Reactivity in the Para Oxo Ketene Route of Ester Hydrolysis. The Effect of Internal Nucleophilicity and the Irrelevance of B Strain

Article abstract of DOI:10.1021/jo00211a016

The hydrolysis of 2,4-dinitrophenyl (DNP) esters of substituted 4-hydroxybenzoic acids obeys the equation k_obsd = (k_a + k_b->)/(1 + +>/K_a) and involves a para oxo ketene intermediate.The k_a term fits a Broensted equation against the pK of the 4-hydroxybenzoate (log k_a = 1.15pK^a - 11.71) provided the 2,6-positions of the benzoate are free.The k_a term for the 2,6-dimethyl-4-hydroxybenzoate ester is 1015-fold larger than that for the parent 4-hydroxybenzoate ester.An electronic effect due to different hydroxyl pK_a's may be calculated from the above linear free energy relationship to contribute 1.6percent of the discrepancy.The other component of the discrepancy is ascribed to a preferred alignment of the ester in the 2,6-dimethyl case perpendicular to the plane of the aromatic ring. < formula> The fused ketene in the microscopic reverse reaction has a LUMO acceptor orbital perpendicular to the plane of the ring, in agreement with our conclusions.Force-field calculations of nonbonding interactions indicate no strain release in the elimination mechanism giving rise to k_a.The dramatic (10⁷-fold) enhancement of the apparent second-order rate constant for alkaline hydrolysis of the 2,6-dimethyl ester compared with that of the corresponding 2',4'-dinitrophenyl 4-methoxy-2,6-dimethylbenzoate is due mostly to the steric strain imposed in the tetrahedral transition state for the latter reaction.This strain is not sufficient, however, to cause the normal B_Ac2 mechanism in the alkaline hydrolysis of mesitoates to change to a "square planar" concerted process.