D. A Evans Phenol Acidity: An Analysis of Resonance& Inductive Effects Chem 206 ■ Phenol Acidity a Is the benzene ring somehow special. i. e "larger resonance space Acetone enol acetone acetone enol Keg 10 a=109H2C his topic has a number of take-home lessons. Most importantly, isis a useful construct on which to discuss the role of FG's in influencing the acidity of this The surprising facts is that the acetone enol has nearby the same pKa as phenol How does one analyze the impact of structure on pKa of a weak Hence, the answer to the above question is no! acid ( pKa>0)? a How important are inductive effects in the stabilization of C6Hso ■ The Approach: vmm时x For equilibria such as that presented X-oH pKa(H2O) above, analyze the effect of stabilizing X一OH CH3-OH 155 more energetic constituent which △G° As the electronegativity of X increases this case is the conjugate base the acidity of X-OH increases CF3CH2-OH 12 Cl-OH 7.5 a Why is phenol so much more acidic than cyclohexanol? pKa of X-OH This argument suggests that the acidity of acetone enol is largely due to inductive stabilization not resonance H pKa(H2O)=10 D HOCI (7.5) H pKa(H2O)=17 acetone enol (10.9) Loudon(pg 730): The enhanced acidity of phenol is due largely to stabilization of its conjugate base by resonance phenol ( 10.0) 0→0 from previous discussion, A 298=-1.4 Log10 Keq =1.4 pKeq AG(stab)=1.4(Pkaphenol-pKa cyclohenanod=1. 4(-7)=9.8 kcal/mol a of X-oh2 2.2 2.4 2.6 2.8 3 3.2 Electronegativity of X 6 8 10 12 14 16 pKa of X–OH HOCl (7.5) HOH (15.7) acetone enol (10.9) phenol (10.0) ■ Why is phenol so much more acidic than cyclohexanol? ■ The Approach: ■ Is the benzene ring somehow special. i.e "larger resonance space." ■ Acetone enol: How important are inductive effects in the stabilization of C6H5O – ■ ? Me H OH H2C O – 2C Me X O – X OH CH3 OH CF3CH2 OH Cl OH X OH Me Me O O FG O – O – FG O FG OH O – O – O OH FG OH OH O – ■ Phenol Acidity: D. A. Evans Phenol Acidity: An Analysis of Resonance & Inductive Effects Chem 206 + H+ This topic has a number of take-home lessons. Most importantly, is is a useful construct on which to discuss the role of FG's in influencing the acidity of this oxygen acid. ■ How does one analyze the impact of structure on pKa of a weak acid (pKa > 0) ? + solvent(H+ ) DG° Energy (1) DG° For equilibria such as that presented above, analyze the effect of stabilizing (or destabilizing) interactions on the more energetic constituent which in this case is the conjugate base. DG° + H+ pKa (H2O) = 10 + H pKa (H2O) = 17 + DG° Loudon (pg 730): "The enhanced acidity of phenol is due largely to stabilization of its conjugate base by resonance." – – – DG° (stab) = 1.4(Pkaphenol – pKacyclohenanol) = 1.4(-7) = 9.8 kcal/mol from previous discussion, D G˚298 = –1.4 Log10 Keq = 1.4 pKeq + H (1) + acetone acetone enol acetone enolate Keq = 10-8 pKa = 10.9 The surprising facts is that the acetone enol has nearly the same pKa as phenol. Hence, the answer to the above question is no! Consider the following general oxygen acid X–OH where X can only stabilize the conjugate base through induction: + H+ pKa(H2O) 15.5 12.4 7.5 As the electronegativity of X increases the acidity of X–OH increases. If you take the calculated electronegativity of an SP2 carbon (2.75) you can see that there is a linear correlation between the electronegativity of X and the pKa of X–OH. This argument suggests that the acidity of acetone enol is largely due to inductive stabilization, not resonance