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

Nitrosation of Enols

Nitrosation of Enols

The nitrosation reaction is one of the methods of preparing 1,2-diketones. The enol tautomer of the starting ketone reacts with sodium nitrite in hydrochloric acid, generating the 1,2-diketone after hydrolysis.

Conjugate Addition to α,β-Unsaturated Carbonyl Compounds

Conjugate Addition to α,β-Unsaturated Carbonyl Compounds

α,β-Unsaturated carbonyl compounds are molecules bearing a carbonyl and alkene functionality in conjugation with each other. The conjugation in the molecule leads to three resonance structures. The hybrid form exhibits two probable electrophilic sites: the carbonyl carbon and the β carbon.

Nucleophilic Addition to the Carbonyl Group: General Mechanism

Nucleophilic Addition to the Carbonyl Group: General Mechanism

The carbonyl carbon in an aldehyde or ketone is the site of a nucleophilic attack due to its electron-deficient nature. Depending on the strength of the incoming nucleophile, the reaction occurs via different mechanistic pathways.
A stronger nucleophile can directly attack the electrophilic center, the carbonyl carbon. The HOMO orbital of the nucleophile interacts with the LUMO (π* antibonding) orbital present on the carbonyl carbon. This interaction breaks the π bond and shifts the...

Conjugate Addition of Enolates: Michael Addition

Conjugate Addition of Enolates: Michael Addition

The attack of a nucleophile at the β carbon of an α,β-unsaturated carbonyl compound is called conjugate addition. Conjugate addition reactions of active methylene compounds, such as β-diketones, β-keto esters, β-keto nitriles, and α-nitro ketones, are called Michael addition reactions.

2° Amines to N-Nitrosamines: Reaction with NaNO2

2° Amines to N-Nitrosamines: Reaction with NaNO₂

Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.

Conjugate Addition (1,4-Addition) vs Direct Addition (1,2-Addition)

Conjugate Addition (1,4-Addition) vs Direct Addition (1,2-Addition)

α,β-Unsaturated carbonyl compounds with two electrophilic sites, the carbonyl carbon, and the β carbon, are susceptible to nucleophilic attack via two modes: conjugate or 1,4-addition and direct or 1,2-addition.
Conjugate addition results in a thermodynamically stable product. The reaction retains the stronger C=O bond at the expense of the weaker C=C π bond. The process is slow as the β carbon is less electrophilic than the carbonyl carbon.
Direct addition products are...

You might also read

Related Articles

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

Sort by

Same author

ASO Visual Abstract: Imaging Overestimates the Local Extent of Breast Tumor After Neoadjuvant Chemotherapy.

Annals of surgical oncology·2026

Same author

Imaging Overestimates the Local Extent of Breast Tumor After Neoadjuvant Chemotherapy.

Annals of surgical oncology·2026

Same author

Zinc (d)-Tartrate Catalyzed Asymmetric Epoxide Ring Opening: Access to Enantioenriched β-Hydroxy Thiols and ADC Linker Compounds.

The Journal of organic chemistry·2026

Same author

Non-surgical deep uterine embryo transfer combined with electroporation-based genome editing enables scalable production of CD163-Knockout pigs.

Theriogenology·2026

Same author

Immunosenescence in Human Disease: Mechanistic Insights and Therapeutic Opportunities.

Biomolecules & therapeutics·2026

Same author

Mild LiOMe-Catalyzed Trifluoromethylation of Carbonyl Compounds.

The Journal of organic chemistry·2026

Search research articles

Related Experiment Video

Updated: Apr 29, 2026

Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyltroponeiron

Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyltroponeiron

Published on: August 12, 2019

Carbamoyl anion addition to nitrones.

Jonathan T Reeves¹, Chris Lorenc, Kaddy Camara

¹Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, United States.

The Journal of Organic Chemistry

|May 30, 2014

Summary

Researchers developed a new synthetic route to α-(N-hydroxy)amino amides using carbamoyl anions and nitrones. Chiral auxiliaries enabled high diastereoselectivity in this direct amidation reaction.

More Related Videos

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

Published on: January 21, 2020

A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s

A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s

Published on: September 25, 2017

Related Experiment Videos

Last Updated: Apr 29, 2026

Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyltroponeiron

Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyltroponeiron

Published on: August 12, 2019

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

Published on: January 21, 2020

A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s

A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s

Published on: September 25, 2017

Area of Science:

Organic Synthesis
Asymmetric Catalysis
Medicinal Chemistry

Background:

N-tert-butyl nitrones are versatile synthons in organic chemistry.
α-(N-hydroxy)amino amides are important structural motifs in pharmaceuticals.
Direct amidation of nitrones remains a synthetic challenge.

Purpose of the Study:

To develop a novel method for synthesizing α-(N-hydroxy)amino amides.
To explore the use of carbamoyl anions in nitrone additions.
To achieve diastereoselective synthesis using chiral auxiliaries.

Main Methods:

Addition of carbamoyl anions, generated from N,N-disubstituted formamides and lithium diisopropylamide (LDA), to N-tert-butyl nitrones.
Employing a tert-leucinol derived chiral auxiliary on the nitrone.
Subsequent derivatization of the products via tert-butyl deprotection or N-deoxygenation.

Main Results:

A direct synthetic route to α-(N-hydroxy)amino amides was established.
The reaction demonstrated broad substrate scope with various formamides and nitrones.
Good diastereoselectivity was achieved when using the chiral auxiliary.
Successful derivatization of the synthesized products was demonstrated.

Conclusions:

The described method provides an efficient and direct access to α-(N-hydroxy)amino amides.
The use of chiral auxiliaries offers a viable strategy for asymmetric synthesis.
This methodology expands the synthetic utility of N-tert-butyl nitrones.