Synthesis Of High-Effective Sulfonylurea Herbicide Nicosulfuron

Nicosulfuron is a sulfonylurea herbicide with high efficiency, low toxicity, low residue and high selectivity, it is one of acetolactate synthase inhibitors (ALS) and widely used to control weeds in com field. The synthesis of Nicosulfuron and its intermediate2-chloro-N,N-dimethylnicotinamide were researched in this dissertation, focusing on the comparison of different routes and the optimization of reaction conditions.Two synthetic routes of2-chloro-N, N-dimethylnicotinamide were researched; Propargyl alcohol and ethyl cyanoacetate were used as the starting materials in route1, underwent oxidation-amination, condensation, cyclization and hydrolysis reaction forming2-chloronicotinic acid, followed acyl chloridized by triphosgene, subsequently amination by dimethylamine to give2-chloro-N,N-dimethylnicotinamide, total yield of67.9%of six steps was obtained; Propargyl alcohol and2-cyano-N,N-dimethylacetamide were used as starting materials in route2, underwent oxidation-amination, condensation and cyclization forming2-chloro-N,N-dimethylnicotinamide directly, total yield of64.5%of three steps was obtained. A method of pressurized hydrogen chloride was used for cyclization reaction of both routes, compared with the performance of atmospheric reaction, which not only the reaction time is reduced by half, but also the amount of hydrogen chloride is reduced, the method avoided the use of high toxic and high pollution raw materials such as phosphorus oxychloride, thionyl choride, decreased the wastes and improved the selectivity of the reaction. At last, a conclusion was drawn that route2have advantage of less waste emissions and lower cost through the comparison with route1.The synthesis of nicosulfuron was starting from2-chloro-N,N-dimethylnicotinamide, via which could obtain N,N-dimethyl-2-sulfamoylnicotinamide, followed by addition with2-isocyanato-4,6-dimethoxypyrimidine to give the title product. Two synthetic routes of N,N-dimethyl-2-sulfamoymicotmarnide were studied.2-mercapto-N,N-dimethylnicotinamide was afforded by using2-chloro-N, N-dimethylnicotinamide and ammonium sulfide as the starting materials in route1, via substitution and acidification; then chlorine and ammine were introduced for oxychloride and ammonlysis reaction successively to give N,N-dimethyl-2-sulfamoylnicotinamide. One pot method was used in route2, the ammonium -N,N-dimethylnicotinamide-2-thiolate which obtained from step one using2-chloro-N,N-dimethylnicotinamide and ammonium sulfide as the starting materials, was oxidized by hydrogen peroxide and sodium hypochlorite successively to give N,N-dimethyl-2-sulfamoylnicotinamide. Ammonium sulfide was used for substitution reaction instead of sodium sulfide and sodium hydrosulfide which disclosed in patents,90.7%yield was obtained, no further purification was needed, and higher yield was obtained. The method of addition with isocyanate to get nicosulfuron had such advantages as good atom economy, simple reaction processing and lower cost over the method of condensation with chloroformate. Through the comparison of waste emissions and cost on materials, route2was better than route1.