Structure-reactivity correlations in nucleophilic substitution reactions of Y-substituted phenyl X-substituted benzoates with anionic and neutral nucleophiles

Article abstract of DOI:10.1039/b607194e

A kinetic study is reported for the reactions of 4-nitrophenyl X-substituted benzoates (1a-l) and Y-substituted phenyl benzoates (2a-l) with two anionic nucleophiles (OH^- and CN^-) and three amines (piperidine, hydrazine, and glycylglycine) in 80 mol% H₂O-20 mol% dimethyl sulfoxide (DMSO) at 25.0 ± 0.1 °C. Each Hammett plot exhibits two intersecting straight lines for the reactions of 1a-l with the anionic nucleophiles and piperidine, while the Yukawa-Tsuno plots for the same reactions are linear. The Hammett plots for the reactions of 2a-l with hydrazine and glycylglycine demonstrate much better linear correlations with σ^- constants than with σ° or σ constants, indicating that the leaving group departure occurs at the rate determining step (RDS). On the contrary, σ^- constants result in poorer Hammett correlation than σ° constants for the corresponding reactions with OH^- and CN^-, indicating that the leaving group departure occurs after the RDS for the reactions with the anionic nucleophiles. The large ρ_X value (1.7 ± 0.1) obtained for the reactions of 1a-l with the anionic nucleophiles supports the proposal that the reactions proceed through an addition intermediate with its formation being the RDS. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b607194e

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Structure–reactivity correlations in nucleophilic substitution reactions of
Y-substituted phenyl X-substituted benzoates with anionic and neutral
nucleophiles†
Ik-Hwan Um,*a Ji-Youn Lee,a Mizue Fujiob and Yuho Tsunob
Received 22nd May 2006, Accepted 16th June 2006
First published as an Advance Article on the web 4th July 2006
DOI: 10.1039/b607194e
A kinetic study is reported for the reactions of 4-nitrophenyl X-substituted benzoates (1a–l) and
Y-substituted phenyl benzoates (2a–l) with two anionic nucleophiles (OH− and CN−) and three amines
(piperidine, hydrazine, and glycylglycine) in 80 mol% H2O–20 mol% dimethyl sulfoxide (DMSO) at
25.0 0.1 ◦C. Each Hammett plot exhibits two intersecting straight lines for the reactions of 1a–l with
the anionic nucleophiles and piperidine, while the Yukawa–Tsuno plots for the same reactions are
linear. The Hammett plots for the reactions of 2a–l with hydrazine and glycylglycine demonstrate much
better linear correlations with r− constants than with r◦ or r constants, indicating that the leaving
group departure occurs at the rate determining step (RDS). On the contrary, r− constants result in
poorer Hammett correlation than r◦ constants for the corresponding reactions with OH− and CN−,
indicating that the leaving group departure occurs after the RDS for the reactions with the anionic
nucleophiles. The large qX value (1.7 0.1) obtained for the reactions of 1a–l with the anionic
nucleophiles supports the proposal that the reactions proceed through an addition intermediate with its
formation being the RDS.
to identify the transition state and T‡ for aminolysis of various
Introduction
carboxylic esters.6–9
Due to their importance in biological processes as well as synthetic
However, the mechanism for reactions with anionic nucleophiles
is not completely understood.10–15 In a series of important studies
by Williams and coworkers, it has been concluded that acyl
group transfer to aryloxide anions occurs through a concerted
pathway.10 The evidence provided was a Brønsted-type plot
with absence of a break (or curvature) when the pKa of the
aryloxide nucleophile corresponded to that of the aryloxide leaving
group.10 The concerted mechanism has been supported through
structure–reactivity correlations reported by Jencks,11a Rossi,11b,c
and Castro,11d–f as well as kinetic isotope effect studies of Hengge,12
Marcus analysis by Guthrie,13a and recent theoretical calculations
by Xie et al.13b On the contrary, Buncel et al. have argued against
a concerted mechanism for acyl group transfer to aryloxides, on
the basis of Hammett plots exhibiting rather poor correlation with
r− but significantly better correlation with r◦ constants.14 Thus,
it has been concluded that the departure of the leaving group
from a tetrahedral intermediate is little advanced, if at all, in
the rate-determining transition state.14 In fact, we have recently
shown spectroscopic evidence, along with kinetic evidence, for an
addition intermediate in the reaction of a cyclic sulfinate ester with
sodium ethoxide in anhydrous ethanol.15a
One of the main reasons for the controversy about the reaction
mechanism is considered to be the lack of systematic studies. The
previous studies were limited mostly to investigation of the effect of
substituents in the attacking nucleophile10 or in the leaving group.14
Thus, we have prepared two series of substrates, 4-nitrophenyl X-
substituted benzoates (1a–l) and Y-substituted phenyl benzoates
(2a–l) and performed a systematic study of nucleophilic substitu-
tion reactions with two representative anionic nucleophiles (OH−
and CN−) and three different amines (piperidine, hydrazine, and
applications, acyl group transfer reactions of esters have been
the subject of extensive experimental and theoretical studies.1–15
One intriguing aspect is whether nucleophilic attack at the
carbonyl carbon occurs concertedly with leaving group departure
[eqn (1)], or whether reaction occurs through a discrete tetrahedral
intermediate [eqn (2)].
(1)
(2)
Aminolysis of esters is now definitely understood to proceed
through a stepwise mechanism.1–5 Curved Brønsted-type plots,
which have often been observed for aminolyses of carboxylic esters
with a good leaving group, support a stepwise mechanism with a
change in the rate-determining step (RDS).1–5 The RDS has been
suggested to change from breakdown of a zwitterionic tetrahedral
intermediate (T‡) to its formation as the attacking amine becomes
more basic than the leaving group by 4 to 5 pKa units.1–5 Recent
computational studies also favor a stepwise mechanism over a
concerted pathway, although some computational studies failed
aDepartment of Chemistry, Ewha Womans University, Seoul, 120-750, Korea.
E-mail: ihum@ewha.ac.kr; Fax: +82-2-3277-2844; Tel: +82-2-3277-2349
bInstitute for Materials Chemistry and Engineering, Kyushu University,
Hakozaki, Higashi-ku, Fukuoka, 812-8581, Japan
† Electronic supplementary information (ESI) available: Kinetic data. See
DOI: 10.1039/b607194e
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Table 2 Summary of second-order rate constants (kN/M−1s−1) for nu-
cleophilic substitution reactions of Y-substituted phenyl benzoates (2a–l)
with OH−, CN−, hydrazine and glycylglycine in 80 mol% H2O–20 mol%
glycylglycine) to obtain more conclusive information about the
reaction mechanism. Detailed reaction mechanisms are presented
herein.
DMSO at 25.0 0.1 ◦
C
kN/M−1s−1
No.
Y
OH−
CN−
Hydrazine
Glycylglycine
2a
2b
2c
2d
2e
2f
2g
2h
2i
3,4-(NO2)2
4-NO2
4-CN
4-CHO
4-COMe
4-COOEt
3-NO2
3-COMe
4-Cl
98.9a
13.4a
—
1.92
0.231
—
0.103
0.0768
—
0.141
0.0359
—
33.1
2.39b
0.538b
—
1.48
0.0240b
0.00446b
0.0140b
0.00161b
6.00 × 10−4b
—
4.72a
3.27a
—
0.201b
0.0836b
—
5.97a
1.80a
—
—
—
—
—
—
0.00520b
—
2j
2k
2l
H
4-Me
4-MeO
0.449a
0.316a
0.389a
0.0102
0.00783
0.00843
—
—
—
a Data taken from reference 14d. b Data taken from reference 5f .
an electron donating group, i.e., kN decreases from 5010 M−1s−1
to 13.4 and 0.0101 M−1s−1 as the substituent X changes from
3,5-(NO2)2 to H and 4-OH, respectively. A similar result has been
obtained for the corresponding reactions with CN− and piperidine.
It is noted that 1l is much less reactive than 1k regardless of the
type of nucleophiles. This is an unexpected result since 4-OH is
a weaker electron donating substituent than 4-NMe2 on the basis
of their r (e.g., r = − 0.37 and −0.77 for 4-OH and 4-NMe2,
respectively) or r+ values (e.g., r+ = − 0.98 and −1.73 for 4-OH
and 4-NMe2, respectively).
The fact that 1l is less reactive than 1k might imply that the
phenolic moiety of substrate 1l exists as a phenoxide form under
the reaction condition. This argument is reasonable since the
phenolic moiety of 1l is considered to be highly acidic. Although
the pKa of the phenolic moiety of 1l has not been reported, it is
expected to be lower than that of ethyl 4-hydroxybenzoate whose
pKa has been reported to be 8.50.16 This is because the ethyl group
of ethyl 4-hydroxybenzoate is a stronger electron donating group
than the 4-nitrophenyl group of 1l. Thus, it is plausible that the
substituent 4-OH in substrate 1l is present as its deprotonated
form, i.e., 4-O− under the kinetic condition.
Results and discussion
Reactions of 1a–l and 2a–l with the anionic and neutral nucle-
ophiles proceeded with quantitative liberation of 4-nitrophenoxide
or the corresponding aryloxide. All reactions in this study obeyed
pseudo-first-order kinetics under conditions of excess nucleophile.
Pseudo-first-order rate constants (kobsd) were determined from the
equation ln(A∞ − At) = − kobsdt + c. Correlation coefficients of
the linear regressions were usually higher than 0.9995. The plots of
kobsd vs. nucleophile concentrations were linear and passed through
the origin. Five different nucleophile concentrations were used to
determine the second-order rate constant (kN) from the slope of the
linear plots. It is estimated from replicate runs that the uncertainty
in rate constants is less than 3%. The kN values determined in
this way are summarized in Tables 1 and 2.
Effect of nonleaving group substituent on reactivity and mechanism
As shown in Table 1, the second-order rate constant (kN) for the
reactions of 1a–l with OH− decreases as the substituent X in the
nonleaving group changes from an electron withdrawing group to
Table 1 Summary of second-order rate constants (kN/M−1s−1) for nu-
cleophilic substitution reactions of 4-nitrophenyl X-substituted benzoates
(1a–l) with OH−, CN−, and piperidine in 80 mol% H2O–20 mol% DMSO
The effect of substituent X on reactivity is illustrated in Fig. 1.
The Hammett plots for the reactions of 1a–l with OH− and
CN− ions consist of two intersecting straight lines (except for
the negative deviation shown by the reactions of 1l). Traditionally,
such a nonlinear Hammett plot has been interpreted as a change
in the RDS.17–19 However, as shown in Fig. 2, the Yukawa–Tsuno
plots for the same reactions are linear with an r value of ca.
0.5, indicating that the nonlinear Hammett plots are definitely
not due to a change in the RDS. Besides, the Hammett plot for
the reactions of 1a–l with piperidine (Fig. 3) also exhibits two
intersecting straight lines with a negative deviation for the reaction
of 1l, while the corresponding Yukawa–Tsuno plot (inset of Fig. 3)
is linear with r = 1.18.
at 25.0 0.1 ◦
C
kN/M−1s−1
No.
X
OH−
CN−
Piperidine
1a
1b
1c
1d
1e
1f
1g
1h
1i
3,5-(NO2)2
4-Cl-3-NO2
4-NO2
4-CN
3-Cl
4-Cl
H
3-Me
4-Me
5010a
715a
42.5
8.17
6.25
4.47
47.5
23.1
531a
21.0b
18.7b
12.8b
8.14b
5.94b
4.56b
3.68b
1.95b
0.259
0.0659
354a
73.8a
39.6a
13.4a
8.90a
5.65a
2.64a
0.144
0.0101
1.33
0.628
0.228
0.189
0.117
0.0460
0.00265
3.57 × 10−4
The Yukawa–Tsuno equation [eqn (3)] has been applied to
numerous reactions in which a partial positive charge develops
in the transition state of the RDS.20
1j
1k
1l
4-MeO
4-NMe2
4-OH
a Data taken from reference 18. b Data taken from reference 5c.
log (kX/kH) = q[r◦ + r(r+ − r◦)]
(3)
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Fig. 1 Hammett plots for the reactions of 4-nitrophenyl X-substituted
benzoates (1a–l) with OH− (᭹) and CN− (᭺) in 80 mol% H2O–20 mol%
DMSO at 25.0 0.1 ◦C. The identity of points is given in Table 1.
Fig. 3 Hammett and Yukawa–Tsuno plot (inset) for the reactions of
4-nitrophenyl X-substituted benzoates (1a–l) with piperidine in 80 mol%
H2O–20 mol% DMSO at 25.0 0.1 ◦C. The identity of points is given in
Table 1.
The magnitude of the r value represents the resonance demand
of the reaction center or the extent of resonance contribution.20
Eqn (3) becomes the Hammett equation when r = 0 or the
Brown–Okamoto equation when r = 1. Since the r value is neither
0 nor 1 in this study, the Yukawa–Tsuno equation results in better
correlation than the Hammett or Brown–Okamoto equations, in
which r or r+ constants alone are used. Thus, one can suggest
that stabilization of the ground state through the resonance
interaction as illustrated in resonance structures I ↔ II and III ↔
IV is responsible for the nonlinear Hammett plots, and the RDS
for the reactions of 1a–l does not vary on changing the electronic
nature of the substituent X in the nonleaving group.
It is noted that 1l is on the linear Yukawa–Tsuno plot regardless
of the type of nucleophile when the r+ value of −2.6 for 4-O−
is used. This result is consistent with the preceding argument
that 4-OH in 1l becomes 4-O− under the kinetic condition. The
r+ value for 4-O− has been calculated by Wepster et al.21 using
the acid dissociation constants of 4-hydroxyphenylacetic acid and
4-nitrophenol in aqueous ethanol, but never been determined
Fig.
2
Yukawa–Tsuno plots for the reactions of 4-nitrophenyl
X-substituted benzoates (1a–l) with OH− (᭹) and CN− (᭺) in 80 mol%
H2O–20 mol% DMSO at 25.0 0.1 ◦C. The identity of points is given in
Table 1.
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directly from kinetic studies. The reported r+ value for 4-O− is
−2.3,21 which is slightly smaller than that determined in this study
(−2.6) but much larger than the r+ value of −1.73 for 4-NMe2.
This is why 1l is much less reactive than 1k and exhibits a significant
negative deviation from the Hammett plots in Fig. 1 and 3.
Effect of leaving group substituent on reactivity and mechanism
To get more information about the reaction mechanism, the effect
of the leaving group substituent on reactivity has been investigated.
As shown in Table 2, the kN for the reactions of Y-substituted
phenyl benzoates (2a–l) with OH− ion decreases as the substituent
Y in the leaving group becomes a weaker electron withdrawing
(or a stronger electron donating) group, i.e., kN decreases from
98.9 M−1s−1 to 3.27 and 0.389 M−1s−1 as the substituent Y changes
from 3,4-(NO2)2 to 4-COMe and 4-MeO, respectively. A similar
result has been obtained for the corresponding reactions with CN−
ion and with the two amine nucleophiles.
Alkaline hydrolysis of aryl benzoates in aqueous MeCN has
been proposed to proceed through a stepwise mechanism, in
which formation of a tetrahedral intermediate is the RDS.22
On the contrary, Williams et al. have concluded that the reac-
tions of 4-nitrophenyl X-substituted benzoates with OH− and
phenoxide ions in aqueous MeCN proceed through a concerted
mechanism.10d The evidence provided for a concerted mechanism
is linear Hammett plots correlated with r constants.10d Williams
et al. have insisted that the Hammett plots should have exhibited
sharp breaks on changing the electronic nature of the substituent
X in the nonleaving benzoyl moiety, if the reaction proceeded
through an intermediate. The absence of a break in the Hammett
plots has been taken as evidence for a concerted mechanism.10d
However, we have clearly shown that a sharp break in Hammett
plots (e.g., Fig. 1 and 3) is not necessarily due to a change in the
RDS in the preceding section.
Fig. 4 Hammett correlations with r− and r◦ constants (inset) for the
reactions of Y-substituted phenyl benzoates (2a–l) with hydrazine (᭹) and
glycylglycine (᭺) in 80 mol% H2O–20 mol% DMSO at 25.0 0.1 ◦C. The
identity of the points is given in Table 2.
If the leaving group departure is involved in the RDS either
in a concerted or stepwise mechanism, a partial negative charge
would develop on the oxygen atom of the leaving aryloxides at
the transition state of the RDS. Since such a negative charge
can be delocalized on the substituent Y in the leaving group
through resonance, r− constants should exhibit a better Hammett
correlation than r or r◦ constants.
The above argument can be proved by the result obtained from
the reactions of 2a–l with hydrazine and glycylglycine. As shown in
Fig. 4, the Hammett plots ex◦hibit much better linear correlations
with r− constants than with r or r constants for the reactions with
the two amines. This result clearly indicates that the leaving group
departure occurs at the RDS for the reactions of 2a–l with these
amines, and the negative charge developed on the oxygen atom
of the leaving aryloxide can be delocalized on the substituent Y
through resonance.
The Hammett plots for the reactions of 2a–l with the anionic
nucleophiles are illustrated in Fig. 5. It is shown that r− constants
exhibit many scattered points on the Hammett plots. This result
contrasts with that obtained for the corresponding reactions
with the amines. However, r◦ constants exhibit only slightly
better correlations than r− constants. Thus, the present result
alone cannot be confidently taken as decisive evidence for one
mechanism over another for the reactions of 1a–l with the anionic
nucleophiles. To obtain additional information about the reaction
Fig. 5 Hammett correlations with r◦ and r− constants (inset) for the
reactions of Y-substituted phenyl benzoates (2a–l) with OH− (᭹) and CN−
(᭺) in 80 mol% H2O–20 mol% DMSO at 25.0 0.1 ◦C. The identity of
points is given in Table 2.
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mechanism, the magnitude of the qX and qY values has
been analyzed in the following section since it can be an indirect
probe for determination of reaction mechanism.
In fact, qX values have been reported to be 0.3 and up to −6.47 for
the reaction of X-substituted benzyl chlorides with OH− ion17a,23a
and for solvolysis of a-methyl X-substituted benzyl chlorides,20a
a
typical SN2 and SN1 reaction, respectively. Jencks has shown that
the nature of the RDS also influences the magnitude of qX for the
reactions of X-substituted benzaldehydes with semicarbazide in
a weakly acidic solution (e.g., pH = 3.9).24 qX has been found to
decrease from a large positive value to near zero as the substituent
changes from electron donating groups to electron withdrawing
ones.24 Jencks has attributed the decrease in the qX value to a
change in the RDS from formation of the addition intermediate
to its breakdown as the substituent changes from electron donating
groups to electron withdrawing ones.24
As mentioned in the preceding section, the leaving group
departure has been suggested to occur at the RDS for the current
aminolysis reactions. Accordingly, the rate of the leaving group
departure would be strongly dependent on the electronic nature
of the substituent Y in the leaving group, which is responsible for
the large qY value (2.16–2.58). However, the substituent X in the
nonleaving group would not exhibit a high sensitivity to the rate of
reactions due to the opposing substituent effect when the leaving
group departure occurs at the RDS. This argument can account
for the fact that qX has been determined to be much smaller (i.e.,
0.68) than the qY value for the aminolysis in the current study. In
this regard, the qX value of 1.7 0.1 obtained for the reactions
of 1a–l with OH− and CN− appears to be too large for reactions
which proceed through an SN2-like mechanism. Such a large qX
value can be taken as indirect evidence that the reactions proceed
through an addition intermediate with its formation being the
RDS. This is in accord with the fact that r◦ constants result in
better Hammett correlation than r− constants for the reactions of
1a–l with OH− and CN− although the difference in the correlation
coefficient is not significant.
Factors influencing magnitude of qX and qY
The qX value has been determined to be ca. 1.7 for the reactions of
1a–l with the anionic nucleophiles OH− and CN− (Fig. 2), while
the qY is ca. 1.0 or 1.5 depending on the substituent constants
used (e.g., r− or r◦) for the corresponding reactions of 2a–l
(Fig. 5). A similar result has been reported for alkaline hydrolysis
of Y-substituted phenyl X-substituted benzoates in 67% H2O–33%
MeCN (v/v).22a Kirsch et al. have found that the substituent in the
benzoyl moiety (X) exerts a greater sensitivity than that in the aryl
moiety (Y), i.e., qX = 2.04 and qY = 1.24.22a The greater sensitivity
shown by the substituent X in the nonleaving group has been
explained in terms of a distance effect under the assumption that
the attack of OH− ion to the carbonyl carbon is the RDS, since
the reaction site is one atom closer to the benzoyl substituent X
than to the aryl substituent Y.22a Thus, one might suggest that the
distance effect is responsible for the fact that the qX is larger than
the qY value for the reactions of 1a–l and 2a–l with the anionic
nucleophiles.
However, an opposite result has been obtained for the reactions
with amines. The value of qX has been determined to be much
smaller than qY for the reactions with amine nucleophiles, i.e.,
qX and qY are 0.68 (Fig. 3) and 2.16–2.58 (Fig. 5), respectively.
Although the substituent Y is one atom further away than the
substituent X from the reaction site, the former exhibits a greater
sensitivity than the latter. Therefore, the distance effect suggested
by Kirsch et al. cannot be solely responsible for the result that qX
is larger than qY for the reactions with OH− and CN− ions.
One can suggest that the type of nucleophile might be an
important factor in determining the qX and qY values, since the
transmission of electronic effects would be more significant for
the reactions with anionic nucleophiles than for those with neutral
amines. In fact, the reactions with the anionic nucleophiles result
in much larger qX values than those with the neutral amine, i.e., the
qX value determined is 1.86 and 1.63 for the reactions of 1a–l with
OH− and CN−, respectively but only 0.68 for the corresponding
reactions with piperidine. Thus, the magnitude of qX appears to
be highly dependent on the nature of the nucleophile (e.g., anionic
vs. neutral).
Conclusions
The present study has allowed us to conclude the following:
(1) The nonlinear Hammett plots obtained for the reactions of
1a–l with OH−, CN−, and piperidine are not due to a change in the
RDS. (2) The linear Yukawa–Tsuno plots suggest that stabilization
of the ground state through resonance interaction between the p-
electron donor substituent X and the carbonyl functionality is
responsible for the nonlinear Hammett plots. (3) Departure of the
leaving group occurs at the RDS for the aminolysis of 1a–l and 2a–
l since the Hammett plots exhibit good linear correlations with r−
constants with a small qX value. (4) The large qX values and better
Hammett correlations with r◦ constants for the corresponding
reactions with OH− and CN− ions suggest that the reactions
proceed through an intermediate with its formation being the
RDS. (5) The nature of reaction mechanism (or RDS) has been
shown to be most important among the factors influencing the
magnitude of qX and qY values.
On the other hand, the magnitude of qY obtained for the
reactions of 2a–l contrasts with that of qX determined for the
reactions of 1a–l. The qY values are 2.16–2.58 and ca. 1.0 (or
1.5) for the reactions of 2a–l with the neutral amines (Fig. 4)
and with the anionic nucleophiles (Fig. 5), respectively. Clearly,
qY is much larger for the reactions with the amines than with the
anionic nucleophiles. Thus, the type of nucleophile cannot be fully
responsible for the fact that qX is larger for the reactions with the
OH− and CN− ions than for those with piperidine.
A small qX value has often been reported for SN2 reactions17a,23
since the electronic effect of substituents in the nonleaving group
can be compensated due to the opposing substituent effect, i.e., an
electron withdrawing substituent would accelerate the attack of
nucleophiles but retard the departure of the negatively charged
leaving group, while an electron donating substituent would
prevent nucleophilic attack but enhance leaving group departure.
Experimental
Materials
Aryl benzoates (X–C6H4CO2C6H4–Y) except 1k and 1l were
prepared from the reaction of X-substituted benzoyl chloride
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with Y-substituted phenol in the presence of triethylamine in
anhydrous ether as reported in the literature.22,25 Substrates 1k
and 1l were prepared from the reactions of 4-nitrophenol and
4-hydroxybenzoic acid (or 4-dimethylaminobenzoic acid) in the
presence of dicyclohexyl carbodiimide in ethyl acetate.25d Their
purity was checked by means of melting point and spectral data
such as IR and H NMR characteristics. Doubly glass distilled
water was further boiled and cooled under nitrogen just before
use. Other chemicals used were of the highest quality available.
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1
Kinetics
The kinetic studies were performed with a UV–vis spectropho-
tometer for slow reactions (t1/2 ≥ 10 s) or with a stopped-flow
spectrophotometer for fast reactions (t1/2 < 10 s) equipped with
a constant temperature circulating bat◦h to keep the temperature
of the reaction mixture at 25.0 0.1 C. All the reactions were
performed in 80 mol% H2O–20 mol% DMSO to eliminate a
solubility problem. The reactions were followed by monitoring
the appearance of the leaving aryloxide at a fixed wavelength
corresponding to the maximum absorption (kmax) of Y–C6H4O−.
All reactions were carried out under pseudo-first-order conditions
in which the concentration of nucleophiles was at least 20 times
greater than that of the substrate. Nucleophile stock solution of
ca. 0.2 M was prepared in a 25.0 mL volumetric flask just before
use and transferred by gastight syringes. The amine stock solution
of ca. 0.2 M was prepared by dissolving 2 equiv. of free amine
(or amine hydrochloride) and 1 equiv. of standardized HCl (or
NaOH) solution to make a self-buffered solution.
Typically, the reaction was initiated by adding 5 lL of a 0.01 M
solution of the substrate in acetonitrile by a syringe to a 10 mm
quartz UV cell containing 2.50 mL of the thermostated reaction
mixture made up of solvent and an aliquot of the nucleophile stock
solution. Generally, the nucleophile concentration was varied over
the range (1–100) × 10−3 M, while the substrate concentration was
2 × 10−5 M. Usually, five different nucleophile concentrations were
employed, and replicate kobsd values were determined to calculate
the second-order rate constants (kN) from the slope of linear plots
of kobsd vs. nucleophile concentrations.
Products analysis
Y-Substituted phenoxide was liberated quantitatively and identi-
fied as one of the reaction products by comparison of the UV–vis
spectra after completion of the reaction with those of the authentic
sample under the same reaction conditions.
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Xie, Y. Zhou, D. Xu and H. Guo, Org. Lett., 2005, 7, 2093–2095.
14 (a) E. Buncel, I. H. Um and S. Hoz, J. Am. Chem. Soc., 1989, 111,
971–975; (b) I. H. Um, S. J. Hwang and E. Buncel, J. Org. Chem., 2006,
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Chem., 2004, 69, 2436–2441; (d) I. H. Um, H. J. Han, J. A. Ahn, S.
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Acknowledgements
This work was supported by Korea Research Foundation (2005-
015-C00256).
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2166; (b) I. Tunon and M. F. Ruiz-Lopez, Chem.–Eur. J., 2005, 11,
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