Van Leusen Imidazole Synthesis and Imidazole Structure

Imidazole is used to treat cutaneous fungal infection, including candidiasis, dermatomycoses, pityriasis versicolor, and vaginal candidiasis.

Structure

Imidazole is a planar, five-membered ring system with three carbons and two nitrogen atoms in the 1- and 3-positions. The systematic name for the compound then is 1,3-diazole. One of the annular nitrogens bears a hydrogen atom and can be regarded as a pyrrole-type nitrogen; the other resembles the nitrogen in pyridine. For this reason it is possible to look upon imidazole as a molecule which has overlapping properties of both pyrrole and pyridine. Contributions of one π-electron from each carbon and the ‘pyridine’ nitrogen and two from the ‘pyrrole’ nitrogen make up an aromatic sextet.

Mechanism of action

Imidazole acts by inhibiting 14-sterol-demethylase.

Van Leusen Imidazole Synthesis

The Van Leusen reaction includes the reactions of Van Leusen Imidazole, and Van Leusen Oxazole Synthesis. The Van Leusen Imidazole Synthesis allows the preparation of imidazoles from aldimines by reaction with tosylmethyl isocyanide (TosMIC), and the Van Leusen oxazole Synthesis, allows the preparation of oxazoles from aldehydes by reaction with TosMIC. (Figure 1) These reactions allow obtaining highly functionalized nuclei of oxazoles and imidazoles to produce relevant drugs.[1]

Figure 1 Van Leusen imidazole and oxazole reactions

The Van Leusen Imidazole Synthesis allows the preparation of imidazoles from aldimines by reaction with tosylmethyl isocyanide (TosMIC). The reaction has later been expanded to a two-step synthesis in which the aldimine is generated in situ: the Van Leusen Three-Component Reaction (vL-3CR).

References

[1] Handbook of Greener Synthesis of Nanomaterials and Compounds[C]. 1900: 0. DOI:10.1016/c2019-0-03121-4.