CNGNGE JOHN MCMURRY CHAPTER 17 Carbonyl Alpha- Substitution and Condensation Reactions THIRD EDITION Organic Chemistry with Biological Applications
CHAPTER 17 Carbonyl AlphaSubstitution and Condensation Reactions
a-Substitution and Carbonyl Condensation Reactions Alpha-substitution reactions occur at the carbon next to the carbonyl carbon-the a position Involve substitution of a-hydrogen :9: An enolate ion by electrophile Proceed through enol or enolate ion intermediate A carbonyl An alpha-substituted compound carbonyl compound Carbonyl condensation reactions occur between two carbonyl An enol partners Combination of a-substitution and nucleophilic addition steps i- New C-C bond Gives B-hydroxy carbonyl compound A carbonyl An enolate A B-hydroxy compound ion carbonyl compound
Alpha-substitution reactions occur at the carbon next to the carbonyl carbon – the a position ▪ Involve substitution of a-hydrogen by electrophile ▪ Proceed through enol or enolate ion intermediate Carbonyl condensation reactions occur between two carbonyl partners ▪ Combination of a-substitution and nucleophilic addition steps ▪ Gives b-hydroxy carbonyl compound α-Substitution and Carbonyl Condensation Reactions
17-1 Keto-Enol Tautomerism Carbonyl compounds with a-hydrogens rapidly equilibrate with corresponding enol(ene alcohol) Interconversion known as keto-eno/tautomerism :Greek tauto,meaning"the same,”and meros,meaning“part” Individual isomers called tautomers Keto tautomer Enol tautomer
Carbonyl compounds with a-hydrogens rapidly equilibrate with corresponding enol (ene + alcohol) ▪ Interconversion known as keto-enol tautomerism ▪ Greek tauto, meaning “the same,” and meros, meaning “part” ▪ Individual isomers called tautomers 17-1 Keto-Enol Tautomerism
Keto-Enol Tautomerism Tautomers are constitutional isomers Isomers are different compounds with different structures Atoms arranged differently Different from resonance structures that differ only in the position of their electrons Most carbonyl compounds exist almost exclusively in the keto form at equilibrium 0 ← H3C CH3 H3C 99.9999% 0.0001% 99.9999999% 0.0000001% Cyclohexanone Acetone
Tautomers are constitutional isomers ▪ Isomers are different compounds with different structures ▪ Atoms arranged differently ▪ Different from resonance structures that differ only in the position of their electrons ▪ Most carbonyl compounds exist almost exclusively in the keto form at equilibrium Keto-Enol Tautomerism
Keto-Enol Tautomerism Tautomers are constitutional isomers The enol tautomer sometimes predominates when it can be stabilized by conjugation or by intramolecular hydrogen bond formation Nonacidic 0: H H:0: Base H HH H H H H Acidic Enolate ion
Tautomers are constitutional isomers ▪ The enol tautomer sometimes predominates when it can be stabilized by conjugation or by intramolecular hydrogen bond formation Keto-Enol Tautomerism