Chapter6AcidandBases,ElectrophilesandNucleophile.pptVIP

k3 k2 k3/k2 1 kobs = k1 log kobs = β1pKa + C1 Special Cases: 1. k1 is rate-determining: k3 k2 k3/k2 ~ 0 kobs = k1k3/k2 log kobs = (β3+β1-β2)pKa + C123 2. k3 is rate-determining: Slope = ? = 0.8 Reference: Bruce and Lipinski, J. Am. Chem. Soc. 1958, 80, 2265. Example 1: reactivity of various imidazoles toward p-nitrophenyl acetate ? High sensitivity of rate constant to basicity of nucleophile is consistent with a late transition state with appreciable +-charge on bonding atom of nucleophile: Appreciable bond making C CH 3 O O N O 2 N N H Y d - d + Castro and Castro, J. Org. Chem. 1981, 46, 2939-2943. Example 2: Acetylation of Substituted Pyridines The nonlinear Br?nsted plot is proof of an intermediate: pKa 6 Breakdown of T± is rate-determining. kobs = k1k3/k2 ? βobs = β3 + β1 - β2 pKa 6 Formation of T± is rate-determining. kobs = k1 ? βobs = β1 pKa ~ 6 Both k1 and k3 are rate-determining. Leaving group abilities match for CH3CO2- (pKa = 4.8) and YPyr when pKa of YPyrH+ is 6.1. Conclusion: A nonlinear Br?nsted plot requires a mechanism with at least one intermediate. Caveat: The converse, that a linear Br?nsted plot requires a concerted mechanism, is not true. Example 3: An unambiguous test for concertedness. Use nucleophiles of the same structural class as the leaving group. T- k3 = k2 when ?pKa = 0 Prediction for a stepwise mechanism: T - ?, if reaction is stepwise, Br?nsted plot must have a break at pKanuc = 7. C H 3 C O O C 6 H 4 N O 2 O C 6 H 4 Y d - d - * Chapter 6: Acid and Bases, Electrophiles and Nucleophiles I. Acid-Base Dissociation A. Water Acting as a Base Since for dilute solution the activity of water is constant: B. Water Acting as An Acid Proceeding as before: Since pKW = pH + pOH = 14 pKb = 14 - pKa Conclusion: stronger bases h