Catalytic activity of proton sponge: Application to Knoevenagel condensation reactions

The catalytic activity of proton sponge 1,8-bisdimethylamino naphthalene (DMAN) (pK(a) = 12.1), tested with Knoevenagel condensation between benzaldehyde and activated methylenic group compounds, was investigated. When the reaction is performed with ethyl acetoacetate (pK(a) = 10.3), the proton sponge stabilizes the protonated form during the abstraction of the proton of the methylenic group. The stability of the protonated form is so high that the desorption step, the return of the proton to the condensed product, becomes the controlling step of the reaction and results in the "poisoning" of the catalyst. It is shown that, in this case, the solvent used plays a determining role in the reaction. Indeed, dimethylsulfoxide (DMSO) can stabilize the open form of the protonated amine due to its hydrogen bond acceptor characteristics. When the intermediate bond angle N-H(+)-N is slightly modified from the original 180 degrees, the rate of deprotonation strongly increases, and the reaction of ethyl acetoacetate with benzaldehyde can then be carried out. The results are discussed on the basis of quantum chemical calculations. The effects of the nature of the solvent on the reaction rate and the mechanism of Knoevenagel condensation on the proton sponge were studied in depth by means of the reaction between ethyl cyanoacetate (pK(a) < 9) and benzaldehyde in solvents of different polarities. (C) 1999 Academic Press.