5-氟烟酸的合成

Synthesis of 5-Fluoronicotinic Acid

以烟酸(Ⅰ)为原料,经3步反应合成5 氟烟酸(Ⅵ)。Ⅰ与SOCl2在50℃回流4h后,除去SOCl2,170℃溴化12h,水解得5 溴烟酸(Ⅲ),收率为91%;Ⅲ于反应釜中,Cu2+为催化剂,与氨水在190℃反应24h,氨化得5 氨基烟酸(Ⅳ),收率为75%;Ⅳ应用希曼反应,在0℃重氮化,HBF4氟代得氟硼酸盐(Ⅴ),70℃热解Ⅴ得Ⅵ,收率77%。5 氟烟酸结构经FTIR、GC-MS证实。

5Fluoronicotinic acid was prepared using nicotinic acid as starting material through three step reactions.Nicotinic acid,refluxed for 4 h with thionyl chloride and excess thionyl chloride evaporated,was brominated at 170 ℃ for 12 h to give 5bromonicotinic acid in 91% yield after hydrolysis.Amination of 5bromonicotinic acid in autoclave by ammonium hydroxide solution with copper sulfite pentahydrate as catalyst at 190 ℃ for 24 h gave 5aminonicotinic acid in 75% yield.By Schiemann reaction,5aminonicotinic acid was diazotized at 0 ℃ in the presence of excess fluoboric acid and the diazonium fluoborate was decomposed in toluene at 70 ℃ to give 5fluoronicotinic acid in 77% yield.The title compound was identified by FTIR and GC-MS.