Robinson Annulation Reaction Mechanism

The Organic Chemistry Tutor
11 May 201821:28
EducationalLearning
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TLDRThis educational video script delves into the Robinson Annulation reaction, a key organic chemistry process for forming six-membered rings. It begins with the formation of an enolate ion from cyclohexanone using a base, followed by a Michael reaction with an α,β-unsaturated ketone. The script explains the nucleophilic attack at the β-carbon, subsequent intramolecular aldol reaction, and the importance of ring stability. It also discusses the impact of base strength on the reaction's direction, comparing different Michael donors and acceptors, and concludes with the final product formation, highlighting the strategic steps involved in this synthetically valuable reaction.

Takeaways
  • 🧪 The Robinson annulation reaction involves the formation of a six-membered ring through a Michael reaction followed by an intramolecular aldol reaction.
  • 🔍 The initial step in the Robinson annulation is the deprotonation of a ketone using a base, typically a hydroxide, to form an enolate ion.
  • 🌀 The enolate ion acts as a nucleophile in the Michael reaction, attacking the beta carbon of an alpha, beta-unsaturated ketone.
  • 🎯 The choice of Michael donor is crucial; a weaker base, such as an enolate ion with two carbonyl groups, is a better Michael donor due to its preference for conjugate addition.
  • ⚛️ The Michael reaction results in a 1,5-dicarbonyl compound, setting the stage for the intramolecular aldol reaction.
  • 🔄 An intramolecular aldol reaction involves the enolate ion attacking another carbonyl carbon, leading to the formation of a six-membered ring.
  • 💧 Protonation of the alkoxide ion by water is necessary to regenerate the hydroxide ion and form a beta-hydroxy ketone.
  • 🔥 Dehydration of the beta-hydroxy ketone requires heat to drive off water and form the final product, a cyclic alpha, beta-unsaturated ketone.
  • 📉 Steric hindrance and electronic effects influence the reactivity of the carbonyl group in the Michael acceptor; aldehydes are more reactive than ketones due to less steric hindrance and higher electrophilicity.
  • 🔬 The pKa values of different compounds determine the strength of the base; enolate ions are stronger bases than hydroxide, which in turn is stronger than an enolate ion between two carbonyl groups.
  • 📚 Understanding the reactivity of the Michael donor, the electrophilicity of the Michael acceptor, and the conditions of the reaction are essential for predicting the major product in Robinson annulation.
Q & A
  • What is the Robinson Annulation reaction?

    -The Robinson Annulation reaction is a method of ring formation in organic chemistry. It involves a Michael reaction followed by an intramolecular aldol reaction, resulting in the formation of a six-membered ring. The reaction typically starts with the deprotonation of a ketone to form an enolate ion, which then reacts with an α,β-unsaturated ketone.

  • What is the role of the hydroxide ion in the initial step of the Robinson Annulation reaction?

    -The hydroxide ion acts as a base to remove the alpha hydrogen from the ketone, leading to the formation of an enolate ion. This step is crucial as it generates the nucleophile needed for the subsequent Michael reaction.

  • What is the significance of the Michael reaction in the Robinson Annulation process?

    -The Michael reaction is the first step in the Robinson Annulation process where the enolate ion, acting as a nucleophile, attacks the β-carbon of an α,β-unsaturated ketone, forming a new C-C bond. This step is key to extending the carbon chain and setting up the conditions for ring closure.

  • Why is the attack of the enolate ion on the β-carbon favored over the carbonyl carbon in the Robinson Annulation?

    -The attack on the β-carbon is favored because it leads to a more stable six-membered ring through the formation of a 1,5-dicarbonyl compound. Attacking the carbonyl carbon would result in a less stable four-membered ring, which is energetically unfavorable.

  • What is the purpose of the water molecule in the intermediate steps of the Robinson Annulation reaction?

    -The water molecule is used to protonate the enolate ion, regenerating the hydroxide ion and forming a β-hydroxy ketone. This step is necessary for the continuation of the reaction and the eventual formation of the six-membered ring.

  • How does the stability of the ring influence the choice of where to remove the alpha hydrogen in the Robinson Annulation?

    -The stability of the ring is a determining factor in the choice of where to remove the alpha hydrogen. In the script, the removal of the alpha hydrogen is chosen to facilitate the formation of a more stable six-membered ring rather than an unstable four-membered ring.

  • What is the role of heat in the dehydration step of the Robinson Annulation reaction?

    -Heat is used to drive off the water molecule in the dehydration step, which is necessary to convert the β-hydroxy ketone into the final product. The heat provides the energy needed to overcome the activation energy barrier for the elimination reaction.

  • Why is the enolate ion with two carbonyl groups considered a better Michael donor than one with a single carbonyl group?

    -An enolate ion with two carbonyl groups is a better Michael donor because it is a weaker base and is more likely to attack the β-carbon rather than the carbonyl carbon. This leads to a higher yield of the desired conjugate addition product, which is crucial for the success of the Robinson Annulation.

  • What is the difference between direct addition and conjugate addition in the context of nucleophilic attack on α,β-unsaturated systems?

    -Direct addition refers to a nucleophile attacking the carbonyl carbon of an α,β-unsaturated system, while conjugate addition involves the nucleophile attacking the β-carbon. The choice between the two depends on the strength of the nucleophile and the accessibility of the carbonyl group.

  • How does the pKa value influence the reactivity of a Michael donor in the Robinson Annulation reaction?

    -The pKa value indicates the acidity of the α-hydrogen in a potential Michael donor. A lower pKa value means the α-hydrogen is more acidic and easier to deprotonate, forming a stronger enolate ion. This stronger enolate ion is a better nucleophile and can more effectively participate in the Michael reaction.

Outlines
00:00
🧪 Robinson Annulation Reaction Overview

This paragraph introduces the Robinson annulation reaction, a process that involves the formation of six-membered rings through a Michael reaction followed by an intramolecular aldol reaction. It begins with the generation of an enolate ion from cyclohexanone using a hydroxide base, which then reacts with an α,β-unsaturated ketone. The focus is on the attack at the β-carbon leading to the formation of the desired product. The summary explains the step-by-step process, including the importance of choosing the correct site for the enolate ion attack, the role of water in the reaction, and the formation of the cyclohexane ring, emphasizing the stability of six-membered rings over four-membered ones.

05:09
🔍 Detailed Walkthrough of Robinson Annulation with Acetone

The second paragraph delves into a specific example of the Robinson annulation reaction using acetone and an α,β-unsaturated ketone under basic conditions. It describes the initial step of deprotonation to form an enolate ion, its subsequent reaction with the β-carbon of the unsaturated ketone, and the formation of a 1,5-dicarbonyl compound as a result of the Michael reaction. The summary continues with the intramolecular aldol reaction, the formation of a β-hydroxy ketone, and the crucial dehydration step to yield the final cyclic product, highlighting the importance of heat in driving the reaction to completion.

10:11
📚 Comparing Michael Donor Strengths in Robinson Annulation

This paragraph compares the effectiveness of different Michael donors in the Robinson annulation reaction, emphasizing the preference of weak bases to attack the β-carbon due to their stabilization by carbonyl groups. It explains that an enolate ion stabilized by two carbonyl groups is a better Michael donor than one with a single carbonyl group, leading to higher yields in the reaction. The summary outlines the steps of deprotonation, conjugate addition, and the subsequent formation of the final product, noting the impact of base strength on the reaction pathway and yield.

15:16
🔬 Factors Influencing Nucleophilic Attack in Michael Reactions

The fourth paragraph discusses the factors that influence the site of nucleophilic attack during Michael reactions, contrasting the behavior of weak and strong bases. It explains that weak bases favor conjugate addition by attacking the β-carbon, while strong bases prefer direct addition by attacking the carbonyl carbon. The summary provides a comparison of different Michael donors and acceptors, including the pKa values of water, ketones, and diketones, and how these values relate to the reactivity and selectivity of the nucleophiles in the Robinson annulation reaction.

20:16
🛠 Enhancing Conjugate Addition Yields in Robinson Annulation

The final paragraph focuses on strategies to increase the yield of the conjugate addition product in the Robinson annulation reaction, such as increasing steric hindrance around the carbonyl group to prevent nucleophilic attack at the carbonyl carbon. It reiterates the importance of considering both the strength of the base and the accessibility of the carbonyl group when predicting the outcome of the reaction. The summary concludes with a recap of the factors affecting nucleophilic attack, reinforcing the principles outlined throughout the script.

Mindmap
Keywords
💡Robinson Annulation Reaction
The Robinson Annulation Reaction is a type of organic reaction that involves the formation of a six-membered ring through a sequence of reactions including a Michael reaction and an intramolecular aldol reaction. It is central to the video's theme as it is the main reaction being discussed and demonstrated. The script describes the step-by-step process of this reaction using different examples, such as the reaction between cyclohexanone and an alpha,beta-unsaturated ketone.
💡Enolate Ion
An enolate ion is a type of ion that is formed when a base removes a hydrogen atom from the alpha carbon of a carbonyl compound. In the context of the video, the enolate ion plays a crucial role as a nucleophile in the Robinson Annulation Reaction, attacking the beta carbon of the Michael acceptor and later participating in the intramolecular aldol reaction. The script mentions the formation of the enolate ion from cyclohexanone as the starting point of the reaction.
💡Michael Reaction
The Michael Reaction is a conjugate addition of a nucleophile to an alpha,beta-unsaturated carbonyl compound. It is a key step in the Robinson Annulation Reaction, where the enolate ion acts as the nucleophile and adds to the beta carbon of the Michael acceptor. The video script illustrates this with the enolate ion attacking the beta carbon, leading to the formation of a new intermediate compound.
💡Nucleophile
A nucleophile is a substance that donates an electron pair to an electrophile in a chemical reaction. In the video, the enolate ion is described as a nucleophile that participates in the Michael reaction and the subsequent intramolecular aldol reaction. The script explains how the nucleophilic enolate ion can attack either the beta carbon or the electrophilic carbonyl group, but the focus is on the beta carbon attack for the Robinson Annulation.
💡Electrophile
An electrophile is a substance that accepts an electron pair in a chemical reaction. In the context of the video, the alpha,beta-unsaturated ketone acts as an electrophile in the Michael reaction, where it is attacked by the nucleophilic enolate ion. The script describes the Michael acceptor as having an alpha and beta carbon, with the beta carbon being the site of nucleophilic attack.
💡Intramolecular Aldol Reaction
An intramolecular aldol reaction is a type of aldol reaction that occurs within the same molecule, leading to the formation of a ring structure. This is the second major step in the Robinson Annulation Reaction discussed in the video. The script explains how, after the Michael reaction, the enolate ion can attack the carbonyl carbon within the same molecule to form a six-membered ring.
💡Cyclohexane Ring
A cyclohexane ring is a six-membered carbon ring that is commonly found in organic chemistry. The video script emphasizes the formation of a cyclohexane ring as the goal of the Robinson Annulation Reaction. It is highlighted that six-membered rings are more stable than four-membered rings, which is why the reaction specifically targets the formation of a cyclohexane ring.
💡Dehydration
Dehydration in the context of organic chemistry refers to the removal of a water molecule from a compound, often facilitated by heat. In the video, dehydration is a step in the Robinson Annulation Reaction where the hydroxyl group is removed to form a double bond, as described in the script when discussing the final steps of the reaction sequence.
💡Steric Hindrance
Steric hindrance occurs when the size or shape of a molecule prevents it from reacting as expected. In the video, the script mentions that the methyl group in a ketone provides steric hindrance to the carbonyl group, making it less accessible to nucleophilic attack and thus affecting the reactivity of the compound in the Robinson Annulation Reaction.
💡pKa
pKa is a measure of the acidity of a substance, indicating the pH at which half of the acid has been deprotonated. The video script uses pKa values to compare the reactivity of different Michael donors and acceptors, explaining how a lower pKa value indicates a stronger acid and a weaker base, which can influence the course of the Robinson Annulation Reaction.
Highlights

Introduction to the Robinson annulation reaction, a method for ring formation in organic chemistry.

Use of cyclohexanone and hydroxide to create an enolate ion through the removal of the alpha hydrogen.

The Michael reaction as a key step in the Robinson annulation, involving the enolate ion as a nucleophile and the alpha beta unsaturated ketone as an electrophile.

The importance of the Michael donor's ability to attack at the beta carbon versus the electrophilic carbonyl group.

Formation of a 1,5-dicarbonyl product as a typical outcome of the Michael reaction.

The intramolecular aldol reaction as the second step in the Robinson annulation, leading to a six-membered ring.

Stability considerations in ring formation, with six-membered rings being more stable than four-membered rings.

The role of water in the reaction, acting as a proton source for the enolate ion.

The dehydration step in the Robinson annulation, facilitated by heat to remove the hydroxyl group.

The final product of the Robinson annulation reaction, a cyclic alpha beta unsaturated ketone.

An example problem involving the reaction of acetone with an alpha beta unsaturated ketone under basic conditions.

The concept of weak bases as Michael donors, favoring conjugate addition over direct addition.

The comparison of the reactivity of aldehydes versus ketones in the context of the Michael acceptor.

The impact of steric hindrance on the accessibility of the carbonyl group for nucleophilic attack.

The pKa values of different compounds and their relation to the strength of the base in the reaction.

The strategic choice of Michael donor to increase the yield of the Robinson annulation reaction.

A summary of the factors influencing the direction of nucleophilic attack in the Robinson annulation, including base strength and carbonyl group accessibility.

Transcripts
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