Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

ortho–para-Directing Activators: –CH3, –OH, –&NoBreak;NH2, –OCH3

ortho–para-Directing Activators: –CH₃, –OH, –⁠NH₂, –OCH₃

All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...

Directing and Steric Effects in Disubstituted Benzene Derivatives

Directing and Steric Effects in Disubstituted Benzene Derivatives

When disubstituted benzenes undergo electrophilic substitution, the product distribution depends on the directing effect of both substituents. When the directing effects of both substituents reinforce each other, a single product is obtained. For example, bromination of p-nitrotoluene occurs ortho to the methyl group and meta to the nitro group, which is the same position, resulting in a single product. However, if the directing effects of the two groups oppose each other, the...

Directing Effect of Substituents: meta-Directing Groups

Directing Effect of Substituents: meta-Directing Groups

Substituents on the benzene ring that direct an incoming electrophile to undergo substitution at the meta position are called meta directors. All meta directors either have a positive charge on the atom directly bonded to the ring or a partial positive charge. These groups function by withdrawing electrons from the ring through inductive and resonance effects. Consider the carbocation intermediates formed upon the addition of an electrophile on nitrobenzene at the...

Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule

Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule

If a set of reactants can yield multiple constitutional isomers, but one of the isomers is obtained as the major product, the reaction is said to be regioselective. In such reactions, bond formation or breaking is favored at one reaction site over others.
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...

[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement

[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement

The Cope rearrangement is classified as a [3,3] sigmatropic shift in 1,5-dienes, leading to a more stable, isomeric 1,5-diene. The reaction involves a concerted movement of six electrons, four from two π bonds and two from a σ bond, via an energetically favorable chair-like transition state.

ortho–para-Directing Deactivators: Halogens

ortho–para-Directing Deactivators: Halogens

Halogens are ortho–para directors. They are more electronegative than carbon. Therefore, as ring substituents, they can withdraw electrons through the inductive effect and deactivate the aromatic ring towards electrophilic substitution. Halogens also have an electron-donating resonance effect on the ring, which influences the orientation of the incoming electrophile. If an electrophile attacks at the ortho or the para position, the halogen donates electrons and stabilizes the intermediate...

You might also read

Related Articles

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

Sort by

Same author

Olefin Metathesis Catalyzed by a Latent Ruthenathiete Complex.

Organometallics·2026

Same author

<i>B</i>‑Alkyl-borabicyclo[3.3.1]nonane Reagents Promote Closed-Shell Nickel-Catalyzed Alkylarylation Toward Encoded Cyclooctene Monomers.

ACS central science·2026

Same author

Polymer Backbone Editing with Cyclopropenes via Olefin Metathesis.

ACS macro letters·2026

Same author

Modulation of Depolymerizable Poly(thioether-thioester) Properties in Reversible Covalent Composites.

ACS macro letters·2025

Same author

Ring-Opening Metathesis Polymerization of Levoglucosenone-Derived Enyne Monomers.

Journal of polymer science (2020)·2025

Same author

Photo-Triggerable Polymerization and Depolymerization of Stiff-Stilbene Lactones.

Journal of the American Chemical Society·2025

Search research articles

Related Experiment Video

Updated: Oct 22, 2025

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly

Published on: February 6, 2020

Modulating Twisted Amide Geometry and Reactivity Through Remote Substituent Effects.

Mizhi Xu, McKinley K Paul, Krista K Bullard

Journal of the American Chemical Society

|August 31, 2021

Summary

Researchers modulated twisted amide reactivity using remote substituents. Electron-donating groups increased amide distortion and nucleophilic substitution rates, revealing substituent-dependent reaction mechanisms.

More Related Videos

Solid-phase Synthesis of [4.4] Spirocyclic Oximes

Solid-phase Synthesis of [4.4] Spirocyclic Oximes

Published on: February 6, 2019

Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function

Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function

Published on: April 26, 2024

Related Experiment Videos

Last Updated: Oct 22, 2025

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly

Published on: February 6, 2020

Solid-phase Synthesis of [4.4] Spirocyclic Oximes

Solid-phase Synthesis of [4.4] Spirocyclic Oximes

Published on: February 6, 2019

Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function

Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function

Published on: April 26, 2024

Area of Science:

Organic Chemistry
Reaction Mechanisms
Synthetic Chemistry

Background:

The reactivity of twisted amides is traditionally linked to their distortion.
Classical bridged bicyclic amides present limitations in modifying amide distortion.
Novel strategies are needed to fine-tune amide geometry and reactivity.

Purpose of the Study:

To investigate the modulation of twisted amide geometry and reactivity.
To explore the impact of remote substituent effects on a single amide scaffold.
To understand the kinetics and mechanisms of substituted twisted amides in ring-opening reactions.

Main Methods:

Computational calculations to determine ground state geometries.
Divergent synthesis to create a library of twisted amide derivatives.
Kinetic and mechanistic studies of the alkylation/halide-rebound ring-opening reaction.

Main Results:

Remote substituents significantly modulate the geometry and reactivity of twisted amides.
Electron-donating substituents increase amide bond distortion and reaction rates.
Reaction rates of nucleophilic substitution span nearly two orders of magnitude.
The rate-limiting step is dependent on the nature of the substituent.

Conclusions:

Remote substituent effects offer a powerful tool for controlling twisted amide properties.
Amide distortion is directly correlated with electron-donating substituent strength.
Reaction pathway and efficiency are influenced by substituent, solvent polarity, and halide ion.