Acyl transfer reactions mediated by cyclodextrins. The reaction of external nucleophiles with encapsulated alkanoate esters of varying chain length

Abstract

The kinetics of the reaction of p-nitrophenyl alkanoates (acetate to decanoate, C₂ to C₁₀) with trifluoroethanol (TFE) in the presence of α-, β-, or hydroxypropyl-β-cyclodextrin (α-, β-, or Hp-β-CD) in basic aqueous solution have been measured. The results are analysed to afford rate constants for nucleophilic attack on the free and CD-bound esters (k_N and k_cN, respectively). Generally speaking, the values of k_N and k_cN are not very different, so that binding the esters to CDs has only modest effects on their reactivities towards TFE, reacting as its anion. However, there is a general trend in k_cN values such that transition-state stabilization increases in a biphasic manner as the alkanoate chain is lengthened from C₂ to C₁₀. For short chains (< C₇) the rise in transition stabilization is gentle but for longer chains (> C₆) is quite steep. This same behaviour is observed for all three CDs, with only minor differences between them, and also when the nucleophile is the anion of 2-mercaptoethanol. It is suggested that there is a change in the mode of transition-state binding of the esters from aryl group inclusion (3^‡) for the short esters to acyl-group inclusion (4^‡) when the acyl chain is lengthened beyond C₆.