Rapid cleavage of cyclic tertiary amides of Kemp's triacid: effects of ring structure.
The piperidyl and prolyl amides of Kemp's triacid (7 and 8, respectively) have been prepared and their rates of intramolecular acylolysis measured as a function of pD. The piperidyl derivative 7 reacts approximately four-times faster (e.g., t(1/2)=3 min at 20 degrees C and pD7.7) than the previously reported pyrrolidyl and methylphenethyl amide derivatives, while the prolyl derivative 8 reacts two-times more slowly (e.g., e.g., t(1/2)=30 min at 20 degrees C and pD7.8). Molecular-mechanics calculations indicate that the nonbonded interactions in the piperidyl derivative 7 are distinct from those in the prolyl, pyrrolidyl, and methylphenethyl amide derivatives, a result that supports the suggestion that ground-state pseudoallylic strain contributes to the enormous reactivity of Kemp's triacid tertiary amides. In sum, the results reported indicate that the Kemp's triacid scaffolding provides a general means of activating tertiary amide derivatives.
Dougan
Michael L
ML
Department of Chemistry, Amherst College, Amherst, MA 01002, USA.
Chin
Jonathan L
JL
Solt
Ken
K
Hansen
David E
DE
D000143:Acids / Q000737:chemistry*; D000577:Amides / Q000737:chemistry*; D007700:Kinetics; D015394:Molecular Structure
D000143:Acids; D000577:Amides