One-pot method for synthesizing mesosulfuron

Abstract

The invention discloses a method for synthesizing mesosulfuron in a one-pot method, comprising: performing a first step reaction of 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoic acid methyl ester and sodium cyanate in the presence of an organic base and in an organic solvent, and directly adding 2-amino-4,6-dimethoxypyrimidine to the untreated system after the first step reaction for a second step reaction. The invention adopts sodium cyanate as a starting material, first reacts with 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoic acid methyl ester to generate a corresponding isocyanate, and then condenses with 2-amino-4,6-dimethoxypyrimidine to obtain mesosulfuron, and the reaction route does not need to separate an intermediate, not only shortens the reaction steps and reaction time, but also has a low production cost, less environmental pollution, and especially has a high reaction yield and product purity, and is suitable for large-scale industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of herbicide synthesis, and particularly relates to a one-pot method for synthesizing mesosulfuron. Background Art

[0002] Mesosulfuron-methyl is chemically known as 2-[3-(4,6-dimethoxypyrimidin-2-yl)ureasulfonyl]-4-methanesulfonamidemethylbenzoate. It is a new sulfonylurea herbicide developed by Bayer in Germany in 2002. Sulfonylurea herbicides are the largest class of herbicides in the world. They mainly work by inhibiting acetolactate synthase, which is absorbed by weed roots and leaves and conducted in the plant body, thereby stopping the growth of weeds and achieving the effect of weed control. The agent has a good control effect on some broad-leaved weeds such as winter wheat, spring wheat, annual grass weeds and chickweed, and the demand for herbicides in my country is on the rise.

[0003] At present, methyl disulfone is mainly obtained by condensing 4-methylsulfonylaminomethyl-2-sulfonylaminobenzoic acid methyl ester [also known as 5-methylsulfonylaminomethyl-2-methoxycarbonylbenzenesulfonamide] and 4,6-dimethoxy-2-phenoxycarbonylaminopyrimidine [see Chinese patent documents CN103333120A, CN106243046A, CN109879817A, CN109897006A, etc.].

[0004] As for methyl 4-methylsulfonylaminomethyl-2-sulfonylaminobenzoate, the prior art is to obtain it by reacting methyl 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoate with ammonia.

[0005] Regarding 4,6-dimethoxy-2-phenoxycarbonylaminopyrimidine, the prior art is to obtain it by reacting 2-amino-4,6-dimethoxypyrimidine with phenyl chloroformate [see Chinese patent documents CN1178526A, CN101423499A, etc.].

[0006] The three-step reaction route for preparing mesosulfuron using 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoic acid methyl ester and 2-amino-4,6-dimethoxypyrimidine as starting materials is as follows:

[0007] .

[0008] The shortcomings of this reaction route are: (1) it requires three steps to obtain methyl disulfone, which has many reaction steps, long reaction time and high reaction cost; (2) the last step will produce phenol-containing wastewater, which has a large amount of three wastes and causes great pollution to the environment; (3) the total yield is low and is not suitable for large-scale industrial production. Summary of the invention

[0009] The object of the present invention is to solve the above problems and provide a method for synthesizing mesosulfuron in one pot using 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoic acid methyl ester and 2-amino-4,6-dimethoxypyrimidine as starting materials. The method has not only fewer reaction steps, shorter reaction time, lower reaction cost, less environmental pollution, but also higher reaction yield and product purity, and is suitable for large-scale industrial production.

[0010] The technical scheme for achieving the purpose of the present invention is: a one-pot method for synthesizing mesosulfuron, comprising the steps of: reacting methyl 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoate with sodium cyanate in an organic solvent in the presence of an organic base in a first step, and directly adding 2-amino-4,6-dimethoxypyrimidine to the untreated system after the first step reaction to carry out a second step reaction.

[0011] The molar ratio of the methyl 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoate to the sodium cyanate is 1:1 to 1:3, preferably 1:1.5.

[0012] The molar ratio of the methyl 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoate to the 2-amino-4,6-dimethoxypyrimidine is 1:1 to 1:2, preferably 1:1.2.

[0013] The molar ratio of the methyl 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoate to the organic base is 1:1 to 1:3, preferably 1:2.

[0014] The organic base is one of pyridine, picoline, triethylamine and DBU, preferably pyridine.

[0015] The weight ratio of the methyl 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoate to the organic solvent is 1:2 to 1:6.

[0016] The organic solvent is one of acetonitrile, propionitrile and dichloromethane, preferably acetonitrile.

[0017] The first step reaction temperature is 10-50°C, preferably 30°C.

[0018] The first step reaction time is 2 to 10 hours, preferably 5 hours.

[0019] The reaction temperature of the second step is ambient temperature (0-40°C, the same below).

[0020] The reaction time of the second step is 1 to 3 hours, preferably 2 hours.

[0021] After the second step reaction is completed, the method further includes: recovering the organic solvent by distillation under reduced pressure, cooling the temperature to ambient temperature, adding water and stirring, adjusting the pH value to 1-2 with acid and stirring, and finally filtering, washing the filter cake with water, and drying.

[0022] The acid is one of hydrochloric acid, sulfuric acid, acetic acid and phosphoric acid, preferably hydrochloric acid.

[0023] The present invention has the positive effects that sodium cyanate is used as a starting material, first reacted with 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoic acid methyl ester to generate corresponding isocyanate, and then condensed with 2-amino-4,6-dimethoxypyrimidine to obtain methyl disulfonyl methyl. The reaction route does not require the separation of intermediates, which not only shortens the reaction steps and reaction time, but also has a low production cost and less environmental pollution. In particular, the method has a high reaction yield and product purity, and is suitable for large-scale industrial production. DETAILED DESCRIPTION

[0024] (Example 1)

[0025] The method for synthesizing mesosulfuron-methyl by one-pot method of the present embodiment is as follows:

[0026] In a 500 mL reaction bottle, 34.1 g (0.1 mol) of methyl 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoate, 9.75 g (0.15 mol) of sodium cyanate, 15.8 g (0.2 mol) of pyridine and 136 g of acetonitrile were added. The first step reaction was carried out under stirring at 30±1°C for 5 h.

[0027] After the central control was qualified, 18.6 g (0.12 mol) of 2-amino-4,6-dimethoxypyrimidine was directly added to the reaction bottle, and the second step reaction was carried out with stirring at ambient temperature for 2 h.

[0028] After the reaction, acetonitrile was recovered by distillation under reduced pressure, and then the temperature was lowered to ambient temperature. 170 g of water was quickly added dropwise to the reaction bottle, and the mixture was stirred for 0.5 h. The pH value was adjusted to 1.5 with hydrochloric acid, and the mixture was stirred for 0.5 h and then filtered. The filter cake was washed with water and dried to obtain 45.4 g of methyl disulfone, with a yield of 90.3% and a purity of 97.3%.

[0029] (Example 2 to Example 7)

[0030] The one-pot synthesis of mesosulfuron in each embodiment is substantially the same as that in Example 1, except for the differences shown in Table 1.

[0031] Table 1

[0032] Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Methyl 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoate 34.1g(0.1mol) 34.1g(0.1mol) 34.1g(0.1mol) 34.1g(0.1mol) 34.1g(0.1mol) 34.1g(0.1mol) 34.1g(0.1mol) Sodium cyanate 9.75g(0.15mol) 13.0g(0.2mol) 6.5g(0.1mol) 9.75g(0.15mol) 9.75g(0.15mol) 9.75g(0.15mol) 9.75g(0.15mol) 2-Amino-4,6-dimethoxypyrimidine 18.6g(0.12mol) 18.6g(0.12mol) 18.6g(0.12mol) 31.0g(0.2mol) 15.5g(0.1mol) 18.6g(0.12mol) 18.6g(0.12mol) Organic base Pyridine 15.8g (0.2mol) Pyridine 15.8g (0.2mol) Pyridine 15.8g (0.2mol) Pyridine 15.8g (0.2mol) Pyridine 15.8g (0.2mol) Triethylamine 20.2g (0.2mol) DBU 30.4g (0.2mol) Mesosulfuron 45.4g 45.3g 43.8g 45.5g 43.2g 44.3g 42.3g Yield 90.3% 90.1% 87.1% 90.5% 85.9% 88.1% 84.1% purity 97.3% 97.1% 95.1% 97.4% 93.3% 94.1% 90.5%

[0033] (Example 8)

[0034] The method for synthesizing mesosulfuron-methyl by one-pot method of the present embodiment is as follows:

[0035] In a 2L reaction bottle, 136.4 g (0.4 mol) of methyl 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoate, 39.0 g (0.6 mol) of sodium cyanate, 63.2 g (0.8 mol) of pyridine and 544 g of acetonitrile were added, and the first step reaction was carried out for 5 hours under stirring at a temperature of 30±1°C.

[0036] After the central control was qualified, 74.4 g (0.48 mol) of 2-amino-4,6-dimethoxypyrimidine was directly added to the reaction bottle, and the second step reaction was carried out for 2 h under stirring at ambient temperature.

[0037] After the reaction, acetonitrile was recovered by vacuum distillation, and then the temperature was lowered to ambient temperature. 680 g of water was quickly added dropwise to the reaction bottle, and the mixture was stirred for 0.5 h. The pH value was adjusted to 1.5 with hydrochloric acid, and the mixture was stirred for 0.5 h and then filtered. The filter cake was washed with water and dried to obtain 183.1 g of methyl disulfone, with a yield of 91.0% and a purity of 97.1%.

Claims

1. A one-pot method for synthesizing mesosulfuron, characterized in that: The method comprises the following steps: performing a first step reaction of methyl 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoate and sodium cyanate in an organic solvent in the presence of an organic base, and directly adding 2-amino-4,6-dimethoxypyrimidine to the untreated system after the first step reaction to perform a second step reaction; the molar ratio of the methyl 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoate to the sodium cyanate is 1:1.5 to 1:3; the molar ratio of the methyl 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoate to the 2-amino-4,6-dimethoxypyrimidine is 1:1.2 to 1:2; the molar ratio of the methyl 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoate to the organic base is 1:2; and the organic base is pyridine.

2. The one-pot method for synthesizing mesosulfuron-methyl according to claim 1, characterized in that: The weight ratio of the methyl 4-methylsulfonylaminomethyl-2-chlorosulfonylbenzoate to the organic solvent is 1:2 to 1:6; the organic solvent is one of acetonitrile, propionitrile and dichloromethane.

3. The one-pot method for synthesizing mesosulfuron-methyl according to claim 1, characterized in that: The reaction temperature of the first step is 10-50° C., and the reaction time is 2-10 hours; the reaction temperature of the second step is ambient temperature, and the reaction time is 1-3 hours.

4. The one-pot method for synthesizing mesosulfuron-methyl according to claim 1, characterized in that: After the second step reaction is completed, the method further includes: recovering the organic solvent by distillation under reduced pressure, cooling the temperature to ambient temperature, adding water and stirring, adjusting the pH value to 1-2 with acid and stirring, and finally filtering, washing the filter cake with water, and drying.

5. The one-pot method for synthesizing mesosulfuron-methyl according to claim 4, characterized in that: The acid is one of hydrochloric acid, sulfuric acid, acetic acid and phosphoric acid.