Synthetic system of 3-cyanomethylbenzoic acid methyl ester and method thereof

Abstract

The invention provides a synthetic system of 3-cyanomethylbenzoic acid methyl ester and a method thereof. The system comprises an acylation reaction vessel used for preparation of m-Toluoyl chloride;a liquid chlorine feeding unit used for storing and conveying liquid chlorine; a chlorination reaction unit which is connected with the acylation reaction vessel and used as a chlorination reaction chamber of m-Toluoyl chloride; a micro-interface generator which is respectively connected with the liquid chlorine feeding unit and the chlorination reaction unit and used for receiving liquid chlorineconveyed by the liquid chlorine feeding unit, crushing the liquid chlorine into micro-droplets with the diameter being micron level and conveying the micro-droplets to the chlorination reaction unitafter the crushing; and an esterification and cyanation reaction unit which is connected with the chlorination reaction unit. In the prior art, m-Toluoyl chloride and liquid chlorine cannot be fully mixed when m-Toluoyl chloride and liquid chlorine react such that yield of 3-cyanomethylbenzoic acid methyl ester is reduced. The above problem is solved by the synthetic system and the method of the invention.

Description

technical field

[0001] The invention relates to the technical field of pharmacy, in particular to a synthesis system and method for methyl m-cyanomethylbenzoate. Background technique

[0002] Profen, also known as ketoprofen, phenylketoprofen, Youbufen, Youprofen or Profenid, the chemical name is α-methyl-3-benzoylphenylacetic acid, which is produced by French Rhone-Poulenc company The excellent 2-arylpropionic acid non-steroidal anti-inflammatory analgesics developed by Farge, Messer and Moutounier in 1967, its mechanism of action is mainly by inhibiting the biological activity of cyclooxygenase and lipoxygenase in the body, thereby Inhibit the synthesis of prostaglandins and leukotrienes, which are prostaglandins and leukotrienes, have the activity of resisting the release of bradykinin, scavenging hydroxyl radicals and stabilizing lysosome membranes, thereby producing good antipyretic, analgesic and anti-inflammatory effects, and enhancing its peripheral Analgesic effect...

Examples

preparation example Construction

[0045] A synthetic method for methyl m-cyanomethylbenzoate, comprising:

[0046] Pump m-toluic acid into the acylation reaction kettle, add excess thionyl chloride to generate m-toluoyl chloride, and transport m-toluoyl chloride to the chlorination reaction kettle, at the same time, liquid chlorine The storage tank transports liquid chlorine to the inside of the micro-interface generator;

[0047] The micro-interface generator breaks the liquid chlorine into micron-scale micro-droplets, and transports the micro-droplets to the chlorination reactor, so that m-toluyl chloride undergoes a chlorination reaction in the chlorination reactor to obtain m- Chloromethylbenzoyl chloride;

[0048] Pump m-chloromethylbenzoyl chloride into the esterification reaction kettle and add dropwise anhydrous methanol to generate methyl m-chloromethylbenzoate. At the same time, add solvent methanol, quaternary ammonium salt catalyst and sodium cyanide to cyanide In the reaction kettle, the tempera...

Embodiment 1

[0054] a): 350 parts of m-toluic acid are pumped into the acylation reaction kettle, 400 parts of thionyl chloride are added, and m-toluic acid chloride is produced by acylation reaction at 65° C.;

[0055] b): m-toluoyl chloride is pumped into the chlorination reaction kettle, and 5% liquid chlorine by weight of m-toluoyl chloride is passed into it under the condition of maintaining 120° C., so that the acylate is converted into a chloride. The reacted m-toluyl chloride is chlorinated again in the chlorination reactor until finally obtaining high-quality m-chloromethylbenzoyl chloride;

[0056] c): The chloride is pumped into the esterification reaction kettle, and 80 parts of anhydrous methanol are added dropwise, and the esterification reaction is carried out at 45° C. to form an esterified product. After the esterification reaction is completed, excess methanol is distilled off;

[0057] d): Add the solvent methanol, 20 parts of trioctylmethyl ammonium chloride, and 150 pa...

Embodiment 2

[0060] a): 350 parts of m-toluic acid are pumped into the acylation reaction kettle, 350 parts of thionyl chloride are added, and m-toluic acid chloride is produced by acylation at 75° C.;

[0061] b): pump m-toluoyl chloride into the chlorination reaction kettle, and feed liquid chlorine with 10% weight of m-toluoyl chloride under the condition of 130°C to convert the acylate into chloride, and recover the non-participated by distillation The reacted m-toluyl chloride is chlorinated again in the chlorination reactor until finally obtaining high-quality m-chloromethylbenzoyl chloride;

[0062] c): The chloride is pumped into the esterification reaction kettle, and 80 parts of anhydrous methanol are added dropwise, and the esterification reaction is carried out at 50° C. to form an esterified product. After the esterification reaction is completed, excess methanol is distilled off;

[0063] d): Add the solvent methanol, 20 parts of trioctylmethyl ammonium chloride, and 150 part...

technical field

[0001] The invention relates to the technical field of pharmacy, in particular to a synthesis system and method for methyl m-cyanomethylbenzoate. Background technique

[0002] Profen, also known as ketoprofen, phenylketoprofen, Youbufen, Youprofen or Profenid, the chemical name is α-methyl-3-benzoylphenylacetic acid, which is produced by French Rhone-Poulenc company The excellent 2-arylpropionic acid non-steroidal anti-inflammatory analgesics developed by Farge, Messer and Moutounier in 1967, its mechanism of action is mainly by inhibiting the biological activity of cyclooxygenase and lipoxygenase in the body, thereby Inhibit the synthesis of prostaglandins and leukotrienes, which are prostaglandins and leukotrienes, have the activity of resisting the release of bradykinin, scavenging hydroxyl radicals and stabilizing lysosome membranes, thereby producing good antipyretic, analgesic and anti-inflammatory effects, and enhancing its peripheral Analgesic effect...

Examples

preparation example Construction

[0045] A synthetic method for methyl m-cyanomethylbenzoate, comprising:

[0046] Pump m-toluic acid into the acylation reaction kettle, add excess thionyl chloride to generate m-toluoyl chloride, and transport m-toluoyl chloride to the chlorination reaction kettle, at the same time, liquid chlorine The storage tank transports liquid chlorine to the inside of the micro-interface generator;

[0047] The micro-interface generator breaks the liquid chlorine into micron-scale micro-droplets, and transports the micro-droplets to the chlorination reactor, so that m-toluyl chloride undergoes a chlorination reaction in the chlorination reactor to obtain m- Chloromethylbenzoyl chloride;

[0048] Pump m-chloromethylbenzoyl chloride into the esterification reaction kettle and add dropwise anhydrous methanol to generate methyl m-chloromethylbenzoate. At the same time, add solvent methanol, quaternary ammonium salt catalyst and sodium cyanide to cyanide In the reaction kettle, the tempera...

Embodiment 1

[0054] a): 350 parts of m-toluic acid are pumped into the acylation reaction kettle, 400 parts of thionyl chloride are added, and m-toluic acid chloride is produced by acylation reaction at 65° C.;

[0055] b): m-toluoyl chloride is pumped into the chlorination reaction kettle, and 5% liquid chlorine by weight of m-toluoyl chloride is passed into it under the condition of maintaining 120° C., so that the acylate is converted into a chloride. The reacted m-toluyl chloride is chlorinated again in the chlorination reactor until finally obtaining high-quality m-chloromethylbenzoyl chloride;

[0056] c): The chloride is pumped into the esterification reaction kettle, and 80 parts of anhydrous methanol are added dropwise, and the esterification reaction is carried out at 45° C. to form an esterified product. After the esterification reaction is completed, excess methanol is distilled off;

[0057] d): Add the solvent methanol, 20 parts of trioctylmethyl ammonium chloride, and 150 pa...

Embodiment 2

[0060] a): 350 parts of m-toluic acid are pumped into the acylation reaction kettle, 350 parts of thionyl chloride are added, and m-toluic acid chloride is produced by acylation at 75° C.;

[0061] b): pump m-toluoyl chloride into the chlorination reaction kettle, and feed liquid chlorine with 10% weight of m-toluoyl chloride under the condition of 130°C to convert the acylate into chloride, and recover the non-participated by distillation The reacted m-toluyl chloride is chlorinated again in the chlorination reactor until finally obtaining high-quality m-chloromethylbenzoyl chloride;

[0062] c): The chloride is pumped into the esterification reaction kettle, and 80 parts of anhydrous methanol are added dropwise, and the esterification reaction is carried out at 50° C. to form an esterified product. After the esterification reaction is completed, excess methanol is distilled off;

[0063] d): Add the solvent methanol, 20 parts of trioctylmethyl ammonium chloride, and 150 part...

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