The α-effect in the SNAr reaction of 1-(4-nitrophenoxy)-2,4-dinitrobenzene with anionic nucleophiles: Effects of solvation and polarizability on the α-effect

Article abstract of DOI:10.1139/cjc-2015-0073

A kinetic study on S_NAr reactions of 1-(4-nitrophenoxy)-2,4-dinitrobenzene (1a) with various anionic nucleophiles in 80 mol% water-20 mol% DMSO at 25.0 °C is reported. The Bronsted-type plot for the reaction of 1a with a series of substituted phenoxides and HOO^- results in an excellent linear correlation with β_nuc = 1.17. However, OH^- exhibits dramatic negative deviation from the Bronsted-type plot, while N₃^-, C₆H₅S^-, and butane-2,3-dione monoximate (Ox^-) deviate positively from linearity. HOO^- is 680-fold more reactive than OH^- but does not exhibit the α-effect. In contrast, Ox^- is 166-fold more reactive than isobasic 4-Cl^-C₆H₄O^- and exhibits the α-effect. Differential solvation effects have been suggested to be responsible for the α-effect in this study, i.e., Ox^- exhibits the α-effect, since it is 5.7 kcal/mol less strongly solvated than 4-Cl^-C₆H₄O^- in the reaction medium, while HOO^- does not show the α-effect due to a strong requirement for partial desolvation before nucleophilic attack. The highly enhanced reactivity of polarizable N₃^- and C₆H₅S^- and extremely decreased reactivity of nonpolarizable OH^- are in accord with the hard-soft acid and base principle.

Full text of DOI:10.1139/cjc-2015-0073

1109
ARTICLE
The ␣-effect in the SNAr reaction of 1-(4-nitrophenoxy)-
2,4-dinitrobenzene with anionic nucleophiles: effects of
solvation and polarizability on the ␣-effect
Ik-Hwan Um, Min-Young Kim, Hyo-Jin Cho, Julian M. Dust, and Erwin Buncel
Abstract: A kinetic study on SNAr reactions of 1-(4-nitrophenoxy)-2,4-dinitrobenzene (1a) with various anionic nucleophiles in
80 mol% water – 20 mol% DMSO at 25.0 °C is reported. The Brønsted-type plot for the reaction of 1a with a series of substituted
phenoxides and HOO− results in an excellent linear correlation with ␤nuc = 1.17. However, OH− exhibits dramatic negative
deviation from the Brønsted-type plot, while N3−, C6H5S−, and butane-2,3-dione monoximate (Ox−) deviate positively from
linearity. HOO− is 680-fold more reactive than OH− but does not exhibit the ␣-effect. In contrast, Ox− is 166-fold more reactive
than isobasic 4-Cl−C6H4O− and exhibits the ␣-effect. Differential solvation effects have been suggested to be responsible for the
␣-effect in this study, i.e., Ox− exhibits the ␣-effect, since it is 5.7 kcal/mol less strongly solvated than 4-Cl−C6H4O− in the reaction
medium, while HOO− does not show the ␣-effect due to a strong requirement for partial desolvation before nucleophilic attack.
The highly enhanced reactivity of polarizable N3− and C6H5S− and extremely decreased reactivity of nonpolarizable OH− are in
accord with the hard–soft acid and base principle.
Key words: ␣-effect, SNAr reaction, 1-(phenoxy)-2,4-dinitrobenzene, solvation, polarizability.
Résumé : Nous présentons une étude cinétique des réactions SNAr entre le 1-(4-nitrophénoxy)-2,4-dinitrobenzène (1a) et divers
nucléophiles anioniques dans un mélange constitué d’eau a` 80 % molaire et de DMSO a` 20 % molaire a` une température de
25,0 °C. La courbe de type Brønsted pour les réactions du composé 1a avec une série de phénoxydes substitués et avec l’ion HOO−
donne lieu a` une excellente corrélation linéaire dont le coefficient ␤nuc = 1,17. Cependant, les ions OH− sont associés a` une
déviation négative importante de la courbe de type Brønsted, tandis que les ions N3−, C6H5S− et butane-2,3-dionemonoximate
(Ox−) dévient de la linéarité de façon positive. L’ion HOO− est 680 fois plus réactif que l’ion OH−, mais ne montre pas d’effet ␣. À
l’inverse, l’ion Ox− est 166 fois plus réactif que l’ion isobasique 4-ClC6H4O− et présente l’effet ␣. Nous avons proposé des effets de
solvatation variables d’un composé a` l’autre pour expliquer l’effet ␣ observé dans cette étude, c.-a`-d. que l’ion Ox− présente l’effet
␣ parce qu’il est moins fortement solvaté dans le milieu réactionnel que l’ion 4-Cl-C6H4O− (différence de 5,7 kcal/mol), tandis que
l’ion HOO− ne montre pas d’effet ␣ en raison de fortes contraintes a` la désolvatation partielle préalable a` l’attaque nucléophile.
La réactivité fortement accrue des ions polarisables N3− et C6H5S− et la réduction extrême de la réactivité de l’ion non polarisable
OH− sont des phénomènes en accord avec le principe de dureté chimique des acides et des bases. [Traduit par la Rédaction]
Mots-clés : effet ␣, réaction SNAr, 1-(phénoxy)-2,4-dinitrobenzène, solvatation, polarisabilité.
that arises from electronic repulsion between the nonbonding
electron pairs, (ii) transition-state (TS) stabilization through a TS
Introduction
Basicity is one of the most commonly used tools to predict
having aromatic or radicaloid character, (iii) thermodynamic sta-
nucleophilic reactivity. However, ␣-nucleophiles (i.e., nucleophiles
bility of reaction products, (iv) polarizability effect, and (v) solvent
bearing one or more nonbonding electron pairs at the atom ␣ to
the nucleophilic center) have often been reported to exhibit ab-
effects.2–14
However, none of the above theories alone have decisively ac-
normally enhanced nucleophilic reactivity, i.e., greater than would
be expected from their basicity.1–14 Thus, the enhanced reactivity
shown by ␣-nucleophiles has been termed the ␣-effect by Edwards
and Pearson.1 Because of this enhanced nucleophilic reactivity,
␣-nucleophiles have been used effectively for breakdown of neu-
rotoxins, antidotes for nerve gases, remediation of sites contami-
nated with toxic organophosphates, etc.3,4
Numerous studies have been carried out to probe the cause of
the ␣-effect phenomenon. Prevalent theories to account for the
␣-effect phenomenon are (i) destabilization of the ground state
counted for the ␣-effect phenomenon. In particular, the solvent
effect on the ␣-effect has been controversial. For example, DePuy
et al. have reported that HOO− does not exhibit any enhanced
reactivity in the gas-phase reactions of methyl formate with HOO−
and OH−.12a Thus, the ␣-effect observed for reactions with HOO− in
water (defined here as the ratio of rate constants for HOO− com-
pared with OH−) has been attributed to a solvent effect, since
HOO− was reported to be 12 kcal/mol less strongly solvated than
OH− in water.13 A similar conclusion has been drawn from gas-
Received 3 February 2015. Accepted 12 March 2015.
I.-H. Um and M.-Y. Kim. Department of Chemistry and Nano Science, Ewha Womans University, Seoul 120-750, Korea.
H.-J. Cho. Department of Chemistry, Duksung Women’s University, Seoul 132-714, Korea.
J.M. Dust. Departments of Chemistry and Environmental Science, Grenfell Campus, Memorial University of Newfoundland, Corner Brook, NL A2H 5G4,
Canada.
E. Buncel. Department of Chemistry, Queen’s University, Kingston, ON K7L 3N6, Canada.
Corresponding authors: Ik-Hwan Um (e-mail: ihum@ewha.ac.kr), Julian M. Dust (e-mail: jmdust@grenfell.mun.ca),
and Erwin Buncel (e-mail: buncele@chem.queensu.ca).
Can. J. Chem. 93: 1109–1114 (2015) dx.doi.org/10.1139/cjc-2015-0073
Published at www.nrcresearchpress.com/cjc on 16 March 2015.

1110
Can. J. Chem. Vol. 93, 2015
Chart 1.
Scheme 1.
were calculated from the slope of linear plots of kobsd versus nu-
cleophile concentration. These constants and relevant pKa values
are summarized in Table 1 for the reactions of 1a with 10 different
anionic nucleophiles. It is estimated from replicate runs that the
uncertainty in the rate constants is less than 3% except for the
reactions with HOO− and C6H5S−. Here, the instability of HOO−
and C6H5S− under the kinetic conditions results in kNu values with
larger uncertainty.
phase reactions of alkyl chlorides with ClO−, BrO−, HOO−, and
RO−12b. In contrast, recent gas-phase studies including computa-
tional methods have shown that ␣-nucleophiles exhibit lower
activation energies than isobasic normal nucleophiles (e.g., HOO−
versus MeO− or EtO−) in gas-phase SN2 reactions of dimethyl
methylphosphonate,15 methyl formate,16 or alkyl halides.17,18
The discrepancies (i.e., presence or absence of the ␣-effect in gas-
phase reactions) have been attributed to significant shifts in ba-
sicity of the nucleophiles between the solution and gas phases.15–18
Although gas-phase studies have reported that the solvent ef-
fect is not an important origin of the ␣-effect,15–18 we have shown
that the ␣-effect in reactions of the substrates in Chart 1 with
butane-2,3-dione monoximate (Ox−) and the reference isobasic
nucleophile 4-chlorophenoxide (4-Cl−C6H4O−) in DMSO–water mix-
tures of varying compositions is strongly dependent on the sol-
vent compositions.14 Notably, the ␣-effect increases as the DMSO
content in the reaction medium increases up to approximately
50 mol% DMSO and then decreases thereafter (i.e., a bell-shaped
␣-effect profile), although the magnitude of the ␣-effect is strongly
dependent on the nature of the electrophilic centers (e.g., C=O
versus C=S, P=O, and SO2).19b Dissection of the ␣-effect into ground-
state and TS contributions through combination of the kinetic
results with our calorimetric study has revealed that desolvation
of Ox− in the ground state leading to the rate-determining TS is
mainly responsible for the increasing ␣-effect up to 50 mol% DMSO,
while differential stability of TS contributes to the decreasing
␣-effect beyond 50 mol% DMSO.14
Our study has now been extended to SNAr reactions of 1-(4-
nitrophenoxy)-2,4-dinitrobenzene (1a) with anionic nucleophiles
bearing various nucleophilic atoms (i.e., a series of Y-substituted
phenoxides, Ox−, HOO−, HO−, N3−, and C6H5S−) in 80 mol%
water − 20 mol% DMSO (Scheme 1). In the present study, we have
examined the relative reactivities of the ␣-nucleophiles (i.e., HOO−
and Ox−) and their reference nucleophiles (i.e., OH− and
4-Cl−C6H4O−, respectively) toward 1a. A Brønsted-type plot has
been constructed to assess the presence–absence of the ␣-effect
and to quantify it. We have also investigated the effect of polariz-
ability on reactivity by employing highly polarizable nucleophiles
(i.e., N3− and PhS−) and nonpolarizable OH−.
Effect of nucleophile bacisity on reactivity
As shown in Table 1, the second-order rate constant for the
reaction of 1a with substituted phenoxide anions increases as
basicity of the nucleophile increases, e.g., kNu increases from
0.000375 to 0.0230 and 0.134 M−1 s−1 as the pKa of the conjugate
acid of the aryloxide increases from 7.95 to 9.38 and 10.19, in turn.
Interestingly, OH− is less reactive than 4-Cl−C6H4O−, although the
former is over 6 pKa units more basic than the latter. In contrast,
N3−, C6H5S−, and Ox− are much more reactive than would be ex-
pected from their basicity.
The effect of nucleophile basicity on reactivity is illustrated in
Fig. 1. As shown in the Brønsted-type plot, the kNu values for the
reactions with aryloxides (1–5) and HOO− (9) result in an excellent
linear correlation (R2 = 0.997) with ␤nuc = 1.17. It is notable that
OH− (10) exhibits extreme negative deviation from the linear
Brønsted-type plot, while N3− (6), C6H5S− (7), and Ox− (8) all deviate
positively from the line. If OH− behaved as one of the normal
nucleophiles that define the Brønsted line, kOH− would be esti-
mated to be 5.3 × 105 M−1 s−1 rather than the value found: 1.21 ×
10−2 M−1 s−1. This 4.4 × 107-fold difference between the hydroxide
rate constants further emphasizes the low reactivity of OH− in this
reaction system. For this set of nucleophiles, it is convincingly
demonstrated that nucleophilic reactivity of these nucleophiles is
not governed solely by their basicity in the current SNAr reaction
of 1a.
A similar result has been reported for reactions of 2,4-dinitrophenyl
methanesulfonate (2) with HOO−, OH−, and the same aryloxides
used in this study (Scheme 2). We have shown that the Brønsted-
type plot for the reaction of 2 with the aryloxides and HOO−
results in an excellent linear correlation with ␤nuc = 1.17, while
again, OH− deviates negatively from linearity. OH− has often ex-
hibited negative deviation from Brønsted-type plots for nucleo-
philic substitution reactions of esters with oxyanions carried out
in water.20 Jencks et al. have concluded that the solvation effect is
responsible for the negative deviation shown by strongly basic
OH− (or alkoxides).20 In fact, OH− has been reported to be 12 and
32 kcal/mol more strongly solvated than HOO− and C6H5O−, re-
spectively, in water.13 However, we have found that the negative
deviation shown by OH− in the reactions of 2 is not solely due to
the differential solvation effect but is also due to a difference in the
reaction mechanisms. Our kinetic results have revealed that the
reaction of 2 with the strongly basic OH− proceeds, in this case,
through an E1cb reversible mechanism, while the corresponding
Results and discussion
Reactions were performed under pseudo-first-order conditions
with the nucleophile concentration in excess (≥20-fold) over the
substrate concentration. All of the reactions in this study obeyed
first-order kinetics with quantitative liberation of 4-nitrophenoxide
ion. Pseudo-first-order rate constants (kobsd) were calculated from
the equation ln(A∞ − At) = −kobsdt + C. The plots of kobsd versus
nucleophile concentration were linear with positive intercepts
due to the contribution of water and (or) OH− from hydrolysis of
the anionic nucleophiles. The second-order rate constants (kNu
)
Published by NRC Research Press

Um et al.
1111
Table 1. Summary of second-order rate constants
(kNu) for the reactions of 1-(4-nitrophenoxy)-2,4-
dinitrobenzene (1a) with anionic nucleophiles in
80 mol% water − 20 mol% DMSO at 25.0 0.1 °C.
of 1a with a series of cyclic secondary amines in MeCN proceeds
through a stepwise mechanism with a Meisenheimer complex,
which decomposes to the products in the rate-determining step
via competitive catalytic and uncatalytic routes.22a In contrast, we
have reported that SNAr reactions of 1-(Y-substituted-phenoxy)-2,
4-dinitrobenzenes (Y = 4-NO2, 4-CN, 4-COMe, 4-CHO, 3-Cl, 4-Cl, H
and 4-Me) with OH− proceed via a stepwise mechanism with for-
mation of a Meisenheimer complex being the rate-determining
step on the basis of the kinetic results that (i) the Brønsted-type
plot is linear with ␤lg = −0.16 and (ii) ␴o constants result in a much
better Hammett correlation than ␴− constants.22b
As shown in Fig. 1, the Brønsted-type plot for the reaction of 1a
with aryloxides and HOO− exhibits an excellent linear correlation
with ␤nuc = 1.17. Such a large ␤nuc value implies that bond forma-
tion between the nucleophile and electrophilic center is fully ad-
vanced in the rate-determining TS. Accordingly, one can suggest
that the SNAr reaction of 1a with the oxyanions proceeds through
a stepwise mechanism with a TS structure similar to a Meisen-
heimer complex (e.g., full bond formation with little leaving
group expulsion). This idea is consistent with the fact that HOO−
and the aryloxides studied are much more basic and poorer nucle-
ofuges than 4-nitrophenoxide. Furthermore, it has generally been
understood that expulsion of the leaving group from an anionic
Meisenheimer complex occurs rapidly after the rate-determining
step to regain the lost aromaticity. Thus, we propose that the
negative deviation shown by OH− in Fig. 1 is not likely due to any
difference in the reaction mechanism or the presence of a com-
petitive process as previously found in the nucleophilic reaction
of 2 (Scheme 2), but rather, strong solvation of highly basic OH−
is responsible for the significantly decreased reactivity, at least
in part.
Nucleophile
pKa
7.95
9.02
9.38
9.95
10.19
4.72
7.80
9.44
11.62
15.74
103kNu (M−1 s−1
)
1
4-CN-C6H4O−
3-Cl-C6H4O−
4-Cl-C6H4O−
C6H5O−
0.375
6.33
23.0
51.2
134
1.99
2
3
4
5
6
7
8
9
10
4-Me-C6H4O−
−
N3
C6H5S−
Ox−
153
3810
8240
12.1
HOO−
HO−
Fig. 1. Brønsted-type plot for the reactions of 1-(4-nitrophenoxy)-2,
4-dinitrobenzene (1a) with anionic nucleophiles in 80 mol% water –
20 mol% DMSO at 25.0 0.1 °C. The identity of the points is given in
Table 1.
Solvation effect on the ␣-effect in the SNAr reaction
The ␣-effect has been defined as a positive deviation exhibited
by an ␣-nucleophile from a Brønsted-type plot. According to this
definition, the reference (or normal) nucleophile should have the
same basicity as the ␣-nucleophile to assess the ␣-effect.2b How-
ever, HOO− and OH− have traditionally been employed as a set of
␣- and normal nucleophiles, respectively, due to the similarity in
their structure, although their basicities are markedly different.2
Table 1 shows that HOO− is 680-fold more reactive than OH−
toward 1a (i.e., kHOO−/kOH− = 680). Traditionally, this is interpreted
as application of the ␣-effect by HOO−. However, HOO− does not
exhibit positive deviation from the Brønsted-type plot shown in
Fig. 1, indicating that the ␣-effect is absent for the reactions of 1a
with HOO−. This demonstrates clearly that assessment of the
␣-effect in a traditional way (i.e., “two-point” comparison of kNu
values for the reactions with HOO− and OH−) can be misleading. In
contrast, Ox− deviates positively from the Brønsted-type plot
shown in Fig. 1 and is 166-fold more reactive than isobasic
4-Cl−C6H4O−, a reference normal nucleophile that conforms to the
Brønsted line. It is apparent that the positive deviation shown by
Ox− represents the ␣-effect in the SNAr reaction of 1a.
Scheme 2.
Solvation effect has been reported to be responsible for the
␣-effect shown by Ox− in various nucleophilic substitution reac-
tions of esters, since our calorimetric study showed that Ox− is up
to 6.86 kcal/mol less strongly solvated than 4-Cl−C6H4O− in water–
DMSO mixtures.14 Similarly, Terrier et al. have also concluded that
solvation effect is an important factor that controls the ␣-effect in
the SNAr reaction of 1-fluoro-2,4-dinitrobenzene with a series of
oximate anions in water as well as in the reaction of 4-nitrophenyl
acetate (PNPA in Chart 1) with a series of ␣-ketoaldoximate an-
ions.31 They found that the magnitude of the ␣-effect decreases
rapidly as basicity of the ␣-nucleophiles increases.31 The decrease
in the ␣-effect for reactions with strongly basic oximate anions
(e.g., pKa > 8) has been attributed to a strong need for partial
desolvation before nucleophilic attack (i.e., asynchronicity or TS
imbalance).31 Note that HOO− would experience stronger TS im-
reaction with weakly basic aryloxides and HOO− proceeds via an
SN2(S), as shown in Scheme 2.21
Deduction of reaction mechanism
Since reaction mechanism is an important factor that determines
reactivity, detailed information on the reaction mechanism is nec-
essary to investigate the cause of the negative deviation shown by
OH− from the linear Brønsted-type plot shown in Fig. 1. It is well
known that SNAr reactions proceed through a stepwise mecha-
nism in which the rate-determining step is dependent on reaction
conditions (e.g., reaction medium, type of nucleophile, and leav-
ing group).19,22–30 We have recently shown that the SNAr reaction
Published by NRC Research Press

1112
Can. J. Chem. Vol. 93, 2015
trobenzenes were used as SNAr substrates.36 However, it should be
noted that the Ritchie study was performed in methanol for N3
and solvent effects may have obscured the inherent polarizability
factor for the azide ion.36 A widely applicable set of electrophilic-
ity (E) and nucleophilicity (N) values have been defined by the
Mayr group from eq. 1:
Table 2. Summary of second-order rate
constants (kNu (M−1s−1)) for the reactions of
PNPB and PNPTB with anionic nucleo-
philes in 80 mol% water − 20 mol% DMSO
at 25.0 0.1 °C.
−
Nucleophile
PNPB
PNPTB
−
N3
0.00234
0.0250
4.20
11.0
342
0.470
(1)
log k(20 °C) ϭ s(E ϩ N)
C6H5S−
OH−
where s represents a sensitivity parameter.37 Electrophile–nucleophile
combination reactions form the basis of eq. 1, where benzhydrylium
ions comprise the set of standard nucleophiles.37 Equation 1 has
been found to be widely applicable to many reactions including
SNAr displacements.4b,22d,22e,30b Moreover, it has been shown that
the Ritchie correlation is a special case subsumed by eq. 1.37
In support of the notion that solvent effects obscure the polar-
Note: The kinetic data were taken from
Um et al.33
balance than Ox−, since the former is over 2 pKa units more basic
than the latter. Therefore, one can attribute the absence of the
␣-effect in the current SNAr reaction to a strong need for partial
desolvation before nucleophilic attack, which is in accord with
the principle of nonperfect synchronization put forward by Ber-
nasconi.32
−
izability factor for N3 in the previous Ritchie study of SNAr dis-
placement, Phan and Mayr have reported that the intrinsic
−
nucleophilicity parameter, N, for N3 has a value of 14.54 in
91% methanol – 9% acetonitrile (v/v) solvent whereas the azide ion
is more nucleophilic in DMSO, N ≈ 20.50 in DMSO.38 Presumably
in the 80 mol% water – 20 mol% DMSO medium of the current
study, N3 is sufficiently desolvated that polarizability becomes
the dominant feature of its enhanced reactivity as a nucleophile
in SNAr displacement.
Polarizability effect on reactivity
It is notable that C6H5S− and N3− ions exhibit positive deviation
from the Brønsted-type plot shown in Fig. 1, although they are not
␣-nucleophiles. In contrast, OH− exhibits extreme negative devia-
tion from linearity. Furthermore, OH− is 12-fold less reactive than
C6H5S− toward 1a, although the former is approximately 8 pKa
units more basic than the latter (Table 1). This is reminiscent of the
kinetic result reported for nucleophilic substitution reactions of
C6H5S−, N3−, and OH− with substrates possessing a polarizable
electrophilic center (e.g., PNPTB in Chart 1).33 As shown in Table 2,
we have previously reported that N3− and C6H5S− become 4.7 × 103-
and 1.4 × 104-fold more reactive, respectively, on changing the
substrate from PNPB in Chart 1 (a C=O centered electrophile) to a
polarizable substrate PNPTB (a C=S centered electrophile). On the
contrary, OH− has resulted in ninefold decreased reactivity on
changing the substrate from PNPB to PNPTB. Furthermore, OH−
−
Conclusions
The current kinetic results have led us to conclude the follow-
ing. (i) The SNAr reaction of 1a in this study proceeds through a
stepwise mechanism with a TS structure similar to a Meisen-
heimer complex (e.g., full bond formation with little leaving
group expulsion). (ii) HOO− is 680-fold more reactive than OH− but
does not deviate from the Brønsted-type plot (i.e., absence of the
␣-effect). This demonstrates clearly that assessment of the ␣-effect
in a traditional way can be misleading. (iii) Solvation effect is
responsible for the ␣-effect shown by Ox−, since it was reported to
be 5.7 kcal/mol less strongly solvated than 4-Cl−C6H4O− in the
reaction medium. Absence of the ␣-effect for the reaction with
HOO− is due to a strong need for partial desolvation before nu-
cleophilic attack. (iv) The high nucleophilic reactivity shown by
N3− and C6H5S− toward polarizable 1a is due to strong interactions
between the polarizable nucleophile and substrate. (v) Both strong
solvation of OH− and weak interaction between the polarizable
substrate 1a and nonpolarizable OH− are responsible for the dra-
matic deviation shown by OH− from the Brønsted-type plot.
−
has been reported to be 23-fold less reactive than N3 toward
PNPTB, although the former is 11 pKa units more basic than the
latter.
The kinetic result obtained from the SNAr reactions of 1a with
C6H5S−, N3−, and OH− appears to be consistent with the hard–soft
−
acid and base principle,34 since C6H5S− and N3 are known to be
highly polarizable bases, while OH− is a nonpolarizable base. This
idea can be further supported by our recent finding that the rate
constant for SNAr reactions of 1a with alkali–metal ethoxides
(EtO−M+, M+ = Li+, Na+, K+, and 18-crown-6-ether complexed K+)
increases with increasing charge polarization of M+ ions (or in-
creasing size of M+ ions, i.e., EtO−Li+ < EtO−Na+ < EtO−K+ < EtO−K+/
18-crown-6-ether).22c Thus, one can suggest that the high polarizability
of C6H5S− and N3− is responsible for their great reactivity toward
1a, whose electrophilic center is highly polarizable due to the
␲-electrons. On the contrary, unfavorable affinity of OH− for the
polarizable electrophilic center as well as strong solvation of OH−
are considered to be responsible for the drammatically decreased
reactivity shown by OH− toward 1a.
Experimental section
Materials
1-(4-Nitrophenoxy)-2,4-dinitrobenzene (1a) was prepared from
the reaction of 1-fluoro-2,4-dinitrobenzene with 4-nitrophenol in
anhydrous ether in the presence of triethylamine, as reported
previously.22a The crude product was purified through column
chromatography. The purity of 1a was checked by means of the
melting point and 1H NMR characteristics. Other chemicals used
in this study were of the highest quality available. Doubly glass-
distilled water was further boiled and cooled under nitrogen just
before use. Due to low solubility of 1a in pure water, 80 mol%
water – 20 mol% DMSO was used as the reaction medium.
It may be argued that the deviations from Brønsted linearity for
C6H5S− and N3− are artifacts of the definition of the Brønsted line,
in that the line is defined by oxygen-centered nucleophiles. How-
ever, this argument is a tautological one. The enhanced reactivity
of the two nucleophiles relative to the Brønsted line is partly a
function of their central nucleophilic atoms, but this, in turn, is
explained by the polarizability of the nucleophilic atoms and
their attendant structures. In fact, sulfur-centered nucleophiles
are well recognized to display enhanced reactivity in SNAr dis-
placement reactions.27a,35
Kinetics
The kinetic study was performed with a UV-vis spectrophotom-
eter equipped with a constant-temperature circulating bath to
maintain the temperature in the reaction cell at 25.0 0.1 °C. The
reaction was followed by monitoring the appearance of the leav-
ing 4-nitrophenoxide ion at 405 nm. All of the reactions were
carried out under pseudo-first-order conditions in which nucleo-
phile concentrations were at least 20 times greater than the sub-
−
The results with N3 are more surprising. By some measures,
N3− has been previously shown to be less reactive than a range of
nucleophiles, notably on the Ritchie N + scale where 1-X–2,4-dini-
Published by NRC Research Press

Um et al.
1113
(d) Bernasconi, C. F.; Murray, C. J. J. Am. Chem. Soc. 1986, 108, 5251. doi:10.
1021/ja00277a032.
(9) (a) Hoz, S.; Buncel, E. Tetrahedron Lett. 1984, 25, 3411. doi:10.1016/S0040-
4039(01)91033-0; (b) Buncel, E.; Hoz, S. Tetrahedron Lett. 1983, 24, 4777. doi:
10.1016/S0040-4039(00)94005-X.
(10) (a) Ghosh, K. K.; Tiwari, S.; Marek, J.; Kuca, K. Lett. Drug Des. Discovery 2010, 7,
194. doi:10.2174/157018010790596650; (b) Ghosh, K. K.; Sinha, D.;
Satnami, M. L.; Dubey, D. K.; Rodriguez-Dafonte, P.; Mundhara, G. L. Langmuir
2005, 21, 8664. doi:10.1021/la051223b.
(11) (a) Dixon, J. E.; Bruice, T. C. J. Am. Chem. Soc. 1972, 94, 2052. doi:10.1021/
ja00761a043; (b) Dixon, J. E.; Bruice, T. C. J. Am. Chem. Soc. 1971, 93, 6592.
doi:10.1021/ja00753a044; (c) Gregory, M. J.; Bruice, T. C. J. Am. Chem. Soc. 1967,
89, 4400. doi:10.1021/ja00993a026.
strate concentration. The aryloxide and butane-2,3-dione monoximate
(Ox−) stock solutions of approximately 0.2 mol/L were prepared by
dissolving 2 equiv. of phenol (or butane-2,3-dione monoxime) and
1 equiv. of standardized NaOH solution to keep the pH constant in
this self-buffered solution. All solutions were freshly prepared
just before use under nitrogen and transferred by gas-tight sy-
ringes. It was found that H2O2 does not react with the substrate in
the absence of a base. Thus, the reaction of 1a with HOO− was
initiated by adding a calculated amount of NaOH stock solution to
a 10 mm quartz UV cell containing 2.50 mL of the thermostatted
reaction mixture made up of solvent, the substrate, and an aliquot
of the H2O2 stock solution. This method could generate HOO− ions
in situ and minimize decomposition of HOO− in the basic con-
dition. The H2O2 to NaOH concentration ratio was kept at 5.0.
Due to low solubility of thiophenol in the reaction medium, a
thiophenoxide–thiophenol stock solution of approximately 0.05 mol/L
was prepared. The reaction was initiated by adding 5 ␮L of a
0.02 mol/L solution of the substrate 1a in CH3CN with a 10 ␮L
syringe into a 10 mm quartz UV cell containing 2.50 mL of the
thermostatted reaction mixture made up of solvent and an ali-
quot of the nucleophile stock solution.
(12) (a) Depuy, C. H.; Della, E. W.; Filley, J.; Grabowski, J. J.; Bierbaum, V. M. J. Am.
Chem. Soc. 1983, 105, 2481. doi:10.1021/ja00346a066; (b) Villano, S. M.;
Eyet, N.; Lineberger, W. C.; Bierbaum, V. M. J. Am. Chem. Soc. 2009, 131, 8227.
doi:10.1021/ja9012084.
(13) Ritchie, J. F. J. Am. Chem. Soc. 1983, 105, 7313. doi:10.1021/ja00363a018.
(14) (a) Um, I. H.; Kang, J. S.; Kim, M. Y.; Buncel, E. J. Org. Chem. 2013, 78, 8689.
doi:10.1021/jo401415f; (b) Um, I. H.; Han, J. Y.; Buncel, E. Chem. Eur. J. 2009, 15,
1011. doi:10.1002/chem.200801534; (c) Um, I. H.; Hwang, S. J.; Buncel, E. J. Org.
Chem. 2006, 71, 915. doi:10.1021/jo051823f; (d) Um, I. H.; Shin, Y. H.; Han, J. Y.;
Buncel, E. Can. J. Chem. 2006, 84, 1550. doi:10.1139/v06-156; (e) Um, I. H.;
Hong, J. Y.; Buncel, E. Chem. Commun. 2001, 27. doi:10.1039/B007000I;
(f) Um, I. H.; Buncel, E. J. Am. Chem. Soc. 2001, 123, 11111. doi:10.1021/ja016917v;
(g) Um, I. H.; Buncel, E. J. Org. Chem. 2000, 65, 577. doi:10.1021/jo9915776.;
(h) Um, I. H.; Park, Y. M.; Buncel, E. Chem. Commun. 2000, 1917. doi:10.1039/
B005610N.
(15) McAnoy, A. M.; Paine, M. R.; Blanksby, S. J. Org, Biomol. Chem. 2008, 6, 2316.
doi:10.1039/b803734e.
(16) (a) Afzal, D.; Fountain, K. R. Can. J. Chem. 2011, 89, 1343. doi:10.1139/v11-113;
(b) Patterson, E. V.; Fountain, K. R. J. Org. Chem. 2006, 71, 8121. doi:10.1021/
jo061275l.
(17) (a) Ren, Y.; Wei, X.-G.; Ren, S.-J.; Lau, K.-C.; Wong, N.-B.; Li, W.-K. J. Comput.
Chem. 2013, 34, 1997. doi:10.1002/jcc.23356; (b) Liang, J.-X.; Geng, Z. Y.;
Wang, Y. C. J. Comput. Chem. 2012, 33, 595. doi:10.1002/jcc.21972;
(c) Wei, X. G.; Sun, X. M.; Wu, W. P.; Ren, Y.; Wong, N. B.; Li, W. K. J. Org. Chem.
2010, 75, 4212. doi:10.1021/jo1006575; (d) Ren, Y.; Yamataka, H. J. Comput.
Chem. 2009, 30, 358. doi:10.1002/jcc.21061; (e) Ren, Y.; Yamataka, H. J. Org.
Chem. 2007, 72, 5660. doi:10.1021/jo070650m; (f) Ren, Y.; Yamataka, H. Chem.
Eur. J. 2007, 13, 677. doi:10.1002/chem.200600203; (g) Ren, Y.;
Yamataka, H. Org. Lett. 2006, 8, 119. doi:10.1021/ol0526930.
(18) (a) Garver, J. M.; Gronert, S.; Bierbaum, V. M. J. Am. Chem. Soc. 2011, 133,
13894. doi:10.1021/ja205741m; (b) Garver, J. M.; Yang, Z.; Nichols, C. M.;
Worker, B. B.; Gronert, S.; Bierbaum, V. M. Int. J. Mass Spectrom. 2012, 316–318,
244. doi:10.1016/j.ijms.2012.02.014; (c) Garver, J. M.; Yang, Z.; Wehres, N.;
Nichols, C. M.; Worker, B. B.; Gronert, S.; Bierbaum, V. M. Int. J. Mass
Spectrom. 2012, 330–332, 182.
(19) (a) Crampton, M. R.; Emokpae, T. A.; Isanbor, C. Eur. J. Org. Chem. 2007, 1378.
doi:10.1002/ejoc.200600968; (b) Crampton, M. R.; Emokpae, T. A.;
Isanbor, C. J. Phys. Org. Chem. 2006, 19, 75. doi:10.1002/poc.997;
(c) Manderville, R. A.; Dust, J. M.; Buncel, E. J. Phys. Org. Chem. 1996, 9, 515.
doi:10.1002/(SICI)1099-1395(199608)9:8<515::AID-POC816>3.0.CO;2-5;
(d) Moutier, G.; Le Guével, E.; Cannes, C.; Terrier, F.; Buncel, E. Eur. J. Org.
Chem. 2001, 3279. doi:10.1002/1099-0690(200109)2001:17<3279::AID-EJOC3279>
3.0.CO;2-9.
Product analysis
4-Nitrophenoxide ion (and (or) its conjugate acid) was liberated
quantitatively and identified as one of the products by compari-
son of the UV-vis spectrum at the end of reaction with the authen-
tic sample under the experimental conditions.
Acknowledgements
This research was supported by the Basic Science Research Pro-
gram through the National Research Foundation of Korea funded
by the Ministry of Education (2012-R1A1B-3001637). Grateful ac-
knowledgment is also afforded to Grenfell Campus, Memorial
University (Vice-President’s Research Fund) (J.M.D.).
References
(1) Edwards, J. O.; Pearson, R. G. J. Am. Chem. Soc. 1962, 84, 16. doi:10.1021/
ja00860a005.
(2) Reviews: (a) Buncel, E.; Um, I. H.; Terrier, F. The Chemistry of Hydroxylamines,
Oximes and Hydroxamic Acids; Wiley Press: West Sussex, 2009, Chap. 17;
bBuncel, E.; Um, I. H. Tetrahedron 2004, 60, 7801. doi:10.1016/j.tet.2004.05.
006; (c) Hoz, S.; Buncel, E. Israel J. Chem. 1985, 26, 313. doi:10.1002/ijch.
198500113.
(3) (a) Fest, C.; Schmidt, K. J. The Chemistry of Organophosphorus Pesticides;
Springer-Verlag: New York, 1971; (b) Heath, D. F. Organophosphorus Poisons;
Pergamon Press: Oxford, 1961.
(4) (a) Terrier, F.; Rodriguez-Dafonte, P.; Le Guevel, E.; Moutiers, G. Org. Biomol.
Chem. 2006, 4, 4352. doi:10.1039/B609658C; (b) Terrier, F.; Lakhdar, S.;
Goumont, R.; Boubaker, T.; Buncel, E. Chem. Commun. 2004, 2586. doi:10.
1039/B410356D; (c) Terrier, F.; Le Guevel, E.; Chatrousse, A. P.; Moutiers, G.;
Buncel, E. Chem. Commun. 2003, 600. doi:10.1039/B212160N.
(20) Jencks, W. P.; Gilchrist, M. J. Am. Chem. Soc. 1968, 90, 2622. doi:10.1021/
ja01012a030.
(21) Um, I. H.; Im, L. R.; Buncel, E. J. Org. Chem. 2010, 75, 8571. doi:10.1021/
jo101978x.
(5) (a) Kamps, J. A. G.; Belle, R.; Mecinovic, J. Org. Biomol. Chem. 2013, 11, 1103.
doi:10.1039/C2OB26929E; (b) Kirby, A. J.; Davies, J. E.; Fox, D. J.;
Hodgson, D. R.; Goeta, A. E.; Lima, M. F.; Priebe, J. P.; Santaballa, J. A.;
Nome, F. Chem. Commun. 2010, 1302. doi:10.1039/B923742A; (c) Kirby, A. J.;
Tondo, D. W.; Medeiros, M.; Souza, B. S.; Priebe, J. P.; Lima, M. F.; Nome, F.
J. Am. Chem. Soc. 2009, 131, 2023. doi:10.1021/ja808746f.
(6) (a) Nigst, T. A.; Antipova, A.; Mayr, H. J. Org. Chem. 2012, 77, 8142. doi:10.1021/
jo301497g; (b) Domingos, J. B.; Longhinotti, E.; Brandao, T. A. S.; Santos, L. S.;
Eberlin, M. N.; Bunton, C. A.; Nome, F. J. Org. Chem. 2004, 69, 7898. doi:10.
1021/jo048737k; (c) Bunton, C. A.; Nome, F.; Quina, F. H.; Romsted, L. S. Acc.
Chem. Res. 1991, 24, 357. doi:10.1021/ar00012a001; (d) Herschlag, D.;
Jencks, W. P. J. Am. Chem. Soc. 1990, 112, 1951. doi:10.1021/ja00161a047;
(e) Jencks, W. P. Chem. Rev. 1985, 85, 511. doi:10.1021/cr00070a001.
(7) (a) Afzal, D.; Fountain, K. R. Can. J. Chem. 2014, 92, 346. doi:10.1139/cjc-2013-
0246; (b) Fountain, K. R. J. Phys. Org. Chem. 2005, 18, 481. doi:10.1002/poc.897;
(c) Fountain, K. R.; Felkerson, C. J.; Driskell, J. D.; Lamp, B. D. J. Org. Chem.
2003, 68, 1810. doi:10.1021/jo0206263; (d) Fountain, K. R.; Tad-y, D. B.;
Paul, T. W.; Golynskiy, M. V. J. Org. Chem. 1999, 64, 6547. doi:10.1021/
jo981902+; (e) Fountain, K. R.; Patel, K. D. J. Org. Chem. 1997, 62, 4795. doi:
10.1021/jo9606012.
(22) (a) Um, I. H.; Kim, M. Y.; Kang, T. A.; Dust, J. M. J. Org. Chem. 2014, 79, 7025.
doi:10.1021/jo5011872; (b) Kang, T. A.; Cho, H. J.; Um, I. H. Bull. Korean Chem.
Soc. 2014, 35, 2135. doi:10.5012/bkcs.2014.35.7.2135; (c) Um, I. H.; Cho, H. J.;
Kim, M. Y.; Buncel, E. Chem. Eur. J. 2014, 20, 13337. doi:10.1002/chem.
201404004; (d) Um, I. H.; Im, L. R.; Kang, J. S.; Bursey, S. S.; Dust, J. M. J. Org.
Chem. 2012, 77, 9738. doi:10.1021/jo301862b; (e) Um, I. H.; Min, S. W.;
Dust, J. M. J. Org. Chem. 2007, 72, 8797. doi:10.1021/jo701549h.
(23) Terrier, F. Nucleophilic Aromatic Displacement: The Influence of the Nitro Group;
Feuer, H., Ed.; Organic Nitro Chem. Ser.; VCH: New York, 1991.
(24) Buncel, E. The Chemistry of Functional Groups. Supplement F. The Chemistry of
Amino, Nitro and Nitroso Compounds; Patai, S., Ed.; Wiley: London, 1982.
(25) (a) Lakhdar, S.; Goumont, R.; Terrier, F.; Boubaker, T.; Dust, J. M.; Buncel, E.
Org. Biomol. Chem. 2007, 5, 1744. doi:10.1039/b702060k; (b) Goumont, R.;
Terrier, F; Vichard, D.; Lakhdar, S.; Dust, J. M.; Buncel, E. Tetrahedron Lett.
2005, 46, 8363. doi:10.1016/j.tetlet.2005.09.159.
(26) (a) Buncel, E.; Dust, J. M.; Terrier, F. Chem. Rev. 1995, 95, 2261. doi:10.1021/
cr00039a001, and references therein; (b) Kurbatov, S.; Lakhdar, S.;
Goumont, R.; Terrier, F. Org. Prep. Proced. Int. 2012, 44, 289. doi:10.1080/
00304948.2012.697701.
(27) (a) Terrier, F. Modern Nucleophilic Aromatic Substitution; Wiley-VCH: New York,
2013, Chap. 1; (b) Terrier, F.; Magnier, E.; Kizilian, E.; Wakselman, C.;
Buncel, E. J. Am. Chem. Soc. 2005, 127, 5563. doi:10.1021/ja0436291;
(c) El-Guesmi, N.; Boubaker, T.; Goumont, F.; Terrier, F. Org. Biomol. Chem.
2008, 6, 4041. doi:10.1039/b810273b.
(8) (a) Bernasconi, C. F.; Leyes, A. E.; Eventova, I.; Rappoport, Z. J. Am. Chem.
Soc. 1995, 117, 1703. doi:10.1021/ja00111a006; (b) Bernasconi, C. F.;
Stronach, M. W. J. Org. Chem. 1991, 56, 1993. doi:10.1021/jo00006a008;
(c) Bernasconi, C. F. Acc. Chem. Res. 1987, 20, 301. doi:10.1021/ar00140a006;
Published by NRC Research Press

1114
Can. J. Chem. Vol. 93, 2015
(28) Tee, O. S. Adv. Phys. Org. Chem. 1994, 29, 1. doi:10.1016/S0065-3160(08)60075-1.
(29) (a) Bernasconi, C. F. Chimia 1980, 34, 1; (b) Bernasconi, C. F. Acc. Chem. Res.
1978, 11, 147. doi:10.1021/ar50124a004.
(30) (a) Dust, J. M.; Manderville, R.A. Can. J. Chem. 1998, 76, 662. doi:10.1139/v98-
028; (b) Terrier, F.; Dust, J. M.; Buncel, E. Tetrahedron 2012, 68, 1829. doi:10.
1016/j.tet.2011.12.009; (c) Buncel, E.; Manderville, R. A.; Dust, J. M. J. Chem.
Soc., Perkin Trans. 2 1997, 1019. doi:10.1039/A605907D.
(31) Buncel, E.; Cannes, C.; Chatrousse, A.-P.; Terrier, F. J. Am. Chem. Soc. 2002,
124, 8766. doi:10.1021/ja020379k.
(32) (a) Bernasconi, C. F. Adv. Phys. Org. Chem. 1992, 27, 119. doi:10.1016/S0065-
3160(08)60065-9; (b) Bernasconi, C. F.; Ni, J. X. J. Am. Chem. Soc. 1993, 115,
5060. doi:10.1021/ja00065a016.
(34) (a) Laurence, C.; Gal, J. F.; Lewis Basicity and Affinity Scale; Wiley-VCH: New
York, 2010;(b) Pearson, R. G.; Songstad, J. J. Am. Chem. Soc. 1967, 89, 1827.
doi:10.1021/ja00984a014.
(35) (a) Bartoli, G.; Todesco, P. E. Acc. Chem. Res. 1977, 10, 125. doi:10.1021/
ar50112a004; (b) Crampton, M. R.; Willison, M. J. J. Chem. Soc. Perkin Trans. 2
1974, 238. doi:10.1039/P29740000238.
(36) Ritchie, C. D.; Sawada, M. J. Am. Chem. Soc. 1977, 99, 3754. doi:10.1021/
ja00453a039.
(37) Mayr, H.; Kempf, B.; Ofial, A. R. Acc. Chem. Res. 2003, 36, 66. doi:10.1021/
ar020094c.
(38) Phan, T. B.; Mayr, H. J. Phys. Org. Chem. 2006, 17, 706.
(33) Um, I. H.; Lee, J. Y.; Bae, S. Y.; Buncel, E. Can. J. Chem. 2005, 83, 1365. doi:10.
1139/v05-157.
Published by NRC Research Press