23.2 Carbonyl Condensations versus Alpha Substitutions
2 min read•may 7, 2024
Carbonyl compounds can undergo two key reactions: condensations and . These processes involve different mechanisms, conditions, and outcomes, shaping how carbonyl groups transform and form new bonds.
Understanding these reactions is crucial for manipulating carbonyl compounds. Condensations join two carbonyls, while alpha substitutions replace hydrogens next to the carbonyl. Mastering these opens up a world of synthetic possibilities in organic chemistry.
Carbonyl Condensations and Alpha Substitutions
Carbonyl condensations vs alpha substitutions
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:
- Reaction between two carbonyl compounds (aldehydes or ketones)
- Catalytic amount of base required (, , )
- Proceeds through mechanism
- formation of one carbonyl compound
- of enolate to second carbonyl compound
- of resulting compound forms product
- Unreacted carbonyl compounds remain in reaction mixture (, ) Alpha substitutions:
- Reaction between carbonyl compound and (, )
- Strong base required (LDA, , )
- Proceeds through mechanism
- Enolate formation of carbonyl compound
- SN2 reaction between enolate and
- All carbonyl compounds consumed during reaction
- Involves a in the alkyl halide
Conditions for alpha-substitution reactions
Base strength:
- Strong bases required for complete enolate formation of carbonyl compound
- Lithium diisopropylamide (LDA)
- Sodium hydride (NaH)
- Sodium amide (NaNH2) Temperature:
- Carried out at low temperatures (-78°C to 0°C)
- Low temperatures favor formation and minimize side reactions Reactant addition order:
- Carbonyl compound first treated with strong base to form enolate
- Alkyl halide then added to reaction mixture
- Ensures enolate present before alkyl halide introduced, favoring desired SN2 reaction
Process of carbonyl condensation reactions
Process:
- Two carbonyl compounds mixed with catalytic amount of base
- Base facilitates enolate formation from one carbonyl compound
- Enolate acts as nucleophile and attacks second carbonyl compound
- Resulting aldol product undergoes dehydration to form -unsaturated carbonyl compound
Conditions:
- Catalytic amount of base sufficient (NaOH, KOH, NaOEt)
- Base regenerated during dehydration step, allowing further reaction catalysis
- Unreacted carbonyl compounds remain
- Nucleophilic carbonyl compound (enolate precursor) used in excess
- Ensures complete reaction of electrophilic carbonyl compound
- Unreacted nucleophilic carbonyl compounds (acetone, ) remain in reaction mixture after condensation complete
Keto-Enol Tautomerism and Enolates
- involves the interconversion between keto and forms
- Enols are unstable tautomers of carbonyl compounds
- formation occurs under equilibrium conditions
- Kinetic enolate formation is favored at low temperatures and with strong, hindered bases
Key Terms to Review (30)
$\alpha,\beta$-unsaturated carbonyl: An $\alpha,\beta$-unsaturated carbonyl is a carbonyl compound (such as a ketone or aldehyde) that has a carbon-carbon double bond adjacent to the carbonyl group. This structural feature is important in the context of carbonyl condensations and alpha substitutions.
$\beta$-hydroxy carbonyl: A $\beta$-hydroxy carbonyl is a functional group in organic chemistry that consists of a carbonyl (C=O) group with a hydroxyl (-OH) group attached to the $\beta$-carbon, which is the second carbon atom from the carbonyl group. This structural feature is important in the context of carbonyl condensation reactions and alpha substitution reactions.
Acetaldehyde: Acetaldehyde is a colorless, flammable organic compound with the chemical formula CH3CHO. It is the simplest aliphatic aldehyde and is an important intermediate in various chemical processes and metabolic pathways.
Acetone: Acetone is a simple organic compound with the chemical formula CH3COCH3. It is a colorless, volatile, flammable liquid that is widely used as a solvent and in various chemical processes. Acetone is a key term that is relevant in the context of several important organic chemistry topics.
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 Condensation: Aldol condensation is a type of organic reaction where an aldehyde or ketone undergoes a nucleophilic addition reaction with another aldehyde or ketone, followed by a dehydration step to form an α,β-unsaturated carbonyl compound known as an enone.
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 Substitutions: Alpha substitutions refer to the replacement of a hydrogen atom on the carbon atom adjacent to a carbonyl group (the alpha carbon) with another substituent. This type of reaction is an important concept in the context of carbonyl condensations and other organic chemistry topics.
Carbonyl Condensations: Carbonyl condensations are a class of organic reactions where two carbonyl-containing compounds, such as aldehydes or ketones, react to form a new carbon-carbon bond. These reactions are important in the synthesis of various organic compounds and are often used in the formation of carbon-carbon bonds.
Cyclohexanone: Cyclohexanone is a cyclic ketone compound with the chemical formula C₆H₁₀O. It is a key intermediate in the synthesis of various organic compounds and is widely used in the chemical industry.
Dehydration: Dehydration is a chemical process in which water is removed from a compound, typically resulting in the formation of a new compound with fewer hydrogen and oxygen atoms. This term is particularly relevant in the context of various organic reactions and transformations, where dehydration plays a crucial role in the preparation and interconversion of different functional groups.
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.
Enolate: An enolate is a negatively charged oxygen-containing species that arises from the removal of a proton from the α-carbon of a carbonyl compound. Enolates are important reactive intermediates in various organic reactions, including aldol condensations, Claisen condensations, and α-substitution reactions.
Ethyl Bromide: Ethyl bromide, also known as bromoethane, is an organic compound with the chemical formula C$_{2}$H$_{5}$Br. It is a colorless, volatile liquid that is commonly used as a fumigant, a solvent, and an intermediate in organic synthesis reactions, particularly in the context of carbonyl condensations and alpha substitutions.
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 Enolate: A kinetic enolate is a reactive intermediate formed in organic chemistry reactions involving carbonyl compounds. It is a negatively charged oxygen-containing species that is generated under kinetic conditions, typically through the use of a strong base, and can undergo further transformations to form new carbon-carbon bonds.
KOH: KOH, or potassium hydroxide, is a strong base that is commonly used in organic chemistry reactions. It plays a crucial role in carbonyl condensations and alpha substitutions, two important topics in the study of organic chemistry.
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.
Leaving group: A leaving group in organic chemistry is an atom or group that detaches from the parent molecule during a nucleophilic substitution (SN2) reaction, forming a lone pair or negative ion. The ease with which a leaving group departs affects the rate and success of the reaction.
Leaving Group: A leaving group is a functional group or atom that is displaced or removed from a molecule during a chemical reaction. It is a key component in many organic reactions, particularly substitution and elimination reactions, as it facilitates the formation of a new bond or the creation of a new product.
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.
NaH: NaH, or sodium hydride, is a strong reducing agent and a common base used in organic chemistry. It is a white, crystalline solid that reacts violently with water and is often used to generate enolate ions, a key intermediate in various organic reactions.
NaNH2: NaNH2, also known as sodium amide, is an important organic compound that plays a crucial role in carbonyl condensations and alpha substitutions. It is a strong base and a useful reagent in organic synthesis.
NaOEt: NaOEt, or sodium ethoxide, is an organometallic compound that serves as a strong base and nucleophile in organic chemistry reactions. It is commonly used in the context of alkylation of enolate ions and carbonyl condensation reactions.
NaOH: NaOH, or sodium hydroxide, is a highly alkaline chemical compound that plays a crucial role in various organic chemistry reactions and processes. It is a strong base that is widely used in a variety of applications, including the discovery of nucleophilic substitution reactions, the SN2 reaction, the E2 reaction, carbonyl condensations, and peptide sequencing through the Edman degradation.
Nucleophilic Addition: Nucleophilic addition is a fundamental organic reaction in which a nucleophile, a species that donates electrons, adds to an electrophilic carbon center, typically a carbonyl carbon, to form a new product. This reaction is central to understanding many important topics in organic chemistry, including functional groups, polar reactions, carbocation stability, reaction stereochemistry, and the chemistry of aldehydes, ketones, alcohols, and other carbonyl-containing compounds.
Nucleophilic addition reaction: A nucleophilic addition reaction is a chemical process where a nucleophile forms a bond with an electrophilic carbon atom of a compound, typically found in aldehydes and ketones. This reaction results in the conversion of the carbonyl group into a more complex, often larger, molecule.
SN2: SN2 is a type of nucleophilic substitution reaction in organic chemistry where a nucleophile attacks the backside of a carbon atom bearing a good leaving group, resulting in the displacement of that leaving group and the inversion of stereochemistry at the carbon center.
Thermodynamic Enolate: A thermodynamic enolate is a type of enolate ion that is formed under thermodynamic control, where the most stable enolate isomer is produced. This is in contrast to kinetic enolates, which are formed under kinetic control and may not be the most thermodynamically stable product.