A preparation method of methyl 2-methylsulfoxide-4-trifluoromethylbenzoate

Abstract

The invention discloses a method for preparing 2-methylsulfoxide-4-trifluoromethyl benzoic acid methyl ester. In an organic solvent, 2-amino-4-trifluoromethyl-benzoic acid methyl ester is used as a raw material, and the product 2-methylsulfoxide-4-trifluoromethyl benzoic acid methyl ester is obtained by diazotization and methyl sulfide etherification in a one-pot reaction at a certain temperature. The inventive method has multiple raw material sources and obvious cost advantages. At the same time, the use of traditional malodorous reagents such as dimethyl disulfide or sodium methyl mercaptide is avoided. The preparation method is safer and more convenient, has a high total yield, and reduces the three wastes, which is conducive to industrialization.

Description

Technical Field

[0001] The invention relates to a method for preparing 2-methylsulfoxide-4-trifluoromethylbenzoic acid methyl ester, and particularly relates to a method for obtaining the product 2-methylsulfoxide-4-trifluoromethylbenzoic acid methyl ester by using 2-amino-4-trifluoromethyl-benzoic acid methyl ester as a raw material through a one-pot reaction of diazotization and methyl sulfide etherification. Background Art

[0002] Methyl 2-methylsulfoxide-4-trifluoromethylbenzoate is an important intermediate for the herbicides pyrasulfone, isoxaflutole, and bispyribac, and is also an important pharmaceutical intermediate. The synthesis methods reported in the literature primarily involve a substitution reaction between 2-chloro(or bromo)-4-trifluoromethyl-benzoate and sodium methyl mercaptan followed by oxidation. The raw materials involved in this process, such as methyl mercaptan or sodium methyl mercaptan, and dimethyl disulfide, are foul-smelling and highly toxic. VOC emissions are uncontrollable at the production site, potentially causing harm to the human body. Summary of the Invention

[0003] The technical problem to be solved by the present invention is to address the deficiencies in the prior art and provide a method for preparing methyl 2-methylsulfoxide-4-trifluoromethylbenzoate. In an organic solvent, methyl 2-amino-4-trifluoromethylbenzoate is used as a raw material, and a one-pot reaction of diazotization and methyl sulfide is performed at a certain temperature to obtain the product methyl 2-methylsulfoxide-4-trifluoromethylbenzoate. The method of the present invention has multiple raw material sources and obvious cost advantages, while avoiding the use of traditional malodorous reagents such as dimethyl disulfide or sodium methyl mercaptan. The preparation method is safer and more convenient, has a high total yield, and reduces the three wastes, which is conducive to industrialization.

[0004] In order to achieve the above object, the present invention adopts the following technical solutions:

[0005] A method for preparing methyl 2-methylsulfoxide-4-trifluoromethylbenzoate comprises the following steps:

[0006] (1) In DMSO solvent, 2-amino-4-trifluoromethylbenzoic acid methyl ester and TBN (tert-butyl nitrite) are added at a certain temperature to carry out diazotization reaction;

[0007] (2) After the diazotization reaction is completed, a catalyst is added to the above-mentioned reaction kettle, and the temperature is raised and kept to perform a substitution reaction to obtain methyl 2-methylsulfoxide-4-trifluoromethylbenzoate;

[0008] The reaction formula is:

[0009]

[0010] In the above technical solution, the preparation method is specifically as follows:

[0011] (1) DMSO, methyl 2-amino-4-trifluoromethylbenzoate, and TBN were added to a reaction vessel in sequence under nitrogen protection, stirred evenly, and then heated to a set temperature; the temperature was maintained until the liquid chromatography normalized content of methyl 2-amino-4-trifluoromethylbenzoate in the total material was less than 1%; and a diazo solution was obtained for the next step;

[0012] (2) Adding catalyst A to the above-mentioned diazo liquid reactor, stirring evenly and then heating to a set temperature; keeping the temperature at this temperature until the liquid chromatography normalized content of the diazo intermediate 2-amino-4-trifluoromethylbenzoate in the total material is less than 1%; adding urea to quench the reaction, desolventizing and recovering DMSO, and recrystallizing with methanol to obtain the product 2-methylsulfoxide-4-trifluoromethylbenzoate.

[0013] In the above technical solution, in step (1), the molar ratio of 2-amino-4-trifluoromethylbenzoic acid methyl ester and TBN is 1:1-5, and the molar ratio of the amount of DMSO to 2-amino-4-trifluoromethylbenzoic acid methyl ester is 1-10:1; in step (2), the molar ratio of 2-amino-4-trifluoromethylbenzoic acid methyl ester and catalyst A is 1-50:1.

[0014] In the above technical solution, the reaction temperature in steps (1) and (2) is -10-80°C.

[0015] In the above technical solution, the catalyst A described in step (2) is any one of BOP, azobisisobutyronitrile, TBHP, and m-CPBA, or a mixture of two of them.

[0016] In the above technical solution, in step (1), the reaction temperature is preferably -10-10°C; in step (2), the reaction temperature is preferably 50-80°C.

[0017] The method of the present invention has multiple sources of raw materials and obvious cost advantages, and avoids the use of traditional malodorous reagents such as dimethyl disulfide or sodium methyl mercaptan. The preparation method is safer and more convenient, has a high total yield, and reduces three wastes, which is conducive to industrialization. DETAILED DESCRIPTION

[0018] The following describes in detail the specific implementation of the technical solution of the present invention, but the present invention is not limited to the following description:

[0019] Example 1: Methyl 2-methylsulfoxide-4-trifluoromethylbenzoate

[0020]

[0021] Small test preparation of target product:

[0022] (1) 21.9 g (0.10 mol) of 2-amino-4-trifluoromethylbenzoic acid methyl ester, 100 mL of DMSO, and 13.7 g (0.12 mol, 90% content) of TBN were added to a 500 mL reactor, and the temperature was lowered to -5 degrees and stirred for reaction for 4 hours. After the liquid phase was qualified, a diazo liquid was obtained; (2) 2 g of catalyst BOP (benzoyl peroxide) was added to the above diazo liquid, and the mixture was slowly heated to 60 degrees and stirred for reaction for 8 hours. After the medium control was qualified, 5 g of urea was added to quench the reaction, and DMSO was recovered under reduced pressure (directly applied to the next batch of reactions) with a recovery rate of 90%. 50 g of methanol was added for recrystallization to obtain 21.3 g of 2-methylsulfoxide-4-trifluoromethylbenzoic acid methyl ester with a yield of 80%;

[0023] Example 2: Methyl 2-methylsulfoxide-4-trifluoromethylbenzoate

[0024]

[0025] Process for preparing target product at kilogram level:

[0026] (1) 2.19 kg (10 mol) of methyl 2-amino-4-trifluoromethylbenzoate, 10 L of DMSO, and 1.37 kg (12 mol, 90% content) of TBN were added to a 50 L reactor, cooled to -5 degrees Celsius, stirred, and reacted for 8 hours. After the liquid phase was qualified, a diazo solution was obtained;

[0027] (2) Add 100 g of azobisisobutyronitrile catalyst to the above diazo solution, slowly heat to 50 degrees and stir to react for 8 hours. After the central control is qualified, add 500 g of urea to quench the reaction, and recover DMSO under reduced pressure (directly apply to the next batch of reactions). The recovery rate is 85%. Add 20 kg of water to force out the crude product. After filtering the crude product, put it back into a 20 L reactor and add 5 kg of methanol for recrystallization to obtain 1.97 kg of methyl 2-methylsulfoxide-4-trifluoromethylbenzoate with a yield of 74%;

[0028] Example 3: Methyl 2-methylsulfoxide-4-trifluoromethylbenzoate

[0029] Small test preparation of target product, comparison of different catalysts A:

[0030] Serial number catalyst Yield 1 BOP9% 80％ 2 Azobisisobutyronitrile 9% 84％ 3 TBHP9% 53％ 4 m-CPBA9% 21％ 5 Azobisisobutyronitrile 20% 88％ 6 Azobisisobutyronitrile 4.5% 74％ 7 Azobisisobutyronitrile 2% 61％

[0031] The above examples are only for illustrating the technical concept and technical features of the present invention and are not intended to limit the scope of protection of the present invention. Any equivalent transformation or modification made based on the essence of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for preparing methyl 2-methylsulfoxide-4-trifluoromethylbenzoate, comprising the following steps: (1) In DMSO solvent, 2-amino-4-trifluoromethylbenzoic acid methyl ester and TBN (tert-butyl nitrite) are added at a certain temperature to carry out diazotization reaction; (2) After the diazotization reaction is completed, a catalyst is added to the reactor, and the temperature is raised and maintained to perform a substitution reaction to obtain methyl 2-methylsulfoxide-4-trifluoromethylbenzoate; The reaction formula is: Wherein, the catalyst in step (2) is any one of BOP, azobisisobutyronitrile, TBHP, and m-CPBA, or a mixture of two thereof.

2. The method according to claim 1, characterized in that The following steps are involved: (1) DMSO, methyl 2-amino-4-trifluoromethylbenzoate, and TBN were added to a reaction vessel in sequence under nitrogen protection, stirred evenly, and then heated to a set temperature; the temperature was maintained until the liquid chromatography-normalized content of methyl 2-amino-4-trifluoromethylbenzoate in the total material was less than 1%; Obtain diazo solution for the next step; (2) Adding a catalyst to the above-mentioned diazo liquid reaction kettle, stirring evenly and then raising the temperature to a set temperature; keeping the temperature at this temperature until the liquid chromatography normalized content of the diazo intermediate 2-amino-4-trifluoromethylbenzoate in the total material is less than 1%; After urea was added to quench the reaction, DMSO was recovered by desolventizing under reduced pressure and recrystallized from methanol to obtain the product methyl 2-methylsulfoxide-4-trifluoromethylbenzoate.

3. The method according to claim 2, characterized in that In step (1), the molar ratio of 2-amino-4-trifluoromethylbenzoic acid methyl ester to TBN is 1:1-5, and the molar ratio of the amount of DMSO to 2-amino-4-trifluoromethylbenzoic acid methyl ester is 1-10:1; in step (2), the molar ratio of 2-amino-4-trifluoromethylbenzoic acid methyl ester to the catalyst is 1-50:

1.

4. The method according to claim 2, characterized in that The reaction temperature in steps (1) and (2) is -10-80°C.

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