Kinetics and Mechanism of the Addition of Benzylamines to Benzylidene-3,5-heptadione in Acetonitrile

Abstract

The addition reaction of benzylamine (XC6H4CH2NH2) to benzylidene-3,5-heptadione (BHD; YC6H(4-)CH=C(COEt)(2)) in acetonitrile is investigated. The rate is slower than the corresponding rate for benzylidenediethylmalonate (YC6H4CH=C(OOEt)(2)) as the result of a greater steric hindrance in the planar dicarbonyl transition state. The kinetic isotope effects (k(H)/k(D)) involving deuterated amine nucleophiles (XC6H4CH2ND2) are greater than 1 (1.37-2.04), indicating N-H bond stretching with concurrent N-C(alpha) and H-C(beta) bond formation in the TS. The trend of change in k(H)/k(D) with variation of substituent X in the nucleophile conforms to the Bell-Evans-Polanyi principle. It has been stressed that the dicarbonyl group activated olefins exhibit insignificant charge imbalance in the TS for the benzylamine additions in acetonitrile as a result of the two strong n(c) --> pi*(C=O) vicinal charge-transfer interactions.

Electrophilicity of 5-Benzylidene-1,3-dimethylbarbituric and -thiobarbituric Acids

“…The reported rate constants for the additions of piperidine to 1b , c in acetonitrile at 25 °C are 20 and 5 times greater than the calculated rate constants for these reactions in DMSO at 20 °C, again showing qualitative agreement. For the reactions of secondary amines with benzylidene Meldrum's acids in aqueous DMSO, Bernasconi postulated an early development of hydrogen bonding on the reaction coordinate that was supposed to be responsible for enhanced intrinsic rate constants k 0 . , Furthermore, Oh et al proposed that the additions of benzyl amines to dicarbonyl activated olefins in acetonitrile proceed through cyclic transition states with four- or six-membered rings, where the amine proton forms a hydrogen bond to C α of the Michael acceptor or to a carbonyl oxygen. − As a consequence, it is possible that the constant higher reactivity of amines in reactions with benzylidenebarbituric acids is due to interactions of the N−H bonds with the developing negative charge on C α or one of the carbonyl oxygens of the Michael acceptor.…”

Mechanistic Assessment of SNAr Displacement of Halides from 1-Halo-2,4-dinitrobenzenes by Selected Primary and Secondary Amines: Brønsted and Mayr Analyses

“…In our previous paper concerning S N Ar displacement we applied Brønsted analysis to assess the rate-determining mechanistic step . Although this tool has been used extensively for nucleophilic reaction at CO, − its application to S N Ar reactions has been more modest …”