Common synthetic reactions of imidazole

Imidazole is an important intermediate in organic synthesis. Many drugs contain this structure, such as the antifungal drugs ketoconazole, miconazole, clotrimazole, etc. The following is a summary of the common synthetic reaction of imidazole.

1. Debus-Radziszewski imidazole synthesis reaction

A three-component condensation of 1,2-dicarbonyl compound, ammonia and aldehyde give an imidazole reaction. The most commonly used dicarbonyl compound is glyoxal, and 1,2-diketone or aldehyde ketone can also be reacted to synthesize various imidazoles.

2. Wallach imidazole synthesis reaction

The reaction of synthesizing 1,2-dialkylimidazole by a N-alkylamide containing a β-nitrogen atom or an α-diamide in phosphorus pentachloride or phosphorus oxychloride. The most commonly used substrate for this reaction is N,N-dialkyloxamide, which is used as a substrate to give 1,2-dialkyl-5-chloroimidazole. This method has certain limitations, but when the alkyl carbon chain is long or the steric hindrance is large, the cyclization rate is low.

3. Bredereck imidazole synthesis

The condensation of α-diketone (or α-hydroxyketone, α-amino ketone, α-mercapto ketone) and formylamide gives the reaction of imidazole.

4. Kaiser-Johnson-Middleton dinitrile cyclization reaction

Under the action of HBr, the dinitrile is used to synthesize a bromine-substituted five-, six- or seven-membered ring heterocyclic ring.

5. Gröbcke-Blackburn-Bienaymé Aminoimidazole Synthesis Reaction

A one-pot condensation of an aldehyde, an isonitrile and 2-aminopyridine, 2-aminopyrimidine, 2-aminopyrazine or 2-aminothiophene, etc., containing a H₂N-C=N structural compound gives an aminoimidazole. This reaction is a multi-component reaction with a mechanism similar to the Ugi reaction.

6. Van Leusen imidazole synthesis reaction

The reaction of aldimine and p-toluenesulfonylmethyl isocyanide (TosMIC) to form an imidazole under basic conditions. Since the activity of the imine is much higher than that of the aldehyde, the reaction is later extended to a three-component reaction (VL-3CR) which is directly closed to the TosMIC one-pot method after directly reacting the aldehyde with an amine to obtain an imine.

Related links: Imidazole

Edited by Suzhou Yacoo Science Co., Ltd.