基于微通道技术合成2-氨基-5-氟-3',4'-二氯联苯

Synthesis of 2-amino-5-fluoro-3',4'-dichlorobiphenyl based on microchannel technology

2-氨基-5-氟-3',4'-二氯联苯是琥珀酸脱氢酶抑制剂(SDHI)类杀菌剂—联苯吡菌胺的重要中间体。基于微通道技术,以3,4-二氯苯胺为原料,经重氮化、中和、与对氟苯胺偶联得到2-氨基-5-氟-3',4'-二氯联苯。系统考察了影响重氮化、中和、偶联3步对反应的影响,并得出优化条件:盐酸与3,4-二氯苯胺当量6:1,亚硝酸钠与3,4-二氯苯胺当量1.1︰1,成盐反应温度60℃,重氮反应温度25℃,氢氧化钠当量6.5︰1,中和温度25℃,偶联最佳温度120℃,对氟苯胺当量10︰1。在此优化条件下合成2-氨基-5-氟-3',4'-二氯联苯粗品含量85%,精制后含量可以达到98.5%,2步总收率65%。

2-Amino-5-fluoro-3',4'-dichlorobenzene is an important intermediate of succinate dehydrogenase inhibitor(SDHI)fungicide,bixafen.Based on microchannel technology,3,4-dichloroaniline was used as raw material to obtain 2-amino-5-fluoro-3',4'-dichlorobiphenyl through diazotization,neutralization,and coupling with p-fluoroaniline.The system investigated the effects of the three steps of diazotization,neutralization,and coupling on the reaction,and obtained optimized conditions:hydrochloric acid and 3,4-dichloroaniline equivalent 6︰1,sodium nitrite and 3,4-dichloroaniline equivalent 1.1︰1,salt formation reaction temperature 60℃,diazotization reaction temperature 25℃,sodium hydroxide equivalent 6.5︰1,neutralization temperature 25℃,optimal coupling temperature 120℃,and p-fluoroaniline equivalent 10︰1.Under these optimized conditions,2-amino-5-fluoro-3',4'-dichlorobiphenyl was synthesized with a crude content of 85%.After refinement,the content can reach 98.5%,and the total yield of the two steps is 65%.