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Related Concept Videos

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.
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.
α-Hydroxy Ketones via Reductive Coupling of Esters: Acyloin Condensation Overview01:19

α-Hydroxy Ketones via Reductive Coupling of Esters: Acyloin Condensation Overview

The pinacol and McMurry reactions involve the reductive coupling of ketones or aldehydes. Similarly, the bimolecular reductive coupling of two ester molecules in the presence of sodium metal in an aprotic solvent yields an α-hydroxy ketone product. The α-hydroxy ketone is also called acyloin, so the reaction is referred to as ‘acyloin condensation.’
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...
Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Overview01:20

Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Overview

The Fischer esterification reaction was developed by the German chemist Emil Fischer in 1895. It is a condensation reaction between carboxylic acids and alcohols in an acidic medium to give esters and water.
Esters to β-Ketoesters: Claisen Condensation Mechanism01:08

Esters to β-Ketoesters: Claisen Condensation Mechanism

Regular Claisen condensation involves the synthesis of β-ketoesters by combining identical ester molecules bearing two α hydrogens in the presence of an alkoxide base. The reaction commences with the deprotonation of the acidic α hydrogen by the base to form a resonance stabilized ester enolate. This nucleophilic ion then attacks the carbonyl center of another ester molecule to generate a tetrahedral alkoxide intermediate. Next, the expulsion of the alkoxide group from the intermediate restores...

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Facile Preparation of 4-Substituted Quinazoline Derivatives
11:51

Facile Preparation of 4-Substituted Quinazoline Derivatives

Published on: February 15, 2016

A practical method for preparation of 4-hydroxyquinolinone esters.

Gregory L Beutner1, Jeffrey T Kuethe, Nobuyoshi Yasuda

  • 1Department of Process Research, Merck and Company, Inc., P.O. Box 2000, Rahway, New Jersey 07065, USA. gregory_beutner@merck.com

The Journal of Organic Chemistry
|August 7, 2007
PubMed
Summary

A new, safer method for synthesizing 4-hydroxyquinolinone esters and amides uses diisopropylethylamine and sodium tert-butoxide. This practical approach avoids hazardous reagents like sodium hydride, enabling broader applications in medicinal chemistry.

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Facile Preparation of 4-Substituted Quinazoline Derivatives
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Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile
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Area of Science:

  • Medicinal Chemistry
  • Organic Synthesis

Background:

  • 4-Hydroxyquinolinone esters are crucial scaffolds in medicinal chemistry.
  • Traditional synthesis methods often employ hazardous reagents like sodium hydride, limiting scalability and safety.

Purpose of the Study:

  • To develop a safer, practical, and general method for synthesizing 4-hydroxyquinolinone esters and amides.
  • To overcome the safety and scalability limitations associated with sodium hydride-based methods.

Main Methods:

  • Utilized a combination of diisopropylethylamine and sodium tert-butoxide.
  • Applied the method to the synthesis of various 4-hydroxyquinolinone esters and amides.

Main Results:

  • Achieved good yields for the target compounds.
  • Demonstrated a practical and safe alternative to existing methods.
  • The new method is suitable for general application.

Conclusions:

  • The described method provides a safe and efficient route to 4-hydroxyquinolinone esters and amides.
  • This advancement facilitates the broader use of these important medicinal motifs in synthesis.