Hofmann carbylamine test

The idea that dichlorocarbene is an intermediate in the basic hydrolysis of chloroform is now one hundred years old. It was first suggested by Geuther in 1862 to explain the formation of carbon monoxide, in addition to formate ions, in the reaction of chloroform (and similarly, bromoform) with alkali. At the end of the last century Nef interpreted several well-known reactions involving chloroform and a base in terms of the intermediate formation of dichlorocarbene. These reactions included the ring expansion of pyrroles to pyridines and of indoles to quinolines, as well as the Hofmann carbylamine test for primary amines and the Reimer-Tiemann formylation of phenols. 

Formerly, isonitriles were perhaps best known to many chemists through the indescribably vile odor of volatile members of the series encountered during the Hofmann carbylamine test for primary amines. Over recent years, however, isonitriles have come into their own as versatile synthetic reagents. Several reliable preparative methods now allow ready access to this family of substances and their remarkable chemistry. Biological pathways to isonitriles are also known, the first such substance isolated being the antibiotic xanthocillin (141), isolated from Penicillium notatumP Isonitrile compounds are also isolated fairly frequently from marine sources. ... 

This reaction was first reported by Hofmann in 1868. It is the synthesis of isonitriles (also known as isocyanides) from primary amines and chloroform in the presence of alkali and is known as the Hofmann isonitrile synthesis, Hofmann carbylamine reaction, or Hofmann carbylamine synthesis. This reaction has been used to test the presence of primary amines from the order of isocyanides. Alternatively, the isonitriles can be prepared by means of the treatment of formamide of primary amines with toluenesulfonyl chloride" or phosphorus oxychloride (POCls)." Currently, the isonitriles have gained much attention in organic synthesis because of their application as versatile building blocks for heterocycles and in multicomponent reactions to generate combinatorial libraries, such as that in the Passerini reaction and Ugi reaction ... 

---