35486-49-8Relevant academic research and scientific papers
18O exchange accompanying the basic hydrolysis of primary, secondary, and tertiary toluamides. 2. The importance of amine leaving abilities from the anionic tetrahedral intermediates
Slebocka-Tilk,Bennet,Keillor,Brown,Guthrie, J. Peter,Jodhan
, p. 8507 - 8514 (2007/10/02)
A series of primary, secondary, and tertiary toluamides (CH3(C6H4)C=ONR1R2) was studied with respect to their hydrolysis and C=O, 18O exchange rate constants in basic media at 100 °C. For the primary amides (R1 = R2 = H) the kex/khyd ratio is 3.7 ± 0.2 and is independent of [OH-]. For the secondary toluamides R1 = H, R2 = Et, iPr, or tBu, the kex/khyd ratio is constant at 0.4-0.75, despite the fact that khyd drops from 1.0 to 0.22 to 0.02 in passing through the series. The tertiary toluamides R1 = R2 = CH3, R1, R2 = (CH2)4 have kex/khyd = 0.01-0.02 in H2O, and that ratio increases somewhat in D2O. 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 R2NH (130-180) > RNH2 (15-20) > NH3 (1.0). These data account for the observed kex/khyd ratios for the corresponding amides and indicate that amine leaving ability determines whether a given amide will exhibit significant 18O exchange.
