Textbook Question
Show how the amino acid alanine can be synthesized from propanoic acid.
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Ch. 17 - Reactions at the Alpha-Carbon
Bruice8th EditionOrganic ChemistryISBN: 9780135213711
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Table of contents
- Ch. 1 - Remembering General Chemistry: Electronic Structure and Bonding (Part 1)31
- Ch. 1 - Remembering General Chemistry: Electronic Structure and Bonding (Part 2)65
- Ch. 2 - Acids and Bases: Central to Understanding Organic Chemistry84
- Ch. 3 - An Introduction to Organic Compounds:Nomenclature, Physical Properties, and Structure183
- Ch. 4 - Isomers: The Arrangement of Atoms in Space121
- Ch. 5 - Alkenes: Structure, Nomenclature, and an Introduction to Reactivity • Thermodynamics and Kinetics83
- Ch. 6 - The Reactions of Alkenes • The Stereochemistry of Addition Reactions175
- Ch. 7 - The Reactions of Alkynes • An Introduction to Multistep Synthesis119
- Ch. 8 - Delocalized Electrons: Their Effect on Stability, pKa, and the Products of a Reaction • Aromaticity and Electronic Effects: An Introduction to the Reactions of Benzene148
- Ch. 9 - Substitution and Elimination Reactions of Alkyl Halides212
- Ch. 10 - Reactions of Alcohols, Ethers, Epoxides, Amines, and Sulfur-Containing Compounds131
- Ch. 11 - Organometallic Compounds60
- Ch. 12 - Radicals90
- Ch. 13 - Mass Spectrometry; Infrared Spectroscopy; UV/Vis Spectroscopy62
- Ch. 14 - NMR Spectroscopy95
- Ch. 15 - Reactions of Carboxylic Acids and Carboxylic Acid Derivatives123
- Ch. 16 - Reactions of Aldehydes and Ketones • More Reactions of Carboxylic Acid Derivatives141
- Ch. 17 - Reactions at the Alpha-Carbon101
- Ch. 18 - Reactions of Benzene and Substituted Benzenes144
- Ch. 19 - More About Amines • Reactions of Heterocyclic Compounds49
- Ch. 20 - The Organic Chemistry of Carbohydrates80
- Ch. 21 - Amino Acids, Peptides, and Proteins57
- Ch. 22 - Catalysis in Organic Reactions and in Enzymatic Reactions35
- Ch. 23 - The Organic Chemistry of the Coenzymes—Compounds Derived from Vitamins1
- Ch. 28 - Pericyclic Reactions58
Chapter 18, Problem 78
A Mannich reaction puts a 
-group on the α-carbon of a ketone. Propose a mechanism for the reaction.
Verified step by step guidance1
The Mannich reaction begins with the formation of an iminium ion. This occurs when a secondary amine (R2NH) reacts with formaldehyde (HCHO) in an acid-catalyzed environment. The formaldehyde is protonated by the acid, making it more electrophilic, and the amine attacks the carbonyl carbon to form a carbinolamine intermediate. This intermediate loses water to form the iminium ion (R2N=CH2).
Next, the ketone (or aldehyde) undergoes enolate formation. In the presence of a base, the α-hydrogen of the ketone is deprotonated, forming the enolate ion. The enolate is a nucleophile due to the negative charge on the oxygen and the resonance-stabilized negative charge on the α-carbon.
The enolate ion then attacks the electrophilic iminium ion. The nucleophilic α-carbon of the enolate adds to the carbon of the iminium ion, forming a new C-C bond. This step is the key carbon-carbon bond-forming step in the Mannich reaction.
The resulting intermediate is protonated to form the final Mannich product. This product contains the R2NCH2 group attached to the α-carbon of the ketone or aldehyde.
Finally, the reaction is neutralized, and the product is isolated. The Mannich product is a β-amino carbonyl compound, which is a versatile intermediate in organic synthesis.
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Key Concepts
Here are the essential concepts you must grasp in order to answer the question correctly.
Mannich Reaction
The Mannich reaction is a three-component reaction that involves the condensation of an amine, formaldehyde, and a ketone or aldehyde to form a β-amino carbonyl compound. This reaction is significant in organic synthesis for introducing amine functionalities into carbon skeletons, which can be further transformed into various bioactive compounds.
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05:09
Heck Reaction
Nucleophilic Addition
Nucleophilic addition is a fundamental reaction mechanism in organic chemistry where a nucleophile attacks an electrophilic carbon atom, typically in a carbonyl group. In the context of the Mannich reaction, the amine acts as the nucleophile, attacking the carbonyl carbon of the ketone, leading to the formation of a tetrahedral intermediate.
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08:27Nucleophilic Addition
Proton Transfer and Rearrangement
Proton transfer and rearrangement are critical steps in many organic reaction mechanisms, including the Mannich reaction. After the nucleophilic addition, the tetrahedral intermediate undergoes proton transfer to stabilize the structure, followed by rearrangement to form the final product, which is a β-amino ketone. Understanding these steps is essential for proposing a complete mechanism.
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06:08Definition of Claisen Rearrangement
Related Practice
Textbook Question
Show how the following compounds can be synthesized. The only carbon-containing compounds available to you for each synthesis are shown.
b.
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Textbook Question
Propose a mechanism for each of the following reactions:
b.
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Textbook Question
A Cannizzaro reaction is the reaction of an aldehyde that has no a-hydrogens with concentrated aqueous sodium hydroxide. In this reaction, half the aldehyde is converted to a carboxylic acid and the other half is converted to an alcohol. Propose a mechanism for the following Cannizzaro reaction:
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Textbook Question
A student tried to prepare the following compounds using aldol condensations. Which of these compounds was she successful in synthesizing? Explain why the other syntheses were not successful.
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Textbook Question
A carboxylic acid is formed when an a-haloketone reacts with hydroxide ion. This reaction is called a Favorskii reaction. Propose a mechanism for the following Favorskii reaction. (Hint: In the first step, HO- removes a proton from the a-carbon that is not bonded to Br; a three-membered ring is formed in the second step; and HO- is a nucleophile in the third step.)
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