Tautomeric Preference and Conformation Locking in Fenobam, Thiofenobam, and Their Analogues: The Decisive Role of Hydrogen Bond Hierarchy

Thomas, Sajesh P and Shashiprabha, K and Vinutha, KR and Nayak, Suresh P and Nagarajan, K and Row, Guru TN (2014) Tautomeric Preference and Conformation Locking in Fenobam, Thiofenobam, and Their Analogues: The Decisive Role of Hydrogen Bond Hierarchy. In: CRYSTAL GROWTH & DESIGN, 14 (8). pp. 3758-3766.

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Abstract

The crystal and molecular structures of the potential antidepressant drug fenobam and its derivatives are examined in terms of the preferred form among the two possible tautomeric structures. In this study, chemical derivatization has been utilized as a means to ``experimentally simulate'' the tautomeric preference and conformational variability in fenobam. Eight new derivatives of fenobam have been synthesized, and structural features have been characterized by single-crystal X-ray diffraction and NMR spectroscopy. The specific tautomeric preference found in all of these compounds and their known crystal forms have been construed in terms of the stabilizing intramolecular N-H center dot center dot center dot O and N-H center dot center dot center dot S hydrogen bonding. The hierarchy of intramolecular hydrogen bonds evidenced as the preference of the C-H center dot center dot center dot O hydrogen bond over C-H center dot center dot center dot N and that of the C-H center dot center dot center dot N hydrogen bond over C-H center dot center dot center dot S explains the two distinct conformations adopted by fenobam and thiofenobam derivatives. The relative energy values of different molecular conformations have been calculated and compared.

Item Type:	Journal Article
Publication:	CRYSTAL GROWTH & DESIGN
Publisher:	AMER CHEMICAL SOC
Additional Information:	Copy right for this article belongs to the AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
Department/Centre:	Division of Chemical Sciences > Solid State & Structural Chemistry Unit
Date Deposited:	04 Sep 2014 11:04
Last Modified:	04 Sep 2014 11:04
URI:	http://eprints.iisc.ac.in/id/eprint/49760

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