキシ−2,
5,7,8−テトラメチルクロマン−2−アセチルヒド
ラゾン(4-(diethylamino)salicylaldehyde N-methyl-6-
hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazo
ne) 収率:38% (物性) 無色結晶(mp.177-179 ℃) PMR(DMSO-d6,δ ppm) :10.22(1H,s),7.98(1H,s),7.35(1
H,s),7.26(1H,d,J=8.8Hz),6.22(1H,dd,J=8.8,2.0Hz),6.
09(1H,d,J=2.0Hz),3.36-3.30(7H,m),3.04(1H,d,J=13.7H
z),2.99(1H,d,J=13.7Hz),2.58-2.50(2H,m),2.02-1.84(1
1H,m),1.31(3H,s),1.11(6H,t,J=7.1Hz) IR(KBr, cm-1):3433,2971,2927,1631,1526,1412,1354,1
256,1073,791
Example 112 4- (Diethylamino) salicylaldehyde N-methyl-6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetylhydrazone (4- (diethylamino) salicylaldehyde N-methyl-6-
hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazo
ne) Yield: 38% (Physical Properties) colorless crystals (mp.177-179 ℃) PMR (DMSO- d 6, δ ppm): 10.22 (1H, s), 7.98 (1H, s), 7.35 (1
H, s), 7.26 (1H, d, J = 8.8Hz), 6.22 (1H, dd, J = 8.8,2.0Hz), 6.
09 (1H, d, J = 2.0Hz), 3.36-3.30 (7H, m), 3.04 (1H, d, J = 13.7H
z), 2.99 (1H, d, J = 13.7 Hz), 2.58-2.50 (2H, m), 2.02-1.84 (1
1H, m), 1.31 (3H, s), 1.11 (6H, t, J = 7.1Hz) IR (KBr, cm -1 ): 3433,2971,2927,1631,1526,1412,1354,1
256,1073,791

【0226】実施例113 N’−(2−ヒドロキシベ
ンジル)−6−ヒドロキシ−2,5,7,8−テトラメ
チルクロマン−2−アセトヒドラジド(N’−(2−h
ydroxybenzyl)−6−hydroxy−
2,5,7,8−tetramethylchroma
n−2−acetohydrazide) 実施例72で合成した化合物サリチルアルデヒド6−ヒ
ドロキシ−2,5,7,8−テトラメチルクロマン−2
−アセチルヒドラゾン 1.53g(4mmol) 及
び 5%Pd/C 0.15g をメタノール 20ml に加え、18時間接
触還元した。触媒をセライトろ去し、溶媒を留去した。
残渣をシリカゲルカラムクロマトグラフィーに付した。
メタノール:クロロホルム=1:33溶出部を溶媒留去
し、結晶を析出させ、その結晶をろ取した。ろ取した結
晶を減圧下で乾燥し、標記化合物 1.31g(収率85%)を得
た。
Example 113 N '-(2-hydroxybenzyl) -6-hydroxy-2,5,7,8-tetramethylchroman-2-acetohydrazide (N'-(2-h
hydroxybenzyl) -6-hydroxy-
2,5,7,8-tetramethylchroma
n-2-acetohydrazide) Compound synthesized in Example 72 Salicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2
1.53 g (4 mmol) of -acetylhydrazone and 0.15 g of 5% Pd / C were added to 20 ml of methanol, and the mixture was catalytically reduced for 18 hours. The catalyst was removed by filtration through Celite, and the solvent was distilled off.
The residue was subjected to silica gel column chromatography.
The solvent was distilled off from the eluted portion of methanol: chloroform = 1: 33 to precipitate crystals, and the crystals were collected by filtration. The crystals collected by filtration were dried under reduced pressure to obtain 1.31 g (yield: 85%) of the title compound.

【0227】(物性) 無色結晶(mp.170-172 ℃) PMR(DMSO-d6,δ ppm) :9.62(1H,s),9.43(1H,d,J=5.9H
z),7.37(1H,s),7.14(1H,d,J=6.4Hz),7.07(1H,t,J=7.6H
z),6.77(1H,d,J=8.3Hz),6.72(1H,t,J=7.6Hz),5.34 (1H,
td,J=5.9,5.9Hz),3.89-3.79(2H,m),2.59-2.41(2H,m),2.
33(1H,d,J=13.7Hz),2.23(1H,d,J=13.7Hz),2.08-1.67(11
H,m),1.27(3H,s) IR(KBr, cm-1):3477,3342,3294,2969,2923,2865,2353,1
647,1635,1488,1455,1264,1239,1168,1088,1033,757
(Physical properties) Colorless crystal (mp. 170-172 ° C.) PMR (DMSO-d 6 , δ ppm): 9.62 (1H, s), 9.43 (1H, d, J = 5.9H)
z), 7.37 (1H, s), 7.14 (1H, d, J = 6.4Hz), 7.07 (1H, t, J = 7.6H
z), 6.77 (1H, d, J = 8.3Hz), 6.72 (1H, t, J = 7.6Hz), 5.34 (1H,
td, J = 5.9,5.9Hz), 3.89-3.79 (2H, m), 2.59-2.41 (2H, m), 2.
33 (1H, d, J = 13.7Hz), 2.23 (1H, d, J = 13.7Hz), 2.08-1.67 (11
H, m), 1.27 (3H, s) IR (KBr, cm -1 ): 3477,3342,3294,2969,2923,2865,2353,1
647,1635,1488,1455,1264,1239,1168,1088,1033,757

【0228】実施例114 N’−(2,4−ジヒドロ
キシベンジル)−6−ヒドロキシ−2,5,7,8−テ
トラメチルクロマン−2−アセトヒドラジド(N'-(2,4-d
ihydroxybenzyl)-6-hydroxy-2,5,7,8-tetramethylchrom
an-2-acetohydrazide) 実施例83で合成した化合物2,4−ジヒドロキシベン
ズアルデヒド6−ヒドロキシ−2,5,7,8−テトラ
メチルクロマン−2−アセチルヒドラゾン 1.59g(4mmo
l) 及び 5%Pd/C 0.16g をメタノール 20ml に加え、24
時間接触還元した。触媒をセライトろ去し、溶媒を留去
した。残渣をシリカゲルカラムクロマトグラフィーに付
した。メタノール:クロロホルム=2:25溶出部を溶媒
留去し、減圧下で乾燥し、標記化合物 0.96g(収率60%)
を得た。
Example 114 N '-(2,4-dihydroxybenzyl) -6-hydroxy-2,5,7,8-tetramethylchroman-2-acetohydrazide (N'-(2,4-d
ihydroxybenzyl) -6-hydroxy-2,5,7,8-tetramethylchrom
an-2-acetohydrazide) Compound synthesized in Example 83 2,4-dihydroxybenzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone 1.59 g (4 mmo
l) and 0.16 g of 5% Pd / C in 20 ml of methanol.
Catalytic reduction was carried out for an hour. The catalyst was removed by filtration through Celite, and the solvent was distilled off. The residue was subjected to silica gel column chromatography. The solvent eluted from methanol: chloroform = 2: 25 was evaporated and dried under reduced pressure to give the title compound (0.96 g, yield 60%).
I got

【0229】(物性) 無色不定形固体PMR(DMSO-d6,δ ppm) :9.44(1H,s),9.38
(1H,d,J=5.4Hz),9.05(1H,s),7.35(1H,s),6.87(1H,d,J=
8.3Hz),6.24(1H,d,J=2.4Hz),6.13(1H,dd,J=8.3,2.4Hz),
5.15 (1H,m),3.72(2H,m),2.58-2.40(2H,m),2.34(1H,d,J
=13.2Hz),2.24(1H,d,J=13.2Hz),2.05-1.69(11H,m),1.28
(3H,s) IR(KBr, cm-1):3301,2978,2928,2353,1717,1651,1627,1
515,1463,1377,1298,1164,1110,1084,978,848
(Physical properties) Colorless amorphous solid PMR (DMSO-d 6 , δ ppm): 9.44 (1H, s), 9.38
(1H, d, J = 5.4Hz), 9.05 (1H, s), 7.35 (1H, s), 6.87 (1H, d, J =
8.3Hz), 6.24 (1H, d, J = 2.4Hz), 6.13 (1H, dd, J = 8.3,2.4Hz),
5.15 (1H, m), 3.72 (2H, m), 2.58-2.40 (2H, m), 2.34 (1H, d, J
= 13.2Hz), 2.24 (1H, d, J = 13.2Hz), 2.05-1.69 (11H, m), 1.28
(3H, s) IR (KBr, cm -1 ): 3301,2978,2928,2353,1717,1651,1627,1
515,1463,1377,1298,1164,1110,1084,978,848

【0230】実施例115 N−ベンゾイル−N’−6
−ヒドロキシ−2,5,7,8−テトラメチルクロマン
−2−アセチルヒドラジン(N-benzoyl-N'-6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetylhydrazine) 安息香酸 0.24g(2mmol) 及びトリエチルアミン 0.33ml
(2.4mmol)を塩化メチレン 10ml に加えて氷冷し、クロ
ロギ酸エチル(ethyl chloroformate) 0.21ml(2.2mmol)
を滴下した。氷冷下で1 時間攪拌した。参考例2で合成
した化合物6−ヒドロキシ−2,5,7,8−テトラメ
チルクロマン−2−アセトヒドラジド 0.56g(2mmol) を
加え、徐々に昇温し室温で20時間攪拌した。反応液にク
ロロホルム50ml を加え、飽和重曹水、飽和食塩水で順
次洗浄し、硫酸マグネシウムで乾燥し、溶媒を留去し
た。残渣をシリカゲルカラムクロマトグラフィーに付
し、メタノール:クロロホルム=1:50溶出部を溶媒留
去し、標記化合物 0.36g(収率47%)を得た。
Example 115 N-benzoyl-N'-6
-Hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazine (N-benzoyl-N'-6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetylhydrazine) benzoic acid 0.24 g (2 mmol) and triethylamine 0.33 ml
(2.4 mmol) was added to 10 ml of methylene chloride and cooled with ice, and ethyl chloroformate (ethyl chloroformate) 0.21 ml (2.2 mmol)
Was added dropwise. The mixture was stirred for 1 hour under ice cooling. 0.56 g (2 mmol) of the compound 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetohydrazide synthesized in Reference Example 2 was added, and the mixture was gradually heated and stirred at room temperature for 20 hours. 50 ml of chloroform was added to the reaction solution, and the mixture was washed sequentially with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the solvent eluted with methanol: chloroform = 1: 50 was distilled off to give 0.36 g (yield 47%) of the title compound.

【0231】(物性) 無色不定形固体 PMR(DMSO-d6,δ ppm) :10.31(1H,s),9.87(1H,s),7.88(2
H,d,J=7.8Hz),7.56(1H,t,J=7.8Hz),7.48(2H,t,J=7.8H
z),7.38(1H,s),2.69-2.39(4H,m),2.10-1.79(11H,m),1.1
8(3H,s) IR(KBr, cm-1):3261,2940,1656,1461,1256,1087
(Physical properties) Colorless amorphous solid PMR (DMSO-d 6 , δ ppm): 10.31 (1H, s), 9.87 (1H, s), 7.88 (2
H, d, J = 7.8Hz), 7.56 (1H, t, J = 7.8Hz), 7.48 (2H, t, J = 7.8H
z), 7.38 (1H, s), 2.69-2.39 (4H, m), 2.10-1.79 (11H, m), 1.1
8 (3H, s) IR (KBr, cm -1 ): 3261,2940,1656,1461,1256,1087

【0232】実施例116 N−6−ヒドロキシ−2,
5,7,8−テトラメチルクロマン−2−アセチル−
N’−サリチルヒドラジン(N-6-hydroxy-2,5,7,8-tetra
methylchroman-2-acetyl-N'-salicylhydrazine) 参考例2で合成した化合物6−ヒドロキシ−2,5,
7,8−テトラメチルクロマン−2−アセトヒドラジド
0.56g(2mmol) 及びサリチル酸 0.28g(2mmol) をジメチ
ルホルムアミド 10ml に加え、攪拌した。この溶液に、
DCC 0.41g(2mmol) を加え、24時間攪拌した。析出物
をろ去し、溶媒を留去した。残渣をシリカゲルカラムク
ロマトグラフィーに付し、酢酸エチル:クロロホルム=
1:1溶出部を溶媒留去し、標記化合物 0.21g(収率26
%)を得た。 (物性) 淡黄色不定形固体 PMR(DMSO-d6,δ ppm) :11.91(1H,s),10.58(1H,brs),10.
19(1H,s),7.89(1H,d,J=7.8Hz),7.42(1H,t,J=7.8Hz),7.3
8(1H,s),6.96-6.89(2H,m),2.68-2.43(4H,m),2.07-1.79
(11H,m),1.39(3H,s) IR(KBr, cm-1):3303,2938,1648,1607,1472,1372,1313,1
259,1162,1086,755
Example 116 N-6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetyl-
N'-salicylhydrazine (N-6-hydroxy-2,5,7,8-tetra
methylchroman-2-acetyl-N'-salicylhydrazine) Compound 6-hydroxy-2,5 synthesized in Reference Example 2.
7,8-tetramethylchroman-2-acetohydrazide
0.56 g (2 mmol) and 0.28 g (2 mmol) of salicylic acid were added to 10 ml of dimethylformamide and stirred. In this solution,
0.41 g (2 mmol) of DCC was added, and the mixture was stirred for 24 hours. The precipitate was removed by filtration, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and ethyl acetate: chloroform =
The solvent was distilled off from the 1: 1 eluted part to give 0.21 g of the title compound (yield 26
%). (Physical properties) Pale yellow amorphous solid PMR (DMSO-d 6 , δ ppm): 11.91 (1H, s), 10.58 (1H, brs), 10.
19 (1H, s), 7.89 (1H, d, J = 7.8Hz), 7.42 (1H, t, J = 7.8Hz), 7.3
8 (1H, s), 6.96-6.89 (2H, m), 2.68-2.43 (4H, m), 2.07-1.79
(11H, m), 1.39 (3H, s) IR (KBr, cm -1 ): 3303,2938,1648,1607,1472,1372,1313,1
259,1162,1086,755

【0233】実施例117 N−フェネチル−6−ヒド
ロキシ−2,5,7,8−テトラメチルクロマン−2−
アセトアミド(N-phenethyl-6-hydroxy-2,5,7,8-tetrame
thylchroman-2-acetamide) 6−ヒドロキシ−2,5,7,8−テトラメチルクロマ
ン−2−酢酸 0.53g(2mmol) 及びフェネチルアミン 0.2
5ml(2mmol)をジメチルホルムアミド 4mlに加え、攪拌し
た。この溶液に、DCC 0.41g(2mmol) を加え、12時間
攪拌した。析出物をろ去し、溶媒を留去した。残渣をシ
リカゲルカラムクロマトグラフィーに付し、メタノー
ル:クロロホルム=1:50溶出部を溶媒留去し、生じた
結晶をろ取した。減圧下で乾燥し、標記化合物 0.30g
(収率17%)を得た。
Example 117 N-phenethyl-6-hydroxy-2,5,7,8-tetramethylchroman-2-
Acetamide (N-phenethyl-6-hydroxy-2,5,7,8-tetrame
thylchroman-2-acetamide) 0.53 g (2 mmol) of 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetic acid and phenethylamine 0.2
5 ml (2 mmol) was added to 4 ml of dimethylformamide and stirred. 0.41 g (2 mmol) of DCC was added to this solution, and the mixture was stirred for 12 hours. The precipitate was removed by filtration, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the solvent was distilled off from the eluted portion of methanol: chloroform = 1: 50, and the resulting crystals were collected by filtration. Dry under reduced pressure to give the title compound 0.30 g
(17% yield).

【0234】(物性) 無色結晶(mp.122-123 ℃) PMR(DMSO-d6,δ ppm) :7.85(1H,brt,J=5.1Hz),7.36(1H,
s),7.28-7.15(5H,m),3.31-3.27(2H,mn),2.71(2H,t,J=7.
1Hz),2.56-2.43(2H,m),2.36(1H,d,J=13.7Hz),2.27(1H,
d,J=13.7Hz),2.05(3H,s),2.02(3H,s),1.96(3H,s),1.92-
1.85(1H,m),1.74-1.67(1H,m),1.26(3H,s) IR(KBr, cm-1):3377,2931,1654,1533,1454,1417,1236,1
176,1089,755,706
(Physical properties) Colorless crystal (mp.122-123 ° C.) PMR (DMSO-d 6 , δ ppm): 7.85 (1H, brt, J = 5.1 Hz), 7.36 (1H,
s), 7.28-7.15 (5H, m), 3.31-3.27 (2H, mn), 2.71 (2H, t, J = 7.
1Hz), 2.56-2.43 (2H, m), 2.36 (1H, d, J = 13.7Hz), 2.27 (1H,
d, J = 13.7Hz), 2.05 (3H, s), 2.02 (3H, s), 1.96 (3H, s), 1.92-
1.85 (1H, m), 1.74-1.67 (1H, m), 1.26 (3H, s) IR (KBr, cm -1 ): 3377,2931,1654,1533,1454,1417,1236,1
176,1089,755,706

【0235】実施例118 N−(2−ヒドロキシフェ
ネチル)−6−ヒドロキシ−2,5,7,8−テトラメ
チルクロマン−2−アセトアミド(N-(2-hydroxypheneth
yl)-6-hydroxy-2,5,7,8-tetramethylchroman-2-acetami
de) 6−ヒドロキシ−2,5,7,8−テトラメチルクロマ
ン−2−酢酸 0.53g(2mmol) 及び2−ヒドロキシフェネ
チルアミン 0.25ml(2mmol)をジメチルホルムアミド 4ml
に加え、攪拌した。この溶液に、DCC 0.41g(2mmol)
を加え、12時間攪拌した。析出物をろ去し、溶媒を留去
した。残渣をシリカゲルカラムクロマトグラフィーに付
し、メタノール:クロロホルム=1:50溶出部を溶媒留
去し、減圧下で乾燥し、標記化合物 0.68g(収率89%)を
得た。 (物性) 無色無定型固体 PMR(DMSO-d6,δ ppm) :9.27(1H,s),7.81(1H,brt,J=5.1H
z),7.35(1H,s),7.03-6.97(2H,m),6.77(1H,d,J=7.8Hz),
6.68(1H,t,J=7.3Hz),3.26(1H,q,J=6.7Hz),2.66(2H,t,J=
7.3Hz),2.60-2.43(1H,m),2.37(1H,d,J=13.2Hz),2.28(1
H,d,J=13.2Hz),2.05-1.88(11H,m),1.78-1.70(1H,m),1.2
8(3H,s) IR(KBr, cm-1):3388,2928,1645,1539,1456,1379,1252,1
085,754
Example 118 N- (2-hydroxyphenethyl) -6-hydroxy-2,5,7,8-tetramethylchroman-2-acetamide (N- (2-hydroxypheneth)
yl) -6-hydroxy-2,5,7,8-tetramethylchroman-2-acetami
de) 0.53 g (2 mmol) of 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetic acid and 0.25 ml (2 mmol) of 2-hydroxyphenethylamine were added to 4 ml of dimethylformamide.
And stirred. 0.41 g (2 mmol) of DCC was added to this solution.
Was added and stirred for 12 hours. The precipitate was removed by filtration, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, the solvent eluted with methanol: chloroform = 1: 50 was evaporated, and the residue was dried under reduced pressure to obtain 0.68 g (yield 89%) of the title compound. (Physical properties) Colorless amorphous solid PMR (DMSO-d 6 , δ ppm): 9.27 (1H, s), 7.81 (1H, brt, J = 5.1H
z), 7.35 (1H, s), 7.03-6.97 (2H, m), 6.77 (1H, d, J = 7.8Hz),
6.68 (1H, t, J = 7.3Hz), 3.26 (1H, q, J = 6.7Hz), 2.66 (2H, t, J =
7.3Hz), 2.60-2.43 (1H, m), 2.37 (1H, d, J = 13.2Hz), 2.28 (1
(H, d, J = 13.2Hz), 2.05-1.88 (11H, m), 1.78-1.70 (1H, m), 1.2
8 (3H, s) IR (KBr, cm -1 ): 3388,2928,1645,1539,1456,1379,1252,1
085,754

【0236】実施例119 プロピオンアルデヒド6−
ヒドロキシ−2,5,7,8−テトラメチルクロマン−
2−アセチルヒドラゾン(propionaldehyde 6-hydroxy-
2,5,7,8-tetramethylchroman-2-acetylhydrazone) 参考例2で合成した化合物6−ヒドロキシ−2,5,
7,8−テトラメチルクロマン−2−アセトヒドラジド
0.56g(2mmol) 及びプロピオンアルデヒド 0.15ml(2mmo
l)をメタノール 10ml に溶かし、室温下で24時間攪拌し
た。溶媒を留去し、残渣をシリカゲルカラムクロマトグ
ラフィーに付した。酢酸エチル:n−ヘキサン=2:1
溶出部を溶媒留去し、酢酸エチル及びn−ヘキサンを加
えて結晶化させ、ろ取した。減圧下で乾燥し、標記化合
物 0.27g(収率42%)を得た。
Example 119 Propionaldehyde 6-
Hydroxy-2,5,7,8-tetramethylchroman-
2-acetylhydrazone (propionaldehyde 6-hydroxy-
(2,5,7,8-tetramethylchroman-2-acetylhydrazone) Compound 6-hydroxy-2,5 synthesized in Reference Example 2.
7,8-tetramethylchroman-2-acetohydrazide
0.56 g (2 mmol) and propionaldehyde 0.15 ml (2 mmo
l) was dissolved in methanol (10 ml) and stirred at room temperature for 24 hours. The solvent was distilled off, and the residue was subjected to silica gel column chromatography. Ethyl acetate: n-hexane = 2: 1
The solvent was distilled off from the eluted portion, and crystallized by adding ethyl acetate and n-hexane, and collected by filtration. Drying under reduced pressure gave 0.27 g (42% yield) of the title compound.

【0237】(物性) 無色結晶(mp.85-89 ℃) PMR(DMSO-d6,δ ppm) :10.89,10.84(1H,each-s),7.44,
7.28(1H,each-t,J=4.9Hz),7.38,7.35(1H,each-s),2.83-
1.76(17H,m),1.33,1.31(3H,each-s),1.02,0.96(3H,each
-t,J=7.6Hz) IR(KBr, cm-1):3393,3214,3057,2972,2933,1660,1560,1
457,1379,1254,1158,1087,1017,922,856
(Physical properties) Colorless crystals (mp. 85-89 ° C.) PMR (DMSO-d 6 , δ ppm): 10.89, 10.84 (1H, each-s), 7.44,
7.28 (1H, each-t, J = 4.9Hz), 7.38,7.35 (1H, each-s), 2.83-
1.76 (17H, m), 1.33,1.31 (3H, each-s), 1.02,0.96 (3H, each
-t, J = 7.6Hz) IR (KBr, cm -1 ): 3393,3214,3057,2972,2933,1660,1560,1
457,1379,1254,1158,1087,1017,922,856

【0238】実施例120〜121 プロピオンアルデヒドを他のアルデヒド化合物に代える
以外は実施例119と実質的に同様に処理して、以下の
化合物を製造した。 実施例120 グリセルアルデヒド6−ヒドロキシ−
2,5,7,8−テトラメチルクロマン−2−アセチル
ヒドラゾン(glyceraldehyde 6-hydroxy-2,5,7,8-tetram
ethylchroman-2-acetylhydrazone) 収率:40% (物性) 無色結晶(mp.110-112 ℃) PMR(DMSO-d6,δ ppm) :11.04,11.00(1H,each-s),7.40,
7.37(1H,each-s),7.33,7.20(1H,each-d,J=6.4Hz),5.22,
5.14(1H,d,J=4.9Hz,t,J=5.6Hz),4.71,4.66(1H,each-t,J
=5.9Hz),2.85-2.33(4H,m),2.09-1.77(11H,m),1.33,1.31
(3H,each-s) IR(KBr, cm-1):3393,3248,3063,2931,2363,2344,1663,1
570,1456,1379,1350,1256,1164,1086
Examples 120 to 121 The following compounds were prepared in substantially the same manner as in Example 119 except that propionaldehyde was replaced with another aldehyde compound. Example 120 Glyceraldehyde 6-hydroxy-
2,5,7,8-tetramethylchroman-2-acetylhydrazone (glyceraldehyde 6-hydroxy-2,5,7,8-tetram
ethylchroman-2-acetylhydrazone) Yield: 40% (Physical Properties) colorless crystals (mp.110-112 ℃) PMR (DMSO- d 6, δ ppm): 11.04,11.00 (1H, each-s), 7.40,
7.37 (1H, each-s), 7.33,7.20 (1H, each-d, J = 6.4Hz), 5.22,
5.14 (1H, d, J = 4.9Hz, t, J = 5.6Hz), 4.71,4.66 (1H, each-t, J
= 5.9Hz), 2.85-2.33 (4H, m), 2.09-1.77 (11H, m), 1.33,1.31
(3H, each-s) IR (KBr, cm -1 ): 3393,3248,3063,2931,2363,2344,1663,1
570,1456,1379,1350,1256,1164,1086

【0239】実施例121 2,2−ジメチル−3−ヒ
ドロキシプロピオンアルデヒド6−ヒドロキシ−2,
5,7,8−テトラメチルクロマン−2−アセチルヒド
ラゾン(2,2-dimethyl-3-hydroxypropionaldehyde 6-hyd
roxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone) 収率:74% (物性) 無色結晶(mp.209−211 ℃) PMR(DMSO-d6,δ ppm) :10.84,10.83(1H,each-s),7.40,
7.39(1H,each-s),7.35,7.23(1H,each-s),4.73,4.69(1H,
each-t,J=5.4Hz),3.29,3.24(2H,each-d,J=5.4Hz),2.85-
2.32(4H,m),2.05-1.76(11H, m),1.33,1.31(3H,each-s),
1.00,0.93(6H,each-s) IR(KBr, cm-1):3407,3258,2928,1649,1569,1457,1347,1
237,1170,1063
Example 121 2,2-Dimethyl-3-hydroxypropionaldehyde 6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetylhydrazone (2,2-dimethyl-3-hydroxypropionaldehyde 6-hyd
roxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone) Yield: 74% (physical properties) Colorless crystals (mp. 209-211 ° C) PMR (DMSO-d 6 , δ ppm): 10.84, 10.83 (1H , each-s), 7.40,
7.39 (1H, each-s), 7.35,7.23 (1H, each-s), 4.73,4.69 (1H, each-s)
each-t, J = 5.4Hz), 3.29,3.24 (2H, each-d, J = 5.4Hz), 2.85-
2.32 (4H, m), 2.05-1.76 (11H, m), 1.33,1.31 (3H, each-s),
1.00,0.93 (6H, each-s) IR (KBr, cm -1 ): 3407,3258,2928,1649,1569,1457,1347,1
237,1170,1063

【0240】実施例122 ベンズアルデヒド6−ヒド
ロキシ−2,5,7,8−テトラメチルクロマン−2−
カルボヒドラゾン(benzaldehyde 6-hydroxy-2,5,7,8-te
tramethylchroman-2-carbohydrazone) 参考例3で合成した化合物6−ヒドロキシ−2,5,
7,8−テトラメチルクロマン−2−カルボヒドラジド
0.53g(2mmol) 及びベンズアルデヒド 0.21ml(2mmol)を
メタノール 10ml に溶かし、70℃で5 時間攪拌した。生
じた結晶をろ取した。減圧下で乾燥し、標記化合物 0.5
8g(収率82%)を得た。
Example 122 Benzaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-
Carbohydrazone (benzaldehyde 6-hydroxy-2,5,7,8-te
(tramethylchroman-2-carbohydrazone) Compound 6-hydroxy-2,5,5 synthesized in Reference Example 3.
7,8-tetramethylchroman-2-carbohydrazide
0.53 g (2 mmol) and 0.21 ml (2 mmol) of benzaldehyde were dissolved in 10 ml of methanol and stirred at 70 ° C. for 5 hours. The resulting crystals were collected by filtration. Dry under reduced pressure to give the title compound 0.5
8 g (82% yield) was obtained.

【0241】(物性) 無色結晶(mp.192-194 ℃) PMR(DMSO-d6,δ ppm) :10.72(1H,s),8.35(1H,s),7.67-
7.64(2H,m),7.48(1H,s),7.45-7.40(3H,m),2.58-2.54(2
H,m),2.34-2.27(1H,m),2.18(3H,s),2.09(3H,s),2.01(3
H,s),1.83-1.76(1H,m),1.50(3H,s) IR(KBr, cm-1):3336,3289,2931,1677,1521,1449,1374,1
255,1193,1134,1113,1086,1058,964,942,755,692,577
(Physical properties) Colorless crystal (mp. 192-194 ° C.) PMR (DMSO-d 6 , δ ppm): 10.72 (1H, s), 8.35 (1H, s), 7.67-
7.64 (2H, m), 7.48 (1H, s), 7.45-7.40 (3H, m), 2.58-2.54 (2
H, m), 2.34-2.27 (1H, m), 2.18 (3H, s), 2.09 (3H, s), 2.01 (3
(H, s), 1.83-1.76 (1H, m), 1.50 (3H, s) IR (KBr, cm -1 ): 3336,3289,2931,1677,1521,1449,1374,1
255,1193,1134,1113,1086,1058,964,942,755,692,577

【0242】実施例123〜125 ベンズアルデヒドを他のアルデヒド化合物に代える以外
は実施例122と実質的に同様に処理して、以下の化合
物を製造した。 実施例123 サリチルアルデヒド6−ヒドロキシ−
2,5,7,8−テトラメチルクロマン−2−カルボヒ
ドラゾン(salicylaldehyde 6-hydroxy-2,5,7,8-tetrame
thylchroman-2-carbohydrazone) 収率:92% (物性) 淡黄色結晶(mp.184-186 ℃) PMR(DMSO-d6,δ ppm) :11.20(1H,s),11.1(1H,s),8.57(1
H,s),7.48(1H,s),7.43(1H,d,J=6.8Hz),7.26(1H,t,J=7.1
Hz),6.90-6.85(2H,m),2.57(2H,m),2.34-2.26(1H,m),2.1
7(3H,s),2.09(3H,s),2.02(3H,s),1.85-1.77(1H,m),1.50
(3H,s) IR(KBr, cm-1):3416,3332,2938,1675,1618,1520,1488,1
456,1373,1272,1256,1237,1201,1140,1114,1086,751
Examples 123 to 125 The following compounds were prepared in substantially the same manner as in Example 122 except that benzaldehyde was replaced with another aldehyde compound. Example 123 Salicylaldehyde 6-hydroxy-
2,5,7,8-tetramethylchroman-2-carbohydrazone (salicylaldehyde 6-hydroxy-2,5,7,8-tetrame
thylchroman-2-carbohydrazone) Yield: 92% (property) pale yellow crystals (mp.184-186 ℃) PMR (DMSO- d 6, δ ppm): 11.20 (1H, s), 11.1 (1H, s), 8.57 (1
H, s), 7.48 (1H, s), 7.43 (1H, d, J = 6.8Hz), 7.26 (1H, t, J = 7.1
Hz), 6.90-6.85 (2H, m), 2.57 (2H, m), 2.34-2.26 (1H, m), 2.1
7 (3H, s), 2.09 (3H, s), 2.02 (3H, s), 1.85-1.77 (1H, m), 1.50
(3H, s) IR (KBr, cm -1 ): 3416,3332,2938,1675,1618,1520,1488,1
456,1373,1272,1256,1237,1201,1140,1114,1086,751

【0243】実施例124 4,6−ジメトキシサリチ
ルアルデヒド6−ヒドロキシ−2,5,7,8−テトラ
メチルクロマン−2−カルボヒドラゾン(4,6-dimethoxy
salicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchrom
an-2-carbohydrazone) 収率:90% (物性) 無色結晶(mp.103-104 ℃) PMR(DMSO-d6,δ ppm) :12.33(1H,s),11.15(1H,s),8.79
(1H,s),7.46(1H,s),6.09(2H,s),3.81(3H,s),3.77(3H,
s),2.56-2.51(2H,m),2.32-2.25(1H,m),2.16(3H,s),2.09
(3H,s),2.02(3H,s),1.82-1.74(1H,m),1.48(3H,s) IR(KBr, cm-1):3465,3282,2937,1673,1631,1604,1539,1
346,1261,1213,1154,1120,816
Example 124 4,6-Dimethoxysalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-carbohydrazone (4,6-dimethoxy
salicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchrom
an-2-carbohydrazone) Yield: 90% (Physical Properties) colorless crystals (mp.103-104 ℃) PMR (DMSO- d 6, δ ppm): 12.33 (1H, s), 11.15 (1H, s), 8.79
(1H, s), 7.46 (1H, s), 6.09 (2H, s), 3.81 (3H, s), 3.77 (3H,
s), 2.56-2.51 (2H, m), 2.32-2.25 (1H, m), 2.16 (3H, s), 2.09
(3H, s), 2.02 (3H, s), 1.82-1.74 (1H, m), 1.48 (3H, s) IR (KBr, cm -1 ): 3465,3282,2937,1673,1631,1604,1539 , 1
346,1261,1213,1154,1120,816

【0244】実施例125 4−(ジエチルアミノ)サ
リチルアルデヒド6−ヒドロキシ−2,5,7,8−テ
トラメチルクロマン−2−カルボヒドラゾン(4-(diethy
lamino)salicylaldehyde 6-hydroxy-2,5,7,8-tetrameth
ylchroman-2-carbohydrazone) 収率:27% (物性) 無色結晶(mp.228-230 ℃) PMR(DMSO-d6,δ ppm) :11.31(1H,s),10.71(1H,s),8.33
(1H,s),7.48(1H,s),7.09(1H,d,J=8.3Hz),6.22(1H,d,J=
8.8Hz),6.08(1H,s),3.34(1H,q,J=6.8Hz),2.60-2.47(2H,
m),2.32-2.25(1H,m),2.17(3H,s),2.09(3H,s),2.01(3H,
s),1.82-1.75(1H,m),1.48(3H,s),1.11(6H,t,J=6.8Hz) IR(KBr, cm-1):3426,3347,2971,2929,1674,1636,1598,1
514,1354,1244,1135
Example 125 4- (Diethylamino) salicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-carbohydrazone (4- (diethy
lamino) salicylaldehyde 6-hydroxy-2,5,7,8-tetrameth
ylchroman-2-carbohydrazone) Yield: 27% (Physical Properties) colorless crystals (mp.228-230 ℃) PMR (DMSO- d 6, δ ppm): 11.31 (1H, s), 10.71 (1H, s), 8.33
(1H, s), 7.48 (1H, s), 7.09 (1H, d, J = 8.3Hz), 6.22 (1H, d, J =
8.8Hz), 6.08 (1H, s), 3.34 (1H, q, J = 6.8Hz), 2.60-2.47 (2H,
m), 2.32-2.25 (1H, m), 2.17 (3H, s), 2.09 (3H, s), 2.01 (3H,
s), 1.82-1.75 (1H, m), 1.48 (3H, s), 1.11 (6H, t, J = 6.8Hz) IR (KBr, cm -1 ): 3426,3347,2971,2929,1674,1636 , 1598,1
514,1354,1244,1135

【0245】実施例126 o−バニリン6−ヒドロキ
シ−2,5,7,8−テトラメチルクロマン−2−ブチ
リルヒドラゾン(o-vanillin 6-hydroxy-2,5,7,8-tetram
ethylchroman-2-butyrylhydrazone) 参考例4で合成した化合物6−ヒドロキシ−2,5,
7,8−テトラメチルクロマン−2−ブチロヒドラジド
0.61g(2mmol) 及びo−バニリン 0.30g(2mmol)をジメ
チルホルムアミド 10ml に溶かし、室温下で15時間攪拌
した。溶媒を留去し、酢酸エチルを加え、水、飽和食塩
水で順次洗浄し、硫酸マグネシウムで乾燥し、溶媒を留
去した。生じた結晶をろ取した。減圧下で乾燥し、標記
化合物 0.85g(収率96%)を得た。
Example 126: o-vanillin 6-hydroxy-2,5,7,8-tetramethylchroman-2-butyrylhydrazone (o-vanillin 6-hydroxy-2,5,7,8-tetram
ethylchroman-2-butyrylhydrazone) Compound 6-hydroxy-2,5,5 synthesized in Reference Example 4.
7,8-tetramethylchroman-2-butyrohydrazide
0.61 g (2 mmol) and 0.30 g (2 mmol) of o-vanillin were dissolved in 10 ml of dimethylformamide, and the mixture was stirred at room temperature for 15 hours. The solvent was distilled off, ethyl acetate was added, and the mixture was washed sequentially with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The resulting crystals were collected by filtration. Drying under reduced pressure gave 0.85 g (96% yield) of the title compound.

【0246】(物性) 無色結晶(mp.197 ℃) PMR(DMSO-d6,δ ppm) :11.52,11.19(1H,each-s),10.96,
9.52(1H,each-s),8.33,8.25(1H,each-s),7.31,7.30(1H,
each-s),7.17,7.05(1H,each-d,J=7.8Hz),6.98,6.94(1H,
each-d,J=7.3Hz),6.82,6.78(1H,each-t,J=8.0Hz),3.82,
3.81(3H,each-s),2.59-2.45(3H,m),2.26-2.17(1H,m),2.
05-1.97(9H,m),1.81-1.51(6H,m),1.19(3H,s) IR(KBr, cm-1):3548,2924,1666,1471,1429,1400,1255,1
088,724
(Physical properties) Colorless crystals (mp. 197 ° C.) PMR (DMSO-d 6 , δ ppm): 11.52, 11.19 (1H, each-s), 10.96,
9.52 (1H, each-s), 8.33,8.25 (1H, each-s), 7.31,7.30 (1H, each-s)
each-s), 7.17,7.05 (1H, each-d, J = 7.8Hz), 6.98,6.94 (1H,
each-d, J = 7.3Hz), 6.82,6.78 (1H, each-t, J = 8.0Hz), 3.82,
3.81 (3H, each-s), 2.59-2.45 (3H, m), 2.26-2.17 (1H, m), 2.
05-1.97 (9H, m), 1.81-1.51 (6H, m), 1.19 (3H, s) IR (KBr, cm -1 ): 3548,2924,1666,1471,1429,1400,1255,1
088,724

【0247】実施例127 4−(ジエチルアミノ)サ
リチルアルデヒド6−ヒドロキシ−2,5,7,8−テ
トラメチルクロマン−2−ブチリルヒドラゾン(4−
(diethylamino)salicylalde
hyde 6−hydroxy−2,5,7,8−te
tramethylchroman−2−butyry
lhydrazone) 参考例4で合成した化合物6−ヒドロキシ−2,5,
7,8−テトラメチルクロマン−2−ブチロヒドラジド
0.61g(2mmol)及び4−(ジエチルアミノ)
サリチルアルデヒド 0.39g(2mmol) をジメチルホルムア
ミド 10ml に溶かし、室温下で15時間攪拌した。溶媒を
留去し、酢酸エチルを加え、水、飽和食塩水で順次洗浄
し、硫酸マグネシウムで乾燥し、溶媒を留去した。生じ
た結晶をろ取した。減圧下で乾燥し、標記化合物0.50g
(収率52%)を得た。
Example 127 4- (Diethylamino) salicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-butyrylhydrazone (4-
(Diethylamino) salicylalde
hydraulic 6-hydroxy-2,5,7,8-te
tramethylchroman-2-butyry
lhydrozone) Compound 6-hydroxy-2,5 synthesized in Reference Example 4.
0.61 g (2 mmol) of 7,8-tetramethylchroman-2-butyrohydrazide and 4- (diethylamino)
0.39 g (2 mmol) of salicylaldehyde was dissolved in 10 ml of dimethylformamide, and the mixture was stirred at room temperature for 15 hours. The solvent was distilled off, ethyl acetate was added, and the mixture was washed sequentially with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The resulting crystals were collected by filtration. Dry under reduced pressure, 0.50 g of the title compound
(Yield 52%).

【0248】(物性) 淡褐色結晶(mp.180 ℃) PMR(DMSO-d6,δ ppm) :11.33,10.92(1H,each-s),11.21,
10.17(1H,each-s),8.10,8.01(1H,each-s),7.31,7.30(1
H,each-s),7.19,7.11(1H,each-d,J=8.8Hz),6.22,6.20(1
H,each-dd,J=8.8,2.4Hz),6.08(1H,d,J=2.4Hz),3.34(4H,
q,J=6.8Hz),2.54-2.45(3H,m),2.21-2.12(1H,m),2.05-1.
97(9H,m),1.79-1.49(6H,m),1.18(3H,s),1.11(6H,t,J=6.
8Hz) IR(KBr, cm-1):3507,2969,1658,1632,1528,1398,1352,1
244,1201,1127,781
(Physical properties) Light brown crystal (mp. 180 ° C.) PMR (DMSO-d 6 , δ ppm): 11.33, 10.92 (1H, each-s), 11.21,
10.17 (1H, each-s), 8.10,8.01 (1H, each-s), 7.31,7.30 (1
H, each-s), 7.19,7.11 (1H, each-d, J = 8.8Hz), 6.22,6.20 (1
H, each-dd, J = 8.8,2.4Hz), 6.08 (1H, d, J = 2.4Hz), 3.34 (4H,
q, J = 6.8Hz), 2.54-2.45 (3H, m), 2.21-2.12 (1H, m), 2.05-1.
97 (9H, m), 1.79-1.49 (6H, m), 1.18 (3H, s), 1.11 (6H, t, J = 6.
8Hz) IR (KBr, cm -1 ): 3507,2969,1658,1632,1528,1398,1352,1
244,1201,1127,781

【0249】実施例128〜129 ヒドラジド化合物を参考例5で合成した化合物6−ヒド
ロキシ−2,5,7,8−テトラメチルクロマン−2−
プロピオノヒドラジド(6-hydroxy-2,5,7,8-tetramethyl
chroman-2-propionohydrazide)に代える以外は実施例1
26又は127と実質的に同様に処理して、以下の化合
物を製造した。 実施例128 o−バニリン6−ヒドロキシ−2,5,
7,8−テトラメチルクロマン−2−プロピオニルヒド
ラゾン(o-vanillin 6-hydroxy-2,5,7,8-tetramethylchr
oman-2-propionylhydrazone) 収率:82% (物性) 無色結晶(mp.191-195 ℃) PMR(DMSO-d6,δ ppm) :11.58,11.20(1H,each-s),10.97,
9.47(1H,each-s),8.33,8.27(1H,each-s),7.34,7.33(1H,
each-s),7.18,7.06(1H,each-d,J=7.8Hz),6.98,6.96(1H,
each-d,J=7.8Hz),6.82,6.79(1H,each-t,J=8.1Hz),3.82,
3.81(3H,each-s),2.80-2.28(4H,m),2.12-1.98(9H,m),1.
95-1.74(4H,m),1.23,1.19(3H,s) IR(KBr, cm-1):3357,2968,2930,1654,1465,1419,1253,1
089,735
Examples 128 to 129 Compounds obtained by synthesizing hydrazide compounds in Reference Example 5 6-hydroxy-2,5,7,8-tetramethylchroman-2-
Propionohydrazide (6-hydroxy-2,5,7,8-tetramethyl
Example 1 except for replacing with chroman-2-propionohydrazide)
Substantially the same as 26 or 127, the following compounds were prepared: Example 128 o-Vaniline 6-hydroxy-2,5,
7,8-tetramethylchroman-2-propionylhydrazone (o-vanillin 6-hydroxy-2,5,7,8-tetramethylchr
oman-2-propionylhydrazone) Yield: 82% (Physical Properties) colorless crystals (mp.191-195 ℃) PMR (DMSO- d 6, δ ppm): 11.58,11.20 (1H, each-s), 10.97,
9.47 (1H, each-s), 8.33,8.27 (1H, each-s), 7.34,7.33 (1H, each-s)
each-s), 7.18,7.06 (1H, each-d, J = 7.8Hz), 6.98,6.96 (1H,
each-d, J = 7.8Hz), 6.82,6.79 (1H, each-t, J = 8.1Hz), 3.82,
3.81 (3H, each-s), 2.80-2.28 (4H, m), 2.12-1.98 (9H, m), 1.
95-1.74 (4H, m), 1.23,1.19 (3H, s) IR (KBr, cm -1 ): 3357,2968,2930,1654,1465,1419,1253,1
089,735

【0250】実施例129 4−(ジエチルアミノ)サ
リチルアルデヒド6−ヒドロキシ−2,5,7,8−テ
トラメチルクロマン−2−プロピオニルヒドラゾン(4-
(diethylamino)salicylaldehyde 6-hydroxy-2,5,7,8-te
tramethylchroman-2-propionylhydrazone) 収率64% (物性) 淡黄色結晶(mp.202-203 ℃) PMR(DMSO-d6,δ ppm) :11.34,10.95(1H,each-s),11.27,
10.16(1H,each-s),8.11,8.02(1H,each-s),7.34(1H,s),
7.19,7.11(1H,each-d,J=8.8Hz),6.23,6.21(1H,each-dd,
J=8.8,2.4Hz),6.10,6.08(1H,each-d,J=2.4Hz),3.35(4H,
q,J=7.1Hz),2.69-2.23(4H,m),2.06-1.98(9H,m),1.93-1.
71(4H,m),1.18(3H,s),1.11(6H,t,J=7.1Hz) IR(KBr, cm-1):3421,2968,2929,1655,1630,1525,1449,1
405,1354,1245,1129,1101,783
Example 129 4- (Diethylamino) salicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-propionylhydrazone (4-
(diethylamino) salicylaldehyde 6-hydroxy-2,5,7,8-te
tramethylchroman-2-propionylhydrazone) 64% yield (Physical Properties) pale yellow crystals (mp.202-203 ℃) PMR (DMSO- d 6, δ ppm): 11.34,10.95 (1H, each-s), 11.27,
10.16 (1H, each-s), 8.11,8.02 (1H, each-s), 7.34 (1H, s),
7.19,7.11 (1H, each-d, J = 8.8Hz), 6.23,6.21 (1H, each-dd,
J = 8.8,2.4Hz), 6.10,6.08 (1H, each-d, J = 2.4Hz), 3.35 (4H,
q, J = 7.1Hz), 2.69-2.23 (4H, m), 2.06-1.98 (9H, m), 1.93-1.
71 (4H, m), 1.18 (3H, s), 1.11 (6H, t, J = 7.1Hz) IR (KBr, cm -1 ): 3421,2968,2929,1655,1630,1525,1449,1
405,1354,1245,1129,1101,783

【0251】実施例130 4−イソプロポキシサリチ
ルアルデヒド3,5−ジ−t−ブチル−4−ヒドロキシ
ベンゾイルヒドラゾン(4-isopropoxysalicylaldehyde
3,5-di-t-butyl-4-hydroxybenzoylhydrazone) 参考例1で合成した化合物3,5−ジ−t−ブチル−4
−ヒドロキシベンゾヒドラジド 1.06g(4mmol) 及び4−
イソプロポキシサリチルアルデヒド 0.72g(4mmol) をエ
タノール 20ml に溶かし、室温下で18時間攪拌した。析
出した結晶をろ取し、減圧下で乾燥し、標記化合物 1.1
5g(収率67%)を得た。
Example 130 4-Isopropoxysalicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone
3,5-di-t-butyl-4-hydroxybenzoylhydrazone) Compound synthesized in Reference Example 1, 3,5-di-t-butyl-4
-Hydroxybenzohydrazide 1.06 g (4 mmol) and 4-
0.72 g (4 mmol) of isopropoxysalicylaldehyde was dissolved in 20 ml of ethanol, and the mixture was stirred at room temperature for 18 hours. The precipitated crystals were collected by filtration and dried under reduced pressure to give the title compound 1.1
5 g (67% yield) was obtained.

【0252】(物性) 淡黄色結晶(mp.243-248 ℃) PMR(DMSO-d6,δ ppm) :11.73(1H,brs),11.71(1H,brs),
8.53(1H,s),7.67(2H,s),7.56(1H,s),7.36(1H,d,J=8.3H
z),6.51-6.44(2H,m),4.65(1H,sept,J=5.9Hz),1.43(18H,
s),1.28(6H,d,J=5.9Hz)
(Physical properties) Light yellow crystal (mp. 243-248 ° C.) PMR (DMSO-d 6 , δ ppm): 11.73 (1H, brs), 11.71 (1H, brs),
8.53 (1H, s), 7.67 (2H, s), 7.56 (1H, s), 7.36 (1H, d, J = 8.3H
z), 6.51-6.44 (2H, m), 4.65 (1H, sept, J = 5.9Hz), 1.43 (18H,
s), 1.28 (6H, d, J = 5.9Hz)

【0253】実施例131〜145 4−イソプロポキシサリチルアルデヒドを他のアルデヒ
ド化合物に代える以外は実施例130と実質的に同様に
処理して、以下の化合物を製造した。 実施例131 3−イソプロポキシサリチルアルデヒド
3,5−ジ−t−ブチル−4−ヒドロキシベンゾイルヒ
ドラゾン(3-isopropoxysalicylaldehyde 3,5-di-t-buty
l-4-hydroxybenzoylhydrazone) 収率47% (物性) 無色結晶(mp.285-289 ℃) PMR(DMSO-d6,δ ppm) :11.85(1H,s),11.21(1H,s),8.62
(1H,s),7.68(2H,s),7.58(1H,s),7.11(1H,dd,J=1.5 and
7.8Hz),7.01(1H,d,J=7.8Hz),6.83(1H,t,J=7.8Hz),4.56
(1H,sept,J=5.9Hz),1.44(18H,s),1.28(6H,d,J=5.9Hz)
Examples 131 to 145 The following compounds were prepared in substantially the same manner as in Example 130 except that 4-isopropoxysalicylaldehyde was replaced with another aldehyde compound. Example 131 3-isopropoxysalicylaldehyde 3,5-di-t-buty
l-4-hydroxybenzoylhydrazone) Yield 47% (Physical properties) Colorless crystal (mp.285-289 ° C) PMR (DMSO-d 6 , δ ppm): 11.85 (1H, s), 11.21 (1H, s), 8.62
(1H, s), 7.68 (2H, s), 7.58 (1H, s), 7.11 (1H, dd, J = 1.5 and
7.8Hz), 7.01 (1H, d, J = 7.8Hz), 6.83 (1H, t, J = 7.8Hz), 4.56
(1H, sept, J = 5.9Hz), 1.44 (18H, s), 1.28 (6H, d, J = 5.9Hz)

【0254】実施例132 2−ヒドロキシ−3−メト
キシシンナムアルデヒド3,5−ジ−t−ブチル−4−
ヒドロキシベンゾイルヒドラゾン(2-hydroxy-3-methoxy
cinnamaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydr
azone) 収率:69% (物性) 淡黄色結晶(mp.152-156 ℃) PMR(DMSO-d6,δ ppm) :11.43(1H,brs),9.11(1H,s),8.62
(1H,s),8.20(1H,br-d,J=8.8Hz),7.61(2H,s),7.50(1H,
s),7.22-7.12(2H,m),7.10-6.97(1H,m),6.92(1H,dd,J=1.
0 and 7.8Hz),6.79(1H,t,J=7.8Hz),3.82(3H,s),1.42(18
H,s) IR(KBr, cm-1):3624,3520,3515,2956,1643,1620,1546,1
477,1439,1363,1305,1259,1238,1069,984,774,727,698
Example 132 2-Hydroxy-3-methoxycinnamaldehyde 3,5-di-tert-butyl-4-
Hydroxybenzoyl hydrazone (2-hydroxy-3-methoxy
cinnamaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydr
azone) Yield: 69% (physical properties) pale yellow crystal (mp. 152-156 ° C) PMR (DMSO-d 6 , δ ppm): 11.43 (1H, brs), 9.11 (1H, s), 8.62
(1H, s), 8.20 (1H, br-d, J = 8.8Hz), 7.61 (2H, s), 7.50 (1H,
s), 7.22-7.12 (2H, m), 7.10-6.97 (1H, m), 6.92 (1H, dd, J = 1.
0 and 7.8Hz), 6.79 (1H, t, J = 7.8Hz), 3.82 (3H, s), 1.42 (18
H, s) IR (KBr, cm -1 ): 3624,3520,3515,2956,1643,1620,1546,1
477,1439,1363,1305,1259,1238,1069,984,774,727,698

【0255】実施例133 3−メチル−6−イソプロ
ピルサリチルアルデヒド3,5−ジ−t−ブチル−4−
ヒドロキシベンゾイルヒドラゾン(3-methyl-6-isopropy
lsalicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhy
drazone) 収率:88% (物性) 淡黄色結晶(mp.>300℃) PMR(DMSO-d6,δ ppm) :12.83(1H,s),11.87(1H,s),9.00
(1H,s),7.69(2H,s),7.62(1H,s),7.14(1H,d,J=8.0Hz),6.
76(1H,d,J=8.0Hz),3.35-3.32(1H,m),2.17(3H,s),1.44(1
8H,s),1.24(6H,d,J=7.0Hz) IR(KBr, cm-1):3620,3205,2961,1635,1600,1547,1458,1
436,1360,1304,1240,1115,962,811
Example 133 3-Methyl-6-isopropylsalicylaldehyde 3,5-di-tert-butyl-4-
Hydroxybenzoyl hydrazone (3-methyl-6-isopropy
lsalicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhy
Drazone) Yield: 88% (property) pale yellow crystals (mp> 300 ℃) PMR ( DMSO-d 6, δ ppm):. 12.83 (1H, s), 11.87 (1H, s), 9.00
(1H, s), 7.69 (2H, s), 7.62 (1H, s), 7.14 (1H, d, J = 8.0Hz), 6.
76 (1H, d, J = 8.0Hz), 3.35-3.32 (1H, m), 2.17 (3H, s), 1.44 (1
8H, s), 1.24 (6H, d, J = 7.0Hz) IR (KBr, cm -1 ): 3620,3205,2961,1635,1600,1547,1458,1
436,1360,1304,1240,1115,962,811

【0256】実施例134 4,6−ジイソプロポキシ
サリチルアルデヒド3,5−ジ−t−ブチル−4−ヒド
ロキシベンゾイルヒドラゾン(4,6-diisopropoxysalicyl
aldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone) 収率:83% (物性) 無色結晶(mp.>300℃) PMR(DMSO-d6,δ ppm) :12.64(1H,s),11.83(1H,s),8.76
(1H,s),7.68(2H,s),7.54(1H,s),6.10-6.06(2H,m),4.73-
4.60(2H,m),1.44(18H,s),1.32(1H,d,J=6.0Hz),1.28(6H,
d,J=6.0Hz) IR(KBr, cm-1):3616,3208,3062,2973,1631,1601,1547,1
501,1435,1346,1324,1303,1239,1155,1114,1067,1023,9
72,930,908,813,708
Example 134 4,6-Diisopropoxysalicylaldehyde 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone (4,6-diisopropoxysalicyl)
aldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone) Yield: 83% (physical properties) colorless crystal (mp.> 300 ℃) PMR (DMSO-d 6 , δ ppm): 12.64 (1H, s), 11.83 (1H, s), 8.76
(1H, s), 7.68 (2H, s), 7.54 (1H, s), 6.10-6.06 (2H, m), 4.73-
4.60 (2H, m), 1.44 (18H, s), 1.32 (1H, d, J = 6.0Hz), 1.28 (6H,
d, J = 6.0Hz) IR (KBr, cm -1 ): 3616,3208,3062,2973,1631,1601,1547,1
501,1435,1346,1324,1303,1239,1155,1114,1067,1023,9
72,930,908,813,708

【0257】実施例135 4−ジメチルアミノサリチ
ルアルデヒド3,5−ジ−t−ブチル−4−ヒドロキシ
ベンゾイルヒドラゾン(4-dimethylaminosalicylaldehyd
e 3,5-di-t-butyl-4-hydroxybenzoylhydrazone) 収率:78% (物性) 黄色結晶(mp.255-272 ℃) PMR(DMSO-d6,δ ppm) :11.62(1H,s),11.58(1H,s),8.44
(1H,s),7.65(2H,s),7.51(1H,s),7.19(1H,d,J=8.7Hz),6.
30(1H,dd,J=2.4 and 8.7Hz),6.17(1H,d,J=2.4Hz),2.96
(6H,s),1.43(18H,s) IR(KBr, cm-1):3411,3221,2957,2911,1630,1600,1522,1
484,1435,1353,1306,1263,1239,1137,980,910,888,852,
822,791,717,700,647
Example 135 4-dimethylaminosalicylaldehyde 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone
e 3,5-di-t-butyl-4-hydroxybenzoylhydrazone) Yield: 78% (physical properties) Yellow crystal (mp. 255-272 ° C) PMR (DMSO-d 6 , δ ppm): 11.62 (1H, s) , 11.58 (1H, s), 8.44
(1H, s), 7.65 (2H, s), 7.51 (1H, s), 7.19 (1H, d, J = 8.7Hz), 6.
30 (1H, dd, J = 2.4 and 8.7Hz), 6.17 (1H, d, J = 2.4Hz), 2.96
(6H, s), 1.43 (18H, s) IR (KBr, cm -1 ): 3411,3221,2957,2911,1630,1600,1522,1
484,1435,1353,1306,1263,1239,1137,980,910,888,852,
822,791,717,700,647

【0258】実施例136 4−ジ−n−プロピルアミ
ノサリチルアルデヒド3,5−ジ−t−ブチル−4−ヒ
ドロキシベンゾイルヒドラゾン(4-di-n-propylaminosal
icylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydraz
one) 収率:57% (物性) 淡黄色結晶(mp.243-248 ℃) PMR(DMSO-d6,δ ppm) :11.55(1H,s),11.53(1H,brs),8.4
1(1H,s),7.65(2H,s),7.50(1H,s),7.15(1H,d,J=8.8Hz),
6.24(1H,dd,J=2.0 and 8.8Hz),6.10(1H,d,J=2.0Hz),3.3
0-3.20(4H,m),1.62-1.48(4H,m),1.43(18H,s),0.90(6H,
t,J=7.3Hz) IR(KBr, cm-1):3624,3207,2958,2871,1632,1599,1519,1
434,1354,1304,1239,1134,1100,893,823,786,702,649
Example 136 4-Di-n-propylaminosalicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone
icylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydraz
one) Yield: 57% (property) pale yellow crystals (mp.243-248 ℃) PMR (DMSO- d 6, δ ppm): 11.55 (1H, s), 11.53 (1H, brs), 8.4
1 (1H, s), 7.65 (2H, s), 7.50 (1H, s), 7.15 (1H, d, J = 8.8Hz),
6.24 (1H, dd, J = 2.0 and 8.8Hz), 6.10 (1H, d, J = 2.0Hz), 3.3
0-3.20 (4H, m), 1.62-1.48 (4H, m), 1.43 (18H, s), 0.90 (6H,
t, J = 7.3Hz) IR (KBr, cm -1 ): 3624,3207,2958,2871,1632,1599,1519,1
434,1354,1304,1239,1134,1100,893,823,786,702,649

【0259】実施例137 3−ヒドロキシピコリンア
ルデヒド3,5−ジ−t−ブチル−4−ヒドロキシベン
ゾイルヒドラゾン(3-hydroxypicolinaldehyde 3,5-di-t
-butyl-4-hydroxybenzoylhydrazone) 収率:51% (物性) 淡黄色結晶(mp.245-252 ℃) PMR(DMSO-d6,δ ppm) :12.17(1H,
s),11.78(1H,s),8.19(1H,d
d,J=1.5 and 4.5Hz),7.72(2
H,s),7.65(1H,s),7.39(1H,
d,J=8.5Hz),7.33(1H,dd,J=
4.5 and 8.5Hz),1.44(18H,
s) IR(KBr, cm−1):3447,3230,2
960,2911,1643,1601,1542,1
445,1330,1304,1237,1178,1
162,1096,887,807,756,703
Example 137 3-Hydroxypicolinaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone
-butyl-4-hydroxybenzoylhydrazone) Yield: 51% (property) pale yellow crystals (mp.245-252 ℃) PMR (DMSO- d 6, δ ppm): 12.17 (1H,
s), 11.78 (1H, s), 8.19 (1H, d
d, J = 1.5 and 4.5 Hz), 7.72 (2
H, s), 7.65 (1H, s), 7.39 (1H,
d, J = 8.5 Hz), 7.33 (1H, dd, J =
4.5 and 8.5 Hz), 1.44 (18H,
s) IR (KBr, cm -1 ): 3447,3230,2
960, 2911, 1643, 1601, 1542, 1
445, 1330, 1304, 1237, 1178, 1
162,1096,887,807,756,703

【0260】実施例138 4−N−ピロリジノサリチ
ルアルデヒド3,5−ジ−t−ブチル−4−ヒドロキシ
ベンゾイルヒドラゾン(4-N-pyrrolidinosalicylaldehyd
e 3,5-di-t-butyl-4-hydroxybenzoylhydrazone) 収率:66% (物性) 黄色結晶(mp.295-298 ℃) PMR(DMSO-d6,δ ppm) :11.66(1H,s),11.54(1H,s),8.42
(1H,s),7.65(2H,s),7.50(1H,s),7.17(1H,d,J=8.8Hz),6.
15(1H,dd,J=2.2 and 8.8Hz),6.02(1H,d,J=2.2Hz),3.32-
3.23(4H,m),2.00-1.92(4H,m),1.43(18H,s) IR(KBr, cm-1):3606,3444,3207,2958,1631,1595,1551,1
523,1485,1434,1355,1344,1307,1253,1 238,1160,1143,1119,1087,961,897,828,780,702
Example 138 4-N-pyrrolidinosalicylaldehyde 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone
e 3,5-di-t-butyl-4-hydroxybenzoylhydrazone) Yield: 66% (physical properties) Yellow crystals (mp. 295-298 ° C) PMR (DMSO-d 6 , δ ppm): 11.66 (1H, s) , 11.54 (1H, s), 8.42
(1H, s), 7.65 (2H, s), 7.50 (1H, s), 7.17 (1H, d, J = 8.8Hz), 6.
15 (1H, dd, J = 2.2 and 8.8Hz), 6.02 (1H, d, J = 2.2Hz), 3.32-
3.23 (4H, m), 2.00-1.92 (4H, m), 1.43 (18H, s) IR (KBr, cm -1 ): 3606,3444,3207,2958,1631,1595,1551,1
523,1485,1434,1355,1344,1307,1253,1 238,1160,1143,1119,1087,961,897,828,780,702

【0261】実施例139 4−N−ピペリジノサリチ
ルアルデヒド3,5−ジ−t−ブチル−4−ヒドロキシ
ベンゾイルヒドラゾン(4-N-piperidinosalicylaldehyde
3,5-di-t-butyl-4-hydroxybenzoylhydrazone) 収率:84% (物性) 淡黄色結晶(mp.273-278 ℃) PMR(DMSO-d6,δ ppm) :11.60(1H,s),11.56(1H,s),8.44
(1H,s),7.65(2H,s),7.50(1H,s),7.20(1H,d,J=8.8Hz),6.
49(1H,dd,J=2.2 and 8.8Hz),6.36(1H,d,J=2.2Hz),3.30-
3.23(4H,m),1.61-1.56(6H,m),1.43(18H,s) IR(KBr, cm-1):3585,3444,2953,1629,1599,1556,1515,1
435,1352,1305,1239,1121,1024,974,667,648
Example 139 4-N-piperidinosalicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone
3,5-di-t-butyl-4-hydroxybenzoylhydrazone) Yield: 84% (physical properties) pale yellow crystal (mp.273-278 ° C) PMR (DMSO-d 6 , δ ppm): 11.60 (1H, s) , 11.56 (1H, s), 8.44
(1H, s), 7.65 (2H, s), 7.50 (1H, s), 7.20 (1H, d, J = 8.8Hz), 6.
49 (1H, dd, J = 2.2 and 8.8Hz), 6.36 (1H, d, J = 2.2Hz), 3.30-
3.23 (4H, m), 1.61-1.56 (6H, m), 1.43 (18H, s) IR (KBr, cm -1 ): 3585,3444,2953,1629,1599,1556,1515,1
435,1352,1305,1239,1121,1024,974,667,648

【0262】実施例140 2−ヒドロキシ−6−メチ
ルニコチンアルデヒド3,5−ジ−t−ブチル−4−ヒ
ドロキシベンゾイルヒドラゾン(2−hydoxy−6
−methylnicotinaldehyde 3,
5−di−t−butyl−4−hydroxyben
zoylhydrazone) 収率:50% (物性) 淡黄色結晶(mp.>280℃) PMR(DMSO-d6,δ ppm) :11.97(1H,s),11.52(1H,s),8.60
(1H,s),7.93(1H,d,J=6.8Hz),7.64(2H,s),7.47(1H,s),6.
15(1H,d,J=6.8Hz),2.24(3H,s),1.44(18H,s) IR(KBr, cm-1):3627,3444,2956,1650,1633,1621,1564,1
484,1435,1354,1307,1240,1162,1105,1070,971,889,77
6,697,582
Example 140 2-Hydroxy-6-methylnicotinaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone (2-hydroxy-6
-Methylnicotinaldehyde 3,
5-di-t-butyl-4-hydroxyben
Zoylhydrazone) Yield: 50% (property) pale yellow crystals (mp> 280 ℃) PMR ( DMSO-d 6, δ ppm):. 11.97 (1H, s), 11.52 (1H, s), 8.60
(1H, s), 7.93 (1H, d, J = 6.8Hz), 7.64 (2H, s), 7.47 (1H, s), 6.
15 (1H, d, J = 6.8Hz), 2.24 (3H, s), 1.44 (18H, s) IR (KBr, cm -1 ): 3627,3444,2956,1650,1633,1621,1564,1
484,1435,1354,1307,1240,1162,1105,1070,971,889,77
6,697,582

【0263】実施例141 4−N−モルホリノサリチ
ルアルデヒド3,5−ジ−t−ブチル−4−ヒドロキシ
ベンゾイルヒドラゾン(4-N-morpholinosalicylaldehyde
3,5-di-t-butyl-4-hydroxybenzoylhydrazone) 収率:82% (物性) 無色結晶(mp.295-298 ℃) PMR(DMSO-d6,δ ppm) :11.66(1H,s),11.62(1H,s),8.47
(1H,s),7.66(2H,s),7.53(1H,s),7.26(1H,d,J=8.8Hz),6.
53(1H,dd,J=1.6 and 8.8Hz),6.42(1H,d,J=1.6Hz),3.75-
3.70(4H,m),3.25-3.17(4H,m),1.43(18H,s) IR(KBr, cm-1):3610,3444,2953,1632,1600,1556,1516,1
434,1358,1306,1246,1238,1121,1045,978,896,784,701,
664
Example 141 4-N-morpholinosalicylaldehyde 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone
3,5-di-t-butyl- 4-hydroxybenzoylhydrazone) Yield: 82% (Physical Properties) colorless crystals (mp.295-298 ℃) PMR (DMSO- d 6, δ ppm): 11.66 (1H, s), 11.62 (1H, s), 8.47
(1H, s), 7.66 (2H, s), 7.53 (1H, s), 7.26 (1H, d, J = 8.8Hz), 6.
53 (1H, dd, J = 1.6 and 8.8Hz), 6.42 (1H, d, J = 1.6Hz), 3.75-
3.70 (4H, m), 3.25-3.17 (4H, m), 1.43 (18H, s) IR (KBr, cm -1 ): 3610,3444,2953,1632,1600,1556,1516,1
434,1358,1306,1246,1238,1121,1045,978,896,784,701,
664

【0264】実施例142 4−(4−エチル−1−ピ
ペラジニル)サリチルアルデヒド3,5−ジ−t−ブチ
ル−4−ヒドロキシベンゾイルヒドラゾン(4-(4-ethyl-
1-piperazinyl)salicylaldehyde 3,5-di-t-butyl-4-hyd
roxybenzoylhydrazone) 収率:52% (物性) 淡黄緑色結晶(mp.250-262 ℃) PMR(DMSO-d6,δ ppm) :11.64(1H,s),11.59(1H,s),8.46
(1H,s),7.65(2H,s),7.53(1H,brs),7.23(1H,d,J=8.8Hz),
6.52(1H,dd,J=2.0 and 8.8Hz),6.40(1H,d,J=2.0Hz),3.2
7-3.20(4H,m),2.50-2.44(4H,m),2.36(2H,q,J=7.1Hz),1.
43(18H,s),1.04(3H,t,J=7.1Hz) IR(KBr, cm-1):3606,3444,3219,2958,2911,2876,2824,1
630,1602,1556,1515,1435,1357,1305,1239,1200,1152,1
124,1025,979,889,846,776,701
Example 142 4- (4-Ethyl-1-piperazinyl) salicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone (4- (4-ethyl-
1-piperazinyl) salicylaldehyde 3,5-di-t-butyl-4-hyd
Roxybenzoylhydrazone) Yield: 52% (property) pale green crystals (mp.250-262 ℃) PMR (DMSO- d 6, δ ppm): 11.64 (1H, s), 11.59 (1H, s), 8.46
(1H, s), 7.65 (2H, s), 7.53 (1H, brs), 7.23 (1H, d, J = 8.8Hz),
6.52 (1H, dd, J = 2.0 and 8.8Hz), 6.40 (1H, d, J = 2.0Hz), 3.2
7-3.20 (4H, m), 2.50-2.44 (4H, m), 2.36 (2H, q, J = 7.1Hz), 1.
43 (18H, s), 1.04 (3H, t, J = 7.1Hz) IR (KBr, cm -1 ): 3606,3444,3219,2958,2911,2876,2824,1
630,1602,1556,1515,1435,1357,1305,1239,1200,1152,1
124,1025,979,889,846,776,701

【0265】実施例143 4−N−ピペリジノ−6−
ヒドロキシサリチルアルデヒド3,5−ジ−t−ブチル
−4−ヒドロキシベンゾイルヒドラゾン(4-N-piperidin
o-6-hydroxysalicylaldehyde 3,5-di-t-butyl-4-hydrox
ybenzoylhydrazone) 収率:62% (物性) 淡黄色結晶(mp.244-246 ℃) PMR(DMSO-d6,δ ppm) :11.55(1H,s),10.95(2H,brs),8.7
6(1H,s),7.66(2H,s),7.49(1H,s),5.90(2H,s),3.25-3.17
(4H,m),1.60-1.50(6H,m),1.43(18H,s) IR(KBr, cm-1):3604,3444,3176,2953,1634,1602,1557,1
435,1325,1304,1238,1191,1123,989,703
Example 143 4-N-piperidino-6
Hydroxysalicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone (4-N-piperidin
o-6-hydroxysalicylaldehyde 3,5-di-t-butyl-4-hydrox
ybenzoylhydrazone) Yield: 62% (physical properties) pale yellow crystal (mp.244-246 ° C) PMR (DMSO-d 6 , δ ppm): 11.55 (1H, s), 10.95 (2H, brs), 8.7
6 (1H, s), 7.66 (2H, s), 7.49 (1H, s), 5.90 (2H, s), 3.25-3.17
(4H, m), 1.60-1.50 (6H, m), 1.43 (18H, s) IR (KBr, cm -1 ): 3604,3444,3176,2953,1634,1602,1557,1
435,1325,1304,1238,1191,1123,989,703

【0266】実施例144 4−N−ピペリジノ−6−
イソプロポキシサリチルアルデヒド3,5−ジ−t−ブ
チル−4−ヒドロキシベンゾイルヒドラゾン(4-N-piper
idino-6-isopropoxysalicylaldehyde 3,5-di-t-butyl-4
-hydroxybenzoylhydrazone) 収率:73% (物性) 淡黄色結晶(mp.>300℃) PMR(DMSO-d6,δ ppm) :12.38(1H,s),11.68(1H,s),8.70
(1H,s),7.66(2H,s),7.47(1H,s),6.06(1H,d,J=2.0Hz),5.
98(1H,d,J=2.0Hz),4.71(1H,sept,J=6.0Hz),3.29-3.24(4
H,m),1.62-1.56(6H,m),1.43(18H,s),1.32(6H,t,J=6.0H
z) IR(KBr, cm-1):3592,3444,2953,1630,1598,1556,1435,1
345,1304,1237,1202,1121,1071,1024,996,805,708
Example 144 4-N-piperidino-6
Isopropoxysalicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone (4-N-piper
idino-6-isopropoxysalicylaldehyde 3,5-di-t-butyl-4
-Hydroxybenzoylhydrazone) Yield: 73% (Physical properties) Light yellow crystal (mp.> 300 ℃) PMR (DMSO-d 6 , δ ppm): 12.38 (1H, s), 11.68 (1H, s), 8.70
(1H, s), 7.66 (2H, s), 7.47 (1H, s), 6.06 (1H, d, J = 2.0Hz), 5.
98 (1H, d, J = 2.0Hz), 4.71 (1H, sept, J = 6.0Hz), 3.29-3.24 (4
H, m), 1.62-1.56 (6H, m), 1.43 (18H, s), 1.32 (6H, t, J = 6.0H
z) IR (KBr, cm -1 ): 3592,3444,2953,1630,1598,1556,1435,1
345,1304,1237,1202,1121,1071,1024,996,805,708

【0267】実施例145 4−(N−メトキシカルボ
ニルメチル)シクロペンチルアミノサリチルアルデヒド
3,5−ジ−t−ブチル−4−ヒドロキシベンゾイルヒ
ドラゾン(4-(N-methoxycarbonylmethyl)cyclopentylami
nosalicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylh
ydrazone) 収率:60% (物性) 淡黄色結晶(mp.215-220 ℃) PMR(DMSO-d6,δ ppm) :11.59(1H,s),11.57(1H,s),8.43
(1H,s),7.65(2H,s),7.51(1H,s),7.19(1H,d,J =8.8Hz),
6.27(1H,dd,J=2.0 and 8.8Hz),6.17(1H,d,J=2.0Hz),4.2
7-4.15(1H,m),4.08(2H,s),3.68(3H,s),1.95-1.85(2H,
m),1.72-1.38(6H,m),1.43(18H,s) IR(KBr, cm-1):3594,3444,3226,2957,1738,1630,1601,1
515,1435,1358,1304,1239,1147,961,789,703
Example 145 4- (N-methoxycarbonylmethyl) cyclopentylaminosalicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone (4- (N-methoxycarbonylmethyl) cyclopentylamido)
nosalicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylh
Ydrazone) Yield: 60% (property) pale yellow crystals (mp.215-220 ℃) PMR (DMSO- d 6, δ ppm): 11.59 (1H, s), 11.57 (1H, s), 8.43
(1H, s), 7.65 (2H, s), 7.51 (1H, s), 7.19 (1H, d, J = 8.8Hz),
6.27 (1H, dd, J = 2.0 and 8.8Hz), 6.17 (1H, d, J = 2.0Hz), 4.2
7-4.15 (1H, m), 4.08 (2H, s), 3.68 (3H, s), 1.95-1.85 (2H,
m), 1.72-1.38 (6H, m), 1.43 (18H, s) IR (KBr, cm -1 ): 3594,3444,3226,2957,1738,1630,1601,1
515,1435,1358,1304,1239,1147,961,789,703

【0268】実施例146 4−イソプロポキシサリチ
ルアルデヒド6−ヒドロキシ−2,5,7,8−テトラ
メチルクロマン−2−アセチルヒドラゾン(4-isopropox
ysalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchro
man-2-acetylhydrazone) 参考例2で合成した化合物6−ヒドロキシ−2,5,
7,8−テトラメチルクロマン−2−アセトヒドラジド
0.84g(3mmol) 及び4−イソプロポキシサリチルアルデ
ヒド 0.54g(3mmol) をエタノール 20ml に溶かし、70℃
で7 時間加熱攪拌した。溶媒を留去し、残渣にヘキサ
ン:酢酸エチル=1:1の混合溶媒を加えて結晶化さ
せ、ろ取した。減圧下で乾燥し、標記化合物1.05g(収率
80%)を得た。 (物性) 無色結晶(mp.199-204 ℃) PMR(DMSO-d6,δ ppm) :11.46,11.17(1H,each-s),11.45,
10.18(1H,each-s),8.23,8.13(1H,each-s),7.41,7.36(2
H,each-s),7.34,7.28(1H,each-d,J=8.3Hz),6.48-6.37(2
H,m),4.63,4.55(1H,each-sept,J=5.8Hz),2.91-2.40(2H,
m),2.06-1.77(11H,m),1.36-1.32(3H,m),1.27,1.26(6H,e
ach-d,J=5.8Hz)
Example 146 4-Isopropoxysalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (4-isopropox)
ysalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchro
man-2-acetylhydrazone) Compound 6-hydroxy-2,5, synthesized in Reference Example 2.
7,8-tetramethylchroman-2-acetohydrazide
0.84 g (3 mmol) and 0.54 g (3 mmol) of 4-isopropoxysalicylaldehyde are dissolved in 20 ml of ethanol, and
For 7 hours. The solvent was distilled off, and the residue was crystallized by adding a mixed solvent of hexane: ethyl acetate = 1: 1, and collected by filtration. Dry under reduced pressure to give 1.05 g of the title compound (yield
80%). (Physical Properties) colorless crystals (mp.199-204 ℃) PMR (DMSO- d 6, δ ppm): 11.46,11.17 (1H, each-s), 11.45,
10.18 (1H, each-s), 8.23,8.13 (1H, each-s), 7.41,7.36 (2
H, each-s), 7.34,7.28 (1H, each-d, J = 8.3Hz), 6.48-6.37 (2
H, m), 4.63,4.55 (1H, each-sept, J = 5.8Hz), 2.91-2.40 (2H,
m), 2.06-1.77 (11H, m), 1.36-1.32 (3H, m), 1.27,1.26 (6H, e
(ach-d, J = 5.8Hz)

【0269】実施例147〜161 4−イソプロポキシサリチルアルデヒドを他のアルデヒ
ド化合物に代える以外は実施例146と実質的に同様に
処理して、以下の化合物を製造した。 実施例147 3−イソプロポキシサリチルアルデヒド
6−ヒドロキシ−2,5,7,8−テトラメチルクロマ
ン−2−アセチルヒドラゾン(3-isopropoxysalicylalde
hyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetyl
hydrazone 収率:82% (物性) 無色結晶(mp.150-154 ℃) PMR(DMSO-d6,δ ppm) :11.59,11.29(1H,each-s),10.91,
9.18(1H,each-s),8.33,8.30(1H,each-s),7.09,7.02(1H,
each-dd,J=1.5and8.1Hz),7.00,6.96(1H,each-dd,J=1.5a
nd8.1Hz),6.81,6.73(1H,each-t,J=8.1Hz),4.58-4.49(1
H,m),2.91-2.43(4H,m),2.06-1.77(11H,m),1.35,1.345(3
H,each-s),1.27,(6H,d,J=5.9Hz)
Examples 147 to 161 The following compounds were prepared in substantially the same manner as in Example 146 except that 4-isopropoxysalicylaldehyde was replaced with another aldehyde compound. Example 147 3-Isopropoxysalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
hyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetyl
hydrazone Yield: 82% (physical properties) Colorless crystals (mp. 150-154 ° C) PMR (DMSO-d 6 , δ ppm): 11.59, 11.29 (1H, each-s), 10.91,
9.18 (1H, each-s), 8.33,8.30 (1H, each-s), 7.09,7.02 (1H,
each-dd, J = 1.5and8.1Hz), 7.00,6.96 (1H, each-dd, J = 1.5a
nd8.1Hz), 6.81,6.73 (1H, each-t, J = 8.1Hz), 4.58-4.49 (1
H, m), 2.91-2.43 (4H, m), 2.06-1.77 (11H, m), 1.35,1.345 (3
H, each-s), 1.27, (6H, d, J = 5.9Hz)

【0270】実施例148 2−ヒドロキシ−3−メト
キシシンナムアルデヒド6−ヒドロキシ−2,5,7,
8−テトラメチルクロマン−2−アセチルヒドラゾン(2
-hydroxy-3-methoxycinnamaldehyde 6-hydroxy-2,5,7,8
-tetramethylchroman-2-acetylhydrazone) 収率:78% (物性) 淡黄色結晶(mp.118-126 ℃) PMR(DMSO-d6,δ ppm) :11.17,11.11(1H,each-s),9.11,
9.06(1H,each-s),7.90,7.76(1H,each-s),7.77,7.75(1H,
each-s),7.19-7.05(2H,m),6.99-6.72(3H,m),3.82,3.81
(3H,each-s),2.62-2.47(2H,m),2.87,2.49(1H,each-d,J=
13.5Hz),2.79,2.41(1H,each-d,J=13.5Hz),2.06-1.94(10
H,m),1.87-1.75(1H,m),1.34,1.32(3H,each-s) IR(KBr, cm-1):3400,3260,2920,1664,1619,1589,1547,1
478,1467,1440,1365,1261,1220,1086,1070,919,775,728
Example 148 2-Hydroxy-3-methoxycinnamaldehyde 6-hydroxy-2,5,7,
8-tetramethylchroman-2-acetylhydrazone (2
-hydroxy-3-methoxycinnamaldehyde 6-hydroxy-2,5,7,8
-tetramethylchroman-2-acetylhydrazone) Yield: 78% (physical properties) Pale yellow crystals (mp. 118-126 ° C) PMR (DMSO-d 6 , δ ppm): 11.17, 11.11 (1H, each-s), 9.11,
9.06 (1H, each-s), 7.90,7.76 (1H, each-s), 7.77,7.75 (1H,
each-s), 7.19-7.05 (2H, m), 6.99-6.72 (3H, m), 3.82,3.81
(3H, each-s), 2.62-2.47 (2H, m), 2.87,2.49 (1H, each-d, J =
13.5Hz), 2.79,2.41 (1H, each-d, J = 13.5Hz), 2.06-1.94 (10
H, m), 1.87-1.75 (1H, m), 1.34,1.32 (3H, each-s) IR (KBr, cm -1 ): 3400,3260,2920,1664,1619,1589,1547,1
478,1467,1440,1365,1261,1220,1086,1070,919,775,728

【0271】実施例149 3−メチル−6−イソプロ
ピルサリチルアルデヒド6−ヒドロキシ−2,5,7,
8−テトラメチルクロマン−2−アセチルヒドラゾン(3
-methyl-6-isopropylsalicylaldehyde 6-hydroxy-2,5,
7,8-tetramethylchroman-2-acetylhydrazone) 収率:75% (物性) 淡黄色結晶(mp.120-123 ℃) PMR(DMSO-d6,δ ppm) :12.54(1H,s),11.62(1H,s)8.74(1
H,s),7.44(1H,s),7.14(1H,d,J=7.8Hz),6.74(1H,d,J=7.8
Hz),3.19(1H,sept,J=6.8Hz),2.65-2.44(4H,m),2.14(3H,
s),2.04(6H,s),1.96(3H,s),2.00-1.80(2H,m),1.35(3H,
s),1.18-1.25(6H,m) IR(KBr, cm-1):3232,2964,2926,1663,1597,1535,1458,1
382,1337,1317,1253,1240,1192,1178,1084,967,815,645
Example 149 3-Methyl-6-isopropylsalicylaldehyde 6-hydroxy-2,5,7,
8-tetramethylchroman-2-acetylhydrazone (3
-methyl-6-isopropylsalicylaldehyde 6-hydroxy-2,5,
7,8-tetramethylchroman-2-acetylhydrazone) Yield: 75% (property) pale yellow crystals (mp.120-123 ℃) PMR (DMSO- d 6, δ ppm): 12.54 (1H, s), 11.62 (1H , s) 8.74 (1
H, s), 7.44 (1H, s), 7.14 (1H, d, J = 7.8Hz), 6.74 (1H, d, J = 7.8
Hz), 3.19 (1H, sept, J = 6.8Hz), 2.65-2.44 (4H, m), 2.14 (3H,
s), 2.04 (6H, s), 1.96 (3H, s), 2.00-1.80 (2H, m), 1.35 (3H,
s), 1.18-1.25 (6H, m) IR (KBr, cm -1 ): 3232,2964,2926,1663,1597,1535,1458,1
382,1337,1317,1253,1240,1192,1178,1084,967,815,645

【0272】実施例150 4,6−ジイソプロポキシ
サリチルアルデヒド6−ヒドロキシ−2,5,7,8−
テトラメチルクロマン−2−アセチルヒドラゾン(4,6-d
iisopropoxysalicylaldehyde 6-hydroxy-2,5,7,8-tetra
methylchroman-2-acetylhydrazone) 収率:52% (物性) 橙色油状物 PMR(DMSO-d6,δ ppm) :12.21(1H,s),11.48(1H,s),8.50
(1H,s),7.42(1H,s),6.07(1H,d,J=2.0Hz),6.05(1H,d,J=
2.0Hz),4.65(2H,sept,J=6.0Hz),2.65-2.38(4H,m),2.05
(3H,s),2.03(3H,s),1.97(3H,s),2.10-1.78(2H,m),1.34
(3H,s),1.29(6H,d,J=6.0Hz),1.26(6H,d,J=6.0Hz)
Example 150 4,6-Diisopropoxysalicylaldehyde 6-hydroxy-2,5,7,8-
Tetramethylchroman-2-acetylhydrazone (4,6-d
iisopropoxysalicylaldehyde 6-hydroxy-2,5,7,8-tetra
methylchroman-2-acetylhydrazone) Yield: 52% (physical properties) Orange oil PMR (DMSO-d 6 , δ ppm): 12.21 (1H, s), 11.48 (1H, s), 8.50
(1H, s), 7.42 (1H, s), 6.07 (1H, d, J = 2.0Hz), 6.05 (1H, d, J =
2.0Hz), 4.65 (2H, sept, J = 6.0Hz), 2.65-2.38 (4H, m), 2.05
(3H, s), 2.03 (3H, s), 1.97 (3H, s), 2.10-1.78 (2H, m), 1.34
(3H, s), 1.29 (6H, d, J = 6.0Hz), 1.26 (6H, d, J = 6.0Hz)

【0273】実施例151 4−ジメチルアミノサリチ
ルアルデヒド6−ヒドロキシ−2,5,7,8−テトラ
メチルクロマン−2−アセチルヒドラゾン(4-dimethyla
minosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylc
hroman-2-acetylhydrazone) 収率:46% (物性) 淡褐色結晶(mp.211-216 ℃) PMR(DMSO-d6,δ ppm) :11.31,11.07(1H,each-s),11.37,
10.16(1H,each-s),8.29,8.15(1H,each-s),7.42,7.37(1
H,each-s),7.19,7.18(1H,each-d,J=8.0Hz),6.28,6.24(1
H,each-dd,J=2.0 and 8.0Hz),6.14,6.11(1H,each-d,J=
2.0Hz),2.95,2.92(6H,each-s),2.65-2.39(4H,m),2.06-
1.77(11H,m),1.34,1.33(3H,each-s) IR(KBr, cm-1):3397,3266,2931,1663,1633,1595,1524,1
443,1361,1266,1218,1173,1140,1112,1084,1007,979,97
3,827,793,716,650,602
Example 151 4-Dimethylaminosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (4-dimethyla
minosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylc
hroman-2-acetylhydrazone) Yield: 46% (property) pale brown crystals (mp.211-216 ℃) PMR (DMSO- d 6, δ ppm): 11.31,11.07 (1H, each-s), 11.37,
10.16 (1H, each-s), 8.29,8.15 (1H, each-s), 7.42,7.37 (1
H, each-s), 7.19,7.18 (1H, each-d, J = 8.0Hz), 6.28,6.24 (1
H, each-dd, J = 2.0 and 8.0Hz), 6.14,6.11 (1H, each-d, J =
2.0Hz), 2.95, 2.92 (6H, each-s), 2.65-2.39 (4H, m), 2.06-
1.77 (11H, m), 1.34,1.33 (3H, each-s) IR (KBr, cm -1 ): 3397,3266,2931,1663,1633,1595,1524,1
443,1361,1266,1218,1173,1140,1112,1084,1007,979,97
3,827,793,716,650,602

【0274】実施例152 4−ジ−n−プロピルアミ
ノサリチルアルデヒド6−ヒドロキシ−2,5,7,8
−テトラメチルクロマン−2−アセチルヒドラゾン(4-d
i-n-propylaminosalicylaldehyde 6-hydroxy-2,5,7,8-t
etramethylchroman-2-acetylhydrazone) 収率:72% (物性) 淡褐色結晶(mp.110-113 ℃) PMR(DMSO-d6,δ ppm) :11.25,11.04(1H,each-s),11.31,
10.09(1H,each-s),8.12,8.04(1H,each-s),7.40,7.35(1
H,each-s),7.14,7.12(1H,each-d,J=8.0Hz),6.23-6.15(1
H,m),6.08-6.05(1H,m),3.28-3.17(4H,m),2.65-2.37(4H,
m),2.06-1.77(11H,m),1.60-1.47(4H,m),1.34,1.33(3H,e
ach-s),0.89(6H,t,J=7.3Hz) IR(KBr, cm-1):3444,3226,2960,2931,2872,1632,1598,1
556,1519,1455,1416,1359,1235,1211,1134,1086,1006,9
20,827,787,751,648
Example 152 4-Di-n-propylaminosalicylaldehyde 6-hydroxy-2,5,7,8
-Tetramethylchroman-2-acetylhydrazone (4-d
in-propylaminosalicylaldehyde 6-hydroxy-2,5,7,8-t
etramethylchroman-2-acetylhydrazone) Yield: 72% (property) pale brown crystals (mp.110-113 ℃) PMR (DMSO- d 6, δ ppm): 11.25,11.04 (1H, each-s), 11.31,
10.09 (1H, each-s), 8.12,8.04 (1H, each-s), 7.40,7.35 (1
H, each-s), 7.14,7.12 (1H, each-d, J = 8.0Hz), 6.23-6.15 (1
H, m), 6.08-6.05 (1H, m), 3.28-3.17 (4H, m), 2.65-2.37 (4H, m
m), 2.06-1.77 (11H, m), 1.60-1.47 (4H, m), 1.34,1.33 (3H, e
ach-s), 0.89 (6H, t, J = 7.3Hz) IR (KBr, cm -1 ): 3444,3226,2960,2931,2872,1632,1598,1
556,1519,1455,1416,1359,1235,1211,1134,1086,1006,9
20,827,787,751,648

【0275】実施例153 3−ヒドロキシピコリンア
ルデヒド6−ヒドロキシ−2,5,7,8−テトラメチ
ルクロマン−2−アセチルヒドラゾン(3-hydroxypicoli
naldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-a
cetylhydrazone) 収率:67% (物性) 黄色結晶(mp.190-195 ℃) PMR(DMSO-d6,δ ppm) :11.93,11.61(1H,each-s),11.51,
10.35(1H,each-s),8.34,8.24(1H,each-s),8.20-8.12(1
H,m),7.45-7.12(3H,m),2.97-2.47(4H,m),2.07-1.80(11
H,m),1.35,1.33(3H,each-s) IR(KBr, cm-1):3444,3208,2929,1685,1557,1446,1418,1
374,1298,1256,1178,1088,1059,1032,807,733,696,682,
560
Example 153 3-Hydroxypicolinaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
naldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-a
cetylhydrazone) Yield: 67% (physical properties) Yellow crystals (mp. 190-195 ° C) PMR (DMSO-d 6 , δ ppm): 11.93, 11.61 (1H, each-s), 11.51,
10.35 (1H, each-s), 8.34,8.24 (1H, each-s), 8.20-8.12 (1
H, m), 7.45-7.12 (3H, m), 2.97-2.47 (4H, m), 2.07-1.80 (11
H, m), 1.35,1.33 (3H, each-s) IR (KBr, cm -1 ): 3444,3208,2929,1685,1557,1446,1418,1
374,1298,1256,1178,1088,1059,1032,807,733,696,682,
560

【0276】実施例154 4−ピロリジノサリチルア
ルデヒド6−ヒドロキシ−2,5,7,8−テトラメチ
ルクロマン−2−アセチルヒドラゾン(4-pyrrolidinosa
licylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman
-2-acetylhydrazone) 収率:85% (物性) 淡黄色結晶(mp.273-278 ℃) PMR(DMSO-d6,δ ppm) :11.27,11.04(1H,each-s),11.41,
10.19(1H,each-s),8.13,8.05(1H,each-s),7.40,7.36(1
H,each-s),7.16,7.14(1H,each-d,J=8.8Hz),6.13,6.09(1
H,each-dd,J=2.0 and 8.8Hz),5.99,5.96(1H,each-d,J=
2.0Hz),3.30-3.20(4H,m),2.83-2.30(4H,m),2.07-1.77(1
1H,m),1.34,1.33(3H,each-s) IR(KBr, cm-1):3444,3195,3041,2969,2936,2922,1632,1
597,1525,1418,1377,1359,1348,1253,1231,1177,1161,1
142,1117,1085,821,787,648
Example 154 4-Pyrrolidinosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (4-pyrrolidinosa
licylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman
-2-acetylhydrazone) Yield: 85% (property) pale yellow crystals (mp.273-278 ℃) PMR (DMSO- d 6, δ ppm): 11.27,11.04 (1H, each-s), 11.41,
10.19 (1H, each-s), 8.13,8.05 (1H, each-s), 7.40,7.36 (1
H, each-s), 7.16,7.14 (1H, each-d, J = 8.8Hz), 6.13,6.09 (1
H, each-dd, J = 2.0 and 8.8Hz), 5.99,5.96 (1H, each-d, J =
2.0Hz), 3.30-3.20 (4H, m), 2.83-2.30 (4H, m), 2.07-1.77 (1
1H, m), 1.34,1.33 (3H, each-s) IR (KBr, cm -1 ): 3444,3195,3041,2969,2936,2922,1632,1
597,1525,1418,1377,1359,1348,1253,1231,1177,1161,1
142,1117,1085,821,787,648

【0277】実施例155 4−ピペリジノサリチルア
ルデヒド6−ヒドロキシ−2,5,7,8−テトラメチ
ルクロマン−2−アセチルヒドラゾン(4-piperidinosal
icylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-
2-acetylhydrazone) 収率:69% (物性) 無色結晶(mp.225-228 ℃) PMR(DMSO-d6,δ ppm) :11.33,11.09(1H,each-s),11.31,
10.07(1H,each-s),8.14,8.07(1H,each-s),7.39,7.34(1
H,each-s),7.18(1H,d,J=8.8Hz),6.47,6.42(1H,each-dd,
J=2.0 and 8.8Hz),6.33,6.31(1H,each-d,J=2.0Hz),3.29
-3.17(4H,m),2.86-2.37(4H,m),2.07-1.78(11H,m),1.60-
1.55(6H,m),1.34(3H,s) IR(KBr, cm-1):3444,2932,1663,1631,1599,1556,1516,1
451,1358,1241,1220,1121,1087,1023,971,791
Example 155 4-Piperidinosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (4-piperidinosal
icylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-
2-acetylhydrazone) Yield: 69% (Physical Properties) colorless crystals (mp.225-228 ℃) PMR (DMSO- d 6, δ ppm): 11.33,11.09 (1H, each-s), 11.31,
10.07 (1H, each-s), 8.14,8.07 (1H, each-s), 7.39,7.34 (1
H, each-s), 7.18 (1H, d, J = 8.8Hz), 6.47,6.42 (1H, each-dd,
J = 2.0 and 8.8Hz), 6.33,6.31 (1H, each-d, J = 2.0Hz), 3.29
-3.17 (4H, m), 2.86-2.37 (4H, m), 2.07-1.78 (11H, m), 1.60-
1.55 (6H, m), 1.34 (3H, s) IR (KBr, cm -1 ): 3444,2932,1663,1631,1599,1556,1516,1
451,1358,1241,1220,1121,1087,1023,971,791

【0278】実施例156 2−ヒドロキシ−6−メチ
ルニコチンアルデヒド6−ヒドロキシ−2,5,7,8
−テトラメチルクロマン−2−アセチルヒドラゾン(2-h
ydroxy-6-methylnicotinaldehyde 6-hydroxy-2,5,7,8-t
etramethylchroman-2-acetylhydrazone) 収率:24% (物性) 淡黄色結晶(mp.176-178 ℃) PMR(DMSO-d6,δ ppm) :11.95,11.91(1H,each-s),11.26,
11.22(1H,each-s),8.25,8.04(1H,each-s),7.85,7.35(1
H,each-d,J=7.5Hz),7.41,7.34(1H,each-s),6.12,5.98(1
H,each-d,J=7.5Hz),2.70-2.48(2H,m),3.02,2.48(1H,eac
h-d,J=13.5Hz),2.74,2.40(1H,each-d,J=13.5Hz),2.22,
2.20(3H,each-s),2.07-1.70(11H,m),1.37,1.33(3H,each
-s) IR(KBr, cm-1):3418,2933,1651,1645,1557,1470,1463,1
455,1379,1256,1209,1132,1088,1061,777,584
Example 156 2-Hydroxy-6-methylnicotinaldehyde 6-hydroxy-2,5,7,8
-Tetramethylchroman-2-acetylhydrazone (2-h
ydroxy-6-methylnicotinaldehyde 6-hydroxy-2,5,7,8-t
etramethylchroman-2-acetylhydrazone) Yield: 24% (property) pale yellow crystals (mp.176-178 ℃) PMR (DMSO- d 6, δ ppm): 11.95,11.91 (1H, each-s), 11.26,
11.22 (1H, each-s), 8.25,8.04 (1H, each-s), 7.85,7.35 (1
H, each-d, J = 7.5Hz), 7.41,7.34 (1H, each-s), 6.12,5.98 (1
H, each-d, J = 7.5Hz), 2.70-2.48 (2H, m), 3.02,2.48 (1H, eac
hd, J = 13.5Hz), 2.74,2.40 (1H, each-d, J = 13.5Hz), 2.22,
2.20 (3H, each-s), 2.07-1.70 (11H, m), 1.37,1.33 (3H, each
-s) IR (KBr, cm -1 ): 3418,2933,1651,1645,1557,1470,1463,1
455,1379,1256,1209,1132,1088,1061,777,584

【0279】実施例157 4−モルホリノサリチルア
ルデヒド6−ヒドロキシ−2,5,7,8−テトラメチ
ルクロマン−2−アセチルヒドラゾン(4-morpholinosal
icylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-
2-acetylhydrazone) 収率:79% (物性) 淡黄色結晶(mp.212-214 ℃) PMR(DMSO-d6,δ ppm) :11.40,11.14
(1H,each−s),11.37,10.14(1
H,each−s),8.18,8.10(1H,ea
ch−s),7.41,7.36(1H,each−
s),7.25,7.23(1H,each−d,J=
8.8Hz),6.51,6.46(1H,each−
dd,J=2.0 and 8.8Hz),6.39,
6.34(1H,each−d,J=2.0Hz),
3.75−3.68(4H,m),3.22−3.10
(4H,m),2.90−2.40(4H,m),2.
07−1.78(11H,m),1.34(3H,s) IR(KBr, cm−1):3459,3227,2
972,2929,1659,1628,1556,1
514,1505,1454,1253,1234,1
192,1118,1086,1047,981,89
4,840,788,667,625
Example 157 4-morpholinosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
icylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-
2-acetylhydrazone) Yield: 79% (property) pale yellow crystals (mp.212-214 ℃) PMR (DMSO- d 6, δ ppm): 11.40,11.14
(1H, each-s), 11.37, 10.14 (1
H, each-s), 8.18,8.10 (1H, ea
ch-s), 7.41, 7.36 (1H, each-
s), 7.25, 7.23 (1H, reach-d, J =
8.8 Hz), 6.51, 6.46 (1H, each-
dd, J = 2.0 and 8.8 Hz), 6.39,
6.34 (1H, each-d, J = 2.0Hz),
3.75-3.68 (4H, m), 3.22-3.10
(4H, m), 2.90-2.40 (4H, m), 2.
07-1.78 (11H, m), 1.34 (3H, s) IR (KBr, cm -1 ): 3459, 3227, 2
972, 2929, 1659, 1628, 1556, 1
514, 1505, 1454, 1253, 1234, 1
192, 1118, 1086, 1047, 981, 89
4,840,788,667,625

【0280】実施例158 4−(4−エチル−1−ピ
ペラジニル)サリチルアルデヒド6−ヒドロキシ−2,
5,7,8−テトラメチルクロマン−2−アセチルヒド
ラゾン(4−(4−ethyl−1−piperazi
nyl)salicylaldehyde 6−hyd
roxy−2,5,7,8−tetramethylc
hroman−2−acetylhydrazone) 収率:65% (物性) 淡桃色結晶(mp.208-222 ℃) PMR(DMSO-d6,δ ppm) :11.37,11.11(1H,each-s),11.33,
10.10(1H,each-s),8.16,8.08(1H,each-s),7.41,7.36(1
H,each-s),7.22,7.21(1H,each-d,J=8.8Hz),6.50,6.45(1
H,each-dd,J=2.0 and 8.8Hz),6.37,6.33(1H,each-d,J=
2.0Hz),3.26-3.14(4H,m),2.70-2.30(10H,m),2.06-1.76
(11H,m),1.34(3H,s),1.03(3H,t,J=7.3Hz) IR(KBr, cm-1):3455,3303,2971,2935,2827,1670,1629,1
601,1557,1515,1450,1380,1356,1217,1201,1161,1124,1
087,1058,1025,980,779,646
Example 158 4- (4-Ethyl-1-piperazinyl) salicylaldehyde 6-hydroxy-2,
5,7,8-Tetramethylchroman-2-acetylhydrazone (4- (4-ethyl-1-piperazi)
nyl) salicylaldehyde 6-hyd
roxy-2,5,7,8-tetramethylc
roman-2-acetylhydrazine yield: 65% (physical properties) pale pink crystal (mp. 208-222 ° C) PMR (DMSO-d 6 , δ ppm): 11.37, 11.11 (1H, each-s), 11.33,
10.10 (1H, each-s), 8.16,8.08 (1H, each-s), 7.41,7.36 (1
H, each-s), 7.22,7.21 (1H, each-d, J = 8.8Hz), 6.50,6.45 (1
H, each-dd, J = 2.0 and 8.8Hz), 6.37,6.33 (1H, each-d, J =
2.0Hz), 3.26-3.14 (4H, m), 2.70-2.30 (10H, m), 2.06-1.76
(11H, m), 1.34 (3H, s), 1.03 (3H, t, J = 7.3Hz) IR (KBr, cm -1 ): 3455,3303,2971,2935,2827,1670,1629,1
601,1557,1515,1450,1380,1356,1217,1201,1161,1124,1
087,1058,1025,980,779,646

【0281】実施例159 4−ピペリジノ−6−ヒド
ロキシサリチルアルデヒド6−ヒドロキシ−2,5,
7,8−テトラメチルクロマン−2−アセチルヒドラゾ
ン(4-piperidino-6-hydroxysalicylaldehyde 6-hydroxy
-2,5,7,8-tetramethylchroman-2-acetylhydrazone) 収率:50% (物性) 淡黄色結晶(mp.240-245 ℃) PMR(DMSO-d6,δ ppm) :11.27,11.11(1H,each-s),10.78,
10.33(1H,each-s),8.44,8.34(1H,each-s),7.40,7.36(1
H,each-s),5.88,5.87(2H,each-s),3.23-3.15(4H,m),2.8
5-2.35(4H,m),2.06-1.76(11H,m),1.60-1.50(6H,m),1.3
4,1.29(3H,each-s)IR(KBr, cm-1):3814,3312,2933,285
3,1639,1597,1526,1452,1417,1255,1202,1121,1085,106
0,855,811
Example 159 4-Piperidino-6-hydroxysalicylaldehyde 6-hydroxy-2,5,
7,8-tetramethylchroman-2-acetylhydrazone (4-piperidino-6-hydroxysalicylaldehyde 6-hydroxy
-2,5,7,8-tetramethylchroman-2-acetylhydrazone) Yield: 50% (Physical properties) Light yellow crystal (mp. 240-245 ° C) PMR (DMSO-d 6 , δ ppm): 11.27, 11.11 (1H , each-s), 10.78,
10.33 (1H, each-s), 8.44,8.34 (1H, each-s), 7.40,7.36 (1
H, each-s), 5.88,5.87 (2H, each-s), 3.23-3.15 (4H, m), 2.8
5-2.35 (4H, m), 2.06-1.76 (11H, m), 1.60-1.50 (6H, m), 1.3
4,1.29 (3H, each-s) IR (KBr, cm -1 ): 3814,3312,2933,285
3,1639,1597,1526,1452,1417,1255,1202,1121,1085,106
0,855,811

【0282】実施例160 4−ピペリジノ−6−イソ
プロポキシサリチルアルデヒド6−ヒドロキシ−2,
5,7,8−テトラメチルクロマン−2−アセチルヒド
ラゾン(4-piperidino-6-isopropoxysalicylaldehyde 6-
hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazo
ne) 収率:76% (物性) 淡桃色結晶(mp.192-195 ℃) PMR(DMSO-d6,δ ppm) :11.33,11.16(1H,each-s),11.96,
11.00(1H,each-s),8.44,8.38(1H,each-s),7.39,7.34(1
H,each-s),6.04(1H,d,J=2.0Hz),5.95(1H,d,J=2.0Hz),4.
66(1H,sept,J=6.0Hz),3.30-3.22(4H,m),2.80-2.37(4H,
m),2.08-1.77(11H,m),1.34(3H,s),1.28(6H,t,J=6.0Hz) IR(KBr, cm-1):3396,3339,2976,2933,1675,1626,1596,1
544,1505,1452,1383,1343,1261,1235,1203,1173,1121,1
087,1062,997,931,923,860,812,474
Example 160 4-Piperidino-6-isopropoxysalicylaldehyde 6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetylhydrazone (4-piperidino-6-isopropoxysalicylaldehyde 6-
hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazo
ne) Yield: 76% (property) pale pink crystals (mp.192-195 ℃) PMR (DMSO- d 6, δ ppm): 11.33,11.16 (1H, each-s), 11.96,
11.00 (1H, each-s), 8.44,8.38 (1H, each-s), 7.39,7.34 (1
H, each-s), 6.04 (1H, d, J = 2.0Hz), 5.95 (1H, d, J = 2.0Hz), 4.
66 (1H, sept, J = 6.0Hz), 3.30-3.22 (4H, m), 2.80-2.37 (4H,
m), 2.08-1.77 (11H, m), 1.34 (3H, s), 1.28 (6H, t, J = 6.0Hz) IR (KBr, cm- 1 ): 3396,3339,2976,2933,1675,1626 , 1596,1
544,1505,1452,1383,1343,1261,1235,1203,1173,1121,1
087,1062,997,931,923,860,812,474

【0283】実施例161 4−(N−メトキシカルボ
ニルメチル)シクロペンチルアミノサリチルアルデヒド
6−ヒドロキシ−2,5,7,8−テトラメチルクロマ
ン−2−アセチルヒドラゾン(4-(N-methoxycarbonylmet
hyl)cyclopentylaminosalicylaldehyde 6-hydroxy-2,5,
7,8-tetramethylchroman-2-acetylhydrazone) 収率:43% (物性) 淡紫色油状物 PMR(DMSO-d6,δ ppm) :11.32,11.10(1H,each-s),11.33,
10.10(1H,each-s),8.14,8.06(1H,each-s),7.42,7.36(1
H,each-s),7.19,7.17(1H,each-d,J=8.8Hz),6.25,6.21(1
H,each-dd,J=2.0 and 8.8Hz),6.14,6.10(1H,each-d,J=
2.0Hz),4.25-4.10(1H,m),4.08-4.02(2H,m),3.68(3H,s),
2.90-2.38(4H,m),2.06-1.78(13H,m),1.72-1.39(6H,m),
1.34,1.33(3H,each-s)
Example 161 4- (N-methoxycarbonylmethyl) cyclopentylaminosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (4- (N-methoxycarbonylmet)
hyl) cyclopentylaminosalicylaldehyde 6-hydroxy-2,5,
7,8-tetramethylchroman-2-acetylhydrazone) Yield: 43% (physical properties) Pale purple oil PMR (DMSO-d 6 , δ ppm): 11.32, 11.10 (1H, each-s), 11.33,
10.10 (1H, each-s), 8.14,8.06 (1H, each-s), 7.42,7.36 (1
H, each-s), 7.19,7.17 (1H, each-d, J = 8.8Hz), 6.25,6.21 (1
H, each-dd, J = 2.0 and 8.8Hz), 6.14,6.10 (1H, each-d, J =
2.0Hz), 4.25-4.10 (1H, m), 4.08-4.02 (2H, m), 3.68 (3H, s),
2.90-2.38 (4H, m), 2.06-1.78 (13H, m), 1.72-1.39 (6H, m),
1.34,1.33 (3H, each-s)

【0284】実施例162 o−バニリン3,5−ジイ
ソプロピル−4−ヒドロキシベンゾイルヒドラゾン(o-v
anillin 3,5-diisopropyl-4-hydroxybenzoylhydrazone) 参考例16で合成した化合物3,5−ジイソプロピル−
4−ヒドロキシベンゾヒドラジド 0.47g(2mmol) 及びo
−バニリン 0.30g(2mmol) をエタノール 20mlに溶か
し、60℃で3 時間攪拌した。析出した結晶をろ取し、減
圧下で乾燥し、標記化合物 0.22g(収率:30%)を得た。
Example 162 o-Vaniline 3,5-diisopropyl-4-hydroxybenzoylhydrazone (ov
anillin 3,5-diisopropyl-4-hydroxybenzoylhydrazone) Compound 3,5-diisopropyl- synthesized in Reference Example 16.
0.47 g (2 mmol) of 4-hydroxybenzohydrazide and o
-0.30 g (2 mmol) of vanillin was dissolved in 20 ml of ethanol, and the mixture was stirred at 60 ° C for 3 hours. The precipitated crystals were collected by filtration and dried under reduced pressure to obtain 0.22 g (yield: 30%) of the title compound.

【0285】(物性) 淡黄色結晶(mp.218-223 ℃) PMR(DMSO-d6,δ ppm) :11.79(1H,s),11.20(1H,s),8.80
(1H,s),8.66(1H,s),7.63(2H,s),7.11(1H,d,J =7.8Hz),
7.02(1H,d,J=7.8Hz),6.88(1H,t,J=7.8Hz),3.82(3H,s),
3.42-3.27(2H,m),1.21(12H,d,J=6.8Hz) IR(KBr, cm-1):3465,3216,3061,2961,1635,1606,1576,1
543,1465,1358,1303,1251,1210,1159,1095,1078,982,94
4,835,778,732
(Physical properties) Light yellow crystal (mp. 218-223 ° C.) PMR (DMSO-d 6 , δ ppm): 11.79 (1H, s), 11.20 (1 H, s), 8.80
(1H, s), 8.66 (1H, s), 7.63 (2H, s), 7.11 (1H, d, J = 7.8Hz),
7.02 (1H, d, J = 7.8Hz), 6.88 (1H, t, J = 7.8Hz), 3.82 (3H, s),
3.42-3.27 (2H, m), 1.21 (12H, d, J = 6.8Hz) IR (KBr, cm -1 ): 3465,3216,3061,2961,1635,1606,1576,1
543,1465,1358,1303,1251,1210,1159,1095,1078,982,94
4,835,778,732

【0286】実施例163〜166 o−バニリンを他のアルデヒド化合物に代える以外は実
施例162と実質的に同様に処理して、以下の化合物を
製造した。 実施例163 4−ジエチルアミノサリチルアルデヒド
3,5−ジイソプロピル−4−ヒドロキシベンゾイルヒ
ドラゾン(4-diethylaminosalicylaldehyde 3,5-diisopr
opyl-4-hydroxybenzoylhydrazone) 収率:64% (物性) 黄色結晶(mp.135-138 ℃) PMR(DMSO-d6,δ ppm) :11.59(1H,s),11.50(1H,s),8.72
(1H,s),8.44(1H,s),7.60(2H,s),7.16(1H,d,J=8.8Hz),6.
24(1H,dd,J=2.2 and 8.8Hz),6.13(1H,d,J=2.2Hz),3.40-
3.28(6H,m),1.21(12H,d,J=6.8Hz),1.12(6H,t,J=7.0Hz) IR(KBr, cm-1):3418,2966,1633,1601,1519,1470,1355,1
295,1249,1206,1133,963,787,733
Examples 163 to 166 The following compounds were prepared in substantially the same manner as in Example 162 except that o-vanillin was replaced with another aldehyde compound. Example 163 4-diethylaminosalicylaldehyde 3,5-diisopropyl-4-hydroxybenzoylhydrazone
opyl-4-hydroxybenzoylhydrazone) Yield: 64% (physical properties) Yellow crystal (mp. 135-138 ° C) PMR (DMSO-d 6 , δ ppm): 11.59 (1H, s), 11.50 (1H, s), 8.72
(1H, s), 8.44 (1H, s), 7.60 (2H, s), 7.16 (1H, d, J = 8.8Hz), 6.
24 (1H, dd, J = 2.2 and 8.8Hz), 6.13 (1H, d, J = 2.2Hz), 3.40-
3.28 (6H, m), 1.21 (12H, d, J = 6.8Hz), 1.12 (6H, t, J = 7.0Hz) IR (KBr, cm -1 ): 3418,2966,1633,1601,1519,1470 , 1355,1
295,1249,1206,1133,963,787,733

【0287】実施例164 4−ジメチルアミノサリチ
ルアルデヒド3,5−ジイソプロピル−4−ヒドロキシ
ベンゾイルヒドラゾン(4-dimethylaminosalicylaldehyd
e 3,5-diisopropyl-4-hydroxybenzoylhydrazone) 収率:65% (物性) 黄色結晶(mp.235-252 ℃) PMR(DMSO-d6,δ ppm) :11.63(1H,s),11.53(1H,s),8.74
(1H,s),8.46(1H,s),7.60(2H,s),7.19(1H,d,J =8.8Hz),
6.31(1H,dd,J=2.2 and 8.8Hz),6.17(1H,d,J=2.2Hz),3.4
0-3.27(2H,m),2.96(6H,s),1.21(12H,d,J=6.8Hz) IR(KBr, cm-1):3417,2962,1632,1602,1523,1469,1444,1
356,1302,1263,1209,1137,1072,979,825,733
Example 164 4-dimethylaminosalicylaldehyde 3,5-diisopropyl-4-hydroxybenzoylhydrazone
e 3,5-diisopropyl-4-hydroxybenzoylhydrazone) Yield: 65% (physical properties) Yellow crystal (mp.235-252 ° C) PMR (DMSO-d 6 , δ ppm): 11.63 (1H, s), 11.53 (1H , s), 8.74
(1H, s), 8.46 (1H, s), 7.60 (2H, s), 7.19 (1H, d, J = 8.8Hz),
6.31 (1H, dd, J = 2.2 and 8.8Hz), 6.17 (1H, d, J = 2.2Hz), 3.4
0-3.27 (2H, m), 2.96 (6H, s), 1.21 (12H, d, J = 6.8Hz) IR (KBr, cm- 1 ): 3417,2962,1632,1602,1523,1469,1444, 1
356,1302,1263,1209,1137,1072,979,825,733

【0288】実施例165 4−イソプロポキシサリチ
ルアルデヒド3,5−ジイソプロピル−4−ヒドロキシ
ベンゾイルヒドラゾン(4-isopropoxysalicylaldehyde
3,5-diisopropyl-4-hydroxybenzoylhydrazone) 収率:75% (物性) 淡黄色結晶(mp.249-256 ℃) PMR(DMSO-d6,δ ppm) :11.72(1H,s),11.68(1H,s),8.77
(1H,s),8.55(1H,s),7.62(2H,s),7.35(1H,d,J=8.8Hz),6.
48(1H,dd,J=1.8 and 8.8Hz),6.45(1H,d,J=1.8Hz),4.65
(1H,sept,J=6.3Hz),3.40-3.27(2H,m),1.28(6H,d,J=6.3H
z),1.21(12H,d,J=6.8Hz) IR(KBr, cm-1):3419,3218,2962,1634,1605,1538,1508,1
468,1358,1333,1295,1255,1203,1113,1075,992,966,93
3,843,835,805,740,643
Example 165 4-Isopropoxysalicylaldehyde 3,5-diisopropyl-4-hydroxybenzoylhydrazone
3,5-diisopropyl-4-hydroxybenzoylhydrazone) Yield: 75% (property) pale yellow crystals (mp.249-256 ℃) PMR (DMSO- d 6, δ ppm): 11.72 (1H, s), 11.68 (1H , s), 8.77
(1H, s), 8.55 (1H, s), 7.62 (2H, s), 7.35 (1H, d, J = 8.8Hz), 6.
48 (1H, dd, J = 1.8 and 8.8Hz), 6.45 (1H, d, J = 1.8Hz), 4.65
(1H, sept, J = 6.3Hz), 3.40-3.27 (2H, m), 1.28 (6H, d, J = 6.3H
z), 1.21 (12H, d, J = 6.8Hz) IR (KBr, cm -1 ): 3419,3218,2962,1634,1605,1538,1508,1
468,1358,1333,1295,1255,1203,1113,1075,992,966,93
3,843,835,805,740,643

【0289】実施例166 4−ピペリジノ−6−イソ
プロポキシサリチルアルデヒド3,5−ジイソプロピル
−4−ヒドロキシベンゾイルヒドラゾン(4-piperidino-
6-isopropoxysalicylaldehyde 3,5-diisopropyl-4-hydr
oxybenzoylhydrazone) 収率:91% (物性) 淡黄色結晶(mp.260-290 ℃) PMR(DMSO-d6,δ ppm) :12.42(1H,s),11.65(1H,s),8.72
(1H,s),8.71(1H,s),7.61(2H,s),6.06(1H,d,J=2.0Hz),5.
97(1H,d,J=2.0Hz),4.72(1H,sept,J=6.0Hz),3.40-3.30(2
H,m),3.30-3.23(4H,m),1.62-1.55(6H,m),1.32(6H,d,J=
6.0Hz),1.21(12H,d,J=7.0Hz) IR(KBr, cm-1):3418,3212,2962,2936,1631,1601,1553,1
465,1347,1206,1119,995,817,734
Example 166 4-Piperidino-6-isopropoxysalicylaldehyde 3,5-diisopropyl-4-hydroxybenzoylhydrazone (4-piperidino-
6-isopropoxysalicylaldehyde 3,5-diisopropyl-4-hydr
Oxybenzoylhydrazone) Yield: 91% (property) pale yellow crystals (mp.260-290 ℃) PMR (DMSO- d 6, δ ppm): 12.42 (1H, s), 11.65 (1H, s), 8.72
(1H, s), 8.71 (1H, s), 7.61 (2H, s), 6.06 (1H, d, J = 2.0Hz), 5.
97 (1H, d, J = 2.0Hz), 4.72 (1H, sept, J = 6.0Hz), 3.40-3.30 (2
H, m), 3.30-3.23 (4H, m), 1.62-1.55 (6H, m), 1.32 (6H, d, J =
6.0Hz), 1.21 (12H, d, J = 7.0Hz) IR (KBr, cm -1 ): 3418,3212,2962,2936,1631,1601,1553,1
465,1347,1206,1119,995,817,734

【0290】実施例167 o−バニリン3−(3,5
−ジ−t−ブチル−4−ヒドロキシフェニル)プロピオ
ニルヒドラゾン(o-vanillin 3-(3,5-di-t-butyl-4-hydr
oxyphenyl)propionylhydrazone) 参考例17で合成した化合物3−(3,5−ジ−t−ブ
チル−4−ヒドロキシフェニル)プロピオノヒドラジド
1.17g(4mmol) 及びo−バニリン 0.61g(4mmol) をエタ
ノール 20ml に溶かし、室温で8 時間撹拌した。析出し
た結晶をろ取し、減圧下で乾燥し、標記化合物 1.22g
(収率:72%)を得た。 (物性) 無色結晶(mp.175-185 ℃) PMR(DMSO-d6,δ ppm) :11.58,11.25(1H,each-s),10.92,
9.48(1H,each-s),8.34,8.28(1H,each-s),7.23,7.08(1H,
each-dd,J=1.5 and 8.1Hz),7.05-6.94(1H,m),6.97,6.95
(2H,each-s),6.83,6.77(1H,each-t,J=8.1Hz),6.70,6.67
(1H,each-s),3.81(3H,s),2.85-2.75(3H,m),2.55-2.43(1
H,m),1.364,1.357(18H,each-s)
Example 167 o-Vaniline 3- (3,5
-Di-t-butyl-4-hydroxyphenyl) propionylhydrazone (o-vanillin 3- (3,5-di-t-butyl-4-hydr)
(oxyphenyl) propionylhydrazone) Compound 3- (3,5-di-t-butyl-4-hydroxyphenyl) propionohydrazide synthesized in Reference Example 17
1.17 g (4 mmol) and 0.61 g (4 mmol) of o-vanillin were dissolved in 20 ml of ethanol, and the mixture was stirred at room temperature for 8 hours. The precipitated crystals were collected by filtration and dried under reduced pressure to give the title compound (1.22 g).
(Yield: 72%) was obtained. (Physical properties) Colorless crystal (mp.175-185 ° C) PMR (DMSO-d 6 , δ ppm): 11.58,11.25 (1H, each-s), 10.92,
9.48 (1H, each-s), 8.34,8.28 (1H, each-s), 7.23,7.08 (1H, each-s)
each-dd, J = 1.5 and 8.1Hz), 7.05-6.94 (1H, m), 6.97,6.95
(2H, each-s), 6.83,6.77 (1H, each-t, J = 8.1Hz), 6.70,6.67
(1H, each-s), 3.81 (3H, s), 2.85-2.75 (3H, m), 2.55-2.43 (1
H, m), 1.364,1.357 (18H, each-s)

【0291】実施例168〜170 o−バニリンを他のアルデヒド化合物に代える以外は実
施例167と実質的に同様に処理して、以下の化合物を
製造した。 実施例168 4−ジエチルアミノサリチルアルデヒド
3−(3,5−ジ−t−ブチル−4−ヒドロキシフェニ
ル)プロピオニルヒドラゾン(4-diethylaminosalicylal
dehyde 3-(3,5-di-t-butyl-4-hydroxyphenyl)propionyl
hydrazone) 収率:72% (物性) 淡褐色結晶(mp.180-182 ℃) PMR(DMSO-d6,δ ppm) :11.28,10.99(1H,each-s),11.33,
10.15(1H,each-s),8.11,8.04(1H,each-s),7.25,7.14(1
H,each-d,J=8.8Hz),6.97,6.94(2H,each-s),6.69,6.67(1
H,each-s),6.23,6.20(1H,each-dd,J=2.3 and 8.8Hz),6.
09,6.07(1H,each-d,J=2.3Hz),3.45-3.30(4H,m),2.83-2.
38(4H,m),1.37,1.36(18H,each-s),1.10,1.096(6H,each-
t,J=7.0Hz) IR(KBr, cm-1):3589,2965,2871,1664,1632,1600,1559,1
527,1401,1355,1246,1129,1016,962,826,784
Examples 168 to 170 The following compounds were prepared in substantially the same manner as in Example 167 except that o-vanillin was replaced with another aldehyde compound. Example 168 4-Diethylaminosalicylaldehyde 3- (3,5-di-tert-butyl-4-hydroxyphenyl) propionylhydrazone (4-diethylaminosalicylal)
dehyde 3- (3,5-di-t-butyl-4-hydroxyphenyl) propionyl
hydrazone) Yield: 72% (physical properties) Light brown crystal (mp. 180-182 ° C) PMR (DMSO-d 6 , δ ppm): 11.28, 10.99 (1H, each-s), 11.33,
10.15 (1H, each-s), 8.11,8.04 (1H, each-s), 7.25,7.14 (1
H, each-d, J = 8.8Hz), 6.97,6.94 (2H, each-s), 6.69,6.67 (1
H, each-s), 6.23,6.20 (1H, each-dd, J = 2.3 and 8.8Hz), 6.
09,6.07 (1H, each-d, J = 2.3Hz), 3.45-3.30 (4H, m), 2.83-2.
38 (4H, m), 1.37,1.36 (18H, each-s), 1.10,1.096 (6H, each-s
t, J = 7.0Hz) IR (KBr, cm -1 ): 3589,2965,2871,1664,1632,1600,1559,1
527,1401,1355,1246,1129,1016,962,826,784

【0292】実施例169 ピリドキサール3−(3,
5−ジ−t−ブチル−4−ヒドロキシフェニル)プロピ
オニルヒドラゾン(pyridoxal 3-(3,5-di-t-butyl-4-hyd
roxyphenyl)propionylhydrazone) 収率:44% (物性) 黄色結晶(mp.205-220 ℃) PMR(DMSO-d6,δ ppm) :13.00(1H,brs),12.56,11.92(1H,
each-s),8.67,8.51(1H,each-s),8.22,8.20(1H,each-s),
6.97,6.96(2H,each-s),6.78-6.67(1H,m),4.76,4.73(2H,
each-s),2.61(3H,s),2.90-2.55(4H,m),1.36(18H,s) IR(KBr, cm-1):3380,2956,1697,1542,1474,1435,1363,1
233,1167,1120,1059,1039,769
Example 169 Pyridoxal 3- (3,3)
5-di-t-butyl-4-hydroxyphenyl) propionyl hydrazone (pyridoxal 3- (3,5-di-t-butyl-4-hyd)
roxyphenyl) propionylhydrazone) Yield: 44% (property) of yellow crystals (mp.205-220 ℃) PMR (DMSO- d 6, δ ppm): 13.00 (1H, brs), 12.56,11.92 (1H,
each-s), 8.67,8.51 (1H, each-s), 8.22,8.20 (1H, each-s),
6.97,6.96 (2H, each-s), 6.78-6.67 (1H, m), 4.76,4.73 (2H,
each-s), 2.61 (3H, s), 2.90-2.55 (4H, m), 1.36 (18H, s) IR (KBr, cm -1 ): 3380,2956,1697,1542,1474,1435,1363, 1
233,1167,1120,1059,1039,769

【0293】実施例170 4−ピペリジノサリチルア
ルデヒド3−(3,5−ジ−t−ブチル−4−ヒドロキ
シフェニル)プロピオニルヒドラゾン(4-piperidinosal
icylaldehyde 3-(3,5-di-t-butyl-4-hydroxyphenyl)pro
pionylhydrazone) 収率:88% (物性) 淡黄色結晶(mp.195-197 ℃) PMR(DMSO-d6,δ ppm) :11.35,11.05(1H,each-s),11.32,
10.14(1H,each-s),8.15,8.08(1H,each-s),7.30,7.19(1
H,each-d,J=8.8Hz),6.97,6.94(2H,each-s),6.69,6.66(1
H,each-s),6.47,6.44(1H,each-dd,J=2.0 and 8.8Hz),6.
34,6.31(1H,each-d,J=2.0Hz),3.28-3.18(4H,m),2.82-2.
40(4H,m),1.61-1.55(6H,m),1.37,1.36(18H,each-s) IR(KBr, cm-1):3444,3195,2952,2862,1660,1631,1600,1
557,1519,1435,1385,1220,1163,1121,1024,972,770,568
Example 170 4-Piperidinosalicylaldehyde 3- (3,5-di-tert-butyl-4-hydroxyphenyl) propionylhydrazone (4-piperidinosal)
icylaldehyde 3- (3,5-di-t-butyl-4-hydroxyphenyl) pro
Pionylhydrazone) Yield: 88% (property) pale yellow crystals (mp.195-197 ℃) PMR (DMSO- d 6, δ ppm): 11.35,11.05 (1H, each-s), 11.32,
10.14 (1H, each-s), 8.15,8.08 (1H, each-s), 7.30,7.19 (1
H, each-d, J = 8.8Hz), 6.97,6.94 (2H, each-s), 6.69,6.66 (1
H, each-s), 6.47,6.44 (1H, each-dd, J = 2.0 and 8.8Hz), 6.
34,6.31 (1H, each-d, J = 2.0Hz), 3.28-3.18 (4H, m), 2.82-2.
40 (4H, m), 1.61-1.55 (6H, m), 1.37,1.36 (18H, each-s) IR (KBr, cm -1 ): 3444,3195,2952,2862,1660,1631,1600,1
557,1519,1435,1385,1220,1163,1121,1024,972,770,568

【0294】実施例171 o−バニリン3,5−ジ−
t−ブチル−4−ヒドロキシシンナモイルヒドラゾン(o
-vanillin 3,5-di-t-butyl-4-hydroxycinnamoylhydrazo
ne) アルゴン気流下、3,5−ジ−t−ブチル−4−ヒドロ
キシケイ皮酸 0.83g(3mmol) 及びo−バニリンヒドラゾ
ン 0.50g(3mmol) の塩化メチレン 10ml 溶液に、トリエ
チルアミン 0.60g(6mmol) 及びビス(2−オキソ−3−
オキサゾリジニル)ホスフィニッククロリド(bis(2-oxo
-3-oxazolidinyl)phosphinic chloride)0.76g(3mmol)
を室温で加えた後、更に、室温で12時間撹拌した。溶媒
を留去し、残渣をシリカゲルカラムクロマトグラフィー
に付した。クロロホルム:メタノール=20:1溶出部
を溶媒留去し、トルエンより再結晶を行った後、減圧下
で乾燥し、標記化合物 0.37g(収率:28%)を得た。 (物性) 黄色結晶(mp.238-245 ℃) PMR(DMSO-d6,δ ppm) :11.77(1H,brs),10.96(1H,brs),
8.39(1H,s),7.58(1H,d,J=16.0Hz),7.45-7.30(3H,m),7.1
3(1H,d,J=8.0Hz),7.01(1H,d,J=8.0Hz),6.85(1H,t,J=8.0
Hz),6.50(1H,d,J=16.0Hz),3.82(3H,s),1.42(18H,s) IR(KBr, cm-1):3444,3197,2956,1651,1621,1616,1463,1
426,1360,1253,1207,1196,1119,1091,1080,975,733
Example 171 o-Vaniline 3,5-di-
t-butyl-4-hydroxycinnamoylhydrazone (o
-vanillin 3,5-di-t-butyl-4-hydroxycinnamoylhydrazo
ne) Under a stream of argon, 0.83 g (3 mmol) of 3,5-di-t-butyl-4-hydroxycinnamic acid and 0.50 g (3 mmol) of o-vanillin hydrazone were added to a 10 ml solution of methylene chloride, and 0.60 g (6 mmol) of triethylamine was added. And bis (2-oxo-3-
Oxazolidinyl) phosphinic chloride (bis (2-oxo
-3-oxazolidinyl) phosphinic chloride) 0.76g (3mmol)
Was added at room temperature, and the mixture was further stirred at room temperature for 12 hours. The solvent was distilled off, and the residue was subjected to silica gel column chromatography. The solvent eluted with chloroform: methanol = 20: 1 was evaporated, recrystallized from toluene, and dried under reduced pressure to obtain 0.37 g (yield: 28%) of the title compound. (Physical properties) Yellow crystal (mp.238-245 ° C) PMR (DMSO-d 6 , δ ppm): 11.77 (1H, brs), 10.96 (1H, brs),
8.39 (1H, s), 7.58 (1H, d, J = 16.0Hz), 7.45-7.30 (3H, m), 7.1
3 (1H, d, J = 8.0Hz), 7.01 (1H, d, J = 8.0Hz), 6.85 (1H, t, J = 8.0Hz)
Hz), 6.50 (1H, d, J = 16.0Hz), 3.82 (3H, s), 1.42 (18H, s) IR (KBr, cm -1 ): 3444,3197,2956,1651,1621,1616,1463 , 1
426,1360,1253,1207,1196,1119,1091,1080,975,733

【0295】実施例172 4−ジエチルアミノサリチ
ルアルデヒド3,5−ジ−t−ブチル−4−ヒドロキシ
シンナモイルヒドラゾン(4-diethylaminosalicylaldehy
de 3,5-di-t-butyl-4-hydroxycinnamoylhydrazone) 3,5−ジ−t−ブチル−4−ヒドロキシケイ皮酸 0.4
7g(1.7mmol) 、4−ジエチルアミノサリチルアルデヒド
ヒドラゾン 0.42g(2mmol) 及び3−(ジエチルホスホリ
ルオキシ)−1,2,3−ベンゾトリアジン−4(3
H)−オン(3-(diethylphosphoryloxy)-1,2,3-benzotri
azin-4(3H)-one) 0.60g(2mmol)のジメチルホルムアミド
10ml 溶液に、トリエチルアミン 0.40g(4mmol) を室温
で加えた後、更に、室温で18時間撹拌した。反応液を水
にあけ、酢酸エチルで抽出した。酢酸エチル層を水、飽
和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥
し、溶媒を留去し、残渣をシリカゲルカラムクロマトグ
ラフィーに付した。クロロホルム:メタノール=30:
1溶出部を溶媒留去し、ヘキサン:酢酸エチル=1:1
より結晶化を行い、結晶をろ取した。ろ取した結晶を減
圧下で乾燥し、標記化合物 0.33g(収率42%)を得た。
Example 172 4-Diethylaminosalicylaldehyde 3,5-di-tert-butyl-4-hydroxycinnamoylhydrazone
de 3,5-di-t-butyl-4-hydroxycinnamoylhydrazone) 3,5-di-t-butyl-4-hydroxycinnamic acid 0.4
7 g (1.7 mmol), 0.42 g (2 mmol) of 4-diethylaminosalicylaldehyde hydrazone and 3- (diethylphosphoryloxy) -1,2,3-benzotriazine-4 (3
H) -one (3- (diethylphosphoryloxy) -1,2,3-benzotri
azin-4 (3H) -one) 0.60 g (2 mmol) of dimethylformamide
After adding 0.40 g (4 mmol) of triethylamine to the 10 ml solution at room temperature, the mixture was further stirred at room temperature for 18 hours. The reaction solution was poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed sequentially with water and saturated saline, dried over magnesium sulfate, the solvent was distilled off, and the residue was subjected to silica gel column chromatography. Chloroform: methanol = 30:
The solvent was distilled off from one eluted part, and hexane: ethyl acetate = 1: 1.
Further crystallization was performed, and the crystals were collected by filtration. The crystals collected by filtration were dried under reduced pressure to give the title compound (0.33 g, yield 42%).

【0296】(物性) 黄色結晶(mp.240-250 ℃) PMR(DMSO-d6,δ ppm) :11.48(1H,s),11.37(1H,s),8.17
(1H,s),7.51(1H,d,J=16.0Hz),7.37(1H,s),7.36(2H,s),
7.16(1H,d,J=9.0Hz),6.48(1H,d,J=16.0Hz),6.24(1H,dd,
J=2.0 and 9.0Hz),6.11(1H,d,J=2.0Hz),3.35(4H,q,J=7.
1Hz),1.42(18H,s),1.11(6H,t,J=7.1Hz) IR(KBr, cm-1):3444,3207,2965,1632,1594,1519,1426,1
355,1242,1208,1133,1022,787
(Physical properties) Yellow crystal (mp. 240-250 ° C.) PMR (DMSO-d 6 , δ ppm): 11.48 (1H, s), 11.37 (1 H, s), 8.17
(1H, s), 7.51 (1H, d, J = 16.0Hz), 7.37 (1H, s), 7.36 (2H, s),
7.16 (1H, d, J = 9.0Hz), 6.48 (1H, d, J = 16.0Hz), 6.24 (1H, dd,
J = 2.0 and 9.0Hz), 6.11 (1H, d, J = 2.0Hz), 3.35 (4H, q, J = 7.
1Hz), 1.42 (18H, s), 1.11 (6H, t, J = 7.1Hz) IR (KBr, cm -1 ): 3444,3207,2965,1632,1594,1519,1426,1
355,1242,1208,1133,1022,787

【0297】実施例173 o−バニリン3−(3,5
−ジイソプロピル−4−ヒドロキシフェニル)プロピオ
ニルヒドラゾン(o-vanillin 3-(3,5-diisopropyl-4-hyd
roxyphenyl)propionylhydrazone) 参考例18で合成した化合物3−(3,5−ジイソプロ
ピル−4−ヒドロキシフェニル)プロピオノヒドラジド
0.79g(3mmol) 及びo−バニリン 0.46g(3mmol) を2−
プロパノール 20ml に溶かし、8 時間加熱環流した。析
出した結晶をろ取し、減圧下で乾燥し、標記化合物 1.0
3g(収率86%)を得た。 (物性) 無色結晶(mp.85-88 ℃) PMR(DMSO-d6,δ ppm) :11.58,11.25(1H,each-s),10.93,
9.50(1H,each-s),8.33,8.28(1H,each-s),7.80,7.78(1H,
each-s),7.23,7.07(1H,each-dd,J=1.5 and 8.0Hz),7.0
0,6.96(1H,each-dd,J=1.5 and 8.0Hz),6.86-6.74(3H,
m),3.81,3.80(3H,each-s),3.26(2H,sept,J=7.0Hz),2.84
-2.74(2H,m),2.50-2.43(2H,m),1.13,1.12(12H,each-s) IR(KBr, cm-1):3444,3252,2960,2867,1670,1609,1470,1
255,1203,1153,1078,778,732,564
Example 173 o-Vaniline 3- (3,5
-Diisopropyl-4-hydroxyphenyl) propionylhydrazone (o-vanillin 3- (3,5-diisopropyl-4-hyd
roxyphenyl) propionylhydrazone) Compound 3- (3,5-diisopropyl-4-hydroxyphenyl) propionohydrazide synthesized in Reference Example 18
0.79 g (3 mmol) and 0.46 g (3 mmol) of o-vanillin in 2-
It was dissolved in 20 ml of propanol and heated under reflux for 8 hours. The precipitated crystals were collected by filtration and dried under reduced pressure to give the title compound 1.0
3 g (86% yield) was obtained. (Physical properties) Colorless crystal (mp.85-88 ° C) PMR (DMSO-d 6 , δ ppm): 11.58,11.25 (1H, each-s), 10.93,
9.50 (1H, each-s), 8.33,8.28 (1H, each-s), 7.80,7.78 (1H, each-s)
each-s), 7.23,7.07 (1H, each-dd, J = 1.5 and 8.0Hz), 7.0
0,6.96 (1H, each-dd, J = 1.5 and 8.0Hz), 6.86-6.74 (3H,
m), 3.81,3.80 (3H, each-s), 3.26 (2H, sept, J = 7.0Hz), 2.84
-2.74 (2H, m), 2.50-2.43 (2H, m), 1.13,1.12 (12H, each-s) IR (KBr, cm -1 ): 3444,3252,2960,2867,1670,1609,1470, 1
255,1203,1153,1078,778,732,564

【0298】実施例174 4−ジエチルアミノサリチ
ルアルデヒド3−(3,5−ジイソプロピル−4−ヒド
ロキシフェニル)プロピオニルヒドラゾン(4-diethylam
inosalicylaldehyde 3-(3,5-diisopropyl-4-hydroxyphe
nyl)propionylhydrazone) o−バニリンを4−ジエチルアミノサリチルアルデヒド
に代える以外は実施例173と実質的に同様に処理して
標記化合物を製造した。 収率:77% (物性) 淡黄色結晶(mp.179-183 ℃) PMR(DMSO-d6,δ ppm) :11.34,10.98(1H,each-s),11.27,
10.16(1H,each-s),8.11,8.04(1H,each-s),7.78(1H,s),
7.24,7.12(1H,each-d,J=9.0Hz),6.85,6.82(2H,each-s),
6.23,6.21(1H,each-dd,J=2.5 and 9.0Hz),6.09,6.07(1
H,each-d,J=2.5Hz),3.40-3.20(6H,m),2.82-2.70(2H,m),
2.45-2.38(2H,m),1.16-1.08(18H,m) IR(KBr, cm-1):3500,2964,1662,1632,1599,1557,1520,1
471,1401,1355,1247,1196,1128,1077,1012,787
Example 174 4-Diethylaminosalicylaldehyde 3- (3,5-diisopropyl-4-hydroxyphenyl) propionylhydrazone (4-diethylam
inosalicylaldehyde 3- (3,5-diisopropyl-4-hydroxyphe
nyl) propionylhydrazone) The title compound was prepared in substantially the same manner as in Example 173 except that o-vanillin was replaced with 4-diethylaminosalicylaldehyde. Yield: 77% (property) pale yellow crystals (mp.179-183 ℃) PMR (DMSO- d 6, δ ppm): 11.34,10.98 (1H, each-s), 11.27,
10.16 (1H, each-s), 8.11,8.04 (1H, each-s), 7.78 (1H, s),
7.24,7.12 (1H, each-d, J = 9.0Hz), 6.85,6.82 (2H, each-s),
6.23,6.21 (1H, each-dd, J = 2.5 and 9.0Hz), 6.09,6.07 (1
H, each-d, J = 2.5Hz), 3.40-3.20 (6H, m), 2.82-2.70 (2H, m),
2.45-2.38 (2H, m), 1.16-1.08 (18H, m) IR (KBr, cm -1 ): 3500,2964,1662,1632,1599,1557,1520,1
471,1401,1355,1247,1196,1128,1077,1012,787

【0299】実施例175〜183 ベンズアルデヒド又は4−フルオロベンズアルデヒドを
他のアルデヒド化合物又はケトン化合物に代える以外は
実施例1又は2と実質的に同様に処理して、以下の化合
物を製造した。 実施例175 6−イソプロポキシ−4−モルホリノサ
リチルアルデヒド3,5−ジ−t−ブチル−4−ヒドロ
キシベンゾイルヒドラゾン(6−isopropoxy
−4−morpholinosalicylaldeh
yde 3,5−di−t−butyl−4−hydr
oxybenzoylhydrazone) 収率:96% (物性) 無色結晶(mp.>300 ℃) PMR(DMSO-d6,δ ppm) : 12.43(1H,s),11.72(1H,s),8.72
(1H,s),7.66(2H,s),7.50(1H,brs),6.12(1H,d,J=1.0Hz),
6.01(1H,d,J=1.0Hz),4.73(1H,sept,J=5.9Hz),3.74-3.69
(4H,m),3.24-3.18(4H,m),1.43(18H,s),1.31(6H,d,J=5.9
Hz) IR(KBr, cm-1):3601,3444,3207,2955,1630,1598,1553,1
506,1446,1435,1347,1332,1303,1239,1201,1121,1071,1
007,973,923,886,798,709,672,582,548
Examples 175 to 183 The following compounds were prepared in substantially the same manner as in Example 1 or 2, except that benzaldehyde or 4-fluorobenzaldehyde was replaced with another aldehyde compound or ketone compound. Example 175 6-Isopropoxy-4-morpholinosalicylaldehyde 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone (6-isopropoxy)
-4-morpholinosalicylaldeh
ide 3,5-di-t-butyl-4-hydr
Oxybenzoylhydrazone) Yield: 96% (Physical Properties) colorless crystals (mp> 300 ℃) PMR ( DMSO-d 6, δ ppm):. 12.43 (1H, s), 11.72 (1H, s), 8.72
(1H, s), 7.66 (2H, s), 7.50 (1H, brs), 6.12 (1H, d, J = 1.0Hz),
6.01 (1H, d, J = 1.0Hz), 4.73 (1H, sept, J = 5.9Hz), 3.74-3.69
(4H, m), 3.24-3.18 (4H, m), 1.43 (18H, s), 1.31 (6H, d, J = 5.9
Hz) IR (KBr, cm -1 ): 3601,3444,3207,2955,1630,1598,1553,1
506,1446,1435,1347,1332,1303,1239,1201,1121,1071,1
007,973,923,886,798,709,672,582,548

【0300】実施例176 4−N−(イソプロポキシ
カルボニルメチル)イソプロピルアミノサリチルアルデ
ヒド3,5−ジ−t−ブチル−4−ヒドロキシベンゾイ
ルヒドラゾン(4-N-(isopropoxycarbonylmethyl)isoprop
ylaminosalicylaldehyde 3,5-di-t-butyl-4-hydroxyben
zoylhydrazone) 収率:80% (物性) 淡黄色結晶(mp.209-213 ℃) PMR(DMSO-d6,δ ppm) : 11.59(2H,s),8.43(1H,s),7.65
(2H,s),7.50(1H,brs),7.18(1H,d,J=8.8Hz),6.22(1H,dd,
J=1.6 and 8.8Hz),6.11(1H,d,J=1.6Hz),4.96(1H,sept,J
=6.4Hz),4.17(1H,sept,J=6.4Hz),4.00(2H,s),1.43(18H,
s),1.22(6H,d,J=6.4Hz),1.15(6H,d,J=6.4Hz) IR(KBr, cm-1):3596,3212,2969,1745,1632,1601,1557,1
518,1465,1435,1402,1359,1305,1251,1239,1205,1182,1
144,1106,1075,955,937,901,833,787,707,646
Example 176 4-N- (isopropoxycarbonylmethyl) isopropylaminosalicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone (4-N- (isopropoxycarbonylmethyl) isoprop
ylaminosalicylaldehyde 3,5-di-t-butyl-4-hydroxyben
Zoylhydrazone) Yield: 80% (property) pale yellow crystals (mp.209-213 ℃) PMR (DMSO- d 6, δ ppm): 11.59 (2H, s), 8.43 (1H, s), 7.65
(2H, s), 7.50 (1H, brs), 7.18 (1H, d, J = 8.8Hz), 6.22 (1H, dd,
J = 1.6 and 8.8Hz), 6.11 (1H, d, J = 1.6Hz), 4.96 (1H, sept, J
= 6.4Hz), 4.17 (1H, sept, J = 6.4Hz), 4.00 (2H, s), 1.43 (18H,
s), 1.22 (6H, d, J = 6.4Hz), 1.15 (6H, d, J = 6.4Hz) IR (KBr, cm- 1 ): 3596,3212,2969,1745,1632,1601,1557,1
518,1465,1435,1402,1359,1305,1251,1239,1205,1182,1
144,1106,1075,955,937,901,833,787,707,646

【0301】実施例177 4−N−(メトキシカルボ
ニルメチル)イソプロピルアミノサリチルアルデヒド
3,5−ジ−t−ブチル−4−ヒドロキシベンゾイルヒ
ドラゾン(4-N-(methoxycarbonylmethyl)isopropylamino
salicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhyd
razone) 収率:68% (物性) 淡黄色結晶(mp.201-203 ℃) PMR(DMSO-d6,δ ppm) : 11.58(1H,s),11.57(1H,s),8.43
(1H,s),7.65(2H,s),7.51(1H,s),7.18(1H,d,J=8.8Hz),6.
23(1H,dd,J=2.0 and 8.8Hz),6.11(1H,d,J=2.0Hz),3.82
(3H,s),4.17(1H,sept,J=6.3Hz),4.07(2H,s),3.68(3H,
s),1.42(18H,s),1.14(6H,d,J=6.3Hz) IR(KBr, cm-1):3618,3444,3219,2956,1754,1632,1601,1
552,1516,1434,1359,1305,1238,1203,1187,1172,1140,1
078,954,906,889,785,703,648
Example 177 4-N- (methoxycarbonylmethyl) isopropylamino salicylaldehyde 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone (4-N- (methoxycarbonylmethyl) isopropylamino
salicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhyd
razone) Yield: 68% (physical properties) pale yellow crystal (mp. 201-203 ° C) PMR (DMSO-d 6 , δ ppm): 11.58 (1H, s), 11.57 (1H, s), 8.43
(1H, s), 7.65 (2H, s), 7.51 (1H, s), 7.18 (1H, d, J = 8.8Hz), 6.
23 (1H, dd, J = 2.0 and 8.8Hz), 6.11 (1H, d, J = 2.0Hz), 3.82
(3H, s), 4.17 (1H, sept, J = 6.3Hz), 4.07 (2H, s), 3.68 (3H,
s), 1.42 (18H, s), 1.14 (6H, d, J = 6.3Hz) IR (KBr, cm -1 ): 3618,3444,3219,2956,1754,1632,1601,1
552,1516,1434,1359,1305,1238,1203,1187,1172,1140,1
078,954,906,889,785,703,648

【0302】実施例178 4−イソプロポキシ−6−
モルホリノサリチルアルデヒド3,5−ジ−t−ブチル
−4−ヒドロキシベンゾイルヒドラゾン(4-isopropoxy-
6-morpholinosalicylaldehyde 3,5-di-t-butyl-4-hydro
xybenzoylhydrazone) 収率:96% (物性) 淡黄色結晶(mp.>300℃) PMR(DMSO-d6,δ ppm) : 12.58(1H,s),11.80(1H,s),8.73
(1H,s),7.63(2H,s),7.56(1H,s),6.22(1H,d,J=2.5Hz),6.
14(1H,d,J=2.5Hz),4.66(1H,sept,J=5.9Hz),3.81-3.75(4
H,m),2.91-2.85(4H,m),1.44(18H,s),1.24(6H,d,J=5.9H
z) IR(KBr, cm-1):3609,3444,2958,2912,1636,1621,1598,1
567,1556,1338,1302,1237,1211,1179,1161,1116,1029,1
011,871,831,706
Example 178 4-Isopropoxy-6
Morpholinosalicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone (4-isopropoxy-
6-morpholinosalicylaldehyde 3,5-di-t-butyl-4-hydro
(xybenzoylhydrazone) Yield: 96% (Physical properties) Pale yellow crystal (mp.> 300 ℃) PMR (DMSO-d 6 , δ ppm): 12.58 (1H, s), 11.80 (1H, s), 8.73
(1H, s), 7.63 (2H, s), 7.56 (1H, s), 6.22 (1H, d, J = 2.5Hz), 6.
14 (1H, d, J = 2.5Hz), 4.66 (1H, sept, J = 5.9Hz), 3.81-3.75 (4
H, m), 2.91-2.85 (4H, m), 1.44 (18H, s), 1.24 (6H, d, J = 5.9H
z) IR (KBr, cm -1 ): 3609,3444,2958,2912,1636,1621,1598,1
567,1556,1338,1302,1237,1211,1179,1161,1116,1029,1
011,871,831,706

【0303】実施例179 5−ジエチルアミノサリチ
ルアルデヒド3,5−ジ−t−ブチル−4−ヒドロキシ
ベンゾイルヒドラゾン(5-diethylaminosalicylaldehyde
3,5-di-t-butyl-4-hydroxybenzoylhydrazone) 収率:84% (物性) 黄色結晶(mp.280-288 ℃) PMR(DMSO-d6,δ ppm):11.76(1H,s),10.59(1H,s),8.59(1
H,s),7.68(2H,s),7.54(1H,s),6.83-6.73(3H,m),3.24(4
H,q,J=6.8Hz),1.44(18H,s),1.05(6H,t,J=6.8Hz) IR(KBr, cm-1):3444,3235,2967,1641,1600,1580,1549,1
498,1435,1359,1304,1274,1236,1181,1141,1119,890,84
3,779,736,698
Example 179 5-Diethylaminosalicylaldehyde 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone
3,5-di-t-butyl-4-hydroxybenzoylhydrazone) Yield: 84% (physical properties) Yellow crystal (mp. 280-288 ° C) PMR (DMSO-d 6 , δ ppm): 11.76 (1H, s), 10.59 (1H, s), 8.59 (1
H, s), 7.68 (2H, s), 7.54 (1H, s), 6.83-6.73 (3H, m), 3.24 (4
H, q, J = 6.8Hz), 1.44 (18H, s), 1.05 (6H, t, J = 6.8Hz) IR (KBr, cm- 1 ): 3444,3235,2967,1641,1600,1580,1549 , 1
498,1435,1359,1304,1274,1236,1181,1141,1119,890,84
3,779,736,698

【0304】実施例180 3,5−ジブロモサリチル
アルデヒド3,5−ジ−t−ブチル−4−ヒドロキシベ
ンゾイルヒドラゾン(3,5-dibromosalicylaldehyde 3,5-
di-t-butyl-4-hydroxybenzoylhydrazone) 収率:82% (物性) 淡黄色結晶(mp.>300℃) PMR(DMSO-d6,δ ppm) : 12.88(1H,brs),12.26(1H,brs),
8.53(1H,s),7.78(1H,d,J=2.5Hz),7.735(1H,d,J=2.5Hz),
7.70(2H,s),7.62(1H,s),1.44(18H,s) IR(KBr, cm-1):3619,3218,3055,2958,1639,1600,1537,1
444,1422,1338,1302,1237,1163,1120,1107,980,950,88
9,863,739,711,684
Example 180 3,5-Dibromosalicylaldehyde 3,5-dibromosalicylaldehyde 3,5-dibromosalicylaldehyde 3,5-
di-t-butyl-4-hydroxybenzoylhydrazone) Yield: 82% (physical properties) pale yellow crystal (mp.> 300 ° C) PMR (DMSO-d 6 , δ ppm): 12.88 (1H, brs), 12.26 (1H, brs),
8.53 (1H, s), 7.78 (1H, d, J = 2.5Hz), 7.735 (1H, d, J = 2.5Hz),
7.70 (2H, s), 7.62 (1H, s), 1.44 (18H, s) IR (KBr, cm- 1 ): 3619,3218,3055,2958,1639,1600,1537,1
444,1422,1338,1302,1237,1163,1120,1107,980,950,88
9,863,739,711,684

【0305】実施例181 3−メトキシ−5−ピペリ
ジノメチルサリチルアルデヒド3,5−ジ−t−ブチル
−4−ヒドロキシベンゾイルヒドラゾン(3-methoxy-5-p
iperidinomethylsalicylaldehyde 3,5-di-t-butyl-4-hy
droxybenzoylhydrazone) 収率:51% (物性) 淡黄色結晶(mp.193-213 ℃) PMR(DMSO-d6,δ ppm) : 11.78(1H,brs),10.87(1H,brs),
8.62(1H,brs),7.67(2H,s),7.57(1H,brs),7.04(1H,s),6.
92(1H,s),3.81(3H,s),3.35(2H,s),2.36-2.26(4H,m),1.5
5-1.40(6H,m),1.43(18H,s) IR(KBr, cm-1):3444,2937,1645,1539,1464,1435,1392,1
369,1301,1263,1236,1162,1115,1039,1010,992,889,86
5,844,701
Example 181 3-methoxy-5-piperidinomethylsalicylaldehyde 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone (3-methoxy-5-p
iperidinomethylsalicylaldehyde 3,5-di-t-butyl-4-hy
Droxybenzoylhydrazone) Yield: 51% (property) pale yellow crystals (mp.193-213 ℃) PMR (DMSO- d 6, δ ppm): 11.78 (1H, brs), 10.87 (1H, brs),
8.62 (1H, brs), 7.67 (2H, s), 7.57 (1H, brs), 7.04 (1H, s), 6.
92 (1H, s), 3.81 (3H, s), 3.35 (2H, s), 2.36-2.26 (4H, m), 1.5
5-1.40 (6H, m), 1.43 (18H, s) IR (KBr, cm -1 ): 3444,2937,1645,1539,1464,1435,1392,1
369,1301,1263,1236,1162,1115,1039,1010,992,889,86
5,844,701

【0306】実施例182 3−メトキシ−5−モルホ
リノメチルサリチルアルデヒド3,5−ジ−t−ブチル
−4−ヒドロキシベンゾイルヒドラゾン(3-methoxy-5-m
orpholinomethylsalicylaldehyde 3,5-di-t-butyl-4-hy
droxybenzoylhydrazone) 収率:67% (物性) 淡黄色結晶(mp.208-218 ℃) PMR(DMSO-d6,δ ppm) : 11.79(1H,brs),10.90(1H,brs),
8.63(1H,brs),7.67(2H,s),7.55(1H,brs),7.06(1H,s),6.
95(1H,s),3.82(3H,s),3.61-3.55(4H,m),3.40(2H,s),2.3
9-2.32(4H,m),1.43(18H,s) IR(KBr, cm-1):3444,3235,2957,1642,1548,1463,1455,1
435,1392,1364,1237,1162,1114,1069,1002,912,867,702
Example 182 3-Methoxy-5-morpholinomethylsalicylaldehyde 3,5-di-tert-butyl-4-hydroxybenzoylhydrazone (3-methoxy-5-m
orpholinomethylsalicylaldehyde 3,5-di-t-butyl-4-hy
droxybenzoylhydrazone) Yield: 67% (physical properties) pale yellow crystal (mp.208-218 ° C) PMR (DMSO-d 6 , δ ppm): 11.79 (1H, brs), 10.90 (1H, brs),
8.63 (1H, brs), 7.67 (2H, s), 7.55 (1H, brs), 7.06 (1H, s), 6.
95 (1H, s), 3.82 (3H, s), 3.61-3.55 (4H, m), 3.40 (2H, s), 2.3
9-2.32 (4H, m), 1.43 (18H, s) IR (KBr, cm -1 ): 3444,3235,2957,1642,1548,1463,1455,1
435,1392,1364,1237,1162,1114,1069,1002,912,867,702

【0307】実施例183 5−(4−エチル−1−ピ
ペラジニル)メチル−3−メトキシサリチルアルデヒド
3,5−ジ−t−ブチル−4−ヒドロキシベンゾイルヒ
ドラゾン(5-(4-ethyl-1-piperazinyl)methyl-3-methoxy
salicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhyd
razone) 収率:63% (物性) 淡黄色結晶(mp.201-210 ℃) PMR(DMSO-d6,δ ppm) : 11.78(1H,brs),10.92(1H,brs),
8.62(1H,brs),7.68(2H,s),7.56(1H,brs),7.03(1H,s),6.
93(1H,s),3.82(3H,s),3.39(2H,s),2.46-2.25(10H,m),1.
43(18H,s),0.98(3H,t,J=7.3Hz) IR(KBr, cm-1):3444,3252,2955,2813,1646,1539,1463,1
454,1435,1393,1365,1302,1236,1164,1118,1004,943,88
8,803
Example 183 5- (4-Ethyl-1-piperazinyl) methyl-3-methoxysalicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone (5- (4-ethyl-1-piperazinyl) ) methyl-3-methoxy
salicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhyd
Razone) Yield: 63% (property) pale yellow crystals (mp.201-210 ℃) PMR (DMSO- d 6, δ ppm): 11.78 (1H, brs), 10.92 (1H, brs),
8.62 (1H, brs), 7.68 (2H, s), 7.56 (1H, brs), 7.03 (1H, s), 6.
93 (1H, s), 3.82 (3H, s), 3.39 (2H, s), 2.46-2.25 (10H, m), 1.
43 (18H, s), 0.98 (3H, t, J = 7.3Hz) IR (KBr, cm -1 ): 3444,3252,2955,2813,1646,1539,1463,1
454,1435,1393,1365,1302,1236,1164,1118,1004,943,88
8,803

【0308】実施例184 6−イソプロポキシ−4−
モルホリノサリチルアルデヒド6−ヒドロキシ−2,
5,7,8−テトラメチルクロマン−2−アセチルヒド
ラゾン(6-isopropoxy-4-morpholinosalicylaldehyde 6-
hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazo
ne) 参考例2で合成した化合物6−ヒドロキシ−2,5,
7,8−テトラメチルクロマン−2−アセトヒドラジド
1.11g(4mmol)及び6−イソプロポキシ−4−モルホリノ
サリチルアルデヒド1.06g(4mmol)を2−プロパノール 3
0ml に溶かし、18時間加熱還流した。溶媒を留去し、残
渣をシリカゲルカラムクロマトグラフィーに付した。酢
酸エチル:n−ヘキサン=3:2溶出部を溶媒留去し、
酢酸エチルを加えて結晶化させ、ろ取した。減圧下で乾
燥し、標記化合物 1.57g (収率75%)を得た。
Example 184 6-Isopropoxy-4-
Morpholinosalicylaldehyde 6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetylhydrazone (6-isopropoxy-4-morpholinosalicylaldehyde 6-
hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazo
ne) Compound 6-hydroxy-2,5, synthesized in Reference Example 2
7,8-tetramethylchroman-2-acetohydrazide
1.11 g (4 mmol) and 1.06 g (4 mmol) of 6-isopropoxy-4-morpholinosalicylaldehyde were added to 2-propanol 3
The mixture was dissolved in 0 ml and heated under reflux for 18 hours. The solvent was distilled off, and the residue was subjected to silica gel column chromatography. Ethyl acetate: n-hexane = 3: 2 The eluted part was evaporated,
Ethyl acetate was added for crystallization and collected by filtration. Drying under reduced pressure gave 1.57 g (yield 75%) of the title compound.

【0309】(物性) 無色結晶(mp.207-210 ℃) PMR(DMSO-d6,δ ppm) : 12.01(1H,s),11.37(1H,s),8.46
(1H,s),7.39(1H,s),6.10(1H,d,J=1.6Hz),6.00(1H,d,J=
1.6Hz),4.68(1H,sept,J=5.9Hz),3.73-3.67(4H,m),3.22-
3,17(4H,m),2.65-2.38(4H,m),2.05(3H,s),2.035(3H,s),
1.97(3H,s),2.04-1.95(1H,m),1.90-1.78(1H,m),1.34(3
H,s),1.28(6H,d,J=5.9Hz) IR(KBr, cm-1):3418,1973,2857,1676,1625,1598,1549,1
505,1447,1377,1338,1267,1236,1197,1172,1124,1113,1
087,1062,1006,930,922,884,671
(Physical properties) Colorless crystals (mp. 207-210 ° C.) PMR (DMSO-d 6 , δ ppm): 12.01 (1H, s), 11.37 (1H, s), 8.46
(1H, s), 7.39 (1H, s), 6.10 (1H, d, J = 1.6Hz), 6.00 (1H, d, J =
1.6Hz), 4.68 (1H, sept, J = 5.9Hz), 3.73-3.67 (4H, m), 3.22-
3,17 (4H, m), 2.65-2.38 (4H, m), 2.05 (3H, s), 2.035 (3H, s),
1.97 (3H, s), 2.04-1.95 (1H, m), 1.90-1.78 (1H, m), 1.34 (3H
H, s), 1.28 (6H, d, J = 5.9Hz) IR (KBr, cm -1 ): 3418,1973,2857,1676,1625,1598,1549,1
505,1447,1377,1338,1267,1236,1197,1172,1124,1113,1
087,1062,1006,930,922,884,671

【0310】実施例185〜188 6−イソプロポキシ−4−モルホリノサリチルアルデヒ
ドを他のアルデヒド化合物に代える以外は実施例184
と実質的に同様に処理して、以下の化合物を製造した。 実施例185 4−N−(イソプロポキシカルボニルメ
チル)イソプロピルアミノサリチルアルデヒド6−ヒド
ロキシ−2,5,7,8−テトラメチルクロマン−2−
アセチルヒドラゾン(4-N-(isopropoxycarbonylmethyl)i
sopropylaminosalicylaldehyde 6-hydroxy-2,5,7,8-tet
ramethylchroman-2-acetylhydrazone) 収率:97% (物性) 淡紫色不定形固体 PMR(DMSO-d6,δ ppm) : 11.34,10.1
1(1H,each−s),11.32,11.08
(1H,each−s),8.13,8.06(1H,
each−s),7.40,7.34(1H,each
−s),7.18,7.16(1H,each−d,J
=8.8Hz),6.20,6.17(1H,each
−dd,J=2.5and8.8Hz),6.08,
6.07(1H,each−d,J=2.5Hz),
5.00−4.90(1H,m),4.20−4.07
(1H,m),3.99,3.95(2H,each−
s),2.84−2.39(4H,m),2.07−
1.78(11H,m),1.34,1.33(3H,
each−s),1.27,(6H,d,J=6.4H
z),1.14(6H,d,J=6.4Hz)
Examples 185 to 188 Example 184 was repeated except that 6-isopropoxy-4-morpholinosalicylaldehyde was replaced by another aldehyde compound.
The following compounds were prepared in substantially the same manner as described above. Example 185 4-N- (isopropoxycarbonylmethyl) isopropylaminosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-
Acetylhydrazone (4-N- (isopropoxycarbonylmethyl) i
sopropylaminosalicylaldehyde 6-hydroxy-2,5,7,8-tet
ramethylchroman-2-acetylhydrazone) Yield: 97% (physical properties) Pale purple amorphous solid PMR (DMSO-d 6 , δ ppm): 11.34, 10.1
1 (1H, each-s), 11.32, 11.08
(1H, etch-s), 8.13, 8.06 (1H,
each-s), 7.40,7.34 (1H, each
-S), 7.18, 7.16 (1H, reach-d, J
= 8.8 Hz), 6.20, 6.17 (1H, each)
−dd, J = 2.5 and 8.8 Hz), 6.08,
6.07 (1H, each-d, J = 2.5Hz),
5.00-4.90 (1H, m), 4.20-4.07
(1H, m), 3.99, 3.95 (2H, each-
s), 2.84-2.39 (4H, m), 2.07-
1.78 (11H, m), 1.34, 1.33 (3H,
each-s), 1.27, (6H, d, J = 6.4H)
z), 1.14 (6H, d, J = 6.4 Hz)

【0311】実施例186 4−N−(メトキシカルボ
ニルメチル)イソプロピルアミノサリチルアルデヒド6
−ヒドロキシ−2,5,7,8−テトラメチルクロマン
−2−アセチルヒドラゾン(4−N−(methoxy
carbonylmethyl)isopropyla
minosalicylaldehyde 6−hyd
roxy−2,5,7,8−tetramethylc
hroman−2−acetylhydrazone) 収率:45% (物性) 淡紫色不定形固体 PMR(DMSO-d6,δ ppm) : 11.33,10.11(1H,each-s),11.3
2,11.08(1H,each-s),8.14,8.06(1H,each-s),7.41,7.36
(1H,each-s),7.19,7.176(1H,each-d,J=8.8Hz),6.22,6.1
8(1H,each-dd,J=2.0 and 8.8Hz),6.085,6.05(1H,each-
d,J=2.0Hz),4.21-4.08(1H,m),4.06,4.02(2H,each-s),3.
68(3H,s),2.84-2.39(4H,m),2.06-1.78(11H,m),1.34,1.3
3(3H,each-s),1.13(6H,d,J=6.4Hz)
Example 186 4-N- (methoxycarbonylmethyl) isopropylaminosalicylaldehyde 6
-Hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (4-N- (methoxy
carbonylmethyl) isopropyla
minosalicylaldehyde 6-hyd
roxy-2,5,7,8-tetramethylc
roman-2-acetylhydrazine) Yield: 45% (physical properties) Light purple amorphous solid PMR (DMSO-d 6 , δ ppm): 11.33, 10.11 (1H, each-s), 11.3
2,11.08 (1H, each-s), 8.14,8.06 (1H, each-s), 7.41,7.36
(1H, each-s), 7.19,7.176 (1H, each-d, J = 8.8Hz), 6.22,6.1
8 (1H, each-dd, J = 2.0 and 8.8Hz), 6.085,6.05 (1H, each-dd
d, J = 2.0Hz), 4.21-4.08 (1H, m), 4.06,4.02 (2H, each-s), 3.
68 (3H, s), 2.84-2.39 (4H, m), 2.06-1.78 (11H, m), 1.34,1.3
3 (3H, each-s), 1.13 (6H, d, J = 6.4Hz)

【0312】実施例187 4−イソプロポキシ−6−
モルホリノサリチルアルデヒド6−ヒドロキシ−2,
5,7,8−テトラメチルクロマン−2−アセチルヒド
ラゾン(4-isopropoxy-6-morpholinosalicylaldehyde 6-
hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazo
ne) 収率:86% (物性) 淡黄色結晶(mp.122-124 ℃) PMR(DMSO-d6,δ ppm): 12.21,11.17(1H,each-s),11.50,
11.41(1H,each-s),8.52,8.41(1H,each-s),7.41,7.35(1
H,each-s),6.19,6.16(1H,each-d,J=2.0Hz),6.12,6.10(1
H,each-d,J=2.0Hz),4.64(1H,sept,J=6.3Hz),3.80-3.74
(4H,m),2.87-2.80(4H,m),2.63-2.41(4H,m),2.07-1.80(1
1H,m), 1.34(3H,s),1.26(6H,d,J=6.3Hz) IR(KBr, cm-1):3418,2974,2929,2857,1669,1653,1622,1
597,1567,1452,1373,1343,1333,1260,1213,1180,1160,1
113,1010,923,871,832
Example 187 4-Isopropoxy-6-
Morpholinosalicylaldehyde 6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetylhydrazone (4-isopropoxy-6-morpholinosalicylaldehyde 6-
hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazo
ne) Yield: 86% (property) pale yellow crystals (mp.122-124 ℃) PMR (DMSO- d 6, δ ppm): 12.21,11.17 (1H, each-s), 11.50,
11.41 (1H, each-s), 8.52,8.41 (1H, each-s), 7.41,7.35 (1
H, each-s), 6.19,6.16 (1H, each-d, J = 2.0Hz), 6.12,6.10 (1
H, each-d, J = 2.0Hz), 4.64 (1H, sept, J = 6.3Hz), 3.80-3.74
(4H, m), 2.87-2.80 (4H, m), 2.63-2.41 (4H, m), 2.07-1.80 (1
1H, m), 1.34 (3H, s), 1.26 (6H, d, J = 6.3Hz) IR (KBr, cm -1 ): 3418,2974,2929,2857,1669,1653,1622,1
597,1567,1452,1373,1343,1333,1260,1213,1180,1160,1
113,1010,923,871,832

【0313】実施例188 5−ジエチルアミノサリチ
ルアルデヒド6−ヒドロキシ−2,5,7,8−テトラ
メチルクロマン−2−アセチルヒドラゾン(5-diethylam
inosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylch
roman-2-acetylhydrazone) 収率:45% (物性) 黄褐色不定形固体 PMR(DMSO-d6,δ ppm) : 11.50,11.28(1H,each-s),10.3
8,9.26(1H,each-s),8.29,8.20(1H,each-s),7.40,7.34(1
H,each-s),6.94-6.64(3H,m),3.27-3.15(4H,m),3.00-2.4
3(4H,m),2.07-1.79(11H,m),1.35,1.33(3H,each-s),1.06
-0.98(6H,m)
Example 188 5-Diethylaminosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone
inosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylch
roman-2-acetylhydrazone) Yield: 45% (Physical properties) Yellowish brown amorphous solid PMR (DMSO-d 6 , δ ppm): 11.50, 11.28 (1H, each-s), 10.3
8,9.26 (1H, each-s), 8.29,8.20 (1H, each-s), 7.40,7.34 (1
H, each-s), 6.94-6.64 (3H, m), 3.27-3.15 (4H, m), 3.00-2.4
3 (4H, m), 2.07-1.79 (11H, m), 1.35,1.33 (3H, each-s), 1.06
-0.98 (6H, m)

【0314】実施例189 3,5−ジブロモサリチル
アルデヒド6−ヒドロキシ−2,5,7,8−テトラメ
チルクロマン−2−アセチルヒドラゾン(3,5-dibromosa
licylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman
-2-acetylhydrazone) 参考例2で合成した化合物6−ヒドロキシ−2,5,
7,8−テトラメチルクロマン−2−アセトヒドラジド
1.67g(6mmol)及び3,5−ジブロモサリチルアルデヒド
1.68g(6mmol) をエタノール30mlに溶かし、室温下で18
時間攪拌した。析出した結晶をろ取し、減圧下で乾燥
し、標記化合物 2.61g (収率80%)を得た。 (物性) 淡黄色結晶(mp.222-228 ℃) PMR(DMSO-d6,δ ppm) : 12.60,10.73(1H,each-s),12.0
0,11.59(1H,each-s),8.27,8.13(1H,each-s),7.77,7.61
(2H,each-s),7.41,7.27(1H,each-s),2.98-2.48(4H,m),
2.06-1.79(11H,m),1.35(3H,s) IR(KBr, cm-1):3448,3198,3059,2970,2939,1666,1609,1
560,1444,1378,1345,1251,1195,1172,1085,926,859,73
8,687
Example 189 3,5-Dibromosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (3,5-dibromosa
licylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman
2-acetylhydrazone) Compound 6-hydroxy-2,5 synthesized in Reference Example 2.
7,8-tetramethylchroman-2-acetohydrazide
1.67 g (6 mmol) and 3,5-dibromosalicylaldehyde
Dissolve 1.68 g (6 mmol) in 30 ml of ethanol, and add
Stirred for hours. The precipitated crystals were collected by filtration and dried under reduced pressure to give the title compound (2.61 g, yield 80%). (Physical properties) pale yellow crystal (mp.222-228 ° C) PMR (DMSO-d 6 , δ ppm): 12.60,10.73 (1H, each-s), 12.0
0,11.59 (1H, each-s), 8.27,8.13 (1H, each-s), 7.77,7.61
(2H, each-s), 7.41,7.27 (1H, each-s), 2.98-2.48 (4H, m),
2.06-1.79 (11H, m), 1.35 (3H, s) IR (KBr, cm -1 ): 3448,3198,3059,2970,2939,1666,1609,1
560,1444,1378,1345,1251,1195,1172,1085,926,859,73
8,687

【0315】実施例190〜192 3,5−ジブロモサリチルアルデヒドを他のアルデヒド
化合物に代える以外は実施例189と実質的に同様に処
理して、以下の化合物を製造した。 実施例190 3−メトキシ−5−ピペリジノメチルサ
リチルアルデヒド6−ヒドロキシ−2,5,7,8−テ
トラメチルクロマン−2−アセチルヒドラゾン(3-metho
xy-5-piperidinomethylsalicylaldehyde 6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetylhydrazone) 収率:68% (物性) 淡黄色結晶(mp.162-170 ℃) PMR(DMSO-d6,δ ppm) : 11.53,11.30(1H,each-s),10.6
2,9.34(1H,each-s),8.33,8.26(1H,each-s),7.41,7.37(1
H,each-s),7.03,7.01(1H,each-d,J=1.2Hz),6.91,6.85(1
H,each-d,J=1.2Hz),3.80,3.79(3H,each-s),3.32,3.30(2
H,each-s),2.93-2.42(4H,m),2.36-2.25(4H,m),2.05-1.7
8(11H,m),1.55-1.34(6H,m),1.35(3H,s) IR(KBr, cm-1):3433,3197,3054,2934,1661,1463,1373,1
262,1197,1162,1109,1087,1037,991,950,855,779,753,7
31
Examples 190 to 192 The following compounds were prepared in substantially the same manner as in Example 189 except that 3,5-dibromosalicylaldehyde was replaced with another aldehyde compound. Example 190 3-methoxy-5-piperidinomethylsalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (3-metho
xy-5-piperidinomethylsalicylaldehyde 6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetylhydrazone) Yield: 68% (property) pale yellow crystals (mp.162-170 ℃) PMR (DMSO- d 6, δ ppm): 11.53,11.30 (1H, each- s), 10.6
2,9.34 (1H, each-s), 8.33,8.26 (1H, each-s), 7.41,7.37 (1
H, each-s), 7.03,7.01 (1H, each-d, J = 1.2Hz), 6.91,6.85 (1
H, each-d, J = 1.2Hz), 3.80,3.79 (3H, each-s), 3.32,3.30 (2
H, each-s), 2.93-2.42 (4H, m), 2.36-2.25 (4H, m), 2.05-1.7
8 (11H, m), 1.55-1.34 (6H, m), 1.35 (3H, s) IR (KBr, cm -1 ): 3433,3197,3054,2934,1661,1463,1373,1
262,1197,1162,1109,1087,1037,991,950,855,779,753,7
31

【0316】実施例191 3−メトキシ−5−モルホ
リノメチルサリチルアルデヒド6−ヒドロキシ−2,
5,7,8−テトラメチルクロマン−2−アセチルヒド
ラゾン(3-methoxy-5-morpholinomethylsalicylaldehyde
6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydr
azone) 収率:82% (物性) 無色結晶(mp.146-150 ℃) PMR(DMSO-d6,δ ppm) : 11.53,11.30(1H,each-s),10.6
3,9.37(1H,each-s),8.33,8.25(1H,each-s),7.41,7.36(1
H,each-s),7.05,7.03(1H,each-d,J=1.2Hz),6.93,6.87(1
H,each-d,J=1.2Hz),3.81,3.80(3H,each-s),3.60-3.53(4
H,m),3.37,3.34(2H,each-s),2.92-2.43(4H,m),2.37-2.3
0(4H,m),2.05-1.78(11H,m),1.34(3H,s) IR(KBr, cm-1):3427,3200,2931,1662,1557,1456,1368,1
262,1196,1163,1113,1087,1033,1004,914,866,794,752,
731
Example 191 3-Methoxy-5-morpholinomethylsalicylaldehyde 6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetylhydrazone (3-methoxy-5-morpholinomethylsalicylaldehyde
6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydr
azone) Yield: 82% (physical properties) Colorless crystals (mp. 146-150 ° C) PMR (DMSO-d 6 , δ ppm): 11.53, 11.30 (1H, each-s), 10.6
3,9.37 (1H, each-s), 8.33,8.25 (1H, each-s), 7.41,7.36 (1
H, each-s), 7.05,7.03 (1H, each-d, J = 1.2Hz), 6.93,6.87 (1
H, each-d, J = 1.2Hz), 3.81,3.80 (3H, each-s), 3.60-3.53 (4
H, m), 3.37,3.34 (2H, each-s), 2.92-2.43 (4H, m), 2.37-2.3
0 (4H, m), 2.05-1.78 (11H, m), 1.34 (3H, s) IR (KBr, cm -1 ): 3427,3200,2931,1662,1557,1456,1368,1
262,1196,1163,1113,1087,1033,1004,914,866,794,752,
731

【0317】実施例192 5−(4−エチル−1−ピ
ペラジニル)メチル−3−メトキシサリチルアルデヒド
6−ヒドロキシ−2,5,7,8−テトラメチルクロマ
ン−2−アセチルヒドラゾン(5-(4-ethyl-1-piperaziny
l)methyl-3-methoxysalicylaldehyde 6-hydroxy-2,5,7,
8-tetramethylchroman-2-acetylhydrazone) 収率:73% (物性) 淡黄色結晶(mp.175-182 ℃) PMR(DMSO-d6,δ ppm) : 11.53,11.30(1H,each-s),10.6
4,9.36(1H,each-s),8.33,8.26(1H,each-s),7.41,7.39(1
H,each-s),7.02(1H,d,J=1.2Hz),6.92,6.85(1H,each-d,J
=1.2Hz),3.80,3.79(3H,each-s),3.36,3.33(2H,each-s),
2.92-2.24(12H,m),2.05-1.78(11H,m),1.35(3H,s),1.00-
0.94(3H,m) IR(KBr, cm-1):3427,3196,2971,2933,2821,1680,1661,1
557,1463,1377,1263,1198,1162,1087,1009,803
Example 192 5- (4-Ethyl-1-piperazinyl) methyl-3-methoxysalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone (5- (4- ethyl-1-piperaziny
l) methyl-3-methoxysalicylaldehyde 6-hydroxy-2,5,7,
8-tetramethylchroman-2-acetylhydrazone) Yield: 73% (property) pale yellow crystals (mp.175-182 ℃) PMR (DMSO- d 6, δ ppm): 11.53,11.30 (1H, each-s), 10.6
4,9.36 (1H, each-s), 8.33,8.26 (1H, each-s), 7.41,7.39 (1
H, each-s), 7.02 (1H, d, J = 1.2Hz), 6.92,6.85 (1H, each-d, J
= 1.2Hz), 3.80,3.79 (3H, each-s), 3.36,3.33 (2H, each-s),
2.92-2.24 (12H, m), 2.05-1.78 (11H, m), 1.35 (3H, s), 1.00-
0.94 (3H, m) IR (KBr, cm -1 ): 3427,3196,2971,2933,2821,1680,1661,1
557,1463,1377,1263,1198,1162,1087,1009,803

【0318】実施例193 N’−(2−ヒドロキシ−
4−イソプロポキシベンジル)−3,5−ジ−t−ブチ
ル−4−ヒドロキシベンゾヒドラジド(N'-(2-hydroxy-4
-isopropoxybenzyl)-3,5-di-t-butyl-4-hydroxybenzohy
drazide) 4−イソプロポキシサリチルアルデヒド3,5−ジ−t
−ブチル−4−ヒドロキシベンゾイルヒドラゾン3.98g
(9.3mmol)のメタノール70ml溶液に氷冷下水素化ホウ素
ナトリウム12.0g(mmol) の水溶液30mlを滴下し、更に1
時間氷冷下撹拌した後、室温で16時間撹拌した。溶媒
を留去し、残渣に水を加え、濃塩酸で中和し、析出した
結晶をろ取した。結晶に水を加え、酢酸エチルで抽出し
た。酢酸エチル層を水、飽和食塩水で洗浄後、硫酸マグ
ネシウムで乾燥し、溶媒を留去した。残渣にヘキサン:
酢酸エチル=2:1の混合溶媒を加えて結晶化させ、そ
れをろ取した。減圧下で乾燥し、標記化合物 2.91g (収
率73%)を得た。
Example 193 N ′-(2-hydroxy-
4-Isopropoxybenzyl) -3,5-di-t-butyl-4-hydroxybenzohydrazide (N '-(2-hydroxy-4
-isopropoxybenzyl) -3,5-di-t-butyl-4-hydroxybenzohy
drazide) 4-Isopropoxysalicylaldehyde 3,5-di-t
-Butyl-4-hydroxybenzoylhydrazone 3.98 g
30 ml of an aqueous solution of 12.0 g (mmol) of sodium borohydride was added dropwise to a 70 ml solution of (9.3 mmol) in methanol under ice-cooling.
After stirring under ice-cooling for an hour, the mixture was stirred at room temperature for 16 hours. The solvent was distilled off, water was added to the residue, the mixture was neutralized with concentrated hydrochloric acid, and the precipitated crystals were collected by filtration. Water was added to the crystals and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. Hexane in the residue:
Crystallization was performed by adding a mixed solvent of ethyl acetate = 2: 1, which was collected by filtration. Drying under reduced pressure gave 2.91 g (yield 73%) of the title compound.

【0319】(物性) 無色結晶(mp.149-153 ℃) PMR(DMSO-d6,δ ppm) : 9.97(1H,d,J=5.4Hz),9.71(1H,
s),7.58(2H,s),7.38(1H,s),7.03(1H,d,J=8.3Hz),6.345
(1H,d,J=2.5Hz),6.29(1H,dd,J=2.5 and 8.3Hz),5.31(1
H,q,J=5.4Hz),4.49(1H,sept,J=5.8Hz),3.84(2H,d,J=5.4
Hz),1.40(18H,s),1.24(6H,d,J=5.8) IR(KBr, cm-1):3634,3284,2960,2872,1628,1586,1540,1
506,1430,1313,1240,1160,1120,1105,992,924,888,843,
800,698,635,
(Physical properties) Colorless crystals (mp. 149-153 ° C.) PMR (DMSO-d 6 , δ ppm): 9.97 (1H, d, J = 5.4 Hz), 9.71 (1H,
s), 7.58 (2H, s), 7.38 (1H, s), 7.03 (1H, d, J = 8.3Hz), 6.345
(1H, d, J = 2.5Hz), 6.29 (1H, dd, J = 2.5 and 8.3Hz), 5.31 (1
H, q, J = 5.4Hz), 4.49 (1H, sept, J = 5.8Hz), 3.84 (2H, d, J = 5.4
Hz), 1.40 (18H, s), 1.24 (6H, d, J = 5.8) IR (KBr, cm -1 ): 3634,3284,2960,2872,1628,1586,1540,1
506,1430,1313,1240,1160,1120,1105,992,924,888,843,
800,698,635,

【0320】実施例194 N’−(4−ジエチルアミ
ノ−2−ヒドロキシベンジル)−3,5−ジ−t−ブチ
ル−4−ヒドロキシベンゾヒドラジド(N'-(4-diethylam
ino-2-hydroxybenzyl)-3,5-di-t-butyl-4-hydroxybenzo
hydrazide) 4−ジエチルアミノサリチルアルデヒド3,5−ジ−t
−ブチル−4−ヒドロキシベンゾイルヒドラゾン 1.32g
(3mmol) 及びシアノ水素化ホウ素ナトリウム0.754g(12m
mol)のTHF30ml 溶液に室温下p−トルエンスルホン酸の
THF溶液10mlを滴下した。室温で3時間撹拌した後、
濃塩酸で酸性とし、溶媒を留去した。残渣を飽和重曹水
で中和し、酢酸エチルで抽出した。酢酸エチル層を水、
飽和食塩水で洗浄後、硫酸マグネシウムで乾燥し、溶媒
を留去した。残渣をシリカゲルカラムクロマトグラフィ
ーに付し、ヘキサン:酢酸エチル=1:1溶出部を溶媒
留去し、標記化合物 0.23g (収率17%)を得た。 (物性) 淡褐色不定形固体 PMR(DMSO-d6,δ ppm) : 9.96(1H,brs),9.33(1H,s),7.59
(2H,s),7.35(1H,brs),6.90(1H,d,J=8.3Hz),6.14(1H,d,J
=2.5Hz),6.07(1H,dd,J=2.5 and 8.3Hz),5.23-5.14(1H,
m),3.82-3.78(2H,m),3.26(4H,q,J=7.1Hz),1.40(18H,s),
1.07(6H,t,J=7.1Hz)
Example 194 N '-(4-diethylamino-2-hydroxybenzyl) -3,5-di-t-butyl-4-hydroxybenzohydrazide (N'-(4-diethylam
ino-2-hydroxybenzyl) -3,5-di-t-butyl-4-hydroxybenzo
hydrazide) 4-diethylaminosalicylaldehyde 3,5-di-t
-Butyl-4-hydroxybenzoylhydrazone 1.32 g
(3 mmol) and 0.754 g of sodium cyanoborohydride (12 m
mol) in THF (30 ml) at room temperature was added dropwise with p-toluenesulfonic acid in THF (10 ml). After stirring for 3 hours at room temperature,
The mixture was acidified with concentrated hydrochloric acid, and the solvent was distilled off. The residue was neutralized with saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate. Ethyl acetate layer with water,
After washing with a saturated saline solution, it was dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the hexane: ethyl acetate = 1: 1 eluate was evaporated to give 0.23 g (yield 17%) of the title compound. (Physical properties) Light brown amorphous solid PMR (DMSO-d 6 , δ ppm): 9.96 (1H, brs), 9.33 (1H, s), 7.59
(2H, s), 7.35 (1H, brs), 6.90 (1H, d, J = 8.3Hz), 6.14 (1H, d, J
= 2.5Hz), 6.07 (1H, dd, J = 2.5 and 8.3Hz), 5.23-5.14 (1H,
m), 3.82-3.78 (2H, m), 3.26 (4H, q, J = 7.1Hz), 1.40 (18H, s),
1.07 (6H, t, J = 7.1Hz)

【0321】実施例195 N’−[2−ヒドロキシ−
4−N−(メトキシカルボニルメチル)シクロペンチル
アミノベンジル]−3,5−ジ−t−ブチル−4−ヒド
ロキシベンゾヒドラジド(N'-[2-hydroxy-4-N-(methoxyc
arbonylmethyl)cyclopentylaminobenzyl)-3,5-di-t-but
yl-4-hydroxybenzohydrazide) 4−N−(メトキシカルボニルメチル)シクロペンチル
アミノサリチルアルデヒド3,5−ジ−t−ブチル−4
−ヒドロキシベンゾイルヒドラゾン1.06g(2mmol)及びシ
アノ水素化ホウ素ナトリウム0.503g(8mmol) のTHF20
ml溶液を1N塩酸溶液でpH4に調整し、室温で3時間
撹拌した後、濃塩酸で酸性とし、溶媒を留去した。残渣
を飽和重曹水で中和し、酢酸エチルで抽出した。酢酸エ
チル層を水、飽和食塩水で洗浄後、硫酸マグネシウムで
乾燥し、溶媒を留去した。残渣をシリカゲルカラムクロ
マトグラフィーに付し、ヘキサン:酢酸エチル=1:1
溶出部を溶媒留去し、標記化合物 0.5g(収率47%)を得
た。
Example 195 N ′-[2-hydroxy-
4-N- (methoxycarbonylmethyl) cyclopentylaminobenzyl] -3,5-di-t-butyl-4-hydroxybenzohydrazide (N '-[2-hydroxy-4-N- (methoxyc
arbonylmethyl) cyclopentylaminobenzyl) -3,5-di-t-but
yl-4-hydroxybenzohydrazide) 4-N- (methoxycarbonylmethyl) cyclopentylaminosalicylaldehyde 3,5-di-t-butyl-4
1.06 g (2 mmol) of hydroxybenzoylhydrazone and 0.503 g (8 mmol) of sodium cyanoborohydride in THF20
The ml solution was adjusted to pH 4 with a 1N hydrochloric acid solution, stirred at room temperature for 3 hours, acidified with concentrated hydrochloric acid, and the solvent was distilled off. The residue was neutralized with saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and hexane: ethyl acetate = 1: 1.
The solvent was distilled off from the eluted portion to obtain 0.5 g (yield 47%) of the title compound.

【0322】(物性) 無色不定形固体 PMR(DMSO-d6,δ ppm) : 9.97(1H,brs),9.41(1H,s),7.58
(2H,s),7.36(1H,s),6.92(1H,d,J=8.3Hz),6.14(1H,d,J=
2.5Hz),6.09(1H,dd,J=2.5 and 8.3Hz),5.25-5.17(1H,
m),4.12-4.00(1H,m),3.95(2H,s),3.65(3H,s),1.92-1.78
(2H,m),1.71-1.35(6H,m),1.40(18H,s)
(Physical properties) Colorless amorphous solid PMR (DMSO-d 6 , δ ppm): 9.97 (1H, brs), 9.41 (1H, s), 7.58
(2H, s), 7.36 (1H, s), 6.92 (1H, d, J = 8.3Hz), 6.14 (1H, d, J =
2.5Hz), 6.09 (1H, dd, J = 2.5 and 8.3Hz), 5.25-5.17 (1H,
m), 4.12-4.00 (1H, m), 3.95 (2H, s), 3.65 (3H, s), 1.92-1.78
(2H, m), 1.71-1.35 (6H, m), 1.40 (18H, s)

【0323】実施例196 N’−(5−ブロモ−2−
ヒドロキシ−3−メトキシベンジル)−3,5−ジ−t
−ブチル−4−ヒドロキシベンゾヒドラジド(N'-(5-bro
mo-2-hydroxy-3-methoxybenzyl)-3,5-di-t-butyl-4-hyd
roxybenzohydrazide) 5−ブロモ−3−メトキシサリチルアルデヒド3,5−
ジ−t−ブチル−4−ヒドロキシベンゾイルヒドラゾン
2.39g (5mmol) のメタノール70ml溶液に氷冷下水素化ホ
ウ素ナトリウム9.55g(25mmol) の水溶液30mlを滴下し、
更に1時間氷冷下撹拌した後、室温で16時間撹拌し
た。溶媒を留去し、残渣に水を加え、濃塩酸で酸性とし
た後、飽和重曹水で中和し、酢酸エチルで抽出した。酢
酸エチル層を水、飽和食塩水で洗浄後、硫酸マグネシウ
ムで乾燥し、溶媒を留去した。残渣にヘキサン:酢酸エ
チル=1:1の混合溶媒を加えて結晶化させ、それをろ
取した。減圧下で乾燥し、標記化合物 1.83g (収率76%)
を得た。
Example 196 N '-(5-bromo-2-
(Hydroxy-3-methoxybenzyl) -3,5-di-t
-Butyl-4-hydroxybenzohydrazide (N '-(5-bro
mo-2-hydroxy-3-methoxybenzyl) -3,5-di-t-butyl-4-hyd
roxybenzohydrazide) 5-bromo-3-methoxysalicylaldehyde 3,5-
Di-t-butyl-4-hydroxybenzoylhydrazone
30 ml of an aqueous solution of 9.55 g (25 mmol) of sodium borohydride was added dropwise to a solution of 2.39 g (5 mmol) in 70 ml of methanol under ice-cooling.
After stirring for 1 hour under ice-cooling, the mixture was stirred at room temperature for 16 hours. The solvent was distilled off, water was added to the residue, acidified with concentrated hydrochloric acid, neutralized with saturated aqueous sodium hydrogen carbonate, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The residue was crystallized by adding a mixed solvent of hexane: ethyl acetate = 1: 1, and collected by filtration. Dry under reduced pressure, 1.83 g of the title compound (76% yield)
I got

【0324】(物性) 無色結晶(mp.214-220 ℃) PMR(DMSO-d6,δ ppm) : 9.45(1H,d,J=6.0Hz),9.35(1H,
s),7.56(2H,s),7.36(1H,s),7.03-6.98(2H,m),5.46(1H,
q,J=6.0Hz),3.92(2H,d,J=6.0Hz),3.80(3H,s),1.40(18H,
s) IR(KBr, cm-1):3627,3293,3268,2956,1628,1600,1581,1
538,1486,1272,1239,1161,1119,1095,996,874,837,747,
699,654
(Physical properties) Colorless crystal (mp. 214-220 ° C.) PMR (DMSO-d 6 , δ ppm): 9.45 (1H, d, J = 6.0 Hz), 9.35 (1H,
s), 7.56 (2H, s), 7.36 (1H, s), 7.03-6.98 (2H, m), 5.46 (1H,
q, J = 6.0Hz), 3.92 (2H, d, J = 6.0Hz), 3.80 (3H, s), 1.40 (18H,
s) IR (KBr, cm -1 ): 3627,3293,3268,2956,1628,1600,1581,1
538,1486,1272,1239,1161,1119,1095,996,874,837,747,
699,654

【0325】実施例197 N’−(3,5−ジブロモ
−2−ヒドロキシベンジル)−3,5−ジ−t−ブチル
−4−ヒドロキシベンゾヒドラジド(N'-(3,5-dibromo-2
-hydroxybenzyl)-3,5-di-t-butyl-4-hydroxybenzohydra
zide) 3,5−ジブロモサリチルアルデヒド3,5−ジ−t−
ブチル−4−ヒドロキシベンゾイルヒドラゾン1.56g(2.
96mmol) のTHF50ml溶液にトリアセトキシ水素化ホウ
素ナトリウム2.51g(11.84mmol)を加え、室温で17時間
撹拌した。飽和重曹水で中和後、溶媒を留去した。残渣
に水を加え、酢酸エチルで抽出した。酢酸エチル層を
水、飽和食塩水で洗浄後、硫酸マグネシウムで乾燥し、
溶媒を留去した。残渣を酢酸エチルに溶解後、ヘキサン
を加えて結晶化させ、結晶をろ取した。減圧下で乾燥
し、標記化合物 1.32g (収率84%)を得た。 (物性) 無色結晶(mp.244-246 ℃) PMR(DMSO-d6,δ ppm) : 11.14(1H,brs),10.19(1H,s),7.
60(3H,s),7.44(1H,brs),7.35(1H,s),5.72(1H,brs),4.02
(2H,s),1.40(18H,s) IR(KBr, cm-1):3618,3294,3239,2959,1631,1599,1530,1
458,1432,1362,1342,1313,1276,1238,1155,1120,1089,1
026,989,956,899,858,771,685
Example 197 N '-(3,5-dibromo-2-hydroxybenzyl) -3,5-di-t-butyl-4-hydroxybenzohydrazide (N'-(3,5-dibromo-2
-hydroxybenzyl) -3,5-di-t-butyl-4-hydroxybenzohydra
zide) 3,5-dibromosalicylaldehyde 3,5-di-t-
1.56 g of butyl-4-hydroxybenzoylhydrazone (2.
961 mmol) in THF (50 ml) was added with sodium triacetoxyborohydride (2.51 g, 11.84 mmol), and the mixture was stirred at room temperature for 17 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated saline, and dried over magnesium sulfate.
The solvent was distilled off. After dissolving the residue in ethyl acetate, hexane was added for crystallization, and the crystals were collected by filtration. Drying under reduced pressure gave 1.32 g (yield 84%) of the title compound. (Physical properties) Colorless crystal (mp.244-246 ° C) PMR (DMSO-d 6 , δ ppm): 11.14 (1H, brs), 10.19 (1H, s), 7.
60 (3H, s), 7.44 (1H, brs), 7.35 (1H, s), 5.72 (1H, brs), 4.02
(2H, s), 1.40 (18H, s) IR (KBr, cm -1 ): 3618,3294,3239,2959,1631,1599,1530,1
458,1432,1362,1342,1313,1276,1238,1155,1120,1089,1
026,989,956,899,858,771,685

【0326】実施例198 N’−ピリドキシル−3,
5−ジ−t−ブチル−4−ヒドロキシベンゾヒドラジド
(N'-pyridoxyl-3,5-di-t-butyl-4-hydroxybenzohydrazi
de) ピリドキサール3,5−ジ−t−ブチル−4−ヒドロキ
シベンゾイルヒドラゾン 2.25g(5mmol) のTHF50ml溶
液にトリアセトキシ水素化ホウ素ナトリウム3.71g(17.5
mmol) を加え、室温で17時間撹拌した。飽和重曹水で
中和後、溶媒を留去した。残渣に水を加え、酢酸エチル
で抽出した。酢酸エチル層を水、飽和食塩水で洗浄後、
硫酸マグネシウムで乾燥し、溶媒を留去した。析出した
結晶をろ取し、少量の酢酸エチルで洗浄後、減圧下で乾
燥し、標記化合物 1.62g (収率78%)を得た。
Example 198 N′-pyridoxyl-3,
5-di-t-butyl-4-hydroxybenzohydrazide
(N'-pyridoxyl-3,5-di-t-butyl-4-hydroxybenzohydrazi
de) Pyridoxal 3,5-di-t-butyl-4-hydroxybenzoylhydrazone 2.25 g (5 mmol) in 50 ml of THF was added to 3.71 g (17.5 g) of sodium triacetoxyborohydride.
mmol) and stirred at room temperature for 17 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue and extracted with ethyl acetate. After washing the ethyl acetate layer with water and saturated saline,
After drying over magnesium sulfate, the solvent was distilled off. The precipitated crystals were collected by filtration, washed with a small amount of ethyl acetate, and dried under reduced pressure to give the title compound (1.62 g, yield 78%).

【0327】(物性) 無色結晶(mp.243-247 ℃) PMR(DMSO-d6,δ ppm) : 10.52(1H,brs),10.19(1H,s),7.
86(1H,s),7.61(2H,brs),7.45(1H,brs),5.62-5.55(1H,
m),5.08(1H,t,J=5.0Hz),4.49(2H,d,J=5.0Hz),4.09(2H,
d,J=5.6Hz),2.36(3H,s),1.41(18H,s) IR(KBr, cm-1):3311,3284,3107,2962,1637,1601,1567,1
433,1418,1361,1326,1302,1255,1237,1115,1097,1019,8
96,768,707
(Physical properties) Colorless crystal (mp. 243-247 ° C.) PMR (DMSO-d 6 , δ ppm): 10.52 (1H, brs), 10.19 (1H, s), 7.
86 (1H, s), 7.61 (2H, brs), 7.45 (1H, brs), 5.62-5.55 (1H,
m), 5.08 (1H, t, J = 5.0Hz), 4.49 (2H, d, J = 5.0Hz), 4.09 (2H,
d, J = 5.6Hz), 2.36 (3H, s), 1.41 (18H, s) IR (KBr, cm -1 ): 3311,3284,3107,2962,1637,1601,1567,1
433,1418,1361,1326,1302,1255,1237,1115,1097,1019,8
96,768,707

【0328】実施例199 N’−ピリドキシル−3,
5−ジ−t−ブチル−4−ヒドロキシベンゾヒドラジド
・塩酸塩(N'-pyridoxyl-3,5-di-t-butyl-4-hydroxybenz
ohydrazide hydrochloride) 実施例198で合成した化合物 1.77g(4.26mmol)のメタ
ノール20ml溶液に4N塩酸−酢酸エチル溶液1.27mlを加
え室温で撹拌した後、酢酸エチルを加えた。析出した結
晶をろ取し、減圧下で乾燥し、標記化合物 1.83g (収率
95%)を得た。 (物性) 無色結晶(mp.210-233(dec)℃) PMR(DMSO-d6,δ ppm) : 10.37(1H,brs),8.13(1H,s),7.6
1(2H,s),7.50(1H,s),4.69(2H,s),4.22(2H,s),2.60(3H,
s),1.40(18H,s) IR(KBr, cm-1):3623,3265,2957,2710,1638,1627,1600,1
469,1432,1391,1314,1242,1159,1120,1097,1014,887,85
5,766,742
Example 199 N′-pyridoxyl-3,
5-di-t-butyl-4-hydroxybenzohydrazide hydrochloride (N'-pyridoxyl-3,5-di-t-butyl-4-hydroxybenz
ohydrazide hydrochloride) To a solution of 1.77 g (4.26 mmol) of the compound synthesized in Example 198 in 20 ml of methanol was added 1.27 ml of a 4N hydrochloric acid-ethyl acetate solution, and the mixture was stirred at room temperature, and then ethyl acetate was added. The precipitated crystals were collected by filtration and dried under reduced pressure to give 1.83 g of the title compound (yield
95%). (Physical Properties) colorless crystals (mp.210-233 (dec) ℃) PMR (DMSO-d 6, δ ppm): 10.37 (1H, brs), 8.13 (1H, s), 7.6
1 (2H, s), 7.50 (1H, s), 4.69 (2H, s), 4.22 (2H, s), 2.60 (3H,
s), 1.40 (18H, s) IR (KBr, cm -1 ): 3623,3265,2957,2710,1638,1627,1600,1
469,1432,1391,1314,1242,1159,1120,1097,1014,887,85
5,766,742

【0329】実施例200 N’−(2−ヒドロキシ−
3−メトキシベンジル)−3,5−ジ−t−ブチル−4
−ヒドロキシベンゾヒドラジド(N'-(2-hydroxy-3-metho
xybenzyl)-3,5-di-t-butyl-4-hydroxybenzohydrazide) o−バニリン3,5−ジ−t−ブチル−4−ヒドロキシ
ベンゾイルヒドラゾン3.98g(10mmol)のTHF40ml溶液
にトリアセトキシ水素化ホウ素ナトリウム4.24g(20mmo
l) を加え室温で17時間撹拌した。飽和重曹水で中和
後、溶媒を留去した。残渣に水を加え、クロロホルムで
抽出した。クロロホルム層を水、飽和食塩水で洗浄後、
硫酸マグネシウムで乾燥し、溶媒を留去した。残渣を酢
酸エチルに溶解後、イソプロピルエーテルを加えて結晶
化させ、結晶をろ取した。減圧下で乾燥し、標記化合物
3.32g(収率81%)を得た。
Example 200 N '-(2-hydroxy-
3-methoxybenzyl) -3,5-di-t-butyl-4
-Hydroxybenzohydrazide (N '-(2-hydroxy-3-metho
xybenzyl) -3,5-di-t-butyl-4-hydroxybenzohydrazide) sodium triacetoxyborohydride in a solution of 3.98 g (10 mmol) of o-vanillin 3,5-di-t-butyl-4-hydroxybenzoylhydrazone in 40 ml of THF 4.24g (20mmo
l) was added and the mixture was stirred at room temperature for 17 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue and extracted with chloroform. After washing the chloroform layer with water and saturated saline,
After drying over magnesium sulfate, the solvent was distilled off. After dissolving the residue in ethyl acetate, isopropyl ether was added for crystallization, and the crystals were collected by filtration. Dry under reduced pressure to give the title compound
3.32 g (81% yield) was obtained.

【0330】(物性) 無色結晶(mp.185-188 ℃) PMR(DMSO-d6,δ ppm) : 9.99(1H,d,J=5.8Hz),9.10(1H,
s),7.58(2H,s),7.38(1H,brs),6.86(1H,dd,J=1.0 and 8.
0Hz),6.82(1H,dd,J=1.0 and 8.0Hz),6.71(1H,t,J=8.0H
z),5.45-5.38(1H,m),3.94(2H,d,J=6.3Hz),3.78(3H,s),
1.39(18H,s) IR(KBr, cm-1):3626,3274,2954,2872,1633,1600,1589,1
525,1481,1430,1391,1361,1348,1311,1273,1239,1162,1
120,1083,1027,991,956,889,841,772,732,697,634
(Physical properties) Colorless crystal (mp.185-188 ° C.) PMR (DMSO-d 6 , δ ppm): 9.99 (1H, d, J = 5.8 Hz), 9.10 (1H,
s), 7.58 (2H, s), 7.38 (1H, brs), 6.86 (1H, dd, J = 1.0 and 8.
0Hz), 6.82 (1H, dd, J = 1.0 and 8.0Hz), 6.71 (1H, t, J = 8.0H
z), 5.45-5.38 (1H, m), 3.94 (2H, d, J = 6.3Hz), 3.78 (3H, s),
1.39 (18H, s) IR (KBr, cm -1 ): 3626,3274,2954,2872,1633,1600,1589,1
525,1481,1430,1391,1361,1348,1311,1273,1239,1162,1
120,1083,1027,991,956,889,841,772,732,697,634

【0331】実施例201 N’−(2−ヒドロキシ−
3−メトキシベンジル)−3,5−ジ−t−ブチル−4
−ヒドロキシベンゾヒドラジド・メタンスルホン酸塩
(N'-(2-hydroxy-3-methoxybenzyl)-3,5-di-t-butyl-4-h
ydroxybenzohydrazide methanesulfonate) 実施例200で合成した化合物 0.2g(0.5mmol)、酢酸エ
チル 2ml及びメタンスルホン酸58mg(0.6mmol) の溶液を
室温で1時間撹拌した。溶媒を留去し、析出した結晶を
ヘキサン:酢酸エチル=2:1の混合溶媒よりろ取し
た。減圧下で乾燥し、標記化合物 196mg (収率79%)を得
た。 (物性) 無色結晶(mp.205-207 ℃(dec)) PMR(DMSO-d6,δ ppm) : 11.20(1H,b
rs),7.68(1H,s),7.59(2H,
s),7.00(1H,dd,J=1.5 and
8.0Hz),6.93(1H,dd,J=1.5 a
nd 8.0Hz),6.80(1H,dd,J=8.
0 and 8.0Hz),4.29(2H,s),
3.82(3H,s),2.33(3H,s),1.4
0(18H,s) IR(KBr, cm−1):3589,3423,2
960,1667,1600,1560,1494,1
439,1390,1328,1276,1242,1
205,1157,1044,972,925,88
9,774,733,554,534
Example 201 N '-(2-hydroxy-
3-methoxybenzyl) -3,5-di-t-butyl-4
-Hydroxybenzohydrazide methanesulfonate
(N '-(2-hydroxy-3-methoxybenzyl) -3,5-di-t-butyl-4-h
ydroxybenzohydrazide methanesulfonate) A solution of 0.2 g (0.5 mmol) of the compound synthesized in Example 200, 2 ml of ethyl acetate and 58 mg (0.6 mmol) of methanesulfonic acid was stirred at room temperature for 1 hour. The solvent was distilled off, and the precipitated crystals were collected by filtration from a mixed solvent of hexane: ethyl acetate = 2: 1. Drying under reduced pressure gave 196 mg (79% yield) of the title compound. (Physical properties) Colorless crystal (mp. 205-207 ° C (dec)) PMR (DMSO-d 6 , δ ppm): 11.20 (1H, b
rs), 7.68 (1H, s), 7.59 (2H,
s), 7.00 (1H, dd, J = 1.5 and)
8.0 Hz), 6.93 (1H, dd, J = 1.5 a)
nd 8.0 Hz), 6.80 (1H, dd, J = 8.
0 and 8.0 Hz), 4.29 (2H, s),
3.82 (3H, s), 2.33 (3H, s), 1.4
0 (18H, s) IR (KBr, cm -1 ): 3589, 3423, 2
960, 1667, 1600, 1560, 1494, 1
439, 1390, 1328, 1276, 1242, 1
205, 1157, 1044, 972, 925, 88
9,774,733,554,534

【0332】実施例202 N’−(2−ヒドロキシ−
3−メトキシベンジル)−3,5−ジ−t−ブチル−4
−ヒドロキシチオベンゾヒドラジド(N’−(2−hy
droxy−3−methoxybenzyl)−3,
5−di−t−butyl−4−hydroxythi
obenzohydrazide) 3,5−ジ−t−ブチル−4−ヒドロキシチオベンゾヒ
ドラジド 560mg(2mmol) 、o−バニリン 304mg(2mmol)
及び1,2−ジクロロエタン20mlの溶液に、トリアセト
キシ水素化ホウ素ナトリウム636mg(3mmol)を加え室温で
17時間撹拌した。飽和重曹水で中和後、溶媒を留去し
た。残渣に水を加え、酢酸エチルで抽出した。酢酸エチ
ル層を水、飽和食塩水で洗浄後、硫酸マグネシウムで乾
燥し、溶媒を留去した。残渣をシリカゲルカラムクロマ
トグラフィーに付し、ヘキサン:酢酸エチル=2:1溶
出部を溶媒留去し、残渣にヘキサン:酢酸エチル=4:
1の混合溶媒を加えて結晶化させ、それをろ取した。減
圧下で乾燥し、標記化合物260mg (収率31%)を得た。
Example 202 N '-(2-hydroxy-
3-methoxybenzyl) -3,5-di-t-butyl-4
-Hydroxythiobenzohydrazide (N '-(2-hy
droxy-3-methoxybenzyl) -3,
5-di-butyl-4-hydroxythithi
Obenzohydrazide 3,5-di-t-butyl-4-hydroxythiobenzohydrazide 560 mg (2 mmol), o-vanillin 304 mg (2 mmol)
To a solution of 20 ml of 1,2-dichloroethane and 1,2-dichloroethane, 636 mg (3 mmol) of sodium triacetoxyborohydride was added, followed by stirring at room temperature for 17 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, the hexane: ethyl acetate = 2: 1 eluted portion was evaporated, and the residue was subjected to hexane: ethyl acetate = 4: 4.
Crystallization was carried out by adding the mixed solvent of No. 1 and it was collected by filtration. Drying under reduced pressure gave 260 mg (31% yield) of the title compound.

【0333】(物性) 淡黄色結晶(mp.183-186 ℃) PMR(DMSO-d6,δ ppm) : 11.82-11.74(1H,m),8.83(1H,br
s),7.45(2H,s),7.37(1H,brs),7.02-6.94(1H,m),6.88(2
H,d,J=7.8Hz),6.72(1H,t,J=7.8Hz),4.12(2H,d,J=6.8H
z),3.78(3H,s),1.39(18H,s) IR(KBr, cm-1):3562,3412,3189,2956,1593,1480,1423,1
348,1279,1222,1110,1088,1007,890,841,782,714
(Physical properties) Light yellow crystal (mp.183-186 ° C.) PMR (DMSO-d 6 , δ ppm): 11.82-11.74 (1H, m), 8.83 (1H, br)
s), 7.45 (2H, s), 7.37 (1H, brs), 7.02-6.94 (1H, m), 6.88 (2
H, d, J = 7.8Hz), 6.72 (1H, t, J = 7.8Hz), 4.12 (2H, d, J = 6.8H
z), 3.78 (3H, s), 1.39 (18H, s) IR (KBr, cm -1 ): 3562,3412,3189,2956,1593,1480,1423,1
348,1279,1222,1110,1088,1007,890,841,782,714

【0334】実施例203 N’−ピリドキシル−3,
5−ジ−t−ブチル−4−ヒドロキシチオベンゾヒドラ
ジド(N'-pyridoxyl-3,5-di-t-butyl-4-hydroxythiobenz
ohydrazide) 3,5−ジ−t−ブチル−4−ヒドロキシチオベンゾヒ
ドラジド 0.84g(3mmol) 、ピリドキサール 0.61g(3mmo
l) 、1,2−ジクロロエタン20ml及びTHF20mlの溶
液に、トリアセトキシ水素化ホウ素ナトリウム1.90g(9m
mol)を加え室温で48時間撹拌した。飽和重曹水で中和
後、溶媒を留去した。残渣に水を加え、酢酸エチルで抽
出した。酢酸エチル層を水、飽和食塩水で洗浄後、硫酸
マグネシウムで乾燥し、溶媒を留去した。残渣をシリカ
ゲルカラムクロマトグラフィーに付し、クロロホルム:
メタノール=10:1溶出部を溶媒留去した。残渣を酢
酸エチルに溶解後、ヘキサンを加えて結晶化させ、結晶
をろ取した。減圧下で乾燥し、標記化合物 0.4g(収率31
%)を得た。
Example 203 N′-pyridoxyl-3,
5-di-t-butyl-4-hydroxythiobenzohydrazide (N'-pyridoxyl-3,5-di-t-butyl-4-hydroxythiobenz
ohydrazide) 3,5-di-t-butyl-4-hydroxythiobenzohydrazide 0.84 g (3 mmol), pyridoxal 0.61 g (3 mmo
l), 1,2-dichloroethane (20 ml) and THF (20 ml) were added to sodium triacetoxyborohydride (1.90 g, 9 ml).
mol) and the mixture was stirred at room temperature for 48 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and chloroform:
The solvent was distilled off from the eluted portion of methanol = 10: 1. After dissolving the residue in ethyl acetate, hexane was added for crystallization, and the crystals were collected by filtration. Dry under reduced pressure to give 0.4 g of the title compound (yield 31
%).

【0335】(物性) 無色結晶(mp.190-192 ℃) PMR(DMSO-d6,δ ppm) : 11.72(1H,brs),9.24(1H,brs),
7.90(1H,s),7.49(2H,s),7.39(1H,s),7.01(1H,brs),5.24
(1H,brs),4.60(2H,s),4.25(2H,s),2.37(3H,s),1.39(18
H,s) IR(KBr, cm-1):3417,3176,2957,1430,1360,1223,1155,1
120,1033,1017,888
(Physical properties) Colorless crystals (mp. 190-192 ° C.) PMR (DMSO-d 6 , δ ppm): 11.72 (1H, brs), 9.24 (1H, brs),
7.90 (1H, s), 7.49 (2H, s), 7.39 (1H, s), 7.01 (1H, brs), 5.24
(1H, brs), 4.60 (2H, s), 4.25 (2H, s), 2.37 (3H, s), 1.39 (18
H, s) IR (KBr, cm -1 ): 3417,3176,2957,1430,1360,1223,1155,1
120,1033,1017,888

【0336】実施例204 N’−(2−ヒドロキシ−
3−メトキシベンジル)−3,5−ジイソプロピル−4
−ヒドロキシベンゾヒドラジド(N'-(2-hydroxy-3-metho
xybenzyl)-3,5-diisopropyl-4-hydroxybenzohydrazide) o−バニリン3,5−ジイソプロピル−4−ヒドロキシ
ベンゾイルヒドラゾン2.78g(7.5mmol) のTHF100ml
溶液にトリアセトキシ水素化ホウ素ナトリウム4.24g(20
mmol) を加え室温で17時間撹拌した。飽和重曹水で中
和後、溶媒を留去した。残渣に水を加え、酢酸エチルで
抽出した。酢酸エチル層を水、飽和食塩水で洗浄後、硫
酸マグネシウムで乾燥し、溶媒を留去した。残渣を酢酸
エチルに溶解後、ヘキサンを加えて結晶化させ、結晶を
ろ取した。減圧下で乾燥し、標記化合物 2.65g (収率95
%)を得た。
Example 204 N '-(2-hydroxy-
3-methoxybenzyl) -3,5-diisopropyl-4
-Hydroxybenzohydrazide (N '-(2-hydroxy-3-metho
xybenzyl) -3,5-diisopropyl-4-hydroxybenzohydrazide) 2.78 g (7.5 mmol) of o-vanillin 3,5-diisopropyl-4-hydroxybenzoylhydrazone in THF 100 ml
4.24 g of sodium triacetoxyborohydride (20
mmol) and stirred at room temperature for 17 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. After dissolving the residue in ethyl acetate, hexane was added for crystallization, and the crystals were collected by filtration. Dry under reduced pressure to give the title compound (2.65 g, yield 95).
%).

【0337】(物性) 淡紫色結晶(mp.170-171 ℃) PMR(DMSO-d6,δ ppm) : 9.97(1H,d,J=6.3Hz),9.13(1H,
s),8.58(1H,brs),7.52(2H,s),6.86(1H,dd,J=1.0 and 6.
8Hz),6.82(1H,dd,J=1.0 and 6.8Hz),6.71(1H,t,J=6.8H
z),5.41(1H,q,J=6.3Hz),3.95(2H,d,J=6.3Hz),3.79(3H,
s),3.29(2H,sept,J=6.8Hz),1.17(12H,d,J=6.8Hz) IR(KBr, cm-1):3439,3294,2964,1631,1587,1468,1441,1
308,1266,1242,1127,1160,1075,770,732
(Physical properties) Light purple crystal (mp. 170-171 ° C.) PMR (DMSO-d 6 , δ ppm): 9.97 (1H, d, J = 6.3 Hz), 9.13 (1H,
s), 8.58 (1H, brs), 7.52 (2H, s), 6.86 (1H, dd, J = 1.0 and 6.
8Hz), 6.82 (1H, dd, J = 1.0 and 6.8Hz), 6.71 (1H, t, J = 6.8H
z), 5.41 (1H, q, J = 6.3Hz), 3.95 (2H, d, J = 6.3Hz), 3.79 (3H,
s), 3.29 (2H, sept, J = 6.8Hz), 1.17 (12H, d, J = 6.8Hz) IR (KBr, cm- 1 ): 3439,3294,2964,1631,1587,1468,1441,1
308,1266,1242,1127,1160,1075,770,732

【0338】実施例205 N’−(2−ヒドロキシ−
3−メトキシベンジル)−3,5−ジイソプロピル−4
−ヒドロキシベンゾヒドラジド・メタンスルホン酸塩
(N'-(2-hydroxy-3-methoxybenzyl)-3,5-diisopropyl-4-
hydroxybenzohydrazide methanesulfonate) 実施例204で合成した化合物 1.49g(4mmol) 、酢酸エ
チル30ml及びメタンスルホン酸0.39g(4mmol)の溶液を室
温で1時間撹拌した。溶媒を留去し、析出した結晶をヘ
キサン:酢酸エチル=2:1の混合溶媒よりろ取した。
減圧下で乾燥し、標記化合物 1.40g (収率75%)を得た。
Example 205 N '-(2-hydroxy-
3-methoxybenzyl) -3,5-diisopropyl-4
-Hydroxybenzohydrazide methanesulfonate
(N '-(2-hydroxy-3-methoxybenzyl) -3,5-diisopropyl-4-
(Hydroxybenzohydrazide methanesulfonate) A solution of 1.49 g (4 mmol) of the compound synthesized in Example 204, 30 ml of ethyl acetate and 0.39 g (4 mmol) of methanesulfonic acid was stirred at room temperature for 1 hour. The solvent was distilled off, and the precipitated crystals were collected by filtration from a mixed solvent of hexane: ethyl acetate = 2: 1.
Drying under reduced pressure gave 1.40 g (yield 75%) of the title compound.

【0339】(物性) 無色結晶(mp.180-185 ℃) PMR(DMSO-d6,δ ppm) : 11.21(1H,brs),8.93(1H,brs),
7.52(2H,s),7.01(1H,d,J=7.8Hz),6.93(1H,d,J=7.8Hz),
6.80(1H,t,J=7.8Hz),4.31(2H,s),3.82(3H,s),3.32(2H,s
ept,J=6.8Hz),2.33(3H,s),1.17(12H,d,J=6.8Hz) IR(KBr, cm-1):3452,2964,1670,1603,1493,1468,1441,1
383,1314,1276,1194,1150,1048,931,775,733
(Physical properties) Colorless crystal (mp. 180-185 ° C.) PMR (DMSO-d 6 , δ ppm): 11.21 (1H, brs), 8.93 (1H, brs),
7.52 (2H, s), 7.01 (1H, d, J = 7.8Hz), 6.93 (1H, d, J = 7.8Hz),
6.80 (1H, t, J = 7.8Hz), 4.31 (2H, s), 3.82 (3H, s), 3.32 (2H, s
ept, J = 6.8Hz), 2.33 (3H, s), 1.17 (12H, d, J = 6.8Hz) IR (KBr, cm -1 ): 3452,2964,1670,1603,1493,1468,1441,1
383,1314,1276,1194,1150,1048,931,775,733

【0340】実施例206 N’−ピリドキシル−3,
5−ジイソプロピル−4−ヒドロキシベンゾヒドラジド
・塩酸塩(N'-pyridoxyl-3,5-diisopropyl-4-hydroxyben
zohydrazide hydrochloride) ピリドキサール3,5−ジイソプロピル−4−ヒドロキ
シベンゾイルヒドラゾン 2.89g(7.5mmol) のTHF100m
l 溶液にトリアセトキシ水素化ホウ素ナトリウム8.48g
(40mmol) を加え室温で17時間撹拌した。溶媒を留去
し、残渣に水を加え、濃塩酸で酸性とした後、クロロホ
ルムを加えた。析出した結晶をろ取し、減圧下で乾燥
し、標記化合物 2.65g (収率83%)を得た。 (物性) 淡黄色結晶(mp.175-213 ℃) PMR(DMSO-d6,δ ppm): 10.38(1H,s),8.74(1H,brs),8.13
(1H,s),7.55(2H,s),4.69(2H,s),4.23(2H,s),3.32(2H,se
pt,J=6.8Hz),2.60(3H,s),1.18(12H,d,J=6.8Hz) IR(KBr, cm-1):3223,3082,2963,2870,1619,1554,1540,1
468,1431,1408,1389,1312,1295,1214,1200,1149,1052,1
017,909,858,774
Example 206 N'-pyridoxyl-3,
5-diisopropyl-4-hydroxybenzohydrazide hydrochloride (N'-pyridoxyl-3,5-diisopropyl-4-hydroxyben
zohydrazide hydrochloride) Pyridoxal 3,5-diisopropyl-4-hydroxybenzoylhydrazone 2.89 g (7.5 mmol) of THF 100m
l 8.48 g of sodium triacetoxyborohydride in solution
(40 mmol) was added and the mixture was stirred at room temperature for 17 hours. The solvent was distilled off, water was added to the residue, and the mixture was acidified with concentrated hydrochloric acid, and then chloroform was added. The precipitated crystals were collected by filtration and dried under reduced pressure to give the title compound (2.65 g, yield 83%). (Physical properties) pale yellow crystal (mp.175-213 ° C) PMR (DMSO-d 6 , δ ppm): 10.38 (1H, s), 8.74 (1H, brs), 8.13
(1H, s), 7.55 (2H, s), 4.69 (2H, s), 4.23 (2H, s), 3.32 (2H, se
pt, J = 6.8Hz), 2.60 (3H, s), 1.18 (12H, d, J = 6.8Hz) IR (KBr, cm -1 ): 3223,3082,2963,2870,1619,1554,1540,1
468,1431,1408,1389,1312,1295,1214,1200,1149,1052,1
017,909,858,774

【0341】実施例207 N’−(2,5−ジヒドロ
キシ−3,4−ジメトキシ−6−メチルベンジル)−
3,5−ジ−t−ブチル−4−ヒドロキシベンゾヒドラ
ジド(N'-(2,5-dihydroxy-3,4-dimethoxy-6-methylbenzy
l)-3,5-di-t-butyl-4-hydroxybenzohydrazide) 2,5−ジヒドロキシ−3,4−ジメトキシ−6−メチ
ルベンズアルデヒド3,5−ジ−t−ブチル−4−ヒド
ロキシベンゾイルヒドラゾン 2.09g(4.56mmol)のTHF
50ml 溶液に、トリアセトキシ水素化ホウ素ナトリウム
3.86g(18.24mmol)を加え室温で17時間撹拌した。飽和
重曹水で中和後、溶媒を留去した。残渣に水を加え、ク
ロロホルムで抽出した。クロロホルム層を水、飽和食塩
水で洗浄後、硫酸マグネシウムで乾燥し、溶媒を留去し
た。残渣をシリカゲルカラムクロマトグラフィーに付
し、ヘキサン:酢酸エチル=1:1溶出部を留去した。
残渣を酢酸エチルに溶解後、ヘキサンを加えて結晶化さ
せ,結晶をろ取した。減圧下で乾燥し、標記化合物 0.5
3g (収率25%)を得た。
Example 207 N ′-(2,5-dihydroxy-3,4-dimethoxy-6-methylbenzyl)-
3,5-di-t-butyl-4-hydroxybenzohydrazide (N '-(2,5-dihydroxy-3,4-dimethoxy-6-methylbenzy
l) -3,5-di-t-butyl-4-hydroxybenzohydrazide) 2,5-dihydroxy-3,4-dimethoxy-6-methylbenzaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone 2.09 g (4.56 mmol) in THF
Add 50 ml sodium triacetoxyborohydride solution
3.86 g (18.24 mmol) was added, and the mixture was stirred at room temperature for 17 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue and extracted with chloroform. The chloroform layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the hexane: ethyl acetate = 1: 1 eluate was distilled off.
After dissolving the residue in ethyl acetate, hexane was added for crystallization, and the crystals were collected by filtration. Dry under reduced pressure to give the title compound 0.5
3 g (yield 25%) was obtained.

【0342】(物性) 淡橙色結晶(mp.190-192 ℃) PMR(DMSO-d6,δppm): 10.15(1H,d,J
=6.0Hz),8.72(1H,s),7.97(1
H,s),7.60(2H,s),7.38(1H,
s),5.12(1H,q,J=6.0Hz),3.9
1(2H,d,J=6.0Hz),3.74(3H,
s),3.73(3H,s),2.17(3H,s),
1.40(18H,s) IR(KBr, cm−1):3418,3076,2
955,1642,1468,1428,1313,1
240,1120,1098,1073,1025,9
66,915,888
(Physical properties) Pale orange crystal (mp. 190-192 ° C.) PMR (DMSO-d 6 , δ ppm): 10.15 (1H, d, J)
= 6.0 Hz), 8.72 (1H, s), 7.97 (1
H, s), 7.60 (2H, s), 7.38 (1H,
s), 5.12 (1H, q, J = 6.0 Hz), 3.9
1 (2H, d, J = 6.0 Hz), 3.74 (3H,
s), 3.73 (3H, s), 2.17 (3H, s),
1.40 (18H, s) IR (KBr, cm -1 ): 3418, 3076, 2
955,1642,1468,1428,1313,1
240, 1120, 1098, 1073, 1025, 9
66,915,888

【0343】実施例208 N’−(2−ヒドロキシ−
3−メトキシ−5−ピペリジノメチルベンジル)−3,
5−ジ−t−ブチル−4−ヒドロキシベンゾヒドラジド
(N’−(2−hydroxy−3−methoxy−
5−piperidinomethylbenzyl)
−3,5−di−t−butyl−4−hydroxy
benzohydrazide) 3−メトキシ−5−ピペリジノメチルサリチルアルデヒ
ド3,5−ジ−t−ブチル−4−ヒドロキシベンゾイル
ヒドラゾン 2.76g(5.57mmol)のTHF 100ml溶液に、ト
リアセトキシ水素化ホウ素ナトリウム4.72g(22.28mmol)
を加え室温で17時間撹拌した。飽和重曹水で中和後、
溶媒を留去した。残渣に水を加え、クロロホルムで抽出
した。クロロホルム層を水、飽和食塩水で洗浄後、硫酸
マグネシウムで乾燥し、溶媒を留去した。残渣をシリカ
ゲルカラムクロマトグラフィーに付し、クロロホルム:
メタノール=9:1溶出部を留去した。残渣を酢酸エチ
ルに溶解後、ヘキサンを加えて結晶化させ,結晶をろ取
した。減圧下で乾燥し、標記化合物 1.50g (収率54%)を
得た。
Example 208 N '-(2-hydroxy-
3-methoxy-5-piperidinomethylbenzyl) -3,
5-di-t-butyl-4-hydroxybenzohydrazide (N '-(2-hydroxy-3-methyoxy-
5-piperidinomethylbenzyl)
-3,5-di-t-butyl-4-hydroxy
Benzohydrazide) To a solution of 2.76 g (5.57 mmol) of 3-methoxy-5-piperidinomethylsalicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone in 100 ml of THF was added 4.72 g of sodium triacetoxyborohydride. (22.28 mmol)
Was added and stirred at room temperature for 17 hours. After neutralization with saturated aqueous sodium bicarbonate,
The solvent was distilled off. Water was added to the residue and extracted with chloroform. The chloroform layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and chloroform:
The eluted part of methanol = 9: 1 was distilled off. After dissolving the residue in ethyl acetate, hexane was added for crystallization, and the crystals were collected by filtration. Drying under reduced pressure gave 1.50 g (yield 54%) of the title compound.

【0344】(物性) 淡黄色結晶(mp.115-118 ℃) PMR(DMSO-d6,δppm): 9.97(1H,d,J=5.0Hz),8.96(1H,s),
7.57(2H,s),7.36(1H,s),6.76(1H,d,J=1.2Hz),6.70(1H,
d,J=1.2Hz),5.42-5.35(1H,m),3.91(2H,d,J=5.4Hz),3.77
(3H,s),3.27(2H,s),2.29-2.20(4H,m),1.46-1.30(6H,m),
1.39(18H,s) IR(KBr, cm-1):3636,3292,2936,1632,1601,1538,1497,1
454,1455,1430,1391,1366,1342,1299,1238,1159,1119,1
097,1039,992,862
(Physical properties) Light yellow crystal (mp. 115-118 ° C.) PMR (DMSO-d 6 , δ ppm): 9.97 (1H, d, J = 5.0 Hz), 8.96 (1H, s),
7.57 (2H, s), 7.36 (1H, s), 6.76 (1H, d, J = 1.2Hz), 6.70 (1H,
d, J = 1.2Hz), 5.42-5.35 (1H, m), 3.91 (2H, d, J = 5.4Hz), 3.77
(3H, s), 3.27 (2H, s), 2.29-2.20 (4H, m), 1.46-1.30 (6H, m),
1.39 (18H, s) IR (KBr, cm -1 ): 3636,3292,2936,1632,1601,1538,1497,1
454,1455,1430,1391,1366,1342,1299,1238,1159,1119,1
097,1039,992,862

【0345】実施例209 N’−(2−ヒドロキシ−
3−メトキシ−5−モルホリノメチルベンジル)−3,
5−ジ−t−ブチル−4−ヒドロキシベンゾヒドラジド
(N'-(2-hydroxy-3-methoxy-5-morpholinomethylbenzyl)
-3,5-di-t-butyl-4-hydroxybenzohydrazide) 3−メトキシ−5−モルホリノメチルサリチルアルデヒ
ド3,5−ジ−t−ブチル−4−ヒドロキシベンゾイル
ヒドラゾン 1.16g(2.33mmol)のTHF 50ml 溶液に、ト
リアセトキシ水素化ホウ素ナトリウム1.98g(9.32mmol)
を加え室温で17時間撹拌した。飽和重曹水で中和後、
溶媒を留去した。残渣に水を加え、クロロホルムで抽出
した。クロロホルム層を水、飽和食塩水で洗浄後、硫酸
マグネシウムで乾燥し、溶媒を留去した。残渣をシリカ
ゲルカラムクロマトグラフィーに付し、クロロホルム:
メタノール=9:1溶出部を留去した。残渣を酢酸エチ
ルに溶解後、ヘキサンを加えて結晶化させ、結晶をろ取
した。減圧下で乾燥し、標記化合物 1.0g(収率85%)を得
た。
Example 209 N ′-(2-hydroxy-
3-methoxy-5-morpholinomethylbenzyl) -3,
5-di-t-butyl-4-hydroxybenzohydrazide
(N '-(2-hydroxy-3-methoxy-5-morpholinomethylbenzyl)
-3,5-di-t-butyl-4-hydroxybenzohydrazide) 3-methoxy-5-morpholinomethylsalicylaldehyde 3,5-di-t-butyl-4-hydroxybenzoylhydrazone 1.16 g (2.33 mmol) in THF 50 ml Into, 1.98 g (9.32 mmol) of sodium triacetoxyborohydride
Was added and stirred at room temperature for 17 hours. After neutralization with saturated aqueous sodium bicarbonate,
The solvent was distilled off. Water was added to the residue and extracted with chloroform. The chloroform layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and chloroform:
The eluted part of methanol = 9: 1 was distilled off. After dissolving the residue in ethyl acetate, hexane was added for crystallization, and the crystals were collected by filtration. Drying under reduced pressure gave 1.0 g (yield 85%) of the title compound.

【0346】(物性) 無色結晶(mp.116-120 ℃) IR(KBr, cm-1):3627,3292,2955,1632,1601,1538,1498,1
455,1430,1392,1349,1330,1298,1238,1154,1116,1070,1
035,1009,910,889,865,795
(Physical properties) Colorless crystals (mp. 116-120 ° C.) IR (KBr, cm −1 ): 3627,3292,2955,1632,1601,1538,1498,1
455,1430,1392,1349,1330,1298,1238,1154,1116,1070,1
035,1009,910,889,865,795

【0347】実施例210 N’−[5−(4−エチル
−1−ピペラジニル)メチル−2−ヒドロキシ−3−メ
トキシベンジル]−3,5−ジ−t−ブチル−4−ヒド
ロキシベンゾヒドラジド(N'-[5-(4-ethyl-1-piperaziny
l)methyl-2-hydroxy-3-methoxybenzyl]-3,5-di-t-butyl
-4-hydroxybenzohydrazide) 5−(4−エチル−1−ピペラジニル)メチル−3−メ
トキシサリチルアルデヒド3,5−ジ−t−ブチル−4
−ヒドロキシベンゾイルヒドラゾン 2.25g(4.3mmol) の
THF 50ml 溶液に、トリアセトキシ水素化ホウ素ナト
リウム3.64g(17.2mmol) を加え室温で17時間撹拌し
た。飽和重曹水で中和後、溶媒を留去した。残渣に水を
加え、クロロホルムで抽出した。クロロホルム層を水、
飽和食塩水で洗浄後、硫酸マグネシウムで乾燥し、溶媒
を留去した。残渣をシリカゲルカラムクロマトグラフィ
ーに付し、クロロホルム:メタノール=10:1溶出部
を留去した。残渣を酢酸エチルに溶解後、ヘキサンを加
えて結晶化させ、結晶をろ取した。減圧下で乾燥し、標
記化合物 0.96g (収率42%)を得た。
Example 210 N '-[5- (4-Ethyl-1-piperazinyl) methyl-2-hydroxy-3-methoxybenzyl] -3,5-di-t-butyl-4-hydroxybenzohydrazide (N '-[5- (4-ethyl-1-piperaziny
l) methyl-2-hydroxy-3-methoxybenzyl] -3,5-di-t-butyl
-4-hydroxybenzohydrazide) 5- (4-ethyl-1-piperazinyl) methyl-3-methoxysalicylaldehyde 3,5-di-t-butyl-4
To a solution of 2.25 g (4.3 mmol) of -hydroxybenzoylhydrazone in 50 ml of THF was added 3.64 g (17.2 mmol) of sodium triacetoxyborohydride and the mixture was stirred at room temperature for 17 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue and extracted with chloroform. Chloroform layer with water,
After washing with a saturated saline solution, it was dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the chloroform: methanol = 10: 1 eluted portion was distilled off. After dissolving the residue in ethyl acetate, hexane was added for crystallization, and the crystals were collected by filtration. Drying under reduced pressure gave 0.96 g (42% yield) of the title compound.

【0348】(物性) 無色結晶(mp.119-125 ℃) PMR(DMSO-d6,δppm): 9.97(1H,d,J=5.8Hz),8.98(1H,s),
7.57(2H,s),7.37(1H,brs),6.76(1H,d,J=1.2Hz),6.70(1
H,d,J=1.2Hz),5.40(1H,q,J=5.8Hz),3.91(2H,d,J=5.8H
z),3.77(3H,s),3.30(2H,s),2.40-2.10(10H,m),1.39(18
H,s),0.95(3H,t,J=7.1Hz) IR(KBr, cm-1):3294,2954,2875,2814,1634,1601,1498,1
430,1392,1359,1344,1301,1238,1162,1121,1097,1013,9
41,889,858,801,695
(Physical properties) Colorless crystal (mp. 119-125 ° C.) PMR (DMSO-d 6 , δ ppm): 9.97 (1H, d, J = 5.8 Hz), 8.98 (1H, s),
7.57 (2H, s), 7.37 (1H, brs), 6.76 (1H, d, J = 1.2Hz), 6.70 (1
H, d, J = 1.2Hz), 5.40 (1H, q, J = 5.8Hz), 3.91 (2H, d, J = 5.8H
z), 3.77 (3H, s), 3.30 (2H, s), 2.40-2.10 (10H, m), 1.39 (18
H, s), 0.95 (3H, t, J = 7.1Hz) IR (KBr, cm -1 ): 3294,2954,2875,2814,1634,1601,1498,1
430,1392,1359,1344,1301,1238,1162,1121,1097,1013,9
41,889,858,801,695

【0349】実施例211 N’−(2−ヒドロキシ−
3−メトキシベンジル)−6−ヒドロキシ−2,5,
7,8−テトラメチルクロマン−2−アセトヒドラジド
(N'-(2-hydroxy-3-methoxybenzyl)-6-hydroxy-2,5,7,8-
tetramethylchroman-2-acetohydrazide) o−バニリン6−ヒドロキシ−2,5,7,8−テトラ
メチルクロマン−2−アセチルヒドラゾン 2.06g(5mmo
l) のメタノール50ml溶液に氷冷下水素化ホウ素ナトリ
ウム6.19g(mmol) の水溶液20mlを滴下し、更に1時間氷
冷下撹拌した後、室温で16時間撹拌した。溶媒を留去
し、残渣に水を加え、濃塩酸で中和した後、酢酸エチル
を加え不溶物をろ取し、水続いて酢酸エチルで洗浄し
た。減圧下で乾燥し、標記化合物 1.62g (収率78%)を得
た。
Example 211 N ′-(2-hydroxy-
3-methoxybenzyl) -6-hydroxy-2,5
7,8-tetramethylchroman-2-acetohydrazide
(N '-(2-hydroxy-3-methoxybenzyl) -6-hydroxy-2,5,7,8-
tetramethylchroman-2-acetohydrazide) o-vanillin 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone 2.06 g (5 mmo
To a solution of l) in 50 ml of methanol was added dropwise 20 ml of an aqueous solution of 6.19 g (mmol) of sodium borohydride under ice-cooling, and the mixture was further stirred for 1 hour under ice-cooling, followed by stirring at room temperature for 16 hours. The solvent was distilled off, water was added to the residue, and the mixture was neutralized with concentrated hydrochloric acid. Ethyl acetate was added, the insolubles were collected by filtration, and the mixture was washed with water and ethyl acetate. Drying under reduced pressure gave 1.62 g (78% yield) of the title compound.

【0350】(物性) 無色結晶(mp.178-180 ℃) PMR(DMSO-d6,δppm): 9.40(1H,d,J=
5.9Hz),8.98(1H,s),7.36(1
H,s),6.84(1H,dd,J=1.5 and
7.8Hz),6.78(1H,dd,J=1.5
and 7.8Hz),6.69(1H,dd,J=
7.8 and 7.8Hz),5.32(1H,q,
J=5.9Hz),3.91−3.79(2H,m),
3.77(3H,s),2.61−2.40(2H,
m),2.33(1H,d,J=13.2Hz),2.
23(1H,d,J=13.2Hz),2.04(3
H,s),2.01(3H,s),1.99(3H,
s),1.93−1.84(1H,m),1.76−
1.67(1H,m),1.27(3H,s) IR(KBr, cm−1):3483,3265,3
225,3080,2939,1634,1555,1
480,1441,1378,1335,1281,1
258,1229,1201,1184,1091,1
070,1010,943,928,858,775,
735,597
(Physical properties) Colorless crystal (mp. 178-180 ° C.) PMR (DMSO-d 6 , δ ppm): 9.40 (1H, d, J =
5.9 Hz), 8.98 (1 H, s), 7.36 (1
H, s), 6.84 (1H, dd, J = 1.5 and
7.8 Hz), 6.78 (1H, dd, J = 1.5)
and 7.8 Hz), 6.69 (1H, dd, J =
7.8 and 7.8 Hz), 5.32 (1H, q,
J = 5.9 Hz), 3.91-3.79 (2H, m),
3.77 (3H, s), 2.61-2.40 (2H,
m), 2.33 (1H, d, J = 13.2 Hz);
23 (1H, d, J = 13.2 Hz), 2.04 (3
H, s), 2.01 (3H, s), 1.99 (3H,
s), 1.93-1.84 (1H, m), 1.76-
1.67 (1H, m), 1.27 (3H, s) IR (KBr, cm -1 ): 3483,3265,3
225, 3080, 2939, 1634, 1555, 1
480, 1441, 1378, 1335, 1281, 1
258,1229,1201,1184,1091,1
070, 1010, 943, 928, 858, 775,
735,597

【0351】実施例212 N’−(2−ヒドロキシ−
4−イソプロポキシベンジル)−6−ヒドロキシ−2,
5,7,8−テトラメチルクロマン−2−アセトヒドラ
ジド(N’−(2−hydroxy−4−isopro
poxybenzyl)−6−hydroxy−2,
5,7,8−tetramethylchroman−
2−acetohydrazide) 4−イソプロポキシサリチルアルデヒド6−ヒドロキシ
−2,5,7,8−テトラメチルクロマン−2−アセチ
ルヒドラゾン 3.00g(6.8mmol) のメタノール60ml溶液に
氷冷下水素化ホウ素ナトリウム9.00g(mmol) の水溶液20
mlを滴下し、更に1時間氷冷下撹拌した後、室温で16
時間撹拌した。溶媒を留去し、残渣に水を加え、濃塩酸
で酸性とした後、飽和重曹水で中和し、酢酸エチルで抽
出した。酢酸エチル層を水、飽和食塩水で洗浄後、硫酸
マグネシウムで乾燥し、溶媒を留去した。残渣を酢酸エ
チルに溶解後、ヘキサンを加えて結晶化させ、結晶をろ
取した。減圧下で乾燥し、標記化合物 2.33g (収率77%)
を得た。
Example 212 N ′-(2-hydroxy-
4-isopropoxybenzyl) -6-hydroxy-2,
5,7,8-Tetramethylchroman-2-acetohydrazide (N ′-(2-hydroxy-4-isopro
(oxybenzyl) -6-hydroxy-2,
5,7,8-tetramethylchroman-
2-acetohydrazide) 4-isopropoxysalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone 9.00 g of sodium borohydride in a 60 ml methanol solution of 3.00 g (6.8 mmol) of methanol (mmol) aqueous solution 20
After stirring for 1 hour under ice-cooling, the mixture was
Stirred for hours. The solvent was distilled off, water was added to the residue, acidified with concentrated hydrochloric acid, neutralized with saturated aqueous sodium hydrogen carbonate, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. After dissolving the residue in ethyl acetate, hexane was added for crystallization, and the crystals were collected by filtration. Dry under reduced pressure, 2.33 g of the title compound (77% yield)
I got

【0352】(物性) 無色結晶(mp.157-162 ℃) PMR(DMSO-d6,δppm): 9.61(1H,s),9.40(1H,d,J=6.3Hz),
7.37(1H,s),6.98(1H,d,J=8.3Hz),6.315(1H,d,J=2.5Hz),
6.27(1H,dd,J=2.5 and 8.3Hz),5.23(1H,q,J=6.3Hz),4.4
7(1H,sept,J=5.9Hz),3.81-3.69(2H,m),2.60-2.40(2H,
m),2.33(1H,d,J=13.2Hz),2.22(1H,d,J=13.2Hz),2.04(3
H,s),2.01(3H,s),1.96(3H,s),1.92-1.82(1H,m),1.76-1.
66(1H,m),1.26(3H,s),1.23(6H,d,J=5.9Hz)
(Physical properties) Colorless crystals (mp. 157-162 ° C.) PMR (DMSO-d 6 , δ ppm): 9.61 (1H, s), 9.40 (1H, d, J = 6.3 Hz),
7.37 (1H, s), 6.98 (1H, d, J = 8.3Hz), 6.315 (1H, d, J = 2.5Hz),
6.27 (1H, dd, J = 2.5 and 8.3Hz), 5.23 (1H, q, J = 6.3Hz), 4.4
7 (1H, sept, J = 5.9Hz), 3.81-3.69 (2H, m), 2.60-2.40 (2H,
m), 2.33 (1H, d, J = 13.2 Hz), 2.22 (1H, d, J = 13.2 Hz), 2.04 (3
H, s), 2.01 (3H, s), 1.96 (3H, s), 1.92-1.82 (1H, m), 1.76-1.
66 (1H, m), 1.26 (3H, s), 1.23 (6H, d, J = 5.9Hz)

【0353】実施例213 N’−[2−ヒドロキシ−
4−N−(イソプロポキシカルボニルメチル)イソプロ
ピルアミノベンジル]−6−ヒドロキシ−2,5,7,
8−テトラメチルクロマン−2−アセトヒドラジド(N'-
[2-hydroxy-4-N-(isopropoxycarbonylmethyl)isopropyl
aminobenzyl]-6-hydroxy-2,5,7,8-tetramethylchroman-
2-acetohydrazide)) 4−N−(イソプロポキシカルボニルメチル)イソプロ
ピルアミノサリチルアルデヒド6−ヒドロキシ−2,
5,7,8−テトラメチルクロマン−2−アセチルヒド
ラゾン 1.5g(2.93mmol) のメタノール50ml溶液に氷冷下
水素化ホウ素ナトリウム4.5g(118mmol) の水溶液20mlを
滴下し、更に1時間氷冷下撹拌した後、室温で16時間
撹拌した。溶媒を留去し、残渣に水を加え、濃塩酸で酸
性とした後、飽和重曹水で中和し、酢酸エチルで抽出し
た。酢酸エチル層を水、飽和食塩水で洗浄後、硫酸マグ
ネシウムで乾燥し、溶媒を留去した。残渣をシリカゲル
カラムクロマトグラフィーに付し、ヘキサン:酢酸エチ
ル=1:1溶出部を留去し、標記化合物を淡桃色不定形
固体として 0.30g (収率20%)を得た。
Example 213 N ′-[2-hydroxy-
4-N- (isopropoxycarbonylmethyl) isopropylaminobenzyl] -6-hydroxy-2,5,7,
8-tetramethylchroman-2-acetohydrazide (N'-
[2-hydroxy-4-N- (isopropoxycarbonylmethyl) isopropyl
aminobenzyl] -6-hydroxy-2,5,7,8-tetramethylchroman-
2-acetohydrazide)) 4-N- (isopropoxycarbonylmethyl) isopropylaminosalicylaldehyde 6-hydroxy-2,
To a solution of 1.5 g (2.93 mmol) of 5,7,8-tetramethylchroman-2-acetylhydrazone in 50 ml of methanol was added dropwise 20 ml of an aqueous solution of 4.5 g (118 mmol) of sodium borohydride under ice-cooling, and further ice-cooled for 1 hour. After stirring, the mixture was stirred at room temperature for 16 hours. The solvent was distilled off, water was added to the residue, acidified with concentrated hydrochloric acid, neutralized with saturated aqueous sodium hydrogen carbonate, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the hexane: ethyl acetate = 1: 1 eluate was distilled off to give 0.30 g (yield: 20%) of the title compound as a pale pink amorphous solid.

【0354】(物性) 淡桃色不定形固体 PMR(DMSO-d6,δppm): 9.39(1H,d,J=5.5Hz),9.32(1H,s),
7.37(1H,s),6.86(1H,d,J=8.8Hz),6.06(1H,d,J=2.5Hz),
6.00(1H,dd,J=2.5 and 8.8Hz),5.13(1H,q,J=5.5Hz),4.9
3(1H,sept,J=6.0Hz),4.00(1H,sept,J=6.6Hz),3.85(2H,
s),3.77-3.65(2H,m),2.60-2.40(2H,m),2.33(1H,d,J=13.
7Hz),2.23(1H,d,J=13.7Hz),2.04(3H,s),2.01(3H,s),1.9
6(3H,s),1.94-1.84(1H,m),1.76-1.67(1H,m),1.28(3H,
s),1.20(6H,d,J=6.0Hz),1.11(6H,d,J=6.6Hz)
(Physical properties) Pale pink amorphous solid PMR (DMSO-d 6 , δ ppm): 9.39 (1H, d, J = 5.5 Hz), 9.32 (1H, s),
7.37 (1H, s), 6.86 (1H, d, J = 8.8Hz), 6.06 (1H, d, J = 2.5Hz),
6.00 (1H, dd, J = 2.5 and 8.8Hz), 5.13 (1H, q, J = 5.5Hz), 4.9
3 (1H, sept, J = 6.0Hz), 4.00 (1H, sept, J = 6.6Hz), 3.85 (2H,
s), 3.77-3.65 (2H, m), 2.60-2.40 (2H, m), 2.33 (1H, d, J = 13.
7Hz), 2.23 (1H, d, J = 13.7Hz), 2.04 (3H, s), 2.01 (3H, s), 1.9
6 (3H, s), 1.94-1.84 (1H, m), 1.76-1.67 (1H, m), 1.28 (3H, m
s), 1.20 (6H, d, J = 6.0Hz), 1.11 (6H, d, J = 6.6Hz)

【0355】実施例214 N’−[2−ヒドロキシ−
4−N−(メトキシカルボニルメチル)シクロペンチル
アミノベンジル]−6−ヒドロキシ−2,5,7,8−
テトラメチルクロマン−2−アセトヒドラジド(N'-[2-h
ydroxy-4-N-(methoxycarbonylmethyl)cyclopentylamino
benzyl]-6-hydroxy-2,5,7,8-tetramethylchroman-2-ace
tohydrazide)) 4−N−(メトキシカルボニルメチル)シクロペンチル
アミノサリチルアルデヒド6−ヒドロキシ−2,5,
7,8−テトラメチルクロマン−2−アセチルヒドラゾ
ン 2.41g(4.48mmol)及びシアノ水素化ホウ素ナトリウム
1.13g(17.92mmol)のTHF 30ml 溶液を1N塩酸溶液で
pH4に調整し、室温で6時間撹拌した。濃塩酸で酸性
とし、溶媒を留去した。残渣を飽和重曹水で中和し、酢
酸エチルで抽出した。酢酸エチル層を水、飽和食塩水で
洗浄後、硫酸マグネシウムで乾燥し、溶媒を留去した。
残渣をシリカゲルカラムクロマトグラフィーに付し、ヘ
キサン:酢酸エチル=1:2溶出部を留去し、標記化合
物を淡橙色無定形固体として0.3g(収率12%)を得た。
Example 214 N ′-[2-hydroxy-
4-N- (methoxycarbonylmethyl) cyclopentylaminobenzyl] -6-hydroxy-2,5,7,8-
Tetramethylchroman-2-acetohydrazide (N '-[2-h
ydroxy-4-N- (methoxycarbonylmethyl) cyclopentylamino
benzyl] -6-hydroxy-2,5,7,8-tetramethylchroman-2-ace
tohydrazide)) 4-N- (methoxycarbonylmethyl) cyclopentylaminosalicylaldehyde 6-hydroxy-2,5,
2.4 g (4.48 mmol) of 7,8-tetramethylchroman-2-acetylhydrazone and sodium cyanoborohydride
A solution of 1.13 g (17.92 mmol) in 30 ml of THF was adjusted to pH 4 with a 1N hydrochloric acid solution and stirred at room temperature for 6 hours. The mixture was acidified with concentrated hydrochloric acid, and the solvent was distilled off. The residue was neutralized with saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off.
The residue was subjected to silica gel column chromatography, and the eluted portion of hexane: ethyl acetate = 1: 2 was distilled off to obtain 0.3 g (yield: 12%) of the title compound as a pale orange amorphous solid.

【0356】(物性) 淡橙色無定形固体 PMR(DMSO-d6,δppm): 9.39(1H,d,J=5.0Hz),9.31(1H,s),
7.36(1H,s),6.87(1H,d,J=8.3Hz),6.116(1H,d,J=2.5Hz),
6.07(1H,dd,J=2.5 and 8.3Hz),5.13(1H,q,J=5.0Hz),4.1
1-4.00(1H,m),3.94(2H,s),3.77-3.66(2H,m),3.65(3H,
s),2.60-2.42(2H,m),2.33(1H,d,J=13.5Hz),2.23(1H,d,J
=13.5Hz),2.04(3H,s),2.01(3H,s),1.97(3H,s),1.94-1.3
8(10H,m),1.28(3H,s)
(Physical properties) Pale orange amorphous solid PMR (DMSO-d 6 , δ ppm): 9.39 (1H, d, J = 5.0 Hz), 9.31 (1H, s),
7.36 (1H, s), 6.87 (1H, d, J = 8.3Hz), 6.116 (1H, d, J = 2.5Hz),
6.07 (1H, dd, J = 2.5 and 8.3Hz), 5.13 (1H, q, J = 5.0Hz), 4.1
1-4.00 (1H, m), 3.94 (2H, s), 3.77-3.66 (2H, m), 3.65 (3H,
s), 2.60-2.42 (2H, m), 2.33 (1H, d, J = 13.5Hz), 2.23 (1H, d, J
= 13.5Hz), 2.04 (3H, s), 2.01 (3H, s), 1.97 (3H, s), 1.94-1.3
8 (10H, m), 1.28 (3H, s)

【0357】実施例215 N’−(5−ブロモ−2−
ヒドロキシ−3−メトキシベンジル)−6−ヒドロキシ
−2,5,7,8−テトラメチルクロマン−2−アセト
ヒドラジド(N'-(5-bromo-2-hydroxy-3-methoxybenzyl)-
6-hydroxy-2,5,7,8-tetramethylchroman-2-acetohydraz
ide) 5−ブロモ−3−メトキシサリチルアルデヒド6−ヒド
ロキシ−2,5,7,8−テトラメチルクロマン−2−
アセチルヒドラゾン 2.46g(5mmol) の1,2−ジクロロ
エタン50ml溶液にトリアセトキシ水素化ホウ素ナトリウ
ム2.12g(10mmol) 及びTHF 50ml を加え室温で15時
間撹拌した。飽和重曹水で中和後、溶媒を留去した。残
渣を酢酸エチル300ml に溶解させ、水、飽和食塩水で洗
浄後、硫酸マグネシウムで乾燥し、溶媒を留去した。残
渣を酢酸エチルに溶解後、ヘキサンを加えて結晶化さ
せ、結晶をろ取した。減圧下で乾燥し、標記化合物 1.7
0g (収率69%)を得た。
Example 215 N ′-(5-bromo-2-
(Hydroxy-3-methoxybenzyl) -6-hydroxy-2,5,7,8-tetramethylchroman-2-acetohydrazide (N '-(5-bromo-2-hydroxy-3-methoxybenzyl)-
6-hydroxy-2,5,7,8-tetramethylchroman-2-acetohydraz
ide) 5-Bromo-3-methoxysalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-
To a solution of 2.46 g (5 mmol) of acetylhydrazone in 50 ml of 1,2-dichloroethane were added 2.12 g (10 mmol) of sodium triacetoxyborohydride and 50 ml of THF, and the mixture was stirred at room temperature for 15 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. The residue was dissolved in 300 ml of ethyl acetate, washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. After dissolving the residue in ethyl acetate, hexane was added for crystallization, and the crystals were collected by filtration. Dry under reduced pressure to give the title compound 1.7
0 g (yield 69%) was obtained.

【0358】(物性) 淡黄褐色固体(mp.103-107 ℃) PMR(DMSO-d6,δppm): 9.38(1H,d,J=6.0Hz),9.20(1H,s),
7.36(1H,s),6.99(2H,s),5.40(1H,q,J=6.0Hz),3.90-3.77
(5H,m),2.60-2.40(2H,m),2.32(1H,d,J=13.5Hz),2.21(1
H,d,J=13.5Hz),2.04(3H,s),2.01(3H,s),1.95(3H,s),1.9
1-1.83(1H,m),1.75-1.65(1H,m),1.26(3H,s) IR(KBr, cm-1):3287,2934,1645,1538,1489,1378,1354,1
296,1232,1087,922,853,832,749,573
(Physical properties) Light yellowish brown solid (mp. 103-107 ° C.) PMR (DMSO-d 6 , δ ppm): 9.38 (1H, d, J = 6.0 Hz), 9.20 (1H, s),
7.36 (1H, s), 6.99 (2H, s), 5.40 (1H, q, J = 6.0Hz), 3.90-3.77
(5H, m), 2.60-2.40 (2H, m), 2.32 (1H, d, J = 13.5Hz), 2.21 (1
H, d, J = 13.5Hz), 2.04 (3H, s), 2.01 (3H, s), 1.95 (3H, s), 1.9
1-1.83 (1H, m), 1.75-1.65 (1H, m), 1.26 (3H, s) IR (KBr, cm -1 ): 3287,2934,1645,1538,1489,1378,1354,1
296,1232,1087,922,853,832,749,573

【0359】実施例216 N’−(3,5−ジブロモ
−2−ヒドロキシベンジル)−6−ヒドロキシ−2,
5,7,8−テトラメチルクロマン−2−アセトヒドラ
ジド(N'-(3,5-dibromo-2-hydroxybenzyl)-6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetohydrazide) 3,5−ジブロモサリチルアルデヒド6−ヒドロキシ−
2,5,7,8−テトラメチルクロマン−2−アセチル
ヒドラゾン 1.61g(2.98mmol)のTHF 50ml 溶液にトリ
アセトキシ水素化ホウ素ナトリウム2.52g(11.92mmol)を
加え室温で15時間撹拌した。飽和重曹水で中和後、溶
媒を留去した。残渣に水を加え酢酸エチルで抽出した。
酢酸エチル層を水、飽和食塩水で洗浄後、硫酸マグネシ
ウムで乾燥し、溶媒を留去した。残渣をシリカゲルカラ
ムクロマトグラフィーに付し、ヘキサン:酢酸エチル=
1:1溶出部を留去し、標記化合物を無色無定形固体と
して 1.45g (収率90%)を得た。
Example 216 N ′-(3,5-dibromo-2-hydroxybenzyl) -6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetohydrazide (N '-(3,5-dibromo-2-hydroxybenzyl) -6-hydroxy-2,
5,7,8-tetramethylchroman-2-acetohydrazide) 3,5-dibromosalicylaldehyde 6-hydroxy-
To a solution of 1.6 g (2.98 mmol) of 2,5,7,8-tetramethylchroman-2-acetylhydrazone in 50 ml of THF was added 2.52 g (11.92 mmol) of sodium triacetoxyborohydride and the mixture was stirred at room temperature for 15 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue, and the mixture was extracted with ethyl acetate.
The ethyl acetate layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and hexane: ethyl acetate =
The 1: 1 eluate was distilled off to give 1.45 g (yield 90%) of the title compound as a colorless amorphous solid.

【0360】(物性) 無色無定形固体 PMR(DMSO-d6,δppm): 10.80(1H,brs),9.63(1H,s),7.60-
7.55(1H,m),7.40-7.30(2H,m),5.71(1H,brs),3.98-3.89
(2H,m)2.57-2.40(2H,m),2.35(1H,d,J=14.0Hz),2.25(1H,
d,J=14.0Hz),2.04(3H,s),2.01(3H,s),1.95(3H,s),1.96-
1.84(1H,m),1.77-1.68(1H,m),1.28(3H,s) IR(KBr, cm-1):3296,2927,1660,1538,1459,1378,1339,1
255,1154,1086,1059,1035,1007,920,858,685
(Physical properties) Colorless amorphous solid PMR (DMSO-d 6 , δ ppm): 10.80 (1H, brs), 9.63 (1H, s), 7.60-
7.55 (1H, m), 7.40-7.30 (2H, m), 5.71 (1H, brs), 3.98-3.89
(2H, m) 2.57-2.40 (2H, m), 2.35 (1H, d, J = 14.0Hz), 2.25 (1H,
d, J = 14.0Hz), 2.04 (3H, s), 2.01 (3H, s), 1.95 (3H, s), 1.96-
1.84 (1H, m), 1.77-1.68 (1H, m), 1.28 (3H, s) IR (KBr, cm -1 ): 3296,2927,1660,1538,1459,1378,1339,1
255,1154,1086,1059,1035,1007,920,858,685

【0361】実施例217 N’−(2−ヒドロキシ−
4−イソプロポキシ−6−モルホリノベンジル)−6−
ヒドロキシ−2,5,7,8−テトラメチルクロマン−
2−アセトヒドラジド(N'-(2-hydroxy-4-isopropoxy-6-
morpholinobenzyl)-6-hydroxy-2,5,7,8-tetramethylchr
oman-2-acetohydrazide) 4−イソプロポキシ−6−モルホリノサリチルアルデヒ
ド6−ヒドロキシ−2,5,7,8−テトラメチルクロ
マン−2−アセチルヒドラゾン 2.86g(5.47mmol)の1,
2−ジクロロエタン50ml溶液にトリアセトキシ水素化ホ
ウ素ナトリウム4.64g(21.88mmol)を加え室温で15時間
撹拌した。飽和重曹水で中和後、溶媒を留去した。残渣
に水を加え酢酸エチルで抽出した。酢酸エチル層を水、
飽和食塩水で洗浄後、硫酸マグネシウムで乾燥し、溶媒
を留去した。残渣をシリカゲルカラムクロマトグラフィ
ーに付し、ヘキサン:酢酸エチル=1:1溶出部を留去
し、標記化合物を淡黄色無定形固体として 0.2g(収率7
%) を得た。
Example 217 N ′-(2-hydroxy-
4-isopropoxy-6-morpholinobenzyl) -6
Hydroxy-2,5,7,8-tetramethylchroman-
2-acetohydrazide (N '-(2-hydroxy-4-isopropoxy-6-
morpholinobenzyl) -6-hydroxy-2,5,7,8-tetramethylchr
oman-2-acetohydrazide) 4-isopropoxy-6-morpholinosalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone 2.86 g (5.47 mmol) of 1,
To a solution of 2-dichloroethane (50 ml) was added sodium triacetoxyborohydride (4.64 g, 21.88 mmol), and the mixture was stirred at room temperature for 15 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue, and the mixture was extracted with ethyl acetate. Ethyl acetate layer with water,
After washing with a saturated saline solution, it was dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the hexane: ethyl acetate = 1: 1: 1 eluate was distilled off to give 0.2 g of the title compound as a pale yellow amorphous solid (yield 7
%).

【0362】(物性) 淡黄色無定形固体 PMR(DMSO-d6,δppm): 9.51(1H,s),9.39(1H,s),7.38(1H,
s),6.00(1H,s),5.96(1H,s),5.45-5.30(1H,m),4.92(1H,s
ept,J=5.8Hz),3.85-3.70(2H,m),3.10-2.95(4H,m),2.62-
2.40(2H,m),2.32(1H,d,J=13.2Hz),2.23(1H,d,J=13.2H
z),2.04(3H,s),2.02(3H,s),1.97(3H,s),1.94-1.84(1H,
m),1.77-1.67(1H,m),1.65-1.40(6H,m),1.27(3H,s),1.24
(6H,d,J=5.8Hz)
(Physical properties) Light yellow amorphous solid PMR (DMSO-d 6 , δ ppm): 9.51 (1H, s), 9.39 (1H, s), 7.38 (1H,
s), 6.00 (1H, s), 5.96 (1H, s), 5.45-5.30 (1H, m), 4.92 (1H, s
ept, J = 5.8Hz), 3.85-3.70 (2H, m), 3.10-2.95 (4H, m), 2.62-
2.40 (2H, m), 2.32 (1H, d, J = 13.2Hz), 2.23 (1H, d, J = 13.2H
z), 2.04 (3H, s), 2.02 (3H, s), 1.97 (3H, s), 1.94-1.84 (1H,
m), 1.77-1.67 (1H, m), 1.65-1.40 (6H, m), 1.27 (3H, s), 1.24
(6H, d, J = 5.8Hz)

【0363】実施例218 N’−(2−ヒドロキシ−
4,6−ジイソプロポキシベンジル)−6−ヒドロキシ
−2,5,7,8−テトラメチルクロマン−2−アセト
ヒドラジド(N'-(2-hydroxy-4,6-diisopropoxybenzyl)-6
-hydroxy-2,5,7,8-tetramethylchroman-2-acetohydrazi
ne) 4,6−ジイソプロポキシサリチルアルデヒド6−ヒド
ロキシ−2,5,7,8−テトラメチルクロマン−2−
アセチルヒドラゾン 2.49g(5mmol) のTHF 50ml 溶液
にトリアセトキシ水素化ホウ素ナトリウム4.22g(20mmo
l) を加え室温で15時間撹拌した。飽和重曹水で中和
後、溶媒を留去した。残渣に水を加え酢酸エチルで抽出
した。酢酸エチル層を水、飽和食塩水で洗浄後、硫酸マ
グネシウムで乾燥し、溶媒を留去した。残渣をシリカゲ
ルカラムクロマトグラフィーに付し、ヘキサン:酢酸エ
チル=1:1溶出部を留去し、標記化合物を淡黄色無定
形固体として 0.61g (収率24%)を得た。
Example 218 N ′-(2-hydroxy-
4,6-diisopropoxybenzyl) -6-hydroxy-2,5,7,8-tetramethylchroman-2-acetohydrazide (N '-(2-hydroxy-4,6-diisopropoxybenzyl) -6
-hydroxy-2,5,7,8-tetramethylchroman-2-acetohydrazi
ne) 4,6-diisopropoxysalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-
To a solution of 2.49 g (5 mmol) of acetylhydrazone in 50 ml of THF was added 4.22 g (20 mmo) of sodium triacetoxyborohydride.
l) was added and the mixture was stirred at room temperature for 15 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the hexane: ethyl acetate = 1: 1 eluate was distilled off to give 0.61 g (yield: 24%) of the title compound as a pale yellow amorphous solid.

【0364】(物性) 淡黄色無定形固体 PMR(DMSO-d6,δppm): 9.75(1H,s),9.39(1H,s),7.37(1H,
s),5.97(2H,s),5.35(1H,brs),4.52-4.42(2H,m),3.82-3.
78(2H,m),2.62-2.40(2H,m),2.32(1H,d,J=13.2Hz),2.23
(1H,d,J=13.2Hz),2.04(3H,s),2.01(3H,s),1.97(3H,s),
1.94-1.84(1H,m),1.77-1.67(1H,m),1.27(3H,s),1.25(6
H,d,J=5.8Hz),1.23(6H,d,J=5.8Hz)
(Physical properties) Pale yellow amorphous solid PMR (DMSO-d 6 , δ ppm): 9.75 (1H, s), 9.39 (1H, s), 7.37 (1H,
s), 5.97 (2H, s), 5.35 (1H, brs), 4.52-4.42 (2H, m), 3.82-3.
78 (2H, m), 2.62-2.40 (2H, m), 2.32 (1H, d, J = 13.2Hz), 2.23
(1H, d, J = 13.2Hz), 2.04 (3H, s), 2.01 (3H, s), 1.97 (3H, s),
1.94-1.84 (1H, m), 1.77-1.67 (1H, m), 1.27 (3H, s), 1.25 (6
(H, d, J = 5.8Hz), 1.23 (6H, d, J = 5.8Hz)

【0365】実施例219 N’−ピリドキシル−6−
ヒドロキシ−2,5,7,8−テトラメチルクロマン−
2−アセトヒドラジド(N'-pyridoxyl-6-hydroxy-2,5,7,
8-tetramethylchroman-2-acetohydrazide) ピリドキサール6−ヒドロキシ−2,5,7,8−テト
ラメチルクロマン−2−アセチルヒドラゾン 2.20g(5mm
ol) のTHF 50ml 溶液にトリアセトキシ水素化ホウ素
ナトリウム3.18g(15mmol) を加え室温で15時間撹拌し
た。飽和重曹水で中和後、溶媒を留去した。残渣に水を
加え酢酸エチルで抽出した。酢酸エチル層を水、飽和食
塩水で洗浄後、硫酸マグネシウムで乾燥し、溶媒を留去
した。残渣を酢酸エチルに溶解後、ヘキサンを加えて結
晶化させ、結晶をろ取した。減圧下で乾燥し、標記化合
物 1.64g (収率76%)を得た。
Example 219 N′-pyridoxyl-6
Hydroxy-2,5,7,8-tetramethylchroman-
2-acetohydrazide (N'-pyridoxyl-6-hydroxy-2,5,7,
8-tetramethylchroman-2-acetohydrazide) pyridoxal 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone 2.20 g (5 mm
ol) in 50 ml of THF was added 3.18 g (15 mmol) of sodium triacetoxyborohydride and stirred at room temperature for 15 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. After dissolving the residue in ethyl acetate, hexane was added for crystallization, and the crystals were collected by filtration. Drying under reduced pressure gave 1.64 g (yield 76%) of the title compound.

【0366】(物性) 無色結晶(mp.163-165 ℃) PMR(DMSO-d6,δppm): 10.42(1H,s),
9.62(1H,d,J=4.0Hz),7.83(1
H,s),7.37(1H,s),5.65(1H,d
d,J=4.0 and 4.0Hz),5.04(1
H,t,J=5.5Hz),4.43(2H,d,J=
4.0Hz),4.05−4.00(2H,m),2.
59−2.42(2H,m),2.36(1H,d,J
=13.5Hz),2.33(3H,s),2.26
(1H,d,J=13.5Hz),2.04(3H,
s),2.01(3H,s),1.95(3H,s),
1.95−1.86(1H,m),1.80−1.69
(1H,m),1.28(3H,s) IR(KBr, cm−1):3273,2931,1
646,1581,1456,1416,1379,1
288,1257,1236,1229,1086,1
061,1033,1007,973,934,92
2,899,777
(Physical properties) Colorless crystals (mp. 163-165 ° C.) PMR (DMSO-d 6 , δ ppm): 10.42 (1H, s),
9.62 (1H, d, J = 4.0 Hz), 7.83 (1
H, s), 7.37 (1H, s), 5.65 (1H, d
d, J = 4.0 and 4.0 Hz), 5.04 (1
H, t, J = 5.5 Hz), 4.43 (2H, d, J =
4.0 Hz), 4.05 to 4.00 (2H, m), 2.
59-2.42 (2H, m), 2.36 (1H, d, J
= 13.5 Hz), 2.33 (3H, s), 2.26
(1H, d, J = 13.5 Hz), 2.04 (3H,
s), 2.01 (3H, s), 1.95 (3H, s),
1.95-1.86 (1H, m), 1.80-1.69
(1H, m), 1.28 (3H, s) IR (KBr, cm -1 ): 3273, 2931, 1
646,1581,1456,1416,1379,1
288,1257,1236,1229,1086,1
061, 1033, 1007, 973, 934, 92
2,899,777

【0367】実施例220 N’−(2−ヒドロキシ−
4,6−ジメトキシベンジル)−6−ヒドロキシ−2,
5,7,8−テトラメチルクロマン−2−アセトヒドラ
ジド(N’−(2−hydroxy−4,6−dime
thoxybenzyl)−6−hydroxy−2,
5,7,8−tetramethylchroman−
2−acetohydrazide) 4,6−ジメトキシサリチルアルデヒド6−ヒドロキシ
−2,5,7,8−テトラメチルクロマン−2−アセチ
ルヒドラゾン 1.95g(4mmol) のTHF 50ml 溶液にトリ
アセトキシ水素化ホウ素ナトリウム3.39g(16mmol) を加
え室温で15時間撹拌した。飽和重曹水で中和後、溶媒
を留去した。残渣に水を加えクロロホルムで抽出した。
クロロホルム層を水、飽和食塩水で洗浄後、硫酸マグネ
シウムで乾燥し、溶媒を留去した。残渣をシリカゲルカ
ラムクロマトグラフィーに付し、ヘキサン:酢酸エチル
=1:1溶出部を留去し、標記化合物を淡黄色無定形固
体として 0.64g (収率33%)を得た。
Example 220 N '-(2-hydroxy-
4,6-dimethoxybenzyl) -6-hydroxy-2,
5,7,8-Tetramethylchroman-2-acetohydrazide (N '-(2-hydroxy-4,6-dime
thoxybenzyl) -6-hydroxy-2,
5,7,8-tetramethylchroman-
2-acetohydrazide) 4.95 g (4 mmol) of 4,6-dimethoxysalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone was added to 3.39 g of sodium triacetoxyborohydride in 50 ml of THF. 16 mmol) and stirred at room temperature for 15 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue and extracted with chloroform.
The chloroform layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the hexane: ethyl acetate = 1: 1 eluate was distilled off to give 0.64 g (yield 33%) of the title compound as a pale yellow amorphous solid.

【0368】(物性) 淡黄色無定形固体 PMR(DMSO-d6,δppm): 9.82(1H,s),9.41(1H,d,J=5.8Hz),
7.37(1H,s),6.01(2H,s),5.30(1H,q,J=5.8Hz),3.80(2H,
d,J=5.8Hz),3.71(3H,s),3.68(3H,s),2.60-2.40(2H,m),
2.32(1H,d,J=13.5Hz),2.21(1H,d,J=13.5Hz),2.04(3H,
s),2.01(3H,s),1.96(3H,s),1.92-1.83(1H,m),1.78-1.65
(1H,m),1.26(3H,s) IR(KBr, cm-1):3296,2934,1624,1593,1513,1456,1379,1
338,1255,1214,1202,1149,1109,1086,1057,1008,922,81
6
(Physical properties) Pale yellow amorphous solid PMR (DMSO-d 6 , δ ppm): 9.82 (1H, s), 9.41 (1H, d, J = 5.8 Hz),
7.37 (1H, s), 6.01 (2H, s), 5.30 (1H, q, J = 5.8Hz), 3.80 (2H,
d, J = 5.8Hz), 3.71 (3H, s), 3.68 (3H, s), 2.60-2.40 (2H, m),
2.32 (1H, d, J = 13.5Hz), 2.21 (1H, d, J = 13.5Hz), 2.04 (3H,
s), 2.01 (3H, s), 1.96 (3H, s), 1.92-1.83 (1H, m), 1.78-1.65
(1H, m), 1.26 (3H, s) IR (KBr, cm -1 ): 3296,2934,1624,1593,1513,1456,1379,1
338,1255,1214,1202,1149,1109,1086,1057,1008,922,81
6

【0369】実施例221 N’−(2,5−ジヒドロ
キシ−3,4−ジメトキシ−6−メチルベンジル)−6
−ヒドロキシ−2,5,7,8−テトラメチルクロマン
−2−アセトヒドラジド(N'-(2,5-dihydroxy-3,4-dimet
hoxy-6-methylbenzyl)-6-hydroxy-2,5,7,8-tetramethyl
chroman-2-acetohydrazide) 2,5−ジヒドロキシ−3,4−ジメトキシ−6−メチ
ルベンズアルデヒド6−ヒドロキシ−2,5,7,8−
テトラメチルクロマン−2−アセチルヒドラゾン 2.36g
(5mmol) のTHF 30ml 溶液にトリアセトキシ水素化ホ
ウ素ナトリウム4.24g(20mmol) を加え室温で15時間撹
拌した。飽和重曹水で中和後、溶媒を留去した。残渣に
水を加え酢酸エチルで抽出した。酢酸エチル層を水、飽
和食塩水で洗浄後、硫酸マグネシウムで乾燥し、溶媒を
留去した。残渣をシリカゲルカラムクロマトグラフィー
に付し、ヘキサン:酢酸エチル=1:2溶出部を留去
し、淡褐色無定形固体を 1.56g (収率66%)得た。酢酸エ
チルに溶解後、4N塩酸−酢酸エチルを加え、塩酸塩化
を行い、淡黄色結晶を1.18g(収率70%)得た。
Example 221 N ′-(2,5-dihydroxy-3,4-dimethoxy-6-methylbenzyl) -6
-Hydroxy-2,5,7,8-tetramethylchroman-2-acetohydrazide (N '-(2,5-dihydroxy-3,4-dimet
hoxy-6-methylbenzyl) -6-hydroxy-2,5,7,8-tetramethyl
chroman-2-acetohydrazide) 2,5-dihydroxy-3,4-dimethoxy-6-methylbenzaldehyde 6-hydroxy-2,5,7,8-
Tetramethylchroman-2-acetylhydrazone 2.36 g
To a solution of (5 mmol) in 30 ml of THF was added 4.24 g (20 mmol) of sodium triacetoxyborohydride and the mixture was stirred at room temperature for 15 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the eluted portion of hexane: ethyl acetate = 1: 2 was distilled off to obtain 1.56 g (66% yield) of a pale brown amorphous solid. After dissolving in ethyl acetate, 4N hydrochloric acid-ethyl acetate was added and hydrochloric acid chloride was performed to obtain 1.18 g (yield 70%) of pale yellow crystals.

【0370】(物性) 淡黄色結晶(mp.139-144 ℃) PMR(DMSO-d6,δppm): 11.19(1H,brs),8.30(1H,brs),4.2
5-4.18(2H,m),3.76(3H,s),3.73(3H,s),2.58-2.40(4H,
m),2.15(3H,s),2.05(3H,s),2.03(3H,s),1.98(3H,s),1.9
2-1.84(1H,m),1.80-1.70(1H,m),1.30(3H,s) IR(KBr, cm-1):3419,2938,1693,1496,1471,1434,1391,1
259,1192,1124,1100,1086,1060,1006,957,921,852
(Physical properties) Light yellow crystal (mp. 139-144 ° C.) PMR (DMSO-d 6 , δ ppm): 11.19 (1H, brs), 8.30 (1H, brs), 4.2
5-4.18 (2H, m), 3.76 (3H, s), 3.73 (3H, s), 2.58-2.40 (4H, m
m), 2.15 (3H, s), 2.05 (3H, s), 2.03 (3H, s), 1.98 (3H, s), 1.9
2-1.84 (1H, m), 1.80-1.70 (1H, m), 1.30 (3H, s) IR (KBr, cm- 1 ): 3419,2938,1693,1496,1471,1434,1391,1
259,1192,1124,1100,1086,1060,1006,957,921,852

【0371】実施例222 N’−(2−ヒドロキシ−
3−メトキシ−5−ピペリジノメチルベンジル)−6−
ヒドロキシ−2,5,7,8−テトラメチルクロマン−
2−アセトヒドラジド(N'-(2-hydroxy-3-methoxy-5-pip
eridinomethylbenzyl)-6-hydroxy-2,5,7,8-tetramethyl
chroman-2-acetohydrazine) 3−メトキシ−5−ピペリジノメチルサリチルアルデヒ
ド6−ヒドロキシ−2,5,7,8−テトラメチルクロ
マン−2−アセチルヒドラゾン 4.14g(8.12mmol)のTH
F 100ml溶液にトリアセトキシ水素化ホウ素ナトリウム
6.89g(32.48mmol)を加え室温で15時間撹拌した。飽和
重曹水で中和後、溶媒を留去した。残渣に水を加え酢酸
エチルで抽出した。酢酸エチル層を水、飽和食塩水で洗
浄後、硫酸マグネシウムで乾燥し、溶媒を留去した。残
渣をシリカゲルカラムクロマトグラフィーに付し、クロ
ロホルム:メタノール=9:1溶出部を留去し、標記化
合物を淡黄色無定形固体として 0.93g (収率22%)を得
た。
Example 222 N '-(2-hydroxy-
3-methoxy-5-piperidinomethylbenzyl) -6
Hydroxy-2,5,7,8-tetramethylchroman-
2-acetohydrazide (N '-(2-hydroxy-3-methoxy-5-pip
eridinomethylbenzyl) -6-hydroxy-2,5,7,8-tetramethyl
chroman-2-acetohydrazine) 3-methoxy-5-piperidinomethylsalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone 4.14 g (8.12 mmol) of TH
F 100 ml solution in sodium triacetoxyborohydride
6.89 g (32.48 mmol) was added, and the mixture was stirred at room temperature for 15 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the chloroform: methanol = 9: 1 eluted portion was distilled off to obtain 0.93 g (yield: 22%) of the title compound as a pale yellow amorphous solid.

【0372】(物性) 淡黄色無定形固体 PMR(DMSO-d6,δppm): 9.46(1H,s),9.17(1H,brs),7.39(1
H,s),7.01(1H,s),6.91(1H,s),5.34(1H,brs),3.85(2H,
s),3.80(3H,s),3.34(2H,s),2.60-2.40(2H,m),2.33(1H,
d,J=13.5Hz),2.23(1H,d,J=13.5Hz),2.04(3H,s),2.01(3
H,s),1.95(3H,s),1.92-1.82(1H,m),1.77-1.30(7H,m),1.
25(3H,s) IR(KBr, cm-1):3280,2935,1651,1500,1455,1378,1343,1
299,1254,1164,1088,1060,1037,935,856,753
(Physical Properties) Light yellow amorphous solid PMR (DMSO-d 6 , δ ppm): 9.46 (1H, s), 9.17 (1H, brs), 7.39 (1
H, s), 7.01 (1H, s), 6.91 (1H, s), 5.34 (1H, brs), 3.85 (2H,
s), 3.80 (3H, s), 3.34 (2H, s), 2.60-2.40 (2H, m), 2.33 (1H,
d, J = 13.5Hz), 2.23 (1H, d, J = 13.5Hz), 2.04 (3H, s), 2.01 (3
H, s), 1.95 (3H, s), 1.92-1.82 (1H, m), 1.77-1.30 (7H, m), 1.
25 (3H, s) IR (KBr, cm -1 ): 3280,2935,1651,1500,1455,1378,1343,1
299,1254,1164,1088,1060,1037,935,856,753

【0373】実施例223 N’−(2−ヒドロキシ−
3−メトキシ−5−モルホリノメチルベンジル)−6−
ヒドロキシ−2,5,7,8−テトラメチルクロマン−
2−アセトヒドラジド(N'-(2-hydroxy-3-methoxy-5-mor
pholinomethylbenzyl)-6-hydroxy-2,5,7,8-tetramethyl
chroman-2-acetohydrazide) 3−メトキシ−5−モルホリノメチルサリチルアルデヒ
ド6−ヒドロキシ−2,5,7,8−テトラメチルクロ
マン−2−アセチルヒドラゾン 2.30g(4.5mmol) のTH
F 100ml溶液にトリアセトキシ水素化ホウ素ナトリウム
3.8g(18mmol)を加え室温で15時間撹拌した。飽和重曹
水で中和後、溶媒を留去した。残渣に水を加え酢酸エチ
ルで抽出した。酢酸エチル層を水、飽和食塩水で洗浄
後、硫酸マグネシウムで乾燥し、溶媒を留去した。残渣
をシリカゲルカラムクロマトグラフィーに付し、クロロ
ホルム:メタノール=10:1溶出部を留去し、標記化
合物を無色無定形固体として 1.85g (収率80%)を得た。
Example 223 N ′-(2-hydroxy-
3-methoxy-5-morpholinomethylbenzyl) -6
Hydroxy-2,5,7,8-tetramethylchroman-
2-acetohydrazide (N '-(2-hydroxy-3-methoxy-5-mor
pholinomethylbenzyl) -6-hydroxy-2,5,7,8-tetramethyl
chroman-2-acetohydrazide) 3-methoxy-5-morpholinomethylsalicylaldehyde 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetylhydrazone 2.30 g (4.5 mmol) of TH
F 100 ml solution in sodium triacetoxyborohydride
3.8 g (18 mmol) was added and the mixture was stirred at room temperature for 15 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and the chloroform: methanol = 10: 1 eluted portion was distilled off to give 1.85 g (yield 80%) of the title compound as a colorless amorphous solid.

【0374】(物性) 無色無定形固体 PMR(DMSO-d6,δppm): 9.40(1H,d,J=5.8Hz),8.92(1H,s),
7.38(1H,s),6.78(1H,s),6.70(1H,s),5.30(1H,q,J=5.8H
z),3.88-3.78(2H,m),3.77(3H,s),3.57-3.52(4H,m),3.31
(2H,s),2.60-2.40(2H,m),2.35-2.20(6H,m),2.04(3H,s),
2.01(3H,s),1.95(3H,s),1.92-1.84(1H,m),1.76-1.67(1
H,m),1.26(3H,s) IR(KBr, cm-1):3388,2931,2863,1651,1499,1456,1378,1
349,1294,1254,1158,1114,1088,1035,1008,918,865,796
(Physical properties) Colorless amorphous solid PMR (DMSO-d 6 , δ ppm): 9.40 (1H, d, J = 5.8 Hz), 8.92 (1H, s),
7.38 (1H, s), 6.78 (1H, s), 6.70 (1H, s), 5.30 (1H, q, J = 5.8H
z), 3.88-3.78 (2H, m), 3.77 (3H, s), 3.57-3.52 (4H, m), 3.31
(2H, s), 2.60-2.40 (2H, m), 2.35-2.20 (6H, m), 2.04 (3H, s),
2.01 (3H, s), 1.95 (3H, s), 1.92-1.84 (1H, m), 1.76-1.67 (1
H, m), 1.26 (3H, s) IR (KBr, cm -1 ): 3388,2931,2863,1651,1499,1456,1378,1
349,1294,1254,1158,1114,1088,1035,1008,918,865,796

【0375】実施例224 N’−[5−(4−エチル
−1−ピペラジニル)メチル−2−ヒドロキシ−3−メ
トキシベンジル]−6−ヒドロキシ−2,5,7,8−
テトラメチルクロマン−2−アセトヒドラジド(N'-[5-
(4-ethyl-1-piperazino)methyl-2-hydroxy-3-methoxybe
nzyl]-6-hydroxy-2,5,7,8-tetramethylchroman-2-aceto
hydrazide) 5−(4−エチル−1−ピペラジニル)メチル−3−メ
トキシサリチルアルデヒド6−ヒドロキシ−2,5,
7,8−テトラメチルクロマン−2−アセチルヒドラゾ
ン 1.57g(2.91mmol)のTHF 100ml溶液にトリアセトキ
シ水素化ホウ素ナトリウム2.47g(11.64mmol)を加え室温
で15時間撹拌した。飽和重曹水で中和後、溶媒を留去
した。残渣に水を加え酢酸エチルで抽出した。酢酸エチ
ル層を水、飽和食塩水で洗浄後、硫酸マグネシウムで乾
燥し、溶媒を留去した。残渣をシリカゲルカラムクロマ
トグラフィーに付し、クロロホルム:メタノール=1
0:1溶出部を留去し、標記化合物を無定形固体として
1.10g (収率70%)を得た。
Example 224 N ′-[5- (4-Ethyl-1-piperazinyl) methyl-2-hydroxy-3-methoxybenzyl] -6-hydroxy-2,5,7,8-
Tetramethylchroman-2-acetohydrazide (N '-[5-
(4-ethyl-1-piperazino) methyl-2-hydroxy-3-methoxybe
nzyl] -6-hydroxy-2,5,7,8-tetramethylchroman-2-aceto
hydrazide) 5- (4-ethyl-1-piperazinyl) methyl-3-methoxysalicylaldehyde 6-hydroxy-2,5,
To a solution of 1.57 g (2.91 mmol) of 7,8-tetramethylchroman-2-acetylhydrazone in 100 ml of THF was added 2.47 g (11.64 mmol) of sodium triacetoxyborohydride and the mixture was stirred at room temperature for 15 hours. After neutralization with saturated aqueous sodium hydrogen carbonate, the solvent was distilled off. Water was added to the residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated saline, dried over magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography, and chloroform: methanol = 1.
The 0: 1 eluted portion was distilled off to give the title compound as an amorphous solid.
1.10 g (70% yield) was obtained.

【0376】(物性) 無定形固体 PMR(DMSO-d6,δppm): 9.40(1H,d,J=5.8Hz),8.91(1H,s),
7.39(1H,s),6.76(1H,d,J=1.2Hz),6.67(1H,d,J=1.2Hz),
5.35-5.28(1H,m),3.87-3.75(2H,m),3.76(3H,s),3.30(2
H,s),2.60-2.18(14H,m),2.04(3H,s),2.01(3H,s),1.95(3
H,s),1.92-1.83(1H,m),1.76-1.66(1H,m),1.26(3H,s),0.
96(3H,t,J=7.1Hz) IR(KBr, cm-1):3390,2934,2819,1651,1498,1455,1378,1
345,1297,1254,1162,1088,1012,939,922,855,801
(Physical properties) Amorphous solid PMR (DMSO-d 6 , δ ppm): 9.40 (1H, d, J = 5.8 Hz), 8.91 (1H, s),
7.39 (1H, s), 6.76 (1H, d, J = 1.2Hz), 6.67 (1H, d, J = 1.2Hz),
5.35-5.28 (1H, m), 3.87-3.75 (2H, m), 3.76 (3H, s), 3.30 (2
H, s), 2.60-2.18 (14H, m), 2.04 (3H, s), 2.01 (3H, s), 1.95 (3
H, s), 1.92-1.83 (1H, m), 1.76-1.66 (1H, m), 1.26 (3H, s), 0.
96 (3H, t, J = 7.1Hz) IR (KBr, cm -1 ): 3390,2934,2819,1651,1498,1455,1378,1
345,1297,1254,1162,1088,1012,939,922,855,801

【0377】実施例225 N’−ピリドキシル−2−
ヒドロキシ−5−メトキシベンゾヒドラジド(N'-pyrido
xyl-2-hydroxy-5-methoxybenzohydrazide hydrochlorid
e) 2−ヒドロキシ−5−メトキシベンゾヒドラジド 1.82g
(10mmol)及びピリドキサール 2.03g(10mmol)をエタノー
ル 50ml に溶かし、3時間室温で撹拌した。溶媒を留去
し、残渣をTHF 100mlに溶解後、トリアセトキシ水素
化ホウ素ナトリウム8.44g(40mmol) を加え室温で17時
間撹拌した。溶媒を留去し、残渣をシリカゲルカラムク
ロマトグラフィーに付し、クロロホルム:メタノール=
10:1溶出部を留去し、淡黄色不定形固体を得た。残
渣をメタノールに溶解後、4N塩酸−酢酸エチル溶液を
加え、結晶化させ、結晶をろ取した。減圧下で乾燥し、
標記化合物 1.28g (収率35%)を得た。
Example 225 N′-pyridoxyl-2-
Hydroxy-5-methoxybenzohydrazide (N'-pyrido
xyl-2-hydroxy-5-methoxybenzohydrazide hydrochlorid
e) 2-hydroxy-5-methoxybenzohydrazide 1.82 g
(10 mmol) and 2.03 g (10 mmol) of pyridoxal were dissolved in 50 ml of ethanol, and the mixture was stirred at room temperature for 3 hours. The solvent was distilled off, the residue was dissolved in THF (100 ml), and sodium triacetoxyborohydride (8.44 g, 40 mmol) was added, followed by stirring at room temperature for 17 hours. The solvent was distilled off, the residue was subjected to silica gel column chromatography, and chloroform: methanol =
The 10: 1 eluted portion was distilled off to obtain a pale yellow amorphous solid. After dissolving the residue in methanol, 4N hydrochloric acid-ethyl acetate solution was added to cause crystallization, and the crystals were collected by filtration. Dried under reduced pressure,
1.28 g (yield 35%) of the title compound were obtained.

【0378】(物性) 黄色粉末(mp.190-200 ℃(dec)) PMR(DMSO-d6,δppm): 11.40(1H,brs),10.56(1H,brs),8.
15(1H,s),7.38(1H,d,J=3.4Hz),7.02(1H,dd,J=3.4 and
8.8Hz),6.90(1H,d,J=8.8Hz),4.72(2H,s),4.30(2H,s),3.
73(3H,s),2.62(3H,s) IR(KBr, cm-1):3251,3048,2941,1607,1548,1491,1466,1
421,1335,1291,1207,1153,1079,1035,938,868,842,835,
759 以上の実施例で得られたアシルヒドラゾン誘導体(I)
の構造を表1〜8に示す。
(Physical properties) Yellow powder (mp. 190-200 ° C. (dec)) PMR (DMSO-d 6 , δ ppm): 11.40 (1H, brs), 10.56 (1H, brs), 8.
15 (1H, s), 7.38 (1H, d, J = 3.4Hz), 7.02 (1H, dd, J = 3.4 and
8.8Hz), 6.90 (1H, d, J = 8.8Hz), 4.72 (2H, s), 4.30 (2H, s), 3.
73 (3H, s), 2.62 (3H, s) IR (KBr, cm -1 ): 3251,3048,2941,1607,1548,1491,1466,1
421,1335,1291,1207,1153,1079,1035,938,868,842,835,
759 Acylhydrazone derivative (I) obtained in the above example
Are shown in Tables 1 to 8.

【0379】[0379]

【表1】 [Table 1]

【0380】 [0380]

【0381】 [0381]

【0382】 [0382]

【0383】[0383]

【表2】 [Table 2]

【0384】 [0384]

【0385】 [0385]

【0386】[0386]

【表3】 [Table 3]

【0387】 [0387]

【0388】 [0388]

【0389】 [0389]

【0390】 [0390]

【0391】 [0391]

【0392】 [0392]

【0393】 [0393]

【0394】[0394]

【表4】 [Table 4]

【0395】[0395]

【表5】 [Table 5]

【0396】 [0396]

【0397】 [0397]

【0398】 [0398]

【0399】 [0399]

【0400】 [0400]

【0401】 [0401]

【0402】[0402]

【表6】 [Table 6]

【0403】[0403]

【表7】 [Table 7]

【0404】[0404]

【表8】 [Table 8]

【0405】 [0405]

【0406】試験例1 アシルヒドラゾン誘導体(I)
のメイラード反応阻害作用 アシルヒドラゾン誘導体(I)のメイラード反応阻害作
用は以下に述べるスクリーニング系により確認された。
0.5Mリン酸ナトリウム緩衝液(pH7.4 )に、ウシ血清ア
ルブミン及びグルコースをそれぞれ5 μg/ml及び1Mの濃
度になるように溶解した。更に、表9記載のアシルヒド
ラゾン誘導体(I)を溶解した後、37℃で2 日間培養し
た。培養後、培養液中のAGE 量を抗AGE 抗体(和光純
薬)を用いた非競合ELISA 法により定量した。非競合EL
ISA 法は、Horiuchi等の方法(Horiuchi S. et al., J.
Biol. Chem., 266, 7329-7332(1991))に準じた。
Test Example 1 Acylhydrazone derivative (I)
The Maillard reaction inhibitory effect of the acylhydrazone derivative (I) was confirmed by the screening system described below.
Bovine serum albumin and glucose were dissolved in 0.5 M sodium phosphate buffer (pH 7.4) to a concentration of 5 μg / ml and 1 M, respectively. Furthermore, after dissolving the acylhydrazone derivative (I) shown in Table 9, the cells were cultured at 37 ° C. for 2 days. After the culture, the amount of AGE in the culture solution was quantified by a non-competitive ELISA method using an anti-AGE antibody (Wako Pure Chemical Industries, Ltd.). Non-competitive EL
The ISA method is based on the method of Horiuchi et al. (Horiuchi S. et al., J.
Biol. Chem., 266, 7329-7332 (1991)).

【0407】アシルヒドラゾン誘導体(I)の抑制率
は、以下の式より算出した。 抑制率(%)=[[(Ca-Cb)-(Da-Db)]/(Ca-Cb)] ×100 Ca:(ウシ血清アルブミン+グルコース)培養液中のAG
E 量 Cb:(ウシ血清アルブミン)培養液中のAGE 量 Da:(ウシ血清アルブミン+グルコース+アシルヒドラ
ゾン誘導体(I))培養液中のAGE 量 Db:(ウシ血清アルブミン+アシルヒドラゾン誘導体
(I))培養液中のAGE 量 種々の濃度におけるアシルヒドラゾン誘導体(I)のAG
E 生成抑制効果を調べて、IC50値を求めた。なお、対照
としてアミノグアニジンについても同様の試験を行っ
た。結果を表9に示す。
The inhibition rate of the acylhydrazone derivative (I) was calculated by the following equation. Inhibition ratio (%) = [[(Ca-Cb)-(Da-Db)] / (Ca-Cb)] × 100 Ca: AG in (bovine serum albumin + glucose) culture solution
E amount Cb: AGE amount in (bovine serum albumin) culture solution Da: (bovine serum albumin + glucose + acylhydrazone derivative (I)) AGE amount in culture solution Db: (bovine serum albumin + acylhydrazone derivative (I)) ) Amount of AGE in culture solution AG of acylhydrazone derivative (I) at various concentrations
E The IC50 value was determined by examining the production inhibitory effect. In addition, the same test was performed for aminoguanidine as a control. Table 9 shows the results.

【0408】[0408]

【表9】 [Table 9]

【0409】試験例2 アシルヒドラゾン誘導体(I)
の抗活性酸化作用 アシルヒドラゾン誘導体(I)の抗活性酸化作用は以下
に述べるような過酸化脂質生成抑制効果を調べるスクリ
ーニング系により確認された。ラット腎組織を0.142M塩
化ナトリウムを含む50mM冷リン酸カリウム緩衝液(pH7.
4 )中でホモジネートし、1000×g で10分間遠心分離し
た後、その上清をラット腎ホモジネートとした。2mg/ml
のラット腎ホモジネート3ml に表10記載のアシルヒド
ラゾン誘導体(I)を1 μM の濃度になるように溶解し
た。この溶液を37℃で15分間加温した後、35% 過塩素酸
水溶液を600 μl 添加し、14000 ×g で10分間遠心分離
した。過酸化脂質の生成量はTBA 法に準じて測定した。
即ち、得られた上清3ml に 0.5% 2-チオバルビツール酸
(TBA )水溶液を1.5ml 添加し、100 ℃で15分間加熱し
た。反応液を冷却後、532nm にて比色測定した。標準液
には、1,1,3,3-テトラエトキシプロパンのメタノール溶
液を用いた。
Test Example 2 Acylhydrazone derivative (I)
The anti-oxidative action of the acylhydrazone derivative (I) was confirmed by a screening system for examining the inhibitory effect of lipid peroxide production as described below. Rat kidney tissue was washed with 50 mM cold potassium phosphate buffer containing 0.142 M sodium chloride (pH 7.
4) After homogenization in the mixture and centrifugation at 1000 × g for 10 minutes, the supernatant was used as rat kidney homogenate. 2mg / ml
The acylhydrazone derivative (I) shown in Table 10 was dissolved in 3 ml of the rat kidney homogenate at a concentration of 1 μM. After heating this solution at 37 ° C. for 15 minutes, 600 μl of a 35% perchloric acid aqueous solution was added, and centrifuged at 14000 × g for 10 minutes. The production amount of lipid peroxide was measured according to the TBA method.
That is, 1.5 ml of 0.5% aqueous solution of 2-thiobarbituric acid (TBA) was added to 3 ml of the obtained supernatant, and the mixture was heated at 100 ° C. for 15 minutes. After cooling the reaction solution, it was colorimetrically measured at 532 nm. A methanol solution of 1,1,3,3-tetraethoxypropane was used as a standard solution.

【0410】アシルヒドラゾン誘導体(I)の抑制率
は、以下の式より算出した。 抑制率(%)=[[(Ta-Tb)-(ta-tb)]/(Ta-Tb)] ×100 Ta:ラット腎ホモジネートを加温後のTBA 値 Tb:ラット腎ホモジネートを加温前のTBA 値 ta:(ラット腎ホモジネート+アシルヒドラゾン誘導体
(I))を加温後のTBA値 tb:(ラット腎ホモジネート+アシルヒドラゾン誘導体
(I))を加温前のTBA値 なお、対照としてアミノグアニジン (1×10-4M)につい
ても同様の試験を行った。結果を表10に示す。
The inhibition rate of the acylhydrazone derivative (I) was calculated by the following equation. Inhibition rate (%) = [[(Ta-Tb)-(ta-tb)] / (Ta-Tb)] × 100 Ta: TBA value after heating rat kidney homogenate Tb: before heating rat kidney homogenate TBA value of ta: TBA value after heating (rat kidney homogenate + acylhydrazone derivative (I)) tb: TBA value before heating (rat kidney homogenate + acylhydrazone derivative (I)) A similar test was performed for guanidine (1 × 10 −4 M). Table 10 shows the results.

【0411】[0411]

【表10】 [Table 10]

【0412】試験例3 アシルヒドラゾン誘導体(I)
の糖尿病性腎症に対する効果 実施例33の化合物を用いて、糖尿病性腎症に対する効
果の試験を実施した。糖尿病ラットは、雄性Wistar系ラ
ット(6週令)にストレプトゾトシン(STZ)50m
g/kgを静脈内投与して作成し、24時間後に血糖値
が200mg/dl以上を示したラットを用いた。この
STZ糖尿病ラットを2群に分け、被検物質投与群(n
=6)には、0.5%メチルセルロース水溶液に懸濁さ
せた前記化合物100mg/kgを、糖尿病対照群(n
=6)には、0.5%メチルセルロース水溶液を5ml
/kg投与した。また、無処置の同週令、同系ラットを
正常対照群(n=6)とし、0.5%メチルセルロース
水溶液を5ml/kg投与した。投与方法は、1日1回
3週間の強制経口投与とした。投与3週間後、尿中アル
ブミン排泄量をELISA法により定量した。結果を図
1に示す。
Test Example 3 Acylhydrazone derivative (I)
The effect of diabetic nephropathy on the diabetic nephropathy was tested using the compound of Example 33. Diabetic rats were treated with male Wistar rats (6 weeks old) at 50 m of streptozotocin (STZ).
Rats having a blood glucose level of 200 mg / dl or more after 24 hours were prepared. The STZ diabetic rats were divided into two groups, and the test substance administration group (n
= 6), 100 mg / kg of the compound suspended in a 0.5% aqueous methylcellulose solution was administered to a diabetic control group (n
= 6), 5 ml of 0.5% aqueous methylcellulose solution
/ Kg. In addition, untreated rats of the same age and the same age were treated as normal control group (n = 6), and 5 ml / kg of 0.5% aqueous methylcellulose solution was administered. The administration method was gavage once a day for 3 weeks. Three weeks after administration, urinary albumin excretion was quantified by ELISA. The results are shown in FIG.

【0413】図1に示すように、糖尿病対照群は正常対
照群に比べて、尿中アルブミン排泄量の増加が認められ
た。これに対して、被検物質投与群では、糖尿病対照群
に比べて尿中アルブミン排泄量の抑制効果が認められ
た。その抑制効果は、糖尿病対照群と比較して57%の
抑制であった。
As shown in FIG. 1, urine albumin excretion was increased in the diabetic control group as compared with the normal control group. On the other hand, the test substance administration group was found to have an effect of suppressing urinary albumin excretion as compared with the diabetic control group. The inhibitory effect was 57% lower than that of the diabetic control group.

【0414】試験例4 急性毒性試験 実施例33の化合物を用いて、単回経口投与毒性試験を
実施した。1群3〜4匹の雄性SD系ラットに0.5%
メチルセルロース水溶液に懸濁させた前記化合物を経口
投与した。投与用量は、500mg/kg、1000m
g/kg、2000mg/kg、投与液量は、10ml
/kgとした。一般症状の観察及び体重測定を実施し、
投与14日目に解剖学的検査を行った。その結果、投薬
による死亡は認められず、また、一般症状、体重の推移
及び解剖学的検査のいずれにおいても変化は全く認めら
れなかった。
Test Example 4 Acute toxicity test A single oral administration toxicity test was carried out using the compound of Example 33. 0.5% in 3-4 male SD rats per group
The compound suspended in an aqueous methylcellulose solution was orally administered. The administration dose is 500 mg / kg, 1000 m
g / kg, 2000mg / kg, dose volume is 10ml
/ Kg. Observation of general symptoms and weight measurement,
An anatomical examination was performed 14 days after administration. As a result, no death due to medication was observed, and no change was observed in any of the general symptoms, changes in body weight, and anatomical examination.

【0415】試験例5 エームス試験 「医薬品毒性試験法ガイドライン」(1989年9月1
1日、薬審1第24号)に準じて、実施例97の化合物
を用いて、復帰突然変異試験(エームス試験(Ames' tes
t))を実施した。即ち、Salmonela typhimurium の4菌
種に前記化合物を加えて培養した後、培地に播種し、培
地の復帰変異コロニー数を観察した。S9Mix(フェ
ノバルビタール及び6−ベンゾフラボンによって酵素誘
導されたラット肝臓由来のS9分画の調製液)の有無に
かかわらず、いずれの菌種においても、復帰変異コロニ
ー数の増加をもたらさなかった。よって、前記化合物の
変異原性は、陰性と判定された。
Test Example 5 Ames Test “Guidelines for Test Methods for Drug Toxicity” (September 1, 1989)
One day, using the compound of Example 97, a reverse mutation test (Ames 'tes test (Ames' tes test)
t)). That is, the compound was added to four strains of Salmonela typhimurium and cultured, and then seeded on a medium, and the number of revertant colonies in the medium was observed. Regardless of the presence or absence of S9Mix (preparation of S9 fraction from rat liver enzymatically induced by phenobarbital and 6-benzoflavone), none of the bacterial species resulted in an increase in the number of revertant colonies. Therefore, the mutagenicity of the compound was determined to be negative.

【0416】[0416]

【発明の効果】アシルヒドラゾン誘導体(I)及びその
医薬組成物は、メイラード反応阻害薬及び抗活性酸化薬
として有用であり、特に糖尿病の各種合併症や老人性疾
患等の疾患に有効である。
The acylhydrazone derivative (I) and the pharmaceutical composition thereof are useful as Maillard reaction inhibitors and anti-active oxidants, and are particularly effective for various complications of diabetes and diseases such as senile diseases.

【図面の簡単な説明】[Brief description of the drawings]

【図1】尿中アルブミン排泄量を示す図である。FIG. 1 is a graph showing the amount of albumin excreted in urine.

───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 FI A61K 31/31 A61K 31/31 31/35 ADP 31/35 ADP 31/40 ADS 31/40 ADS 31/44 31/44 31/445 ABL 31/445 ABL 31/47 31/47 31/495 AGZ 31/495 AGZ 31/535 31/535 C07C 235/16 C07C 235/16 A 243/38 243/38 243/40 243/40 251/68 251/68 251/76 251/76 251/80 251/80 251/84 251/84 251/86 251/86 251/88 251/88 255/66 255/66 259/10 259/10 327/56 327/56 C07D 213/42 C07D 213/42 213/64 213/64 213/65 213/65 215/14 215/14 295/12 295/12 A Z 307/52 307/52 311/72 101 311/72 101 333/22 333/22 405/12 213 405/12 213 215 215 407/12 307 407/12 307 409/12 311 409/12 311 (72)発明者 柴山 利恵 埼玉県入間郡大井町鶴ヶ岡5丁目3番1号 日清製粉株式会社創薬研究所内────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. 6 Identification code FI A61K 31/31 A61K 31/31 31/35 ADP 31/35 ADP 31/40 ADS 31/40 ADS 31/44 31/44 31 / 445 ABL 31/445 ABL 31/47 31/47 31/495 AGZ 31/495 AGZ 31/535 31/535 C07C 235/16 C07C 235/16 A 243/38 243/38 243/40 243/40 251/68 251/68 251/76 251/76 251/80 251/80 251/84 251/84 251/86 251/86 251/88 251/88 255/66 255/66 259/10 259/10 327/56 327 / 56 C07D 213/42 C07D 213/42 213/64 213/64 213/65 213/65 215/14 215/14 295/12 295/12 AZ 307/52 307/52 311/72 101 311/72 101 333 / 22 333/22 405/12 213 405/12 213 215 215 407/12 307 407/12 307 409/12 311 409/12 311 (72) Inventor Rie Shibayama 5-3 Tsurugaoka, Oimachi, Iruma-gun, Saitama Number 1 No. Nisshin Flour Milling Co., Ltd.

Claims (8)

【特許請求の範囲】[Claims] 【請求項1】 次式(I): X−W−Y [式中、Xは、次式(A): 【化1】 (式中、R1 及びR2 は、同一又は異なって、C1-4
アルキル基を表し、R3は水素原子又はC1-4 −アルキ
ル基を表し、n1 は0〜2を表す。)で示される基、次
式(B): 【化2】 (式中、R4 及びR5 は、同一又は異なって、C1-4
アルキル基を表し、R6は水素原子又はC1-4 −アルキ
ル基を表す。)で示される基、次式(C): 【化3】 (式中、R7 、R8 、R9 、及びR10は、同一又は異な
って、C1-4 −アルキル基を表し、R11は水素原子又は
1-4 −アルキル基を表し、n2 は0〜3を表す。)で
示される基、又は次式(D): 【化4】 (式中、R27はC1-4 −アルキル基を表し、R28は水素
原子、ハロゲン原子、水酸基又はC1-4 −アルコキシ基
を表す。)で示される基を表し;Yは、フリル基、チエ
ニル基、ピロリル基、ピリジル基、2−ヒドロキシ−6
−メチルピリジン−3−イル基、C1-4 −アルキル基、
次式(E): 【化5】 (式中、R12、R13、R14、R15及びR16は、同一又は
異なって、水素原子、ハロゲン原子、水酸基、C1-4
アルコキシ基、C1-4 −アルキル−カルボニルオキシ
基、ニトロ基、シアノ基、フェニル基、モルホリノ基、
ピロリジノ基、ピペリジノ基、ピペラジノ基もしくはア
ミノ基(当該ピペラジノ基又はアミノ基中の窒素原子は
1-4 −アルキル基、C5-8 −シクロアルキル基及びC
1-4 −アルコキシ−カルボニルメチル基から選ばれる1
又は2個の基で置換されていてもよい。)又は含窒素複
素環置換−メチル基を表し、また、R12とR13、又はR
15とR16は共同して縮合6員環を形成してもよい。)で
示される基、次式(F): 【化6】 (式中、R17、R18及びR19は、同一又は異なって、水
素原子又はC1-4 −アルキル基を表す。)で示される
基、次式(G): 【化7】 (式中、R20及びR21は、同一又は異なって、水素原子
又はC1-4 −アルキル基を表す。)で示される基、又は
次式(H): 【化8】 (式中、R22、R23及びR24は、同一又は異なって、水
素原子又はC1-4 −アルキル基を表す。)で示される基
を表し;Wは、次式(J): 【化9】 (式中、R25及びR26は、同一又は異なって、水素原子
又はC1-4 −アルキル基を表し、また、R26は、前記式
(E)中のR16と共同してトリメチレン基を形成しても
よく、Z1 は酸素原子又は硫黄原子を表す。)で示され
る基、次式(K): 【化10】 (式中、Z2 は酸素原子又は硫黄原子を表す。)で示さ
れる基、次式(L): 【化11】 (式中、Z3 及びZ4 は、同一又は異なって、酸素原子
又は硫黄原子を表す。)で示される基、次式(M): 【化12】 (式中、Z5 は酸素原子又は硫黄原子を表す。)で示さ
れる基、次式(N): 【化13】 (式中、Z6 及びZ7 は、同一又は異なって、酸素原子
又は硫黄原子を表す。)で示される基、次式(O): 【化14】 (式中、Z8 及びZ9 は、同一又は異なって、酸素原子
又は硫黄原子を表す。)で示される基、次式(P): −CH=N−N=CH− (P) で示される基、又は次式(Q): 【化15】 (式中、Z10は酸素原子又は硫黄原子を表す。)で示さ
れる基を表す。]で示される化合物又はその薬学的に許
容される塩を有効成分として含有する医薬組成物。
1. The following formula (I): X—W—Y wherein X is the following formula (A): (In the formula, R 1 and R 2 are the same or different, and are C 1-4-
Represents an alkyl group, R 3 represents a hydrogen atom or a C 1-4 -alkyl group, and n 1 represents 0 to 2. A group represented by the following formula (B): (Wherein, R 4 and R 5 are the same or different, and are C 1-4-
Represents an alkyl group, and R 6 represents a hydrogen atom or a C 1-4 -alkyl group. A group represented by the following formula (C): (Wherein R 7 , R 8 , R 9 and R 10 are the same or different and represent a C 1-4 -alkyl group, R 11 represents a hydrogen atom or a C 1-4 -alkyl group, and n 2 represents 0 to 3), or the following formula (D): (Wherein, R 27 represents a C 1-4 -alkyl group, and R 28 represents a hydrogen atom, a halogen atom, a hydroxyl group or a C 1-4 -alkoxy group); Group, thienyl group, pyrrolyl group, pyridyl group, 2-hydroxy-6
-Methylpyridin-3-yl group, C 1-4 -alkyl group,
The following formula (E): (Wherein, R 12 , R 13 , R 14 , R 15 and R 16 are the same or different and each represents a hydrogen atom, a halogen atom, a hydroxyl group, C 1-4-
Alkoxy, C 1-4 -alkyl-carbonyloxy, nitro, cyano, phenyl, morpholino,
A pyrrolidino group, a piperidino group, a piperazino group or an amino group (the nitrogen atom in the piperazino group or the amino group is a C 1-4 -alkyl group, a C 5-8 -cycloalkyl group and a C 5-8 -cycloalkyl group;
1 selected from 1-4 -alkoxy-carbonylmethyl groups
Or it may be substituted by two groups. ) Or a nitrogen-containing heterocyclic-substituted methyl group, and R 12 and R 13 , or R
15 and R 16 may together form a fused 6-membered ring. A group represented by the following formula (F): (Wherein, R 17 , R 18 and R 19 are the same or different and each represent a hydrogen atom or a C 1-4 -alkyl group), a group represented by the following formula (G): (Wherein R 20 and R 21 are the same or different and each represent a hydrogen atom or a C 1-4 -alkyl group), or a group represented by the following formula (H): (Wherein, R 22 , R 23 and R 24 are the same or different and each represent a hydrogen atom or a C 1-4 -alkyl group); W represents the following formula (J): 9 (Wherein R 25 and R 26 are the same or different and each represent a hydrogen atom or a C 1-4 -alkyl group, and R 26 is a trimethylene group in cooperation with R 16 in the above formula (E). And Z 1 represents an oxygen atom or a sulfur atom.), A group represented by the following formula (K): (Wherein, Z 2 represents an oxygen atom or a sulfur atom), a group represented by the following formula (L): (Wherein Z 3 and Z 4 are the same or different and each represent an oxygen atom or a sulfur atom), a group represented by the following formula (M): (Wherein, Z 5 represents an oxygen atom or a sulfur atom), a group represented by the following formula (N): (Wherein Z 6 and Z 7 are the same or different and each represent an oxygen atom or a sulfur atom), a group represented by the following formula (O): (Wherein, Z 8 and Z 9 are the same or different and each represent an oxygen atom or a sulfur atom), represented by the following formula (P): -CH = NN-CH- (P) Or a group represented by the following formula (Q): (In the formula, Z 10 represents an oxygen atom or a sulfur atom.) Or a pharmaceutically acceptable salt thereof as an active ingredient.
【請求項2】 メイラード反応阻害薬である請求項1記
載の医薬組成物。
2. The pharmaceutical composition according to claim 1, which is a Maillard reaction inhibitor.
【請求項3】 抗活性酸素薬である請求項1記載の医薬
組成物。
3. The pharmaceutical composition according to claim 1, which is an antireactive oxygen drug.
【請求項4】 次式(I’): X−W−Y [式中、Xは、次式(A): 【化16】 (式中、R1 及びR2 は、同一又は異なって、C1-4
アルキル基を表し、R3は水素原子又はC1-4 −アルキ
ル基を表し、n1 は0〜2を表す。)で示される基、次
式(B): 【化17】 (式中、R4 及びR5 は、同一又は異なって、C1-4
アルキル基を表し、R6は水素原子又はC1-4 −アルキ
ル基を表す。)で示される基、次式(C): 【化18】 (式中、R7 、R8 、R9 、及びR10は、同一又は異な
って、C1-4 −アルキル基を表し、R11は水素原子又は
1-4 −アルキル基を表し、n2 は0〜3を表す。)で
示される基、又は次式(D): 【化19】 (式中、R27はC1-4 −アルキル基を表し、R28は水素
原子、ハロゲン原子、水酸基又はC1-4 −アルコキシ基
を表す。)で示される基を表し;Yは、フリル基、チエ
ニル基、ピロリル基、ピリジル基、2−ヒドロキシ−6
−メチルピリジン−3−イル基、C1-4 −アルキル基、
次式(E): 【化20】 (式中、R12、R13、R14、R15及びR16は、同一又は
異なって、水素原子、ハロゲン原子、水酸基、C1-4
アルコキシ基、C1-4 −アルキル−カルボニルオキシ
基、ニトロ基、シアノ基、フェニル基、モルホリノ基、
ピロリジノ基、ピペリジノ基、ピペラジノ基もしくはア
ミノ基(当該ピペラジノ基又はアミノ基中の窒素原子は
1-4 −アルキル基、C5-8 −シクロアルキル基及びC
1-4 −アルコキシ−カルボニルメチル基から選ばれる1
又は2個の基で置換されていてもよい。)又は含窒素複
素環置換−メチル基を表し、また、R12とR13、又はR
15とR16は共同して縮合6員環を形成してもよい。)で
示される基、次式(F): 【化21】 (式中、R17、R18及びR19は、同一又は異なって、水
素原子又はC1-4 −アルキル基を表す。)で示される
基、次式(G): 【化22】 (式中、R20及びR21は、同一又は異なって、水素原子
又はC1-4 −アルキル基を表す。)で示される基、又は
次式(H): 【化23】 (式中、R22、R23及びR24は、同一又は異なって、水
素原子又はC1-4 −アルキル基を表す。)で示される基
を表し;Wは、次式(J): 【化24】 (式中、R25及びR26は、同一又は異なって、水素原子
又はC1-4 −アルキル基を表し、Z1 は酸素原子又は硫
黄原子を表す。)で示される基、次式(K): 【化25】 (式中、Z2 は酸素原子又は硫黄原子を表す。)で示さ
れる基、次式(L): 【化26】 (式中、Z3 及びZ4 は、同一又は異なって、酸素原子
又は硫黄原子を表す。)で示される基、次式(M): 【化27】 (式中、Z5 は酸素原子又は硫黄原子を表す。)で示さ
れる基、次式(N): 【化28】 (式中、Z6 及びZ7 は、同一又は異なって、酸素原子
又は硫黄原子を表す。)で示される基、次式(O): 【化29】 (式中、Z8 及びZ9 は、同一又は異なって、酸素原子
又は硫黄原子を表す。)で示される基、次式(P):−
CH=N−N=CH− (P)で示される基、又は次
式(Q): 【化30】 (式中、Z10は酸素原子又は硫黄原子を表す。)で示さ
れる基を表す。但し、Xが3,5−ジ−t−ブチル−4
−ヒドロキシフェニル基であり、Yがフェニル基又は2
−ヒドロキシフェニル基であり、かつ、Wが−CONH
NHCO−である場合を除く。]で示される化合物又は
その薬学的に許容される塩。
4. The following formula (I ′): X—W—Y, wherein X is the following formula (A): (In the formula, R 1 and R 2 are the same or different, and are C 1-4-
Represents an alkyl group, R 3 represents a hydrogen atom or a C 1-4 -alkyl group, and n 1 represents 0 to 2. And a group represented by the following formula (B): (Wherein, R 4 and R 5 are the same or different, and are C 1-4-
Represents an alkyl group, and R 6 represents a hydrogen atom or a C 1-4 -alkyl group. A group represented by the following formula (C): (Wherein R 7 , R 8 , R 9 and R 10 are the same or different and represent a C 1-4 -alkyl group, R 11 represents a hydrogen atom or a C 1-4 -alkyl group, and n 2 represents 0 to 3), or the following formula (D): (Wherein, R 27 represents a C 1-4 -alkyl group, and R 28 represents a hydrogen atom, a halogen atom, a hydroxyl group or a C 1-4 -alkoxy group); Group, thienyl group, pyrrolyl group, pyridyl group, 2-hydroxy-6
-Methylpyridin-3-yl group, C 1-4 -alkyl group,
The following formula (E): (Wherein, R 12 , R 13 , R 14 , R 15 and R 16 are the same or different and each represents a hydrogen atom, a halogen atom, a hydroxyl group, C 1-4-
Alkoxy, C 1-4 -alkyl-carbonyloxy, nitro, cyano, phenyl, morpholino,
A pyrrolidino group, a piperidino group, a piperazino group or an amino group (the nitrogen atom in the piperazino group or the amino group is a C 1-4 -alkyl group, a C 5-8 -cycloalkyl group and a C 5-8 -cycloalkyl group;
1 selected from 1-4 -alkoxy-carbonylmethyl groups
Or it may be substituted by two groups. ) Or a nitrogen-containing heterocyclic-substituted methyl group, and R 12 and R 13 , or R
15 and R 16 may together form a fused 6-membered ring. A group represented by the following formula (F): (Wherein R 17 , R 18 and R 19 are the same or different and each represent a hydrogen atom or a C 1-4 -alkyl group), a group represented by the following formula (G): (Wherein R 20 and R 21 are the same or different and each represent a hydrogen atom or a C 1-4 -alkyl group) or a group represented by the following formula (H): (Wherein, R 22 , R 23 and R 24 are the same or different and each represent a hydrogen atom or a C 1-4 -alkyl group); W represents the following formula (J): Embedded image (Wherein R 25 and R 26 are the same or different and each represent a hydrogen atom or a C 1-4 -alkyl group, and Z 1 represents an oxygen atom or a sulfur atom); ): Embedded image (Wherein Z 2 represents an oxygen atom or a sulfur atom), a group represented by the following formula (L): (Wherein Z 3 and Z 4 are the same or different and each represent an oxygen atom or a sulfur atom), a group represented by the following formula (M): (Wherein, Z 5 represents an oxygen atom or a sulfur atom), a group represented by the following formula (N): (Wherein Z 6 and Z 7 are the same or different and each represent an oxygen atom or a sulfur atom), a group represented by the following formula (O): (Wherein, Z 8 and Z 9 are the same or different and each represent an oxygen atom or a sulfur atom), a group represented by the following formula (P):-
CH = NN—CH— a group represented by (P) or the following formula (Q): (In the formula, Z 10 represents an oxygen atom or a sulfur atom.) Provided that X is 3,5-di-t-butyl-4
A hydroxyphenyl group, and Y is a phenyl group or 2
-Hydroxyphenyl group, and W is -CONH
Except when it is NHCO-. Or a pharmaceutically acceptable salt thereof.
【請求項5】 前記式(I’)において、Wが前記式
(J)で示される基である請求項4記載の化合物又はそ
の薬学的に許容される塩。
5. The compound according to claim 4, wherein in the formula (I ′), W is a group represented by the formula (J) or a pharmaceutically acceptable salt thereof.
【請求項6】 前記式(I’)において、Wが前記式
(K)で示される基である請求項4記載の化合物又はそ
の薬学的に許容される塩。
6. The compound or a pharmaceutically acceptable salt thereof according to claim 4, wherein in the formula (I ′), W is a group represented by the formula (K).
【請求項7】 前記式(I’)において、Xが前記式
(A)で示される基である請求項4記載の化合物又はそ
の薬学的に許容される塩。
7. The compound according to claim 4, wherein in the formula (I ′), X is a group represented by the formula (A) or a pharmaceutically acceptable salt thereof.
【請求項8】 前記式(I’)において、Xが前記式
(C)で示される基である請求項4記載の化合物又はそ
の薬学的に許容される塩。
8. The compound according to claim 4, wherein X in the formula (I ′) is a group represented by the formula (C), or a pharmaceutically acceptable salt thereof.
JP10177222A 1997-07-04 1998-06-24 Acylhydrazone derivative Withdrawn JPH11106371A (en)

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