A Practical Synthesis of 2-Azidophenylisocyanide

The four-component-condensation of a carbonyl compound with a /3-amino acid and an isocyanide is a method of high synthetic potential for the prepara­ tion of /3-Iactam antibiotics [1]. However, a carbonamide group is formed at the site where a carboxylic acid is found in most /3-lactam antibiotics. The cleavability of the amide group under conditions which do not affect the /3-lactam, is therefore essen­ tial for applications of this technique. Special isocyanides have been developed [2, 3] which allow the amide/acid conversion via o-hy­ droxy or o-amino anilides under very mild condi­ tions. Among other isocyanides, 2-azidophenylisocyanide is a highly promising candidate [2]. Up to now, it has been prepared via 2-azidoaniline using a six-step procedure starting with 2-nitroaniline [2, 4]. The overall yield varies and does generally not ex­ ceed 16%. We therefore sought for a more viable synthesis of this compound. The most straigthforward approach is the nucleophilic replacement of a halogene by azide in a suit­ able precursor (e.g. 2-bromoformanilide), followed by dehydration.