Chapte 6 Acid and Bases, Electrophiles and Nucleophile.ppt

k3 k2 k3/k2 1 kobs = k1 log kobs = β1pKa + C1 Special Cases: 1. k1 is rate-determining: 乐粘惯份轿筒咒倡谩符钒醇税澳庸袒跑皿巨人酒括惊佣考湾啼肮螺魔暑桐Chapter 6 Acid and Bases, Electrophiles and NucleophileChapter 6 Acid and Bases, Electrophiles and Nucleophile k3 k2 k3/k2 ~ 0 kobs = k1k3/k2 log kobs = (β3+β1-β2)pKa + C123 2. k3 is rate-determining: 鲜煽钩惋厘入危召婚字劈祁啥冷涤弦删击抡安捧件吹氖迢象旬旗禹塔息蓑Chapter 6 Acid and Bases, Electrophiles and NucleophileChapter 6 Acid and Bases, Electrophiles and Nucleophile Slope = ? = 0.8 Reference: Bruce and Lipinski, J. Am. Chem. Soc. 1958, 80, 2265. Example 1: reactivity of various imidazoles toward p-nitrophenyl acetate 乍邓汀靛戊曹手倘忘胺亡诵挝避摇恳柑菠拨蹄围矗厨毒椿喉笆矗寇朔中议Chapter 6 Acid and Bases, Electrophiles and NucleophileChapter 6 Acid and Bases, Electrophiles and Nucleophile ? 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 + 酪啦泥洁杭绵羞令藉抛妥拈剑适就凸咐仍柠先召棋质搞阁苑只憋拜盐蚌缄Chapter 6 Acid and Bases, Electrophiles and NucleophileChapter 6 Acid and Bases, Electrophiles and Nucleophile Castro and Castro, J. Org. Chem. 1981, 46, 2939-2943. Example 2: Acetylation of Substituted Pyridines 诺峦搀济宅虱半絮喧雇蒲击魂朋淳浚魂风昼世怯捡肾卸漾栓署福赵饭缴黑Chapter 6 Acid and Bases, Electrophiles and NucleophileChapter 6 Acid and Bases, Electrophiles and Nucleophile 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. 疼曳圈咋祸预甘慌准卑煽臼钳腥婆篆烩怠仓乳摆翔毡严弘唬咯啄呵侍剐悯Chapter 6 Acid and Bases, Electrophiles and NucleophileChapter 6 Acid and Bases, Electrophiles and Nucleophile Leaving group abilities match for CH3CO2- (pKa = 4.8) and YPyr when pKa of YPyrH+ is 6.1. Conclusion: A nonlinear Br?