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The Influence of Nucleophile Substituents on the Orientation in the Reaction between 2,4‐Difluoronitrobenzene and Lithium Phenoxides in Liquid Ammonia
Author(s) -
Politanskaya Larisa,
Malykhin Evgenij,
Shteingarts Vitalij
Publication year - 2001
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200101)2001:2<405::aid-ejoc405>3.0.co;2-6
Subject(s) - chemistry , substituent , fluorine , nucleophile , stereochemistry , medicinal chemistry , lithium (medication) , electronic effect , amination , nucleophilic substitution , steric effects , alkyl , crystallography , organic chemistry , medicine , endocrinology , catalysis
The dependence of the orientation of aryloxydefluorination of 2,4‐difluoronitrobenzene ( 1 ) ( o / p ratio) by the action of X‐substituted lithium phenoxides 2 (X = p ‐OMe, p ‐Me, p ‐Et, p ‐ i Pr, p ‐ t Bu, m ‐Me, H, p ‐F) in liquid ammonia in the temperature range from −55 to −35 °C has been investigated. The enthalpic preference for ortho ‐fluorine substitution decreases with weakening substituent electron‐donating capability in the order: p ‐OMe > p ‐Me ≈ p ‐Et > m ‐Me > H ⩾ p ‐F. The predominant fluorine substitution at the ortho position for X = p ‐Me, p ‐Et turns into a preference for substitution at the para position when X = p ‐ i Pr, and this increases further on going to X = p ‐ t Bu. PM3, AM1 and MNDO MO calculations showed greater stability of the intermediate anionic σ‐complexes formed on nucleophile addition at the para position, thus suggesting that the predominant ortho substitution manifested for X = p ‐OMe, m ‐Me, H, p ‐F and p ‐Alk = Me, Et is due to control over orientation by the charge distribution in the substrate. The substrate electronic structure, as a controlling factor, is probably changed by the relative stability of intermediate anionic σ‐complexes on going to p ‐Alk = i Pr, t Bu, as a consequence of an enhancement of the substituent’s electron‐withdrawing nature with the increase in alkyl group polarizability in the order: p ‐Me ≈ p ‐Et < p ‐ i Pr < p ‐ t Bu.