Evans. Annis Kinetic Acidity: Carbon versus Oxygen Acids Chem 206 ■ Kinetic Acidity a Kinetic Acidity vS Leaving Group Ability: E1cb Elimination Reactions Observation: The thermodynamic acidities of phenol and nitromethane are Stirling, Chem. Commun. 1975, 940 ely 10: however, using a common base, phenol is deprotonated 10 times as fast. Ph- base 9②a Base 8 Proton transfers from c-h bonds are slow Ka HX 10 ■Why??? reater the structural reorganization of the leaving group during Most carbon acids are stabilized by resonance. Hence significant E1cb elimination the slower the rate of elim structural reorganization must accompany deprotonation a Protonation of Conjugate bases Kinetic product O-H electron density O-H electron density is still here oLi- C-H electron density C-H electron density ow resides here. and nucle Jack Hine: Least Motion Principle(Adv. Phys. Org. Chem. 1977, 15. 1) have moved to accomodate Lowry Richardson, 3rd Edition, pp 205-206 The greater the structural reorganization during deprotonation, the lower hose elementary reactions that involve the least change in the kinetic acidity atomic posiitons will be favoredO H Proton transfers from C-H Bonds are slow. O H Observation: The thermodynamic acidities of phenol and nitromethane are both approximately 10; however, using a common base, phenol is deprotonated 10+6 times as fast. N O O H H N O–H O H H H3C N O O N O O H H H N O O H H O H2C N O O O Base Base Base Base Ph S X O O OLi Ph S OPh O O H3O + Ph S X O O O–H Ph S PPh3 O O H3O + Ph S CN O O Ph S O O O H X – Evans, Annis Chem 206 ■ Kinetic Acidity Kinetic Acidity: Carbon versus Oxygen Acids Most carbon acids are stabilized by resonance. Hence significant structural reorganization must accompany deprotonation. O-H electron density is here. O-H electron density is still here. C-H electron density now resides here, and nuclei have moved to accomodate rehybridization. C-H electron density is here. rel rate: 1 rel rate: 10+6 ■ Why??? The greater the structural reorganization during deprotonation, the lower the kinetic acidity ■ Kinetic Acidity vs. Leaving Group Ability: E1cb Elimination Reactions base rds krel = 1 krel = <10–8 krel = 10+4 + pKa HX 10 0 9.5 Stirling, Chem. Commun. 1975, 940 The greater the structural reorganization of the leaving group during E1cb elimination, the slower the rate of elimination. + ■ Protonation of Conjugate bases Kinetic product Kinetic product Keq ~ 10+5 Jack Hine: Least Motion Principle (Adv. Phys. Org. Chem. 1977, 15, 1) Lowry & Richardson, 3rd Edition, pp 205-206 Those elementary reactions that involve the least change in atomic posiitons will be favored pKa(H2O) ~10 pKa(H2O) ~10