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Updated: Oct 17, 2025

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid
Published on: November 15, 2017
Total Synthesis of Glipizide and Glibenclamide in Continuous Flow
Cloudius R Sagandira1, Agnes Z Khasipo1, Paul Watts1
1Department of Chemistry, Nelson Mandela University, University Way, Port Elizabeth, 6031, South Africa.
Abstract:
Glipizide and glibenclamide remain some of the widely prescribed antidiabetic sulfonylurea drugs for the treatment of type 2 diabetes mellitus. Herein the authors report on an isocyanate-free synthetic procedure towards the preparation of these on demand drugs at multigram scale using continuous flow technology. The safety concern over the use of isocyanates in most of the existing synthetic routes was dealt with in this present work by using N-carbamates synthesised in situ from activation of amines with chloroformates as safer alternatives. An overall yield of 80-85 % was obtained for the semi-telescoped steps within 10 min total residence time.
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