3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-甲酸的合成

以2,3-二氯吡啶为起始原料,通过水合肼亲核取代、马来酸二乙酯环合制得2-(3-氯-2-吡啶基)-5-氧-3-吡唑烷甲酸乙酯(5);5经苯磺酰氯酯化、溴化氢溴化制得3-溴-1-(3-氯-2-吡啶基)-4,5-二氢-1H-吡唑-5-甲酸乙酯(7);7经脱氢、水解合成了用于制备氯虫酰胺的关键中间体--3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-甲酸,总收率39.5%,其结构经~1H NMR和MS确证.

Synthesis of 3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic Acid

Ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate(5) was prepared from 2,3-dichloropyidine by nucleophilic substitution with aqueous hydrazine, and then cyclization with diethyl maleate. Ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate(7) was prepared from 5 by esterification with benzenesulfonyl chloride, and then bromination with hydrogen bromide. A key intermediate for preparing chlorantraniliprole, 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid(1), was synthesized from 7 by dehydrogenation and hydrolysis in overall yield of 39.5%. The structures were confirmed by ~1H NMR and MS.