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Related Concept Videos

Acid Halides to Amides: Aminolysis01:07

Acid Halides to Amides: Aminolysis

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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...
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Amines to Amides: Acylation of Amines01:19

Amines to Amides: Acylation of Amines

2.4K
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...
2.4K
Preparation of Amides01:29

Preparation of Amides

3.0K
Amides are synthesized by treating carboxylic acids with amines in the presence of dehydrating agents like dicyclohexylcarbodiimide (DCC).
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
3.0K
Preparation of 1° Amines: Azide Synthesis01:22

Preparation of 1° Amines: Azide Synthesis

3.9K
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...
3.9K
Preparation of Amines: Reductive Amination of Aldehydes and Ketones01:38

Preparation of Amines: Reductive Amination of Aldehydes and Ketones

2.7K
Carbonyl compounds and primary amines undergo reductive amination first to produce imines, followed by secondary amines in the same reaction mixture, using selective reducing agents like sodium cyanoborohydride or sodium triacetoxyborohydride. Reductive amination produces different degrees of substitution of amines depending on the starting amine substrate.
2.7K
Amides to Amines: LiAlH4 Reduction01:20

Amides to Amines: LiAlH4 Reduction

4.5K
Amide reduction with strong reducing agents like lithium aluminum hydride proceeds through a nucleophilic acyl substitution to form amines. Primary, secondary, and tertiary amides yield primary, secondary, and tertiary amines, respectively.
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate.
4.5K

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Development and Applications of an Amide Linchpin Reagent.

Bhavana Uppalapati1, Maxime A Aubry1, Qiang Wang1

  • 1Centre for Catalysis Research and Innovation, Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie-Curie Pvt, Ottawa, ON, K1N 6N5, Canada.

Angewandte Chemie (International Ed. in English)
|November 22, 2024
PubMed
Summary

Researchers developed a novel amide linchpin reagent for synthesizing diverse amides. This doubly electrophilic building block enables controlled, chemoselective amide bond construction through unique reaction pathways.

Keywords:
amideschemoselectivitylinchpinmasked isocyanateunsymmetrical ureas

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Area of Science:

  • Organic Chemistry
  • Synthetic Chemistry
  • Methodology Development

Background:

  • Linchpin reagents are versatile building blocks enabling selective functionalization.
  • Efficient synthesis of diverse amide classes, including challenging ones, remains a key goal in organic chemistry.
  • Existing methods for amide synthesis often lack the desired chemoselectivity or scope.

Purpose of the Study:

  • To develop and validate the first amide linchpin reagent.
  • To demonstrate its utility as a doubly electrophilic building block for amide synthesis.
  • To explore its application in constructing challenging amide structures, lactams, and ureas.

Main Methods:

  • Development of a novel amide linchpin reagent.
  • Rhodium-catalyzed electrophilic amination for initial functionalization.
  • Subsequent derivatization using Grignard reagents or alkylating agents to form secondary and tertiary amides.

Main Results:

  • Successful synthesis of various amides, including secondary and tertiary amides, using the linchpin reagent.
  • High chemoselectivity achieved by controlled reactivity at sequential electrophilic sites.
  • Demonstrated potential for forming lactams and unsymmetrical ureas, highlighting the reagent's broad applicability.

Conclusions:

  • The developed amide linchpin reagent represents a significant advancement in synthetic methodology.
  • It enables atypical amide bond construction with high control and selectivity.
  • This reagent broadens the synthetic toolkit for accessing diverse nitrogen-containing compounds.