Crystal structures of vortioxetine and its methanol monosolvate

Abstract

Vortioxetine, C18H22N2S, (1), systematic name 1-{2-[(2,4-dimethylphenyl)sulfanyl]phenyl}piperazine, a new drug used to treat patients with major depressive disorder, has been crystallized as the free base and its methanol monosolvate, C18H22N2S·CH3OH, (2). In both structures, the vortioxetine molecules have similar conformations: in (1), the dihedral angle between the aromatic rings is 80.04 (16)° and in (2) it is 84.94 (13)°. The C—S—C bond angle in (1) is 102.76 (14)° and the corresponding angle in (2) is 103.41 (11)°. The piperazine ring adopts a chair conformation with the exocyclic N—C bond in a pseudo-equatorial orientation in both structures. No directional interactions beyond normal van der Waals contacts could be identified in the crystal of (1), whereas in (2), the vortioxetine and methanol molecules are linked by N—H...O and O—H...N hydrogen bonds, generating [001] chains.

Keywords

• crystal structure
• vortioxetine
• major depressive disorder
• hydrogen bonding