CHEMISTRY 226 THE ALDOL REACTION 1. Descriptive: The aldol reaction is a base-catalyzed reaction of a carbonyl compound. Technically, the term aldol reaction refers to nucleophilic addition of an enolate anion derived from an aldehyde to the carbonyl group of another molecule of the same aldehyde. The usage has been expanded to include any enolate anion addition to a carbonyl group. In an aldol reaction, one molecule serves as the enolate anion precursor; the other serves as the enolate anion acceptor. 2. The aldol reaction at low temperature: preparation of a ?-hydroxy aldehyde ? The general reaction RCH2CHO OH , 5o H2O (a ?-hydroxy aldehyde)2 RCH2CH CHCHO R OH ? Specific example ? Comments -The new carbon-carbon bond is formed between the ?-carbon of one molecule and the carbonyl carbon of the other. -Requirement: the aldehyde must have at least one ?-hydrogen (removed to form the enolate anion. -The reaction is catalytic in base -Ketones normally fail to react 3. Mechanism of the aldol reaction at low temperature CH3CHO + OH CH2CHO + H2O CH2CHO+CH3CH O CH3CH CH2CHO O CH3CH CH2CHO O + H2O CH3CH OH CH2CHO + OH 4. The aldol reaction at elevated temperature: synthesis of ???-unsaturated carbonyl compounds ? The general reaction RCH2CHO OH, 100 o H2O RCH2CH CCHO R (an ???-unsaturated aldehyde) ? Specific example CH3CHO CH3CHCH2CHO OH 2 OH, 80o H2O CH3CH CHCHO CH3CHO CH3CHCH2CHO OH 2 OH, 5o H2O ? Comments -Formation of an ???-unsaturated carbonyl compound requires two ?-hydrogens (one removed in the formation of the enolate anion, the second in the dehydration step. -Under basic conditions at elevated temperature, the ?-hydroxy aldehyde is an unstable intermediate and undergoes dehydration. 5. Mechanism of dehydration of ?-hydroxy aldehyde (E1CB mechanism) CH3CH OH CH2CHO + OH CH3CH CHCHOCH3CH OH CHCHO - OH 6. Variations on the aldol theme ? The acid-catalyzed aldol reaction (via an enol intermediate) H (mesityl oxide) C H3C H3C CHCCH3 O ( - H2O)CH3 C OH CH3 CH2CCH3 O HCH 3 C O CH3 ? The crossed aldol reaction (successful if only one reactant has ?-hydrogens) . CH O + CH3CHO OH -(aq) CH CHCHO ? The crossed aldol reaction with a ketone as enolate anion precursor (the Claisen-Schmidt reaction) CH3O CHO + C O H3C 50% KOH CH CH C O CH3O ? The intramolecular aldol reaction: cyclization to form five- and six-membered rings. Cyclization is normally accompanied by dehydration. 1,4-Dicarbonyl compounds produce cyclopentenone derivatives; 1,5-dicarbonyl compounds form cyclohexanone derivatives. jasmone OH-, 100o H2O O O O O CH3 OH-, 100o O O H2O 7. Summary: The aldol reaction is an important method for forming carbon-carbon covalent bonds. It also provides a direct route to ???-unsaturated carbonyl compounds. The double bond is always formed between the carbonyl carbon of one reactant and the ?-carbon of the other. C O + H2C C O C C C O DeCamp Mark Microsoft Word - Aldol Reaction _new_
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