Synthesis Of 2-amino-5-cyano-n,3-dimethylbenzamide

Cyantraniliprole,as pesticide of the second generation inhibitor of ryania receptor, belongs to the anthranilic diamides. Cyantraniliprole has unique mechanism of action.It is broad-spectrum efficient and environment friendly. It is meaningful to research the synthesis of the important intermediate of 2-amino-5-cyano-N,3-dimethyl benzamide, because Cyantraniliprole was the first insecticide to control the chewing mouthparts and sucking mouthparts pests at the same time.This article has summarize the preparation method of Cyantraniliprole and its intermediate 2-amino-5-cyano-N,3-dimethyl benzamide. On the basis of analysis and researching,the synthetic route of 2-amino-5-cyano-N,3-dimethyl benzamide was designed. 2-amino-N,3-dimethyl benzamide was made from 3-dimethyl-2-nitro benzoic acid through two different routes.in this process solid phosgene, an aqueous methylamine, hydrazine hydrate as raw materials was also needed.then obtained 2-amino-5-bromo-N,3-dimethyl benzamide by oxybromination,and at last got 2-amino-5-cyano-N,3-dimethyl benzamide by cyano substitution.In the preparation of 2-amino-N,3-dimethyl benzamide,the condition of route one was : the ferric trichloride/activated carbon as catalyst of nitro-reduction n(3-dimethyl-2-nitro 3-dimethyl-2-nitro) : n(hydrazine hydrate)=1:2, reaction temperature 70℃, m(ferric chloride hexahydrate) : m(3- methyl- 2- nitro benzoic acid)=10%.the yield of 2-amino-3-methyl benzoic acid was 96.2%,purity was 99.5%.in the preparation of cyclization and amidation reaction,n(2-amino-3-methyl benzoic acid):n(solid-phosgene)=3:1.3,m(pyridine):m(2-amino-3-dimethyl benzoic acid)=8%,reaction temperature 70℃,n(methylamine):n(2-Amino-3-methyl benzoic acid)=1.2:1,yield of cyclization and amidation reaction was 90.8%,the purity was 98.4%. total yield of route one was 85%. Route two: In the preparation of chloroformylation reaction, m(DMF): m(3-methyl-2-nitrobenzoic acid) = 3%, pre-reaction temperature is 70 ℃, then gradually be warmed to 78 ℃; the temperature of acylation reaction was 50 ℃, n(3-dimethyl-2-nitro benzoic acid): n methylamine) = 1: 2.5, the total yield of two steps was 93.2%, purity of N, 3-dimethyl-2-nitro benzamide was 98.6%; In the reaction of nitro reduction, the solvent was ethanol, dosage of hydrazine hydrate was 5% excess, the catalyst can be applied for 4 times, the yield was 96.2%,purity of N, 3-dimethyl-2-nitro benzamide was 99.2%.the total yield of N, 3-dimethyl-2-nitro benzamide in route two was 89.7%. In the oxidation bromide reaction, n(HBr): n(2-amino-N, 3-methyl benzamide) = 1.5: 1, n(H2O2): n(2-amino-N,3-dimethyl benzamide) = 1.2: 1, after the completion of the dropwise addition of hydrogen peroxide,the temperature would be warmed 5 ℃per hour, until TLC is detected that there is no starting material. Yield of 2-amino-5-bromo-N,3-dimethyl benzamide was 94.0 %. cuprous cyanide was selected as cyanide reagent in nitrile reaction, N- methyl pyrrolidone was as reaction solvent,and the reaction proceed at reflux temperature. Yield of 2-amino-5-cyano-N,3-dimethyl benzamide was 95%, mp is 203.0-203.5 ℃.