Kinetic and Thermodynamic Conformational Polymorphs of Bis(p-tolyl) Ketone p-Tosylhydrazone:  The Curtin−Hammett Principle in Crystallization

Bis(p-tolyl) ketone p-tosylhydrazone (2) crystallized as three conformational polymorphs, forms 1−3, under different conditions. The crystal structure of form 1 has an N−H···OS dimer synthon, but forms 2 and 3 have no strong hydrogen bonds even though the molecule contains an SO₂NH group. Polymorphs 1 and 3 are assigned as kinetic and thermodynamic forms on the basis of the criteria of lower energy, higher melting point, and higher density for the latter modification. Calculation of both intramolecular (E_conf) and intermolecular energy (U_latt) gave a crystal energy difference (ΔE_total) of 2.54 kcal mol^-1 between forms 1 and 3, whereas metastable and disappearing form 2 has much a higher energy of 8.71 kcal mol^-1. Sulfonamide 2 is a rare example of a polymorph cluster wherein strong hydrogen bonds stabilize kinetic form 1 whereas thermodynamic polymorph 2 has excellent close packing but no hydrogen bonds. A Curtin−Hammett energy profile for the crystallization of conformational polymorphs 1 and 3 is proposed that is consistent with structural, thermochemical, and computational data. Hydrogen bonding in tolyl compound 2 is compared with other benzophenone hydrazones varying at the para-position (e.g., H, F, Cl, Br). The bimolecular N−H···OS dimer is present in crystal structures 3−6 as well as in the CH₂Cl₂ solvate of 2 and benzene solvates of chloro 5 and bromo 6 hydrazones.