Science of Synthesis

Braverman, S.; Cherkinsky, M.; Birsa, M. L., Science of Synthesis, (2005) 18, 122.

Base-induced β-elimination of a haloform from N-substituted trihaloacetamides ‌145‌ is an attractive route to isocyanates ‌146‌ that does not involve utilization of highly toxic reagents (‌Scheme 82‌).[‌404‌] The starting trichloro- and tribromoacetamides ‌145‌ are easily handled crystalline solids with long shelf-lives. They are readily prepared by the reaction of the appropriate amines with commercial trichloro- or tribromoacetyl chloride, respectively. Both alkyl- and aryl-substituted amides ‌145‌ under the action of 1,8-diazabicyclo[5.4.0]undec-7-ene in polar aprotic solvents, such as acetonitrile or dimethyl sulfoxide, can be quantitatively transformed into the corresponding isocyanates. As expected from the reaction mechanism, the rate of reaction exhibits a strong dependence on the nature of the trihalomethyl group. Thus, while tribromoacetamides react at room temperature, elimination of chloroform from the corresponding trichloro derivatives requires heating at 80°C. Sterically hindered isocyanates, such as mesityl or tert-butyl isocyanates, have been isolated in good yields, whereas the isolated yields of unhindered isocyanates (100% conversion) are lower due to competitive hydrolysis under the reaction conditions. However, all isocyanates can be trapped as ureas or urethanes in yields of 80–92%.

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