Process for full water phase synthesis of pharmaceutical intermediate dimethyl cyanoiminodithio-carbonate

[0020] Example 1:

[0021] The feed ratio (mole) is: calcium cyanamide: sodium carbonate: carbon disulfide = 1:1.02:1.2 in the first step, and calcium cyanamide: dimethyl sulfate = 1:2.2 in the second step.

[0022] In the first step, add 35g of industrial grade calcium cyanamide (containing 20% ​​available nitrogen), 140ml of water, and then add 27g of sodium carbonate to mix in a three-necked flask with a stirrer, and add the catalyst cetyltrimethyl bromide 0.3g ammonium chloride, add 18.19mLCS dropwise 2 , Control the temperature at 40℃~43℃, stir the mixture until CS 2 All dissolved (about 4 hours). The mixture is filtered while hot without cooling, the filtrate is collected, and the filter residue is treated with 60 ml of water. The washing liquid is collected separately, and the washing liquid is used for the preparation of the next batch. The filtrate was directly used in the next methylation reaction.

[0023] In the second step, take the mother liquor of the disodium dibasic

[0024] Example 2:

[0025]The method is the same as in Example 1. The feed ratio (mole) is changed to the first step (calcium cyanamide: sodium carbonate: carbon disulfide = 1:1.02:1.2), and the second step (calcium cyanamide: dimethyl sulfate = 1: 2.1) The calcium cyanamide is still 35g, and the catalyst is changed to cetyltriethylammonium chloride.

[0026] In the first step, add 35g of commercial calcium cyanamide (industrial grade, 20% available nitrogen), 120ml of water, and then add 27g of sodium carbonate to mix in a three-necked flask with a stirrer, and add the catalyst cetyltrimethyl 0.3g ammonium bromide, add 18.19mLCS dropwise 2 , Control the temperature to 40℃~45℃, stir the mixture until CS 2 All dissolved (about 3 hours). The mixture is filtered while hot without cooling, the filtrate is collected, and the filter residue is treated with 60 ml of water. The washing liquid is collected separately, and the washing liquid is used for the preparation of the next batch. The f

[0028] Example 3:

[0029] The method is the same as in Example 1. The feed ratio (mole) is changed to the first step (calcium cyanamide: sodium carbonate: carbon disulfide = 1:1: 1.1), and the second step (calcium cyanamide: dimethyl sulfate = 1: 2.0), the calcium cyanamide is 35g, and the catalyst is changed to phenyltrimethylammonium chloride.

[0030] In the first step, add 35g of commercial calcium cyanamide (industrial grade, 20% available nitrogen), 160ml of water, add 26.5g of sodium carbonate to the three-necked flask with a stirrer, and add the catalyst cetyltrimethyl 0.3g ammonium bromide, add 16.6mLCS dropwise 2 , Control the temperature at 35℃~42℃, stir the mixture until CS 2 All dissolved (about 5 hours). The mixture is filtered while hot without cooling, the filtrate is collected, and the filter residue is treated with 60 ml of water. The lotion is collected separately and used for the next batch of preparation. The filtrate is directly used in the next methylation rea