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Mechanism of nucleophilic substitutions at phenacyl bromides with pyridines. A computational study of intermediate and transition state
Author(s) -
Fábián Attila,
Ruff Ferenc,
Farkas Ödön
Publication year - 2008
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.1412
Subject(s) - chemistry , phenacyl , pyridine , phenacyl bromide , nucleophile , substituent , bromide , tetrahedral carbonyl addition compound , medicinal chemistry , nucleophilic substitution , electrophile , reaction rate constant , transition state , computational chemistry , crystallography , stereochemistry , photochemistry , organic chemistry , kinetics , catalysis , physics , quantum mechanics
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 CO 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 Å. 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 CO, than to the C atom of the CH 2 Br 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 S N 2 attack of pyridine at the CH 2 Br group. The calculated structural parameters of the S N 2 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 S N 2 substitution agree well with the data calculated from the results of kinetic experiments and correlate with the σ Py substituent constants, derived for pyridines, and with the Hammett σ constants, when the substituents (4‐MeO‐4‐NO 2 ) are varied on the pyridine or on the phenacyl bromide reactants. Copyright © 2008 John Wiley & Sons, Ltd.