CN116903545A - Synthesis method of formamidesulfuron-methyl - Google Patents

Abstract

The invention discloses a synthetic method of foramsulfuron, which comprises the following steps: (1) taking 2-chlorosulfonic acid-4-nitro-N, N-dimethylbenzamide as a starting material, firstly carrying out isocyanate reaction with sodium cyanate, and then carrying out condensation reaction with 2-amino-4, 6-dimethoxy pyrimidine to obtain an intermediate N, N-dimethyl-2- { N- [ N- (4, 6-dimethoxy pyrimidine-2-yl) -aminocarbonyl ] -aminosulfonyl } -4-nitrobenzamide; (2) the intermediate N, N-dimethyl-2- { N- [ N- (4, 6-dimethoxy pyrimidine-2-yl) -aminocarbonyl ] -sulfamoyl } -4-nitrobenzamide is catalyzed and hydrogenated in the presence of formic acid to obtain foramsulfuron. The synthesis method has the advantages of lower production cost, higher reaction yield and higher product purity, and is suitable for industrial mass production.

Description

Synthesis method of formamidesulfuron-methyl

Technical field

The invention belongs to the technical field of herbicide synthesis, and specifically relates to a synthesis method of formamidesulfuron-methyl.

Background technique

Formamidesulfuron-methyl, also known as formamidopyrimidine, chemical name: 1-(4,6-dimethoxypyrimidin-2-yl)-3-(2-dimethylaminocarbonyl-5-formamido) Phenylsulfonyl)urea is a new sulfonylurea herbicide developed by Bayer CropScience in Germany. It is used to control many grass weeds and broadleaf weeds in corn fields. It is good for subsequent rotation crops and the environment. very safe.

Chinese patent document CN1414955A discloses a preparation method of carboxamidesulfuron-methyl, which is prepared from the intermediate N,N-dimethyl-2-{N-[N-(4,6-dimethoxypyrimidine-2- [Basic]-aminocarbonyl]-aminosulfonyl}-4-nitrobenzamide is catalytically hydrogenated in the presence of formic acid to obtain formamidesulfuron-methyl [see Example 5].

The reaction formula is as follows:

.

For the above intermediate N,N-dimethyl-2-{N-[N-(4,6-dimethoxypyrimidin-2-yl)-aminocarbonyl]-aminosulfonyl}-4-nitrobenzene For the preparation of formamide, the existing technologies mainly include the following:

1. Chinese patent document CN1414955A discloses using N,N-dimethyl-2-aminosulfonyl-4-nitrobenzamide as the starting material, first reacting with phosgene, and then reacting with 2-amino-4,6 -Condensation of dimethoxypyrimidine gives the above intermediate [see Example 5].

The shortcomings of this method are: (1) phosgene, one of the raw materials, is not friendly to the human body and the environment; (2) the yield is low, less than 70%, and is not suitable for industrial large-scale production.

2. Chinese patent document CN1311782A discloses using 2-amino-4,6-dimethoxypyrimidine as the starting material, first reacting with phosgene, and then reacting with N,N-dimethyl-2-aminosulfonyl-4 -Condensation of nitrobenzamide gives the above intermediate [see Example 4 and Example 6].

The shortcomings of this method are: (1) Phosgene, one of the raw materials, is not friendly to the human body and the environment; (2) The yield of Example 4 is also low, only about 70%; although the yield of Example 6 reaches 85 About %, but the tributylamine used is a highly toxic substance and difficult to obtain, so it is not suitable for large-scale industrial production.

3. Chinese patent document CN1202884A discloses the above-mentioned intermediate obtained by the one-step condensation of 4,6-dimethoxy-2-phenoxycarbonylaminopyrimidine and 2-dimethylaminocarbonyl-5-nitrobenzenesulfonamide [see implementation Example 7].

The disadvantages of this method are: (1) 4,6-dimethoxy-2-phenoxycarbonylaminopyrimidine, one of the raw materials, is expensive and difficult to obtain; (2) the by-product content is high and difficult to separate and purify. As a result, the purity of the product is low and it is not suitable for industrial large-scale production.

Contents of the invention

The purpose of the present invention is to solve the above problems and provide a synthesis method of formamidesulfuron-methyl with lower production cost, higher reaction yield, higher product purity, and suitable for industrial large-scale production.

The technical solution to achieve the object of the present invention is: a synthesis method of formamidesulfuron-methyl, which has the following steps:

① Use 2-chlorosulfonic acid-4-nitro-N,N-dimethylbenzamide as the starting material, first perform an isocyanate reaction with sodium cyanate, and then react with 2-amino-4,6-dimethylbenzamide Oxypyrimidine undergoes a condensation reaction to obtain the intermediate N,N-dimethyl-2-{N-[N-(4,6-dimethoxypyrimidin-2-yl)-aminocarbonyl]-aminosulfonyl} -4-Nitrobenzamide;

②Intermediate N,N-dimethyl-2-{N-[N-(4,6-dimethoxypyrimidin-2-yl)-aminocarbonyl]-aminosulfonyl}-4-nitrobenzyl The amide is catalytically hydrogenated in the presence of formic acid to give formamidesulfuron-methyl.

The specific synthesis route is as follows:

.

In the above step ①, the molar ratio of the 2-chlorosulfonic acid-4-nitro-N,N-dimethylbenzamide and the sodium cyanate is 1:1 to 1:3, preferably 1: 1.5.

In the above step ①, the molar ratio of the 2-chlorosulfonic acid-4-nitro-N,N-dimethylbenzamide and the 2-amino-4,6-dimethoxypyrimidine is 1: 0.8～1:1.5, preferably 1:1.

In the above step ①, the isocyanate reaction is carried out in the presence of an organic solvent; the organic solvent is one of acetonitrile, propionitrile, and dichloromethane, preferably acetonitrile.

In the above step ①, the isocyanation reaction is carried out in the presence of an organic base; the organic base is one of pyridine, picoline and triethylamine, preferably pyridine.

The molar ratio of the 2-chlorosulfonic acid-4-nitro-N,N-dimethylbenzamide to the organic base is 1:1 to 1:3, preferably 1:2.

For the method of the above step ②, refer to Chinese patent document CN1414955A.

The invention has positive effects: the synthesis method of the invention has lower production cost, higher reaction yield, higher product purity, and is suitable for industrial large-scale production.

Detailed ways

(Example 1)

The preparation method of formamidesulfuron-methyl in this embodiment is as follows:

①In a 1L reaction bottle, add 58.5g of 2-chlorosulfonic acid-4-nitro-N,N-dimethylbenzamide (0.2mol), 19.5g of sodium cyanate (0.3mol) and 300g of acetonitrile, control the temperature to 30°C, add 31.6g of pyridine (0.4mol) dropwise, stir at 30°C for 5 hours, and then add 31.0g of 2-amino-4,6 to the reaction bottle. -Dimethoxypyrimidine (0.2 mol), stir at 30°C for condensation reaction for 2 hours.

After the reaction is completed, acetonitrile is first recovered by distillation under reduced pressure, then 340g of water is quickly added dropwise to the reaction bottle, and then the pH is adjusted to about 1 with hydrochloric acid, stirred for 0.5h, and filtered with suction. After the solid is washed with water and dried, 84.0g of the intermediate is obtained. N,N-dimethyl-2-{N-[N-(4,6-dimethoxypyrimidin-2-yl)-aminocarbonyl]-aminosulfonyl}-4-nitrobenzamide, The yield was 92.5%, and the HPLC purity was 97.1%.

② In a 1L reaction bottle, add 84.0g of the intermediate N,N-dimethyl-2-{N-[N-(4,6-dimethoxypyrimidin-2-yl)- obtained in step ① Aminocarbonyl]-Aminosulfonyl}-4-nitrobenzamide (0.185mol), 0.05g sodium molybdate, 3g wet palladium carbon catalyst (palladium content 5wt%, water content 50wt%) and 250mL formic acid, Stir and mix evenly, replace with nitrogen three times, and control the temperature at 35°C to introduce hydrogen for 4 hours.

After the reaction is completed, filter with suction and concentrate the filtrate. Add 250 mL of ethyl acetate to the residue and dissolve it at 40-50°C. Then cool the solution to 0-5°C to precipitate a solid. After stirring for 2 hours, filter and use 50 mL of ethyl acetate to filter the cake. After washing and drying, 79.6 g of formamidesulfuron-methyl was obtained, with a yield of 95.2% and a purity of 98.2%.

Table 1

Example 1 Example 2 Example 3 Example 4 Example 5 2-Chlorosulfonic acid-4-nitro-N,N-dimethylbenzamide 58.5g (0.2mol) 58.5g (0.2mol) 58.5g (0.2mol) 58.5g (0.2mol) 58.5g (0.2mol) sodium cyanate 19.5g (0.3mol) 19.5g (0.3mol) 19.5g (0.3mol) 23.4g (0.36mol) 15.6g (0.24mol) 2-amino-4,6-dimethoxypyrimidine 31.0g (0.2mol) 31.0g (0.2mol) 31.0g (0.2mol) 31.0g (0.2mol) 31.0g (0.2mol) organic base 31.6g pyridine (0.4mol) 37.2g methylpyridine (0.4mol) 40.4g triethylamine (0.4mol) 37.9g pyridine (0.48mol) 25.3g pyridine (0.32mol) Intermediate weight 84.0g 84.4g 81.3g 84.6g 82.0g Yield 92.5% 93.0% 89.5% 93.2% 90.3% HPLC purity 97.1% 97.3% 96.5% 97.5% 96.7%

Claims (8)

1. A synthesis method of formamidesulfuron-methyl, which has the following steps: ① Use 2-chlorosulfonic acid-4-nitro-N,N-dimethylbenzamide as the starting material, first perform an isocyanate reaction with sodium cyanate, and then react with 2-amino-4,6-dimethylbenzamide Oxypyrimidine undergoes a condensation reaction to obtain the intermediate N,N-dimethyl-2-{N-[N-(4,6-dimethoxypyrimidin-2-yl)-aminocarbonyl]-aminosulfonyl} -4-Nitrobenzamide; ②Intermediate N,N-dimethyl-2-{N-[N-(4,6-dimethoxypyrimidin-2-yl)-aminocarbonyl]-aminosulfonyl}-4-nitrobenzyl The amide is catalytically hydrogenated in the presence of formic acid to give formamidesulfuron-methyl. 2. The synthetic method of carbamatesufuron-methyl according to claim 1, characterized in that: in the above step ①, the 2-chlorosulfonic acid-4-nitro-N, N-dimethylbenzamide and The molar ratio of sodium cyanate is 1:1 to 1:3. 3. The synthetic method of carbamatesufuron-methyl according to claim 2, characterized in that: in the above-mentioned step ①, the 2-chlorosulfonic acid-4-nitro-N, N-dimethylbenzamide and The molar ratio of sodium cyanate is 1:1.5. 4. The synthetic method of carbamatesufuron-methyl according to claim 1, characterized in that: in the above step ①, the 2-chlorosulfonic acid-4-nitro-N, N-dimethylbenzamide and The molar ratio of the 2-amino-4,6-dimethoxypyrimidine is 1:0.8～1:1.5. 5. The synthetic method of carbamatesufuron-methyl according to claim 4, characterized in that: in the above step ①, the 2-chlorosulfonic acid-4-nitro-N, N-dimethylbenzamide and The molar ratio of the 2-amino-4,6-dimethoxypyrimidine is 1:1. 6. The synthesis method of formamidesulfuron-methyl according to claim 1, characterized in that: the organic solvent is one of acetonitrile, propionitrile, and dichloromethane. 7. The synthetic method of formamidesulfuron-methyl according to claim 1, characterized in that: in the above-mentioned step ①, the isocyanate reaction is carried out in the presence of an organic base; the organic base is pyridine, methyl One of pyridine and triethylamine; the molar ratio of the 2-chlorosulfonic acid-4-nitro-N,N-dimethylbenzamide to the organic base is 1:1 to 1:3. 8. The synthetic method of carbamatesulfuron-methyl according to claim 7, characterized in that: the organic base is pyridine; the 2-chlorosulfonic acid-4-nitro-N, N-dimethylbenzyl The molar ratio of amide to the organic base is 1:2.