知识与财富的链接
以三氟乙酰乙酸乙酯和氰基乙酰胺为原料,经环合、氯化、氰基水解、催化氢解4步反应得到4-三氟甲基烟酸,总收率达48.3%。其结构经1HNMR、MS分析测试技术确证。通过考察各步反应条件,得出最佳工艺条件为:氯化反应中,n(2,6-二羟基-4-三氟甲基烟腈)∶n(三乙胺)∶n(四甲基氯化铵)=1∶2∶1,产率80.8%;氰基水解的最佳溶剂为体积比4∶1的硫酸-硝酸混合溶剂,产率92.7%;催化氢解反应中,n(2,6-二氯-4-三氟甲基烟酸)∶n(醋酸钠)=1∶2,10%Pd/C的用量为2,6-二氯-4-三氟甲基烟酸质量的6%,产率90.4%。
Starting from trifluoroacetoacetate and cyanoacetamide, via cyclization, chlorination, hydrolysis, hydrogenolysis, 4-trifluoromethylnicotinic acid was obtained. The total product yield was 48.3%. Its structure as well as intermediate of each reaction was confirmed by MS, 1H NMR. Comparing to the reaction conditions of each step, optimal conditions were that :In the chlorination reaction, n(tetramethylammonium chloride): n(Triethylamine):n（2,6-dihydroxy-4-(trifluoromethyl)nicotionitrile）=1:2:1 ,the yield of target product is 80.8％; The best solvent of hydrolysis is a mixed solvent of Sulfuric acid and nitric acid (volume ratio 4:1),the yield is 92.7％;In the hydrogenolysis reaction,n (2,6-dichloro-4-(trifluoromethyl)nicotinic Acid):n(sodium acetate) =1:2, The weight of 10％ Pd∕C is six percent of 2,6-dichloro-4-(trifluoromethyl)nicotinic acid, the yield of target product is 90.4％.
