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Intermolecular interaction energies and molecular conformations in N ‐substituted 4‐aryl‐2‐methylimidazoles with promising in vitro antifungal activity
Author(s) -
Elejalde Nerith-Rocio,
Butassi Estefanía,
Zacchino Susana,
Macías Mario A.,
Portilla Jaime
Publication year - 2019
Publication title -
acta crystallographica section b
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.604
H-Index - 33
ISSN - 2052-5206
DOI - 10.1107/s2052520619013271
Subject(s) - aryl , chemistry , intermolecular force , molecule , crystallography , stereochemistry , miconazole , alkoxy group , hydrochloride , antifungal , alkyl , organic chemistry , medicine , dermatology
A convenient one‐pot synthesis of 4‐aryl‐2‐methyl‐ N ‐phenacylimidazoles (4) through a microwave‐assisted pseudo‐tricomponent reaction of α‐bromoacetophenones (1) with acetamidine hydrochloride (2) is reported. Ketones (4) were successfully used as substrates for the preparation of the respective N ‐(2‐hydroxyethyl)imidazoles (5) with yields up to 87%. The synthesized compounds were characterized by NMR and high‐resolution mass spectrometry analyses, and several structures were confirmed and studied by single‐crystal X‐ray diffraction. The analysis of the whole‐of‐molecule interactions shows that, despite the difference in the atom–atom contacts forming the crystals, dispersion energies make the largest contribution to the formation of the solids, giving an isotropic tendency in the topology of the energy framework diagrams for pairs of molecules. In addition, the in vitro antifungal activity of both families of compounds [ketones (4) and alcohols (5)] against Candida albicans and Cryptococcus neoformans was evaluated, where the 2,4‐dichlorophenyl‐substituted alcohol (5 f ), an isomer of the drug miconazole, showed the highest activity (IC 50 = 7.8 µg ml −1 against C. neoformans ).