Aldol Condensation Reaction Mr. R. B. Gawade M. Sc. NET / GATE Assistant Professor Department of Chemistry S. M. Joshi College Hadapsar Pune

Aldehydes undergo nucleophilic addition. Some thoughts... RCH2CH O RCHCH O •• 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

•• RCHCH O • • – RCH2CH 3

O – RCHCH RCHCH RCHCH RCH2CH RCH2CH RCH2CH O O O H – •• • • • • •• • • 3

RCHCH O – – RCH2CH O RCHCH RCH2CH O RCHCH H RCH2CH O 2RCH2CH O RCH2CH •• • • – – RCH2CH O •• • • RCHCH RCH2CH O •• • • RCHCH H •• RCH2CH O •• • • •• 2RCH2CH O RCH2CH OH CHCH O R NaOH 3

Aldol Addition RCH2CH OH CHCH O R product is called an "aldol" because it is both an aldehyde and an alcohol 5

Aldol Addition of Acetaldehyde 2CH3CH O CH3CH OH CH2CH O NaOH, H2O 5°C Acetaldol (50%) 6

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

Aldol Condensation 2RCH2CH O RCH2CH OH CHCH O R NaOH 3

Aldol Condensation 2RCH2CH O RCH2CH OH CHCH O R NaOH 3

Aldol Condensation 2RCH2CH O RCH2CH OH CHCH O R NaOH heat O RCH2CH CCH 3

Aldol Condensation 2RCH2CH O RCH2CH OH CHCH O R NaOH NaOH heat heat O CCH R 3

Aldol Condensation of Butanal 2CH3CH2CH2CH O NaOH, H2O 80-100°C 6

Aldol Condensation of Butanal 2CH3CH2CH2CH O NaOH, H2O 80-100°C CH3CH2CH2CH CCH O CH2CH3 (86%) 6

Dehydration of Aldol Addition Product OH H C O C O dehydration of b-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 a,b-unsaturated aldehyde 12

Aldol reactions of ketones 2CH3CCH3 O O CH3CCH2CCH3 OH CH3 2% 98% the equilibrium constant for aldol addition reactions of ketones is usually unfavorable 16

Intramolecular Aldol Condensation (96%) Na2CO3, H2O heat O OH via: 19

Intramolecular Aldol Condensation (96%) Na2CO3, H2O heat even ketones give good yields of aldol condensation products when the reaction is intramolecular 19

18.10 Mixed Aldol Condensations

What is the product? O O NaOH + CH3CH2CH CH3CH There are 4 possibilities because the reaction mixture contains the two aldehydes plus the enolate of each aldehyde. 21

What is the product? CH3CH O CH3CH2CH O + CH3CH OH CH2CH O CH2CH O O – • • – – CH3CHCH •• 21

What is the product? CH3CH O CH3CH2CH O + CH3CH2CH OH CHCH O CH3 CH2CH • • – – CH3CHCH •• 21

What is the product? CH3CH O CH3CH2CH O + CH3CH OH CHCH O CH3 CH2CH O • • – – CH3CHCH •• 21

What is the product? CH3CH O CH3CH2CH O + CH3CH2CH OH CH2CH O CH2CH O • • – – CH3CHCH •• 21

In order to effectively carry out a mixed aldol condensation: need to minimize reaction possibilities usually by choosing one component that cannot form an enolate 22

formaldehyde cannot form an enolate HCH formaldehyde cannot form an enolate formaldehyde is extremely reactive toward nucleophilic addition 23

Formaldehyde O HCH (CH3)2CHCH2CH O (CH3)2CHCHCH O CH2OH + (52%) K2CO3 water- ether (52%) 23

aromatic aldehydes cannot form an enolate CH3O CH O aromatic aldehydes cannot form an enolate 24

Aromatic Aldehydes CH3O CH O CH3CCH3 O + NaOH, H2O 30°C CH3O CH CHCCH3 (83%) 24

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