Catalysis of the Debromination of 4-Alkyl-4-bromo-2,5-cyclohexadienones in Aqueous Solution by α-Cyclodextrin

Article abstract of DOI:10.1021/ja00218a036

α-Cyclodextrin (CD) has little or no effect on the rates of enolization of transient 4-bromo-2,5-cyclohexadienones (2), formed during the aqueous bromination of alkylphenols.In contrast, saturation kinetics and large catalytic effect are observed for the debromination of the title dienones (4), formed by ipso bromine attack on 4-alkylphenols (alkyl = Me, Et, i-Pr, n-pr, t-Bu, 3,4-diMe).With the exception of the n-propyl case, the extent of the catalysis k_c/k_u = 23-78) and the dissociation constant of the CD.dienone complexes (K_d = 2.32-4.83 mM) show surprisingly little variation for the different alkyl groups.The simplest interpretation of the results is that the CD-catalyzed debromination reaction involves attack by free bromide ion on the CD.dienone complex.However, the kinetically equivalent pathway, the reaction between the free dienone 4 and the CD complex of bromide ion, is much more consistent with the low sensitivity of the catalysis to the length and size of the different alkyl groups.For this mechanism the rate enhancements are much larger (2400-4600) and almost constant.They imply that Br^- in its CD complex is a stronger nucleophile than bromide ion that is completely solvated by water.The preferred mechanism is the microscopic reverse of that postulated for the CD-catalyzed bromination of phenols.The common transition state for the ipso bromination of 5 (R=Me) and the debromination of 4 (R=Me) is strongly bound by CD (K_d ca. 4.5 1E-5 M).