KINETICS OF AMINE ADDITION TO BENZYLIDENEMALONODIALDEHYDE IN 50-PERCENT ME2SO-50-PERCENT WATER

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 50% aqueous Me2SO at 20-degrees-C. The reaction leads to a zwitterionic adduct, PhCH(RR'NH+)C(CHO)2-(T(A)+/-), that is in fast acid-base equilibrium with the anionic adduct, PhCH(RR'N)C(CHO)2-(T(A)-). 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 pK(a) 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, k-omicron 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 alpha-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 pK(a) of the amine. This result is attributed to a low beta-nuc(n) value.