J . Am. Chem. SOC.1992, 114, 3092-3098
3092
greater than 1OO:l in favor of C-N cleavage for the hydroxyl derivatives 5 and 6 (the To formed from dimethylbenzamide).2,'8 Several reasons for the partitioning difference were advanced by McClelland,20 the most reasonable being a hydrogen bonding stabilization of the remaining OH group in 5 or 6 with solvent (not possible with 4) that develops in the TS for C-N cleavage. Our observation of SKIE effects near unity for the breakdown supports of To produced from 2a or N,2,4-trimethyla~etanilide~ that rationale and extends it to accommodate a solvent-promoted
proton removal from the OH group concurrent with the C-N cleavage. Acknowledgment. We gratefully acknowledge the continuing financial support of the University of Alberta and the Natural Sciences and Engineering Research Council of Canada. In addition they acknowledge the donors of the Petroleum Research Fund, administered by the American Chemical Society, for partial support of this work.
Base-Catalyzed Hydrolysis and l 8 0 =C Exchange Kinetics for Toluamides Containing Amine Portions of Reduced Basicity. N-Toluoyl-3,3,4,4-tetrafluoropyrrolidine and N-Toluoylpyrrole R. S. Brown,*,+A. J. Bennet,+H.Slebocka-Tilk,t and A. Jodhant Contribution from the Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2, and Mass Spectrometry Laboratory, Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2. Received August 16, 1991 Abstract: Base-catalyzedhydrolysis and exchange kinetics for N-toluoyltetrafluoropyrrolidine(IV) and N-toluoylpyrrole (V) have been determined as a function of [OH-] at 73 and 25 'C respectively, p = 1.0 (KCl). Both amides exhibit khydvs [OH-] profiles that contain first-order and second-order domains in [OH-]. For IV at low [OH-] where both the hydrolysis = 9.0, and this value is progressively reduced as [OH-] increases. and exchange kinetics are first order in [OH-], kex/khyd The solvent kinetic isotope effect for hydrolysis of IV at low [OH-] is slightly inverse (khyd)H/D= 0.72, and at high [OH-] becomes 1.54, suggestive of a change in mechanism from one involving spontaneous expulsion of amide anion at low [OH-] to one involving a proton in flight concurrent with amide anion expulsion at high [OH-]. For V, the khydprofile from pH 8.5 to 13.7 is approximately linear but shows a small inflection point at pH 10.8. At the same time, the k,, vs [OH-] profile = 0.24) but plateaus above pH 10.8 so that the k,, and khydprofiles diverge. for V at low [OH-] is first order in [OH-] (kex/khyd The hydrolytic and exchange processes for these amides are analyzed as involving a mechanism wherein the low [OH-] domain involves reversible attack of OH- on the amide to form To- followed by spontaneous C-N cleavage to expel the amide anion ratios for either without general acid assistance by solvent or with a small component of it. The difference in the kcx/khyd the two amides is explicable since the pyrrolide anion is a better leaving group than the tetrafluoropyrrolidide anion. At higher [OH-], second-order terms in [OH-] come into play wherein OH- deprotonates To- concurrently with expulsion of the amide anion. This process effectively halts the reversal and I8O=C exchange at high [OH-], since each time To- is produced it immediately undergoes OH- promoted breakdown to products. A unified picture of base promoted hydrolysis of toluamides containing amine portions of basicity varying over 15 pKa units is presented.
-
Introduction On the basis of carbonyl I8Oexchange studies and DzOsolvent kinetic isotope effects (SKIE),a common hydrolytic mechanism for the tertiary amides (1-111) in base was proposed.] For each
Scheme 1"
r,
9
OH 0
0
R-e-N
khydr the ratelimiting step in each hydrolysis is k2 and involves not OH- attack but cleavage of the C-N bond. The attack step ( k , ) of OH- on IV at 73 OC is -21 times faster than the attack on IIIIzBat 100 OC (4.3 X M-' s-l vs 2.0 X le3M-l SI). This is the expected result if the amine portion in IV is less electron donating to the C = O than the amine in 111. However, khyd for IV at low [OH-] (where there is not a second order in [OH-] term) is 2.4 X M-' s-l while the khyd for I11 at 73 OCIZbis 430 times slower at (IO) Bender, M. L.; Heck, H. d'A. J . Am. Chem. SOC.1967, 89, 121 1 . ( I 1) The temperature induced change in the partitioning of To- depends upon the enthalpy differences ( A M * ) between the transition states leading to product and starting material.
0.82
@OH
0.70
t
)3
@OH
0 (HOH)3OH +A 070 I 2 2
)3
0
Ij-/ \
A r !
0-H
WOHi
I.09
0.88
To
Figure 3. Proposed mechanism and fractionation factors for attack of OH- on amide IV or V with a TS 0.6 along the reaction pathway. (Bold H's have indicated fractionation factors; all other H's are unity.)
TW
,4r
4.. ."
OH
t
\
HO
I
