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

Example 6

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

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

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

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

18.8 Some Chemical and Stereochemical Consequences of Enolization

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

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

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

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

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

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

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

18.9 The Aldol Condensation

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

3

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

Aldol Addition of Acetaldehyde 6

Aldol Addition of n-Butanal 6

Aldol Condensation 3

Aldol Condensation of Butanal 6

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

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

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

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

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

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 5.7-5.12 (elimination reactions) Review 17-7-17.7 (carbonyl addition)