Inclusion complexation of (cyclo)alkanes and (cyclo)alkanols with 6-O-modified cyclodextrins

Abstract

Novel α- and/or β-cyclodextrin benzoates (2α, 2β), methyl phthalate (3β), tethered benzamide (4β) and 2-naphthoate (5β) have been synthesized. The complex stability constants (K_s) of these cyclodextrin derivatives with a series of acyclic and cyclic hydrocarbons, and alcohols have been determined in water to reveal the role of the hydrophilic group in the guest molecule, and to evaluate the individual contribution of weak interactions involved in inclusion complexation by cyclodextrin. The free energy of complexation (–ΔG °) increases linearly to a certain limit with extending chain length or ring size (N_C) of the guests, giving unit increments per methylene (–dΔG °/dN_C). Interestingly, the unit increment obtained is independent of the host’s size or substituent introduced, but is a critical function of the guest type. Thus, a remarkably large –dΔG °/dN_C value of 5.4 kJ mol^–1 has been obtained for the cycloalkane series, whereas much smaller, but conventional, values have been recorded for cycloalkanols (3.3 kJ mol^–1), alkanes (3.1 kJ mol^–1) and alkanols (2.7 kJ mol^–1). No significant isotope effects on K_s are observed when deuterated cyclohexane is complexed with the same cyclodextrins. Similarly, there is no significant effect when deuterated water is used as solvent. Moderate enantioselectivities of up to 2.0 are obtained with some chiral guests.

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