Conformational, concomitant polymorphs of 4,4-diphenyl-2,5- cyclohexadienone: Conformation and lattice energy compensation in the kinetic and thermodynamic forms

Abstract

4,4-Diphenyl-2,5-cyclohexadienone (1) crystallized as four conformational polymorphs and a record number of 19 crystallographically independent molecules have been characterized by low-temperature X-ray diffraction: form A (P2 1, Z′=1), form B (P1̄, Z′ = 4), form C (P1̄, Z′=12), and form D (Phca, Z′ = 2). We have now confirmed by variable-temperature powder X-ray diffraction that form A is the thermodynamic polymorph and B is the kinetic form of the enantiotropic system A-D. Differences in the packing of the molecules in these polymorphs result from different acidic C-H donors approaching the C=O acceptor in C-H⋯O chains and in synthons I-III, depending on the molecular con formation. The strength of the C-H⋯O interaction in a particular structure correlates with the number of symmetry-independent conformations (Z′) in that polymorph, that is, a short C-H⋯O interaction leads to a high Z′ value. Molecular conformation (Econf) and lattice energy (Ulatt) contributions compensate each other in crystal structures A, B, and D resulting in very similar total energies: Etotal of the stable form A = 1.22 kcal mol1, the metastable form B = 1.49 kcal mol-3, and form D = 1.98 kcal mol-1. Disappeared polymorph C is postulated as a high-Z′ high-energy precursor of kinetic form B. Thermodynamic form A matches with the third lowest energy frame based on the value of U latt determined in the crystal structure prediction (Cerius 2, COMPASS) by full-body minimization. Re-ranking the calculated frames on consideration of both Econf (Spartan 04) and U latt energies gives a perfect match of frame #1 with stable structure A. Diphenylquinone 1 is an experimental benchmark used to validate accurate crystal structure energies of the kinetic and thermodynamic polymorphs separated by < 0.3 kcal mol-1 (∼1.3kJ mol-1). © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.