Created by Professor William Tam & Dr. Phillis Chang Ch Chapter 18 Reactions at the  Carbon of Carbonyl Compounds Enols and Enolates

 What is a keto form ? A structure that contains a carbonyl. E.g. aldehyde, ketone, ester, acid, etc.  What is an enol ? A compound that has an alkene and an OH attached to the same carbon atom.  What is an enolate ?  An enol with the proton removed. May be formed by removing a proton from the  carbon atom of a keto form. Keto, enol and enolate structures:

  What is an  carbon ? A carbon atom adjacent to a carbonyl.   What is an  hydrogen ?  A hydrogen attached to an  carbon atom.  The  carbon and  hydrogens:   Hydrogens are weakly acidic (pK a = 19 – 20) due to the e-withdrawing C=O.

Ch Reactions at the  Carbon of Carbonyl Compounds: Enols and Enolates This shows a reaction at the carbonyl carbon atom. Tetrahedral intermediate

Ch The Acidity of the  Hydrogens of Carbonyl Compounds: Enolate Anions Comparison of pKas.

Ch Resonance structures for the delocalized enolates  Removal of  H forms a resonance stabilized enolate. Deprotonation:

Ch Protonation of oxygen.  Protonation of  carbon. Protonation:

Ch Keto and Enol Tautomers  Interconvertible keto and enol forms are called tautomers, and their interconversion is called tautomerization.  The keto and enol forms are in equilibrium (not resonance structures) because a proton transfer occurs.

Ch E.g.

Ch Resonance stabilization of the enol form E.g.

Ch Reactions via Enols & Enolates 3A. Racemization Racemization at an  carbon takes place in the presence of acids or bases

Ch  Base-Catalyzed Enolization:

Ch  Acid-Catalyzed Enolization:

Ch B.Halogenation at the  Carbon

Ch  Base-Promoted Halogenation:

Ch  Acid-Promoted Halogenation:

Ch C. The Haloform Reaction

Ch  The Iodoform reaction:

Ch  Mechanism:

Ch ●Acyl Substitution Step:

Ch D.  -Halo Carboxylic Acids: The Hell – Volhard – Zelinski Reaction

Ch  Example:

Ch  Mechanism:

Ch  Further reaction of an  halo acid:

Ch Lithium Enolates

Ch  Prep. of lithium diisopropylamide: (LDA)

Ch A.Regioselective Formation of Enolates  Formation of a Kinetic Enolate: This enolate is formed faster because the hindered strong base removes the less hindered proton faster. (Dimethoxyethane)

Ch  Formation of a Thermodynamic Enolate: This enolate is more stable because the double bond is more highly substituted. It is the predominant enolate at equilibrium.

Ch B.Direct Alkylation of Ketones via Lithium Enolates Lithium diisopropylamide = LDA or LiN(iPr) 2.

Ch C.Direct Alkylation of Esters

Ch  Examples:

Ch Enolates of  -Dicarbonyl Compounds

Ch  Recall:   -hydrogens of  -dicarbonyl compounds are more acidic:

Ch Contributing resonance structures Resonance hybrid

Ch Synthesis of Methyl Ketones: The Acetoacetic Ester Synthesis

Ch  Synthesis of monosubstituted methyl ketones:

Ch  Synthesis of disubstituted methyl ketones:

Ch

Ch  Synthesis of  -keto acids and  -diketones:

Ch A.Acylation  Synthesis  -diketones:

Ch Synthesis of Substituted Acetic Acids: The Malonic Ester Synthesis

Ch  Synthesis of substituted acetic acid:

Ch  Synthesis of monoalkylacetic acid:

Ch  Synthesis of dialkylacetic acid:

Ch  Example 1:

Ch  Example 2:

Ch Further Reactions of Active Hydrogen Compounds

Ch  Example:

Ch Synthesis of Enamines: Stork Enamine Reactions

Ch  2° amines most commonly used to prepare enamines: ●e.g.

Ch (a) (b)

Ch  Synthesis of  -diketones:

Ch  Synthesis of  -keto esters:

Ch  Enamines can also be used in Michael additions:

Ch Summary of Enolate Chemistry 1.Formation of an Enolate: Resonance- stabilized enolate

Ch Racemization: Enantiomers

Ch Halogenation of Aldehydes & Ketones:  Specific example: haloform reaction:

Ch Halogenation of Carboxylic Acids: The HVZ Reaction:

Ch Direct Alkylation via Lithium Enolates:  Specific example:

Ch Direct Alkylation of Esters:

Ch Acetoacetic Ester Synthesis:

Ch Malonic Ester Synthesis:

Ch Stork Enamine Reaction:

Ch  END OF CHAPTER 18 