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

Preparation of 1° Amines: Gabriel Synthesis01:28

Preparation of 1° Amines: Gabriel Synthesis

4.5K
Direct alkylation is not a suitable method for synthesizing amines because it produces polyalkylated products. Gabriel synthesis is the most preferred method to exclusively make primary amines. The method uses phthalimide, which contains a protected form of nitrogen that participates in alkylation only once to predominantly give primary amines.
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
4.5K
Acid Halides to Amides: Aminolysis01:07

Acid Halides to Amides: Aminolysis

4.1K
Aminolysis is a nucleophilic acyl substitution reaction, where ammonia or amines act as nucleophiles to give the substitution product. Acid halides react with ammonia, primary amines, and secondary amines to yield primary, secondary, and tertiary amides, respectively.
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
4.1K
Amines to Alkenes: Hofmann Elimination01:16

Amines to Alkenes: Hofmann Elimination

3.2K
Alkenes can be obtained from amines via an E2 elimination. The amine is first converted into a good leaving group, such as a quaternary ammonium salt. This is accomplished by treating the amine with an excess of alkyl halide, which results in a halide salt. Next, the halide salt is transformed into a hydroxide salt that functions as a base to enable elimination.
Under thermal conditions, the hydroxide can abstract a proton from the β carbon; this generates an alkene with the simultaneous...
3.2K
Amides to Amines: LiAlH4 Reduction01:20

Amides to Amines: LiAlH4 Reduction

6.2K
Amide reduction with strong reducing agents like lithium aluminum hydride proceeds through a nucleophilic acyl substitution to form amines. Primary, secondary, and tertiary amides yield primary, secondary, and tertiary amines, respectively.
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate.
6.2K
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview01:07

Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview

3.6K
In the presence of an aqueous base and a halogen, primary amides can lose the carbonyl (as carbon dioxide) and undergo rearrangement to form primary amines. This reaction, called the Hofmann rearrangement, can produce primary amines (aryl and alkyl) in high yields without contamination by secondary and tertiary amines.
3.6K
Amines to Amides: Acylation of Amines01:19

Amines to Amides: Acylation of Amines

3.4K
Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
3.4K

You might also read

Related Articles

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

Sort by
Same author

Late-Stage Aryl NCF<sub>3</sub> and SCF<sub>3</sub> Installation Enabled by Coupling Flow-Generated Anions with Aryl Thianthrenium Salts.

Journal of the American Chemical Society·2026
Same author

Direct δ-Lactone Synthesis From Free Alcohols via Photoinduced δ-C(sp<sup>3</sup>)-H Carbonylation in Flow.

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

Slug-flow microchannel enables efficient and controllable preparation of sensitive protein nanoparticles.

Communications chemistry·2026
Same author

Electroreductive Cleavage of C(sp<sup>3</sup>)-N Bonds in Saturated <i>N</i>-Carbonyl Heterocycles.

Journal of the American Chemical Society·2026
Same author

Photon Management in Photochemical Synthesis and Reactor Scale-Up.

Accounts of chemical research·2026
Same author

Reductive radical chain initiation through the thermal generation of carbon dioxide radical anion.

Nature synthesis·2026

Related Experiment Video

Updated: Jan 12, 2026

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

10.7K

Flow-Enabled, Modular Access to α,α-Difluoromethylene Amines.

Dmitrii Nagornîi1, Pietro Ronco1,2, Khadijah Anwar1

  • 1Flow Chemistry Group, Van't Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam, Science Park 904 XH, Amsterdam, 1098, The Netherlands.

Angewandte Chemie (International Ed. in English)
|October 31, 2025
PubMed
Summary
This summary is machine-generated.

Researchers developed a safe, scalable flow chemistry method to generate difluoromethylene amine anions. This approach enables late-stage difluoromethylene group installation, expanding synthetic strategies in medicinal and fluorine chemistry.

Keywords:
DifluorinationFlow chemistryIsosteresLate‐stage functionalizationLibrary synthesis

More Related Videos

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
09:45

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors

Published on: April 27, 2017

11.1K
Application of Elemental Lanthanides in the Selective C-F Activation of Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes
10:10

Application of Elemental Lanthanides in the Selective C-F Activation of Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes

Published on: July 28, 2018

6.8K

Related Experiment Videos

Last Updated: Jan 12, 2026

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

10.7K
Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
09:45

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors

Published on: April 27, 2017

11.1K
Application of Elemental Lanthanides in the Selective C-F Activation of Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes
10:10

Application of Elemental Lanthanides in the Selective C-F Activation of Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes

Published on: July 28, 2018

6.8K

Area of Science:

  • Medicinal Chemistry
  • Fluorine Chemistry
  • Organic Synthesis

Background:

  • The alpha,alpha-difluoromethylene amine (NCF2R) motif is valuable in medicinal chemistry.
  • Existing methods for synthesizing NCF2R compounds are often impractical or lack modularity.

Purpose of the Study:

  • To develop a safe, scalable, and modular flow-based strategy for generating NCF2R anions.
  • To enable the late-stage installation of the CF2 group under mild conditions.

Main Methods:

  • Utilized a packed-bed microreactor with caesium fluoride for on-demand generation of NCF2R anions.
  • Employed a flow-based strategy for efficient synthesis and diversification.

Main Results:

  • Successfully generated NCF2R anions safely and scalably.
  • Demonstrated late-stage installation of the CF2 group, avoiding hazardous reagents and minimizing waste.
  • Achieved diversification through carboxylic acid, sulfonamide, and electrophile points, accessing a broad range of NCF2R compounds.
  • Confirmed tolerance of various functional groups and compatibility with downstream reactions.

Conclusions:

  • The developed flow chemistry protocol provides a versatile platform for incorporating NCF2 motifs.
  • This method expands synthetic accessibility for NCF2R compounds in medicinal and fluorine chemistry.
  • The strategy supports late-stage functionalization of complex scaffolds and is compatible with cross-coupling reactions.