Synthesis and solid state self-assembly of a 1,4-diazepine derivative: Water cluster as molecular glue and conformational isomerism

Abstract

Diazepine (a seven membered heterocycle) derivatives have emerged as “privileged structures” in chemical biology and medicinal chemistry. In this article, synthesis of a 1, 4-diazepine derivative 4 from flavone 3 in excellent yield is described. The solid state self-assembly pertaining to diazepine derivative 4 was investigated with X-ray crystallography. Fascinatingly, the solid state structure of 4 represents a remarkable example of water cluster acting as structural glue to instigate conformational isomerism and hence facilitate the crystallization process by compensating the imbalance of hydrogen-bond donors and acceptors. NBO and QTAIM based calculations show that the hydrogen-bonding network of water molecules and hyper conjugative interactions play a vital role for stabilization of structure in the solid state. To our knowledge, presented here is the first illustration of any solvent cluster stabilizing the solid-state structure in a diazepine family. In addition, the crystal structure of flavone 3 hitherto not reported is also reported.