《有机化学》课程PPT教学课件（Official PPT of Organic Chemistry, 7th Edition, L. G. Wade, Jr.Pearson Education）Chapter 22 Condensations and Alpha Substitutions of Carbonyl Compounds

Organic Chemistry,7th Edition L.G.Wade,Jr. Chapter 22 Condensations and Alpha Substitutions of Carbonyl Compounds Copyright 2010 Pearson Education,Inc

Chapter 22 Copyright © 2010 Pearson Education, Inc. Organic Chemistry, 7th Edition L. G. Wade, Jr. Condensations and Alpha Substitutions of Carbonyl Compounds

Alpha Substitution enolate ion Copyright 2010 Pearson Prentice Hall,Inc. Alpha substitution is the substitution of one of the hydrogens attached to the alpha-carbon for an electrophile. The reaction occurs through an enolate ion intermediate. Chapter 22 2

Chapter 22 2 Alpha Substitution ▪ Alpha substitution is the substitution of one of the hydrogens attached to the alpha-carbon for an electrophile. ▪ The reaction occurs through an enolate ion intermediate

Condensation with an Aldehyde or Ketone OH ROH RO enolate ketone addition product Copyright 2010 Pearson Prentice Hall,Inc The enolate ion attacks the carbonyl group to form an alkoxide. Protonation of the alkoxide gives the addition product:a B-hydroxy carbonyl compound. Chapter 22 3

Chapter 22 3 Condensation with an Aldehyde or Ketone ▪ The enolate ion attacks the carbonyl group to form an alkoxide. ▪ Protonation of the alkoxide gives the addition product: a b-hydroxy carbonyl compound

Condensation with Esters RO enolate ester tetrahedral intermediate substitution product Copyright 2010 Pearson Prentice Hall.,Inc. The enolate adds to the ester to form a tetrahedral intermediate. Elimination of the leaving group (alkoxide)gives the substitution product (a B-carbonyl compound). Chapter 22 4

Chapter 22 4 Condensation with Esters ▪ The enolate adds to the ester to form a tetrahedral intermediate. ▪ Elimination of the leaving group (alkoxide) gives the substitution product (a b-carbonyl compound)

Keto-Enol Tautomers keto form enol form (99.99%) (0.01%) Tautomerization is an interconversion of isomers that occur through the migration of a proton and the movement of a double bond. Tautomers are not resonance form. Chapter 22 5

Chapter 22 5 Keto–Enol Tautomers O H H OH H keto form (99.99%) enol form (0.01%) ▪ Tautomerization is an interconversion of isomers that occur through the migration of a proton and the movement of a double bond. ▪ Tautomers are not resonance form

Base-Catalyzed Tautomerism HO: C=C +-OH enol form keto form enolate ion (vinyl alcohol) Copyright2010 Pearson Prentice Hall,Inc. In the presence of strong bases,ketones and aldehydes act as weak proton acids. A proton on the a carbon is abstracted to form a resonance- stabilized enolate ion with the negative charge spread over a carbon atom and an oxygen atom. The equilibrium favors the keto form over the enolate ion. Chapter 22 6

Chapter 22 6 Base–Catalyzed Tautomerism ▪ In the presence of strong bases, ketones and aldehydes act as weak proton acids. ▪ A proton on the a carbon is abstracted to form a resonance￾stabilized enolate ion with the negative charge spread over a carbon atom and an oxygen atom. ▪ The equilibrium favors the keto form over the enolate ion

Acid-Catalyzed Tautomerism HO: HO: C=C+H,0 keto form protonated carbonyl enol form Copyright 2010 Pearson Prentice Hall,Inc. In acid,a proton is moved from the a-carbon to oxygen by first protonating oxygen and then removing a proton from the carbon. Chapter 22 7

Chapter 22 7 Acid-Catalyzed Tautomerism ▪ In acid, a proton is moved from the a-carbon to oxygen by first protonating oxygen and then removing a proton from the carbon

Racemization enolizable hydrogens CH, CH H+or-OH a carbons (R)configuration enol (achiral) (S)configuration Copyright2010 Pearson Prentice Hall,Inc. For aldehydes and ketones,the keto form is greatly favored at equilibrium. ■ If a chiral carbon has an enolizable hydrogen atom,a trace of acid or base allows that carbon to invert its configuration,with the enol serving as the intermediate.This is called racemization. Chapter 22 8

Chapter 22 8 Racemization ▪ For aldehydes and ketones, the keto form is greatly favored at equilibrium. ▪ If a chiral carbon has an enolizable hydrogen atom, a trace of acid or base allows that carbon to invert its configuration, with the enol serving as the intermediate. This is called racemization

Acidity of a Hydrogens pKa for a H of aldehyde or ketone ~20. Much more acidic than alkane or alkene (pKa 40)or alkyne(pKa 25). Less acidic than water (pKa 15.7)or alcohol (pKa 16-19). Only a small amount of enolate ion is present at equilibrium. Chapter 22 9

Chapter 22 9 Acidity of a Hydrogens ▪ pKa for a H of aldehyde or ketone ~20. ▪ Much more acidic than alkane or alkene (pKa > 40) or alkyne (pKa = 25). ▪ Less acidic than water (pKa = 15.7) or alcohol (pKa = 16–19). ▪ Only a small amount of enolate ion is present at equilibrium

Formation and Stability of Enolate lons O H :0 R 1R'+OR R-C- R- ROH pKa=16-18 ketone or aldehyde major pKa20 enolate ion Example :Q一CH,CH3 CHCH,OH pKa=15.9 cyclohexanone ethoxide ion cyclohexanone enolate pKa =19 (equilibrium lies to the left) Copyright2010 Pearson Prentice Hall,Inc. The equilibrium mixture contains only a small fraction of the deprotonated,enolate form. Chapter 22 10

Chapter 22 10 Formation and Stability of Enolate Ions ▪ The equilibrium mixture contains only a small fraction of the deprotonated, enolate form