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Related Concept Videos

Acid Halides to Esters: Alcoholysis01:12

Acid Halides to Esters: Alcoholysis

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:
Esters to Carboxylic Acids: Acid-Catalyzed Hydrolysis01:13

Esters to Carboxylic Acids: Acid-Catalyzed Hydrolysis

Hydrolysis of esters under acidic conditions proceeds through a nucleophilic acyl substitution. In the presence of excess water, the reaction proceeds in a reversible manner, forming carboxylic acids and alcohols.
During hydrolysis, the ester is first activated towards nucleophilic attack through the protonation of the carboxyl oxygen atom by the acid catalyst. The protonation makes the ester carbonyl carbon more electrophilic. In the next step, water acts as a nucleophile and adds to the...
Alkylation of β-Diester Enolates: Malonic Ester Synthesis01:14

Alkylation of β-Diester Enolates: Malonic Ester Synthesis

Malonic ester synthesis is a method to obtain α substituted carboxylic acids from ꞵ-diesters such as diethyl malonate and alkyl halides.
Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis01:07

Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis

Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and β-keto esters. The reaction occurs in the presence of an alkoxide base that abstracts the acidic proton of the β-keto esters. The step results in an enolate ion which is doubly stabilized. The enolate then reacts with an alkyl halide via the SN2 process to produce an alkylated ester intermediate with a new C–C bond. The hydrolysis of the intermediate, followed by acidification, results in an alkylated β-keto acid.
Acid Halides to Carboxylic Acids: Hydrolysis01:01

Acid Halides to Carboxylic Acids: Hydrolysis

Hydrolysis of acid halides is a nucleophilic acyl substitution reaction in which acid halides react with water to give carboxylic acids. The reaction occurs readily and does not require acid or a base catalyst.
As shown below, the mechanism involves a nucleophilic attack by water at the carbonyl carbon to form a tetrahedral intermediate. This is followed by the reformation of the carbon–oxygen π bond along with the departure of a halide ion. A final proton transfer step yields carboxylic acid...
Preparation of Amines: Alkylation of Ammonia and Amines01:30

Preparation of Amines: Alkylation of Ammonia and Amines

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...

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Synthesis of High Purity Nonsymmetric Dialkylphosphinic Acid Extractants
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Published on: October 19, 2017

Alkylation of H-phosphinate esters under basic conditions.

Isabelle Abrunhosa-Thomas1, Claire E Sellers, Jean-Luc Montchamp

  • 1Department of Chemistry, Texas Christian University, TCU Box 298860, Fort Worth, Texas 76129, USA.

The Journal of Organic Chemistry
|March 14, 2007
PubMed
Summary

Researchers developed a new, direct alkylation method for H-phosphinate esters using lithium bis(trimethylsilyl)amide (LHMDS). This efficient process works at low temperatures and yields moderate to good results for various substrates, including precursors to GABA analogues.

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Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines
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Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Published on: January 3, 2018

Area of Science:

  • Organic Chemistry
  • Synthetic Chemistry
  • Phosphorus Chemistry

Background:

  • H-phosphinate esters are versatile intermediates in organic synthesis.
  • Direct alkylation of phosphorus compounds can be challenging.
  • Existing methods often require harsh conditions or specific substrates.

Purpose of the Study:

  • To develop an efficient and general procedure for the direct alkylation of H-phosphinate esters.
  • To explore the scope and limitations of the new alkylation method.
  • To demonstrate the utility of the method in synthesizing GABA analogues or their precursors.

Main Methods:

  • Direct alkylation of H-phosphinate esters using lithium bis(trimethylsilyl)amide (LHMDS) as a base.
  • Low-temperature reaction conditions.
  • Utilizing a wide range of H-phosphinate esters and electrophiles, including secondary iodides and primary chlorides.

Main Results:

  • Successful direct alkylation of H-phosphinate esters was achieved with moderate to good isolated yields.
  • The reaction demonstrated broad substrate scope, accommodating various H-phosphinate esters and electrophiles.
  • This marks the first reported alkylation of H-phosphinate esters using secondary iodides or primary chlorides.
  • The method provides access to GABA analogues or their synthetic precursors.

Conclusions:

  • A novel, efficient, and general method for the direct alkylation of H-phosphinate esters has been established.
  • The developed procedure offers a simplified approach for synthesizing functionalized H-phosphinate esters.
  • This methodology expands the synthetic utility of H-phosphinate esters and facilitates the preparation of valuable chemical entities like GABA analogues.