Sandmeyer Reaction

In 1884, Swiss chemist Traugott Sandmeyer attempted to synthesize phenylacetylene from benzenediazonium chloride and copper(I) acetylide. However, the main product he isolated was chlorobenzene, and no trace of the desired product was found. On careful examination of the reaction, it was discovered that copper(I) chloride was formed in situ, which catalyzed the replacement of the diazonium group with a chlorine atom. Following this discovery, the substitution of aryldiazonium salts with halides or pseudo halides became known as the Sandmeyer reaction.

The required aryldiazonium halides are generally prepared from the corresponding arylamines via diazotization using either sodium nitrite and aqueous hydrochloric acid, or alkyl nitrites such as tert-butyl nitrite under anhydrous conditions. These aryldiazonium compounds are prepared and reacted in situ with copper(I) chloride, bromide, or cyanide to obtain the corresponding aryl halide or nitrile.

The Sandmeyer reaction has been used in many successful synthesis campaigns, including the preparation of the anti-psychotic drug flupentixol as well as neoamphimedine, a compound that has anti-cancer properties.