Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Nucleophilic Aromatic Substitution: Addition–Elimination (SNAr)01:30

Nucleophilic Aromatic Substitution: Addition–Elimination (SNAr)

4.8K
Nucleophilic substitution in aromatic compounds is feasible in substrates bearing strong electron-withdrawing substituents positioned ortho or para to the leaving group. The reaction proceeds via two steps: the addition of the nucleophile and the elimination of the leaving group.
The reaction begins with an attack of the nucleophile on the carbon that holds the leaving group. This results in the delocalization of the π electrons over the ring carbons. The resonance interaction between...
4.8K
Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN101:14

Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN1

2.8K
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,...
2.8K
Nucleophilic Aromatic Substitution: Elimination–Addition01:11

Nucleophilic Aromatic Substitution: Elimination–Addition

5.1K
Simple aryl halides do not react with nucleophiles. However, nucleophilic aromatic substitutions can be forced under certain conditions, such as high temperatures or strong bases. The mechanism of substitution under such conditions involves the highly unstable and reactive benzyne intermediate. Benzyne contains equivalent carbon centers at both ends of the triple bond, each of which is equally susceptible to nucleophilic attack. This 50–50 distribution of products is...
5.1K
Nucleophilic Substitution Reactions02:34

Nucleophilic Substitution Reactions

19.7K
Historical perspective
In 1896, the German chemist Paul Walden discovered that he could interconvert pure enantiomeric (+) and (-) malic acids through a series of reactions. This conversion suggested the involvement of optical inversion during the substitution reaction. Further, in 1930, Sir Christopher Ingold described for the first time two different forms of nucleophilic substitution reactions, which are known as SN1 (nucleophilic substitution unimolecular) and SN2 (nucleophilic substitution...
19.7K
Electrophilic Aromatic Substitution: Overview01:16

Electrophilic Aromatic Substitution: Overview

14.4K
In an electrophilic aromatic substitution reaction, an electrophile substitutes for a hydrogen of an aromatic compound.
14.4K
Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene01:13

Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene

7.5K
Bromination and chlorination of aromatic rings by electrophilic aromatic substitution reactions are easily achieved, but fluorination and iodination are difficult to achieve. Fluorine is so reactive that its reaction with benzene is difficult to control, resulting in poor yields of monofluoroaromatic products. To address this, Selectfluor reagent is used as a fluorine source in which a fluorine atom is bonded to a positively charged nitrogen.
7.5K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Multimodal deep learning for predicting WHO/ISUP grading in renal tumors on CT using a self-attention-based model: variable Vision Transformer (vViT).

European journal of radiology open·2026
Same author

Carbonylative Aminative Suzuki-Miyaura Coupling: Pd-Catalyzed Synthesis of Amides from Vinyl/Aryl Halides and Boronic Acids.

Journal of the American Chemical Society·2026
Same author

Author Correction: Synthesis of enantioenriched atropisomers by biocatalytic deracemization.

Nature·2026
Same author

Pd-Catalyzed Arylative Lossen Rearrangement: Synthesis of Secondary Amines from Aryl/Alkyl Carboxylic Acids and Aryl Halides.

Journal of the American Chemical Society·2026
Same author

Catalyst-Controlled Chemoselective β-Mannosylation of Phenols Via Attractive Noncovalent Interactions.

Journal of the American Chemical Society·2026
Same author

Ab Initio Molecular Dynamics Simulations for Organic Chemists─It is About Time!

Journal of the American Chemical Society·2026

Related Experiment Video

Updated: Feb 7, 2026

Fabricating Complex Culture Substrates Using Robotic Microcontact Printing R- µCP and Sequential Nucleophilic Substitution
08:23

Fabricating Complex Culture Substrates Using Robotic Microcontact Printing R- µCP and Sequential Nucleophilic Substitution

Published on: October 31, 2014

10.9K

Concerted nucleophilic aromatic substitutions.

Eugene E Kwan1, Yuwen Zeng1, Harrison A Besser1

  • 1Department of Chemistry & Chemical Biology, Harvard University, Cambridge, MA, USA.

Nature Chemistry
|July 18, 2018
PubMed
Summary

This study challenges the traditional view of nucleophilic aromatic substitution (SNAr) reactions. Using kinetic isotope effect studies, researchers found evidence that these common reactions may occur through a concerted mechanism, not a two-step process.

More Related Videos

Bioorthogonal Chemical Imaging of Cell Metabolism Regulated by Aromatic Amino Acids
10:42

Bioorthogonal Chemical Imaging of Cell Metabolism Regulated by Aromatic Amino Acids

Published on: May 12, 2023

1.6K
Transformation of Organic Household Leftovers into a Peat Substitute
08:43

Transformation of Organic Household Leftovers into a Peat Substitute

Published on: July 9, 2019

8.9K

Related Experiment Videos

Last Updated: Feb 7, 2026

Fabricating Complex Culture Substrates Using Robotic Microcontact Printing R- µCP and Sequential Nucleophilic Substitution
08:23

Fabricating Complex Culture Substrates Using Robotic Microcontact Printing R- µCP and Sequential Nucleophilic Substitution

Published on: October 31, 2014

10.9K
Bioorthogonal Chemical Imaging of Cell Metabolism Regulated by Aromatic Amino Acids
10:42

Bioorthogonal Chemical Imaging of Cell Metabolism Regulated by Aromatic Amino Acids

Published on: May 12, 2023

1.6K
Transformation of Organic Household Leftovers into a Peat Substitute
08:43

Transformation of Organic Household Leftovers into a Peat Substitute

Published on: July 9, 2019

8.9K

Area of Science:

  • Organic Chemistry
  • Reaction Mechanisms
  • Physical Chemistry

Background:

  • Nucleophilic aromatic substitution (SNAr) is a cornerstone reaction in pharmaceutical and chemical research.
  • The established mechanism involves a two-step addition-elimination pathway via a Meisenheimer complex.

Purpose of the Study:

  • To investigate the mechanism of prototypical SNAr reactions.
  • To provide evidence for a concerted reaction pathway.

Main Methods:

  • Utilized 12C/13C kinetic isotope effect (KIE) studies.
  • Employed computational analyses.
  • Developed a novel technique using 19F NMR for precise isotopic fractionation quantification.

Main Results:

  • Kinetic isotope effect measurements provided evidence supporting a concerted mechanism for SNAr reactions.
  • The new 19F NMR technique allows KIE measurements on small (10 mg) natural abundance samples.
  • This method enables detailed mechanistic analysis of C-F bond formation/cleavage reactions.

Conclusions:

  • Prototypical SNAr reactions likely proceed through concerted mechanisms, diverging from the widely accepted two-step model.
  • The developed 19F NMR-based KIE technique is a practical tool for mechanistic studies involving C-F bonds.