Continuous deacylation of amides in a high-temperature and high-pressure microreactor

Abstract

The deacylation of amides, which is widely employed in the pharmaceutical industry, is not a fast reaction under normal conditions. To intensify this reaction, a high-temperature and high-pressure continuous microreaction technology was developed, whose space-time yield was 49.4 times that of traditional batch reactions. Using the deacylation of acetanilide as a model reaction, the effects of the temperature, pressure, reaction time, molar ratio of reactants, and water composition on acetanilide conversion were carefully studied. Based on the rapid heating and cooling capabilities, the kinetics of acetanilide deacylation at high temperatures were investigated to determine the orders of reactants and activation energy. This microreaction technology was further applied to a variety of other amides to understand the influence of substituents and steric hindrance on the deacylation reaction.

Graphical abstract

Keywords

amide deacylation / microreactor / flow chemistry / reaction intensification

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Acknowledgments

We gratefully acknowledge the financial support from the National Natural Science Foundation of China (Grant No. 21991104) and the Shandong Province Major Science and Technology Innovation Project (Grant No. 2019JZZY020401).

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