高收率氟吡菌酰胺中间体的绿色合成工艺

针对目前氟吡菌酰胺中间体（2-3-氯-5-(三氟甲基)吡啶-2-基]乙胺(5)）合成路线长、操作复杂，产品收率低、工业生产成本高等问题，本文系统开展了(5)绿色合成工艺的研发。以2,3-二氯-5-(三氟甲基)吡啶(1)为原料，选择将亲核取代、脱羧两步反应合为一锅法制得2-3-氯-5-(三氟甲基)吡啶-2-基]乙腈(3)，之后将催化加氢还原和水解连续进行得到氟吡菌酰胺中间体(5)的盐酸盐。在一锅法中详细考察了溶剂、碱、pH等重要因素对收率的影响。优选溶剂为DMF、碱为无水碳酸钾、pH为0.5~1，产品(3)收率达到88.1%，纯度98.5%。在加氢还原和水解连续反应中探索了催化剂种类、加氢反应时间和温度以及水解中盐酸用量等影响。结果表明，采用5% Pd/C催化剂（型号R5K1），在加氢反应温度15℃、反应时间12h、水解时38%浓盐酸用量为n_(HCl)∶n₍₃₎=5.5，产品(5)收率达78.8%，纯度为96.2%。同时，实现了工艺中各步溶剂以及Pd/C催化剂的高效回收套用，为该中间体的清洁工业生产提供了新技术支撑。

Green synthesis of fluopyram intermediates in high yield

In view of the problems of the current fluopyram intermediate (2-3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethanamine(5)) synthesis route, complicated operation, low product yield and high industrial production cost, the research and development of the green synthetic process of (5) was systematically carried out. In particular, using 2,3-dichloro-5-(trifluoromethyl)pyridine(1) as raw material, the two-step reaction of nucleophilic substitution and decarboxylation was conducted via one-pot method to prepare 2-3-chloro-5-(trifluoromethyl)pyridin-2-yl]acetonitrile(3). Afterwards, catalytic hydrogenation reduction and hydrolysis were carried out to obtain fluopyram intermediate (5) hydrochloride. Based on the analysis of the reaction mechanism, the effects of solvent, alkali, pH and other important factors on the yield were investigated in one-pot method. The preferred solvent was DMF, the base was anhydrous potassium carbonate, the pH was 0.5—1, the yield of product (3) reached 88.1%, and the purity was 98.5%. In the hydrogenation reduction and hydrolysis reactions, the effects of catalyst types, hydrogenation reaction time and temperature were explored. The results show that the yield of product (5) reaches 78.8% and the purity is 96.2% by using 5% Pd/C catalyst (type R5K1). The optimal reaction conditions are as follows: the hydrogenation reaction temperature is 15℃, the reaction time is 12h, and the amount of 38% concentrated hydrochloric acid is n_(HCl)∶n₍₃₎ =5.5. At the same time, the efficient reuse of recovered solvent and the Pd/C catalyst in each step is realized, which provides a new technology support for the clean industrial production of the intermediate.