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

Base-Promoted α-Halogenation of Aldehydes and Ketones00:51

Base-Promoted α-Halogenation of Aldehydes and Ketones

α-Halogenation of aldehydes and ketones is a reaction involving the substitution of α hydrogens with halogens in the presence of a base.  The reaction begins with the abstraction of  α hydrogen by the base to produce a nucleophilic enolate ion. This intermediate undergoes a subsequent nucleophilic substitution with the halogen to produce a monohalogenated carbonyl compound. If the starting substrate has more than one α hydrogen, it is difficult to stop the reaction at the stage of...
Halogenation of Alkenes02:46

Halogenation of Alkenes

Halogenation is the addition of chlorine or bromine across the double bond in an alkene to yield a vicinal dihalide. The reaction occurs in the presence of inert and non-nucleophilic solvents, such as methylene chloride, chloroform, or carbon tetrachloride.
Consider the bromination of cyclopentene. Molecular bromine is polarized in the proximity of the π electrons of cyclopentene. An electrophilic bromine atom adds across the double bond, forming a cyclic bromonium ion intermediate.
Acid-Catalyzed α-Halogenation of Aldehydes and Ketones01:21

Acid-Catalyzed α-Halogenation of Aldehydes and Ketones

By replacing an α-hydrogen with a halogen, acid-catalyzed α-halogenation of aldehydes or ketones yields a monohalogenated product
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...
Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids02:04

Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids

Diols are compounds with two hydroxyl groups. In addition to syn dihydroxylation, diols can also be synthesized through the process of anti dihydroxylation. The process involves treating an alkene with a peroxycarboxylic acid to form an epoxide. Epoxides are highly strained three-membered rings with oxygen and two carbons occupying the corners of an equilateral triangle. This step is followed by ring-opening of the epoxide in the presence of an aqueous acid to give a trans diol.
Nucleophilic Aromatic Substitution: Elimination–Addition01:11

Nucleophilic Aromatic Substitution: Elimination–Addition

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 confirmed through isotopic...
Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide02:44

Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide

Alkenes are converted to 1,2-diols or glycols through a process called dihydroxylation. It involves the addition of two hydroxyl groups across the double bond with two different stereochemical approaches, namely anti and syn. Dihydroxylation using osmium tetroxide progresses with syn stereochemistry.

You might also read

Related Articles

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

Sort by
Same author

A Brønsted acid-base approach for the net monoselective C-F substitution of (trifluoromethyl)alkanes.

Chemical science·2026
Same author

Direct Aziridine Synthesis from Amines and Styrene Derivatives via a Base-Promoted Oxidative Cascade Reaction.

Journal of the American Chemical Society·2025
Same author

A strategy for the controllable generation of organic superbases from benchtop-stable salts.

Chemical science·2024
Same author

Direct Benzylic C-H Etherification Enabled by Base-Promoted Halogen Transfer.

Angewandte Chemie (International ed. in English)·2024
Same author

Direct C-H Hydroxylation of <i>N</i>-Heteroarenes and Benzenes <i>via</i> Base-Catalyzed Halogen Transfer.

Journal of the American Chemical Society·2024
Same author

Synthetic Advantages of Defluorinative C-F Bond Functionalization.

Angewandte Chemie (International ed. in English)·2023

Related Experiment Video

Updated: Jul 12, 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

Amide α-C-H oxidative coupling reactions enabled by base-promoted halogen transfer.

Faith E Kidd1, Cristian Vásquez Tapia Vera1, Jeffrey S Bandar1

  • 1Department of Chemistry Colorado State University Fort Collins Colorado 80523 USA jeff.bandar@colostate.edu.

Chemical Science
|July 11, 2026
PubMed
Summary

This study introduces a new method for directly coupling amide α-C-H bonds with various nucleophiles. This efficient oxidative coupling simplifies the synthesis of α-substituted amides.

More Related Videos

Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium Under Mild Reaction Conditions
11:44

Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium Under Mild Reaction Conditions

Published on: March 20, 2014

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
08:12

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species

Published on: August 16, 2018

Related Experiment Videos

Last Updated: Jul 12, 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

Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium Under Mild Reaction Conditions
11:44

Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium Under Mild Reaction Conditions

Published on: March 20, 2014

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
08:12

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species

Published on: August 16, 2018

Area of Science:

  • Organic Chemistry
  • Synthetic Chemistry

Background:

  • Traditional synthesis of α-substituted amides often involves multi-step processes.
  • Existing methods for direct functionalization of amide α-C-H bonds are challenging.

Purpose of the Study:

  • To develop a novel, direct, base-promoted protocol for the oxidative coupling of amide α-C-H bonds.
  • To provide a streamlined and modular alternative to conventional amide synthesis.

Main Methods:

  • Utilized mild bases and inexpensive 2-bromothiophenes as halogen oxidants.
  • Employed a synergistic deprotonation, halogenation, and substitution sequence.
  • Achieved direct oxidative coupling of amide α-C-H bonds with O-, S-, and N-pronucleophiles.

Main Results:

  • Successfully demonstrated a one-step protocol for α-functionalization of amides.
  • Overcame limitations of traditional two-step enolate formation/halogenation methods.
  • Enabled efficient synthesis of α-substituted amides from readily available starting materials.

Conclusions:

  • The described protocol offers a significant advancement in amide synthesis.
  • This method provides a versatile and efficient route to α-substituted amides.
  • The approach simplifies synthetic strategies, reducing step count and improving modularity.