Studies on the Synthetic Process of 2-Amino-5-chloro-N, 3-dimethylbenzamide and Ethyl 2-Methylacetoacetate
|School||Hunan Normal University|
|Keywords||Chlorantraniliprole Pirimicarb Ethyl 2-methylacetoacetate 2-Amino-5-chloro-N,3-dimethylbenzamide Synthetic Process|
2-Amino-5-chloro-N,3-dimethylbenzamide is the key intermediate of synth-esis of chlorantraniliprole. Ethyl 2-methylacetoacetate is the key intermediate of synthesis of pirimicarb. This paper has summarized the optimization on the synthesis process of the 2-Amino-5-chloro-N,3-dime-thylbenzamide and ethyl 2-methylacetoacetate.Two reasonable synthesis routes of 2-Amino-5-chloro-N,3-dimethyl-benza-mide were evaluated in this paper, that were obtained from 3-methyl-2-nitroben-zoic acid. A-route target compound was obtained via catalyzed reduction, cyclization, methylamination and chlorination, the yield and purity of the product was≥82% and≥97.9%, respectively. During the process of preparing 2-amino-3-methyl benzoic acid, high requirements for equipment was resolved by using FeO(OH)/C-catalyzed reduction with hydrazine hydrate. During the process of preparing 2-Amino-5-chloro-N,3-dimethylbenzamide, the suitable chlorination reagent was determined via large quantity of experiment and exploration. From this, the yield and purity of the product was≥89.4% and≥97.9%. The total yield increased about 17%.In the process of synthesis, cyclization, methylamineation and chlorination in one pot because of their solvent was unanimous, which avoided purification of the intermediate product and simplified the process, therefore the route was more suited for industrialization production. B-route TM was obtained via catalyzed reduction, chlorination, cyclization and methylamination, the yield and purity of the product was≥84.3% and≥97.6%. respectively. The total yield increased about 17.8%.Two reasonable synthesis routes of ethyl 2-methylacetoacetate were explored. A-route was enamine synthesis.2-methylacetoacetate was obtained from methyl aceto acetate, via piperidine nucleophilie, acid dehydration and methylamination. During the process of preparing 2-hexahy dropyridine ethyl crotonate, it was favourable toward the next step reaction by using piperidine as the nucleophilic reagent. The yield and purity of the product was≥96.4%and≥96%. The total yield increased about 5.4%. This method without using basic catalyst, could avoid self-condensation by-products. From this, the yield and purity of the product was≥85.4% and≥96.3%, respectively. B-route was catalytic hydrogenation synthesis. The synthesis of 2-methylacetoacetate was got from formaldehyde condensation and hydrogenation reduction with hydrogenation catalyst. During the process of preparing the target compound, the suitable hydrogenation catalyst was selected and reaction conditions, such as amount of catalyst, reaction time and so on, were optimized. Then the yield and purity of the product was≥91.7% and≥99%. Raw material was cheap, the yield and purity was high, post-treatm-ent was simple. Therefore, the method was more suitable for industrial.The by-products and its important intermediates were separated, and then characterized by NMR and MS. It’s found that the structures of target product and important intermediates were confirmed.