AbstractThe hydrolysis of sterically hindered phenolic esters is of practical importance. The influence of the steric bulk of 2,6‐substituents (R) in various esters and the volume of the acyl group (R1) on these reactions have been studied theoretically. The differences (ΔΔHf) between semiempirical heats of formation (ΔHf) of the products and reactants were calculated for the formation of the tetrahedral intermediates—the rate‐determining step of a base‐catalyzed process. An analysis of the ΔΔHfvalues and of the calculated optimized low‐energy geometries indicated that the reactivity of esters generally decreased with the increase of the bulk ofR, while the size ofR1had less influence. However, electronic (resonance) effects ofR1were noticed in the case of unsubstituted phenolates. On the other hand, calculated global enthalpy changes for the reactions do not correctly reflect the influence of the steric factors over the hydrolysis of the hindered esters. © 1992 John