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Related Concept Videos

SN2 Reaction: Stereochemistry02:23

SN2 Reaction: Stereochemistry

9.7K
In an SN2 reaction, the nucleophilic attack on the substrate and departure of the leaving group occurs simultaneously through a transition state. As the nucleophile approaches the substrate from the back-side, the configuration of the substrate carbon changes from tetrahedral to trigonal bipyramidal and then back to tetrahedral, leading to an inversion in the configuration of the product.
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not...
9.7K
SN2 Reaction: Mechanism02:27

SN2 Reaction: Mechanism

14.5K
The kinetic studies of SN2 reactions suggest an essential feature of its mechanism: it is a single-step process without intermediates. Here, both the nucleophile and the substrate participate in the rate-determining step.
The presence of the more electronegative halogen in the substrate creates a polarized carbon-halide bond. The halide pulls the electron cloud generating an electrophilic center at the carbon atom. Thus, the carbon atom carries a partial positive charge while the halide has a...
14.5K
Aldehydes and Ketones with HCN: Cyanohydrin Formation Mechanism01:10

Aldehydes and Ketones with HCN: Cyanohydrin Formation Mechanism

3.2K
Cyanohydrins are formed when cyanide nucleophiles and carbonyl compounds like aldehydes and ketones react. A strong base, the cyanide ion, catalyzes cyanohydrin formation. The ions are generated from HCN under aqueous conditions. Once the cyanide ions are generated, the first step involves the nucleophilic attack of the cyanide ions on the electrophilic carbonyl carbon. This attack shifts the π electrons from the C=O to the oxygen atom forming the alkoxide ion intermediate. The alkoxide anion...
3.2K
Aldehydes and Ketones with HCN: Cyanohydrin Formation Overview01:32

Aldehydes and Ketones with HCN: Cyanohydrin Formation Overview

2.8K
Cyanohydrins are compounds that contain –CN and –OH groups on the same carbon atom. They are formed by the nucleophilic addition of the cyanide ions to the carbonyl group. Cyanide ions are highly basic and nucleophilic and can be generated from HCN under aqueous conditions. However, since HCN is a weak acid, the number of cyanide ions generated is very small. Hence, a small amount of base or KCN/NaCN is added to HCN to increase the concentration of the cyanide ions in the reaction...
2.8K
SN1 Reaction: Mechanism02:25

SN1 Reaction: Mechanism

12.0K
Kinetic studies of ionization of a tertiary halide in a protic solvent suggest that only the substrate participates in the rate-determining step (slow step). The nucleophile is involved only after the slowest step. The SN1 reaction takes place in a multiple-step mechanism. 
Firstly, the haloalkane ionizes to generate a carbocation intermediate and a halide ion. This heterolytic cleavage is highly endothermic with large activation energy. The ionization of the substrate, facilitated by a...
12.0K
Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions01:20

Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions

1.9K
Arenediazonium substitution reactions occur when the diazonium group is substituted by various functional groups such as halides, hydroxyl, nitrile, etc. For instance, arenediazonium salts react with copper(I) salts of chloride, bromide, or cyanide to form corresponding aryl chlorides, bromides, and nitriles. These reactions are named Sandmeyer reactions. Although the mechanism of this reaction is complicated, as illustrated in Figure 1, they are believed to progress via an aryl copper...
1.9K

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Related Experiment Video

Updated: Jul 16, 2025

Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes
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The isocyanide SN2 reaction.

Pravin Patil1,2, Qiang Zheng2, Katarzyna Kurpiewska3

  • 1Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry and Czech Advanced Technology and Research Institute, Palackӯ University in Olomouc, Olomouc, Czech Republic.

Nature Communications
|September 19, 2023
PubMed
Summary
This summary is machine-generated.

Isocyanides are newly discovered nucleophiles in SN2 reactions, enabling efficient synthesis of diverse secondary amides. This breakthrough offers a novel pathway for drug discovery and complex molecule construction.

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Area of Science:

  • Organic Chemistry
  • Synthetic Chemistry
  • Medicinal Chemistry

Background:

  • SN2 reactions are fundamental in synthesizing drugs and natural products.
  • Common nucleophiles include cyanide, oxygen, nitrogen, sulfur, and phosphorus.
  • Isocyanides possess unique electronic properties but their SN2 potential was unexplored.

Purpose of the Study:

  • To investigate the nucleophilic potential of isocyanides in SN2 reactions.
  • To develop a novel synthetic route for secondary amides using isocyanides.

Main Methods:

  • Exploration of isocyanides as nucleophiles in SN2 reactions with alkyl halides.
  • Utilizing in situ nitrilium ion hydrolysis for amide formation.
  • Developing a 3-component reaction system.

Main Results:

  • Isocyanides were confirmed as versatile nucleophiles in SN2 reactions.
  • A novel method for synthesizing highly substituted secondary amides was established.
  • The reaction demonstrated broad substrate scope, functional group tolerance, and scalability.

Conclusions:

  • Isocyanides offer a new avenue for amide synthesis, expanding chemical diversity.
  • This method provides an alternative to classical amide coupling reactions.
  • The isocyanide nucleophile acts as an Umpolung amide carbanion synthon.