Conformational Polymorphism and Isomorphism of Molecular Rotors with Fluoroaromatic Rotators and Mestranol Stators

We report the synthesis and characterization of four molecular rotors <b>2</b>, <b>3</b>, <b>4</b>, and <b>5</b> containing 2-fluoro-, 2,3-difluoro-, 2,5-difluoro-, and 2,3,5,6-tetrafluoro-substituted 1,4-phenylene rotators, respectively, that are axially linked through the triple bonds of rigid mestranol (3-methoxy-17α-ethynylestradiol) stators. Crystallization experiments using solvent mixtures of hexanes–ethyl acetate and acetonitrile–dichloromethane gave rise to polymorphic, pseudopolymorphic, and isomorphic crystals. Whereas two solids were obtained for compound <b>2</b>, four were indentified in the cases of compounds <b>3</b> and <b>4</b>, and three for compound <b>5</b>. The 13 solid forms were characterized by single-crystal and powder X-ray diffraction, infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. Two sets of isomorphous structures were obtained for solvated and solvent-free structures of compounds <b>3</b>–<b>5</b>. While polymorphic behavior of these compounds arises from their conformational freedom in solution, their isomorphism arises from the closely isosteric relation that exists between hydrogen and fluorine atoms.