Crystal engineering of bicyclo[3.3.0]octane derivatives

Abstract

The concept of awkward shape has been proved to be a powerful tool in deliberately designing and obtaining alternative crystal forms. Awkward shape stands for a type of relatively rigid molecular configuration which does not allow the molecule itself to pack efficiently, leaving more energetically favoured crystal forms possible, such as solvate, hydrate and co-crystal. The bicyclo[3.3.0]octane ring structure is a typical example with a dish-like awkward shape. Bicyclo[3.3.0]octane derivatives were finely designed and have been successfully synthesized in our lab. Different crystallisation behaviour of all these compounds were explored by growing X-ray quality crystals simply by changing the recrystallization solvent at room temperature and pressure (except one case). In chapter 2, the racemic compound 2,4,6,8-tetracarbomethoxybicyclo[3.3.0]octa-2,6-diene-3,7-diol (tetraester) yielded a second apohost polymorph from methanol at 0℃. We also have obtained a family of closely related inclusion compounds. In addition, tetraester also shows unique properties when mixed solvents were applied as recrystallization solvent. In chapter 3, mono-, di-, trimethylated compounds have lost their potential of forming multiple crystal forms. The tetramethyl tetraester was found to adopt four apohost polymorphs in which C-H O interactions dominate. In chapter 4, di-n-butyl, dibenzyl and dinaphthyl compounds yielded only one solvent free crystal form. The dipyridyl compound adopts five crystal forms including two apohost polymorphs, two hydrate polymorphs and a benzene solvate. The dithienyl compound exclusively includes small alcohols as co-crystals. In chapter 5, a family of V-shaped molecules has been designed and successfully synthesized as host compounds affording the property of including guest v solvents. They exhibit completely different crystallisation behaviour compared to their structural isomers. It is demonstrated here that supramolecular awkwardness can be used as a powerful tool for designing compounds that are prone to yielding more than one crystal forms, but prediction of the exact crystal packing is still a challenge beyond our current understanding.