Sonogashina偶联法合成芳基末端炔的工艺改进

以对二溴苯(Ⅰa)、1,3,5-三溴苯(Ⅰb)和2-甲基-3-丁炔-2-醇(Ⅱ)为原料,在PdC l2、PPh3和CuI的催化作用下进行Sonogash ina偶联反应,偶联产物在KOH作用下发生消去反应,分别得到对溴苯乙炔(Ⅳa)、对二乙炔基苯(Ⅳa′)、1,3,5-三乙炔基苯(Ⅳb)。研究发现,在合成中间体1,4-二(3-羟基-3-甲基-1-丁炔)苯时,选择n(Ⅰa)∶n(Ⅱ)=1∶3较为适合;共催化剂n(CuI)∶n(Ⅱ)≈0.01时产率较高;水对偶联反应无影响。粗产物经硫酸铜溶液萃取、硅胶过滤、重结晶、真空升华进行分离提纯得到纯产品。3种产物的收率分别为75%、72%、70%。产物用IR、GC-MS、1HNMR进行了确证。

Improvement on Synthesis Method of Terminal Aryl Acetylenes with Sonogashina Coupling

Using 1,4-dibromobenzene(Ⅰa),1,3,5-tribromobenzene(Ⅰb) and 2-methyl-3-butyn-2-ol(Ⅱ) as starting materials and PdCl2,triphenylphosphine,CuI and KOH as catalysts,1-bromo-4-ethynylbenzene(Ⅳa),1,4-diethynylbenzene(Ⅳa′) and 1,3,5-triethynylbenzene(Ⅳb) were synthesized by Sonogashina coupling reaction and elimination reaction.The suitable molar ratio of Ⅰa:Ⅱ for synthesizing 1,4-bis(3-hydroxy-3-methyl-1-butynyl) benzene was 1∶3.When the molar ratio of CuI/Ⅱ was about 0.01,the product yield was high.Water had no obvious interference on the coupling reaction.The products obtained were purified by extraction with copper sulfate solution,filtration through silica gel,recrystallization and vacuum sublimation.The isolated yields were 75%,72% and 70%,respectively.The final products were characterized and confirmed by IR,GC-MS and 1HNMR.