摘要
5-醛基嘧啶是三氟苯嘧啶的关键中间体之一,在传统的间歇合成过程中存在正丁基锂的安全使用、超低温的实现、收率偏低等问题。以5-溴嘧啶为原料,通过微反应器连续合成5-醛基嘧啶,考察了正丁基锂的用量、停留时间、反应温度以及淬灭剂的用量和淬灭时间对反应的影响。结果表明:当进料物质的量比为n(5-溴嘧啶)∶n(正丁基锂)∶n(甲酸乙酯)=1.00∶1.03∶1.06,溴锂交换停留时间为50 s,第二段停留时间为40.8 s,反应温度为-62℃时较佳,提纯后收率可达61.5%;淬灭时使用4倍用量饱和氯化铵溶液作淬灭剂,淬灭时间10 min最佳。
5-Aldehyde pyrimidine is one of the key intermediates of trifluorophenyl pyrimidine.The traditional batch synthesis process has problems such as the safe use of n-butyl lithium,the realization of ultra-low temperature,and the low yield.In this paper,5-bromopyrimidine was used as the raw material to continuously synthesize 5-aldehyde pyrimidine in a microreactor.The influence of the amount of n-butyllithium,residence time,reaction temperature,and the amount of quencher and quenching time on the reaction were investigated.The experimental results show that when the feed molar ratio is n(5-bromopyrimidine)∶n(n-butyl lithium)∶n(ethyl formate)=1.00∶1.03∶1.06,the lithium-bromide exchange residence time is 50 s,the second residence time is 40.8 s,and the reaction temperature is-62℃,the yield can reach 61.5%;4 times amount of saturated ammonium chloride solution is used as the quenching agent when quenching,and the best quenching time is 10 minutes.
作者
张皓
殷俊
廖本仁
ZHANG Hao;YIN Jun;LIAO Benren
出处
《上海化工》
CAS
2020年第6期8-12,共5页
Shanghai Chemical Industry
基金
上海市科学技术委员会科研计划项目(18DZ1112702)。
关键词
微反应器
5-醛基嘧啶
溴锂交换
Microreactor
5-Aldehyde pyrimidine
Lithium-bromide exchange
