Kinetics of Amine Addition to Benzylidenemalonodialdehyde in 50percent Me2SO-50percent water

Article abstract of DOI:10.1021/jo00006a008

The kinetics of the reaction of benzylidenemalonodialdehyde with piperidine, morpholine, n-butylamine, 2-methoxyethylamine, glycinamide, glycine ethyl ester, cyanomethylamine, and semicarbazide have been determined in 50percent aqueous Me2SO at 20 deg C.The reaction leads to a zwitterionic adduct, PhCH(RR'NH(1+))C(CHO)2(1-) (T_A(+/-)), that is in fast acid-base equilibrium with the anionic adduct, PhCH(RR'N)C(CHO)2(1-) (T_A(1-)).With strongly basic amines at high pH there is also attack of the amine on one of the carbonyl groups, which acts as a rapid preequilibrium.Rate constants for the formation of T_A(+/-) (k1) and its reverse (k-1), as well as equilibrium constants (K1 = k1/k-1) and the pKa of T_A(+/-) were determined for all the amines.Intrinsic rate constants (k0 = k1 = k-1 when K1 = 1) were calculated.The intrinsic rate constants are lower than those for amine addition to benzylidene Meldrum's acid.This is consistent with the greater role played by resonance in stabilizing T_A(+/-) derived from benzylidenemalonodialdehyde.However, k0 for piperidine/morpholine addition to benzylidenemalonodialdehyde is much higher than for the reaction of benzylideneacetylacetone with the same amines, indicating that the rate-depressing effect of intramolecular hydrogen bonding in T_A(+/-) derived from benzylidenemalonodialdehyde is much smaller than that in T_A(+/-) derived from benzylideneacetylacetone.Even though semicarbazide is an α-effect nucleophile, no enhancement of k1 was observed, but K1, estimated on the basis of a structure-reactivity relationship, is larger than expected based on the pKa of the amine.This result is attributed to a low ν_nucⁿ value.