Conformational Polymorphism. 2. Crystal Energetics by Computational Substitution. Further Evidence for the Sensitivity of the Method

The effect of crystal forces on molecular conformations has been investigated using a combination of experimental X-ray crystallography and theoretical lattice energy and ab initio calculations. We have extended techniques developed previously which take advantage of and rationalize the phenomena of conformational polymorphism—the existence of two or more crystal forms of the same molecule existing in significantly different conformations. Lattice energy calculations in conjunction with ab initio molecular orbital studies on the model compound N-(P-chlorobenzylidene)-p-chloroaniline have been applied to answer the question as to why this molecule does not pack in a structure containing the ordered, low-energy, molecular conformation. The molecule was packed in the P2₁ lattice containing its dimethyl analogue. The lattice energy was minimized with three different potentials and the results were analyzed in terms of “partial atomic energy” contributions. All potentials showed the structure of the dichloro compound to be less stable than either the stable Pccn or metastable P&& observed structures (by 1.5 and 2.5 kcal, respectively). The analysis in terms of the partial atomic energies showed the relative lack of stability to arise from the relatively unfavorable energetic environments of the aniline ring (including its CI) as compared with its environment in the observed crystals. Finally comparison of the total energies (lattice plus intramolecular energy as obtained by molecular orbital calculations) accounted for the “observed nonexistence” of the low-energy conformation structure.