Cycloalkanone-Based Threo and Erythro Aldols as Supramolecular Synthons in Crystal Engineering

Abstract

Aldols are bifunctional molecules possessing OH and CO groups, which are able to act as both hydrogen donors and/or acceptors. Despite their high potential as supramolecular synthons, in comparison to their two carbon less homologues, carboxylic acids, the structures of aldols, and their crystals have not been systematically studied. We have designed synthons on the basis of the ab initio calculated syn-CO/OH and OC−C(α)−C(β) eclipsed conformation of the simplest aldol and have synthesized 16 cycloalkanone-based threo/erythro aldols, which are systematically installed with structural determinants. The molecular conformations, the hydrogen-bonding patterns, the location of OH protons, the crystal structures, and the packing efficiency have been analyzed by X-ray diffraction to relate synthons with crystals. Generally, the stable syn/eclipsed conformations are maintained in the C(3)-unsubstituted cyclohexanone-based aldols, and the racemic synthons crystallize via an S(6) monomer or a heterochiral dimer by way of van der Waals forces. The enantiomerically pure aldols, however, tend to form intermolecular hydrogen bonds generating a helix chain. Introduction of a C(3) substituent completely destroys the stable conformation yielding an unusual C(2)−C(3) trans-diaxial conformation. This enables the formation of an intermolecularly hydrogen-bonded long chain column with a screw axis or glide plane, which can crystallize through CH···O or van der Waals interaction.