Study On The Synthesis Of Bupirimate

Bupirimate is a kind of pyrimidine fungicides with excellent biological activity.At present,bupirimate mainly adopts the process route of nitroguanidine in our country.However,in this process,nitroguanidine is an energetic materials,which has poor thermal stability and has great potential safety hazards.Cyanamide and ethylamine were used as starting materials in this paper,and the complete synthesis of bupirimate was achieved by adding,neutralizing,cyclizing and esterifying.The process was optimized and the structural formula of each poduct was determined by ¹H NMR,¹³C NMR,FT-IR,MS and other characterization methods.（1）N-ethylguanidine sulfate was formed from cyanamide with ethylamine under the action of concentrated sulfuric acid.The precise control of drip time is realized by using the micro constant drip addition.Under the best conditions:the molar ratio of ethylamine/sulfuric acid/cyanamide was 1.5:0.5:1,the addition time of cyanamide was 5 h,and the reaction temperature was 35°C.The yield of N-ethylguanidine sulfate was 72.4%（based on cyanamide）,and the purity was 96.1%,which was 8%higher than the literature value.An accurate determination of N-ethylguanidine sulfate by non-aqueous titration of perchlorate-glacial acetic acid standard solution was established.（2）N-ethylguanidine sulfate and sodium hydroxide were cyclinized with ethyl 2-n-butyl-acetoacetate by"one-pot method".Under optimal conditions,the yield of 5-n-butyl-2-ethyl-amino-4-hydroxy-6-methylpyrimidine was 84.3%（based on ethyl 2-n-butyl-acetoacetate）,and the purity up to 98.5%.Compared with literature,the isomer was determined and its structure was analyzed by single crystal diffraction method,and the reaction mechanism was analyzed and explored by the deep relationship of single crystal structure,which laid a foundation for directional control of such reactions in the future.（3）During the synthesis of bupirimate,due to the special structure of 5-n-butyl-2-ethyl-amino-4-hydroxy-6-methylpyrimidine,the traditional acid-binding agents are prone to side reactions,the yield and purity of the target product are low.In this paper,bupirimate was synthesized using milder sodium bicarbonate instead of sodium carbonate as an acid-binding agent.The optimal process conditions were obtained through single factor experiments and orthogonal experiments.The molar ratio of methyl-4-hydroxy-6-methylpyrimidine/Na HCO₃/N,N-dimethylsulfamoyl chloride was 1:2.2:1.4,the reaction temperature was 110°C and the reaction time was 8 h.The yield of product was 84.3%（based on 5-n-butyl-2-ethylamino-4-hydroxy-6-methylpyrimidine）,its purity up to 97.0%,and the mechanism of the reaction was briefly investigated.