Solvent influence on reaction mechanism of the nucleophilic substitution of beta-substituted alkoxyvinyl trifluoromethyl ketones with piperidine

摘要

Multiple linear regressions of solvent effects on reactivity of beta-substituted beta-alkoxyvinyl trifluoromethyl ketones (RO)-O-1-CR2=CH-COCF3 (1a, b) [(1a), R-1=R-2=CH3; (1b), R-1=C2H5, R-2=C(CH3)(3)) with piperidine (2) [(CH2)(5)NH) in nine aprotic and six protic solvents were obtained. Values of In k in dimethyl sulfoxide are out of the regression in view of electrophilic solvent catalysis. For 1a (E-s-Z-o-Z) and 1b (Z-s-Z-o-Z), single regressions were obtained for all studied solvents, whereas for 1b (E-s-Z-o-Z) and 1b (E-s-Z-o-E) protic and aprotic solvents form separate correlations. In the first two cases, the rate retardation due to nucleophile protonation by alcohols is compensated by the rate acceleration via electrophilic solvent assistance whereas in the second two cases the rate retardation predominates and protic solvents form separate correlations with Reichardt's solvent parameter ET. Hence, in those cases the reaction rate depends mostly on the solvent's hydrogen-bond donor (HBD) acidity (alpha). The poor proton-donating ability of enones 1a, b accounts for the negligible effect of solvent's basicity (P) on the reaction rate. For systems for which a single regression is observed, the main influence on the reaction rates comes from the solvent's dipolarity/polarizability (pi*). Copyright (C) 2008 John Wiley & Sons, Ltd.