Crystal structure of olanzapine and its solvates. Part 3. Two and three-component solvates with water, ethanol, butan-2-ol and dichloromethane

Crystalline solvates of olanzapine (1), 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine, have been characterized by an X-ray analysis and thermal (DSC) data. Crystallization of 1 from ethanol gives a solid containing both water and ethanol molecules; the solvate 1 · H₂O · EtOH (2:2:1) is monoclinic with the space group P2₁/c and the unit-cell volume V = 3752.8(12) Å³. Butan-2-ol forms with 1 solvate which is also a three-component phase, 1 · H₂O · BuOH, but its stoichiometry is different (1:1:1). The space group for this crystal is P2₁/c and the unit-cell volume V = 2216.5(7) Å³. Crystalline olanzapine dichloromethane solvate (2:1), 1 · CH₂Cl₂, is triclinic with the space group .The characteristic feature of all crystal structures is presence of a pair of olanzapine molecules which form dimer stabilized by multiple weak C–Hπ interactions between the N-methylpiperazine fragment and the phenyl / thiophene systems. Theoretical calculations have been performed indicating that the total C–Hπ binding energy is about 8 kcal mol⁻¹. In the crystal structure, the self-assembled olanzapine molecular dimers are arranged into parallel crystal planes. Packing of the layers proceeds in two ways in which structural motives are replicated by (i) perpendicular translation forming columns, and (ii) rotation around the twofold screw axis (parallel to the layer).