Conglomerate formative precursor of chiral drug timolol: 3-(4-Morpholino-1,2,5-thiadiazol-3-yloxy)-propane-1,2-diol

• Crystallization features of chiral drug timolol precursor are investigated.
• 3-(4-N-morpholino-1,2,5-thiadiazol-3-yloxy)-propane-1,2-diol is a conglomerate formative compound.
• Hydrogen O–H⋯O′H bonds are responsible for dense character of homochiral crystal packing.
• Near-ideal phase behavior of the studied diol create the preconditions for its obtaining in an enantiopure form.

Solid state properties of 3-(4-N-morpholino-1,2,5-thiadiazol-3-yloxy)-propane-1,2-diol 3, the synthetic precursor of popular drug timolol, have been investigated. The original solubility test, the data of X-ray diffraction and DSC methods indicate that the compound is prone to spontaneous resolution. Diol 3 crystallizing from both enantiopure or racemic feed material forms “guaifenesin-like” crystal packing in which the classic H-bonded bilayers, framed in both sides by hydrophobic molecular fragments, act as the basic supramolecular motif. The main chain conformation of the molecules in the crystals of diol 3 differs from that in the guaifenesin crystals, and this fact changes the absolute configuration of spiral columns formed by intermolecular hydrogen bonds in crystals of 3 as compared with guaifenesin crystals.