The Synthesis Of A Neonicotinoid Insecticide And The Technology Optimization Of Its Intermediates

With the improvement of agricultural productivity and emphasis on environmental safety, people propose higher requirements on pesticides. Compared with traditional pesticides, systemic insecticides show more superior features, among which new neonicotinoid insecticides represent evidently. As the third generation of new neonicotinoid insecticide, dinotefuran has a novel structure, high efficiency, low toxicity and good selectivity which present a vast application prospect. According to the literature research and the laboratory existing conditions, selected three important intermediates during the synthesis process which have the enormous economic value. Optimized the synthesis technology and found out ways to decrease production period. Finally completed the synthesis of dinotefuran, purified the product and confirmed its structure through a variety of characterizations.Synthesized O-methylisourea sulfate through cyanamide and methanol with concentrated sulfuric acid existing. The optimized reaction conditions were as follows, the molar ratio of methanol, cyanamide, concentrated sulfuric acid was 11.5:2.3:1, reacted at 10℃ for 3h. The optimized crystallization conditions were as follows, added acetone whose mass equivalent as reaction solution under room temperature, stirred at 450rpm and finally gave a yield of 77.3%. O-methyl-N-nitroisourea was synthesized through O-methylisourea sulfate by the mixed sulfuric acid and nitric acid. The molar ratio of sulfuric acid, nitric acid, O-methylisourea sulfate was 5.2:1.3:1, reacted at 0℃ for 8h and gave a yield of 84.5%. The total yield was 65.3% according to cyanamide.1-methyl-3-nitroguanidine was synthesized by nitroguanidine and methylamine under alkaline environment. The optimized conditions were as follows, the molar ratio of methylamine and nitroguanidine was 1.3:1, pH was about 11～12, reacted at 50℃ for 3h and gave a yield of 81.2%. 1-methyl-3-nitroguanidine reacted with methylamine and formaldehyde to synthesize 1,5-dimethyl-2-phosphite amino-1,3,5-triazine. The optimized conditions were as follows, the molar ratio of formaldehyde, methylamine and 1-methyl-3-nitroguanidine was 3.5:1.5:1, reacted at 70℃ for 7h and gave a yield of 74.3%. The total yield was 60.3% according to nitroguanidine.Synthesized 1,1,2-ethanetricarboxylic acid triethyl ester through using diethylmalonate and ethyl chloroacetate as raw material with sodium alkoxide existing. The optimized conditions were as follows, chloroacetate was added into the mixture of diethyl malonate and sodium alkoxide, the molar ratio of diethyl malonate, sodium and chloroacetate was 1.2:1.2:1, reacted at 80℃ for 8h and gave a yield of 60.7%. The product was reduced by sodium borohydride in the tertiary butanol-methanol system to generate 2-hydroxymethyl-1,4-butanediol, it was directly used for the next step without further separation and characterization. Used 1.2wt% TsOH as the catalyst to stimulate dehydrating under 120℃ and the yield of tetrahydro-3-furanylmethanol finally reached 43.1%. The total yield was 26.2% according to diethylmalonate.The prepared tetrahydrofuran-3-methanol reacted with TsCl to generate ester. The product condensed with 1,5-dimethyl-2-phosphite amino-1,3,5-triazine with the effect of sodium methoxide, hydrolyzed using hydrochloric acid to generate dinotefuran at a yield of 42.6%. The crude product was cooled to crystallize and purified by the column chromatography to give the pure compound.