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

ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH301:11

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

7.8K
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...
7.8K
Directing Effect of Substituents: ortho–para-Directing Groups01:14

Directing Effect of Substituents: ortho–para-Directing Groups

9.2K
Ortho–para directors are substituent groups attached to the benzene ring and direct the addition of an electrophile to the positions ortho or para to the substituent. All electron-donating groups are considered ortho–para directors. They donate electrons to the ring and make the ring more electron-rich. The ring is therefore susceptible to the addition of electrophiles. Substituents such as amino, hydroxy, or alkoxy, containing lone pairs on the atom adjacent to the ring, donate...
9.2K
ortho–para-Directing Deactivators: Halogens01:24

ortho–para-Directing Deactivators: Halogens

7.0K
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...
7.0K
meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H01:13

meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H

7.0K
All meta-directing substituents are deactivating groups. These substituents withdraw electrons from the aromatic ring, making the ring less reactive toward electrophilic substitution. For example, the nitration of nitrobenzene is 100,000 times slower than that of benzene because of the deactivating effect of the nitro group. The first step in an electrophilic aromatic substitution is the addition of an electrophile to form a resonance-stabilized carbocation. The energy diagrams for...
7.0K
Protecting Groups for Aldehydes and Ketones: Introduction01:23

Protecting Groups for Aldehydes and Ketones: Introduction

9.3K
Protecting groups are compounds that can bind to a specific functional group in the presence of other functional groups to protect them from undesired chemical reactions. These compounds can selectively bind to particular functional groups and advance chemoselective reactions in polyfunctional systems (Figure 1). After the functional group has served its purpose, it is removed by reacting it with specific compounds.
9.3K
Directing Effect of Substituents: meta-Directing Groups01:09

Directing Effect of Substituents: meta-Directing Groups

6.3K
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...
6.3K

You might also read

Related Articles

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

Sort by
Same author

Conformation-driven C3-C(<i>sp</i> <sup>3</sup>)-H arylation of saturated azacycles using Pd catalyst.

Nature catalysis·2026
Same author

Ligand-Enabled Stereoselective Coupling of Methylene C(sp<sup>3</sup>)─H Bonds With Alkenyl Bromide via Pd<sup>II</sup>/Pd<sup>0</sup>/Pd<sup>II</sup> Catalysis.

Angewandte Chemie (International ed. in English)·2026
Same author

Ligand-Enabled Ag-Free Cross-Coupling of Methylene C(sp<sup>3</sup>)-H Bonds in Aliphatic Acids with C(sp<sup>2</sup>) Bromides.

Journal of the American Chemical Society·2026
Same author

Ligand-Enabled Pd-Catalyzed C(sp<sup>3</sup>)-H/C(sp<sup>2</sup>)-H Coupling.

Journal of the American Chemical Society·2026
Same author

Precise Editing of Indolines at Different Positions via SET and CMD Pathways.

JACS Au·2026
Same author

Formal Diels-Alder reaction of saturated carboxylic acids via C-H activation.

Nature chemistry·2026

Related Experiment Video

Updated: Mar 9, 2026

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides CHIPS
06:34

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides CHIPS

Published on: June 20, 2014

14.5K

Diverse ortho-C(sp2)-H Functionalization of Benzaldehydes Using Transient Directing Groups.

Xi-Hai Liu1, Hojoon Park2, Jun-Hao Hu1

  • 1School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology , Wuhan 430070, People's Republic of China.

Journal of the American Chemical Society
|December 23, 2016
PubMed
Summary

This study introduces a new transient directing group strategy for versatile ortho-C(sp2)-H functionalizations of benzaldehydes. This method enables palladium-catalyzed arylation, chlorination, bromination, and iridium-catalyzed amidation without auxiliary groups.

More Related Videos

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
08:43

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Published on: January 19, 2016

10.9K
Achieving Moderate Pressures in Sealed Vessels Using Dry Ice As a Solid CO2 Source
06:26

Achieving Moderate Pressures in Sealed Vessels Using Dry Ice As a Solid CO2 Source

Published on: August 17, 2018

10.6K

Related Experiment Videos

Last Updated: Mar 9, 2026

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides CHIPS
06:34

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides CHIPS

Published on: June 20, 2014

14.5K
Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
08:43

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Published on: January 19, 2016

10.9K
Achieving Moderate Pressures in Sealed Vessels Using Dry Ice As a Solid CO2 Source
06:26

Achieving Moderate Pressures in Sealed Vessels Using Dry Ice As a Solid CO2 Source

Published on: August 17, 2018

10.6K

Area of Science:

  • Organic Chemistry
  • Catalysis
  • Synthetic Methodology

Background:

  • Palladium-catalyzed C-H functionalizations using transient directing groups are primarily limited to C-H arylation.
  • Benzaldehyde substrates possess unique reactivity challenges for C-H activation due to potential catalyst poisoning and competing directing groups.

Purpose of the Study:

  • To develop a versatile ortho-C(sp2)-H functionalization strategy for benzaldehydes.
  • To expand the scope of metal-catalyzed C-H functionalization beyond arylation using transient directing groups.
  • To demonstrate the applicability of the developed method in complex molecule synthesis.

Main Methods:

  • In situ formation of transient directing groups via imine linkage on benzaldehyde substrates.
  • Palladium(II)-catalyzed C-H arylation, chlorination, and bromination.
  • Iridium(III)-catalyzed C-H amidation.

Main Results:

  • Achieved diverse ortho-C(sp2)-H functionalizations of benzaldehydes, including arylation, chlorination, bromination, and amidation.
  • Demonstrated that the transient directing groups effectively override other coordinating functional groups.
  • Successfully applied the methodology for late-stage diversification of a drug analogue.

Conclusions:

  • The transient directing group strategy significantly broadens the scope of metal-catalyzed C-H functionalization for benzaldehydes.
  • This approach offers a powerful tool for synthesizing complex organic molecules and functionalizing drug analogues.
  • The developed method overcomes limitations of previous strategies, enabling multiple reaction types with high efficiency.