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Related Concept Videos

Directing Effect of Substituents: meta-Directing Groups01:09

Directing Effect of Substituents: meta-Directing Groups

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Substituents on the benzene ring that direct an incoming electrophile to undergo substitution at the meta position are called meta directors. All meta directors either have a positive charge on the atom directly bonded to the ring or a partial positive charge. These groups function by withdrawing electrons from the ring through inductive and resonance effects. Consider the carbocation intermediates formed upon the addition of an electrophile on nitrobenzene at the...
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Chemical Shift: Internal References and Solvent Effects01:17

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In an NMR sample, precise measurement of the absolute absorption frequencies of nuclei is difficult. A standard internal reference compound is added, and the frequency difference between the reference signal and sample signals is measured.
The internal reference compound generally used in NMR spectroscopy is tetramethylsilane (TMS). TMS is preferred because it is chemically inert, soluble in NMR solvents, and easily removable. Also, the highly shielded methyl protons in TMS yield an intense...
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Directing Effect of Substituents: ortho–para-Directing Groups01:14

Directing Effect of Substituents: ortho–para-Directing Groups

8.0K
Ortho–para directors are substituent groups attached to the benzene ring and direct the addition of an electrophile to the positions ortho or para to the substituent. All electron-donating groups are considered ortho–para directors. They donate electrons to the ring and make the ring more electron-rich. The ring is therefore susceptible to the addition of electrophiles. Substituents such as amino, hydroxy, or alkoxy, containing lone pairs on the atom adjacent to the ring, donate...
8.0K
Directing and Steric Effects in Disubstituted Benzene Derivatives01:18

Directing and Steric Effects in Disubstituted Benzene Derivatives

3.8K
When disubstituted benzenes undergo electrophilic substitution, the product distribution depends on the directing effect of both substituents. When the directing effects of both substituents reinforce each other, a single product is obtained. For example, bromination of p-nitrotoluene occurs ortho to the methyl group and meta to the nitro group, which is the same position, resulting in a single product. However, if the directing effects of the two groups oppose each other, the...
3.8K
Substituent Effects on Acidity of Carboxylic Acids01:31

Substituent Effects on Acidity of Carboxylic Acids

7.6K
The acidity of carboxylic acids is influenced by the nature of the substituents bounded to the functional group. The acid strength is determined by the stability of the carboxylate anion—the conjugate base formed by dissociating the corresponding carboxylic acid.
7.6K
Inductive Effects on Chemical Shift: Overview01:27

Inductive Effects on Chemical Shift: Overview

1.9K
The protons in unsubstituted alkanes are strongly shielded with chemical shifts below 1.8 ppm. Methine, methylene, and methyl protons appear at approximately 1.7, 1.2 and 0.7 ppm, while the proton signal from methane appears at 0.23 ppm. An electronegative substituent, such as chlorine, withdraws the electron density from the protons, increasing their chemical shift. Progressive substitution of the hydrogens in methane by chlorine shifts the proton signals increasingly downfield, to 3.05 ppm in...
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Updated: Dec 18, 2025

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method
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Quantifying Through-Space Substituent Effects.

Rebecca J Burns1, Ioulia K Mati1, Kamila B Muchowska1

  • 1EaStCHEM School of Chemistry, University of Edinburgh, Joseph Black Building, David Brewster Road, Edinburgh, EH9 3FJ, UK.

Angewandte Chemie (International Ed. in English)
|June 17, 2020
PubMed
Summary
This summary is machine-generated.

Through-space substituent effects significantly impact molecular interactions and reaction kinetics, challenging traditional through-bond explanations. These non-classical effects, observed in conformational studies, offer new insights into chemical reactivity.

Keywords:
electrostatic interactionsnoncovalent interactionssubstituent effects

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Area of Science:

  • Physical Organic Chemistry
  • Computational Chemistry
  • Molecular Interactions

Background:

  • Traditional models often overemphasize through-bond electronic effects of substituents.
  • Separating through-bond and through-space contributions in molecular systems is experimentally challenging.
  • A deeper understanding of through-space effects is crucial for accurate predictions of chemical behavior.

Purpose of the Study:

  • To experimentally investigate and quantify the significance of through-space substituent effects.
  • To explore the influence of through-space effects on molecular interactions and reaction kinetics.
  • To challenge and refine existing models of substituent effects in organic chemistry.

Main Methods:

  • Measurement of 267 conformational equilibrium constants across eleven solvents.
  • Transposition of conformational data onto the Hammett substituent constant scale.
  • Comparison of experimental findings with calculated electrostatic potentials.

Main Results:

  • Dominant through-space substituent effects were identified, defying classical descriptions.
  • Nitro (NO2) groups showed unexpected electron-donating behavior when positioned over a biaryl bond.
  • Conformational changes modulated or inverted the electronic influence of methoxy (OMe) and hydroxyl (OH) groups.

Conclusions:

  • Through-space effects play a critical, often dominant, role in molecular properties and reactivity.
  • Conformational analysis provides a powerful tool for uncovering non-classical substituent behaviors.
  • Experimental conformational data serve as superior predictors of reaction kinetics compared to theoretical potentials.