An infrared study of intramolecular hydrogen-bonding in the histamine H2-receptor antagonists, burimamide, metiamide, cimetidine, and related compounds

Abstract

The i.r. spectra of N-methyl-N′-[4-(5-methylimidazol-4-yl)butyl]thiourea (methylburimamide), N-(4-imidazol-4-ylbutyl)-N′-methylthiourea (burimamide), N-methyl-N′-{2-[(5-methylimidazol-4-yl)methylthio]ethyl}thiourea (metamide), N-{2-[(imidazol-4-yl)methylthio]ethyl}-N′-methylthiourea (thiaburimamide), and N-cyano-N′-methyl-N″-[2-(4-methyl-5-imidazolylmethyl)thieothyl]guanidine (cimetidine) in bromoform have been recorded in the 3 500–3 200 cm^–1 region and compared with those of some closely related model compounds. The results show that all five compounds can form intramolecular hydrogen bonds in solution. Several possible hydrogen-bonded conformations are considered. Metiamide and thiaburimamide probably adopt an eight-membered ring conformation in which the basic imidazole nitrogen atom is hydrogen-bonded to the thiourea NH group nearer to the imidazole ring. The population of the hydrogen-bonded conformations increases when CH₂ is replaced by S in the side chain.