Equilibration of N-(2-cyanoethyl)pyridinium cations with substituted pyridines and acrylonitrile. A change in rate-determining step in an E1cb reaction

Article abstract of DOI:10.1021/ja00180a034

The rates of equilibration of N-(2-cyanoethyl)pyridinium cations (1) with the corresponding pyridines and acrylonitrile have been measured in aqueous solutions of ionic strength 0.1 at 25 °C. Second-order rate constants (k_OH) have been obtained for the hydroxide ion catalyzed elimination reactions of 16 ring-substituted 1 having pyridine leaving groups of pK_BH in the range 1.5-9.7. Bronsted plots of log k_OH vs pK_BH are "concave down" with two distinct linear regions having β_1g = -0.30 (for pK_BH < 5.8) and β_1g = -0.93 (for pK_BH > 5.8). This observation is consistent with a change in rate-determining step within an E1cb reaction mechanism from rate-determining deprotonation of 1 (i.e., (E1cb)_irrev) for pK_BH < 5.8 to rate-determining leaving-group expulsion from the carbanionic intermediate (i.e., (E1cb)_rev) for pK_BH > 5.8. This interpretation is supported by ¹H NMR spectral observations in basic D₂O, which show no incorporation of deuterium into the acrylonitrile product for pK_BH < 5.8 but do show D for H exchange of the methylene protons that are a to the cyano group at a rate that is faster than elimination for pK_BH > 5.8. Rates of nucleophilic attack of pyridines and pyridinone anions (pK_BH > 6) upon acrylonitrile have also been measured. These display a linear Br?nsted plot of β_nuc = 0.20. Combination of β_1g and β_nuc gives β_eq = 0.13 for the Michael-type addition of pyridinium cations to acrylonitrile to produce 1. Although the rates of the addition of pyridines of pK_BH < 6 are too slow for convenient measurement in the current study, the combination of the measured rate and equilibrium Bronsted parameters allows the demonstration of the change in rate-determining step in these addition reactions from rate-determining nucleophilic attack (carbanion formation) with β_nuc = 0.20 for pyridines of pK_BH > 5.8 to rate-determining protonation of the carbanionic intermediate with β_nuc = 0.83 for pyridine nucleophiles of pK_BH < 5.8. General-base catalysis of the elimination reactions is observable in the (E1cb)_irrev region but is extremely weak under the current experimental conditions.