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Nucleophilic substitution reactions promoted by oligoethylene glycols: a mechanistic study of ion‐pair S N 2 processes facilitated by Lewis base
Author(s) -
Kim JuYoung,
Kim Dong Wook,
Song Choong Eui,
Chi Dae Yoon,
Lee Sungyul
Publication year - 2013
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.3010
Subject(s) - chemistry , nucleophile , lewis acids and bases , nucleophilic substitution , substitution reaction , base (topology) , medicinal chemistry , metal , organic chemistry , catalysis , mathematical analysis , mathematics
We present a mechanistic study for nucleophilic substitution (S N 2) reactions facilitated by multifunctional n ‐oligoethylene glycols ( n ‐oligoEGs) using alkali metal salts MX (M + = Cs + , K + , X – = F – , Br – , I – , CN – ) as nucleophilic agents. Density functional theory method is employed to elucidate the underlying mechanism of the S N 2 reaction. We found that the nucleophiles react as ion pairs, whose metal cation is ‘coordinated’ by the oxygen atoms in oligoEGs acting as Lewis base to reduce the unfavorable electrostatic effects of M + on X – . The two terminal hydroxyl (−OH) function as ‘anchors’ to collect the nucleophile and the substrate in an ideal configuration for the reaction. Calculated barriers of the reactions are in excellent agreement with all experimentally observed trends of S N 2 yields obtained by using various metal cations, nucleophiles and oligoEGs. The reaction barriers are calculated to decrease from triEG to pentaEG, in agreement with the experimentally observed order of efficiency (triEG < tetraEG < pentaEG). The observed relative efficiency of the metal cations Cs + versus K + is also nicely demonstrated (larger [better] barrier [efficiency] for Cs + than for K + ). We also examine the effects of the nucleophiles (F – , Br – , I – , CN – ), finding that the magnitudes of reaction barriers are F – > CN – > Br – > I – , elucidating the observation that the yield was lowest for F – . It is suggested that the role of oxygen atoms in the promoters is equivalent to that of –OH group in bulky alcohols ( tert ‐butyl or amyl‐alcohol) for S N 2 fluorination reactions previously studied in our lab. Copyright © 2012 John Wiley & Sons, Ltd.