Unraveling the impact of hydrogen bonding and C‒H…π(CN) interactions in crystal engineering of cyclic aminobenzonitriles: A combined X-ray crystallographic and computational investigation

Abstract

The essential role of organic crystals in drug development represents a significant research area and remains enduringly topical within the pharmaceutical industry. In the present study, four cyclic aminobenzonitriles 3a-d were prepared through the nucleophilic aromatic substitution reaction of 4-fluorobenzonitrile with various cyclic amines. The synthesized compounds were obtained in moderate to good yields and structurally characterized by FTIR, NMR spectroscopy, mass spectrometry and X-ray crystallography. The crystal packing of these compounds predominantly involves the use of hydrogen bonding interactions (C-H…N, C-H…S, C-H…O) and aromatic contacts (C-H…π(ring & CN), π…π) to govern the complex structural topology. These noncovalent interactions were further evaluated by molecular electrostatic potential (MEP) surface analysis and DFT energy calculations confirming the importance of π-stacking and CH…π interactions, either involving the arene or the π-system of the cyano groups. These interactions have been further characterized using the QTAIM/NCIplot computational tool.