1. 18.6 Base-Catalyzed Enolization: Enolate Anions

2. Acidity of a-Hydrogen O R2C CR' H O – R2C CR' + H+ pKa = 16-20 •• • •35

3. Acidity of a-Hydrogen O R2C CR' H R2C CR' O – + H+ R2C CR' O –••
R2C
CR'
• • H ••
R2C
CR' O
• • –
+ H+
R2C
CR' O ••
• • –
pKa = 16-20 35

4. Acidity of a-Hydrogen O R2C CR' H R2C CR' O – + H+ enolate ion R2C CR'••
R2C
CR'
• • H
R2C
CR' O ••
• • –
+ H+
enolate ion
R2C
CR' O
• • – ••
pKa = 16-20 35

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

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

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

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

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

10. Acidity of a-Hydrogen
(CH3)2CHCH O
CCH3 O
pKa = 15.5
pKa = 15.8 40

11. b-Diketones are much more acidic
CH3CCH2CCH3 O
pKa = 9 40

12. b-Diketones are much more acidic
H3C C
CH3 O H
Ka = 10–9
H3C C
CH3 O H H+ + •• – 41

13. b-Diketones are much more acidic
enolate of b-diketone is stabilized; negative charge is shared by both oxygens O O – C •• C
H3C C
CH3 H 41

14. b-Diketones are much more acidic
H3C C
CH3 O H – ••
• •
H3C C
CH3 O H •• –
• • 41

15. b-Diketones are much more acidic– H C
CH3 O ••
• •
H3C
H3C C
CH3 O H •• –
• • 41

16. 18.7 The Haloform Reaction 8

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. 6

18. Example (CH3)3CCCH3 O Br2, NaOH, H2O (CH3)3CCONa O + CHBr3 H+
(CH3)3CCOH O
(71-74%) 6

19. 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.
(CH3)3CCCH3 O
ArCCH3 O
RCH2CCH3 O
yes
yes no 6

20. First stage is substitution of all available a hydrogens by halogen
Mechanism
First stage is substitution of all available a hydrogens by halogen
RCCH3 O
RCCX3 O
X2, HO–
X2, HO–
RCCH2X O
RCCHX2 O
X2, HO– 6

21. Mechanism
Formation of the trihalomethyl ketone is followed by its hydroxide-induced cleavage RC O
• • ••
CX3 •• – RC O
• • HO
CX3 HO
• • – •• + •• RC O
• • •• RC O
• • OH – –
• •
CX3 +
HCX3 +
• • 6

22. 18.8 Some Chemical and Stereochemical Consequences of Enolization

23. Hydrogen-Deuterium Exchange+
4D2O
KOD, heat O D +
4DOH 2

24. Mechanism O H
• • •• OD
• • – •• + H O
• • – •• •• +
HOD •• 2

25. Mechanism H O
• • – •• 2

26. Mechanism O H D
• • •• OD
• • – •• + H O
• • – •• OD •• D 2

27. Stereochemical Consequences of Enolization
H3O+
50% R 50% S C
CC6H5 O H
CH3CH2
H3C
50% R 50% S
100% R
H2O, HO– 2

28. Enol is achiral C
CC6H5 O H
CH3CH2
H3C
CC6H5 OH C
H3C
CH3CH2 R 2

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

30. Results of Rate Studies
Equal rates for: racemization H-D exchange bromination iodination
Enol is intermediate and its formation is rate-determining C
CC6H5 O H
CH3CH2
H3C 2