Pitfalls in assessing the α-effect: Reactions of substituted phenyl methanesulfonates with HOO-, OH-, and substituted phenoxides in H2O

Article abstract of DOI:10.1021/jo101978x

Toward resolving the current controversy regarding the validity of the α-effect, we have examined the reactions of Y-substituted phenyl methanesulfonates 1a-1l with HOO^-, OH^-, and Z-substituted phenoxides in the gas phase versus solu

Full text of DOI:10.1021/jo101978x

pubs.acs.org/joc
Pitfalls in Assessing the r-Effect: Reactions of Substituted Phenyl
Methanesulfonates with HOO-, OH-, and Substituted Phenoxides in
H2O
Ik-Hwan Um,*,† Li-Ra Im,† and Erwin Buncel*,‡
†Department of Chemistry and Nano Science, Ewha Womans University, Seoul 120-750, Korea, and
‡Department of Chemistry, Queen’s University, Kingston, Ontario, Canada K7L 3N6
ihum@ewha.ac.kr; buncele@queensu.ca
Received October 7, 2010
Toward resolving the current controversy regarding the validity of the R-effect, we have examined the
reactions of Y-substituted phenyl methanesulfonates 1a-1l with HOO-, OH-, and Z-substituted
phenoxides in the gas phase versus solution (H2O). Criteria examined in this work are the following:
(1) Brønsted-type and Hammett plots for reactions with HOO-and OH-, (2) comparison of βlg
values reported previously for the reactions of Y-substituted phenyl benzenesulfonates 2a-2k with
HOO- (βlg = -0.73) and OH- (βlg = -0.55), and for those of 1a-1l with HOO- (βlg = -0.69) and
OH- (βlg = -1.35), and (3) Brønsted-type plot showing extreme deviation of OH- for reactions of
2,4-dintrophenyl methanesulfonate 1a with aryloxides, HOO-, and OH-, signifying extreme
solvation vs different mechanisms. The results reveal significant pitfalls in assessing the validity of
current interpretations of the R-effect. The extreme negative deviation by OH- must be due, in part,
to the difference in their reaction mechanisms. Thus, the apparent dependence of the R-effect on
leaving-group basicity found in this study has no significant meaning due to the difference in
operating mechanisms. The current results argue in favor of a further criterion, i.e., a consistency in
mechanism for the R-nucleophiles and normal nucleophiles.
Introduction
described originally by Edwards and Pearson as the R-
effect,1 continues to be controversial.2-19 Prevalent theories
on the R-effect phenomenon include ground-state (GS)
destabilization, transition-state (TS) stabilization, thermo-
dynamic stabilization of products. and solvent effects.2-19
Impetus for these studies has recently come from two fronts:
(1) development of new mass spectrometric techniques,
which have provided insight into gas-phase reactivity, and
(2) rapid advances in calculational methods.3-6
The origin of the enhanced reactivity that is generally
observed for nucleophiles possessing an atom with an un-
shared electron pair adjacent to the nucleophilic center,
(1) Edwards, J. O.; Pearson, R. G. J. Am. Chem. Soc. 1962, 84, 16–24.
(2) Reviews: (a) Buncel, E.; Um, I. H.; Terrier, F. The Chemistry of
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2009; Chapter 17. (b) Buncel, E.; Um, I. H. Tetrahedron 2004, 60, 7801–7825.
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Beselov, V. Ya. Russ. Chem. Rev. 1978, 47, 631–648. (e) Fina, N. J.; Edwards,
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DOI: 10.1021/jo101978x
r
Published on Web 11/18/2010
J. Org. Chem. 2010, 75, 8571–8577 8571
2010 American Chemical Society

Um et al.
JOCArticle
Because of the absence of solvent, the mass spectrometric
studies are deemed to address experimentally the fundamental
question of whether, inthe absence of solvents, R-nucleophiles
intrinsically display greater reactivity than normal nucleophiles.3,4
Of course, this conundrum is also addressed through calcu-
lational studies.4-6 Thus, interestingly, in a recent gas-phase
study of the reactions of R-nucleophiles with alkyl chlorides,
using a tandem flowing afterglow-selected ion flow tube
instrument, Bierbaum et al. concluded that “the R-effect is
not due to an intrinsic property of the anion but instead due
to a solvent effect”.3a This is in contradiction to a study of
hydroperoxide anion with dimethyl methylphosphonate in a
modified quadrupole ion trap mass spectrometer, combined
with a DFT calculational study, which concluded that
CHART 1
A further development of the Hoz SET model for the R-effect
has been reported by computing barrier heights at the HF/
6-311þþG (2df, 2p) level of theory.5 In methyl transfer from
methyl formate to HOO- and EtO- (gas-phase acidity-matched),
a 3.6 kcal/mol lowering of TS was found, i.e., more single
electron transfer character with HOO- than with HO- or
EtO-.5 This bolstered our earlier suggestion of TS stabilization
derived in the earlier solution studies of methyl transfer from
aryl methyl sulfates to hydrazine and glycine ethyl ester.7
Studies of solvent effects on the R-effect have produced a
wealth of information.17-19 The remarkable discovery of
bell-shaped solvent effect plots suggested a differential sol-
vent effect when kinetic studies aided by ΔH of solution of
the substrates in Chart 1, possessing CdO, PdO, SO2, and
CdS centers, with butane-2,3-dione monoximate and p-chloro-
phenoxide were performed in DMSO-H2O mixtures.17-19
The two-phase plots indicated differential TS stabilization in
DMSO-rich media and differential GS destabilization in
H2O-rich media.17-19 The above results amply illustrate
the complexity of solvent effects on the R-effect.
In the present study we have examined the relative reactiv-
ities of HOO- and OH- as bases and as nucleophiles in their
reaction with Y-substituted phenyl methanesulfonates 1a-1l.
OH- is a strong enough base in deprotonation, enabling an
E1cb pathway; however, because of its lower basicity and
enhanced nucleophilicity (R-effect), reaction of HOO- pro-
ceeds via an SN2(S) mechanism. On the other hand, in the
reaction of substituted phenoxides with 2,4-dinitrophenyl
methanesulfonate 1a, OH- is slightly more reactive than
HOO-, i.e., lack of an R-effect (Table 1).
HOO- reacts with lower activation energy (7.8 kJ mol-1
)
compared to CH3O-, in accord with a gas-phase R-effect.4
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Results
Reactions were performed under pseudo-first-order con-
ditions with the concentration of nucleophiles in excess over
the substrate concentration. All reactions obeyed first-order
kinetics with quantitative liberation of Y-substituted phen-
oxide ion. Pseudo-first-order rate constants (kobsd) were
calculated from the equation ln(A¥ - At) = -kobsdt þ C.
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84, 1550–1556. (b) Um, I. H.; Hong, J. Y.; Buncel, E. Chem. Commun. 2001,
27–28. (c) Um, I. H.; Buncel, E. J. Am. Chem. Soc. 2001, 123, 11111–11112.
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Chem. 2002, 67, 8475–8480. (b) Um, I. H.; Lee, E. J.; Buncel, E. J. Org. Chem.
2001, 66, 4859–4864. (c) Um, I. H.; Park, Y. M.; Buncel, E. Chem. Commun.
2000, 1917–1918.
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TABLE 1. Summary of Second-Order Rate Constants for Reactions of
Y-Substituted Phenyl Methanesulfonates 1a-1l with HOO- and HO- in
H2O at 25.0 ( 0.1 ꢀC
Y
pKa
103kHOO-/M-1 s-1
103kHO-/M-1 s-1
2,4-(NO2)2 (1a)
3,4-(NO2)2 (1b)
4-NO2-2-Cl (1c)
4-NO2 (1d)
4-CHO (1e)
4-CN (1f)
4-COCH3 (1g)
3-NO2 (1h)
3-CHO (1i)
3-Cl (1j)
4.11
5.42
5.45
7.14
7.66
7.95
8.05
8.35
8.98
9.02
9.19
9.38
101 000
7 730
4 640
315
232
a
71.1
96.4
39.6
a
309 000
40 100
19 500
67.6
6.90
4.26
1.54
1.93
0.246
0.168
0.137
0.0697
3-COCH3 (1k)
4-Cl (1l)
21.3
a
aRate constants could not be measured due to the interference by
HOO-.
TABLE 2. Summary of Second-Order Rate Constants for Reactions of
2,4-Dinitrophenyl Methanesulfonate 1a with Substituted Phenoxides,
HOO-, and OH- in H2O at 25.0 ( 0.1 ꢀC
FIGURE 1. Dependence of the R-effect on leaving-group basicity
for reactions of Y-substituted phenyl methanesulfonates 1a-1l with
HOO- and HO- in H2O at 25.0 ( 0.1 ꢀC.
entry
Z
pKa
103 kArO-/M-1 s-1
1
2
3
4
5
6
7
4-CNPhO-
3-ClPhO-
4-ClPhO-
PhO-
7.95
9.02
9.38
9.95
10.19
11.62
15.7
4.23
116
193
626
SO2-centered electrophiles20,21 or even up to 104 in reactions
of benzonitriles, with an sp-hybridized electrophilic center.22
Figure 1 illustrates the magnitude of the R-effect assessed
by a traditional method (i.e., the kHOO-/kOH- ratio) as a
function of the leaving-group basicity. The plot of log-
(kHOO-/kOH-) vs the pKa of the conjugated acids of the
leaving aryloxides is linear with a slope of 0.66, although
some scattered points are present. The current result appears
to be similar to the reports that the magnitude of the R-effect
increases linearly as the leaving-group basicity increases for
methyl transfer reactions of Y-substituted phenyl methyl
sulfates with hydrazine and glycine ethyl ester (i.e., an SN2
mechanism)7 as well as nucleophilic substitution reactions of
Y-substituted phenyl benzoates with hydrazine and
glycylglycine.23 The reactions of aryl benzoates with hydra-
zine and glycylglycine have been shown to proceed through
the same mechanism, i.e., a stepwise mechanism in which
breakdown of a zwitterionic tetrahedral intermediate is the
rate-determining step (RDS).23 In contrast, the current
reactions of 1a-1l with HOO- and HO- are not considered
to proceed through the same mechanism on the basis of the
significant difference in βlg values between the two reaction
series, as shown in Figure 2.
As shown in Figure 2, the Brønsted-type plots exhibit
excellent linear correlation. However, the slope of the Brønsted-
type plots (βlg) is significantly different, i.e., βlg=-0.69 for
reactions with HOO- and βlg=-1.35 for the corresponding
reactions with OH-. The βlg value for the reactions of 1a-1k
with HOO- (βlg = -0.69) is practically the same as that
reported previously for the reactions of 2a-2k with HOO-
(βlg=-0.73).21 Thus, one can suggest that the reactions of 1a-1k
with HOO- proceed through the same mechanism as those of
Y-substituted phenyl benzenesulfonates 2a-2k with HOO-. In
contrast, a βlg value of -1.35 implies that the reactions of 1a-1l
4-MePhO-
HOO-
2 090
101 000 a
309 000 b
HO-
akHOO-. bkOH-
.
The plots of kobsd vs nucleophile concentration for the
reactions with HOO- and Z-substituted phenoxide anions
were linear with positive intercepts due to the contribution of
H2O and/or OH- from hydrolysis of the anionic nucleo-
philes (see Figures S1-S14 in the Supporting Information).
The second-order rate constants (kN) were calculated from
the slope of linear plots of kobsd vs [nucleophile] and are
summarized in Table 1 for the reactions of 1a-1l with HOO-
and OH- and in Table 2 for those of 1a with Z-substituted
phenoxide anions. It is estimated from replicate runs that the
uncertainty in the rate constants is less than (3%.
Discussion
a. Unusual Reversal in Reactivity of Hydroperoxide vs
Hydroxide. Table 1 shows that the second-order rate con-
stant for the reaction with HOO- decreases as leaving-group
basicity increases, e.g., kHOO- decreases from 101 M-1 s-1 to
0.315 and 0.0213 M-1 s-1 as the pKa of the conjugate acid of
the leaving group increases from 4.11 to 7.14 and 9.19, in
turn. Similar results are shown for the corresponding reac-
tions with OH-, e.g., kOH- decreases from 309 M-1 s-1 to
6.76 ꢀ 10-2 and 6.97 ꢀ 10-5 M-1 s-1 as the pKa of the
conjugate acid of the leaving group increases from 4.11 to
7.14 and 9.38, in turn. It is important to note that HOO- is
more reactive than OH- for the reactions of substrates
possessing a poor leaving group (e.g., 1d-1k). However,
the former is less reactive than the latter for the reactions of
substrates bearing a good leaving group (e.g., 1a-1c). This is
quite an unexpected result since HOO- has often been reported
to exhibit significantly enhanced reactivity compared to
OH- for various nucleophilic reactions performed in H2O,
e.g., rate enhancement of ca. 102 in reactions of CdO- and
(20) Jencks, W. P.; Gilchrist, M. J. Am. Chem. Soc. 1968, 90, 2622–2637.
(21) Um, I. H.; Im, L. R. Bull. Kor. Chem. Soc. 2009, 30, 2393–2397.
(22) Mclssac, J. E., Jr.; Subbaraman, J.; Mulhausen, H. A.; Behrman,
E. J. J. Org. Chem. 1972, 37, 1037–1041.
(23) Um, I. H.; Chung, E. K.; Lee, S. M. Can. J. Chem. 1998, 76, 729–737.
J. Org. Chem. Vol. 75, No. 24, 2010 8573

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would develop on the O atom of the leaving aryloxide at the
transition state of the RDS. In this case, one might expect that
σꢀ constants would result in a better Hammett correlation than
σ- constants.
To investigate the nature of RDS, Hammett plots have
been constructed with σꢀ and σ- constants. As shown in
Figure 3, σꢀ constants (A) result in significantly poorer
correlation with scattered points than σ- constants (B),
indicating that leaving-group departure is advanced in the
transition state of RDS. This result excludes a stepwise
mechanism (path a). Thus, one can conclude that the reac-
tions of 1a-1k with HOO- proceed through an SN2(S)
mechanism, in which departure of the leaving group and
attack of the nucleophile occur simultaneously. This mech-
anism can be further supported by the fact that βlg = -0.69,
which is typical for reactions reported to proceed through a
concerted mechanism (e.g., aminolysis, alkaline hydrolysis,
and ethanolysis of Y-substituted phenyl diphenylphosphi-
nates and phosphinothioates).25
c. Hydroxide Reaction Pathways: E1cb (rev.) vs E1cb
(irrev.), E2, SN2(S), or Two-Step Addition/Elimination. The
large negative βlg value (i.e., -1.35) found for the reactions of
1a-1l with OH- implies that departure of the leaving group
is significantly advanced in the transition state of RDS. To
examine this idea, Hammett plots have been constructed
using σꢀ and σ- constants. As shown in Figure 4, the
Hammett plot correlated with σꢀ constants exhibits highly
scattered points (A), while that correlated with σ- constants
results in better correlation (B). This supports the above idea
that departure of the leaving group is significantly advanced
in the transition state of RDS.
FIGURE 2. Brønsted-type plots for reactions of Y-substituted
phenyl methanesulfonates 1a-1l with HOO- (A) and HO- (B) in
H2O at 25.0 ( 0.1 ꢀC. The identity of points is given in Table 1.
with OH- proceed through a different mechanism from the
corresponding reactions with HOO- (βlg=-0.69).
Many different pathways are possible for the reactions of
1a-1l as shown in Scheme 1, e.g., (a) a two-step addition/
elimination mechanism, (b) an SN2(S) mechanism (a con-
certed bimolecular nucleophilic displacement at sulfur, fol-
lowing the first suggestion of SN2(P) nomenclature in the
related organophosphate system),24 (c) an E2 mechanism,
and (d) an E1cb reversible or E1cb irreversible mechanism.
b. Hydroperoxide Reaction Pathways: One-Step SN2(S) vs
Two-Step Addition/Elimination, E2, E1cb (irrev.), or E1cb
(rev.). It is evident that the reactions of Y-substituted phenyl
benzenesulfonates 2a-2k would proceed either through a
two-step addition/elimination mechanism (e.g., Scheme 1,
path a) or through an SN2(S) pathway (e.g., path b) but
cannot proceed through an E2 (e.g., path c) or E1cb mecha-
nism (e.g., path d) due to the absence of acidic protons. Thus,
one can suggest that the reactions of 1a-1k would proceed
also through a two-step addition/elimination mechanism or
through an SN2(S) pathway on the basis of the similarity in
their βlg values, as mentioned above.
The fact that σ- constants exhibits better correlation than
σꢀ constants excludes a two-step addition/elimination mech-
anism (i.e., path a in Scheme 1). This is because, if the
reactions proceed through an addition/elimination mecha-
nism, expulsion of the leaving group should occur after the
RDS on the basis of the fact that OH- is much more basic
and a poorer nucleofuge than aryloxides. One can also rule
out an E1cb irreversible mechanism, in which departure of
the leaving group occurs after the RDS.
If the reactions proceed through a stepwise mechanism with
an addition intermediate, the RDS should be formation of the
intermediate. This is because HOO- is more basic and a poorer
nucleofuge than the leaving aryloxides. Thus, if the reactions
proceed through a stepwise mechanism, no negative charge
Therefore, three different pathways remain for the reac-
tions of 1a-1l with OH-, e.g., an SN2(S), an E2, or an E1cb
reversible mechanism. The reactions of Y-substituted phenyl
benzenesulfonates 2a-2k with OH- have been reported to
proceed through an SN2(S) mechanism on the basis of the
SCHEME 1. Plausible Pathways for Reactions of 1a-1l with Anionic Nucleophiles: (a) Two-Step Addition/Elimination, (b) SN2(S), (c)
E2, and (d) E1cb Reversible or E1cb Irreversible Mechanisms
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FIGURE 3. Hammett plots correlated with σꢀ (A) and σ- constants (B) for reactions of Y-substituted phenyl methanesulfonates 1b-1k with
HOO- in H2O at 25.0 ( 0.1 ꢀC. The identity of points is given in Table 1.
FIGURE 4. Hammett plots correlated with σꢀ (A) and σ- constants (B) for reactions of Y-substituted phenyl methanesulfonates 1b-1l with
HO- in H2O at 25.0 ( 0.1 ꢀC. The identity of the points is given in Table 1.
linear Brønsted-type plot with βlg = -0.55.26 The βlg value
of -1.35 suggests that the reactions of 1a-1l with OH- do
not proceed through an SN2(S) mechanism. Such a large βlg
value excludes also an E2 mechanism, since βlg values have
been reported to be -0.5 ( 0.1 for reactions proceeding through
an E2 mechanism.27a-c Thus, the large βlg suggests that the
reactions of 1a-1l with OH- proceedthroughanE1cbreversible
mechanism, in which expulsion of the leaving group occurs in
the RDS. This can be supported by the report that hydrolysis of
aryl 3,5-dimethyl-4-hydroxybenzenesulfonates proceeds
through an E1cb mechanism on the basis of βlg=-1.55.27d
To examine the above argument that the reactions of
1a-1l with OH- proceed through an E1cb reversible mech-
anism, deuterium exchange experiments have been performed
by allowing substrate 1d to react with NaOD in 80 mol %
(24) (a) Kirby, A. J.; Younas, M. J. Chem. Soc. B 1970, 1165–1172. (b)
Williams, A.; Naylor, R. A. J. Chem. Soc. B 1971, 1973–1979.
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7330. (c) Um, I. H.; Park, J. E.; Shin, Y. H. Org. Biomol. Chem. 2007, 5, 3539–
3543. (d) Um, I. H.; Akhtar, K.; Shin, Y. H.; Han, J. Y. J. Org. Chem. 2007,
72, 3823–3829. (e) Um, I. H.; Shin, Y. H.; Han, J. Y.; Mishima, M. J. Org.
Chem. 2006, 71, 7715–7720.
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1
D2O/20 mol % CD3CN. The H NMR spectrum of the
methyl moiety of 1d taken from the reaction mixture (Figure 5)
shows overlapping spectra of undeuterated, monodeuterated,
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Um et al.
JOCArticle
FIGURE 5. 1H NMR spectrum of the methyl group of 1d after
partial reaction with NaOD in 80 mol % D2O/20 mol % CD3CN.
FIGURE 6. Brønsted-type plot for reactions of 2,4-dinitrophenyl
methanesulfonate 1a with Z-substituted phenoxides (1-5), HOO-
(6), and OH- (7) in H2O at 25.0 ( 0.1 ꢀC. The identity of points is
given in Table 2. Point 7 (i.e., OH-) is excluded in calculations of the
slope and correlation coefficient.
and dideuterated methyl groups, indicating that deprotonation
and reprotonation of the methyl group occur. The observation
of deuterium exchange is consistent with an E1cb reversible
mechanism.
d. Pitfalls in Assessing the r-Effect. The R-effect was
defined as a positive deviation from a Brønsted-type nucleo-
philicity plot.2c Thus, the reference (or normal) nucleophile
should have the same basicity as the R-nucleophile in order
to assess the R-effect. However, HOO- and OH- have
traditionally been employed as the R-nucleophile and nor-
mal nucleophile, respectively, although their basicities are
significantly different.3,22,28 Our current study shows that
assessment of the R-effect in a traditional way (e.g., compar-
ison of rate constants for reactions with HOO- and OH-)
can be misleading. For example, the R-effect for the reactions
of 1a-1k with HOO- and OH- illustrated in Figure 1 has
no significant meaning since the two series of reactions
proceed through different mechanisms, as mentioned in the
preceding section, e.g., an SN2(S) mechanism for the reac-
tions with HOO- but an E1cb reversible pathway for those
with OH-.
We have performed reactions of 1a with a series of
Z-substituted phenoxides and constructed a Brønsted-type
plot in Figure 6, including the data for the reactions with
HOO- and OH-. Aryloxides have been chosen as a series of
normal nucleophiles in this study, since they would behave as
a nucleophile rather than as a base due to their weak basicity.
The second-order rate constants (kArO-) are summarized in
Table 2, together with kHOO- and kOH- values for comparison.
e. Solvation Effects. As shown in Figure 6, reactions of 1a
with the aryloxides and HOO- result in an excellent linear
Brønsted-type plot, while OH- deviates negatively from
linearity. The fact that the aryloxides and HOO- result in
excellent linear correlation, with βnuc=1.17, suggests that the
reactions of 1a with the aryloxides and HOO- proceed
through a common mechanism, i.e., an SN2(S) mechanism.
This is reasonable since aryloxides are not basic enough to
proceed through an E2 or E1cb mechanism. One can also
exclude an addition/elimination mechanism. This is because,
if the reactions proceed through an addition/elimination
mechanism, leaving-group departure would occur after the
RDS, as mentioned above. One then might expect a βnuc
value of 0.3 ( 0.1, as reported previously for nucleophilic
substitution reactions of esters which proceed through a
stepwise mechanism, with formation of an intermediate
being the RDS (e.g., aminolysis and pyridinolysis of esters
possessing a good leaving group).29-31 Clearly, the βnuc value
of 1.17 is too large for a stepwise mechanism, in which
leaving-group departure occurs after the RDS. Thus, one
can suggest that reactions of 1a with aryloxides also proceed
through an SN2(S) mechanism.
It is important to note that OH- deviates negatively from
the linear Brønsted-type plot, as shown in Figure 6. Such
negative deviation has often been reported for reactions with
OH- performed in H2O.20 Solvation effect has been sug-
gested to be responsible for the deviation since OH- is
known to be 12 kcal/mol more strongly solvated than HOO-
in H2O.32 However, it is apparent that the negative deviation
shown by OH- in the current study is not solely due to the
(29) (a) Um, I. H.; Yoon, S. R.; Park, H. R.; Han, H. J. Org. Biomol.
Chem. 2008, 6, 1618–1624. (b) Um, I. H.; Park, Y. M.; Fujio, M.; Mishima,
M.; Tsuno, Y. J. Org. Chem. 2007, 72, 4816–4821. (c) Um, I. H.; Lee, J. Y.;
Fujio, M.; Tsuno, Y. Org. Biomol. Chem. 2006, 4, 2979–2985. (d) Um, I. H.;
Jeon, S. E.; Seok, J. A. Chem. Eur. J. 2006, 12, 1237–1243. (e) Um, I. H.; Lee,
J. Y.; Lee, H. W.; Nagano, Y.; Fujio, M.; Tsuno, Y. J. Org. Chem. 2005, 70,
4980–4987. (f) Um, I. H.; Fujio, M.; Tsuno, Y. J. Org. Chem. 2004, 69, 3937–
3942. (g) Um, I. H.; Lee, S. E.; Kwon, H. J. J. Org. Chem. 2002, 67, 8999–
9005.
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J. Org. Chem. 2004, 69, 6711–6714.
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Um et al.
JOCArticle
differential solvation effect but is also due to the difference in
reaction mechanisms, as discussed in the preceding section.
was prepared by dissolving 2 equiv of Z-substituted phenol and
1 equiv of standardized NaOH solution to keep the pH constant
in this self-buffered solution. All solutions were prepared freshly
just before use under nitrogen and transferred by gastight
syringes. It was found that HOOH does not react with the
substrate in the absence of a base. Thus, the reaction of 1a-1k
with HOO- was initiated by adding a calculated amount of ca.
0.5 M NaOH stock solution to a 10 mm quartz UV cell contain-
ing 2.50 mL of the thermostated reaction mixture made up of
solvent, the substrate, and an aliquot of the HOOH stock
solution. This method could generate HOO- ion in situ and
minimize decomposition of HOO- in the basic condition. The
[HOOH]/[NaOH] ratio was kept at 5.0. The reaction with OH-
or aryloxide was initiated by adding 5 μL of a 0.02 M solution of
the substrate in CH3CN by a 10 μL 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 NaOH or
aryoxide stock solution.
Conclusions
Our study has allowed us to conclude the following: (1)
The reactions of 1a-1k with HOO- proceed through an
SN2(S) mechanism, while the corresponding reactions with
OH- occur through an E1cb reversible pathway. (2) The
dependence of the R-effect on leaving-group basicity found
in this study has no significant meaning since the reactions of
1a-1l with HOO- and OH- proceed through different
reaction mechanisms, SN2(S) vs E1cb (rev.). (3) Reactions
of 1a with a series of aryloxides and HOO- result in an
excellent linear Brønsted-type plot, while OH- exhibits
extreme negative deviation from the linearity. The negative
deviation is not solely due to solvation effect but is due, in
part, to the difference in their reaction mechanisms. (4) The
current results argue in favor of a further criterion, i.e.,
constancy in reaction of the R- and normal-nucleophiles.
(5) Assessment of the R-effect by a traditional way based just
on comparison of the rate constants of the R-nucleophiles
and normal nucleophiles can be misleading. Controversial
gas-phase results arise, in some cases, from different mecha-
nisms for the chosen R-nucleophile compared to the normal
nucleophile.
Product Analysis. Y-substituted phenoxide was liberated
quantitatively and identified as one of the products by compar-
ison of the UV-vis spectrum at the end of reaction with that of
the authentic sample under the experimental conditions.
1
Deuterium Exchange Experiments. The H NMR spectra of
substrate 1d in 80 mol % D2O/20 mol % CD3CN were taken
before and after addition of NaOD to check for deuterium
exchange at the methyl group (Figures S15-S18, Supporting
Information). The deuterated methyl signal resulted in upfield
shifts of ca. 0.015 ppm with splitting due to H-D coupling (J =
2.5 Hz), which are characteristic of partial deuteriation of
methyl groups.34
Experimental Section
Materials. Compounds 1a-1l were prepared from the reac-
tion of methanesulfonyl chloride with Y-substituted phenols in
anhydrous ether in the presence of triethylamine as reported
previously.33 The crude products were purified through column
chromatography. The purity of 1a-1l was checked by means of
Acknowledgment. This research was supported by Basic
Science Research Program through the National Research
Foundation of Korea (NRF), funded by the Ministry of
Education, Science and Technology (2009-0075488), and by
NSERC of Canada. L.-R.I. is also grateful for the BK 21
Scholarship.
1
the melting points and H NMR characteristics. Other chemi-
cals used, including H2O2 and phenols, were of the highest
quality available. Doubly glass-distilled water was further
boiled and cooled under nitrogen just before use.
Kinetics. The kinetic study was performed with a UV-vis
spectrophotometer for slow reactions (e.g., t1/2 g 10 s) or with a
stopped-flow spectrophotometer for fast reactions (e.g., t1/2 <
10 s), 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
leaving Y-substituted phenoxide ion. All the reactions were
carried out under pseudo-first-order conditions in which nucleo-
phile concentrations were at least 20 times greater than the
substrate concentration. The ca. 0.2 M aryloxide stock solution
Supporting Information Available: Tables S1-S9, kinetic
conditions and data for reactions of 1a-1l with HOO-; Tables
S10-S21, kinetic data for reactions of 1a-1l with OH-; Tables
S22-S26, kinetic data for reactions of 1a with Z-substituted
phenoxides; Figures S1-S9, plots of kobsd vs [HOO-] for
reactions of 1a-k; Figures S10-S14, plots of kobsd vs [ArO-]
for the reactions of 1a with Z-substituted phenoxides; Figures
S15-S18, 1H NMR spectra of the methyl group of 1d in 80 mol
% D2O/20 mol % CD3CN before and after addition of NaOD.
This material is available free of charge via the Internet at http://
pubs.acs.org.
(33) (a) Crossland, R. K.; Servis, K. L. J. Org. Chem. 1970, 35, 3195–3196.
(b) Pregel, M. J.; Buncel, E. J. Am. Chem. Soc. 1993, 115, 10–14.
(34) Emsley, J. W.; Feency, J.; Sutcliffe, L. H. High Resolution NMR
Spectroscopy; Pergamon Press: Oxford, 1965.
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