阅读说明：本技术 一种2-氯-4-甲砜基苯甲酸的制备方法 (Preparation method of 2-chloro-4-methylsulfonylbenzoic acid ) 是由 朱磊 李雄 吴革晓 李博解 张瑶瑶 夏彩芬 何边阳 于 2021-08-31 设计创作，主要内容包括：本发明公开一种2-氯-4-甲砜基苯甲酸的制备方法,属于药物化学技术领域。该2-氯-4-甲砜基苯甲酸的制备方法,包括以下步骤：S1、调节微通道反应器的温度为100-110℃；所述微通道反应器中装载有非均相催化剂,所述非均相催化剂由壳聚糖溶于水,之后加入醋酸钴和醋酸锰搅拌反应,之后洗涤干燥制得；S2、向所述微通道反应器中持续通入预热的空气,之后将预热的2-氯-1-甲基-4-(甲磺酰基)苯的冰醋酸溶液通入所述微通道反应器中进行催化反应制得所述2-氯-4-甲砜基苯甲酸。实现了在较低温度下制备得到2-氯-4-甲砜基苯甲酸,而且2-氯-4-甲砜基苯甲酸的产率可高达97.2％。(The invention discloses a preparation method of 2-chloro-4-methylsulfonylbenzoic acid, and belongs to the technical field of pharmaceutical chemistry. The preparation method of the 2-chloro-4-methylsulfonylbenzoic acid comprises the following steps: s1, adjusting the temperature of the microchannel reactor to be 100-110 ℃; the microchannel reactor is loaded with a heterogeneous catalyst, the heterogeneous catalyst is prepared by dissolving chitosan in water, adding cobalt acetate and manganese acetate, stirring for reaction, and then washing and drying; s2, continuously introducing preheated air into the microchannel reactor, and then introducing a preheated glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene into the microchannel reactor for catalytic reaction to prepare the 2-chloro-4-methylsulfonylbenzoic acid. The 2-chloro-4-methylsulfonylbenzoic acid can be prepared at a lower temperature, and the yield of the 2-chloro-4-methylsulfonylbenzoic acid can reach 97.2 percent.)

1. The preparation method of 2-chloro-4-methylsulfonylbenzoic acid is characterized by comprising the following steps:

s1, adjusting the temperature of the microchannel reactor to be 100-110 ℃; the microchannel reactor is loaded with a heterogeneous catalyst, the heterogeneous catalyst is prepared by dissolving chitosan in water, adding cobalt acetate and manganese acetate, stirring for reaction, and then washing and drying;

s2, continuously introducing preheated air into the microchannel reactor, and then introducing a preheated glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene into the microchannel reactor for catalytic reaction to prepare the 2-chloro-4-methylsulfonylbenzoic acid.

2. The method for producing 2-chloro-4-methylsulfonylbenzoic acid according to claim 1, wherein in step S2, the mass fraction of 2-chloro-1-methyl-4- (methylsulfonyl) benzene in the glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 20% to 30%.

3. The method of producing 2-chloro-4-methylsulfonylbenzoic acid according to claim 1, wherein the flow rate of the glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene in step S2 is 1 to 3 mL/min.

4. The method of producing 2-chloro-4-methylsulfonylbenzoic acid according to claim 1, wherein in step S2, the flow rate of the air is 20 to 30 mL/min.

5. The method of claim 4, wherein in step S2, air is continuously pumped into the microchannel reactor at a pressure of 100KPa to 120KPa by a mechanical pump.

6. The method for producing 2-chloro-4-methylsulfonylbenzoic acid according to claim 1, wherein the temperature of the stirring reaction in step S1 is 70 to 80 ℃.

7. The method for producing 2-chloro-4-methylsulfonylbenzoic acid according to claim 6, wherein the stirring reaction time in step S1 is 10 to 12 hours.

8. The method for preparing 2-chloro-4-methylsulfonylbenzoic acid according to claim 1, wherein in step S1, the material ratio of the chitosan to the water is 100 g: 1-2L; the mass ratio of the cobalt acetate to the manganese acetate is 1-2: 1; the mass ratio of the chitosan to the cobalt acetate is 50: 1-2.

9. The method of producing 2-chloro-4-methylsulfonylbenzoic acid according to claim 1, wherein the drying temperature in step S1 is 90 to 100 ℃.

10. The method for producing 2-chloro-4-methylsulfonylbenzoic acid according to claim 9, wherein the drying time in step S1 is 20 to 24 hours.

Technical Field

The invention relates to the technical field of pharmaceutical chemistry, in particular to a preparation method of 2-chloro-4-methylsulfonylbenzoic acid.

Background

Vismodegib (Vismodegib) is the first oral, highly selective, small molecule inhibitor of the Hedgehog signaling pathway developed by ross roche pharmaceutical company, resident U.S. pharmaceutical factory. The Hedgehog signaling pathway plays an important role in numerous physiological processes such as cell recognition and proliferation during embryonic development and tissue formation, and stem cell maintenance, tissue repair and regeneration in adults. Generally, expression is not active in adults. Changes of each key component of the Hedgehog signal pathway can cause abnormal activation of the pathway and induce tumor occurrence, and skin cancer, pancreatic cancer, liver cancer, gastric cancer, lung cancer, colon cancer and the like are reported.

Vismodegib, marketed under the name eridger and english under the name Vismodegib, is a therapeutic drug for symptomatic metastatic Basal Cell Carcinoma (BCC) or locally advanced BCC adult patients who are not amenable to surgical or radiotherapy treatment.

At present, the method for synthesizing the vismodegib mainly comprises the original patent WO 2006028958; US 7888364; CN 101072755A; in 2016, GeneTak corporation published an article (DOI:10.1021/acs. oprd.6b00208); and other related patents CN 108003091a, CN 107200708A, etc.

The more mature method for preparing CMSBA is now the oxidation of 2-chloro-1-methyl-4- (methylsulfonyl) benzene. The traditional oxidation process is catalytic oxidation in a reaction kettle by using a homogeneous catalyst containing Co and Mn ions. The process needs high temperature (180-. At the same time, the homogeneous catalyst is difficult to separate from the product.

Disclosure of Invention

The invention aims to overcome the technical defects, provides a preparation method of 2-chloro-4-methylsulfonylbenzoic acid, and solves the technical problem of high temperature in the prior art for preparing 2-chloro-4-methylsulfonylbenzoic acid.

In order to achieve the technical purpose, the technical scheme of the invention provides a preparation method of 2-chloro-4-methylsulfonylbenzoic acid, which comprises the following steps:

s1, adjusting the temperature of the microchannel reactor to be 100-110 ℃; the microchannel reactor is loaded with a heterogeneous catalyst, the heterogeneous catalyst is prepared by dissolving chitosan in water, adding cobalt acetate and manganese acetate, stirring for reaction, and then washing and drying;

s2, continuously introducing preheated air into the microchannel reactor, and then introducing a preheated glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene into the microchannel reactor for catalytic reaction to prepare the 2-chloro-4-methylsulfonylbenzoic acid.

Further, in step S2, the mass fraction of 2-chloro-1-methyl-4- (methylsulfonyl) benzene in the glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 20% to 30%.

Further, in step S2, the flow rate of the glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 1-3 mL/min.

Further, in step S2, the flow rate of the air is 20-30 mL/min.

Further, in step S2, air is continuously pumped into the microchannel reactor at a pressure of 100KPa to 120KPa by a mechanical pump.

Further, in step S1, the temperature of the stirring reaction is 70-80 ℃.

Further, in step S1, the stirring reaction time is 10-12 h.

Further, in step S1, the material ratio of the chitosan to the water is 100 g: 1-2L; the mass ratio of the cobalt acetate to the manganese acetate is 1-2: 1; the mass ratio of the chitosan to the cobalt acetate is 50: 1-2.

Further, in step S1, the temperature of the drying is 90 to 100 ℃.

Further, in step S1, the drying time is 20-24 h.

Compared with the prior art, the invention has the beneficial effects that: dissolving chitosan in water, adding cobalt acetate and manganese acetate, stirring for reaction, washing and drying to obtain a heterogeneous catalyst, arranging the heterogeneous catalyst in a microchannel reactor, adjusting the reaction temperature to be 110 ℃ plus 100 ℃, continuously introducing air for preheating, introducing a glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene into the microchannel reactor for catalytic reaction to obtain the 2-chloro-4-methylsulfonylbenzoic acid, wherein the reaction temperature can be reduced to 110 ℃ plus 100 ℃ under the action of the specific heterogeneous catalyst, so that the 2-chloro-4-methylsulfonylbenzoic acid can be prepared at a lower temperature, and the yield of the 2-chloro-4-methylsulfonylbenzoic acid can be up to 97.2%.

Drawings

FIG. 1 shows NMR spectra of 2-chloro-1-methyl-4- (methylsulfonyl) benzene as a starting material in examples of the present invention and comparative examples¹³C spectrum;

FIG. 2 is an NMR hydrogen spectrum of 2-chloro-4-methylsulfonylbenzoic acid obtained in example 1 of the present invention.

Detailed Description

The specific embodiment provides a preparation method of 2-chloro-4-methylsulfonylbenzoic acid, which comprises the following steps:

s1, adjusting the temperature of the microchannel reactor to be 100-110 ℃; the microchannel reactor is loaded with a heterogeneous catalyst, the heterogeneous catalyst is prepared by dissolving chitosan in water, adding cobalt acetate and manganese acetate, stirring and reacting at 70-80 ℃ for 10-12h, washing with water, and drying at 90-100 ℃ for 20-24h, and the heterogeneous catalyst is required to be briquetted, wherein the specific forming condition is determined according to the selection of a reaction channel; the material ratio of the chitosan to the water is 100 g: 1-2L; the mass ratio of the cobalt acetate to the manganese acetate is 1-2: 1; the mass ratio of the chitosan to the cobalt acetate is 50: 1-2;

s2, continuously introducing preheated air into the microchannel reactor at the pressure of 100-120 KPa through a mechanical pump, then introducing a preheated glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene into the microchannel reactor for catalytic reaction to prepare the 2-chloro-4-methylsulfonylbenzoic acid, collecting a liquid product at a sample outlet, wherein the mass fraction of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene in the glacial acetic acid solution of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 20-30%, the flow rate of the glacial acetic acid solution of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 1-3mL/min, the flow rate of the air is 20-30 mL/min.

For safety reasons, setting the pressure in the microchannel reactor to be more than 120KPa or the temperature to be more than 110 ℃, an alarm is given, the input of gas and liquid is stopped, and the heating is stopped.

The structural formula of 2-chloro-1-methyl-4- (methylsulfonyl) benzene (compound I) is as follows:

the structural formula of 2-chloro-4-methylsulfonylbenzoic acid (compound II) is as follows:

the structural formula of 2-chloro-4- (methylsulfonyl) benzoyl chloride (compound III) is as follows:

the yield of the product prepared by the microchannel reactor is over 95 percent, and the product can be directly produced in the next step. The starting compound I cannot be further acylchlorinated to give compound III, so that no side reactions occur. Meanwhile, the compound III of the next step is dissolved in water, while the compound I and the compound II are both insoluble in water, so that the subsequent products can be conveniently separated and reused.

Compared with the traditional homogeneous catalyst, the catalytic activity of the heterogeneous catalyst is generally not superior to that of the homogeneous catalyst for the same reaction. However, in the present application, the solubility of air participating in the reaction, especially air in glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene, is very low, and the catalytic activity is not fully reflected to the catalyst, which appears to be not high, but the heterogeneous catalyst, especially the catalyst containing metal elements, having a porous structure, and capable of selectively adsorbing reactants (specific gas and liquid) by solid catalysis, in the present application, can increase the concentration of local reaction, so that the catalytic activity is higher than that of the homogeneous catalyst.

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

NMR of 2-chloro-1-methyl-4- (methylsulfonyl) benzene as a starting material in the following examples or comparative examples¹³The spectrum C is shown in figure 1, and the solvent used is deuterated methanol.

Example 1

This example provides a method for preparing 2-chloro-4-methylsulfonylbenzoic acid, which includes the following steps:

s1, adjusting the temperature of the microchannel reactor to 100 ℃; the microchannel reactor is loaded with a heterogeneous catalyst, the heterogeneous catalyst is prepared by dissolving chitosan in water, adding cobalt acetate and manganese acetate, stirring and reacting at 80 ℃ for 12h, washing with water, and drying at 100 ℃ for 24 h; the material ratio of the chitosan to the water is 100 g: 1L; the mass ratio of the cobalt acetate to the manganese acetate is 2: 1; the mass ratio of the chitosan to the cobalt acetate is 50: 1;

s2, continuously introducing air preheated to 100 ℃ into the microchannel reactor at the pressure of 100KPa through a mechanical pump, then introducing a glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene preheated to 100 ℃ into the microchannel reactor for catalytic reaction to prepare the 2-chloro-4-methylsulfonylbenzoic acid, collecting liquid products at a sample outlet, wherein the mass fraction of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene in the glacial acetic acid solution of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 30 percent, the flow rate of the glacial acetic acid solution of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 1mL/min, and the flow rate of the air is 20 mL/min.

The yield of the obtained 2-chloro-4-methylsulfonylbenzoic acid was 96.5%.

The hydrogen spectrum of 3-chloro-4-methylsulfonylbenzoic acid is shown in FIG. 2, the solvent used is deuterated methanol, and the signal of 5ppm in the spectrum is water, which indicates that 2-chloro-4-methylsulfonylbenzoic acid is successfully prepared.

The preparation method of example 1 was repeated 10 times without replacing the heterogeneous catalyst in the same microchannel reactor, and the yields of 2-chloro-4-methylsulfonylbenzoic acid obtained were all above 95%.

Example 2

This example provides a method for preparing 2-chloro-4-methylsulfonylbenzoic acid, which includes the following steps:

s1, adjusting the temperature of the microchannel reactor to 110 ℃; the microchannel reactor is loaded with a heterogeneous catalyst, the heterogeneous catalyst is prepared by dissolving chitosan in water, adding cobalt acetate and manganese acetate, stirring and reacting at 70 ℃ for 10 hours, washing with water, and drying at 90 ℃ for 20 hours; the material ratio of the chitosan to the water is 100 g: 1.5L; the mass ratio of the cobalt acetate to the manganese acetate is 1: 1; the mass ratio of the chitosan to the cobalt acetate is 50: 2;

s2, continuously introducing air preheated to 110 ℃ into the microchannel reactor at the pressure of 100KPa through a mechanical pump, then introducing a glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene preheated to 110 ℃ into the microchannel reactor for catalytic reaction to prepare the 2-chloro-4-methylsulfonylbenzoic acid, collecting liquid products at a sample outlet, wherein the mass fraction of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene in the glacial acetic acid solution of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 25 percent, the flow rate of the glacial acetic acid solution of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 2mL/min, and the flow rate of the air is 30 mL/min.

The yield of the obtained 2-chloro-4-methylsulfonylbenzoic acid was 97.2%.

Example 3

This example provides a method for preparing 2-chloro-4-methylsulfonylbenzoic acid, which includes the following steps:

s1, adjusting the temperature of the microchannel reactor to 100 ℃; the microchannel reactor is loaded with a heterogeneous catalyst, the heterogeneous catalyst is prepared by dissolving chitosan in water, adding cobalt acetate and manganese acetate, stirring and reacting at 75 ℃ for 12h, washing with water, and drying at 100 ℃ for 20 h; the material ratio of the chitosan to the water is 100 g: 2L; the mass ratio of the cobalt acetate to the manganese acetate is 1: 2; the mass ratio of the chitosan to the cobalt acetate is 50: 1.5;

s2, continuously introducing air preheated to 100 ℃ into the microchannel reactor at the pressure of 110KPa through a mechanical pump, then introducing a glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene preheated to 100 ℃ into the microchannel reactor for catalytic reaction to prepare the 2-chloro-4-methylsulfonylbenzoic acid, collecting liquid products at a sample outlet, wherein the mass fraction of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene in the glacial acetic acid solution of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 20 percent, the flow rate of the glacial acetic acid solution of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 3mL/min, and the flow rate of the air is 25 mL/min.

The yield of the obtained 2-chloro-4-methylsulfonylbenzoic acid was 96.3%.

Example 4

This example provides a method for preparing 2-chloro-4-methylsulfonylbenzoic acid, which includes the following steps:

s1, adjusting the temperature of the microchannel reactor to 100 ℃; the microchannel reactor is loaded with a heterogeneous catalyst, the heterogeneous catalyst is prepared by dissolving chitosan in water, adding cobalt acetate and manganese acetate, stirring and reacting at 80 ℃ for 11h, washing with water, and drying at 100 ℃ for 22 h; the material ratio of the chitosan to the water is 100 g: 1L; the mass ratio of the cobalt acetate to the manganese acetate is 2: 1; the mass ratio of the chitosan to the cobalt acetate is 50: 1;

s2, continuously introducing air preheated to 100 ℃ into the microchannel reactor at the pressure of 100KPa through a mechanical pump, then introducing a glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene preheated to 100 ℃ into the microchannel reactor for catalytic reaction to prepare the 2-chloro-4-methylsulfonylbenzoic acid, collecting liquid products at a sample outlet, wherein the mass fraction of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene in the glacial acetic acid solution of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 25 percent, the flow rate of the glacial acetic acid solution of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 2mL/min, and the flow rate of the air is 30 mL/min.

The yield of the obtained 2-chloro-4-methylsulfonylbenzoic acid was 96.4%.

Example 5

This example provides a method for preparing 2-chloro-4-methylsulfonylbenzoic acid, which includes the following steps:

s1, adjusting the temperature of the microchannel reactor to 100 ℃; the microchannel reactor is loaded with a heterogeneous catalyst, the heterogeneous catalyst is prepared by dissolving chitosan in water, adding cobalt acetate and manganese acetate, stirring and reacting at 80 ℃ for 12h, washing with water, and drying at 100 ℃ for 24 h; the material ratio of the chitosan to the water is 100 g: 1L; the mass ratio of the cobalt acetate to the manganese acetate is 1.5: 1; the mass ratio of the chitosan to the cobalt acetate is 50: 1;

s2, continuously introducing air preheated to 100 ℃ into the microchannel reactor at the pressure of 100KPa through a mechanical pump, then introducing a glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene preheated to 100 ℃ into the microchannel reactor for catalytic reaction to prepare the 2-chloro-4-methylsulfonylbenzoic acid, collecting liquid products at a sample outlet, wherein the mass fraction of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene in the glacial acetic acid solution of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 30 percent, the flow rate of the glacial acetic acid solution of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 1.5mL/min, and the flow rate of the air is 20 mL/min.

The yield of the obtained 2-chloro-4-methylsulfonylbenzoic acid was 97.1%.

Example 6

This example provides a method for preparing 2-chloro-4-methylsulfonylbenzoic acid, which includes the following steps:

s1, adjusting the temperature of the microchannel reactor to 105 ℃; the microchannel reactor is loaded with a heterogeneous catalyst, the heterogeneous catalyst is prepared by dissolving chitosan in water, adding cobalt acetate and manganese acetate, stirring and reacting at 80 ℃ for 12h, washing with water, and drying at 100 ℃ for 24 h; the material ratio of the chitosan to the water is 100 g: 2L; the mass ratio of the cobalt acetate to the manganese acetate is 2: 1; the mass ratio of the chitosan to the cobalt acetate is 50: 1;

s2, continuously introducing air preheated to 105 ℃ into the microchannel reactor at the pressure of 110KPa through a mechanical pump, then introducing a glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene preheated to 105 ℃ into the microchannel reactor for catalytic reaction to prepare the 2-chloro-4-methylsulfonylbenzoic acid, collecting liquid products at a sample outlet, wherein the mass fraction of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene in the glacial acetic acid solution of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 25 percent, the flow rate of the glacial acetic acid solution of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene was 2.5mL/min, and the flow rate of the air was 25 mL/min.

The yield of the obtained 2-chloro-4-methylsulfonylbenzoic acid was 95.1%.

Example 7

This example provides a method for preparing 2-chloro-4-methylsulfonylbenzoic acid, which includes the following steps:

s1, adjusting the temperature of the microchannel reactor to 110 ℃; the microchannel reactor is loaded with a heterogeneous catalyst, the heterogeneous catalyst is prepared by dissolving chitosan in water, adding cobalt acetate and manganese acetate, stirring and reacting at 80 ℃ for 12h, washing with water, and drying at 100 ℃ for 24 h; the material ratio of the chitosan to the water is 100 g: 2L; the mass ratio of the cobalt acetate to the manganese acetate is 1: 1; the mass ratio of the chitosan to the cobalt acetate is 50: 1;

s2, continuously introducing air preheated to 110 ℃ into the microchannel reactor at the pressure of 105KPa through a mechanical pump, then introducing a glacial acetic acid solution of 2-chloro-1-methyl-4- (methylsulfonyl) benzene preheated to 110 ℃ into the microchannel reactor for catalytic reaction to prepare the 2-chloro-4-methylsulfonylbenzoic acid, collecting liquid products at a sample outlet, wherein the mass fraction of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene in the glacial acetic acid solution of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 20 percent, the flow rate of the glacial acetic acid solution of the 2-chloro-1-methyl-4- (methylsulfonyl) benzene is 3mL/min, and the flow rate of the air is 30 mL/min.

The yield of the obtained 2-chloro-4-methylsulfonylbenzoic acid was 96.8%.

Comparative example 1

The comparative example differs from example 1 in that the heterogeneous catalyst does not contain cobalt acetate and the process is otherwise the same.

The yield of the obtained 2-chloro-4-methylsulfonylbenzoic acid was 76.8%.

Comparative example 2

The comparative example differs from example 1 in that the heterogeneous catalyst does not contain manganese acetate and the process is otherwise the same.

The yield of the obtained 2-chloro-4-methylsulfonylbenzoic acid was 66.8%.

Other beneficial effects are as follows:

1. the production pressure is greatly reduced from 5 atm reaction condition to about 1 atm, which can reduce the production risk and prolong the service life of the apparatus.

2. And a heterogeneous catalyst is used for replacing a homogeneous catalyst, so that the catalyst and a product are conveniently separated.

3. The microchannel reaction device can reduce labor, automate all production processes, is intelligent, reduces production risks while reducing labor cost, and can increase yield.

The above-described embodiments of the present invention should not be construed as limiting the scope of the present invention. Any other corresponding changes and modifications made according to the technical idea of the present invention should be included in the protection scope of the claims of the present invention.