Crystal structure study of (E)-3-(4-nitrobenzyloxyimino)hexahydroazepin-2-one using synchrotron radiation

NOHA, 3-(4-nitrobenzyloxyimino)hexahydroazepin-2-one, is a potent anticonvulsive agent. It occurs in two stereoisomers. the Z and E forms. (E)-NOHA is about 1.5 times more active than (Z)-NOHA. While accurate structural data are available for (Z)-NOHA, those for the E form hare remained, until recently, highly speculative due to the lack of single crystals of suitable size for X-ray analysis and to the instability of the E isomer under radiation exposure. For structure-activity correlation purposes, efforts have been made to solve the crystal structure of the E isomer. Data collection from tiny needle crystals has been performed using synchrotron radiation. An initial molecular-packing model of this compound was obtained by energy-based and X-ray data modelling and successfully refined by molecular-dynamics methods: space group P2(1)/c, a = 6.225 (5), b = 17.885 (5), c = 12.157(5)Angstrom, beta = 92.35(5)degrees, R factor = 3.5% for 343 reflections. In this contribution the crystal and molecular structure of (E)-NOHA is reported and the role of the hydrogen bond acting as the driving force in the intermolecular assembly in the (E)-NOHA crystal is highlighted.