KR900008129B1 - Process for the preparation of benzoic acid derivation - Google Patents
Process for the preparation of benzoic acid derivation Download PDFInfo
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- KR900008129B1 KR900008129B1 KR1019880000705A KR880000705A KR900008129B1 KR 900008129 B1 KR900008129 B1 KR 900008129B1 KR 1019880000705 A KR1019880000705 A KR 1019880000705A KR 880000705 A KR880000705 A KR 880000705A KR 900008129 B1 KR900008129 B1 KR 900008129B1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C63/00—Compounds having carboxyl groups bound to a carbon atoms of six-membered aromatic rings
- C07C63/04—Monocyclic monocarboxylic acids
- C07C63/06—Benzoic acid
- C07C63/10—Halides thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
- C07C51/21—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with molecular oxygen
- C07C51/255—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with molecular oxygen of compounds containing six-membered aromatic rings without ring-splitting
- C07C51/265—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with molecular oxygen of compounds containing six-membered aromatic rings without ring-splitting having alkyl side chains which are oxidised to carboxyl groups
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
본 발명은 의약, 농약 및 기타산업에 있어서 매우 중요한 합성 중간체로 알려진 벤조산 유도체(I)의 제조방법에 관한 것이다.The present invention relates to a process for the preparation of benzoic acid derivative (I), which is known as a synthetic intermediate which is very important in medicine, pesticides and other industries.
여기서 X는 할로겐이다.Where X is halogen.
일반식(I)의 범주내에서 특히 중요한 화합물은 2,4-디클로로-5-플루오로 벤조산, 2,4-디브로모-5-플루오로 벤조산 그리고 2-클로로-4,5-디플루오로 벤조산 등이다.Particularly important compounds within the scope of formula (I) are 2,4-dichloro-5-fluoro benzoic acid, 2,4-dibromo-5-fluoro benzoic acid and 2-chloro-4,5-difluoro Benzoic acid and the like.
일반적으로 이미 공지된 화합물인 2,4-디할로-5-플루오로 벤조산을 공업적으로 제조하는 데는 상당한 문제점이 있는 것으로 알려져 있다.It is generally known that there are significant problems in the industrial preparation of 2,4-dihalo-5-fluorobenzoic acid, which is already known compound.
그 대표적인 방법으로 DE 3142856의 방법을 들 수 있는데 즉, 2,4-디클로로-5-플루오로 벤조산을 제조하기 위하여 3-아미노-4,6-디클로로 톨루엔으로부터 25기압의 고압하에서 탈아조 반응을 시켜 2,4-디클로로-5-플루오로 톨루엔을 얻고 이로부터 한 반응기 내의 두 단계의 클로로화 반응을 통하여 2,4-디클로로-5-플루오로 벤잘 클로라이도와 2,4-디클로로-5-플루오로-1-트리클로로 메칠 벤젠을 제조한 다음, 농황산으로 처리하여 목적하는 2,4-디클로로-5-플루오로벤조산을 제조하였다. (DE 3142856 및 일특소59 -137429)A typical method is DE 3142856, ie, deazo reaction from 3-amino-4,6-dichlorotoluene under high pressure of 25 atmospheres to prepare 2,4-dichloro-5-fluorobenzoic acid. 2,4-dichloro-5-fluoro toluene was obtained from the 2,4-dichloro-5-fluoro benzal chlorido and 2,4-dichloro-5-fluoro through two stages of chlorolation reactions in one reactor. -1-trichloromethyl benzene was prepared and then treated with concentrated sulfuric acid to give the desired 2,4-dichloro-5-fluorobenzoic acid. (DE 3142856 and Specialty 59-137429)
그런데 여기서 각종의 다른 공지된 방법으로 다양하게 얻어지는 2,4-디클로로-5-플루오로 톨루엔의 메칠기를 카르복실산기로 바꾸기 위하여 삼단계의 반응을 거쳐야 하며 중간체인 클로로화 화합물을 분리하기 위하여 공업적으로 사용하기 어려운 칼럼을 이용한 강압 분별 증류를 해야하는 단점이 있다.However, in order to convert the methyl group of 2,4-dichloro-5-fluorotoluene, which is variously obtained by various other known methods, to undergo a carboxylic acid group, it is required to undergo a three-step reaction and industrially to separate an intermediate chloroated compound. There is a disadvantage in that the forced fractional distillation using a column difficult to use.
따라서 본 발명자 등은 종래의 다단계 반응의 단점을 개선하기 위하여 직접 산화시키는 방법을 통하여 한단계 반응으로 목적하는 벤조산 유도체(I)을 제조하였다.Therefore, the present inventors prepared the desired benzoic acid derivative (I) as a one-step reaction through a direct oxidation method in order to improve the disadvantage of the conventional multi-step reaction.
일반적으로 톨루엔 유도체를 벤조산 유도체로 산화시키는 방법은 많이 알려져 있으나, 본 발명의 출발물질인 2,4-디할로-5-플루오로 톨루엔 유도체(II)를 일반적인 산화제로 산화시켜 목적하는 벤조산 유도체(I)을 합성하는 방법은 상당히 어려운 반응으로 거의 알려져 있지 않다.Generally, there are many known methods for oxidizing toluene derivatives to benzoic acid derivatives. ) Is rarely known as a very difficult reaction.
여기에서 X는 할로겐이다.Where X is halogen.
본 발명자 등은 상기와 같은 산화 방법을 개발하고자 많은 산화반응을 검토한 결과, 과망간산 칼륨을 염기 존재하에서 물과 피리딘 혼합 용매로 환류시킨 결과 목적하는 벤조산 유도체(I)을 높은 수율로 간단히 합성할 수 있었다.The present inventors have studied many oxidation reactions to develop the oxidation method as described above. As a result of refluxing potassium permanganate with a mixed solvent of water and pyridine in the presence of a base, the desired benzoic acid derivative (I) can be easily synthesized in high yield. there was.
여기에서 M은 소디움 또는 칼륨, Y는 하이드로겐 카보네이트, 카보네이트, 하이드록사이드 등이다.Wherein M is sodium or potassium, Y is hydrogen carbonate, carbonate, hydroxide and the like.
이들 반응에서 과망간산 칼륨의 양은 2-10배 당량이며, 염기로는 중조, 칼륨 하이드로겐 카보네이트, 소디움 카보네이트, 칼륨 카보네이트, 소디움 하이드록사이드, 칼륨 하이드록사이드 등이고 용매로는 물과 피리딘 혼합 용매이며 빈응 시간은 10-48시간이다.In these reactions, the amount of potassium permanganate is 2-10 times the equivalent, and the base is sodium bicarbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, etc., and the solvent is a mixed solvent of water and pyridine. The time is 10-48 hours.
다음 실시예에서 본 발명을 좀더 구체적으로 설명하고자 한다.In the following examples, the present invention will be described in more detail.
실시예 1Example 1
2,4-디브로모-5-플루오로 톨루엔 19g(70.9밀리몰)과 과망간산 칼륨 34g(215밀리몰), 피리딘 80ml, 물160ml, 소디움 하이드록사이드 19g을 넣고 18시간 환류시킨다.19 g (70.9 mmol) of 2,4-dibromo-5-fluoro toluene, 34 g (215 mmol) of potassium permanganate, 80 ml of pyridine, 160 ml of water, and 19 g of sodium hydroxide were added and refluxed for 18 hours.
생성되는 고체를 여과하고 여액을 감압증류하여 피리딘을 제거한 후 10% 염산으로 산성화하면 백색의 고체인 2,4-디브로모-5-플루오로 벤조산 15.1g을 얻는다. (m.p. 139-141℃, 수율 71.5%)The resulting solid was filtered, the filtrate was distilled under reduced pressure to remove pyridine and acidified with 10% hydrochloric acid to give 15.1 g of a white solid 2,4-dibromo-5-fluorobenzoic acid. (m.p. 139-141 ℃, yield 71.5%)
실시예 2Example 2
2,4-디클로로-5-플루오로 톨루엔 21.5g(120밀리몰)과 과망간산 칼륨 57g(360밀리몰) 피리딘 90ml, 물180ml, 소디움 하이드록사이드 20g을 넣고 24시간 환류시킨다.21.5 g (120 mmol) of 2,4-dichloro-5-fluoro toluene, 90 g of potassium permanganate (360 mmol) pyridine, 180 ml of water, and 20 g of sodium hydroxide were added and refluxed for 24 hours.
생성되는 고체를 여과하고 여액을 감압증류하여 피리딘을 제거한 후 10% 염산으로 산성화하면 백색의 고체인 2,4-디클로로-5-플루오로 벤조산 18.5g을 얻는다. (m.p. 141-142℃, 수율 73.4%)The resulting solid was filtered, the filtrate was distilled under reduced pressure to remove pyridine and acidified with 10% hydrochloric acid to obtain 18.5 g of a white solid 2,4-dichloro-5-fluorobenzoic acid. (m.p. 141-142 ° C., yield 73.4%)
실시예 3Example 3
2-클로로-4,5-디플루오로 톨루엔 19.6g(120밀리몰)과 과망간산 칼륨 51.3g(324밀리몰) 피리딘 80ml, 물 160ml, 소디움 하이드록사이드 19g을 넣고 24시간 환류시킨다.19.6 g (120 mmol) of 2-chloro-4,5-difluoro toluene, 51.3 g (324 mmol) of potassium permanganate, 80 ml of water, and 19 g of sodium hydroxide were added to reflux for 24 hours.
생성되는 고체를 여과하고 여액을 감압증류하여 피리딘을 제거한 후 10% 염산으로 산성화하면 백색의 고체인 2-클로로-4,5-디플루오로 벤조산 17.5g을 얻는다. (m.p. 141-143℃, 수율 75%)The resulting solid was filtered, the filtrate was distilled under reduced pressure to remove pyridine, and acidified with 10% hydrochloric acid to obtain 17.5 g of 2-chloro-4,5-difluorobenzoic acid as a white solid. (m.p. 141-143 ° C, yield 75%)
실시예 4Example 4
2,4-디클로로-5-플루오로 톨루엔 19.7(110밀리몰)과 과망간산 칼륨 52. 2g(330밀리몰), 피리딘 80ml, 물 160ml, 소디움카보네이트 18g을 넣고 24시간 환류시킨다.19.7 (110 mmol) of 2,4-dichloro-5-fluoro toluene, 52.2 g (330 mmol) of potassium permanganate, 80 ml of pyridine, 160 ml of water, and 18 g of sodium carbonate were added and refluxed for 24 hours.
생성되는 고체를 여과하고 여액을 감압증류하여 피리딘을 제거한 후 10% 염산으로 산성화하면 백색의 고체 2,4-디클로로-5-플루오로 벤조산 16.4g을 얻는다. (수율 71.0%)The resulting solid was filtered, the filtrate was distilled under reduced pressure to remove pyridine and acidified with 10% hydrochloric acid to give 16.4 g of a white solid 2,4-dichloro-5-fluorobenzoic acid. (Yield 71.0%)
실시예 5Example 5
2,4-디클로로-5-플루오로 톨루엔 21.5g(120밀리몰)과 과망간산칼륨 57g(360밀리몰), 피리딘 90ml, 물 180ml, 소디움하드로겐 카보네이트 20g을 넣고 24시간 환류시킨다.21.5 g (120 mmol) of 2,4-dichloro-5-fluoro toluene, 57 g (360 mmol) of potassium permanganate, 90 ml of pyridine, 180 ml of water and 20 g of sodium hydrogen carbonate were added and refluxed for 24 hours.
생성되는 고체를 여과하고 여액을 감압증류하여 피리딘을 제거한 후 10% 염산으로 산성화 하면 백색의 고체인 2,4-디클로로-5-플루오로 벤조산 18.0g을 얻는다. (수율 71.5%)The resulting solid was filtered, the filtrate was distilled under reduced pressure to remove pyridine and acidified with 10% hydrochloric acid to give 18.0 g of 2,4-dichloro-5-fluorobenzoic acid as a white solid. (Yield 71.5%)
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019880000705A KR900008129B1 (en) | 1988-01-29 | 1988-01-29 | Process for the preparation of benzoic acid derivation |
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| Application Number | Priority Date | Filing Date | Title |
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| KR1019880000705A KR900008129B1 (en) | 1988-01-29 | 1988-01-29 | Process for the preparation of benzoic acid derivation |
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| Publication Number | Publication Date |
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| KR890011818A KR890011818A (en) | 1989-08-22 |
| KR900008129B1 true KR900008129B1 (en) | 1990-10-31 |
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