JPH01102072A - Production of epoxide derivative - Google Patents
Production of epoxide derivativeInfo
- Publication number
- JPH01102072A JPH01102072A JP62259481A JP25948187A JPH01102072A JP H01102072 A JPH01102072 A JP H01102072A JP 62259481 A JP62259481 A JP 62259481A JP 25948187 A JP25948187 A JP 25948187A JP H01102072 A JPH01102072 A JP H01102072A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- reaction
- compound
- epichlorohydrin
- lower alkyl
- 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.)
- Pending
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 150000002118 epoxides Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 12
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 239000003518 caustics Substances 0.000 claims abstract description 7
- 239000003513 alkali Substances 0.000 claims abstract description 6
- 125000003118 aryl group Chemical group 0.000 claims abstract description 5
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical group [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims abstract description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 4
- 125000005843 halogen group Chemical group 0.000 claims abstract description 4
- 150000002924 oxiranes Chemical class 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 abstract description 16
- YBPAYPRLUDCSEY-UHFFFAOYSA-N 2-(4-hydroxyphenyl)acetamide Chemical compound NC(=O)CC1=CC=C(O)C=C1 YBPAYPRLUDCSEY-UHFFFAOYSA-N 0.000 abstract description 8
- XENVCRGQTABGKY-ZHACJKMWSA-N chlorohydrin Chemical compound CC#CC#CC#CC#C\C=C\C(Cl)CO XENVCRGQTABGKY-ZHACJKMWSA-N 0.000 abstract description 5
- 239000003444 phase transfer catalyst Substances 0.000 abstract description 5
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 abstract description 4
- 239000000203 mixture Substances 0.000 abstract description 4
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 abstract description 3
- 229960002274 atenolol Drugs 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 239000002904 solvent Substances 0.000 abstract description 3
- 230000001800 adrenalinergic effect Effects 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 239000011541 reaction mixture Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- 239000004593 Epoxy Substances 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 3
- FAYGEALAEQKPDI-UHFFFAOYSA-N 4-(2-methoxyethyl)phenol Chemical compound COCCC1=CC=C(O)C=C1 FAYGEALAEQKPDI-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- KQGBLRILCYSUFE-UHFFFAOYSA-N 4-(oxiran-2-ylmethoxy)benzamide Chemical compound C1=CC(C(=O)N)=CC=C1OCC1OC1 KQGBLRILCYSUFE-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- KXHPPCXNWTUNSB-UHFFFAOYSA-M benzyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1=CC=CC=C1 KXHPPCXNWTUNSB-UHFFFAOYSA-M 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- -1 methanol Chemical class 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Epoxy Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明はエポキサイド誘導体く関する。[Detailed description of the invention] [Industrial application field] The present invention relates to epoxide derivatives.
本発明忙よって得られるエポキサイド誘導体はアテノロ
ールなどのβ−アドレナリン作動神経速断作用を有する
薬物の中間体として有用である。The epoxide derivatives obtained by the present invention are useful as intermediates for drugs such as atenolol that have a fast-acting action on β-adrenergic nerves.
下記式（５）
（式中ム「はアリール基を表わす）
で表わされるエポキシ化合物を製造する方法は特公昭５
５−５２８７．５３−１７５８７等に示されている。A method for producing an epoxy compound represented by the following formula (5) (in which "m" represents an aryl group) is described in Japanese Patent Publication No. 5, Sho 5.
5-5287.53-17587 etc.
しかし、従来の製造方法は一般に反応未達の中間生成物
が多量に副生ずるため精製工程や蒸留工程が必要で収率
、が極めて低く工業的に難点を有している。However, conventional production methods generally produce a large amount of unreacted intermediate products as by-products, requiring purification steps and distillation steps, resulting in extremely low yields and industrial difficulties.
本発明は高純度のエポキシ化合物を高収率で製造する方
法を提供する。The present invention provides a method for producing high purity epoxy compounds in high yields.
本発明は式（１）
％式％（１）
Ｃ式中Ａ「はアリール基である）で示される化合物とエ
ピクロルヒドリンを式（２）
％式％（２）
Ｃ式中、Ｒ′は０１〜４の低級アルキル基ＳＲはベンジ
ル基又はＣ１〜８の低級アルキル基、Ｘはハロゲン原子
又はサルフェート基を示す）の相関移動触媒の存在下に
反応させ１次いで苛性アルカリを添加して反応完結させ
ることを特徴とする式（３）ｃ式中Ａ「は前記に同じ）
で表わされるエポキサイド誘導体の製法に関する。The present invention combines a compound represented by the formula (1) (1) where A is an aryl group and epichlorohydrin with the formula (2) (2) where R' is 01- The lower alkyl group SR in No. 4 is a benzyl group or a C1-8 lower alkyl group, and X is a halogen atom or a sulfate group. In the formula (3) c, A "is the same as above."
This invention relates to a method for producing an epoxide derivative represented by:
上記式（１）におけるＡ「のアリール基としてはカルバ
モイルアルキルフェニル基。The aryl group of A in the above formula (1) is a carbamoylalkylphenyl group.
などがあげられる。etc. can be mentioned.
式（２）におけるＸとしては例えば塩素原子、臭素原子
、ヨウ素原子などのハロゲン原子やサルフェート基があ
げられる。Ｒ′としては例えばメチル、エチル、プロピ
ル、ブチルなどのＣ１〜Ｃ４の低級アルキル基があげら
れる。Ｒとしては例えばベンジル基、又はメチル、エチ
ル、プロピル、ブチル、ペンチル、ヘキシル、ヘプチル
、オクチルなどのＣ１−Ｃ８のアルキル基などがあげら
れる。Examples of X in formula (2) include halogen atoms such as chlorine atom, bromine atom, and iodine atom, and sulfate groups. Examples of R' include C1 to C4 lower alkyl groups such as methyl, ethyl, propyl, and butyl. Examples of R include a benzyl group, or a C1-C8 alkyl group such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl.
式（２）の相関移動触媒としてはヂトラメチルアンモニ
ウムクロライド又はブロマイド、テトラブチルアンモニ
ウムクロライド又はブロマイド、ベンジルトリメチルア
ンモニウムクロライド又はブロマイド、ベンジルトリエ
チルアンモニウムクロライド又はブロマイド、ベンジル
トリエチルアンそニウムメチルサルフェートなどがあげ
られる。Examples of the phase transfer catalyst of formula (2) include ditramethylammonium chloride or bromide, tetrabutylammonium chloride or bromide, benzyltrimethylammonium chloride or bromide, benzyltriethylammonium chloride or bromide, benzyltriethylamsonium methyl sulfate, etc. .
苛性アルカリとしては ＫＯＨ、ＮａＯＨ等があげられ
る。Examples of caustic alkalis include KOH and NaOH.
本発明の式（５）のエポキシ化合物としては例えられる
。Examples of the epoxy compound of formula (5) of the present invention include:
次に本発明の製法について説明する。Next, the manufacturing method of the present invention will be explained.
本発明の反応は次の経路で進行する。The reaction of the present invention proceeds through the following route.
■の反応は式（１）の化合物とこれに対して２〜１０倍
モル好まＬ＜ｔｉ ４〜５モルのエピクロルヒドリンを
（１）Ｋ対して少なくともｏ、ｏ ｏ ｓ倍モル好まし
くは０・０１〜０．１倍モルの相間移動触媒の存在下に
好ましくは４０〜８０℃の温度範囲で０．５〜２時間反
応させる。In the reaction (2), the compound of formula (1) is mixed with the compound of formula (1) preferably 2 to 10 times the molar amount, L<ti, and 4 to 5 mol of epichlorohydrin is at least o, o o s times the molar amount of (1) K, preferably 0.01 The reaction is preferably carried out at a temperature range of 40 to 80°C for 0.5 to 2 hours in the presence of ~0.1 times the mole of phase transfer catalyst.
この反応に当り、所望により溶媒を使用してもよい。溶
媒としては１例えばメタノール、イノプロピルアルコー
ル、ｔ−ブチルアルコールナトのアルコール類、ジメチ
ルホルムアミド、ジメチルスルホキシド、ジオキサンな
どがあげられる。In this reaction, a solvent may be used if desired. Examples of the solvent include alcohols such as methanol, inopropyl alcohol, t-butyl alcohol, dimethylformamide, dimethyl sulfoxide, and dioxane.
■の反応は好ましくは（１）と等モルの苛性アルカリを
加え、７０℃〜８０℃で１〜５時間反応を行う。苛性ア
ルカリは次式の如（クロルヒドリンに作用しエポキサイ
ドを形成させる。In the reaction (2), preferably an equimolar amount of caustic alkali is added to (1) and the reaction is carried out at 70°C to 80°C for 1 to 5 hours. Caustic alkali acts on chlorohydrin to form epoxide according to the following formula.
Ｃ式中１Ｍはに、Ｎａを示す）。1M in formula C represents Na).
本発明の方法によると（１）、■の反応において相間移
動触媒を用いることによりエピクロルヒドリンの使用モ
ル比を減少させ、不純物の副生を抑え、■の反応におい
て苛性アルカリを加えることにより反応中間体であるク
ロルヒドリンをはぼ完全にエポキサイドに変換せしめる
ため従来法に較ベエボキサイドの収率及び品質が飛躍的
だ向上する。（２） ＋ （１） で高純度のエポキ
サイドが得られるためこれを濾過分離及び精製や蒸留を
行う必要が無く、−浴でＯのアミノ化が可能である。し
かも先の触媒効果忙より、低温、短時間の反応が可能で
オートクレーブなどの特殊装置が不要である。According to the method of the present invention (1), the molar ratio of epichlorohydrin used is reduced by using a phase transfer catalyst in the reaction (2), suppressing the by-product of impurities, and the reaction intermediate is reduced by adding caustic alkali in the reaction (2). Since the chlorohydrin is almost completely converted into epoxide, the yield and quality of epoxide are dramatically improved compared to conventional methods. (2) + Since a highly pure epoxide can be obtained in (1), it is not necessary to perform filtration separation, purification or distillation, and O can be aminated in a − bath. Moreover, because of the catalytic effect described above, the reaction can be carried out at low temperatures and in a short time, and special equipment such as an autoclave is not required.
Ｎ）、 （２）の効果により、従来公知の技術に較べ収
率１品質、操作の単純化など大幅に改善され。Due to the effects of N) and (2), the yield, quality, and operational simplicity are greatly improved compared to conventionally known techniques.
工業的製法として極めて優れたものである。This is an extremely excellent industrial manufacturing method.
実施例１
ｐ−ヒドロキシフェニルアセタミ）ＭＯ，６９゜テトラ
ブチルアンモニウムプロマイ）’０．３５？及びエピク
ロルヒドリン２５．９９Ｃ４当量比）の混合物を６５℃
〜６６℃で１時間加熱し、ＫＱＨフレーク４．１．ｆを
メタノール２０ｄに溶かした溶液を６５〜７０℃で加え
、７０〜７２℃で１時間加熱する。（反応液を一部サン
プリングしＨＰＬＣ分析を行うとクロルヒドリン体Ｏ，
Ｓ％を含む）１反応終了後、水７０ｍを加え減圧下、メ
タノール及び未反応のエピクロルヒドリンを留去し、１
−ｐ−カルパモイルメチルフエノキシー２，３−エポキ
シプロパン１２．８ｔを含む濃縮液を得た。ｐ−ヒドロ
キシフェニルアセタミドからの収率ａ Ｓ、Ｓ％に相当
する。Example 1 p-hydroxyphenylacetami) MO, 69°tetrabutylammonium promy)'0.35? and epichlorohydrin (25.99 C4 equivalent ratio) at 65°C.
Heat at ~66°C for 1 hour to form KQH flakes 4.1. A solution of f dissolved in 20 d of methanol is added at 65-70°C, and heated at 70-72°C for 1 hour. (A portion of the reaction solution was sampled and HPLC analysis revealed that chlorohydrin O,
After completion of the reaction, 70 ml of water was added and methanol and unreacted epichlorohydrin were distilled off under reduced pressure.
A concentrated solution containing 12.8 t of -p-carpamoylmethylphenoxy-2,3-epoxypropane was obtained. Yield a from p-hydroxyphenylacetamide corresponds to S, S%.
実施例２
ｐ−（β−メトキシエチル）フェノール１５．２２、テ
トラメチルアンモニウムクロライド０．２９゜エピクロ
ルヒドリンＳ７ｆ及びメタノール２０：ｄの混合物を６
５℃で１時間加熱し、 ＮａＯＨフレーク４．２ＩＰを
６５〜７０℃の温度で分割添加し。Example 2 A mixture of p-(β-methoxyethyl)phenol 15.22, tetramethylammonium chloride 0.29° epichlorohydrin S7f and methanol 20:d
Heat at 5°C for 1 hour and add NaOH flakes 4.2 IP in portions at a temperature of 65-70°C.
７０〜７５℃で１時間加熱する。Heat at 70-75°C for 1 hour.
反応終了後、水を加え、メタノール及び未反応のエピク
ロルヒドリンを留去し、２−エポキシ−３−（ｐ−（β
−メトキシエチル）−フェノキシフ−プロパン１８．８
ｐを含む濃縮液が得られた。原料ｐ −（β−メトキシ
エチル）フェノールからの収率９０．２チに相当する。After the reaction is complete, water is added, methanol and unreacted epichlorohydrin are distilled off, and 2-epoxy-3-(p-(β
-methoxyethyl)-phenoxif-propane 18.8
A concentrated solution containing p was obtained. This corresponds to a yield of 90.2% from the raw material p-(β-methoxyethyl)phenol.
比較例（特公昭５３−５２８７の追試結果）ｐ−ヒドロ
キシフェニルアセタミド５．２ｆ、エピクロルヒドリン
２５ａｔ（Ｉｓ当量）及びピペリジン６滴の混合物を９
５〜１００℃で６時間加熱する。混合物を冷却し、濾過
し、固体生成物をメタノールから再結晶化させると１−
ｐ−カルバモイルフェノキシ−２，３−エポキシプロパ
ン２．９２が得られた。収率６５．４％に相当する。尚
、ＨＰ’ＬｒＣ分析の結果１本生成物中にクロルヒドリ
ン体が１０．４％含まれていた。Comparative example (Results of follow-up test of Japanese Patent Publication No. 53-5287) A mixture of 5.2f of p-hydroxyphenylacetamide, 25at of epichlorohydrin (Is equivalent) and 6 drops of piperidine was
Heat at 5-100°C for 6 hours. The mixture is cooled, filtered, and the solid product is recrystallized from methanol to give 1-
2.92 g of p-carbamoylphenoxy-2,3-epoxypropane was obtained. This corresponds to a yield of 65.4%. As a result of HP'LrC analysis, one product contained 10.4% of chlorohydrin.
参考例１
実施例１の方法によ抄得られたエボキプイド体濃縮液に
メタノール４２Ｒ１及び工ＰＡ３０ＩＩｔ（５当量比）
を加え、４５〜５０℃で１時間加熱した。Reference Example 1 Methanol 42R1 and PA30IIt (5 equivalent ratio) were added to the evokipoid concentrate obtained by the method of Example 1.
was added and heated at 45 to 50°C for 1 hour.
（ＨＰＬＣ分析の結果、Ｏ，Ｓ時間の時点で反応物中に
未反応エポキシ体は確認されなかった）。(As a result of HPLC analysis, no unreacted epoxy substance was confirmed in the reaction product at the time of O, S).
反応終了後、減圧下インプロピルアミン及びメタノール
を留去し、２Ｎの塩酸を加え、ｐＨ−７，ＯＫ調整し不
溶解分を濾過水洗する。After the reaction is completed, inpropylamine and methanol are distilled off under reduced pressure, 2N hydrochloric acid is added to adjust the pH to -7, and insoluble matter is filtered and washed with water.
Ｆ、洗液を一緒ＩＣＬ、活性炭処理を行い１次いで３０
％ＮａＯＨでｐＨ＝１１に調整し、晶出した結晶を一過
、水洗し、乾燥するとアテノロール１４ｆが得られた。F. Combine the washing liquid with ICL and activated carbon treatment for 1 and 30 minutes.
The pH was adjusted to 11 with % NaOH, and the crystals thus crystallized were washed with water and dried to obtain atenolol 14f.
原料のｐ−ヒドロキシフェニルアセタミドからの通算収
率＝７５％であった。The total yield from the raw material p-hydroxyphenylacetamide was 75%.
参考例２
実施例２の方法により得られたエポキシサイド体濃縮液
を用い、参考例１と同様の条件でアミノ化を行い、２Ｎ
、ＨＣｌを加え、ｐＨ＝７に調整したのち、Ｆ遇し、不
純物を除去する。メチレンク胃リドで抽出しメチレンク
ロリド層を蒸発させると１−イングロビルアミノー３−
（ｐ−（β−メトキシエチル）−フェノキシ〕−プロパ
ノールー２の塩酸塩（メトプロノロール）２４・４ｆが
得うした。原料の１）−（β−メトキシエチル）−フェ
ノールからの通算収率＝８０．４％であった。Reference Example 2 Using the epoxide body concentrate obtained by the method of Example 2, amination was carried out under the same conditions as Reference Example 1, and 2N
, HCl was added to adjust the pH to 7, and then treated with F to remove impurities. After extraction with methylene chloride and evaporation of the methylene chloride layer, 1-inglobylamino-3-
(p-(β-methoxyethyl)-phenoxy]-propanol-2 hydrochloride (methopronolol) 24.4f was obtained. Total yield from raw material 1)-(β-methoxyethyl)-phenol= It was 80.4%.
特許出願人 日本化薬株式会社Patent applicant: Nippon Kayaku Co., Ltd.
Claims (1)
式、化学式、表等があります▼（２） （式中、Ｒ′はＣ＿１＿〜＿４の低級アルキル基、Ｒは
ベンジル基又はＣ＿１＿〜＿８の低級アルキル基、Ｘは
ハロゲン原子又はサルフェート基を示す）の相間移動触
媒の存在下に反応させ次いで苛性アルカリを添加して反
応完結させることを特徴とする式（３）▲数式、化学式
、表等があります▼（３） （式中、Ａｒは前記に同じ）で表わされるエポキサイド
誘導体の製造法。(1) A compound represented by the formula Ar-OH (1) (in the formula, Ar is an aryl group) and epichlorohydrin are combined with the formula (2) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (2) (in the formula, R' is a lower alkyl group of C_1_ to_4, R is a benzyl group or a lower alkyl group of C_1_ to_8, X is a halogen atom or a sulfate group), and then reacted by adding caustic alkali. A method for producing an epoxide derivative represented by formula (3) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(3) (in the formula, Ar is the same as above).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62259481A JPH01102072A (en) | 1987-10-16 | 1987-10-16 | Production of epoxide derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62259481A JPH01102072A (en) | 1987-10-16 | 1987-10-16 | Production of epoxide derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01102072A true JPH01102072A (en) | 1989-04-19 |
Family
ID=17334676
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62259481A Pending JPH01102072A (en) | 1987-10-16 | 1987-10-16 | Production of epoxide derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01102072A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0435068A2 (en) * | 1989-12-27 | 1991-07-03 | Daiso Co., Ltd. | Process for producing optically active atenolol and intermediate thereof |
| WO1998012186A1 (en) * | 1996-09-18 | 1998-03-26 | Daiso Co., Ltd. | Process for the preparation of glycidyl ethers |
| US6982349B1 (en) * | 2003-10-31 | 2006-01-03 | Emcure Pharmaceuticals Limited | Process for producing atenolol of high optical purity |
| WO2011043204A1 (en) * | 2009-10-06 | 2011-04-14 | 住友化学株式会社 | Method for producing diepoxy compound |
| CN104086510A (en) * | 2014-07-10 | 2014-10-08 | 中昊(大连)化工研究设计院有限公司 | Synthetic method of naphthylglycidic ether |
| WO2021247667A1 (en) * | 2020-06-03 | 2021-12-09 | Swimc Llc | Oxirane-functional vinyl monomers and methods for making the same |
-
1987
- 1987-10-16 JP JP62259481A patent/JPH01102072A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0435068A2 (en) * | 1989-12-27 | 1991-07-03 | Daiso Co., Ltd. | Process for producing optically active atenolol and intermediate thereof |
| WO1998012186A1 (en) * | 1996-09-18 | 1998-03-26 | Daiso Co., Ltd. | Process for the preparation of glycidyl ethers |
| US6087512A (en) * | 1996-09-18 | 2000-07-11 | Daiso Co., Ltd. | Process for preparation of glycidyl ether |
| US6982349B1 (en) * | 2003-10-31 | 2006-01-03 | Emcure Pharmaceuticals Limited | Process for producing atenolol of high optical purity |
| WO2011043204A1 (en) * | 2009-10-06 | 2011-04-14 | 住友化学株式会社 | Method for producing diepoxy compound |
| CN104086510A (en) * | 2014-07-10 | 2014-10-08 | 中昊(大连)化工研究设计院有限公司 | Synthetic method of naphthylglycidic ether |
| WO2021247667A1 (en) * | 2020-06-03 | 2021-12-09 | Swimc Llc | Oxirane-functional vinyl monomers and methods for making the same |
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