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Related Concept Videos

Acid Halides to Amides: Aminolysis01:07

Acid Halides to Amides: Aminolysis

4.6K
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...
4.6K
Amines to Alkenes: Hofmann Elimination01:16

Amines to Alkenes: Hofmann Elimination

3.6K
Alkenes can be obtained from amines via an E2 elimination. The amine is first converted into a good leaving group, such as a quaternary ammonium salt. This is accomplished by treating the amine with an excess of alkyl halide, which results in a halide salt. Next, the halide salt is transformed into a hydroxide salt that functions as a base to enable elimination.
Under thermal conditions, the hydroxide can abstract a proton from the β carbon; this generates an alkene with the simultaneous...
3.6K
Preparation of Amines: Alkylation of Ammonia and Amines01:30

Preparation of Amines: Alkylation of Ammonia and Amines

5.0K
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...
5.0K
Base-Promoted α-Halogenation of Aldehydes and Ketones00:51

Base-Promoted α-Halogenation of Aldehydes and Ketones

4.3K
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...
4.3K
Amines to Amides: Acylation of Amines01:19

Amines to Amides: Acylation of Amines

3.8K
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...
3.8K
Acid Halides to Esters: Alcoholysis01:12

Acid Halides to Esters: Alcoholysis

4.4K
Alcoholysis is a nucleophilic acyl substitution reaction in which an alcohol functions as a nucleophile. Acid halides react with alcohol to produce esters. The mechanism proceeds in three steps:
4.4K

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Updated: Mar 28, 2026

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
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A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species

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Amine-to-Halogen Exchange Enables an Amine-Acid Etherification.

Andrew McGrath1, Sandip Kumar Das1, Eunjae Shim2

  • 1Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.

JACS Au
|March 27, 2026
PubMed
Summary

This study introduces a new amine-acid etherification reaction for creating valuable alkyl ethers. This versatile method uses amine-halogen exchange and selective reduction, enabling diverse applications in pharmaceuticals and materials.

Keywords:
C−O cross-couplingamine-acidetherificationhalogenationhigh-throughput experimentation

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Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile
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Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile

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Last Updated: Mar 28, 2026

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Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile
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Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile

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Area of Science:

  • Organic Chemistry
  • Synthetic Methodology
  • Catalysis

Background:

  • Ether synthesis is crucial across pharmaceutical, fragrance, materials, and agrichemical industries.
  • Conventional methods for synthesizing certain alkyl ethers can be challenging and limited in scope.
  • Accessing diverse chemical structures, including medicinally relevant compounds, remains an ongoing challenge in organic synthesis.

Purpose of the Study:

  • To develop a novel and versatile method for direct ether bond formation from readily available aliphatic amines and carboxylic acids.
  • To establish a robust etherification reaction suitable for late-stage diversification and building block repurposing.
  • To enable straightforward synthesis of medicinally relevant α-deuterated ethers and explore extensions to other nucleophiles.

Main Methods:

  • Development of a one-pot etherification reaction involving amine-halogen exchange followed by ester-selective reduction.
  • Utilizing free aliphatic amines and carboxylic acids as starting materials.
  • Employing high-throughput experimentation, computational studies, and mechanistic investigations to optimize the reaction.

Main Results:

  • Successful direct formation of C-(sp3)-O ether bonds from diverse alkyl amines and carboxylic acids.
  • Demonstrated suitability for late-stage diversification and building block repurposing, expanding chemical space access.
  • Achieved straightforward synthesis of α-deuterated ethers and extended the deamination strategy to phenolic ethers and halide products.
  • Identified specific reagents enabling selective ester reduction in the presence of secondary amides, crucial for the one-pot process.

Conclusions:

  • The developed amine-acid etherification reaction provides a versatile platform for constructing diverse ethers from abundant feedstocks.
  • The methodology offers a powerful tool for synthetic chemists, particularly in drug discovery and materials science.
  • The amine-halogen exchange strategy presents a broadly applicable approach for synthesizing various oxygen-containing compounds and halides.