CN103044241A - Synthesis method of m-phenyl formyl phenylacetic acid - Google Patents

Synthesis method of m-phenyl formyl phenylacetic acid Download PDF

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CN103044241A
CN103044241A CN2012104839929A CN201210483992A CN103044241A CN 103044241 A CN103044241 A CN 103044241A CN 2012104839929 A CN2012104839929 A CN 2012104839929A CN 201210483992 A CN201210483992 A CN 201210483992A CN 103044241 A CN103044241 A CN 103044241A
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reaction
benzoyl
acid
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毛羽
丁炬平
张仁延
余强
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Cgenetech Suzhou China Co Ltd
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Cgenetech Suzhou China Co Ltd
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Abstract

The invention discloses a synthesis method of m-phenyl formyl phenylacetic acid, belonging to the technical fields of medicine and chemical industries. The m-phenyl formyl phenylacetic acid is an important medical intermediate. According to the synthesis method, a simple and practicable reaction for substituting halogens by a cyano group is obtained via exploration and practice; simultaneously, the concentration range of sulphuric acid used during hydrolysis for the cyano group in 3-benzoyl phenyl acetonitrile and the proper temperature of the reaction are determined, thus obtaining the synthesised m-phenyl formyl phenylacetic acid. The synthesis process is moderate in reaction conditions, simple in after-treatment and easy to industrialize.

Description

The synthetic method of a kind of benzoyl toluylic acid
Technical field
The present invention relates to the synthetic process of a kind of benzoyl toluylic acid, belong to medicine, chemical technology field.
Background technology
Between the benzoyl toluylic acid be a kind of white solid, be a kind of important medicine intermediate, this patent provide synthetic between a kind of method of benzoyl toluylic acid.
Summary of the invention
The synthetic method of of the present invention benzoyl toluylic acid; that employing 3-methyl benzoyl chloride is raw material; under cold condition; under the aluminum trichloride (anhydrous) effect, react with benzene; obtain 3-methyldiphenyl ketone; 3-methyldiphenyl ketone and N-bromosuccinimide react in carbon tetrachloride solution; obtain 3-brooethyl benzophenone; 3-brooethyl benzophenone and trimethylsilyl cyanide reaction; obtain 3-benzoyloxy phenyl acetonitrile; 3-benzoyloxy phenyl acetonitrile and 70% sulfuric acid reaction obtain a benzoyl toluylic acid.
The synthetic method of above-mentioned benzoyl toluylic acid is characterized in that: described 3-methyldiphenyl ketone and N-bromosuccinimide react in carbon tetrachloride solution, and wherein solvent does not singly refer to tetracol phenixin, and methylene dichloride, chloroform etc. all can react.
The synthetic method of above-mentioned benzoyl toluylic acid is characterized in that: described 3-benzoyloxy phenyl acetonitrile and 70% sulfuric acid reaction, wherein the concentration range of aqueous sulfuric acid is 50 ~ 80%.
The synthetic method of above-mentioned benzoyl toluylic acid; it is characterized in that: be that employing 30g3-methyl benzoyl chloride is raw material and 38.8g aluminum trichloride (anhydrous); under cold condition; drip 80mL benzene; after dripping; rising to room temperature reaction spends the night; after reaction is finished; after the processing of reaction solution usefulness 50mL frozen water; filter; filter cake dissolves with methylene dichloride; use respectively sodium bicarbonate and saturated common salt water washing; anhydrous sodium sulfate drying; obtain 34g3-methyldiphenyl ketone; 3-methyldiphenyl ketone is dissolved in the 800mL tetracol phenixin; then add the 33gN-bromo-succinimide and spend the night in 75 degree reactions, after reaction is finished, be cooled to room temperature; Rotary Evaporators spins off reaction solvent; residue is poured in the 150mL water, used dichloromethane extraction, anhydrous sodium sulfate drying; obtain 48.3g3-brooethyl benzophenone; after 3-brooethyl benzophenone is dissolved in the 300mL acetonitrile, add 29.3g salt of wormwood, then drip the 21.3g trimethylsilyl cyanide; being warming up to 80 degree reactions spends the night; after reacting completely, add 100mL1mol/LNaOH solution, then use ethyl acetate extraction; organic layer is used the 1mol/LNaOH solution washing again; after the saturated nacl aqueous solution washing, the chromatography column purifying obtains 17g3-benzoyloxy phenyl acetonitrile, and 3-benzoyloxy phenyl acetonitrile and 170mL70% sulfuric acid spend the night in 120 degree reactions; after reaction is finished; add the 80mL frozen water, have solid to separate out, filter; after the acetic acid ethyl dissolution drying, be spin-dried for to get benzoyl toluylic acid between 9.1g.
Above-mentioned with the 3-methyl benzoyl chloride, benzene, N-bromosuccinimide and trimethylsilyl cyanide etc. for raw material synthetic between chemical reaction and the reaction formula of benzoyl toluylic acid as follows:
(1) reaction equation of 3-methyl benzoyl chloride and benzene and Aluminum chloride anhydrous is:
Figure 249473DEST_PATH_IMAGE002
(2) reaction equation of 3-methyldiphenyl ketone and N-bromosuccinimide is:
(3) reaction equation of 3-brooethyl benzophenone and trimethylammonium cyanogen silicon is:
Figure 955578DEST_PATH_IMAGE006
(4) reaction equation of 3-benzoyloxy phenyl acetonitrile and 70 ~ 80% aqueous sulfuric acids is:
Figure 769950DEST_PATH_IMAGE008
Behind the solid filtering of (5) separating out, most of impurity can be removed with ethyl acetate and sherwood oil, finally 99% product can be got.
Embodiment
Embodiment:
The synthetic method of described benzoyl toluylic acid; that employing 30g3-methyl benzoyl chloride is raw material and 38.8g aluminum trichloride (anhydrous); under cold condition; drip 80mL benzene; after dripping; rising to room temperature reaction spends the night; after reaction is finished; after the processing of reaction solution usefulness 50mL frozen water; filter; filter cake dissolves with methylene dichloride; use respectively sodium bicarbonate and saturated common salt water washing; anhydrous sodium sulfate drying; obtain 34g3-methyldiphenyl ketone; 3-methyldiphenyl ketone is dissolved in the 800mL tetracol phenixin; then add the 33gN-bromo-succinimide and spend the night in 75 degree reactions, after reaction is finished, be cooled to room temperature; Rotary Evaporators spins off reaction solvent; residue is poured in the 150mL water, used dichloromethane extraction, anhydrous sodium sulfate drying; obtain 48.3g3-brooethyl benzophenone; after 3-brooethyl benzophenone is dissolved in the 300mL acetonitrile, add 29.3g salt of wormwood, then drip the 21.3g trimethylsilyl cyanide; being warming up to 80 degree reactions spends the night; after reacting completely, add 100mL1mol/LNaOH solution, then use ethyl acetate extraction; organic layer is used the 1mol/LNaOH solution washing again; after the saturated nacl aqueous solution washing, the chromatography column purifying obtains 17g3-benzoyloxy phenyl acetonitrile, and 3-benzoyloxy phenyl acetonitrile and 170mL70% sulfuric acid spend the night in 120 degree reactions; after reaction is finished; add the 80mL frozen water, have solid to separate out, filter; after the acetic acid ethyl dissolution drying, be spin-dried for to get benzoyl toluylic acid between 9.1g.

Claims (4)

1. the synthetic method of a benzoyl toluylic acid; that employing 3-methyl benzoyl chloride is raw material; under cold condition; under the aluminum trichloride (anhydrous) effect, react with benzene; obtain 3-methyldiphenyl ketone; 3-methyldiphenyl ketone and N-bromosuccinimide react in carbon tetrachloride solution; obtain 3-brooethyl benzophenone; 3-brooethyl benzophenone and trimethylsilyl cyanide reaction; obtain 3-benzoyloxy phenyl acetonitrile; 3-benzoyloxy phenyl acetonitrile and 70% sulfuric acid reaction obtain a benzoyl toluylic acid.
As claimed in claim between the synthetic method of benzoyl toluylic acid; it is characterized in that: described 3-methyldiphenyl ketone and N-bromosuccinimide react in carbon tetrachloride solution; wherein solvent does not singly refer to tetracol phenixin, and methylene dichloride, chloroform etc. all can react.
As claimed in claim between the synthetic method of benzoyl toluylic acid, it is characterized in that: described 3-benzoyloxy phenyl acetonitrile and 70% sulfuric acid reaction, wherein the concentration range of aqueous sulfuric acid is 50 ~ 80%.
As claimed in claim between the synthetic method of benzoyl toluylic acid; it is characterized in that: be that employing 30g3-methyl benzoyl chloride is raw material and 38.8g aluminum trichloride (anhydrous); under cold condition; drip 80mL benzene; after dripping; rising to room temperature reaction spends the night; after reaction is finished; after the processing of reaction solution usefulness 50mL frozen water; filter; filter cake dissolves with methylene dichloride; use respectively sodium bicarbonate and saturated common salt water washing; anhydrous sodium sulfate drying; obtain 34g3-methyldiphenyl ketone; 3-methyldiphenyl ketone is dissolved in the 800mL tetracol phenixin; then add the 33gN-bromo-succinimide and spend the night in 75 degree reactions, after reaction is finished, be cooled to room temperature; Rotary Evaporators spins off reaction solvent; residue is poured in the 150mL water, used dichloromethane extraction, anhydrous sodium sulfate drying; obtain 48.3g3-brooethyl benzophenone; after 3-brooethyl benzophenone is dissolved in the 300mL acetonitrile, add 29.3g salt of wormwood, then drip the 21.3g trimethylsilyl cyanide; being warming up to 80 degree reactions spends the night; after reacting completely, add 100mL1mol/LNaOH solution, then use ethyl acetate extraction; organic layer is used the 1mol/LNaOH solution washing again; after the saturated nacl aqueous solution washing, the chromatography column purifying obtains 17g3-benzoyloxy phenyl acetonitrile, and 3-benzoyloxy phenyl acetonitrile and 170mL70% sulfuric acid spend the night in 120 degree reactions; after reaction is finished; add the 80mL frozen water, have solid to separate out, filter; after the acetic acid ethyl dissolution drying, be spin-dried for to get benzoyl toluylic acid between 9.1g.
CN2012104839929A 2012-11-26 2012-11-26 Synthesis method of m-phenyl formyl phenylacetic acid Pending CN103044241A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3828093A (en) * 1967-07-31 1974-08-06 Allen & Hanburys Ltd Benzoylphenylacetic acids and related compounds
CN102321010A (en) * 2011-10-13 2012-01-18 安徽东盛制药有限公司 Preparation method for (2S, 3aR, 7aS)-octahydro indole-2-benzyl formate

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3828093A (en) * 1967-07-31 1974-08-06 Allen & Hanburys Ltd Benzoylphenylacetic acids and related compounds
CN102321010A (en) * 2011-10-13 2012-01-18 安徽东盛制药有限公司 Preparation method for (2S, 3aR, 7aS)-octahydro indole-2-benzyl formate

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
罗海南: "三甲基硅化腈在有机合成中的应用", 《有机化学》 *

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Application publication date: 20130417