Radziszewski reaction

What is Radziszewski reaction?

The Radziszewski reaction is a condensation reaction of an α-dicarbonyl compound, an aldehyde and two equivalents of dry ammonia in alcohol, resulting in the synthesis of an imidazole derivative. This reaction was first reported by Debus in 1858, developed by Radziszewski beginning in 1882, and further modified by Weidenhagen in 1935.

Radziszewski reaction - general reaction scheme
Radziszewski reaction

R1R4 = H, alkyl, aryl (see list of acronyms)

The Radziszewski reaction is also known as the Weidenhagen synthesis, Debus-Radziszewski imidazole synthesis, or Radziszewski synthesis. Imidazole is also referred to as glyoxaline due to this reaction. The term imidazole was originally chosen as the name for such molecules by Hantzsch and given official recognition.

Various α-dicarbonyl compounds, including glyoxal, pyruvaldehyde, porphyrin-2,3-diones, and benzil, have been successfully used in this reaction to synthesize corresponding imidazole derivatives. The replacement of one equivalent ammonia with a primary amine results in the formation of 1-substituted imidazoles.

Although Radziszewski reaction generally gives poor yields of imidazoles and suffers from some side reactions, the condensation of benzil with benzaldehyde and ammonia in alcohol gives nearly a quantitative yield of 2,3,5-triphenylimidazole. This reaction is useful for the preparation of imidazoles with a substituent at position 2 from adjacent di-carbonyl compounds.

The Radziszewski reaction is the only reaction of industrial importance for the production of imidazole derivatives.