Clemizole is an H₁ antagonist.

Synthesis

Benzimidazoles substituted with an alkylamine at position 2 have a venerable history as H₁ antihistaminic agents. The standard starting material for many benzimidazoles consists of phenylenediamine, or its derivatives. Clemizole synthesis

Reaction of that compound with chloroacetic acid can be rationalized by invoking initial formation of the chloromethyl amide.

Imide In organic chemistry, an imide is a functional group consisting of two acyl groups bound to nitrogen. The compounds are structurally related to acid anhydrides, although imides are more resistant to hydrolysis. In terms of commercial applications, ...

formation with the remaining free amino group closes the ring to afford 2-chloromethyl benzimidazole (3). Displacement of halogen with

pyrrolidine Pyrrolidine, also known as tetrahydropyrrole, is an organic compound with the molecular formula (CH2)4NH. It is a cyclic secondary amine, also classified as a saturated heterocycle. It is a colourless liquid that is miscible with water and most ...

affords the alkylation product. The proton on the fused imidazole nitrogen is then removed by reaction with

sodium hydride Sodium hydride is the chemical compound with the empirical formula Na H. This alkali metal hydride is primarily used as a strong yet combustible base in organic synthesis. NaH is a saline (salt-like) hydride, composed of Na+ and H− ions, in co ...

. Treatment of the resulting anion with α,4-dichlorotoluene gives the H₁ antihistaminic agent clemizole (5).

References

Benzimidazoles Chloroarenes H1 receptor antagonists Pyrrolidines {{respiratory-system-drug-stub

Synthesis

See also

References