1. 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

2. Example 6

3. 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. 6

4. 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. 6

5. First stage of a haloform reaction is substitution of all available hydrogens by halogen atoms.
Mechanism 6

6. Formation of the tri-a-halomethyl ketone is followed by its hydroxide-induced cleavage
Mechanism 6

7. 18.8 Some Chemical and Stereochemical Consequences of Enolization

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

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

10. Mechanism O H – D + OD – O H D OD • • •• •• • • ••
Bridgehead Carbonyl Compounds? 2

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

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

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

14. 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

15. 18.9 The Aldol Condensation

16. Some thoughts... RCH2CH O RCHCH O OH – HOH + + – pKa = 16-20 pKa = 16•• OH
• • – ••
HOH + + •• –
pKa = 16-20
pKa = 16
A basic solution contains comparable amounts of the aldehyde and its enolate.
Aldehydes undergo nucleophilic addition.
Enolate ions are nucleophiles.
What about nucleophilic addition of enolate to aldehyde? 2

17. 3

18. Aldol Addition
This product is called an "aldol" because it is both an aldehyde and an alcohol 5

19. Aldol Addition of Acetaldehyde6

20. Aldol Addition of n-Butanal6

21. Aldol Condensation 3

22. Aldol Condensation of Butanal6

23. Dehydration of Aldol Addition ProductOH H C O C O
dehydration of -hydroxy aldehyde can be catalyzed by either acids or bases 12

24. Dehydration of Aldol Addition ProductOH H C O OH C O
• • –
NaOH
in base, the enolate is formed 12

25. Dehydration of Aldol Addition ProductOH H C O OH C O
• • –
NaOH
the enolate loses hydroxide to form the ,-unsaturated aldehyde 12

26. Aldol reactions of ketones
the equilibrium constant for aldol addition reactions of ketones is usually unfavorable 16

27. Intramolecular Aldol Condensation
even ketones give good yields of aldol condensation products when the reaction is intramolecular 19

28. Information Suggested Problems: 18.26-18.37
New Chp. 15 & 17 problem set now available
Office Hour: Today, 3.30 P.M., SES 170
Revise Chapter (elimination reactions)
Review (carbonyl addition)