Oxygen-18 exchange accompanying the basic hydrolysis of primary, secondary, and tertiary toluamides. 2. The importance of amine leaving abilities from the anionic tetrahedral intermediate

A series of primary, secondary, and tertiary toluamides (CH 3 (CH 6 H 4 )C=ONR 1 R 2 ), was studied with respect to their hydrolysis and C=O. 18 O exchange rate constants in basic media at 100°C. Analysis of the energetics of the various possible intermediates, and their barriers for interconversion and breakdown, produces a mechanism consistent with presently known experimental data. The reaction proceeds stepwise via the addition of OH − to produce an anionic intermediate (T − ). Breakdown of T − to product involves a water-mediated proton switch to give an anionic zwitterion followed by rate-limiting C-N cleavage. By study of the partitioning of unsymmetrical amidines in base at 100°C, an order of leaving ability from an anionic intermediate is established where R 2 NH (130-180)>RNH 2 (15-20)>NH 3 (1.0). These data account for the observed k ex /k hyd ratios for the corresponding amides and indicate that amine leaving ability determines wheter a given amide will exhibit significant 18 O exchange