Mechanism of nucleophilic substitutions at phenacyl bromides with pyridines. A computational study of intermediate and transition state

Attila Fábián, Ferenc Ruff, O. Farkas

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

DFT computations have been performed on nucleophilic substitutions of phenacyl bromides with pyridines to Investigate the mechanism of the reaction. In contrast with earlier suppositions, tetrahedral Intermediate Is not formed by the addition of pyridine on the C=O group of phenacyl bromide, because the total energy of the reacting species increases continuously, when the distance between the N and C(=O) atoms of reactants is shorter than 2.7 A. At a greater distance, however, a bridged complex of the reactants is observed, in which the N atom of pyridine is slightly closer to the C atom of the C=O, than to the C atom of the CH2Br group of phenacyl bromide, the distances are 2.87 and 3.05 Å, respectively. The attractive forces between the oppositely polarized N and C(=O) atoms in the complex decrease the free energy of activation of the 5N2 attack of pyridine at the CH2Br group. The calculated structural parameters of the 5N2 transition states (TS) indicate, that earlier TSs are formed when the pyridine nucleophile bears electron-donating (e-d) groups, while electron-withdrawing (e-w) groups on phenacyl bromide substrate Increase the tightness of the TS. Free energies of activation computed for the SN2 substitution agree well with the data calculated from the results of kinetic experiments and correlate with the σPy, substituent constants, derived for pyridines, and with the Hammett σ constants, when the substituents (4-MeO-4-NO2) are varied on the pyridine or on the phenacyl bromide reactants.

Original languageEnglish
Pages (from-to)988-996
Number of pages9
JournalJournal of Physical Organic Chemistry
Volume21
Issue number11
DOIs
Publication statusPublished - Nov 2008

Fingerprint

Pyridines
bromides
pyridines
Substitution reactions
substitutes
Atoms
Free energy
atoms
Chemical activation
Nucleophiles
Electrons
free energy
activation
Discrete Fourier transforms
tightness
nucleophiles
phenacyl bromide
pyridine
bears
attack

Keywords

  • Activation strain analysis
  • DFT calculations
  • Free energy of activation
  • Nucleophilic substitution
  • Phenacyl bromides
  • Substituent constants for pyridines
  • Substituent effect

ASJC Scopus subject areas

  • Organic Chemistry
  • Physical and Theoretical Chemistry

Cite this

Mechanism of nucleophilic substitutions at phenacyl bromides with pyridines. A computational study of intermediate and transition state. / Fábián, Attila; Ruff, Ferenc; Farkas, O.

In: Journal of Physical Organic Chemistry, Vol. 21, No. 11, 11.2008, p. 988-996.

Research output: Contribution to journalArticle

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N2 - DFT computations have been performed on nucleophilic substitutions of phenacyl bromides with pyridines to Investigate the mechanism of the reaction. In contrast with earlier suppositions, tetrahedral Intermediate Is not formed by the addition of pyridine on the C=O group of phenacyl bromide, because the total energy of the reacting species increases continuously, when the distance between the N and C(=O) atoms of reactants is shorter than 2.7 A. At a greater distance, however, a bridged complex of the reactants is observed, in which the N atom of pyridine is slightly closer to the C atom of the C=O, than to the C atom of the CH2Br group of phenacyl bromide, the distances are 2.87 and 3.05 Å, respectively. The attractive forces between the oppositely polarized N and C(=O) atoms in the complex decrease the free energy of activation of the 5N2 attack of pyridine at the CH2Br group. The calculated structural parameters of the 5N2 transition states (TS) indicate, that earlier TSs are formed when the pyridine nucleophile bears electron-donating (e-d) groups, while electron-withdrawing (e-w) groups on phenacyl bromide substrate Increase the tightness of the TS. Free energies of activation computed for the SN2 substitution agree well with the data calculated from the results of kinetic experiments and correlate with the σPy, substituent constants, derived for pyridines, and with the Hammett σ constants, when the substituents (4-MeO-4-NO2) are varied on the pyridine or on the phenacyl bromide reactants.

AB - DFT computations have been performed on nucleophilic substitutions of phenacyl bromides with pyridines to Investigate the mechanism of the reaction. In contrast with earlier suppositions, tetrahedral Intermediate Is not formed by the addition of pyridine on the C=O group of phenacyl bromide, because the total energy of the reacting species increases continuously, when the distance between the N and C(=O) atoms of reactants is shorter than 2.7 A. At a greater distance, however, a bridged complex of the reactants is observed, in which the N atom of pyridine is slightly closer to the C atom of the C=O, than to the C atom of the CH2Br group of phenacyl bromide, the distances are 2.87 and 3.05 Å, respectively. The attractive forces between the oppositely polarized N and C(=O) atoms in the complex decrease the free energy of activation of the 5N2 attack of pyridine at the CH2Br group. The calculated structural parameters of the 5N2 transition states (TS) indicate, that earlier TSs are formed when the pyridine nucleophile bears electron-donating (e-d) groups, while electron-withdrawing (e-w) groups on phenacyl bromide substrate Increase the tightness of the TS. Free energies of activation computed for the SN2 substitution agree well with the data calculated from the results of kinetic experiments and correlate with the σPy, substituent constants, derived for pyridines, and with the Hammett σ constants, when the substituents (4-MeO-4-NO2) are varied on the pyridine or on the phenacyl bromide reactants.

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