Acids and Bases in Organic Chemistry

ACIDS & BASES : ACIDS & BASES IN ORGANIC CHEMISTRY

ACIDS & BASES : ACIDS & BASES As steps in rxn mechanisms As catalysts In conformational analysis (e.g., a acid pKa’s and protein folding)

OBJECTIVES : OBJECTIVES Identify most acidic H in structure Estimate Kab

FIVE STRUCTURAL FEATURES : FIVE STRUCTURAL FEATURES electronegativity inductive (‘EN-2’) hybridization resonance bond dissociation energy

FIVE STRUCTURAL FEATURES : FIVE STRUCTURAL FEATURES electronegativity inductive (‘EN-2’) hybridization resonance bond dissociation energy stability of c base reactivity of acid

ELECTRONEGATIVITY : ELECTRONEGATIVITY The more EN the atom bearing the negative charge....in the c base....the more stable the c base...and the more acidic the acid. CH4.........55 NH3........35 H2O.........16 HF..........3.5

INDUCTIVE : INDUCTIVE EN functional groups close to a H acidify that H. The more EN...and/or the closer the group....the larger the effect. CF3CO2H......0.30 CCl3CO2H......0.70 CH3CO2H.....4.7

INDUCTIVE : INDUCTIVE CH3CO2H.....4.7 CF3(CH2)3CO2H.......4.6

HYBRIDIZATION : HYBRIDIZATION

RESONANCE : RESONANCE ethanol vs acetic acid CH3CH2OH CH3CO2H

RESONANCE : RESONANCE ethanol vs acetic acid CH3CH2OH CH3CO2H

RESONANCE : RESONANCE ethanol vs acetic acid CH3CH2OH.....16 CH3CO2H....4.7 Both O-H Both O-sp3 (some inductive from carbonyl for a acid)

RESONANCE DELOCALIZATION STABILIZES ACETATE : RESONANCE DELOCALIZATION STABILIZES ACETATE

ACETONE vs Di-tert-BUTYL ETHER : ACETONE vs Di-tert-BUTYL ETHER

PHENOL vs CYCLOHEXANOL : PHENOL vs CYCLOHEXANOL

CUMMULATIVE EFFECT : CUMMULATIVE EFFECT acetone vs 2,4-pentanedione

BOND DISSOCIATION ENERGY : BOND DISSOCIATION ENERGY HF HCl HBr HI HI > HBr > HCl > HF opposite EN’s increasing BDE’s

BOND DISSOCIATION ENERGY : BOND DISSOCIATION ENERGY H2S > H2O Up/down a group

FINDING THE MOST ACIDIC H : FINDING THE MOST ACIDIC H Identify one or more.....or none...of the five structural factors The more factors for a given H....the more acidic For same # factors, consult pKa table

FINDING THE MOST ACIDIC H : FINDING THE MOST ACIDIC H

FIND...AND ORDER....THE THREE MOST ACID H’s : FIND...AND ORDER....THE THREE MOST ACID H’s

FIND...AND ORDER....THE FOUR MOST ACID H’s : FIND...AND ORDER....THE FOUR MOST ACID H’s

PREDICTING ACID-BASE EQUILIBRIA : PREDICTING ACID-BASE EQUILIBRIA An acid-base reaction is favorable (Kab >>1) when a weaker c acid is formed from a stronger acid An acid-base reaction is favorable when the DpKa for acid-to-c acid goes up

STEPS:Org-H + B- Org- + BH : STEPS:Org-H + B- Org- + BH Identify most acidic H in Org-H Estimate pKa for Org-H comparable structure from table additional factors in Org-H? Estimate pKa for BH If pKa (Org-H) < pKa (BH), Kab > 1 If pKa (Org-H) > pKa (BH), Kab < 1 Kab ??

STEPS : STEPS ID most acidic H in Org-H Identify factors in Org-H Identify factors in BH Kab < 1: more factors in BH Kab > 1: fewer factors in BH

EXAMPLES : EXAMPLES

THE REACTION : THE REACTION

pKa Table : pKa Table ............. ........... CH3CO2H 4.7 ........... ........... H2O 15.7 CH3CH2OH 16.4 .............. ............. NH3 35 ..............

pKa Table : pKa Table ............. ........... CH3CO2H 4.7 ........... ........... H2O 15.7 CH3CH2OH 16.4 .............. ............. NH3 35 ..............

THE REACTION : THE REACTION ~ 35 ~ 16 If pKa (Org-H) < pKa (BH), Kab > 1 If pKa (Org-H) > pKa (BH), Kab < 1

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NOT IN TABLE.... : NOT IN TABLE.... ????

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