Curtius rearrangement

The Curtius reaction (also Curtius degradation or Curtius rearrangement ) is a reaction in the field of organic chemistry. It occurs during the heating of a carboxylic acid azides R -CO- N3 and is closely related to the Lossen rearrangement, the Hofmann amide degradation or the Schmidt reaction. The reaction is mainly used in order to reduce carboxylic acids to the primary amines, but it can also be obtained depending upon reaction conditions isocyanates, carbamates or urea derivatives. The reaction is named after its discoverer, the German chemist Theodor Curtius (1857 - 1928). In the following reaction overview all leaving groups are not listed with.

The Curtius rearrangement is carried out in the presence of tert-butanol, Boc-protected amine can be obtained, and accordingly, in the presence of benzyl alcohol, the Cbz -protected amines. Add water as a solvent always arise the free amines.

The Carbonsäureazide required can also be obtained by reacting the carboxylic acid with diphenylphosphoryl azide or a mixed anhydride with ethyl chloroformate over alternatively.

Reaction mechanism

Carbonsäureazide 2 arise, for example, by nucleophilic substitution at the carboxyl carbon of carboxylic acid chlorides 1 and sodium azide. When heated, they are deposited in a concerted reaction with release of molecular nitrogen initially in 3 to isocyanates. The often formulated as short-lived intermediates Nitrenes Unlikely to occur. When performing in an inert solvent, the final product of the reaction isocyanates stay while they continue to react in the presence of water to give the corresponding carbamic acid, which is decarboxylated directly and as an end product, the primary amine 4 results. In the presence of alcohols stable carbamic acid ester formed ( carbamates) and 5 of amines substituted ureas 6