Test for primary amines

The carbylamine or taocyanide test for primary amines Section IV,100,(i) is so extremely delicate that it will detect traces of primary amines in secondary and tertiary amines it must therefore be applied with due regard to this factor. 

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. 

Reaction with chloroform under basic conditions is a common test for primary amines, both aliphatic and aromatic, since isocyanides have very strong bad odors. The reaction probably proceeds by an SnIcB mechanism with dichlorocarbene as an intermediate ... 

Aliphatic and aromatic primary amines on heating with ehloroform and ethanolic potassium hydroxide form isocyanides or earbylamines which are foul smelling substances. Secondary and tertlaiy amines do not show this reaction. This reaction is known as carbylamine reaction or Isocyanlde test and Is used as a test for primary amines. 

The isonitriles formed have a characteristic poisonous odour. When used as a test for primary amines they should be destroyed (hydrolysed) by pouring into cone, hydrochloric acid—using a fume cupboard for the entire operation. 

Confirmatory tests for primary amines. Carbylandne test. To 1 ml of 0.5 M-alco-holic potassium hydroxide solution (or to a solution prepared by dissolving a fragment of potassium hydroxide half the size of a pea in 1 ml of ethanol) add 0.05-0.1 g of the amine and 3 drops of chloroform, and heat to boiling. A carby-lamine (isocyanide) is formed and will be readily identified by its extremely nauseating odour (CAUTION) ... 

Fig. 9.28. Reactions occurring in the "Ninhydrin Test" for primary amines in general and a-amino acids in particular. The characteristic blue coloring is due to the formation of the anionic dye B.

Tests for Primary Amines.—The constitution of R—NC for the isocyanides is supported also by their synthesis from primary amines. When a primary amine, R—NH2, is treated with chloroform in alkaline solution an iso-cyanide is formed. Chloroform (p. 183), is tri-chlor methane, CHCI3. The reaction is. 

Hofmann s Iso-cyanide or Iso-nitrile Reaction.— As the iso-cyanides have a very characteristic odor, their formation is easily detected and the reaction is used as a test for primary amines. 

In this reaction the nitrogen changes from tri-valent to penta-valent, or according to the other view in regard to the constitution of iso-cyanides (p. 71), the carbon changes from tetravalent to bivalent. It will be recalled that this reaction has been met with before (p. 70), and is known, as Hofmann s iso-nitrile reaction. It is a test for primary amines as it is necessary for the amine to have two hydrogen atoms in order to withdraw two chlorine atoms from the chloroform. The characteristic odor of the iso-nitrile makes the reaction a distinctive test, for either a primary amine or for chloroform. 

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. ... 

Gautier and Hoffman developed the first syntheses of isocyanides in 1867 (Scheme 7.1). Gautier s work with isocyanides pioneered the discovery of the isomeric relationship between isocyanides and nitriles [9]. Hoffman s synthesis is currently used as a chemical test for primary amines. 

---