Synthesis and Antimicrobial Activity of N′-Heteroarylidene-1-adamantylcarbohydrazides and (±)-2-(1-Adamantyl)-4-acetyl-5-[5-(4-substituted phenyl-3-isoxazolyl)]-1,3,4-oxadiazolines

The reaction of adamantane-1-carbohydrazide (1) with heterocyclic aldehydes, namely 5-(4-chlorophenyl)isoxazole-3-carboxaldehyde (2a), 5-(4-methylphenyl)isoxazole-3-carboxaldehyde (2b), 5-(4-methoxyphenyl)isoxazole-3-carboxaldehyde (2c), 1H-imidazole-2-carboxaldehyde and 2-butyl-4-chloro-1H-imidazole-5-carboxaldehyde, in ethanol, yielded the corresponding N′-heteroarylidene-1-adamantylcarbohydrazides 3a, 3b, 3c, 4 and 5, respectively, in good yields. The 4-acetyl-1,3,4-oxadiazoline analogues 6a‑c were prepared in 48–55% yields by heating their corresponding N′-heteroarylidene-1-adamantylcarbohydrazides 3a–c with acetic anhydride for two hours. Compounds 3a–c, 4, 5 and 6a–c were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 4 and 5 displayed potent broad-spectrum antimicrobial activity, while compounds 3a–c showed good activity against the Gram-positive bacteria.