《有机化学》课程PPT教学课件（Organic Chemistry，5th Edition，L. G. Wade, Jr.，Prentice Hall）Chapter 22 Alpha Substitution and Condensations of Enols and Enolate Ions

Organic Chemistry,5th Edition L.G.Wade,Jr. Chapter 22 Alpha Substitution and Condensations of Enols and Enolate lons Jo Blackburn Richland College,Dallas,TX Dallas County Community College District ©2003，Prentice Hall

Chapter 22 Alpha Substitution and Condensations of Enols and Enolate Ions Jo Blackburn Richland College, Dallas, TX Dallas County Community College District © 2003, Prentice Hall Organic Chemistry, 5th Edition L. G. Wade, Jr

Alpha Substitution Replacement of a hydrogen on the carbon adjacent to the carbonyl,C=O. Step 1:Deprotonation Step 2:Attack on electrophile H enolate ion Chapter 22

Chapter 22 2 Alpha Substitution Replacement of a hydrogen on the carbon adjacent to the carbonyl, C=O. enolate ion =>

Condensation with Aldehyde or Ketone Enolate ion attacks a C=O and the alkoxide is protonated.The net result is addition. ROH Chapter 22 3=>

Chapter 22 3 Condensation with Aldehyde or Ketone Enolate ion attacks a C=O and the alkoxide is protonated. The net result is addition. C O C _ C O C O C C O _ ROH C O C C OH =>

Condensation with Esters Loss of alkoxide ion results in nucleophilic acyl substitution. Step 1:Addition of the enolate Step 2:Elimination of the alkoxide C=0 COR- +RO- enolate ester substitution product Chapter 22 4

Chapter 22 4 Condensation with Esters Loss of alkoxide ion results in nucleophilic acyl substitution. =>

Keto-Enol Tautomers Tautomers are isomers which differ in the placement of a hydrogen. One may be converted to the other. 。In base: Step 1:Deprotonation on C Step 2:Reprotonation on O HO: C=( enol form keto form enolate ion (vinyl alcohol) Chapter 22 5

Chapter 22 5 Keto-Enol Tautomers • Tautomers are isomers which differ in the placement of a hydrogen. • One may be converted to the other. • In base: =>

Keto-Enol Tautomers(2) Tautomerism is also catalyzed by acid. 。In acid: Step /Protonation on O Step 2:Deprotonation on C H HO: >C=C+H,0 keto form protonated carbonyl enol form => Chapter 22 6

Chapter 22 6 Keto-Enol Tautomers (2) • Tautomerism is also catalyzed by acid. • In acid: =>

Equilibrium Amounts For aldehydes and ketones,the keto form is greatly favored at equilibrium. An enantiomer with an enolizable hydrogen can form a racemic mixture. enolizable hydrogens CH3 CH3 H+orOH H a carbons (R)configuration enol (achiral) (S)configuration Chapter 22 7=>

Chapter 22 7 Equilibrium Amounts • For aldehydes and ketones, the keto form is greatly favored at equilibrium. • An enantiomer with an enolizable hydrogen can form a racemic mixture. =>

D 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). In the presence of hydroxide or alkoxide ions,only a small amount of enolate ion is present at equilibrium. => Chapter 22 8

Chapter 22 8 Acidity of -Hydrogens • pKa for -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). • In the presence of hydroxide or alkoxide ions, only a small amount of enolate ion is present at equilibrium. =>

Enolate Reaction enolate ion reacts with E+ RC—CH—R +H20 人→E R-C-CH2-R' +OH R-C CHR As enolate ion reacts with the electrophile,the equilibrium E shifts to produce more. => Chapter 22 9

Chapter 22 9 Enolate Reaction => As enolate ion reacts with the electrophile, the equilibrium shifts to produce more

Acid-Base Reaction to Form Enolate Very strong base is required for complete reaction. CH3 CH3 HC HC H3CN-H n-BuLi Lithium HC-CH3 HC ~CH3 diisopropylamide O Li" LDA (-C3H)2N-H pK=19 pK2=40 Chapter 22

Chapter 22 10 Acid-Base Reaction to Form Enolate Very strong base is required for complete reaction. Lithium diisopropylamide N H HC CH3 H3C HC CH3 H3C n-BuLi N HC CH3 H3C HC CH3 H3C Li + _ O H H O - Li + H LDA + C3H7 ) (i- 2N H pKa = 19 pKa = 40 =>