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Chapter 15

α-Carbon Chemistry: Enols, Enolates, and Enamines

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Chapter 15 α-Carbon Chemistry: Enols, Enolates, and Enamines

Multiple Halogenation of Methyl Ketones: Haloform Reaction

A method involving the transformation of methyl ketones to carboxylic acids using excess base and halogen is called the haloform reaction. It begins with …

α-Halogenation of Carboxylic Acid Derivatives: Overview

Unlike aldehydes and ketones, carboxylic acids do not readily participate in α halogenation reactions via enols or enolate intermediates. However, …

Reactivity of Enols

Enols are a class of compounds where a hydroxyl group is attached to a carbon–carbon double bond, which implies that it is a vinyl alcohol. A …

Reactivity of Enolate Ions

Enolate ions are formed by the acid–base reaction of a carbonyl compound with a base. This leads to deprotonation of the α hydrogen atom, …

Regioselective Formation of Enolates

As depicted in the figure below, the unsymmetrical ketones can form two possible enolates: less substituted or more substituted enolates. Usually, …

Acid-Catalyzed α-Halogenation of Aldehydes and Ketones

By replacing an α-hydrogen with a halogen, acid-catalyzed α-halogenation of aldehydes or ketones yields a monohalogenated product In the first …

Base-Promoted α-Halogenation of Aldehydes and Ketones

α-Halogenation of aldehydes and ketones is a reaction involving the substitution of α hydrogens with halogens in the presence of a base. …

α-Bromination of Carboxylic Acids: Hell–Volhard–Zelinski Reaction

The method to achieve α-brominated carboxylic acids using a mixture of phosphorus tribromide and bromine is known as the …

Base-Catalyzed Aldol Addition Reaction

As depicted in Figure 1, base-catalyzed aldol addition involves adding two carbonyl compounds in aqueous sodium hydroxide to form a β-hydroxy …

Dehydration of Aldols to Enals: Base-Catalyzed Aldol Condensation

This lesson delves into the aldol condensation catalyzed by bases, where aldols undergo dehydration to enals. As shown in Figure 1, the β-hydroxy …

Intramolecular Aldol Reaction

Intramolecular aldol reaction occurs in dicarbonyl compounds such as dialdehydes, diketones, and keto-aldehydes. The dicarbonyl compounds possess more …

Crossed Aldol Reaction Using Weak Bases

This lesson deals with the crossed aldol reaction using weak bases. The self-condensation of an aldehyde having α hydrogen is prevented by adding it …

Crossed Aldol Reaction Using Strong Bases: Directed Aldol Reaction

The reaction between two different carbonyl compounds comprising α hydrogen in the presence of a strong base like lithium diisopropylamide (LDA) to …

Esters to β-Ketoesters: Claisen Condensation Overview

Regular Claisen condensation is a base-promoted reaction involving identical esters with two α hydrogens, condensing to produce β-ketoesters. It …

Intramolecular Claisen Condensation of Dicarboxylic Esters: Dieckmann Cyclization

Dieckmann cyclization is an intramolecular Claisen condensation of diesters. The reaction occurs in the presence of a base and generates a cyclic …

β-Dicarbonyl Compounds via Crossed Claisen Condensations

Crossed Claisen condensations are base-promoted reactions between two different ester molecules producing β-dicarbonyl compounds. The reaction …

α-Alkylation of Ketones via Enolate Ions

Ketones with α protons are deprotonated by strong bases like lithium diisopropylamide (LDA) to form enolate ions. The anion is stabilized by …

Conjugate Addition to α,β-Unsaturated Carbonyl Compounds

α,β-Unsaturated carbonyl compounds are molecules bearing a carbonyl and alkene functionality in conjugation with each other. The conjugation in …

Conjugate Addition of Enolates: Michael Addition

The attack of a nucleophile at the β carbon of an α,β-unsaturated carbonyl compound is called conjugate addition. Conjugate addition …

Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction

α-Substituted ketones or aldehydes can be synthesized from enamines by the Stork enamine reaction, named after its pioneer Gilbert Stork. Enamines …

Formation of β-Aminoalkyl Carbonyl Compounds: The Mannich Reaction

Types of Enols and Enolates

Aldehydes and ketones form enols, although only about 1% of the enol is present at the equilibrium for simple monocarbonyl compounds. The enol form is …

Enolate Mechanism Conventions

When a carbonyl compound is treated with a strong base, the α position gets deprotonated to give a resonance-stabilized intermediate called an …

Stereochemical Effects of Enolization

The chiral α-carbon of the carbonyl compound is the stereocenter of the molecule. As shown in the figure below, when such a carbonyl compound …

Reactions of α-Halocarbonyl Compounds: Nucleophilic Substitution

Nucleophilic substitution in α-halocarbonyl compounds can be achieved via an SN2 pathway. The reaction in α-haloketones is generally carried out …

C–C Bond Formation: Aldol Condensation Overview

Aldol condensation is an important route in synthetic organic chemistry used to generate a new carbon–carbon bond under basic or acidic conditions. …

Acid-Catalyzed Aldol Addition Reaction

The aldol reaction of a ketone under acidic conditions successfully forms an unsaturated carbonyl as the final product instead of an aldol. The …

Dehydration of Aldols to Enones: Acid-Catalyzed Aldol Condensation

As shown in Figure 1, under acidic conditions, the β-hydroxy ketone undergoes dehydration via an E1 elimination reaction to form an enone. Figure 1. …

C–C Bond Cleavage: Retro-Aldol Reaction

The reverse of the aldol addition reaction is called the retro-aldol reaction. Here, the carbon–carbon bond in the aldol product is cleaved under …

Crossed Aldol Reactions: Overview

Crossed aldol addition is the reaction between two different carbonyl compounds under acidic or basic conditions. Here, both the carbonyl compounds …

Ketones with Nonenolizable Aromatic Aldehydes: Claisen–Schmidt Condensation

Benzaldehyde, like formaldehyde, lacks an α hydrogen and cannot enolize to form an enolate. Hence, the reaction of benzaldehyde with a ketone in the …

β-Hydroxyesters via Crossed Aldol Addition: Reformatsky Reaction

Aldol Condensation with β-Diesters: Knoevenagel Condensation

The Knoevenagel condensation is an aldol-type reaction involving the condensation of aldehydes or ketones with active methylene compounds such as …

Esters to β-Ketoesters: Claisen Condensation Mechanism

Regular Claisen condensation involves the synthesis of β-ketoesters by combining identical ester molecules bearing two α hydrogens in the …

Aldol Condensation vs Claisen Condensation

Aldol condensation is an acid or base-catalyzed condensation between aldehydes or ketones to give an α,ꞵ-unsaturated carbonyl compound. A …

Factors Affecting α-Alkylation of Ketones: Choice of Base

α-Alkylation of ketones is achieved in the presence of alkyl halides and a base. The reaction proceeds via the formation of an enolate ion followed …

Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis

Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and β-keto esters. The reaction occurs in the presence of an alkoxide …

Alkylation of β-Diester Enolates: Malonic Ester Synthesis

Malonic ester synthesis is a method to obtain α substituted carboxylic acids from ꞵ-diesters such as diethyl malonate and alkyl halides. The …

Conjugate Addition (1,4-Addition) vs Direct Addition (1,2-Addition)

α,β-Unsaturated carbonyl compounds with two electrophilic sites, the carbonyl carbon, and the β carbon, are susceptible to nucleophilic …

Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation

Robinson annulation is a base-catalyzed reaction for the synthesis of 2-cyclohexenone derivatives from 1,3-dicarbonyl donors (such as cyclic diketones, …

Nonenolizable Aldehydes to Acids and Alcohols: The Cannizzaro Reaction

The Cannizzaro reaction is a base-promoted redox reaction producing a primary alcohol and a carboxylic acid from two molecules of a nonenolizable …

Nitrosation of Enols

The nitrosation reaction is one of the methods of preparing 1,2-diketones. The enol tautomer of the starting ketone reacts with sodium nitrite in …

Synthesis of Indoxyl-glycosides for Detection of Glycosidase Activities

Indoxyl glycosides proved to be valuable and versatile tools for monitoring glycosidase activities. Indoxyls are released by enzymatic hydrolysis and are …

Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach

Methine-bridged conjugated bicyclic aromatic compounds are common constituents of a range of biologically relevant molecules such as porphyrins, …

Designed for Molecular Recycling: A Lignin-Derived Semi-aromatic Biobased Polymer

The development of chemically recyclable biopolymers offers opportunities within the pursuit of a circular economy. Chemically recyclable biopolymers make …