Regioselectivity a n d th e Na tu r e of th e Rea ction Mech a n ism in
Nu cleop h ilic Su bstitu tion Rea ction s of 2,4-Din itr op h en yl
X-Su bstitu ted Ben zen esu lfon a tes w ith P r im a r y Am in es
Ik-Hwan Um,* J in-Young Hong, J ung-J oo Kim, Ok-Mi Chae, and Sun-Kun Bae†
Department of Chemistry, Ewha Womans University, Seoul 120-750, Korea
ihum@mm.ewha.ac.kr
Received February 11, 2003
Second-order rate constants have been measured for the reaction of 2,4-dinitrophenyl X-substituted
benzenesulfonates with a series of primary amines. The nucleophilic substitution reaction proceeds
through competitive S-O and C-O bond fission pathways. The S-O bond fission occurs dominantly
for reactions with highly basic amines or with substrates having a strong electron-withdrawing
group in the sulfonyl moiety. On the other hand, the C-O bond fission occurs considerably for the
reactions with low basic amines or with substrates having a strong electron-donating group in the
sulfonyl moiety, emphasizing that the regioselectivity is governed by both the amine basicity and
the electronic effect of the sulfonyl substituent X. The apparent second-order rate constants for
the S-O bond fission have resulted in a nonlinear Brønsted-type plot for the reaction of
2,4-dinitrophenyl benzenesulfonate with 10 different primary amines, suggesting that a change in
the rate-determining step occurs upon changing the amine basicity. The microscopic rate constants
(k1 and k2/k-1 ratio) associated with the S-O bond fission pathway support the proposed mechanism.
The second-order rate constants for the S-O bond fission result in good linear Yukawa-Tsuno
plots for the aminolyses of 2,4-dinitrophenyl X-substituted benzenesulfonates. However, the second-
order rate constants for the C-O bond fission show no correlation with the electronic nature of the
sulfonyl substituent X, indicating that the C-O bond fission proceeds through an SNAr mechanism
in which the leaving group departure occurs rapidly after the rate-determining step.
In tr od u ction
the leaving group; i.e., a change in the RDS occurs from
breakdown of an addition intermediate to its formation
as the attacking amine becomes more basic than the
leaving group by 4-5 pKa units.1a,2,3,5 Therefore, the
electronic nature of the substituent in the attacking
amine as well as in the leaving group has been under-
stood to influence the reaction mechanism significantly.
However, we have recently shown that the electronic
effect of the substituent in the benzoyl moiety (the
nonleaving group) does not significantly affect the reac-
tion mechanism for aminolyses of 4-nitrophenyl and 2,4-
dinitrophenyl X-substituted benzoates.5b,c A similar result
The mechanism of nucleophilic substitution reactions
of carbonyl, phosphoryl, and sulfonyl compounds has
been the subject of many recent investigations due to the
interest in biological processes as well as synthetic
applications.1-7 Aminolyses of carboxylic esters have
generally been suggested to proceed through an addition
intermediate in which the rate-determining step (RDS)
is dependent on the basicity of the attacking amine and
† Department of Chemistry, Kunsan National University, Kunsan
573-701, Korea.
has been found for the corresponding reactions with
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10.1021/jo034190i CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/21/2003
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J . Org. Chem. 2003, 68, 5180-5185