UV-Induced 1,3,4-Oxadiazole Formation from 5-Substituted Tetrazoles and Carboxylic Acids in Flow.

Luke Green,Keith Livingstone,Simon Peace,Craig Jamieson,Sophie Bertrand

doi:10.1002/chem.202002896

Abstract

A range of 1,3,4‐oxadiazoles have been synthesized using a UV‐B activated flow approach starting from carboxylic acids and 5‐substituted tetrazoles. The application of UV light represents an attractive alternative to the traditional thermolytic approach and has demonstrated comparable efficiency and versatility, with a diverse substrate scope, including the incorporation of highly substituted amino acids.

Highlights

A range of 1,3,4-oxadiazoles have been synthesized using a UV-B activated flow approach starting from carboxylic acids and 5-substituted tetrazoles
Whilst the above methods are effective, most require the synthesis of bespoke starting materials with both the 2- and 5-substituents pre-installed
The Huisgen reaction between a tetrazole and an acylating reagent is one approach in which two separate components can be combined in a single step to furnish the desired 1,3,4oxadiazole.[9,10,11,12]

Summary

Introduction

A range of 1,3,4-oxadiazoles have been synthesized using a UV-B activated flow approach starting from carboxylic acids and 5-substituted tetrazoles. The Huisgen reaction between a tetrazole and an acylating reagent is one approach in which two separate components can be combined in a single step to furnish the desired 1,3,4oxadiazole.[9,10,11,12] Initial reaction between the tetrazole and acyl chloride or acid anhydride yields a 2-acyltetrazole intermediate which decomposes in a concerted manner to the corresponding nitrile imine upon heating. (c) This work: 1,3,4-oxadiazole synthesis from photochemical activation of N-acyl tetrazoles in flow.

Results

Conclusion