Crystal structures of five new substituted tetrahydro-1-benzazepines with potential antiparasitic activity

Abstract

Tetrahydro-1-benzazepines have been described as potential antiparasitic drugs for the treatment of chagas disease and leishmaniasis, two of the most important so-called `forgotten tropical diseases' affecting South and Central America, caused byTrypanosoma cruziandLeishmania chagasiparasites, respectively. Continuing our extensive work describing the structural characteristics of some related compounds with interesting biological properties, the crystallographic features of three epoxy-1-benzazepines, namely (2SR,4RS)-6,8-dimethyl-2-(naphthalen-1-yl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, (1), (2SR,4RS)-6,9-dimethyl-2-(naphthalen-1-yl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, (2), and (2SR,4RS)-8,9-dimethyl-2-(naphthalen-1-yl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, (3), all C22H21NO, and two 1-benzazepin-4-ols, namely 7-fluoro-cis-2-[(E)-styryl]-2,3,4,5-tetrahydro-1H-1-benzazepin-4-ol, C18H18FNO, (4), and 7-fluoro-cis-2-[(E)-pent-1-enyl]-2,3,4,5-tetrahydro-1H-1-benzazepin-4-ol, C15H20FNO, (5), are described. Some peculiarities in the crystallization behaviour were found, involving significant variations in the crystalline structures as a result of modest changes in the peripheral substituents in (1)–(3) and the occurrence of discrete disorder due to the molecular overlay of enantiomers with more than one conformation in (5). In particular, an interesting phase change on cooling was observed for compound (5), accompanied by an approximate fourfold increase of the unit-cell volume and a change of theZ′ value from 1 to 4. This transition is a consequence of the partial ordering of the pentenyl chains in half of the molecules breaking half of the \overline{3} symmetry axes observed in the room-temperature structure of (5). The structural assembly in all the title compounds is characterized by not only (N,O)—H...(O,N) hydrogen bonds, but also by unconventional C—H...O contacts, resulting in a wide diversity of packing.