Regiochemistry of N‐substitution of some 4(5)‐substituted imidazoles under solvent‐free conditions

Abstract magnified image Imidazole‐4(5)‐carboxaldehyde and 4(5)‐cyanoimidazole were N‐benzylated and N‐methylated using benzyl chloride and methyl iodide on zinc oxide (ZnO), alumina, and KF/alumina under basic conditions without solvent. Triethylamine (Et3N) or potassium carbonate was added as base in the reactions on ZnO and alumina. Imidazole‐4(5)‐carboxaldehyde was also benzylated on silica and carbon nanotubes. The effect of bases and solids on the product distribution of 1,4‐ and 1,5‐substituted compounds was investigated. In some cases, the product ratios were different for imidazole‐4(5)‐carboxaldehyde and 4(5)‐cyanoimidazole. In the reactions on KF/alumina the 1,4‐product was favored for both compounds. The combination of Et3N and ZnO favored the 1,5‐product, however for the nitrile effect was not so pronounced. When N‐benzylation and methylation of the aldehyde were performed in the presence of catalytic amount of zinc chloride with Et3N as base, the product distributions were the same as in the reactions on ZnO. Nitrile gave different product ratios on ZnO and in the presence of ZnCl2. In addition, a mixture of N‐benzylimidazole and 1,3‐dibenzylimidazolium was produced when imidazole was benzylated on KF/alumina. Only the latter product was afforded when two equivalents of benzyl chloride were used.