Related Experiment Video
Updated: Jun 19, 2026
07:56
Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyl(tropone)iron
Published on: August 12, 2019
Amphoteric amino aldehydes reroute the aza-Michael reaction
1Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada M5S 3H6.
Journal of the American Chemical Society
|October 28, 2009
Summary
Stable dimeric amino aldehydes undergo a domino reaction with unsaturated aldehydes to create novel compounds. This discovery highlights the potential of amphoteric molecules in chemical synthesis and reaction development.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Catalysis
Background:
- Amphoteric amino aldehydes are known to exist as stable dimers.
- Domino reactions offer efficient synthetic pathways by performing multiple transformations sequentially.
- Controlling reactivity based on molecular structure is crucial in organic synthesis.
Purpose of the Study:
- To investigate the domino reaction between dimeric amphoteric amino aldehydes and alpha,beta-unsaturated aldehydes.
- To explore the influence of the dimeric state on reaction outcomes.
- To discover novel cyclization pathways and synthetic applications of amphoteric molecules.
Main Methods:
- Utilizing dimeric amphoteric amino aldehydes in aza-Michael/aldol domino reactions.
- Employing reaction conditions that maintain dimer stability.
- Characterizing the resulting 1,5-aminohydroxyaldehydes using analytical techniques.
Main Results:
- High yields and diastereoselectivities of stable 1,5-aminohydroxyaldehydes were achieved.
- The dimeric nature of the amino aldehydes was critical for directing the reaction pathway.
- A novel 8-(enolendo)-exo-trig cyclization was successfully achieved by controlling dimer dissociation.
Conclusions:
- Amphoteric amino aldehydes can be effectively utilized in domino reactions, leading to valuable products.
- The inherent dimeric structure of these molecules enables unique reactivity and stereochemical control.
- This study expands the scope of reaction discovery using amphoteric molecules in organic synthesis.
Related Concept Videos
01:22Preparation of 1° Amines: Azide Synthesis
Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
01:07Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
In the presence of an aqueous base and a halogen, primary amides can lose the carbonyl (as carbon dioxide) and undergo rearrangement to form primary amines. This reaction, called the Hofmann rearrangement, can produce primary amines (aryl and alkyl) in high yields without contamination by secondary and tertiary amines.
01:19Amines to Amides: Acylation of Amines
Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...
01:07Acid Halides to Amides: Aminolysis
Aminolysis is a nucleophilic acyl substitution reaction, where ammonia or amines act as nucleophiles to give the substitution product. Acid halides react with ammonia, primary amines, and secondary amines to yield primary, secondary, and tertiary amides, respectively.
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
01:11Aryldiazonium Salts to Azo Dyes: Diazo Coupling
The reaction of weakly electrophilic aryldiazonium (also called arenediazonium) salts with highly activated aromatic compounds leads to the formation of products with an —N=N— link, called an azo linkage. This reaction, presented in Figure 1, is known as diazo coupling and occurs without the loss of the nitrogen atoms of the aryldiazonium salt. Highly activated aromatic compounds such as phenols or arylamines favor the diazo coupling reaction. The coupling generally occurs at the para position.
01:26Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism
The Hofmann and Curtius rearrangement reactions can be applied to synthesize primary amines from carboxylic acid derivatives such as amides and acyl azides. In the Hofmann rearrangement, a primary amide undergoes deprotonation in the presence of a base, followed by halogenation to generate an N-haloamide. A second proton abstraction produces a stabilized anionic species, which rearranges to an isocyanate intermediate via an alkyl group migration from the carbonyl carbon to the neighboring...