Influence of halogen atoms and hydrogen bonds in the crystal structure of 1,2,4-trisubstituted imidazoles having haloaryl groups

Abstract

A new family of trisubstituted imidazoles having the privileged 1-haloarylethanol group at position 1 was synthesized by a microwave-assisted reduction reaction of N-aroyilmethyl-imidazoles. Structures of halogenated precursors (4-FPh, 4-ClPh, 4-BrPh) and the reduction product 4-bromophenyl substituted were studied via single X-ray crystallography (SXRC) and computational calculations. The halogen atoms’ effect on the crystal structure was analyzed using electrostatic potentials mapped over Hirshfeld surfaces, allowing us to confirm that fluorine atoms do not form σ-holes; instead, these atoms have negative electrostatic potentials all over the atomic position favoring the formation of short CH‧‧‧F hydrogen bonds that are similar in length to classic hydrogen bonds. However, such σ-hole effects in chlorine and bromine atoms induce the formation of CCl‧‧‧π and C-Br‧‧‧O interactions in the absence of strong hydrogen bonding. This remark is confirmed in 4c, where the hydroxyl group forms strong OH‧‧‧N hydrogen bonds avoiding the bromine atoms to form other interactions apart from the typical CH‧‧‧Br contacts despite their potential behavior to induce other interactions via σ-holes.