# Enzymatic aminolysis in continuous flow: an efficient strategy for the synthesis of salicylamide derivatives

## TL;DR

This paper presents a green and efficient method using enzymes in a microreactor to synthesize salicylamide derivatives with potential drug applications.

## Contribution

A novel continuous-flow enzymatic aminolysis strategy for synthesizing salicylamide derivatives is developed and optimized.

## Key findings

- 34 salicylamide derivatives were synthesized with ideal yields using the continuous-flow method.
- The continuous-flow approach outperformed conventional batch methods in terms of space-time yield.
- The method allows for precise modification of the salicylamide skeleton for drug screening.

## Abstract

Salicylamide derivatives with different amine substitutions demonstrate potent biological activities such as anti-tumor, antibacterial and neuroprotective properties. In this work, a green and efficient strategy for the synthesis of salicylamide derivatives catalyzed by Lipozyme®TL IM from Thermomyces lanuginosus in continuous flow microreactors was developed. Enzymatic aminolysis from methyl salicylate and amines (cyclic and linear aliphatic amines, aryl alkyl amines, tryptamines) in a continuous-flow microreactor was used for the synthesis of salicylamide derivatives. Reaction parameters were optimized, and continuous flow was compared with conventional batch methods using space-time yield (STY). This strategy showed broad substrate applicability, enabling the synthesis of 34 salicylamide derivatives with ideal yields. It provides a novel sustainable approach for precise modification of the salicylamide skeleton, offering valuable compounds for drug screening and structure–activity relationship studies.

Reaction parameters were optimized in a K2CO3/Lipozyme® TL IM catalyzed continuous-flow microreactor. An efficient biocatalytic strategy afforded 34 salicylamide derivatives. This work supports their synthesis and industrialization.