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

Abstract

We report the synthesis and characterization of four molecular rotors 2, 3, 4, and 5 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 2, four were indentified in the cases of compounds 3 and 4, and three for compound 5. 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 3–5. 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.