JP3536480B2 - 4,5-Dihalogeno-6-dihalogenomethylpyrimidine and process for producing the same - Google Patents
4,5-Dihalogeno-6-dihalogenomethylpyrimidine and process for producing the sameInfo
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- JP3536480B2 JP3536480B2 JP28061695A JP28061695A JP3536480B2 JP 3536480 B2 JP3536480 B2 JP 3536480B2 JP 28061695 A JP28061695 A JP 28061695A JP 28061695 A JP28061695 A JP 28061695A JP 3536480 B2 JP3536480 B2 JP 3536480B2
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- Japan
- Prior art keywords
- dihalogeno
- compound
- dihalogenomethylpyrimidine
- formula
- represented
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Description
【０００１】[0001]
【発明の属する技術分野】本発明は、医薬，農薬などの
中間体として有用である新規な４，５−ジハロゲノ−６
−ジハロゲノメチルピリミジンに関するものである。TECHNICAL FIELD The present invention relates to a novel 4,5-dihalogeno-6 useful as an intermediate for medicines, agricultural chemicals and the like.
-Dihalogenomethylpyrimidine.
【０００２】[0002]
【従来の技術】本発明の目的化合物に近似するハロゲノ
メチルピリミジン誘導体としては、例えば、特開昭５９
−８９６７０号公報に、次式：2. Description of the Related Art As a halogenomethylpyrimidine derivative similar to the object compound of the present invention, for example, JP-A-59 / 59
In Japanese Patent Publication No. 89670, the following formula:
【０００３】[0003]
【化４】 [Chemical 4]
【０００４】〔式中、ＹはＣＨ2 Ｘ（ＸはＦ，Ｃｌ又は
Ｂｒを表す。）又はＣＨ＝ＣＲ1 Ｒ2（Ｒ1 はＦ，Ｃｌ
又はＢｒを表し、Ｒ2 はＨ，Ｆ，Ｃｌ，Ｂｒ又はＣＲ3
Ｒ4 Ｒ 5 を表す。Ｒ3 ，Ｒ4 及びＲ5 は、各々独立して
Ｆ，Ｃｌ又はＢｒを表す。）を表し；ＡはＨ、ＯＨ、Ｓ
Ｈ、Ｆ、Ｃｌ、Ｂｒ、ＯＲ6 又はＯＲ6 （Ｒ6 は炭素数
１〜４個のアルキル基又は炭素数２〜４個のハロアルキ
ル基を表す。）、ＮＲ7Ｒ8 （Ｒ7 及びＲ8 は、各々独
立してＨ，炭素数１〜４個のアルキル基，炭素数３もし
くは４個のアルケニル基又はＲ7 とＲ8 とが一緒になっ
て酸素原子で任意に置換された炭素数３〜７個のポリメ
チレン鎖を形成してもよい。）を表す。ただし、Ｙ，Ｒ
1 〜Ｒ8 及びＡの定義は、この化合物に限定する。〕で
示される化合物が記載されている。しかし、本発明のよ
うな４，５−ジハロゲノ−６−ジハロゲノメチルピリミ
ジンについての記載は認められない。[Wherein Y is CH2X (X is F, Cl or
Represents Br. ) Or CH = CR1R2(R1Is F, Cl
Or represents Br, R2Is H, F, Cl, Br or CR3
RFourR FiveRepresents R3, RFourAnd RFiveAre each independently
Represents F, Cl or Br. ) Is represented; A is H, OH, S
H, F, Cl, Br, OR6Or OR6(R6Is the carbon number
1 to 4 alkyl groups or 2 to 4 carbon haloalkyls
Represents a radical. ), NR7R8(R7And R8Are each German
Vertically, H, alkyl group having 1 to 4 carbon atoms, 3 carbon atoms
Or 4 alkenyl groups or R7And R8Together with
Polymer having 3 to 7 carbon atoms optionally substituted with oxygen atoms
It may form a ethylene chain. ) Represents. However, Y, R
1~ R8And the definition of A is limited to this compound. 〕so
The compounds shown have been described. However, according to the present invention
Una 4,5-dihalogeno-6-dihalogenomethyl pyrimi
No mention of gin is allowed.
【０００５】[0005]
【発明が解決しようとする課題】本発明の目的は、医
薬，農薬などの中間体として有用である新規な４，５−
ジハロゲノ−６−ジハロゲノメチルピリミジンを提供す
ることである。DISCLOSURE OF THE INVENTION The object of the present invention is to provide a novel 4,5-containing compound useful as an intermediate for medicines, agricultural chemicals, etc.
Dihalogeno-6-dihalogenomethylpyrimidine.
【０００６】[0006]
【課題を解決するための手段】本発明者らは、前記の課
題を解決するために検討した結果、新規な４，５−ジハ
ロゲノ−６−ジハロゲノメチルピリミジンを合成する方
法を見出し、本発明を完成するに至った。即ち、本発明
は次の通りである。第１の発明は、次式（１）：DISCLOSURE OF THE INVENTION As a result of studies to solve the above-mentioned problems, the present inventors have found a method for synthesizing a novel 4,5-dihalogeno-6-dihalogenomethylpyrimidine, and have found the present invention. Has been completed. That is, the present invention is as follows. The first invention is represented by the following formula (1):
【０００７】[0007]
【化５】 [Chemical 5]
【０００８】（式中、Ｘ1 ，Ｘ2 及びＹは、ハロゲン原
子を表す。）で示される４，５−ジハロゲノ−６−ジハ
ロゲノメチルピリミジンに関するものである。第２の発
明は、次式（２）：(Wherein X 1 , X 2 and Y represent a halogen atom), and 4,5-dihalogeno-6-dihalogenomethylpyrimidine. The second invention is the following formula (2):
【０００９】[0009]
【化６】 [Chemical 6]
【００１０】（式中、Ｙは前記と同義である。）で示さ
れる６−メチルピリミジン誘導体と次式（３）：(Wherein Y has the same meaning as defined above) and a 6-methylpyrimidine derivative represented by the following formula (3):
【００１１】[0011]
【化７】 [Chemical 7]
【００１２】（式中、Ｘはハロゲン原子を表す。）で示
されるハロゲン類とを反応させることを特徴とする前記
の式（１）で示される４，５−ジハロゲノ−６−ジハロ
ゲノメチルピリミジンの製法に関するものである。(In the formula, X represents a halogen atom.) A 4,5-dihalogeno-6-dihalogenomethylpyrimidine represented by the above formula (1) is characterized by reacting with halogens. It relates to the manufacturing method of.
【００１３】[0013]
【発明の実施の形態】以下、本発明について詳細に説明
する。目的化合物である新規な４，５−ジハロゲノ−６
−ジハロゲノメチルピリミジン〔化合物（１）〕並びに
その製造原料〔化合物（２）〕で表したＸ1 ，Ｘ2 及び
Ｙは、次の通りである。BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below. Novel 4,5-dihalogeno-6 which is a target compound
- X 1, X 2 and Y expressed in dihalogeno methylpyrimidine [Compound (1)] as well as its raw material [compound (2)] are as follows.
【００１４】Ｘ1 ，Ｘ2 及びＹとしては、ハロゲン原子
を挙げることができる。ハロゲン原子としては、塩素原
子，ヨウ素原子，臭素原子，フッ素原子などを挙げるこ
とができるが；塩素原子，臭素原子が好ましい。化合物
（１）としては、前記の各種の置換基を組み合わせたも
のを挙げることができるが、具体的には、後述の表１中
に記載した化合物１〜７を挙げることができる。化合物
（１）は、次に示すように、化合物（２）と化合物
（３）とを溶媒中で反応させることによって製造するこ
とができる。Examples of X 1 , X 2 and Y include a halogen atom. Examples of the halogen atom include chlorine atom, iodine atom, bromine atom, fluorine atom and the like; chlorine atom and bromine atom are preferable. Examples of the compound (1) include compounds in which the above various substituents are combined, and specific examples thereof include compounds 1 to 7 described in Table 1 below. Compound (1) can be produced by reacting compound (2) with compound (3) in a solvent as shown below.
【００１５】[0015]
【化８】 [Chemical 8]
【００１６】（式中、Ｘ1 ，Ｘ2 及びＹは、前記と同義
である。）
溶媒の種類としては、本反応に直接関与しないものであ
れば特に限定されず、例えば、ベンゼン，トルエン，キ
シレン，メチルナフタリン，石油エーテル，リグロイ
ン，ヘキサン，クロルベンゼン，ジクロルベンゼン，塩
化メチレン，クロロホルム，ジクロルエタン，トリクロ
ルエチレン，シクロヘキサンのような塩素化された又は
されていない芳香族，脂肪族，脂環式の炭化水素類；ジ
エチルエーテル，テトラヒドロフラン，ジオキサンなど
のようなエーテル類；前記溶媒の混合物を挙げることが
できる。(In the formula, X 1 , X 2 and Y have the same meanings as described above.) The kind of solvent is not particularly limited as long as it does not directly participate in the reaction, and examples thereof include benzene, toluene, Chlorinated or non-chlorinated aromatics such as xylene, methylnaphthalene, petroleum ether, ligroin, hexane, chlorobenzene, dichlorobenzene, methylene chloride, chloroform, dichloroethane, trichloroethylene, cyclohexane, aliphatic, alicyclic Hydrocarbons; ethers such as diethyl ether, tetrahydrofuran, dioxane, etc .; mixtures of the above solvents.
【００１７】溶媒の使用量は、化合物（２）が５〜８０
重量％になるようにして使用することができるが；１０
〜５０重量％が好ましい。反応温度は、特に限定されな
いが、室温から使用する溶媒の沸点以下の温度範囲内で
あり；１５〜６０℃が好ましい。反応時間は、前記の濃
度，温度によって変化するが；通常２〜１０時間であ
る。化合物（２）は、例えば、ジャーナル・オブ・ケミ
カル・ソサィエティ（Ｊ．Ｃ．Ｓ）３４７８〜３４８１
（１９５５年）に記載の方法に準じて、次式に示すよう
に行うことによって、製造することができる。The amount of the solvent used is 5 to 80 for the compound (2).
It can be used by making it to be a weight%; 10
-50% by weight is preferred. The reaction temperature is not particularly limited, but is within a temperature range from room temperature to the boiling point of the solvent used or less; 15 to 60 ° C. is preferable. The reaction time varies depending on the above-mentioned concentration and temperature; it is usually 2 to 10 hours. The compound (2) can be obtained, for example, from Journal of Chemical Society (JCS) 3478 to 3481.
According to the method described in (1955), it can be produced by carrying out as shown in the following formula.
【００１８】[0018]
【化９】 [Chemical 9]
【００１９】（式中、Ｙは前記と同義である。）
以上のようにして製造された化合物（１）は、反応終了
後、抽出，濃縮，濾過などの通常の後処理を行い、必要
に応じて再結晶，各種クロマトグラフィーなどの公知の
手段で適宜精製することができる。化合物（１）として
は、後述の表１中に示した化合物１〜７などを挙げるこ
とができる。(In the formula, Y has the same meaning as described above.) The compound (1) produced as described above is subjected to usual post-treatments such as extraction, concentration and filtration after the completion of the reaction, and then, if necessary, Accordingly, it can be appropriately purified by a known means such as recrystallization or various chromatography. Examples of the compound (1) include compounds 1 to 7 shown in Table 1 below.
【００２０】[0020]
【実施例】以下、本発明を実施例によって具体的に説明
する。なお、これらの実施例は、本発明の範囲を限定す
るものではない。
実施例１
(1) ４，５−ジクロロ−６−ジクロロメチルピリミジン
（化合物１）の合成
４，５−ジクロロ−６−メチルピリミジン（１６ｇ）を
クロロホルム（１００ｍｌ）に溶解し、約５０℃に加温
・攪拌下に塩素ガスを１時間吹き込んだ。反応終了後、
反応液に窒素ガスを吹き込み、溶存する過剰の塩素ガス
を除いた。次いで、減圧下にクロロホルムを留去し、得
られた油状物をカラムクロマトグラフィー（ワコーゲル
Ｃ−２００、トルエン溶出）で精製することによって、
無色油状液体である目的物を８．５ｇ得た。EXAMPLES The present invention will be specifically described below with reference to examples. It should be noted that these examples do not limit the scope of the present invention. Example 1 (1) Synthesis of 4,5-dichloro-6-dichloromethylpyrimidine (Compound 1) 4,5-Dichloro-6-methylpyrimidine (16 g) was dissolved in chloroform (100 ml) and heated to about 50 ° C. Chlorine gas was blown in for 1 hour while being heated and stirred. After the reaction,
Nitrogen gas was blown into the reaction solution to remove dissolved excess chlorine gas. Then, chloroform was distilled off under reduced pressure, and the obtained oily substance was purified by column chromatography (Wakogel C-200, eluted with toluene).
8.5 g of the target substance which is a colorless oily liquid was obtained.
【００２１】1Ｈ−ＮＭＲ（ＣＤＣｌ3 ）δｐｐｍ ７．１０（ｓ，１Ｈ）、９．００（ｓ，１Ｈ） 1 H-NMR (CDCl 3 ) δppm 7.10 (s, 1H), 9.00 (s, 1H)
【００２２】(2) ４−ブロモ−５−クロロ−６−ジブロ
モメチルピリミジン（化合物２）の合成
４，５−ジクロロ−６−メチルピリミジン（３２．６
ｇ）をクロロホルム（３００ｍｌ）に溶解し、約５０℃
に加温・攪拌下に臭素（１００．８ｇ）を滴下した後、
４時間攪拌した。反応終了後、反応液に窒素ガスを吹き
込み、溶存する過剰の臭素を除いた。次いで、トルエン
に溶解して砕氷水中に注ぎ、トルエン層を分取した。ト
ルエン層を飽和重曹水で洗浄し、水洗した後に無水硫酸
ナトリウムで乾燥した。減圧下にクロロホルムを留去
し、得られた結晶をｎ−ヘキサンによって再結晶するこ
とによって、無色砂状結晶である目的物を３１．０ｇ得
た。(2) Synthesis of 4-bromo-5-chloro-6-dibromomethylpyrimidine (Compound 2) 4,5-dichloro-6-methylpyrimidine (32.6)
g) is dissolved in chloroform (300 ml) and the temperature is about 50 ° C.
After adding bromine (100.8 g) to the mixture with heating and stirring,
Stir for 4 hours. After completion of the reaction, nitrogen gas was blown into the reaction solution to remove dissolved excess bromine. Then, it was dissolved in toluene and poured into crushed ice water to separate the toluene layer. The toluene layer was washed with saturated aqueous sodium hydrogen carbonate, washed with water, and dried over anhydrous sodium sulfate. Chloroform was distilled off under reduced pressure, and the obtained crystals were recrystallized from n-hexane to obtain 31.0 g of the desired product as colorless sand crystals.
【００２３】1Ｈ−ＮＭＲ（ＣＤＣｌ3 ）δｐｐｍ ７．００（ｓ，１Ｈ）、８．９２（ｓ，１Ｈ） 1 H-NMR (CDCl 3 ) δppm 7.00 (s, 1H), 8.92 (s, 1H)
【００２４】(3) ４，５−ジクロロ−６−ジブロモメチ
ルピリミジン（化合物７）の合成
４，５−ジクロロ−６−メチルピリミジン（３２．６
ｇ）をクロロホルム（３００ｍｌ）に溶解し、約５０℃
に加温・攪拌下に臭素（６７．２ｇ）を滴下した後、４
時間攪拌した。反応終了後、反応液に窒素ガスを吹き込
み、溶存する過剰の臭素を除いた。次いで、トルエンに
溶解して砕氷水中に注ぎ、トルエン層を分取した。トル
エン層を飽和重曹水で洗浄し、水洗した後に無水硫酸ナ
トリウムで乾燥した。減圧下にクロロホルムを留去し、
得られた油状物をカラムクロマトグラフィー（ワコーゲ
ルＣ−２００、トルエン溶出）で精製した後、ｎ−ヘキ
サンによって再結晶することによって、無色針状結晶で
ある目的物を２０．５ｇ得た。(3) Synthesis of 4,5-dichloro-6-dibromomethylpyrimidine (Compound 7) 4,5-dichloro-6-methylpyrimidine (32.6)
g) is dissolved in chloroform (300 ml) and the temperature is about 50 ° C.
Bromine (67.2 g) was added dropwise to the mixture with heating and stirring, and then 4
Stir for hours. After completion of the reaction, nitrogen gas was blown into the reaction solution to remove dissolved excess bromine. Then, it was dissolved in toluene and poured into crushed ice water to separate the toluene layer. The toluene layer was washed with saturated aqueous sodium hydrogen carbonate, washed with water, and dried over anhydrous sodium sulfate. Distill off chloroform under reduced pressure,
The obtained oily substance was purified by column chromatography (Wakogel C-200, eluted with toluene) and then recrystallized from n-hexane to obtain 20.5 g of the target substance as colorless needle crystals.
【００２５】1Ｈ−ＮＭＲ（ＣＤＣｌ3 ）δｐｐｍ ７．００（ｓ，１Ｈ）、８．９８（ｓ，１Ｈ） 1 H-NMR (CDCl 3 ) δppm 7.00 (s, 1H), 8.98 (s, 1H)
【００２６】(4) 表１中のその他の化合物（１）の合成
前記(1) 及び(2) のいずれかの方法に準じて、表１中の
その他の化合物（１）を合成した。(4) Synthesis of other compound (1) in Table 1 Other compound (1) in Table 1 was synthesized according to any one of the methods (1) and (2).
【００２７】[0027]
【表１】 [Table 1]
【００２８】[0028]
【発明の効果】本発明の新規な４，５−ジハロゲノ−６
−ジハロゲノメチルピリミジンは、医薬，農薬などの中
間体として有用である。The novel 4,5-dihalogeno-6 of the present invention
-Dihalogenomethylpyrimidine is useful as an intermediate for medicines, agricultural chemicals and the like.
Claims (2)
で示される４，５−ジハロゲノ−６−ジハロゲノメチル
ピリミジン。1. The following formula (1): (In the formula, X 1 , X 2 and Y represent a halogen atom.)
4,5-dihalogeno-6-dihalogenomethylpyrimidine represented by
る６−メチルピリミジン誘導体と次式（３）： 【化３】 （式中、Ｘはハロゲン原子を表す。）で示されるハロゲ
ン類とを反応させることを特徴とする請求項１記載の式
（１）で示される４，５−ジハロゲノ−６−ジハロゲノ
メチルピリミジンの製法。2. The following formula (2): (Wherein Y has the same meaning as described in claim 1) and a 6-methylpyrimidine derivative represented by the following formula (3): The 4,5-dihalogeno-6-dihalogenomethylpyrimidine represented by the formula (1) according to claim 1, wherein the halogen represented by the formula (wherein X represents a halogen atom) is reacted. Manufacturing method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28061695A JP3536480B2 (en) | 1995-10-27 | 1995-10-27 | 4,5-Dihalogeno-6-dihalogenomethylpyrimidine and process for producing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28061695A JP3536480B2 (en) | 1995-10-27 | 1995-10-27 | 4,5-Dihalogeno-6-dihalogenomethylpyrimidine and process for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH09124613A JPH09124613A (en) | 1997-05-13 |
| JP3536480B2 true JP3536480B2 (en) | 2004-06-07 |
Family
ID=17627533
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP28061695A Expired - Fee Related JP3536480B2 (en) | 1995-10-27 | 1995-10-27 | 4,5-Dihalogeno-6-dihalogenomethylpyrimidine and process for producing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3536480B2 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103772369B (en) | 2012-10-25 | 2016-12-21 | 沈阳中化农药化工研发有限公司 | Homopiperony lamine compounds and application thereof |
| EP3760617B1 (en) | 2012-10-25 | 2023-03-22 | Shenyang Sinochem Agrochemicals R&D Co., Ltd. | Substituted pyrimidine compound and uses thereof |
| CN104710409B (en) | 2013-12-13 | 2019-06-04 | 沈阳中化农药化工研发有限公司 | Pyrazolyl pyrimidines aminated compounds and purposes |
| CN111263757A (en) | 2017-11-29 | 2020-06-09 | 沈阳中化农药化工研发有限公司 | Substituted pyrimidine compound and preparation method and application thereof |
-
1995
- 1995-10-27 JP JP28061695A patent/JP3536480B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH09124613A (en) | 1997-05-13 |
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