Host–Guest Complexations of a Diastereoisomeric Mixture of cis- and trans-1,4-Bis(diphenylhydroxymethyl)cyclohexane in Pyridine and Methylpyridine Solutions: Significant Inclusion Selectivities and an Uncommon Host Conformation

Abstract

A 0.85:0.15 cis:trans diastereoisomeric mixture of 1,4-bis(diphenylhydroxymethyl)cyclohexane has been shown to form host–guest inclusion compounds with pyridine (PYR) and the three isomeric methylpyridines (2MP, 3MP, 4MP). Diastereoisomeric mixtures of the host compound were found in the crystalline products, but with the trans isomer dominating, ranging from 69% for PYR to 97% for 4MP. Crystals selected from these mixtures for SCXRD analysis were found to comprise the cis host species (H1) for PYR and 3MP and the trans isomer (H2) in the case of 2MP and 4MP. Thermal experiments established that the most stable inclusion complex is obtained with PYR because its release occurs at a higher temperature compared with the three MPs in their respective complexes. In mixed solvent crystallization experiments, the host was usually selective toward PYR, unsurprising given that the PYR complex is the most stable of the four. We therefore suggest that this host compound has potential to separate binary mixtures of the guest solutions considered here. SCXRD analysis also established that the (guest)N···H–O(H1) hydrogen bond is shorter for PYR than the MPs, which is consistent with the higher selectivity of the host species observed for PYR. Hirshfeld surface analyses revealed more extensive C···H/H···C and H···N/N···H interactions between PYR and the host compared compared to the host–guest complexes of the MPs. The crystal structure determination on H1·2(PYR) furthermore revealed that the cyclohexyl ring adopts the unexpected boat conformation. Conformational analysis of H1·2(PYR) as well as the individual host compounds was performed through molecular modeling at the molecular mechanics (MMFF) and DFT (ωB97X-D/6-31G*) levels. This established that when the diastereoisomeric host mixture is crystallized from PYR, a comparatively high-energy host–guest complex is preferred, with a high-energy boat conformer of cis-1,4-bis(diphenylhydroxymethyl)cyclohexane being selected.

The cyclohexyl moiety of the host compound 1,4-bis(diphenylhydroxymethyl)cyclohexane adopted a higher energy boat conformation in its complex with its preferred guest species, pyridine.