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Nucleophilic Substitution Reactions02:34

Nucleophilic Substitution Reactions

Historical perspective
In 1896, the German chemist Paul Walden discovered that he could interconvert pure enantiomeric (+) and (-) malic acids through a series of reactions. This conversion suggested the involvement of optical inversion during the substitution reaction. Further, in 1930, Sir Christopher Ingold described for the first time two different forms of nucleophilic substitution reactions, which are known as SN1 (nucleophilic substitution unimolecular) and SN2 (nucleophilic substitution...
Nucleophiles02:30

Nucleophiles

The word “nucleophile” has a Greek root and translates to nucleus-loving. Nucleophiles are either negatively charged or neutral species with a pair of electrons in a high-energy occupied molecular orbital (HOMO). As these species tend to donate electron pairs, nucleophiles are considered Lewis bases as well. Negatively charged species, like OH−, Cl−, or HS−, with one or several pairs of electrons, are typically nucleophiles. Similarly, neutral species such as ammonia, amines, water, and alcohol...
Electrophilic Aromatic Substitution: Overview01:16

Electrophilic Aromatic Substitution: Overview

In an electrophilic aromatic substitution reaction, an electrophile substitutes for a hydrogen of an aromatic compound.
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...
Nucleophilic Aromatic Substitution: Addition–Elimination (SNAr)01:30

Nucleophilic Aromatic Substitution: Addition–Elimination (SNAr)

Nucleophilic substitution in aromatic compounds is feasible in substrates bearing strong electron-withdrawing substituents positioned ortho or para to the leaving group. The reaction proceeds via two steps: the addition of the nucleophile and the elimination of the leaving group.
The reaction begins with an attack of the nucleophile on the carbon that holds the leaving group. This results in the delocalization of the π electrons over the ring carbons. The resonance interaction between the...
Electrophiles02:28

Electrophiles

This lesson explains the definition, classification, and characteristic features of an electrophile that are key features of nucleophilic substitution reactions. An analysis of their charge and orbital picture helps understand their reactivity for seeking electrons. Electrophiles can be classified into positive and neutral species. Other classes include free radicals and polar functional groups.
While a positive electrophile, like a proton, reacts due to its vacant, low-energy 1s orbital, the...

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Synthesizing Amino Acids Modified with Reactive Carbonyls in Silico to Assess Structural Effects Using Molecular Dynamics Simulations
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Published on: April 26, 2024

Nucleophilic substitution: a charge density perspective.

Travis E Jones1

  • 1Molecular Theory Group, Colorado School of Mines, Golden, Colorado 80401, USA. trjones@mines.edu

The Journal of Physical Chemistry. A
|April 7, 2012
PubMed
Summary
This summary is machine-generated.

This study introduces bond bundles, a new model for predicting activating groups in nucleophilic aromatic substitution reactions. The research reveals that bond bundle shape and nonbonding regions significantly influence molecular reactivity.

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Area of Science:

  • Quantum chemistry
  • Organic chemistry
  • Chemical reactivity

Background:

  • Nucleophilic aromatic substitution is a fundamental reaction in organic chemistry.
  • Predicting reactivity and identifying activating groups remains a challenge.
  • Existing models may not universally apply to all molecular and solid-state systems.

Purpose of the Study:

  • To develop a general description of nucleophilic reactions using bond bundles.
  • To predict novel activating groups for aromatic rings.
  • To rationalize anomalously reactive systems.

Main Methods:

  • Utilizing bond bundles, an extension of the quantum theory of atoms in molecules.
  • Analyzing the shape of the bond bundle between substrate and leaving group.
  • Investigating the presence of nonbonding regions in molecular systems.

Main Results:

  • Reactivity is correlated with bond bundle shape and nonbonding regions.
  • Closed bond bundles exhibit higher reactivity compared to open ones.
  • Nonbonding regions enhance molecular reactivity.

Conclusions:

  • The bond bundle approach offers a versatile method for studying reactivity in diverse systems.
  • This model successfully rationalizes the reactivity of strained heterocyclic and sulfide-activated aromatic rings.
  • The findings provide new insights into the factors governing nucleophilic substitution reactions.