Change of rate limiting step in general acid-catalyzed benzo[a]pyrene diol epoxide hydrolysis

Abstract

The rates of reaction of (±)-7β,8α-Dihydroxy-9α,10α-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (1) in 1:9 dioxane-water buffer solutions containing primary amines whose pK(a) values span the range of 5.410.7 have been determined. For those amines with pK(a) values < ca. 8, only the acid form (RNH3/+) gives rise to a kinetic term for reaction with 1. The rate- limiting step of this reaction is general acid-catalyzed epoxide ring opening to yield a discrete α-hydroxycarbocation, followed by a fast reaction of this intermediate with solvent. The intermediate α-hydroxycarbocation is sufficiently stable so that its reactions with external nucleophiles and bases compete with its reaction with solvent. For those amines with pK(a) > ca. 8, both acid and base forms of the buffer react with 1. The magnitude of the kinetic term in the base form of the amine (RNH2) increases with amine pK(a) and is attributed to nucleophilic addition of the amine to the epoxide group. Curvatures in plots of the kinetic term due to buffer (k(buff)) as a function of the mole fraction of buffer acid for substituted ammonium ions with pK(a) > 8 are interpreted in terms of a change in rate-limiting step of the general acid-catalyzed pathway from epoxide ring opening at low amine base concentrations to reaction of amine base acting as either a general base or nucleophile with an α-hydroxycarbocation at higher amine base concentrations. Thus, epoxide ring opening of I in buffer solutions of the more basic amines is a reversible reaction. Rate and product studies of the reaction of 1 in acid solutions (pH 5.5) and in Tris buffer solutions containing sodium azide show that azide ion is effective in trapping the α- hydroxycarbocation intermediate, subsequent to its rate-limiting formation by reaction of 1 with either H+ or Tris-H+. These results demonstrate that the intermediate formed from epoxide ring opening of 1 with acids has a sufficient lifetime so that its reaction with azide ion competes with its reaction with solvent.