Acylanthranils. 10. Influence of Hydrogen Bonding on Hydrolysis of Acetylanthranil in Organic Solvents

Article abstract of DOI:10.1021/jo01307a027

The hydrolysis of acetylanthranil (1) to give o-acetamidobenzoic acid (2) in organic solvents at room temperature was monitored by proton NMR and/or gravimetrically.The results show that the second-order rate constant in benzene is about equal to that in water at pH 6.8.The corresponding rate constant for hydrolysis by a stoichiometric amount of water in proton-acceptor solvents decreases in the order benzene > dimethyl-d6 sulfoxide > acetone-d6 > dimethylformamide-d7 > pyridine, and for hydrolysis in proton donor solvents, it decreases in the order benzene > chloroform-d > acetonitrile-d3.The observed second-order rate "constant" in organic solvents, however, is not a true constant, since it increases linearly with water concentration.It was observed also that the plots of log /<1> as a function of time, t, show an inflection at some time, t_i, that appears to correspond to a critical equilibrium concentration of available proton from the acid product 2.The magnitude of t_i is decreased considerably by addition of 2 at time zero, and it is eliminated completely by addition of HCl.On the other hand, it is increased considerably by addition of solutes that are strong proton acceptors, such as 1,8-bis(dimethylamino)naphthalene or 1,4-diazabicyclo<2.2.2>octane.These results are consistent with the hypothesis that hydrolysis of 1 in organic solvents involves interaction with molecular clusters of water such as (H2O)n in benzene, S*HOH*S or (HOH*S)n in proton-acceptor solvents, S, and H2O*HS in proton donor solvents, SH.