Effect of Nucleophile Basicity on Intramolecular Nucleophilic Aminolysis Reactions of Carbonate Diesters

Article abstract of DOI:10.1021/ja00404a036

The rates of phenol release from para-substituted phenyl 2-pyridylethyl carbonates have been measured in H2O at 25 deg C (μ 0.5 M).The pH-rate constant profiles are sigmoidal, showing participation by the pyridine neutral base species.The D2O solvent isotope effect is nearly unity, indicating that participation is by a nucleophilic reaction.The Hammett ρ value for intramolecular pyridine assisted phenol release is +2.2, and the fit is better with ?^- than with ?, indicating considerable C-O bond breaking in the transition state.The effective molarity of the neighboring pyridine of p-nitrophenyl 2-pyridylethyl carbonate is 81 M in comparison with pyridine acting as a bimolecular catalyst in the hydrolysis of ethyl p-nitrophenyl carbonate.Intramolecular nucleophilic attack is 217 times more favorable when a five-membered ring is formed with phenyl 2-pyridylmethyl carbonate than in the case of phenyl 2-pyridylethyl carbonate where the reaction proceeds via a six-membered ring.The effective molarity of neighboring pyridine in the 2-pyridylmethyl series is 2x10³ M.Sigmoidal pH-rate constant profiles were also obtained with neighboring imidazole, N,N-dimethylamino, and N-methylpiperidine nucleophiles.Values of the limiting rate constants (k_B) are similar in spite of pK_app values which vary from 3.9 to 10.The effective molarity of the dimethylamino group of p-nitrophenyl N,N-dimethylaminopropyl carbonate is only 32 M in comparison to reaction of triethylamine with ethyl p-nitrophenyl carbonate.On the other hand, the effective molarity of the dimethylamino group of p-nitrophenyl o-(N,N-dimethylamino)phenyl carbonate (pK_app=3.9) is > 10⁵ M.The most efficient intramolecular nucleophiles in reactions of p-nitrophenyl carbonate diesters are those of low pK_a.In contrast, with analogous carboxylate esters the converse is the case, even though the rate constants for bimolecular aminolysuis of p-nitrophenyl acetate and ethyl p-nitrophenyl carbonate are closely similar.These results may indicate that C-N bond formation is not complete in the transition states of the intramolecular reactions.