A series of (E)-5-(arylideneamino)-1-tert-butyl-1H-pyrrole-3-carbonitriles and their reduction products to secondary amines: syntheses and X-ray structural studies

Abstract

An efficent access to a series of N-(pyrrol-2-yl)amines, namely (E)-1-tert-butyl-5-[(4-chlorobenzylidene)amino]-1H-pyrrole-3-carbonitrile, CHClN, (7a), (E)-1-tert-butyl-5-[(2,4-dichlorobenzylidene)amino]-1H-pyrrole-3-carbonitrile, CHClN, (7b), (E)-1-tert-butyl-5-[(pyridin-4-ylmethylene)amino]-1H-pyrrole-3-carbonitrile, CHN, (7c), 1-tert-butyl-5-[(4-chlorobenzyl)amino]-1H-pyrrole-3-carbonitrile, CHClN, (8a), and 1-tert-butyl-5-[(2,4-dichlorobenzyl)amino]-1H-pyrrole-3-carbonitrile, CHClN, (8b), by a two-step synthesis sequence (solvent-free condensation and reduction) starting from 5-amino-1-tert-butyl-1H-pyrrole-3-carbonitrile is described. The syntheses proceed via isolated N-(pyrrol-2-yl)imines, which are also key synthetic intermediates of other valuable compounds. The crystal structures of the reduced compounds showed a reduction in the symmetry compared with the corresponding precursors, viz. Pbcm to P-1 from compound (7a) to (8a) and P2/c to P-1 from compound (7b) to (8b), probably due to a severe change in the molecular conformations, resulting in the loss of planarity observed in the nonreduced compounds. In all of the crystals, the supramolecular assembly is controlled mainly by strong (N,C)-H...N hydrogen bonds. However, in the case of (7a)-(7c), C-H...Cl interactions are strong enough to help in the three-dimensional architecture, as observed in Hirshfeld surface maps.

Synthesis and in vitro Antifungal Evaluation of Novel N‐Substituted 4‐Aryl‐2‐methylimidazoles

“…Once 4‐aryl‐2‐methyl‐ N ‐phenacylimidazoles 5 a–e were obtained, and due to the importance of the 2‐aryl‐2‐hydroxyethyl fragment in antifungal drugs, we developed a simple method to convert the carbonyl group of 5 into a hydroxyl group to generate the corresponding N ‐(2‐aryl‐2‐hydroxyethyl)imidazole 6 . We found that the reduction reaction via protocols described in the literature (NaBH 4 in methanol),, was achieved at 50 °C, giving the expected alcohols 6 a–e in high yields (Scheme ). The reduction on the N‐ phenacylimidazole 5 c proceeded with the lowest yield (70%) because this substrate possessed an electron‐donor group, making it exhibit less reactivity towards addition of hydrides due to the lower electrophilicity of the carbonyl carbon.…”

Intermolecular interaction energies and molecular conformations in N-substituted 4-aryl-2-methylimidazoles with promising in vitro antifungal activity

“…This connection keeps the atoms that constitute the 4-arylimidazole fragment in a nearly planar conformation, except for (4f) where a high level of distortion was observed. These results suggest that the steric effect that occurs inside the phenacyl group of (4f) [Cl atom at position 2 on the benzene ring (Macías, Castillo et al, 2018) and the C O, Fig. 2(a)] is responsible for its molecular conformation.…”

“…Except for compound (4f), it was found that their principal fragments, the 4-arylimidazolic and phenacyl moieties, are perpendicularly oriented with respect to each other. The 2,4-dichlorophenyl-substituted imidazole (4f) exhibited a semi-parallel conformation, possibly due to the steric effect that can occur inside its phenacyl group, that is, between the Cl atom at position 2 on the benzene ring (Macías, Castillo et al, 2018) and the carbonyl group [ Fig. 2(a)].…”

Studies via X-ray analysis on intermolecular interactions and energy frameworks based on the effects of substituents of three 4-aryl-2-methyl-1H-imidazoles of different electronic nature and their in vitro antifungal evaluation

“…benzamidine and pivalimidamide hydrochlorides). Therefore, we use microwave-assisted organic synthesis (MAOS) in this study since this method tends to favour cyclocondensation reactions using poorly soluble reagents (Katritzky et al, 2006;Orrego-Herná ndez et al, 2015;Macías et al, 2018). Gratifyingly, we recently succeeded in obtaining crystals of suitable size and quality for single-crystal X-ray diffraction analysis of the three 1H-imidazoles 2-methyl-4-phenyl-1H-imidazole, (3a), 4-(4-chlorophenyl)-2methyl-1H-imidazole hemihydrate, (3b), and 4-(4-methoxyphenyl)-2-methyl-1H-imidazole, (3c), by recrystallization from methanol.…”