Microwave‐assisted synthesis of N‐vanillylformamide

Abstract

The Leuckart reaction is a fast and convenient method of synthesis of various formamides and amines and has been successfully used for the synthesis of many biologically active compounds, including agrochemicals and pharmaceuticals. Surprisingly, it has never been used for the synthesis of vanillylamine (I) from vanillin (II) via the intermediate N‐vanillylformamide (III). In the literature, the intermediate III is described only once, when it was obtained via the formylation of I, not by the reductive amination of II. In this work, we report a successful synthesis of III from II via a microwave assisted Leuckart reaction. This method provides a new synthetic pathway to I, which is a valuable intermediate in the synthesis of a number of biologically‐active compounds. This method can also be used for the synthesis of other hydroxy‐substituted benzylamines.The project is supported by NIH grant P20 RR016741 from the NCRR.