scoresvideos
Organic Chemistry
Table of Contents
Unit 23 Overview: Carbonyl Condensation Reactions
23.1 Carbonyl Condensations: The Aldol Reaction
23.2 Carbonyl Condensations versus Alpha Substitutions
23.3 Dehydration of Aldol Products: Synthesis of Enones
23.4 Using Aldol Reactions in Synthesis
23.5 Mixed Aldol Reactions
23.6 Intramolecular Aldol Reactions
23.7 The Claisen Condensation Reaction
23.8 Mixed Claisen Condensations
23.9 Intramolecular Claisen Condensations: The Dieckmann Cyclization
23.10 Conjugate Carbonyl Additions: The Michael Reaction
23.11 Carbonyl Condensations with Enamines: The Stork Enamine Reaction
23.12 The Robinson Annulation Reaction
23.13 Some Biological Carbonyl Condensation Reactions

🥼organic chemistry review

23.3 Dehydration of Aldol Products: Synthesis of Enones

Citation:

Aldol dehydration is a key step in aldol condensations, turning aldol products into enones. This process involves removing water from the β-hydroxy carbonyl compound, creating a carbon-carbon double bond that's conjugated with the carbonyl group.

Understanding the mechanism and effects of dehydration is crucial for predicting products and controlling reactions. Whether base or acid-catalyzed, dehydration shifts equilibrium towards product formation, making it a powerful tool in organic synthesis.

Dehydration of Aldol Products

Mechanism of aldol product dehydration

  • Base-catalyzed dehydration involves hydroxide ($OH^-$) abstracting an alpha hydrogen from the aldol product forming a carbanion which then eliminates the hydroxyl group resulting in a carbon-carbon double bond (enone) while the hydroxide acts as a base and leaves as water
  • Acid-catalyzed dehydration starts with protonation of the hydroxyl group of the aldol product by the acid catalyst followed by elimination of water forming a carbocation that undergoes further elimination to form a carbon-carbon double bond (enone) and a base (often water) abstracts a proton from the alpha carbon to neutralize the charge
  • The dehydration step is an elimination reaction, which can proceed through either an E1 or E2 mechanism depending on the reaction conditions

Effects of dehydration on aldol equilibrium

  • Aldol condensation is an equilibrium process favoring the forward aldol addition reaction at low temperatures and the reverse retro-aldol reaction at high temperatures
  • Dehydration of the aldol product removes it from the equilibrium mixture shifting the equilibrium towards product formation (Le Chatelier's principle) and increasing the overall yield
    • Often carried out under heating to promote elimination of water and drive the equilibrium towards enone product formation

Predicting enone products from aldol condensations

  • Aldehyde-aldehyde condensation forms $\alpha,\beta$-unsaturated aldehydes (enals) like butanal self-condensing to 2-ethylhex-2-enal
  • Ketone-aldehyde condensation forms $\alpha,\beta$-unsaturated ketones with the double bond closer to the ketone such as acetone and propanal condensing to 4-methylpent-3-en-2-one
  • Ketone-ketone condensation forms $\alpha,\beta$-unsaturated ketones with the double bond at the most substituted position (acetone self-condensing to 4-methylpent-3-en-2-one known as mesityl oxide)
  • For unsymmetrical ketones, regioselectivity depends on the stability of the enolate intermediate
    • More substituted enolates are typically favored leading to more substituted enones
  • The resulting enone products exhibit conjugation between the carbonyl group and the newly formed double bond

Reaction Control in Aldol Dehydrations

  • Thermodynamic control favors the formation of the most stable product, often resulting in the more substituted alkene
  • Kinetic control leads to the faster-forming product, which may not always be the most thermodynamically stable

Key Terms to Review (24)

Kinetic control: Kinetic control in organic chemistry refers to reaction conditions under which the product distribution is determined by the rate at which products are formed, favoring the formation of products that are formed fastest. These conditions often lead to products that are not necessarily the most stable but are reached more quickly due to lower activation energies.
Thermodynamic control: In organic chemistry, thermodynamic control describes conditions under which the products of a reaction are determined by the relative stability of the products rather than the rates at which they are formed. This often results in the formation of the most stable product over time, even if it is not the most rapidly produced.
Conjugation: Conjugation refers to the overlap or sharing of atomic orbitals, resulting in the delocalization of electrons across a system of connected atoms. This concept is central to understanding resonance, the stability of certain molecules and ions, and the interpretation of various spectroscopic techniques in organic chemistry.
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.
Carbocation: A carbocation is a positively charged carbon atom that is part of an organic molecule. These reactive intermediates play a crucial role in various organic reactions, including electrophilic additions, nucleophilic substitutions, and elimination reactions.
Le Chatelier's Principle: Le Chatelier's principle states that when a system at equilibrium is subjected to a change in one of the factors (concentration, temperature, or pressure) determining the equilibrium, the system will shift to counteract the change and establish a new equilibrium. This principle helps predict the direction of a system's response to disturbances.
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.
Regioselectivity: Regioselectivity refers to the preference of a chemical reaction to occur at a specific site or region of a molecule, leading to the formation of one regioisomeric product over another. This concept is particularly important in the context of electrophilic addition reactions of alkenes, electrophilic aromatic substitution, and other organic transformations.
Kinetic Control: Kinetic control refers to the principle that the initial product formed in a reaction is determined by the reaction pathway that has the lowest activation energy, regardless of the thermodynamic stability of the final products. It describes how the kinetics of a reaction, rather than just the thermodynamics, can dictate the outcome of a transformation.
Thermodynamic Control: Thermodynamic control refers to the principle that the most stable and thermodynamically favored product will be the predominant product of a reaction, regardless of the kinetic pathway. It is a concept that governs the outcome of various organic chemistry reactions, including those related to energy diagrams, elimination reactions, electrophilic additions to conjugated dienes, and the dehydration of aldol products.
Elimination Reaction: An elimination reaction is a type of organic reaction in which two atoms or groups are removed from a molecule, typically resulting in the formation of a carbon-carbon double bond or a carbon-carbon triple bond. This process is an important step in the synthesis of alkenes and alkynes, as well as in various other organic transformations.
E2 Mechanism: The E2 mechanism, or bimolecular elimination reaction, is a type of organic reaction where a base removes a hydrogen atom and a leaving group from adjacent carbon atoms, resulting in the formation of a carbon-carbon double bond. This mechanism is particularly important in the preparation of alkynes through the elimination of dihalides, as well as in the dehydration of aldol products to form enones.
Hydroxide: Hydroxide (OH-) is a negatively charged ion composed of one oxygen atom and one hydrogen atom. It is a key reactive species in many organic chemistry reactions, including the SN2 reaction and the dehydration of aldol products to form enones.
E1 Mechanism: The E1 mechanism, or unimolecular elimination, is a type of elimination reaction where a leaving group is removed from a substrate in a two-step process, resulting in the formation of an alkene. This mechanism is particularly relevant in the context of the SN1 reaction and the dehydration of aldol products to form enones.
Base-Catalyzed Dehydration: Base-catalyzed dehydration is a chemical reaction in which a base, such as a hydroxide ion or alkoxide ion, facilitates the removal of water from a compound, typically an alcohol or aldol product, to form an alkene or enone. This process is an important synthetic step in the preparation of unsaturated carbonyl compounds.
Enone: An enone is a functional group consisting of a carbon-carbon double bond adjacent to a carbonyl group (ketone or aldehyde). Enones are important intermediates in organic synthesis, particularly in the context of aldol condensations and enamine reactions.
Aldol Product Dehydration: Aldol product dehydration is a chemical reaction that occurs after an aldol condensation, where the newly formed aldol product undergoes a dehydration step to yield an α,β-unsaturated carbonyl compound known as an enone. This process is a key synthetic strategy in the preparation of enones from carbonyl compounds.
α,β-Unsaturated Aldehydes: α,β-Unsaturated aldehydes are a class of organic compounds characterized by the presence of a carbonyl group (aldehyde) adjacent to a carbon-carbon double bond. These structural features make α,β-unsaturated aldehydes highly reactive and useful intermediates in organic synthesis, particularly in the context of the dehydration of aldol products to form enones.
Enals: Enals, short for 'α,β-unsaturated aldehydes', are a class of organic compounds characterized by the presence of a carbon-carbon double bond adjacent to the carbonyl group of an aldehyde. These compounds are of great importance in organic chemistry, particularly in the context of reactions involving aldol condensation and the synthesis of enones.
α,β-unsaturated ketones: α,β-unsaturated ketones are a class of organic compounds that feature a carbonyl group (a ketone) directly attached to a carbon-carbon double bond. This structural feature gives rise to unique reactivity and synthetic applications, particularly in the context of the dehydration of aldol products to form enones.
Acid-Catalyzed Dehydration: Acid-catalyzed dehydration is a chemical reaction in which a compound, typically an alcohol or a carbonyl compound, is converted to an alkene through the removal of a water molecule. This process is facilitated by the presence of an acid catalyst, which helps to activate the reactants and stabilize the transition state.
Retro-aldol reaction: The retro-aldol reaction is the reverse of the aldol condensation, where an aldol product undergoes cleavage to regenerate the original carbonyl compounds. This process is crucial in understanding the mechanism and synthesis of various organic compounds.
Mesityl Oxide: Mesityl oxide is an organic compound with the formula CH3C(O)C(CH3)=CH2. It is a colorless, flammable liquid with a pungent odor, commonly used as a solvent and an intermediate in the synthesis of other organic compounds. In the context of this chapter, mesityl oxide is an important product formed during the dehydration of aldol condensation reactions.
Carbanion: A carbanion is a negatively charged species that contains a carbon atom with three bonds and a lone pair of electrons, giving it a formal negative charge. This species is crucial in various organic reactions, as it acts as a strong nucleophile and can participate in forming new bonds by attacking electrophiles.