Conformation and tautomerism of methoxy-substituted 4-phenyl-4-thiazoline-2-thiones: A combined crystallographic and ab initio investigation

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.The crystal structures of the regioisomeric 4-(2/4-methoxyphenyl)-4-thiazoline-2-thiones reveal the thione tautomeric form for both, in agreement with the results of ab initio calculations [PBE/6-311G(d,p)]. The conformations found in the crystals are also compared to data from an ab initio energy-relaxed scan.