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

Ch About The Authors These PowerPoint Lecture Slides were created and prepared by Professor William Tam and his wife, Dr. Phillis Chang. Professor William Tam received his B.Sc. at the University of Hong Kong in 1990 and his Ph.D. at the University of Toronto (Canada) in He was an NSERC postdoctoral fellow at the Imperial College (UK) and at Harvard University (USA). He joined the Department of Chemistry at the University of Guelph (Ontario, Canada) in 1998 and is currently a Full Professor and Associate Chair in the department. Professor Tam has received several awards in research and teaching, and according to Essential Science Indicators, he is currently ranked as the Top 1% most cited Chemists worldwide. He has published four books and over 80 scientific papers in top international journals such as J. Am. Chem. Soc., Angew. Chem., Org. Lett., and J. Org. Chem. Dr. Phillis Chang received her B.Sc. at New York University (USA) in 1994, her M.Sc. and Ph.D. in 1997 and 2001 at the University of Guelph (Canada). She lives in Guelph with her husband, William, and their son, Matthew.

Ch Reactions at the  Carbon of Carbonyl Compounds: Enols and Enolates  Hydrogens are weakly acidic (pK a = 19 – 20)

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

Ch Resonance structures for the delocalized enolates

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Ch Keto and Enol Tautomers  Interconvertible keto and enol forms are called tautomers, and their interconversion is called tautomerization

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Ch Resonance stabilization of the enol form

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

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Ch  Mechanism

Ch ●Acyl Substitution Step

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

Ch  Example

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Ch

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Ch Lithium Enolates

Ch  Preparation 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.

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

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

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

Ch A.Acylation  Synthesis  -diketones

Ch Synthesis of Substituted Acetic Acids: The Malonic Ester Synthesis

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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 