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Related Concept Videos

Preparation of 1° Amines: Azide Synthesis01:22

Preparation of 1° Amines: Azide Synthesis

3.8K
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...
3.8K
Aryldiazonium Salts to Azo Dyes: Diazo Coupling01:11

Aryldiazonium Salts to Azo Dyes: Diazo Coupling

2.9K
The reaction of weakly electrophilic aryldiazonium (also called arenediazonium) salts with highly activated aromatic compounds leads to the formation of products with an —N=N— link, called an azo linkage. This reaction, presented in Figure 1, is known as diazo coupling and occurs without the loss of the nitrogen atoms of the aryldiazonium salt. Highly activated aromatic compounds such as phenols or arylamines favor the diazo coupling reaction. The coupling generally occurs at the...
2.9K
Aromatic Hydrocarbon Cations: Structural Overview01:18

Aromatic Hydrocarbon Cations: Structural Overview

2.7K
Cycloheptatriene is a neutral monocyclic unsaturated hydrocarbon that consists of an odd number of carbon atoms and an intervening sp3 carbon in the ring. The three double bonds in the ring correspond to 6 π electrons, which is a Huckel number, and therefore satisfies the criteria of 4n + 2 π electrons. However, the intervening sp3 carbon disrupts the continuous overlap of p orbitals. As a result, cycloheptatriene is not aromatic.
Removing one hydrogen from the intervening CH2 group...
2.7K
Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN101:14

Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN1

2.1K
Treating arylamines with nitrous acid gives aryldiazonium salts that are effective substrates in nucleophilic aromatic substitution reactions. The diazonio group in these salts can be easily displaced by different nucleophiles, yielding a wide variety of substituted benzenes. The leaving group departs as nitrogen gas, and this easy elimination is the driving force for the substitution reaction.
In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo,...
2.1K
Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions01:20

Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions

1.8K
Arenediazonium substitution reactions occur when the diazonium group is substituted by various functional groups such as halides, hydroxyl, nitrile, etc. For instance, arenediazonium salts react with copper(I) salts of chloride, bromide, or cyanide to form corresponding aryl chlorides, bromides, and nitriles. These reactions are named Sandmeyer reactions. Although the mechanism of this reaction is complicated, as illustrated in Figure 1, they are believed to progress via an aryl copper...
1.8K
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

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Related Experiment Video

Updated: Jun 6, 2025

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
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Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

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"Angular" Spirocyclic Azetidines: Synthesis, Characterization, and Evaluation in Drug Discovery.

Alexander A Kirichok1,2, Hennadii Tkachuk1, Kostiantyn Levchenko1,3

  • 1Enamine Ltd, Winston Churchill st. 78, 02094, Kyiv, Ukraine.

Angewandte Chemie (International Ed. in English)
|December 2, 2024
PubMed
Summary
This summary is machine-generated.

Newly synthesized spirocyclic azetidines serve as effective bioisosteres for common heterocycles in drug discovery. These novel compounds yield patent-free analogs of existing drugs with maintained activity and properties.

Keywords:
bioisosteresdrug designmedicinal chemistrysmall ringsspirocycles

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Synthesis and Purification of Iodoaziridines Involving Quantitative Selection of the Optimal Stationary Phase for Chromatography
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Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
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Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
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Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

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Synthesis and Purification of Iodoaziridines Involving Quantitative Selection of the Optimal Stationary Phase for Chromatography
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Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
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Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay

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Area of Science:

  • Medicinal Chemistry
  • Organic Synthesis
  • Drug Discovery

Background:

  • Spirocyclic azetidines are under-explored heterocyclic scaffolds.
  • Common saturated six-membered heterocycles are frequently used in drug structures.
  • Bioisosterism is a key strategy for drug optimization.

Purpose of the Study:

  • To synthesize and characterize novel angular spirocyclic azetidines.
  • To evaluate the potential of these azetidines as bioisosteres for six-membered heterocycles.
  • To incorporate azetidines into known drug structures to create new analogs.

Main Methods:

  • Synthesis of angular spirocyclic azetidines.
  • Characterization of synthesized compounds.
  • Incorporation of azetidines into Sonidegib and Danofloxacine scaffolds.
  • Evaluation of physicochemical properties and biological activity of analogs.

Main Results:

  • Successful synthesis and characterization of novel spirocyclic azetidines.
  • Demonstrated bioisosteric replacement of morpholine and piperazine moieties.
  • Generated patent-free analogs of Sonidegib and Danofloxacine.
  • Analogs retained similar physicochemical properties and high biological activity.

Conclusions:

  • Angular spirocyclic azetidines are viable and valuable bioisosteres.
  • These scaffolds offer a route to novel, patent-free drug analogs.
  • The findings support the utility of spirocyclic azetidines in drug discovery programs.