title: Conformation and tautomerism of methoxy-substituted 4-phenyl-4-thiazoline-2-thiones: a combined crystallographic and ab initio investigation.
abstract: 4-Phenyl-4-thiazoline-2-thiol is an active pharmaceutical compound, one of whose activities is as a human indolenamine dioxygenase inhibitor. It has been shown recently that in both the solid state and the gas phase, the thiazolinethione tautomer should be preferred. As part of both research on this lead compound and a medicinal chemistry program, a series of substituted arylthiazolinethiones have been synthesized. The molecular conformations and tautomerism of 4-(2-methoxyphenyl)-4-thiazoline-2-thione and 4-(4-methoxyphenyl)-4-thiazoline-2-thione, both C10H9NOS2, are reported and compared with the geometry deduced from ab initio calculations [PBE/6-311G(d,p)]. Both the crystal structure analyses and the calculations establish the thione tautomer for the two substituted arylthiazolinethiones. In the crystal structure of the 2-methoxyphenyl regioisomer, the thiazolinethione unit was disordered over two conformations. Both isomers exhibit similar hydrogen-bond patterns [R2(2)(8) motif] and form dimers. The crystal packing is further reinforced by short S...S interactions in the 2-methoxyphenyl isomer. The conformations of the two regioisomers correspond to stable geometries calculated from an ab initio energy-relaxed scan.
authors.affiliation: University of Namur, 61 rue Bruxelles, B5000 Namur, Belgium.
authors.forename: Monaem
authors.initials: M
authors.lastname: Balti
authors.affiliation: University of Namur, 61 rue Bruxelles, B5000 Namur, Belgium.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Norberg
authors.affiliation: Chemistry Department, University of Tunis El Manar, 1068 Tunis, Tunisia.
authors.forename: Mohamed Lotfi
authors.initials: ML
authors.lastname: Efrit
authors.affiliation: University of Namur, 61 rue Bruxelles, B5000 Namur, Belgium.
authors.forename: Steve
authors.initials: S
authors.lastname: Lanners
authors.affiliation: University of Namur, 61 rue Bruxelles, B5000 Namur, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Wouters
mesh_terms: D018360:Crystallography, X-Ray; D019281:Dimerization; D006860:Hydrogen Bonding; D007536:Isomerism; D008958:Models, Molecular; D008968:Molecular Conformation; D053778:Thiazolidines / Q000737:chemistry*
chemical_list: D053778:Thiazolidines; C033089:thiazoline-2-thione
keywords: 4-phenyl-4-thiazoline-2-thione; S...S interactions; ab initio investigation; active pharmaceutical compound; computational chemistry; conformation; crystal structure; medicinal chemistry; tautomerism