Continuous,efficient and safe synthesis of 1-oxa-2-azaspiro[2.5]octane in a microreaction system  

作　　者：Jinpei Huang Xingwei Lu Xuejing Zhang Yiqiang Jin Yifeng Zhou 

机构地区：[1]College of Life Science,China Jiliang University,Hangzhou 310018,China [2]Apeloa Pharmaceutical Co.,Ltd.,Dongyang 322118,China

出　　处：《Chinese Journal of Chemical Engineering》2023年第9期37-42,共6页中国化学工程学报（英文版）

基　　金：the support of the National Natural Science Foundation of China(22108264)for this work。

摘　　要：1-Oxa-2-azaspiro[2.5]octane,as one of N-H oxaziridines,is a selective electrophilic aminating agent for N-,S-,C-,and O-nucleophiles.It has the features of stereoselectivity and the absence of formation of strongly acidic or basic byproducts,leading to considerable interest in the development of organic synthetic methods.Currently,the economically feasible route of production of 1-oxa-2-azaspiro[2.5]octane is the reaction of cyclohexanone with ammonia and sodium hypochlorite.However,due to strong exothermic reactions,massive gas release and heterogeneous reaction,the controllability,efficiency and safety of the reaction are in great difficulty using batch technology.In this paper,a microreaction system containing predispersion,reaction and phase separation was introduced into the preparation of 1-oxa-2-azaspiro[2.5]octane.The research results showed that precise control of the process including droplet dispersion,temperature control,reaction time control and fast continuous phase separation,was the key to process intensification.Under optimal conditions,the concentration of 1-oxa-2-azaspiro[2.5]octane in product obtained by microreaciton system(~2.0 mol·L^(-1))was much higher than that obtained by batch technology(0.2-0.4 mol·L^(-1)),which demonstrated that the continuous-flow synthesis would be a more efficient substitute for batch synthesis.Meanwhile,the results of the derivation experiments also showed that the aminating agent solution with higher concentration was more advantageous in the applications.

关 键 词：Multiphase reaction MICROREACTOR SYNTHESIS Oxaziridine Process intensification 

分 类 号：O62[理学—有机化学]