D. A. Evans Acidity Trends for Carbonyl Related Compounds Chem 206 I The Gibbs Relationship a Medium Effects on the pKa of HOH AG°= RTIo K HOH pKa Medium 23RT=14 The gas phase ionization of HOH is HOH or△G°=-23RTg1K att= endothermic by 391 kcal/mol !! DMSO in kcal. mor1 △G298=-14l0g1 279(est) Vacuum Representative pKa Data △G298=14pk≈14pK Substrate HOH Hence, pKa is proportional to the free energy change 7. 7.7 0 290 13.7 C6H5OH 18.0 99 8.1 2. 8 kcal/mol Reaction coordinate O2N-CH3 17.2 7.2 I Medium Effects Consider the ionization process Ph-C-CH 246 7.6 H-A solvent= A:+ solvent(H) The change in pKa in going from water to DMSO is increasingly diminished as the conjugate base becomes resonance stabilized(Internal solvation) In the ionization of an acid in solution, the acid donates a proton to the medium. The more basic the medium, the larger the dissociation equilibrium. The ability of the medium to stabilize the conjugate base also plays an important role in the promotion of ionization. Let us consider two solvents, HOH and DMSO and the performance of ubstrate HOH these solvents in the ionization process. 160 2.1 The Protonated Solvent Conjug Base Stabiliz 0→H—A 164 DMSo HO-S+ No H-bonding Capacity 133 As shown ough HOH can stabilize anions via H-bonding, DMSO cannot NCCN 11.1 11.2 will show a greater propensity to dissociate in HOH. As illustrated below the acidity constants of water in HOH, DMSO and in a vacuum dramatically reflect this trend.31.2 14.7 29.0 18.0 17.2 24.6 17 10.0 9.9 15.3 7.0 15.7 18.1 16.0 13.3 8.9 16.4 13.3 11.1 11.2 H A H O + H H S + Me Me HO O H H A – HA A EtO OEt O O Me Me O O HOH C6H5OH NC CN HSH MeOH O2N–CH3 Ph C O CH3 DMSO DMSO HOH HOH HOH DMSO D. A. Evans Chem 206 D G° = - RT ln K or D G° = – 2.3 RT log10 K 2.3 RT = 1.4 at T = 298 K in kcal × mol-1 D G°298 = - 1.4 log10 Keq with pK = – log10 D G°298 = 1.4 pKeq » 1.4 pKa K Hence, pKa is proportional to the free energy change Keq pKeq D G° 1 10 100 0 - 1 - 2 0 - 1.4 - 2.8 kcal/mol Energy Reaction coordinate D G° ■ The Gibbs Relationship Consider the ionization process: + solvent + solvent(H+ A: ) – In the ionization of an acid in solution, the acid donates a proton to the medium. The more basic the medium, the larger the dissociation equilibrium. The ability of the medium to stabilize the conjugate base also plays an important role in the promotion of ionization. Let us consider two solvents, HOH and DMSO and the performance of these solvents in the ionization process. The Protonated Solvent Conjug. Base Stabiliz. Water DMSO No H-bonding Capacity As shown above, although HOH can stabilize anions via H-bonding, DMSO cannot. Hence, a given acid will show a greater propensity to dissociate in HOH. As illustrated below the acidity constants of water in HOH, DMSO and in a vacuum dramatically reflect this trend. ■ Medium Effects HOH pKa Medium 15.7 31 279 (est)** Vacuum ** The gas phase ionization of HOH is endothermic by 391 kcal/mol !!! Substrate D pKa 15.5 7.7 13.7 8.1 7.2 7.6 ■ Medium Effects on the pKa of HOH ■ Representative pKa Data Acidity Trends for Carbonyl & Related Compounds The change in pKa in going from water to DMSO is increasingly diminished as the conjugate base becomes resonance stabilized (Internal solvation!). Substrate D pKa 2.1 3.1 0 4.5