INCLUSION COMPLEXATION OF (CYCLO)ALKANES AND (CYCLO)ALKANOLS WITH 6-O-MODIFIED CYCLODEXTRINS

Novel alpha- and/or beta-cyclodextrin benzoates(2 alpha, 2 beta), meth yl phthalate (3 beta), tethered benzamide (4 beta) and 2-naphthoate (5 beta) have been synthesized. The complex stability constants (K-s) of these cyclodextrin derivatives with a series of acyclic and cyclic hy drocarbons, and alcohols have been determined in water to reveal the r ole of the hydrophilic group in the guest molecule, and to evaluate th e individual contribution of weak interactions involved in inclusion c omplexation by cyclodextrin. The free energy of complexation (-Delta G degrees) increases linearly to a certain limit with extending chain l ength or ring size (N-C) of the guests, giving unit increments per met hylene (-d Delta G degrees/dN(C)). Interestingly, the unit increment o btained is independent of the host's size or substituent introduced, b ut is a critical function of the guest type. Thus, a remarkably large -d Delta G degrees/dN(C) value of 5.4 kJ mol(-l) has been obtained for the cycloalkane series, whereas much smaller, but conventional, value s 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 effe cts 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.