Microwave-Intensified Hofmann Carbylamine Reaction Enabled by Span® 80: Rapid Access to Isocyanides in a Biphasic System

Description

Wender Alves Silva, Sayuri Cristina Santos Takada, and Saulo Tarso Alves Passos report a 2026 greener route to isocyanides, versatile building blocks for drug discovery and multi-component reactions. These compounds are rarely sold and classically made by hazardous methods. The new protocol generates the reactive intermediate from chloroform and sodium hydroxide in near-stoichiometric amounts, using a biodegradable detergent-like helper called Span 80 to move reactants between liquid phases under microwave heating.

The method produced a wide range of isocyanides, from simple aliphatic and aromatic types to ones built from amino acids, in yields of 43 to 96 percent within 30 minutes. It skips the usual water workup and avoids toxic dehydrating agents such as phosphorus oxychloride. The authors present it as a faster, cleaner way to stock a class of reagents many labs currently avoid making.

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Source: https://europepmc.org/article/MED/PMC13467631