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Related Concept Videos

Aryldiazonium Salts to Azo Dyes: Diazo Coupling01:11

Aryldiazonium Salts to Azo Dyes: Diazo Coupling

4.2K
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 para...
4.2K
1° Amines to Diazonium or Aryldiazonium Salts: Diazotization with NaNO2 Mechanism01:37

1° Amines to Diazonium or Aryldiazonium Salts: Diazotization with NaNO2 Mechanism

5.3K
Nitrous acid is a relatively weak and unstable acid prepared in situ by the reaction of sodium nitrite and cold, dilute hydrochloric acid. In an acidic solution, the nitrous acid undergoes protonation when it loses water to form a nitrosonium ion—an electrophile. Nitrous acid reacts with primary amines to give diazonium salts. The reaction is called diazotization of primary amines.
5.3K
Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions01:20

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

2.7K
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...
2.7K
Carboxylic Acids to Methylesters: Alkylation using Diazomethane01:33

Carboxylic Acids to Methylesters: Alkylation using Diazomethane

3.2K
Carboxylic acids react with diazomethane in an ether solvent via alkylation at the carboxylate oxygen atom to give methyl esters of the corresponding acid with excellent yields.
3.2K
Diazonium Group Substitution: –OH and –H01:19

Diazonium Group Substitution: –OH and –H

3.5K
Nitrous acid, a weak acid, is prepared in situ via the reaction of sodium nitrite with a strong acid under cold conditions. This nitrous acid prepared in situ reacts with primary arylamines to form arenediazonium salts. Such reactions are known as diazotization reactions. As shown in Figure 1, the formation of arenediazonium salts begins with the decomposition of nitrous acid in an acidic solution to give nitrosonium ions.
3.5K
Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN101:14

Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN1

3.1K
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,...
3.1K

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Updated: Apr 10, 2026

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid
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Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid

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Safe by Design Flow Technology for Diazoacetonitrile Generation and Direct Conversion to Pyrazoles.

Dušan Bošković1, Stefan Loebbecke1, Calogero Giancarlo Piscopo1

  • 1Energetic Materials Department, Fraunhofer Institute for Chemical Technology ICT, Pfinztal, Germany.

Chemistryopen
|April 9, 2026
PubMed
Summary
This summary is machine-generated.

A novel continuous flow process safely generates and utilizes diazoacetonitrile (DAN) for synthesizing 3 cyano 1H pyrazoles. This method enhances safety by avoiding intermediate isolation, paving the way for greener chemical synthesis.

Keywords:
continuous flowdiazoacetonitrilegreen methodshazardous chemistrypyrazole

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A Scalable Balz-Schiemann Reaction Protocol in a Continuous Flow Reactor
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A Scalable Balz-Schiemann Reaction Protocol in a Continuous Flow Reactor
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A Scalable Balz-Schiemann Reaction Protocol in a Continuous Flow Reactor

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Area of Science:

  • Organic Chemistry
  • Process Chemistry
  • Green Chemistry

Background:

  • Diazo compounds offer efficient synthetic pathways but pose significant safety risks.
  • Handling, storage, and preparation of diazo compounds are hazardous, limiting their widespread use.
  • Energetic intermediates like diazoacetonitrile (DAN) require careful management in chemical synthesis.

Purpose of the Study:

  • To develop a safe, continuous flow process for generating and consuming diazoacetonitrile (DAN).
  • To synthesize 3 cyano 1H pyrazoles via a telescoped [3+2] cycloaddition reaction using DAN.
  • To improve the safety profile of processes involving hazardous diazo intermediates.

Main Methods:

  • A continuous flow system was designed for in-situ generation of DAN in aqueous solution.
  • Biphasic extraction transferred DAN into an organic phase for immediate reaction with activated alkynes.
  • Operating parameters including solvent, temperature, residence time, and pressure were optimized.
  • Dichloromethane and benzonitrile were evaluated as extraction and reaction media.

Main Results:

  • The process successfully generated and consumed DAN in a telescoped [3+2] cycloaddition to yield 3 cyano 1H pyrazoles.
  • Optimized conditions yielded approximately 60%-80% NMR yields with methyl propiolate.
  • A 2-hour continuous run resulted in a 37% isolated yield after recrystallization.
  • Benzonitrile supported higher DAN concentrations in the organic phase, while dichloromethane aided isolation.

Conclusions:

  • The developed continuous flow and biphasic extraction workflow significantly enhances the safety of using energetic diazo intermediates like DAN.
  • This approach avoids the isolation and accumulation of hazardous intermediates, contributing to safer chemical manufacturing.
  • The study demonstrates the potential of continuous flow technology for greener and more efficient synthesis by eliminating reaction steps.