A series ofN-(2-phenylethyl)nitroaniline derivatives as precursors for slow and sustained nitric oxide release agents

Abstract

2,4-Dinitro-N-(2-phenylethyl)aniline, C14H13N3O4, (I), crystallizes with one independent molecule in the asymmetric unit. The adjacent amine and nitro groups form an intramolecular N—H...O hydrogen bond. Theanticonformation about the ethyl C—C bond leads to the phenyl and aniline rings being essentially parallel. Molecules are linked into dimers by intermolecular N—H...O hydrogen bonds, such that each amine H atom participates in a three-centre interaction with two nitro O atoms. Though the dimers pack so that the arene rings of adjacent molecules are parallel, the rings are staggered and π–π interactions do not appear to be favoured. 4,6-Dinitro-N,N′-bis(2-phenylethyl)benzene-1,3-diamine, C22H22N4O4, (II), differs from (I) in the presence of a second 2-phenylethylamine group on the substituted ring. Compound (II) also crystallizes with one unique molecule in the asymmetric unit. Both amine groups are involved in intramolecular N—H...O hydrogen bonds with adjacent nitro groups. Although one ethyl group adopts ananticonformation as in (I), the other isgauche, with the result that the pendant phenyl rings are not parallel. The amine group that is part of thegaucheconformation participates in a three-centre N—H...O hydrogen bond with the nitro group of a neighbouring molecule, leading to dimers as in (I). The other amine H atom does not form any intermolecular hydrogen bonds. The packing leads to separations ofca3.4 Å of the parallelantiphenyl and aminobenzene rings. 2-Cyano-4-nitro-N-(2-phenylethyl)aniline, C15H13N3O2, (III), differs from (I) only in having a cyano group in place of the 2-nitro group. The absence of the adjacent nitro group eliminates the intramolecular N—H...O hydrogen bond. Molecules of (III) adopt the sameanticonformation about the ethyl group as in (I), but crystallize in the higher-symmetry monoclinic space groupP21/n. The molecules are linked into dimersviaN—H...N amine–cyano hydrogen bonds, while the nitro groups are not involved in any N—H...O interactions. Owing to the different symmetry, the molecules pack in a herringbone pattern with fewer face-to-face interactions between the rings. The closest such interactions are about 3.5 Å between rings that are largely slipped past one another. 4-Methylsulfonyl-2-nitro-N-(2-phenylethyl)aniline, C15H16N2O4S, (IV), differs from (I) in having a methylsulfonyl group in place of the 4-nitro group. The intramolecular N—H...O hydrogen bond is present as in (I). However, unlike (I), the conformation about the ethyl group isgauche, so the two arene rings are nearly perpendicular rather than parallel. The packing is significantly different from the other three structures in that there are no intermolecular hydrogen bonds involving the N—H groups. The molecules are arranged in tetragonal columns running along thecaxis, with the aniline rings mostly parallel and separated byca3.7 Å. Taken together, these structures demonstrate that modest changes in functional groups cause significant differences in molecular conformation, intermolecular interactions and packing.