22.6 Reactivity of Enolate Ions
2 min read•may 7, 2024
Enolate ions are key players in organic reactions, packing more punch than their cousins. Their resonance-stabilized structure gives them superpowers, making them more reactive and versatile nucleophiles. Understanding enolates is crucial for grasping carbonyl chemistry.
These negatively charged ions can attack various electrophiles, leading to α-substituted products or enol derivatives. But beware of challenges like multiple halogenations! Mastering enolate chemistry opens doors to a world of synthetic possibilities in organic reactions.
Enolate Ion Reactivity
Enolate ions vs enols
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- Enolate ions are more stable than enols
- delocalizes negative charge between and oxygen in enolate ions
- Enols lack resonance stabilization localizing electron density on oxygen
- Higher reactivity of enolate ions compared to enols
- Increased electron density on alpha carbon and oxygen enhances of enolate ions
- Enolate ions capable of reacting with broader range of electrophiles (alkyl halides, )
- explains the equilibrium between ketones and their enol forms
Enolate reactions with electrophiles
- Alpha carbon of enolate ions undergoes SN2 reaction with electrophiles
- Produces α-substituted carbonyl compounds
- α-alkylated ketones or esters formed by reaction with alkyl halides ()
- Oxygen of enolate ions reacts with electrophiles via addition-elimination mechanism
- Forms enol ethers or esters as products
- β-keto esters produced by reaction with acid chlorides ()
- occurs when an acts as a nucleophile, attacking the carbonyl group of another molecule
Base-promoted α-halogenation of ketones
- Strong base abstracts alpha hydrogen from ketone to generate (NaOH)
- Enolate ion reacts with halogen source at alpha carbon (Br2, I2)
- Challenges:
- Multiple halogenation results in mixture of mono-, di-, trihalogenated products
- Trihalogenated products susceptible to
- Base-promoted cleavage of trihalomethyl group yields and (CHCl3, CHBr3)
- Difficult to control extent of halogenation
- Low temperatures and precise stoichiometry help limit multiple halogenation
- Bulky bases improve selectivity for monohalogenation (LDA)
Enolate Formation and Stability
- : The rate of enolate formation (kinetic) may differ from the relative stability (thermodynamic) of possible enolates
- values of α-hydrogens influence the ease of enolate formation and their relative acidity
Key Terms to Review (30)
Acetyl Chloride: Acetyl chloride is an organic compound with the chemical formula CH3COCl. It is a colorless, volatile liquid that is commonly used as a reagent in organic synthesis reactions, particularly in the formation of carboxylic acid derivatives.
Acid Chloride: An acid chloride, also known as an acyl chloride, is a highly reactive organic compound derived from a carboxylic acid. It contains a carbonyl group (C=O) bonded to a chlorine atom, making it a versatile and important functional group in organic chemistry.
Acid chlorides: Acid chlorides are a class of organic compounds characterized by the presence of a carbonyl group (C=O) bonded to a chlorine atom. They are derived from carboxylic acids by replacing the hydroxyl group (OH) with a chlorine atom.
Aldaric acid: Aldaric acid is a type of dicarboxylic acid obtained by oxidizing both the aldehyde and primary alcohol groups of an aldose to carboxylic acids. It represents the fully oxidized form of a monosaccharide where all potential reactive sites have been converted to carboxyl groups.
Aldol reaction: The Aldol reaction is a chemical reaction in organic chemistry where two aldehydes or ketones, or one of each, react together in the presence of a base to form a β-hydroxyaldehyde or β-hydroxyketone. It is a fundamental process for forming carbon-carbon bonds and is widely used in the synthesis of complex molecules.
Aldol Reaction: The aldol reaction is a type of carbonyl condensation reaction that involves the nucleophilic addition of an enolate ion to a carbonyl compound, followed by an elimination step to form an α,β-unsaturated carbonyl compound.
Alkyl halide: An alkyl halide is an organic compound in which one or more hydrogen atoms in an alkane (saturated hydrocarbon) have been replaced by a halogen atom (fluorine, chlorine, bromine, or iodine). This substitution results in a molecule with distinct chemical and physical properties compared to its alkane precursor.
Alkyl Halide: An alkyl halide is a type of organic compound that consists of an alkyl group (a hydrocarbon chain) bonded to a halogen atom (fluorine, chlorine, bromine, or iodine). These compounds are important intermediates in many organic reactions, including polar reactions, elimination reactions, and substitution reactions.
Alpha Carbon: The alpha carbon is the carbon atom directly attached to a functional group, such as a carbonyl group in aldehydes and ketones, or to the carboxyl group in amino acids. It is a crucial structural feature that influences the reactivity and properties of these organic compounds.
Carboxylate Salt: A carboxylate salt is a type of ionic compound formed by the reaction between a carboxylic acid and a base, resulting in the replacement of the acidic hydrogen with a metal cation. These salts are important in the context of the reactivity of enolate ions, as they can be involved in various organic reactions.
Electrophile: An electrophile is a species that is attracted to electron-rich regions and seeks to form new bonds by accepting electron density. Electrophiles play a crucial role in many organic reactions, including polar reactions, electrophilic aromatic substitution, and nucleophilic acyl substitution, among others.
Enol: An enol is an organic compound that contains a carbon-carbon double bond where one of the carbon atoms is also bonded to a hydroxyl (OH) group. Enols are important intermediates in various organic reactions, including the hydration of alkynes, alpha-substitution reactions of carbonyl compounds, and carbonyl condensation reactions.
Enol Ether: An enol ether is a type of organic compound containing a carbon-oxygen double bond adjacent to a carbon-carbon double bond. These compounds are characterized by the presence of an ether group attached to the $\alpha$-carbon of an alkene, giving them unique reactivity and synthetic utility.
Enolate ion: An enolate ion is a negatively charged intermediate formed from the deprotonation of an alpha carbon adjacent to a carbonyl group in aldehydes and ketones. It plays a crucial role in various organic reactions, including nucleophilic addition and substitution reactions.
Enolate Ion: An enolate ion is a type of conjugate base formed when the alpha hydrogen of a carbonyl compound is removed, resulting in a negatively charged oxygen atom adjacent to a carbon-carbon double bond. This reactive intermediate is a key player in various organic reactions, including conjugate nucleophilic additions, reactions of carboxylic acids, and carbonyl condensation reactions.
Haloform: The haloform reaction is a chemical reaction that involves the conversion of a methyl ketone or aldehyde into a trihalomethane (haloform) and a carboxylic acid. This reaction is particularly important in the context of the reactivity of enolate ions, as it represents a key transformation that can occur with these nucleophilic species.
Haloform reaction: The haloform reaction is a chemical process where a methyl ketone is converted into a carboxylate and a haloform (a compound containing three halogen atoms bonded to a carbon atom) through the action of halogens in the presence of base. It highlights the reactivity of enolate ions formed from carbonyl compounds by alpha-substitution.
Haloform Reaction: The haloform reaction is a chemical reaction that involves the conversion of a methyl ketone or secondary alcohol into a haloform (a trihalomethane) and a carboxylic acid. This reaction is particularly important in the context of the reactivity of enolate ions, as it demonstrates how these reactive intermediates can be leveraged to selectively functionalize carbonyl compounds.
Keto-Enol Tautomerism: Keto-enol tautomerism is the reversible chemical equilibrium between a keto (carbonyl) form and an enol form of a compound. This process is particularly relevant in the context of carbonyl chemistry, as it affects the reactivity and properties of these compounds.
Kinetic vs Thermodynamic Enolates: Enolates are negatively charged intermediates formed during the enolization of carbonyl compounds. The terms 'kinetic' and 'thermodynamic' refer to the different factors that govern the formation and reactivity of these enolate species. Understanding the distinction between kinetic and thermodynamic enolates is crucial in the context of their reactivity, as outlined in Section 22.6 of the course material.
LDA (Lithium Diisopropylamide): LDA, or lithium diisopropylamide, is a powerful organometallic base commonly used in organic chemistry for the deprotonation of alpha-hydrogen atoms, generating highly reactive enolate ions. This key term is closely related to various topics in the study of carbonyl chemistry, including enolate ion formation, reactivity, and subsequent reactions.
Methyl Iodide: Methyl iodide, also known as iodomethane, is a colorless, volatile organic compound with the chemical formula CH3I. It is a widely used alkyl halide that serves as a versatile reagent in various organic chemistry reactions, particularly in the context of enolate ion reactivity and carbonyl condensation reactions.
Nucleophilicity: Nucleophilicity refers to the ability of a species to donate electrons and form a covalent bond with an electrophilic center. It is a key concept in organic chemistry that governs the reactivity and selectivity of many important reactions, including substitution, addition, and elimination reactions.
PKa: pKa, or the acid dissociation constant, is a measure of the strength of an acid in a solution. It represents the pH at which a particular acid is 50% dissociated into its conjugate base. This value is crucial in understanding the behavior and properties of acids, bases, and their reactions in organic chemistry.
Resonance Stabilization: Resonance stabilization is a phenomenon where the delocalization of electrons in a molecule or ion leads to a more stable configuration compared to a single Lewis structure. This concept is crucial in understanding the behavior and properties of various organic compounds, including their acidity, basicity, reactivity, and stability.
α-Alkylated Ketone: An α-alkylated ketone is a carbonyl compound where a carbon atom adjacent to the carbonyl group (the α-carbon) has an alkyl substituent attached. These compounds exhibit unique reactivity due to the presence of the α-alkyl group, which influences the acidity of the α-hydrogen and the stability of the resulting enolate ion.
α-Halogenation: α-Halogenation is a chemical reaction where a halogen atom (such as chlorine, bromine, or iodine) is introduced onto the α-carbon, which is the carbon atom adjacent to a carbonyl group (a carbon-oxygen double bond). This reaction is particularly relevant in the context of carboxylic acid reactions, the reactivity of enols, and the reactivity of enolate ions.
α-Substituted Carbonyl Compound: An α-substituted carbonyl compound is a type of organic compound where a substituent group is attached to the carbon atom adjacent to the carbonyl group (the α-carbon). These compounds exhibit unique reactivity patterns that are central to the topics of enol reactivity and enolate ion chemistry.
β-Keto ester: A β-keto ester is an organic compound containing a ketone functional group (carbonyl) and an ester group, where the carbonyl carbon is positioned two carbons away from the ester oxygen. This structure makes the hydrogen atoms on the carbon between the carbonyl and ester groups (alpha hydrogens) particularly acidic, facilitating their removal and formation of enolate ions.
β-keto ester: A β-keto ester is a type of organic compound that contains a ketone group (C=O) at the β-carbon position relative to an ester functional group. These compounds are important intermediates in various organic reactions, particularly in the context of enolate ion reactivity, the Claisen condensation reaction, and certain biological carbonyl condensation reactions.