Change of Rate Limiting Step in General Acid-Catalyzed Benzo[a]pyrene Diol Epoxide Hydrolysis

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 5.4−10.7 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 1 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.