Hofmann rearrangement nitrene intermediate

Preparation from Nitrene Intermediates. A convenient, small-scale method for the conversion of carboxyhc acid derivatives into isocyanates involves electron sextet rearrangements, such as the ones described by Hofmann and Curtius (12). For example, treatment of ben2amide [55-21-0] with halogens leads to an A/-haloamide (2) which, in the presence of base, forms a nitrene intermediate (3). The nitrene intermediate undergoes rapid rearrangement to yield an isocyanate. Ureas can also be formed in the process if water is present (18,19). 

Treatment of amides with bromine in alkaline medium promotes the Hofmann rearrangement, which may or may not involve a free nitrene intermediate." The oxidation of primary amides with lead tetraacetate and the resulting Lossen rearrangement also produces isocyanates, with the possible intervention of an acylni-... 

It was assumed that the rearrangement of N-anionic intermediate 181 into isocyanate 182 occurs as a synchronous process including the formation of a new C—N bond and the withdrawal of the anion acid (X ), but without formation of the intermediate nitrene. According to early papers, information about yields of naphthostyryl 174 (R = H), which is obtained from naphthaloimide 178 (R = H) by the Hofmann reaction, is contradictory. The procedure has been checked and developed preparatively by... 

Nitrenes are also obtained as reaction intermediates in Hofmann, Schmidt and Lossen rearrangements. 

Hie Hofmann, Losseir and Curtins rearrangements (Scheme 6.38) are also thought to occur via an acyl nitrene-type intermediate and involve the migration of an R group to form an isocyanate. In the related Schmidt... 

Nitrenes were first proposed as reactive intermediates in the Lossen rearrangement by Tiemann in 1891, and subsequently by Stieglitz (1896) to account for the mechanisms of the related Hofmann, Curtius, and Beckmann rearrangements. Apart from an extensive amount of work by Curtius on the thermal decomposition of aryl and sulphonyl azides, interest in nitrenes declined until the reemergence of carbene chemistry in the 1950s. Reviews on nitrene chemistry by Kirmse (1959), Horner (1963), and Abramovitch (1964) reflected this renewed interest in nitrenes and provided a stimulus for the immense research effort undertaken in the 1960s, which has been surveyed in many reviews and two books.Of particular note are two chapters by Abramovitch" describing all facets of nitrenes, and an excellent chapter devoted specifically to aryl- and hetarylnitrenes by P. A. S. Smith. The present chapter is intended to update these reviews and it is hoped that it will stimulate further work, particularly on the synthetic aspects of intermolecular arylnitrene reactions. 

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