18.6 Base-Catalyzed Enolization: Enolate Anions

1. 18.6Base-Catalyzed Enolization:Enolate Anions

2. •• O •• R2C CR' H Acidity of a-Hydrogen •• O •• – R2C CR' + H+ •• pKa = 16-20

3. •• •• O O •• •• – R2C R2C CR' CR' •• H •• – O •• •• R2C CR' Acidity of a-Hydrogen + H+ pKa = 16-20

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

5. Mechanism of Enolization(Base-catalyzed) •• O •• R2C CR' – •• O H •• •• H

6. – •• O •• •• R2C CR' Mechanism of Enolization(Base-catalyzed) •• O H •• H

7. H – •• O H O •• •• •• R2C CR' Mechanism of Enolization(Base-catalyzed) ••

8. H – •• O H O •• •• •• R2C CR' Mechanism of Enolization(Base-catalyzed) ••

9. H – O •• •• •• Mechanism of Enolization(Base-catalyzed) •• O H •• R2C CR'

10. O O (CH3)2CHCH CCH3 Acidity of a-Hydrogen pKa = 15.5 pKa = 15.8

11. O O CH3CCH2CCH3 b-Diketones are much more acidic pKa = 9

12. O O C C C H3C CH3 H H O O – C C •• + H+ C H3C CH3 H b-Diketones are much more acidic Ka = 10–9

13. O O b-Diketones are much more acidic enolate of b-diketone is stabilized; negative charge is shared by both oxygens – C C •• C H3C CH3 H

14. – •• •• O O •• •• •• C C C H3C CH3 H •• •• O O •• •• C C •• C H3C CH3 – H b-Diketones are much more acidic

15. •• •• O O •• •• •• C C C CH3 H •• •• O O •• •• C C •• C H3C CH3 – H b-Diketones are much more acidic – H3C

16. 18.7The Haloform Reaction

17. The Haloform Reaction Under basic conditions, halogenation of a methyl ketone often leads to carbon-carbon bond cleavage. Such cleavage is called the haloform reaction because chloroform, bromoform, or iodoform is one of the products.

18. O (CH3)3CCCH3 O (CH3)3CCONa O (CH3)3CCOH Example Br2, NaOH, H2O + CHBr3 H+ (71-74%)

19. O O O ArCCH3 (CH3)3CCCH3 RCH2CCH3 The Haloform Reaction The haloform reaction is sometimes used as a method for preparing carboxylic acids, but works well only when a single enolate can form. yes yes no

20. O O RCCH3 RCCX3 O O RCCH2X RCCHX2 Mechanism First stage is substitution of all available a hydrogens by halogen X2, HO– X2, HO– X2, HO–

21. – •• •• O O •• •• •• •• – CX3 CX3 HO RC RC •• •• HO •• •• •• •• O O •• •• – •• •• CX3 RC RC O OH •• •• •• Mechanism Formation of the trihalomethyl ketone is followed by its hydroxide-induced cleavage + – + + HCX3 ••

22. 18.8Some Chemical and StereochemicalConsequences of Enolization

23. O H H H H O D D D D Hydrogen-Deuterium Exchange + 4D2O KOD, heat + 4DOH

24. •• O •• – H H •• OD •• H H •• – •• O •• •• H H H Mechanism + •• + HOD ••

25. – •• O •• •• H H H Mechanism

26. •• O •• – H D •• OD •• H H •• – •• O •• •• H •• H OD D H •• Mechanism +

27. H O H3C CC6H5 C CH3CH2 Stereochemical Consequences of Enolization H3O+ 50% R50% S 50% R50% S 100% R H2O, HO–

28. H H3C OH O H3C C CC6H5 CC6H5 C CH3CH2 CH3CH2 Enol is achiral R

29. O C H3C OH C CC6H5 H CH3CH2 O H3C CC6H5 C CH3CH2 Enol is achiral H3C H CC6H5 S 50% CH3CH2 50% R

30. H O H3C CC6H5 C CH3CH2 Results of Rate Studies Equal rates for:racemizationH-D exchangebrominationiodination Enol is intermediate and its formation is rate-determining