Nucleophilic Addition to Olefines. 19. Abnormally High Intrinsic Barrier in the Reaction of Piperidine and Morpholine with Benzylideneacetylacetone

Article abstract of DOI:10.1021/ja00284a043

The title reaction leads to the formation of the zwitterionic Michael adduct T^+/- (PhCH(R2NH⁺)C(COCH3)2^-) which is in rapid acid-base equilibrium with its anionic form T^-(PhCH(R2N)C(COCH3)2^-).Rate (k₁, k_-1) and equilibrium constants (K₁) for nucleophilic addition and the pK_a of the T^+/- adducts were determined in 50percent Me2SO - 50percent water at 20 deg C.From an interpolation of the rate constants to K₁ = 1 an intrinsic rate constant, log k₀ = 0.3, was determined.This value deviates negatively by approximately 2.5 log units from a correlation of log k₀ for amine addition to five olefins of the type PhCH=CXY, with log k₀ for the deprotonation of the corresponding carbon acids CH2XY.Two major factors are believed to contribute to this depressed intrinsic rate constant or enhanced intrinsic barrier: (1) steric inhibition of resonance in T^+/- with the steric effect developing ahead of C-N bond formation (this conclusion is supported by an X-ray crystallographic study of p-methoxybenzylideneacetylacetone which showes that steric hindrance to optimal ?-overlap in the adduct T^+/- is already present in the substrate); (2) intramolecular hydrogen bonding in T^+/-, which is inferred from abnormally high pK_a values and whose development lags behind C-N bond formation.These effects are shown to be manifestation of the Principle of Nonperfect Synchronization.