THEORETICAL INVESTIGATIONS OF CONFORMATIONAL ASPECTS OF POLYMORPHISM - PART-1 - O-ACETAMIDOBENZAMIDE

o-Acetamidobenzamide crystallises in two polymorphs designated alpha a nd beta. In the alpha-polymorph an intramolecular hydrogen bond is pre sent, which is not found in the conformation adopted in the beta-polym orph. The geometries of the molecules found in the crystal structures have been studied in detail using molecular mechanics, semi empirical and ab initio quantum chemistry techniques. Conformational energy diff erences have been evaluated, and gas phase potential energy surfaces g enerated to explore the conformational freedom of o-acetamidobenzamide . It has been found that both observed solid state conformations occur close to, but not actually at, minima on the calculated gas phase pot ential energy surfaces. Conformational energy differences of 8-10 kcal mol(-1) have been found between the conformers found in the crystals, depending on the method used for the calculation. Based on lattice en ergy calculations for both polymorphs it would appear that the less st able conformation is not compensated for by an equivalent stabilisatio n of the crystal lattice. The total (intra-and inter-molecular) energy difference between polymorphs is greater than that conventionally acc epted. The difficulties of using theoretical tools in conformational s tudies and the implications of our findings for ab initio crystal stru cture prediction are discussed.