Abstract An efficient and regioselective synthesis of novel 4‐aryl‐2‐methyl‐ N ‐phenacylimidazoles 5 by a microwave‐assisted pseudo‐tricomponent reaction between acetamidine hydrochloride ( 3 ) and α‐bromoacetophenones 2 has been developed. The reduction of the carbonyl group of the ketones 5 offered the corresponding N ‐(2‐hydroxyethyl)imidazoles 6 in good yields. Novel N ‐substituted imidazoles 5 and 6 were tested for antifungal activity against two clinically important fungi Candida albicans and Cryptococcus neoformans . The results showed that all compounds displayed very low activity against C. albicans . In contrast, compounds 5 and 6 were active against C. neoformans . Among them, ketones 5 showed better activity than alcohols 6 , with IC 50 values as low as 15.6 μg/mL for some of them. The difluorinated compound 5 e showed the best activity against C. neoformans , followed by the dichlorinated derivative 5 b . The difluorinated compound 5 e showed the best activity against C. neoformans , followed by the dichlorinated derivative 5 b .