What are the Two Starting Materials for a Robinson Annulation? [SOLVED]

Knowing what are the two starting materials for a Robinson annulation will help you solve some problems. This article will discuss the introduction of the two main materials in Robinson annulation, the mechanism of Robinson annulation, and some sample questions, answers, and explanations that will help you learn.

Two Starting Materials for a Robinson Annulation

Introduction to Robinson Annulation

Robinson annulation is an essential reaction in organic chemistry that plays a significant role in the synthesis of polycyclic compounds. Named after Sir Robert Robinson, this reaction combines a Michael addition and an intramolecular aldol condensation to form six-membered rings, which are commonly found in steroids, alkaloids, and other bioactive molecules.

To perform Robinson annulation, two specific starting materials are required. So what are the two starting materials for a Robinson annulation? Here are the answers:

    1. α,β-unsaturated ketone (Michael acceptor)
    2. Ketone with α hydrogen (Michael donor)

These two reactants undergo a Michael addition followed by an aldol condensation, leading to the formation of a new six-membered ring with conjugated double bonds.

The Two Starting Materials for Robinson Annulation

Here are what are the two starting materials for a Robinson annulation and their explanations:

1. α,β-Unsaturated Ketone (Michael Acceptor)

After knowing what are the two starting materials for a Robinson annulation, the first important starting material in Robinson annulation is α,β-unsaturated ketone, which acts as a Michael acceptor. This compound contains a carbonyl group (C=O) conjugated to a C=C double bond. The electrophilic β carbon of α,β-unsaturated ketone allows it to undergo conjugate addition (1,4 addition) with a nucleophile.

Examples of α,β-unsaturated ketones:

    • Methyl vinyl ketone (MVK, CH3CH=CHCOCH3)
    • Cyclohexanone (C6H8O)
    • Chalcones (aryl-substituted α,β-unsaturated ketones)

These molecules serve as the acceptor in the Michael addition step, facilitating the reaction with the second starting material.

2. Ketone with an α-Hydrogen (Michael Donor)

The second starting material is a ketone (or a cyclic ketone) that contains at least one α-hydrogen. These ketones act as nucleophiles (Michael donors) because they can form an enolate under basic conditions. The enolate generated from these ketones attacks the β-carbon of the α,β-unsaturated ketone in a conjugate addition reaction.

Examples of ketones with α-hydrogen:

    • Cyclohexanone (C6H10O)
    • Acetone (CH3COCH3)
    • Methyl ethyl ketone (MEK, CH3COCH2CH3)

After the Michael addition, an intramolecular aldol condensation occurs, leading to the formation of a fused six-membered ring system.

Mechanism of Robinson Annulation

Robinson annulation is a two-step reaction mechanism that involves Michael addition followed by intramolecular aldol condensation, leading to the formation of a fused six-membered ring system. So it is important to know what are the two starting materials for a Robinson annulation. Below is a deeper look into each step, along with additional examples.

Step 1: Michael’s Addition

    • A base (e.g., NaOH, LDA) deprotonates the Michael donor (ketone with α-hydrogen), forming an enolate ion.
    • The enolate acts as a nucleophile and attacks the β-carbon of the α,β-unsaturated ketone (Michael acceptor) in a 1,4-conjugate addition.
    • The intermediate is protonated, leading to a stabilized β-keto compound.

Example: Michael Addition Between Cyclohexanone and Methyl Vinyl Ketone

Cyclohexanone + Methyl Vinyl Ketone→ Base​ → β-Keto Intermediate

This β-keto intermediate then undergoes aldol condensation.

Step 2: Intramolecular Aldol Condensation

    • The base deprotonates the α-carbon of the newly formed β-keto compound, generating a second enolate.
    • This enolate attacks the carbonyl carbon of the same molecule, forming a new six-membered ring through intramolecular aldol addition.
    • Dehydration occurs, removing a water molecule and forming a conjugated enone system in the final product.

Example: Formation of 2-methyl-2-decalone

β-Keto Intermediate→ Base,Heat → ​2-Methyl-2-Decalone

This final product is a fused bicyclic system containing a conjugated enone, which is common in natural products and pharmaceuticals.

Additional Example: Robinson Annulation with Cyclopentanone

Some other examples that apply what are the two starting materials for Robinson annulation:

Reactants:
    • Cyclopentanone (Michael donor)
    • Cyclohexanone (Michael acceptor)
Reaction Mechanism:
    • Michael addition: The enolate of cyclopentanone adds to cyclohexanone.
    • Aldol condensation: The newly formed β-keto compound undergoes ring closure.
    • Dehydration: The product is a fused bicyclic ketone.

Final Product: 2-Methyl-2-Octalone

This reaction showcases how different ketones can be used to synthesize complex cyclic structures.

Example of Robinson Annulation Reaction

Knowing what are the two starting materials for a Robinson annulation will make it easier for you to work on the example problems. A classic example of Robinson annulation involves the reaction between cyclohexanone (Michael donor) and methyl vinyl ketone (Michael acceptor). Reaction Steps:

Michael Addition:

    • Cyclohexanone forms an enolate under basic conditions.
    • The enolate attacks methyl vinyl ketone at the β-position, forming a new β-keto intermediate.

Aldol Condensation:

    • The β-keto intermediate undergoes an intramolecular aldol reaction, forming a new six-membered ring.
    • Dehydration leads to a conjugated enone system.

Final Product: 2-Methyl-2-decalone (bicyclic compound).

Quiz and Exam Questions on Robinson Annulation

After knowing what are the two starting materials for a Robinson annulation, here we provide some examples of questions and answers, along with explanations that will help you understand:

Question 1: What are the two starting materials required for a Robinson annulation?

Answer:

    1. An α,β-unsaturated ketone (Michael acceptor)
    2. A ketone with an α-hydrogen (Michael donor)

Explanation:

If we look at what are the two starting materials for a Robinson annulation, Robinson annulation involves a Michael addition followed by an aldol condensation, which requires an α,β-unsaturated ketone to act as the electrophile and a ketone with an α hydrogen to act as the nucleophile.

Question 2: Which compounds can act as a Michael acceptor in a Robinson annulation?

A) Cyclohexanone
B) Acetone
C) Methyl vinyl ketone
D) Ethanol

Answer: C) Methyl vinyl ketone

Explanation:

If you understand what are the two starting materials for a Robinson annulation, only methyl vinyl ketone contains an α,β-unsaturated carbonyl system, which makes it suitable as a Michael acceptor. Cyclohexanone and acetone do not have the required double bond, and ethanol is not a ketone.

Question 3: What is the role of a base in a Robinson annulation reaction?

A) It acts as a catalyst in aldol condensation
B) It generates the enolate ion
C) It acts as a reducing agent
D) It forms the final product directly

Answer: B) It generates the enolate ion

Explanation:

Bases (e.g., NaOH, LDA) deprotonate the α-carbon of the ketone, producing an enolate, which serves as a nucleophile for the Michael addition step. This can be understood in terms of the mechanism of what are the two starting materials for a Robinson annulation.

Question 4: What is the product of the Robinson annulation between cyclohexanone and methyl vinyl ketone?

A) 2-Methyl-2-decalone
B) Benzophenone
C) Acetophenone
D) Cyclopentanone

Answer: A) 2-Methyl-2-decalone

Explanation:

The reaction between cyclohexanone and methyl vinyl ketone leads to the formation of a fused bicyclic system, 2-Methyl-2-decalone, through the Robinson annulation mechanism.

Question 5: Which step in Robinson annulation is responsible for ring formation?

A) Michael addition
B) Intramolecular aldol condensation
C) Proton transfer
D) Dehydration

Answer: B) Intramolecular aldol condensation

Explanation:

The Michael addition connects the two reactants, but the intramolecular aldol condensation forms the new six-membered ring, making it a crucial step in the annulation process.

Question 6: Mechanism-Based Multiple Choice

Which of the following is the correct sequence of steps in a Robinson annulation reaction?

A) Aldol condensation → Michael addition → Dehydration
B) Michael addition → Aldol condensation → Dehydration
C) Michael addition → Dehydration → Aldol condensation
D) Enolate formation → Direct cyclization → Dehydration

Answer: B) Michael addition → Aldol condensation → Dehydration

Explanation:

    • Step 1: Michael Addition → The enolate of the ketone attacks the α,β-unsaturated ketone via a 1,4-conjugate addition.
    • Step 2: Intramolecular Aldol Condensation → The new β-keto compound forms an enolate again, which reacts with the ketone’s carbonyl group to create a six-membered ring.
    • Step 3: Dehydration → The intermediate undergoes dehydration to form a conjugated enone system.

Question 7: Choosing a Suitable Michael Acceptor

Which of the following compounds CANNOT serve as a Michael acceptor in a Robinson annulation?

A) Methyl vinyl ketone
B) Chalcone
C) Cyclohexanone
D) Acetone

Answer: D) Acetone

Explanation:

    • A Michael acceptor must have an α,β-unsaturated carbonyl system (C=C-C=O) to accept nucleophilic attack.
    • Methyl vinyl ketone, chalcone, and cyclohexanone all contain α, and β-unsaturation, making them good acceptors.
    • Acetone lacks a C=C bond and cannot act as a Michael acceptor, but it can be a Michael donor.

Question 8: Predicting Enolate Formation

Which of the following ketones is MOST reactive in forming an enolate for a Robinson annulation?

A) Cyclopentanone
B) Cyclohexanone
C) 3-Pentanone
D) Acetophenone

Answer: B) Cyclohexanone

Explanation:

    • Enolate formation requires an α-hydrogen and good enolate stabilization.
    • Cyclohexanone forms an enolate easily due to the favorable six-membered ring strain and stability.
    • Cyclopentanone also forms an enolate but is slightly less stable.
    • 3-Pentanone can form an enolate but is less common in Robinson annulation.
    • Acetophenone has steric hindrance from the phenyl ring, making enolate formation less favorable.

Further Exploration of Robinson Annulation: Mechanistic Insights & Applications

Having discussed what are the two starting materials for a Robinson annulation, now that we have covered the basic mechanics of Robinson annulation, let’s dive deeper:

1. Detailed Stepwise Mechanism with Resonance Structures

Step 1: Formation of the Enolate (Michael Donor Activation)

    • The Michael donor (e.g., cyclohexanone) is deprotonated at the α-position by a strong base (such as NaOH or LDA), forming an enolate ion.
    • The enolate is stabilized by resonance between the negatively charged oxygen and the α-carbon.

Cyclohexanone + Base→ Enolate Formation

Step 2: Michael Addition (Conjugate Addition to Michael Acceptor)

    • The enolate nucleophile attacks the β-carbon of the α,β-unsaturated ketone (e.g., methyl vinyl ketone) in a 1,4-conjugate addition.
    • A new C-C bond is formed, generating a β-keto intermediate.

Enolate + Methyl Vinyl Ketone→ Michael Addition Product

Step 3: Enolate Formation for Aldol Condensation

    • The β-keto intermediate contains a new α-hydrogen, which can be deprotonated again by the base, forming another enolate ion.
    • This enolate undergoes intramolecular nucleophilic attack on the carbonyl carbon within the same molecule, leading to ring formation.

β-Keto Intermediate → Base​ → New Enolate Formation

Step 4: Intramolecular Aldol Addition

The new enolate attacks the carbonyl group within the same molecule, forming a new six-membered ring via an intramolecular aldol condensation.

Enolate + Carbonyl → Cyclized Aldol Intermediate

Step 5: Dehydration (Formation of Conjugated Enone System)

Under heating conditions, dehydration occurs, eliminating a water molecule and forming a conjugated enone product.

Cyclized Aldol Intermediate→ Heat→ ​Conjugated Enone

This leads to the final fused bicyclic ketone, which is the hallmark of Robinson annulation products.

2. Factors Affecting Reactivity and Selectivity

Choice of Base

    • Weak bases (e.g., NaOH, EtONa) favor enolate formation for Michael addition.
    • Strong bases (e.g., LDA, NaH) are required for regioselective enolate generation.

Steric and Electronic Effects

    • Bulky ketones may hinder enolate formation.
    • Electron-withdrawing groups on the Michael acceptor enhance electrophilicity, increasing reactivity.

Temperature Effects

    • Mild conditions favor aldol addition (kinetic product).
    • Higher temperatures drive dehydration, forming the final enone product (thermodynamic product).

3. Applications in Natural Product Synthesis

Robinson annulation is widely used in the synthesis of complex polycyclic natural products, including:

A. Steroid Biosynthesis

Many steroids, such as testosterone and cortisone, contain fused six-membered rings that can be constructed using Robinson annulation.

Example: Synthesis of Androstenedione Precursor

Michael Addition + Aldol Cyclization→ Steroid Core Formation

B. Alkaloid Synthesis

Alkaloids like quinine and morphine have bicyclic structures that can be synthesized using Robinson annulation as a key step.

C. Pharmaceutical Applications

Many anti-inflammatory and anticancer drugs contain polycyclic frameworks derived from Robinson annulation reactions.

If you want to learn more and practice solving problems, our platform is the right place for you. Our platform provides clear explanations and valid sample questions to help you master the topics. With structured lessons and exercises, you can improve your understanding and achieve your academic goals effectively.

Robinson annulation is a powerful reaction for building fused six-membered rings in organic synthesis. What are the two starting materials for a Robinson annulation, an α,β-unsaturated ketone, and a ketone with α hydrogen, undergoing Michael addition followed by aldol condensation. This reaction is invaluable in the synthesis of complex natural products, including steroids and alkaloids.

By understanding the mechanism, key intermediates, and reaction conditions, as well as several examples of practice questions, students can master the principle of Robinson annulation and apply it in synthetic chemistry.

FAQ’s

  1. What are the two starting materials for a Robinson annulation?

The two starting materials are an α,β-unsaturated ketone (Michael acceptor) and a β-keto ester or β-ketone (Michael donor).

  1. Why are these materials necessary?

The Michael acceptor provides an electrophilic site for conjugate addition, while the Michael donor forms an enolate for nucleophilic attack.

  1. Can any ketone be used as a Michael donor?

No, only β-keto esters or β-diketones with acidic hydrogen can form stable enolates.

  1. What is a common example of each material?

Typical examples include methyl vinyl ketone (MVK) as the Michael acceptor and 2,4-pentanedione as the Michael donor.

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