Process for the preparation of 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid

Abstract

This invention discloses a method for preparing 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid. Using 2-chloro-3-methyl-4-methanesulfonylbenzoic acid as the starting material, hydrobromic acid as the reducing agent and sodium bromate as the oxidizing agent, both provide bromide ions. Sulfuric acid provides acidic conditions to promote the redox reaction, and bromination is carried out under the action of an initiator to obtain 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid. The method of this invention uses hydrobromic acid as the reducing agent and sodium bromate as the oxidizing agent, releasing active bromine under acidic conditions. This active bromine, when participating in bromination, can generate more of the specific brominated product 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid, thereby obtaining a higher reaction yield and product purity. The method of this invention avoids the safety issues associated with hydrogen peroxide, uses inexpensive reagents, has low production costs, is simple to operate, has simple post-processing, and causes less environmental pollution, making it suitable for large-scale production.

Description

Technical Field

[0001] This invention belongs to the field of herbicide intermediate preparation technology, specifically relating to a method for preparing 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid, a key intermediate for furazolidone and cyclosulfonyl ketone. Background Technology

[0002] Furazolidone and cyclosulfonyl, as triketone HPPD inhibitor herbicides, belong to the triketone herbicide family. This structural feature endows them with similar chemical properties and reactivity, blocking the biosynthetic pathways of endoplasmoquinone and tocopherol in plants by inhibiting the activity of 4-hydroxyphenylpyruvate dioxide (HPPD). Both are highly effective against weeds in farmland, especially those resistant to traditional herbicides, and exhibit low residue characteristics, making them safe for subsequent crops and meeting the needs of sustainable agricultural development.

[0003] 3-Bromomethyl-2-chloro-4-methanesulfonylbenzoic acid is a key intermediate in the synthesis of furazolidone and cyclosulfonylbenzoic acid. Currently, the preparation of 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid is mainly obtained by bromination of 2-chloro-3-methyl-4-methanesulfonylbenzoic acid. The main bromination systems are as follows: I. The bromination system disclosed in Chinese patent document CN117024382A is: bromination reagent (bromine, etc.) + acid catalyst (concentrated sulfuric acid, etc.).

[0004] The drawback of this bromination system is that it produces a large number of byproducts, resulting in a product content of only 85.0%.

[0005] II. The bromination system disclosed in Chinese patent documents CN112778171A and CN116283680A is: brominating agent (hydrobromic acid, etc.) + oxidizing agent (hydrogen peroxide) + initiator (azobisisobutyronitrile, benzoyl peroxide, etc.).

[0006] The bromination system can achieve a reaction yield and product purity of over 95%, but it has the following shortcomings: (1) It has low safety. Hydrogen peroxide is easily decomposed under acidic conditions. If it is added too quickly or the local concentration is too high, it will generate heat and oxygen, which poses a risk of material spillage and explosion; (2) CN112778171A is relatively complicated to operate and requires the initiator to be added once every hour (for 5 to 6 hours), which is not suitable for automated continuous production; (3) CN116283680A uses a large amount of methanol for post-processing, which increases the consumption of organic solvents and VOCs emissions, and the environmental protection treatment cost is higher.

[0007] III. The bromination system disclosed in Chinese patent document CN1553891A [WO2003022800 family] is: N-bromosuccinimide + bromine + initiator or bromine + exposure lamp irradiation.

[0008] The shortcomings of this bromination system are that N-bromosuccinimide is not only expensive and uneconomical for large-scale production, but also has limited reaction selectivity and bromination efficiency due to conditions, poor solubility, and the industrial conversion rate needs to be improved. Summary of the Invention

[0009] The purpose of this invention is to solve the above-mentioned problems and provide a method for preparing 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid that not only has high reaction yield and product purity, but is also simple to operate, easy to process, and especially safe.

[0010] The technical solution to achieve the purpose of this invention is: a method for preparing 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid, using 2-chloro-3-methyl-4-methanesulfonylbenzoic acid as the starting material, hydrobromic acid as the reducing agent, and sodium bromate as the oxidizing agent. Both provide bromide ions, and sulfuric acid provides acidic conditions to promote the redox reaction. Under the action of an initiator, bromination is carried out to obtain 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid.

[0011] The molar ratio of 2-chloro-3-methyl-4-methanesulfonylbenzoic acid to hydrobromic acid is 1:1 to 1:2, preferably 1:1.2 to 1:1.4.

[0012] The hydrobromic acid is preferably a 40wt% aqueous solution of hydrobromic acid.

[0013] The molar ratio of 2-chloro-3-methyl-4-methanesulfonylbenzoic acid to sodium bromate is 1:0.1 to 1:1, preferably 1:0.4 to 1:0.6.

[0014] The sodium bromate is preferably a 10 wt% aqueous solution of sodium bromate.

[0015] The molar ratio of 2-chloro-3-methyl-4-methanesulfonylbenzoic acid to sulfuric acid is 1:0.1 to 1:1, preferably 1:0.4 to 1:0.6.

[0016] The sulfuric acid is preferably a 40wt% aqueous solution of sulfuric acid.

[0017] The molar ratio of 2-chloro-3-methyl-4-methanesulfonylbenzoic acid to the initiator is 1:0.01 to 1:0.1, preferably 1:0.04 to 1:0.06.

[0018] The initiator is azobisisobutyronitrile or benzoyl peroxide, preferably azobisisobutyronitrile.

[0019] The reaction is carried out in the presence of an organic solvent, which is one of dichloromethane, dichloroethane, chloroform, and acetonitrile, preferably dichloroethane; the amount of the organic solvent is 4 to 8 times the weight of the 2-chloro-3-methyl-4-methanesulfonylbenzoic acid.

[0020] The reaction temperature is 40–90°C, preferably 75–85°C.

[0021] The positive effects of this invention are: (1) The method of this invention uses hydrobromic acid as a reducing agent and sodium bromate as an oxidizing agent to release active bromine under acidic conditions. When the active bromine participates in bromination, it can generate more specific bromination products, such as 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid, thereby obtaining a higher reaction yield and product purity; (2) The method of this invention can avoid the problem of low safety of hydrogen peroxide, uses lower reagents, has lower production costs, is easy to operate, has simple post-processing, and causes less environmental pollution, making it suitable for large-scale production. Detailed Implementation

[0022] (Example 1) The specific preparation method of 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid in this embodiment is as follows: 180 g of dichloroethane, 95.0 g (0.063 mol) of 10 wt% sodium bromate aqueous solution, and 30.0 g (0.12 mol) of 2-chloro-3-methyl-4-methanesulfonylbenzoic acid were added to the reaction apparatus. The mixture was stirred and heated to reflux. First, 1.0 g (0.006 mol) of azobisisobutyronitrile was added, followed by the slow addition of a mixture consisting of 31.2 g (0.154 mol) of 40 wt% hydrobromic acid aqueous solution and 14.5 g (0.06 mol) of 40 wt% sulfuric acid aqueous solution. After the addition was complete, the reaction was maintained at reflux until the reaction decolorized. After the reaction was completed, the reaction solution was cooled to room temperature, filtered, and dried to obtain 35.8 g of white solid. The yield was 90.5%, and the HPLC purity was 97.3%.

[0023] (Comparative Example 1: N-bromosuccinimide (NBS) was used as the brominating agent) The specific preparation method of 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid in this comparative example is as follows: 180 g of dichloroethane, 30 g (0.12 mol) of 2-chloro-3-methyl-4-methanesulfonylbenzoic acid, 38.6 g (0.22 mol) of N-bromosuccinimide, and 4.0 g (0.024 mol) of azobisisobutyronitrile were added to the reaction apparatus. The mixture was stirred and heated to reflux until the reaction decolorized. After the reaction was completed by sampling and monitoring, the reaction solution was cooled to room temperature, filtered, and dried to obtain 30.4 g of white solid. The yield was 76.9%, and the HPLC purity was 96.8%.

[0024] (Comparative Example 2, using 1,3-dibromo-5,5-dimethylhydantoin as the brominating agent) The specific preparation method of 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid in this comparative example is as follows: 180 g of dichloroethane, 30 g (0.12 mol) of 2-chloro-3-methyl-4-methanesulfonylbenzoic acid, and 4.0 g (0.024 mol) of azobisisobutyronitrile were added to the reaction apparatus. The mixture was stirred and heated to reflux. 34.5 g (0.12 mol) of 1,3-dibromo-5,5-dimethylhydantoin was added in portions. After the addition was complete, the reaction was maintained at reflux until the reaction decolorized. After the reaction was completed, the reaction solution was cooled to 50 °C, filtered, and dried to obtain 25.2 g of white solid. The yield was 63.8%, and the HPLC purity was 94.6%.

[0025] As can be seen from Example 1, Comparative Example 1 and Comparative Document 2, the product of Example 1 has higher purity, and the reaction yield is significantly higher than that of Comparative Example 1 and Comparative Example 2.

[0026] (Examples 2 to 5) The preparation methods of each embodiment are basically the same as those of Example 1, and the differences are shown in Table 1.

[0027] Table 1 40wt% hydrobromic acid aqueous solution 31.2g (0.154mol) 29.2g (0.144mol) 34.0g (0.168mol) 24.3g (0.12mol) 36.5g (0.18mol) 10wt% sodium bromate aqueous solution 95.0g (0.063mol) 75.5g (0.05mol) 105.7g (0.07mol) 45.3g (0.03mol) 135.9g (0.09mol) 40wt% sulfuric acid aqueous solution 14.5g (0.06mol) 12.25g (0.05mol) 17.15g (0.07mol) 7.35g (0.03mol) 22.05g (0.09mol) product 35.8g 34.9g 36.1g 31.9g 36.3g yield 90.5% 88.3% 91.3% 80.7% 91.8% purity 97.3% 97.1% 97.5% 95.8% 97.6%

Claims

1. A method for preparing 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid, characterized in that: Starting with 2-chloro-3-methyl-4-methanesulfonylbenzoic acid, hydrobromic acid was used as a reducing agent and sodium bromate as an oxidizing agent. Both provided bromide ions, and sulfuric acid provided acidic conditions to promote the redox reaction. Under the action of an initiator, bromination yielded 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid.

2. The method for preparing 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid according to claim 1, characterized in that: The molar ratio of 2-chloro-3-methyl-4-methanesulfonylbenzoic acid to hydrobromic acid is 1:1 to 1:

2.

3. The method for preparing 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid according to claim 1, characterized in that: The hydrobromic acid is a 40wt% aqueous solution of hydrobromic acid.

4. The method for preparing 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid according to claim 1, characterized in that: The molar ratio of 2-chloro-3-methyl-4-methanesulfonylbenzoic acid to sodium bromate is 1:0.1 to 1:

1.

5. The method for preparing 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid according to claim 1, characterized in that: The sodium bromate is a 10 wt% aqueous solution of sodium bromate.

6. The method for preparing 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid according to claim 1, characterized in that: The molar ratio of 2-chloro-3-methyl-4-methanesulfonylbenzoic acid to sulfuric acid is 1:0.1 to 1:

1.

7. The method for preparing 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid according to claim 1, characterized in that: The sulfuric acid is a 40wt% aqueous solution of sulfuric acid.

8. The method for preparing 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid according to claim 1, characterized in that: The molar ratio of 2-chloro-3-methyl-4-methanesulfonylbenzoic acid to the initiator is 1:0.01 to 1:0.1; the initiator is azobisisobutyronitrile or benzoyl peroxide.

9. The method for preparing 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid according to claim 1, characterized in that: The reaction is carried out in the presence of an organic solvent, which is one of dichloromethane, dichloroethane, chloroform, and acetonitrile; the amount of the organic solvent used is 4 to 8 times the weight of the 2-chloro-3-methyl-4-methanesulfonylbenzoic acid.

10. The method for preparing 3-bromomethyl-2-chloro-4-methanesulfonylbenzoic acid according to claim 1, characterized in that: The reaction temperature is 40–90°C.