Cyclodextrin catalysis of the pH-independent hydrolyses of acetals

Abstract

The spontaneous hydrolysis reactions of 2-(4-nitrophenoxy)tetrahydropyran (6a) and 2-(4-cyanophenoxy)tetrahydropyran (6b) are accelerated in the presence of α-cyclodextrin (α-CD), but are slowed by the addition of β-CD, γ-CD, or mono[2-O-(carboxymethyl)]-β-CD (β-CD-acid 5). The observed rate constants for the hydrolysis reactions in the presence of CD are consistent with the CD-catalysed reaction occurring from a 1∶1 complex of cyclodextrin with the substrate. In contrast, hydrolysis does not occur from the 1∶1 complex for reactions conducted at high pH values at which ionisation of the CD becomes important. The spontaneous hydrolysis reactions for both anomers of 2-deoxyglucopyranosylpyridinium salts are markedly accelerated by the addition of β-CD. In these reactions, the binding affinity of the β-CD cavity for the heteroaromatic ring of the pyridinium substrate increases in response to a decreasing positive charge on the ring moiety that occurs with approach to the transition state, and this results in catalysis.