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

doi:10.1016/j.cjche.2023.03.001

Abstract

Abstract: 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.

Key words: Multiphase reaction, Microreactor, Synthesis, Oxaziridine, Process intensification

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

Jinpei Huang, Xingwei Lu, Xuejing Zhang, Yiqiang Jin, Yifeng Zhou. Continuous, efficient and safe synthesis of 1-oxa-2-azaspiro [2.5] octane in a microreaction system[J]. Chinese Journal of Chemical Engineering, 2023, 61(9): 37-42.

Jinpei Huang, Xingwei Lu, Xuejing Zhang, Yiqiang Jin, Yifeng Zhou. Continuous, efficient and safe synthesis of 1-oxa-2-azaspiro [2.5] octane in a microreaction system[J]. 中国化学工程学报, 2023, 61(9): 37-42.

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