The carbylamine reaction (also known as the Hoffmann isocyanide synthesis) is the synthesis of an isocyanide by the reaction of a primary amine, chloroform, and base. The conversion involves the intermediacy of dichlorocarbene.

Illustrative is the synthesis of tert-butyl isocyanide from tert-butylamine in the presence of catalytic amount of the phase transfer catalyst benzyltriethylammonium chloride.^[1]

Me₃CNH₂ + CHCl₃ + 3 NaOH → Me₃CNC + 3 NaCl + 3 H₂O

Similar reactions have been reported for aniline. It is used to prepare secondary amines.

As it is only effective for primary amines, the carbylamine reaction can be used as a chemical test for their presence. In this context, the reaction is also known as Saytzeff's isocyanide test.^[2] In this reaction, the analyte is heated with alcoholic potassium hydroxide and chloroform. If a primary amine is present, the isocyanide (carbylamine) is formed, as indicated by a foul odour. The carbylamine test does not give a positive reaction with secondary and tertiary amines.

The mechanism involves the addition of amine to dichlorocarbene, a reactive intermediate generated by the dehydrohalogenation of chloroform. Two successive base-mediated dehydrochlorination steps result in formation of the isocyanide.

• Isodiazomethane
• Carbene