Chapter 18 Enols and Enolates

1. Chapter 18Enols and Enolates

2. 18.1The -Carbon Atom and its pKa

3. O CH3CH2CH2CH Terminology • The reference atom is the carbonyl carbon. • Other carbons are designated , , , etc. on the basis of their position with respect to the carbonyl carbon. • Hydrogens take the same Greek letter as the carbon to which they are attached.   

4. •• •• O O •• •• – R2C R2C CR' CR' •• H Enolate ion •• – O pKa = 16-20 •• •• R2C CR' Acidity of -Hydrogen + H+

5. O O (CH3)2CHCH CCH3 pKa = 15.5 pKa = 18.3 Acidity of -Hydrogen

6. O O C C C H3C CH3 H H O O – C C •• + H+ C H3C CH3 H -Diketones Are Much More Acidic pKa = 9

7. – •• •• O O •• •• •• C C C H3C CH3 H •• •• O O •• •• C C •• C H3C CH3 – H -Diketones Are Much More Acidic • Enolate of -diketone is stabilized; negative charge is shared by both oxygens.

8. – – •• •• •• •• O O O O •• •• •• •• •• •• C C C C C C H3C H3C CH3 CH3 H H •• •• O O •• •• C C •• C H3C CH3 – H -Diketones Are Much More Acidic

9. 18.2The Aldol Condensation

10. O O – •• •• RCH2CH RCHCH OH HOH •• •• •• Some Thoughts... + + • A basic solution contains both the aldehyde and its enolate. • Aldehydes undergo nucleophilic addition. • Enolate ions are nucleophiles. • What about nucleophilic addition of enolate to aldehyde? •• – pKa = 16-20 pKa = 15.7

11. •• O •• •• •• O – O •• •• RCHCH RCHCH RCHCH RCH2CH RCH2CH RCH2CH O O •• H O •• •• •• •• •• – •• O O NaOH RCH2CH CHCH 2 RCH2CH R OH ••

12. O RCH2CH CHCH R OH Aldol Addition • Product is called an "aldol" because it is both an aldehyde and an alcohol.

13. O O NaOH, H2O 2 CH3CH CH3CH CH2CH 5°C OH Aldol Addition of Acetaldehyde Acetaldol(50%)

14. O 2 CH3CH2CH2CH O CHCH CH3CH2CH2CH CH2CH3 OH (75%) Aldol Addition of Butanal KOH, H2O 6°C

15. O O RCH2CH CHCH 2 RCH2CH R OH Aldol Condensation NaOH

16. O O RCH2CH CHCH 2 RCH2CH R OH heat NaOH,heat O RCH2CH CCH R Aldol Condensation NaOH

17. O 2 CH3CH2CH2CH O CCH CH3CH2CH2CH CH2CH3 (86%) Aldol Condensation of Butanal NaOH, H2O 80-100°C

18. C C O O H C C OH C C Dehydration of Aldol Addition Product • Dehydration of -hydroxy aldehyde can becatalyzed by either acids or bases.

19. C C O O H – C C •• OH OH C C Dehydration of Aldol Addition Product • In base, the enolate is formed. NaOH

20. C C O O H – C C •• OH OH C C Dehydration of Aldol Addition Product • The enolate loses hydroxide to form the ,-unsaturated aldehyde. NaOH

21. O O OH 2% 2 CH3CCH3 CH3CCH2CCH3 98% CH3 Aldol Reactions of Ketones • The equilibrium constant for aldol addition reactions of ketones is usually unfavorable.

22. O O O O (96%) via: OH Intramolecular Aldol Condensation Na2CO3, H2O heat

23. O O O (96%) Intramolecular Aldol Condensation • Even ketones give good yields of aldol condensation products when the reaction is intramolecular. Na2CO3, H2O heat

24. 18.3Mixed Aldol Condensations

25. O O CH3CH2CH CH3CH What Is the Product? • There are 4 possibilities because the reaction mixture contains the two aldehydes plus the enolate of each aldehyde. NaOH +

26. O O CH3CH2CH CH3CH O CH3CH CH2CH O O OH – CH2CH •• What Is the Product? + – CH3CHCH ••

27. O O CH3CH2CH CH3CH O CH3CH2CH CHCH O O CH3 OH – CH2CH •• What Is the Product? + – CH3CHCH ••

28. O O CH3CH2CH CH3CH O CH3CH CHCH O O CH3 OH – CH2CH •• What Is the Product? + – CH3CHCH ••

29. O O CH3CH2CH CH3CH O CH3CH2CH CH2CH O O OH – CH2CH •• What Is the Product? + – CH3CHCH ••

30. In Order to Effectively Carry Outa Mixed Aldol Condensation: • Need to minimize reaction possibilities. • Usually by choosing one component that cannot form an enolate.

31. O HCH Formaldehyde • Formaldehyde cannot form an enolate. • Formaldehyde is extremely reactive toward nucleophilic addition.

32. O O O HCH (CH3)2CHCH2CH (CH3)2CHCHCH CH2OH Formaldehyde K2CO3 + water-ether (52%)

33. O CH3O CH Aromatic Aldehydes • Aromatic aldehydes cannot form an enolate.

34. O O CH3CCH3 CH3O CH O CHCCH3 CH3O CH Aromatic Aldehydes + NaOH, H2O 30°C (83%)

35. Converting Ketones to Enolates for Reaction with Aldehyde • Use very strong base like lithium diisopropylamide (LDA), then react with aldehyde.

36. 18.4Alkylation of Enolate Anions

37. Enolate Ions in SN2 Reactions • Enolate ions are nucleophiles and react withalkyl halides. • With a very strong base like LDA, simple enolates can be alkylated without competition from aldol condensation. • Enolates derived from -diketones are more readily alkylated than simple enolates.

38. O O O O CH3CCH2CCH3 CH3 Example K2CO3 + CH3I CH3CCHCCH3 (75-77%)

39. 18.5 Enolization and Enol Content

40. H •• O H O •• •• •• R2C CR' H O H •• •• H •• O H •• R2C CR' Enolization (or Keto-EnolTautomerism) Ketone or aldehyde (keto form) Note: keto and enol forms are constitutional isomers. Enol

41. Mechanism of Enolization(Base-Catalyzed) •• O •• R2C CR' – •• O H •• •• H

42. H – •• O H O •• •• •• •• R2C CR' Mechanism of Enolization(Base-Catalyzed) •• O H •• H

43. H – •• O H O •• •• •• R2C CR' Mechanism of Enolization(Base-Catalyzed) ••

44. H – O •• •• •• Mechanism of Enolization(Base-Catalyzed) •• O H •• R2C CR'

45. H •• O H O •• •• + H R2C CR' H Mechanism of Enolization(Acid-Catalyzed)

46. Mechanism of Enolization(Acid-Catalyzed) H + •• H O O •• •• H R2C CR' H

47. H O •• •• H Mechanism of Enolization(Acid-Catalyzed) + •• H O R2C CR' H

48. •• H O •• R2C CR' H + O H •• H Mechanism of Enolization(Acid-Catalyzed)

49. OH O R2CHCR' R2C CR' Enol Content • Percent enol is usually very small. • Keto form usually 45-60 kJ/mol more stablethan enol. • C=O is stronger than C=C. keto enol

50. OH O CH3CH H2C CH OH O CH3CCH3 H2C CCH3 Enol Content Acetaldehyde K = 3 x 10-7 Acetone K = 6 x 10-9