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Acid Halides to Amides: Aminolysis01:07

Acid Halides to Amides: Aminolysis

2.7K
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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Base-Promoted α-Halogenation of Aldehydes and Ketones00:51

Base-Promoted α-Halogenation of Aldehydes and Ketones

3.4K
α-Halogenation of aldehydes and ketones is a reaction involving the substitution of α hydrogens with halogens in the presence of a base.  The reaction begins with the abstraction of  α hydrogen by the base to produce a nucleophilic enolate ion. This intermediate undergoes a subsequent nucleophilic substitution with the halogen to produce a monohalogenated carbonyl compound. If the starting substrate has more than one α hydrogen, it is difficult to stop the reaction...
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Preparation of Amines: Alkylation of Ammonia and Amines01:30

Preparation of Amines: Alkylation of Ammonia and Amines

3.3K
Alkylation is one of the methods used to prepare amines. Direct alkylation of ammonia or a primary amine with an alkyl halide gives polyalkylated amines along with a quaternary ammonium salt through successive SN2 reactions. This process of making the quaternary salt through the direct alkylation method is called exhaustive alkylation.
Each alkylation step makes the nitrogen center more nucleophilic, which triggers successive alkylations until a quaternary ammonium salt is formed. Considering...
3.3K
Preparation of 1° Amines: Gabriel Synthesis01:28

Preparation of 1° Amines: Gabriel Synthesis

3.5K
Direct alkylation is not a suitable method for synthesizing amines because it produces polyalkylated products. Gabriel synthesis is the most preferred method to exclusively make primary amines. The method uses phthalimide, which contains a protected form of nitrogen that participates in alkylation only once to predominantly give primary amines.
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
3.5K
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
Electrophilic Addition to Alkynes: Halogenation02:38

Electrophilic Addition to Alkynes: Halogenation

8.2K
Introduction
Halogenation is another class of electrophilic addition reactions where a halogen molecule gets added across a π bond. In alkynes, the presence of two π bonds allows for the addition of two equivalents of halogens (bromine or chlorine). The addition of the first halogen molecule forms a trans-dihaloalkene as the major product and the cis isomer as the minor product. Subsequent addition of the second equivalent yields the tetrahalide.
8.2K

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Updated: Jun 15, 2025

A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
07:06

A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis

Published on: February 16, 2020

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Aryne Aminohalogenation Using Protic Amines Enabled by Halogen Transfer.

Joshua T Gavin1, Lars W Anderson1, Courtney C Roberts1

  • 1Department of Chemistry, University of Minnesota─Twin Cities, Minneapolis, Minnesota 55455, United States.

Organic Letters
|August 28, 2024
PubMed
Summary

This study introduces a new method for aryne difunctionalization using halogen transfer reagents and protic amines. This approach overcomes limitations of previous methods, enabling efficient aminohalogenation of N-heterocyclic scaffolds.

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Area of Science:

  • Organic Chemistry
  • Synthetic Methodology

Background:

  • Aryne difunctionalization is a key area in synthetic organic chemistry.
  • A significant limitation in current aryne difunctionalization methods involves the requirement for nucleophiles with proton sources.
  • Developing new strategies to overcome this limitation is crucial for expanding the scope of aryne chemistry.

Purpose of the Study:

  • To develop a novel method for aryne aminohalogenation difunctionalization.
  • To enable the use of protic amines in aryne difunctionalization reactions.
  • To demonstrate the broad applicability of the developed method to various N-heterocyclic scaffolds.

Main Methods:

  • Utilizing halogen transfer reagents in conjunction with protic amines and arynes.
  • Employing a range of N-heterocyclic scaffolds for the difunctionalization reactions.
  • Characterization of the synthesized products and demonstration of their synthetic utility through derivatization.

Main Results:

  • Successfully achieved aryne aminohalogenation difunctionalization using protic amines.
  • Obtained yields of up to 86% for the desired difunctionalized products.
  • Demonstrated the method's effectiveness with diverse N-heterocyclic amine substrates.

Conclusions:

  • The developed method effectively overcomes the limitation of proton sources in aryne difunctionalization.
  • This new protocol provides a valuable tool for the synthesis of complex molecules containing N-heterocyclic motifs.
  • The synthetic utility of the products is confirmed through subsequent derivatization reactions.