Medium effects on the α-effect in DMSO-H2O mixtures - Comparative studies of p-nitrophenyl benzoate and acetate - Dissection of ground-state and transition-state effects

Article abstract of DOI:10.1139/V06-156

In a study of the origin of the α-effect and its dependence on the nature of the reaction medium as well as structural effects, we report herein a kinetic study of the reactions of p-nitrophenyl benzoate (PNPB) with butan-2,3-dione monoximate (Ox^-, α-nucleophile) and p-chlorophenoxide (p-ClPhO^-, the reference nucleophile) in dimethyl sulfoxide (DMSO)-H₂O mixtures of varying compositions at 25.0 ± 0.1°C. The second-order rate constants (k_N) decrease modestly on addition of DMSO to the medium up to 10 mol% DMSO but increase significantly beyond that point for both nucleophiles. Ox^- is more reactive than p-ClPhO^- in all solvent mixtures studied (i.e., the α-effect). The α-effect increases as the DMSO content in the medium increases up to 40 mol% DMSO and then decreases beyond that point resulting in a bell-shaped α-effect profile. The bell-shaped α-effect profile obtained for the current reaction is similar to that found previously for the corresponding reaction of p-nitrophenyl acetate (PNPA), differing notably however, in the magnitude of the α-effect beyond 40 mol% DMSO. The PNPB/p-ClPhO^- reaction gains greater rate enhancement than the PNPA/p-ClPhO^- reaction in the DMSO-rich region, resulting in the smaller α-effect for PNPB beyond 40 mol% DMSO. It is proposed that the observed modulation of the α-effect by the solvent medium is explicable as a ground-state effect in the H₂O-rich region and a transition-state effect in the DMSO-rich region.

Full text of DOI:10.1139/V06-156

1550
Medium effects on the ␣-effect in DMSO–H2O
mixtures — Comparative studies of p-nitrophenyl
benzoate and acetate — Dissection of ground-
state and transition-state effects
Ik-Hwan Um, Young-Hee Shin, Jeong-Yoon Han, and Erwin Buncel
Abstract: In a study of the origin of the α-effect and its dependence on the nature of the reaction medium as well as
structural effects, we report herein a kinetic study of the reactions of p-nitrophenyl benzoate (PNPB) with butan-2,3-
dione monoximate (Ox–, α-nucleophile) and p-chlorophenoxide (p-ClPhO–, the reference nucleophile) in dimethyl
sulfoxide (DMSO)–H2O mixtures of varying compositions at 25.0 0.1 °C. The second-order rate constants (kN) de-
crease modestly on addition of DMSO to the medium up to 10 mol% DMSO but increase significantly beyond that
point for both nucleophiles. Ox– is more reactive than p-ClPhO– in all solvent mixtures studied (i.e., the α-effect). The
α-effect increases as the DMSO content in the medium increases up to 40 mol% DMSO and then decreases beyond
that point resulting in a bell-shaped α-effect profile. The bell-shaped α-effect profile obtained for the current reaction is
similar to that found previously for the corresponding reaction of p-nitrophenyl acetate (PNPA), differing notably how-
ever, in the magnitude of the α-effect beyond 40 mol% DMSO. The PNPB/p-ClPhO– reaction gains greater rate en-
hancement than the PNPA/p-ClPhO– reaction in the DMSO-rich region, resulting in the smaller α-effect for PNPB
beyond 40 mol% DMSO. It is proposed that the observed modulation of the α-effect by the solvent medium is explica-
ble as a ground-state effect in the H2O-rich region and a transition-state effect in the DMSO-rich region.
Key words: medium effect, the α-effect, ground state, transition state, solvation, desolvation.
Résumé : Dans le cadre d’une étude sur l’origine de l’effet α et de sa dépendance sur la nature du milieu réactionnel
ainsi que des effets structuraux, on a réalisé une étude cinétique des réactions du benzoate de p-nitrophényle (BPNP)
avec le monoximate de la butane-2,3-dione (Ox–, α-nucléophile) et le p-chlorophénolate (p-ClPhO–, le nucléophile de
référence), dans des mélanges de diméthylsulfoxyde (DMSO)–eau (H2O) de compositions variables, à 25,0 0,1 °C.
Jusqu’à une concentration de 10 mole %, les constantes de vitesse du deuxième ordre (kN) diminuent légèrement par
addition de DMSO; au-delà de ce point, elles augmentent toutefois d’une façon significative pour les deux nucléophi-
les. Le nucléophile Ox– est plus réactif que le p-ClPhO– dans tous les mélanges de solvant étudiés, c’est-à-dire qu’il
présente l’effet α. Jusqu’à une concentration de 40 mole % de DMSO, l’effet α augmente avec une augmentation de la
concentration de DMSO; au-delà de ce point, il diminue ce qui conduit à un profil d’effet α qui est en forme de
cloche. Le profil d’effet α en forme de cloche qui est obtenu pour cette réaction est semblable à celui qui a été ob-
servé antérieurement pour la réaction correspondante de l’acétate de p-nitrophényle (APNP); il diffère toutefois dans
l’amplitude de l’effet α au-delà de la concentration de 40 mole % en DMSO. Dans la région riche en DMSO compor-
tant plus de 40 mole % de DMSO, la réaction du BPNP–p-ClPhO– conduit à une augmentation beaucoup plus grande
de la vitesse que celle observée pour la réaction du APNP–p-ClPhO–. On propose donc que la modulation observée de
l’effet α par la nature du solvant (figure 2) peut être expliquée par un effet de l’état fondamental dans la région riche
en eau et un effet de l’état de transition dans la région riche en DMSO.
Mots clés : effet de solvant, effet α, état fondamental, état de transition, solvatation, désolvatation.
[Traduit par la Rédaction] Um et al. 1556
Received 14 August 2006. Accepted 10 October 2006. Published on the NRC Research Press Web site at http://canjchem.nrc.ca on
16 November 2006.
I.-H. Um,1 Y.-H. Shin, and J.-Y. Han. Division of Nano Sciences and Department of Chemistry, Ewha Womans University, Seoul
120–750, Korea.
E. Buncel.2 Department of Chemistry, Queen’s University, Kingston, ON K7L 3N6, Canada and Division of Nano Sciences and
Department of Chemistry, Ewha Womans University, Seoul 120–750, Korea.
1Corresponding author (e-mail: ihum@ewha.ac.kr).
2Corresponding author (e-mail: buncele@queensu.ca)
Can. J. Chem. 84: 1550–1556 (2006)
doi:10.1139/V06-156
© 2006 NRC Canada

Um et al.
1551
Scheme 1.
with different electrophilic centers (i.e., p-nitrophenyl
diphenylphosphinate and benzenesulfonate) and with differ-
ent leaving groups (i.e., substituted phenyl acetates) (7c–7e).
Introduction
Nucleophiles possessing one or more nonbonding electron
pairs at the position α to the nucleophilic center exhibit en-
hanced reactivity compared with reference nucleophiles of
similar basicity (the α-effect) (1). Various proposals have
been advanced to account for the α-effect phenomenon, in-
cluding destabilization of the ground state (GS) through
electronic repulsion between nonbonding electron pairs, sta-
bilization of product (thermodynamic α-effect), stabilization
of the transition state (TS), a TS having aromatic or radi-
caloid character, as well as a solvent medium effect (1–11).
However, up to this time there is no general agreement as to
which factor(s) are predominant as the origin(s) of this phe-
nomenon. Our studies have been largely directed toward elu-
cidating the role of the solvent medium (7–10).
In the best known protic polar solvent, water, anionic
nucleophiles are expected to be highly solvated through H-
bonding (12, 13). Transfer to an aprotic polar solvent such
as DMSO should result in loss of H-bonding, however, ion–
dipole and polarizability interactions could become domi-
nant (12, 13). The generally observed increased nucleophilic
reactivity of small (hard) anions in DMSO with respect to
water was first highlighted in studies by Parker (13). How-
ever, this effect may operate differentially when comparing
two nucleophiles, as must be the case when considering the
α-effect. Differential solvation could be exhibited in
imbalanced transition states as well as in differences in
ground state solvation and desolvation (14). To probe such
differential effects, we have combined kinetic and thermody-
namic studies for α-effect systems as a function of incremen-
tal modulation of the solvent medium from pure water to
DMSO (7, 9).
The definition of the α-effect adopted recently is a positive
deviation exhibited by an α-nucleophile from a Brønsted-
type nucleophilicity plot (1a, 1b). According to this defini-
tion, the reference nucleophile is one which possesses the
same basicity as the α-nucleophile but does not deviate from
the Brønsted-type plot.
Some years ago, we performed nucleophilic substitution
reactions of p-nitrophenyl acetate (PNPA) with butan-2,3-
dione monoximate (Ox–, α-nucleophile) and p-chloro-
phenoxide (p-ClPhO–, the reference nucleophile) in dimethyl
sulfoxide (DMSO)–H2O mixtures at 25.0 0.1 °C (7a). The
pKa of the conjugate acids of the two nucleophiles has been
reported to vary in a parallel manner in the DMSO–H2O
mixtures studied. Unexpectedly, we found that the α-effect
increases as the DMSO content in the medium increases up
to ca. 50 mol% DMSO and then decreases on further addi-
tion of DMSO, resulting in a bell-shaped α-effect profile
(7a). Such a bell-shaped α-effect profile cannot be accounted
for in terms of basicity changes with solvent variation and
was also found for the corresponding reactions of substrates
However, a contrasting result was reported by Moss et al.
(11) for the reactions of PNPA with o-iodosylbenzoate as the
α-effect nucleophile and p-ClPhO– as reference nucleophile,
i.e., the α-effect decreased steadily as the mol% DMSO was
increased. Since the basicity of o-iodosylbenzoate was not
determined in the DMSO–H2O mixtures, one cannot exclude
the possibility that the decreasing α-effect trend could be
due to variation in pKa for the conjugate acid of o-iodosyl-
benzoate with mol% DMSO. In fact, we have recently
shown that variation of the basicity of the α-nucleophile is
an important factor in determining the magnitude of the α-
effect in the reactions of PNPA with Ox– and p-ClPhO– in
MeCN–H2O mixtures (8). While the α-effect increases
continuously as the mol% MeCN in the medium increases,
Ox– becomes more basic than p-ClPhO– with increasing
mol% MeCN in the medium. Accordingly, the increasing ba-
sicity difference between Ox– and p-ClPhO– was held re-
sponsible for the increasing α-effect in MeCN–H2O mixtures
(8).
There has been an upsurgence of interest in recent years
in studies of solvent effects on reaction kinetics, equilibria,
and chemistry more generally (12). For example, renewed
interest has been engendered by studies into environmentally
benign or “green” solvents including ionic solvents and
supercritical water (15). Any practical use of such new
media will require an in-depth examination of the physical
organic chemistry of these systems. DMSO has emerged as
the prototypical aprotic solvent of choice for a wide range of
reactions (12, 13). One may cite a few landmark studies:
those of Cram in the area of stereocontrol in isotopic H ex-
change and carbanion chemistry more generally (16), Cox
and Stewart on the H– basicity scale (17), and Parker (13) on
nucleophilic reactivity, as well as the extensive investiga-
tions of Bordwell (18) into acidities in DMSO. Studies of
mixed solvent systems have yielded a wealth of information
on structure–reactivity relationships (19). In this context, we
have focused on DMSO–H2O mixed media and more re-
cently on MeCN–H2O media (7–9).
As mentioned above, one key difference between H2O and
DMSO is the enhanced polarizability of the latter solvent,
which may be expected to extend to DMSO-rich media as
well. To test the significance of this factor we have extended
our study to p-nitrophenyl benzoate (PNPB) as the substrate.
Here, a change of a methyl in PNPA for a phenyl group in
PNPB provides a test compound that should exhibit greater
polarizability interactions with the DMSO solvent compo-
nent. The reaction studied is that of PNPB with Ox– and p-
ClPhO– anions (Scheme 1) as part of the α-effect phenome-
non, as modulated by systematic change of mol% DMSO in
DMSO–H2O mixtures.
© 2006 NRC Canada

1552
Can. J. Chem. Vol. 84, 2006
Table 1. Summary of second-order rate constants for reactions of PNPB with Ox– and p-ClPhO– in
various DMSO–H2O mixtures at 25.0 0.1 °C.
DMSO
(mol%)
pKa
(OxH)
kOx–
((mol/L)–1s–1)
pKa
(p-ClPhOH)
kp-ClPhO–
((mol/L)–1s–1)
α-effect
kOx– /kp-ClPhO-
9.44
10.04
10.68
11.33
12.06
12.86
13.69
14.51
15.32
16.14
22.5
20
34.2
75.7
186
9.38
9.94
0.255
0.144
0.185
0.347
0.814
2.21
5.73
15.5
44.8
162
88
139
185
218
229
206
187
152
120
72
0
10
20
30
40
50
60
70
80
90
10.58
11.21
11.93
12.73
13.54
14.34
15.14
15.95
455
1070
2360
5360
11700
Note: The pKa data were taken from ref. 7b.
Results
Fig. 1. Logarithmic plots of relative rate constants,
log k(DMSO−H O) / k(H O), vs. mol% DMSO for reactions of PNPB
(and PNPA in inset) with Ox– (᭹) and p-ClPhO– (᭺) at 25.0
0.1 °C. The data for reactions of PNPA were taken from ref. 7a.
2
2
The kinetic study was performed spectrophotometrically
under pseudo-first-order conditions with the nucleophile in
excess. All the reactions in this study obeyed pseudo-first-
order kinetics and pseudo-first-order rate constants (kobsd
)
were obtained from plots of ln (A∞–At) vs. t, which were lin-
ear over 90% of the total reaction. Second-order rate con-
stants (kNu) were determined from the slopes of the linear
plots of kobsd vs. the nucleophile concentration. These plots
had only small intercept values, indicating that the contribu-
tion of hydroxide and (or) water to kobsd is negligible (see
Supplementary data for detailed kinetic data).3 It is esti-
mated from replicate runs that the uncertainty in the rate
constants is less than 3%. The kNu values determined are
summarized in Table 1 for the reactions of PNPB with Ox–
and p-ClPhO– in DMSO–H2O mixtures of varying composi-
tions.
Discussion
Effect of medium on reactivity
The rate data presented in Table 1 and exhibited in Fig. 1
show a nonuniform behaviour as the DMSO content of the
medium is varied. Now, it is well-known that the properties
of DMSO–H2O mixtures exhibit anomalous behavior up to
33 mol% DMSO (7, 12, 20). This has been interpreted as
resulting from rigidification of water–water H bonding in-
duced by the addition of DMSO or the strong tendency of
DMSO to form complexes with two water molecules (7, 12,
20). In the present system we have observed that the reactiv-
ity of p-ClPhO– and Ox– decreases modestly in the low
DMSO region (<20 mol% DMSO) but increases signifi-
cantly in the high DMSO region. This initial decline in reac-
tivity is more significant for p-ClPhO– than for Ox–.
Focusing on the high DMSO region, it is generally ac-
cepted that GS destabilization of anionic nucleophiles is re-
sponsible for the rate enhancement in this region relative to
pure water (12, 13). Loss of H bonding in going to DMSO-
rich media will effectively destabilize the anionic nucleo-
phile (see Introduction). This desolvation of the anion
enhances reactivity. For p-ClPhO– and Ox–, in fact, we have
recently found through calorimetric measurements that these
anions become desolvated to the extent of 10.2 and
13.2 kcal/mol (1 cal = 4.184 J), respectively, as the medium
is changed from pure water to 90 mol% DMSO (7b).
The effect of medium change on reactivity can be ex-
pressed as the ratio of the second-order rate constant in
DMSO–H2O mixtures over the corresponding rate constant
in pure H2O, i.e., k(DMSO−H O) /k(H O). As shown in Fig. 1,
this rate constant ratio decreases as the medium changes
from H2O to 10 mol% DMSO with both Ox– and p-ClPhO–.
Beyond 10 mol% DMSO the relative rate for Ox– increases
linearly as the mol% DMSO increases, while p-ClPhO–
exhibits slightly upward curvature resulting in a crossover.
2
2
3 Supplementary data for this article are available on the journal Web site (http://canjchem.nrc.ca) or may be purchased from the Depository
of Unpublished Data, Document Delivery, CISTI, National Research Council Canada, Ottawa, ON K1A 0R6, Canada. DUD 5097. For more
information on obtaining material refer to http://cisti-icist.nrc-cnrc.gc.ca/irm/unpub_e.shtml.
© 2006 NRC Canada

Um et al.
1553
Fig. 2. Plots of the α-effect (kOx-/kp-ClPhO–) vs. mol% DMSO for
reactions of PNPA with Ox– and p-ClPhO– (᭹) and PNPB with
Ox– and p-ClPhO– (᭺) at 25.0 0.1 °C. The data for reactions
of PNPA were taken from ref. 7a.
Dissection of medium effect into GS and TS
contributions
Studies of the relationship between the magnitude of the
α-effect, Brønsted basicity, and medium effects have re-
vealed a remarkable behaviour of oximate reactivity that is,
however, still not fully understood (2, 21). Terrier et al. (2a)
studied the reaction of PNPA with a series of pyridinium
carbaldoximates in H2O and found that the Brønsted-type
plot is linear for reactions of low basic oximates (pKa < ~8),
but levels off for more basic oximates (pKa ≥ 8). In a study
of reactions of PNPB with a series of acetophenone
oximates in 20 and 90 mol% DMSO, we observed that in 20
mol% DMSO the Hammett plot is linear with ρ = +0.20, but
in 90 mol% DMSO ρ = –0.15 (21). The positive ρ value ob-
tained for the reactions in 20 mol% DMSO is striking since
it corresponds to a decrease in reactivity of the oximate with
a stronger base strengthening substituent. A similar result
has recently been found by Terrier and coworkers (2b) for
reactions of bis(p-nitrophenyl)phenylphosphonate with a se-
ries of oximates in H2O. The Brønsted-type plot exhibited a
negative βnuc value in the region of pKa > ~9, indicating that
more basic oximates become less reactive.
We have recently reported (7b) from a calorimetric study
that both Ox– and p-ClPhO– become desolvated on addition
of DMSO to water and the former experiences higher
desolvation than the latter. The difference in desolvation en-
ergy between Ox– and p-ClPhO– (∆∆Hsol) became large as
the DMSO content in the medium increased up to 40 mol%
DMSO and then remained nearly constant beyond that point.
Thus, ∆∆Hsol increased from 0 to 0.6, 1.8, and 3.2 kcal/mol
as the medium changes from pure water to 10, 20, and 40
mol% DMSO, in turn, but remained nearly constant on fur-
ther addition of DMSO (7b). The increasing trend in ∆∆Hsol
up to 40 mol% DMSO was found to parallel the increasing
α-effect trend observed over that medium range, indicating
that the difference in GS desolvation between Ox– and p-
ClPhO– may be responsible for the increasing α-effect trend
for the reactions of PNPA in this solvent region. However,
since ∆∆Hsol remains constant beyond 40 mol% DMSO the
GS effect cannot account for the decreasing α-effect trend in
that medium range.
Recalling that our calorimetric study has shown that Ox– is
more destabilized than p-ClPhO– throughout the range
of DMSO–H2O mixtures studied, we conclude that
destabilization of the anionic nucleophile GS cannot be
solely responsible for the rate enhancement in the high
DMSO region.
The bell-shaped ␣-effect
As shown in Table 1, Ox– exhibits much larger kN values
than p-ClPhO– for the reaction of PNPB in all the medium
compositions investigated (i.e., the α-effect). Interestingly, as
illustrated in Fig. 2 up to 40 mol% DMSO the magnitude of
the α-effect (kOx– /kp-ClPhO–) increases as the DMSO content
in the medium increases. Beyond that point there is a de-
crease in the α-effect, resulting in a bell-shaped α-effect pro-
file. The bell-shaped α-effect profile found for PNPB is
similar to that found previously for the comparable reactions
of PNPA, differing notably however in the magnitude of the
α-effect beyond 40 mol% DMSO; the PNPB system exhibits
a much smaller α-effect than the PNPA system in this
DMSO-rich region.
Previously, we introduced a methodology for the dissec-
tion of medium effects into GS and TS contributions (see
also refs. 12, 13, 22, 23). Figure 3 shows a qualitative two-
dimensional energy profile for a reaction carried out in two
T
different media, H2O and a DMSO–H2O mixture. δGtr can
be evaluated from the measurable transfer free energies of
‡
reactants (δGtrR) and the kinetic activation parameters (δGtr )
as given by eq. [1].
The origin of the bell-shaped ␣-effect
‡
T
R
A further striking aspect of the α-effect plots in Fig. 2 is
that up to 30 mol% DMSO the plots for PNPB and PNPA
are virtually superimposable but diverge thereafter; the PNPB
curve reaches a maximum at 40 mol% DMSO while the
maximum for PNPA is found at 50 mol% DMSO. Also the
α-effect maximum occurs at 230 for PNPB and at 285 for
PNPA. While the advent of the maximum in the bell-shaped
α-effect profile at a lower DMSO content with PNPB, rela-
tive to PNPA, is concordant with the higher polarizability as-
sociated with the change from Me to Ph, the different
response of the two systems to medium change beyond
40 mol% DMSO bears further analysis.
[1]
δ∆Gtr = δGtr – δGtr
This methodology can be applied to enthalpy and entropy
parameters as well. This allows the dissection of the effect
of medium on the α-effect into GS and TS effects through
the combination of the calorimetrically measured enthalpies
of solution (∆Hsol) and the kinetically determined activation
parameters. For the reaction of PNPA with Ox– and p-
ClPhO–, we have found that in the DMSO-rich region the TS
becomes more stabilized for p-ClPhO– than for Ox– resulting
in a smaller α-effect (7b). Accordingly, differential solvation
of the two TSs was proposed to be responsible for the de-
© 2006 NRC Canada

1554
Can. J. Chem. Vol. 84, 2006
Fig. 3. Illustration of the relationship between the transfer free
energies of reactants (δGtrR) and the transition state (δGtrT) and
the free energies of activation for a reaction occurring in the
two-solvent systems.
Fig. 4. Plots of log k(DMSO–H2O)/k(H2O) vs. transfer enthalpies
(∆∆Htr) for reactions of PNPA (᭺) and PNPB (᭹) with Ox– and
p-ClPhO– at 25.0 0.1 °C. The data for reaction of PNPA were
taken from ref. 7b.
creasing α-effect trend for the reactions of PNPA beyond the
break point of 40–50 mol% DMSO (7b). For the current
PNPB system, one can also conclude that the origin of the
increasing and decreasing α-effect trend found with medium
change can be attributed to the same factors as for the PNPA
system, i.e., dominant GS effect in the H2O-rich region and
TS effect in the DMSO-rich region, which demonstrates the
generality of this methodology.
Table 2. Transfer enthalpies (∆∆Htr, kcal/mol)
from 0 to 90 mol% DMSO for single ions of
p-ClPhO– and Ox– at 25.0 °C.
∆∆Htr (kcal/mol)
p-ClPhO–
The effect of medium change on reactivity can be illus-
trated in a different way via Fig. 4, showing a plot of the
logarithmic relative rate constants for the reactions of PNPA
and PNPB with Ox– and p-ClPhO– vs. the transfer enthalpies
from H2O to DMSO–H2O mixtures (∆∆Htr) for the two
nucleophiles (Table 2). ∆∆Htr represents the extent of GS
desolvation for Ox– and p-ClPhO– ions as the medium
changes from H2O to DMSO–H2O mixtures (7b). Accord-
ingly, if the GS effect were solely responsible for the relative
rate constants one should have observed a linear correlation
DMSO (mol%)
Ox–
0
10
20
30
40
50
60
70
80
90
0
0
1.4
5.1
8.3
0.8
3.3
5.4
6.7
8.0
8.6
9.0
9.5
10.2
9.9
11.4
11.9
12.4
12.7
13.2
between ∆∆Htr and log k(DMSO−H O) /k(H O). Contrariwise,
Fig. 4 exhibits nonlinear correlations, i.e., the increase in the
relative rate constant is small on changing ∆∆Htr from 0 to
8 kcal/mol for p-ClPhO– and from 0 to 11 kcal/mol for Ox–.
However, for p-ClPhO– the relative rate constant increases
significantly as ∆∆Htr changes from 8 to 10 kcal/mol while
for Ox– the change is from 11 to 13 kcal/mol. These results
further emphasize that the GS effect is not solely responsible
for the medium effect on reactivity but that a TS effect also
contributes to the rate enhancement in the DMSO-rich re-
gion.
2
2
Note: Data were taken from ref. 7b.
those for the reactions of PNPB with Ox– throughout the
whole ∆∆Htr range. However, a contrasting result is shown
for the reactions with p-ClPhO–, i.e., the points for the reac-
tions of PNPA lie above those for the reactions of PNPB up
to ∆∆Htr = ~7 kcal/mol, but are situated below beyond that
point. This result indicates that the reactions of PNPB with
p-ClPhO– gain greater rate enhancement than the corre-
sponding reactions of PNPA with the same ∆∆Htr value in
the DMSO-rich medium. The contrasting α-effect behaviour
for the PNPB and PNPA systems, as exhibited in Fig. 2 for
the DMSO-rich region, is therefore accounted for.
Notably in Fig. 4, the curved lines for the reactions of
PNPA and PNPB with p-ClPhO– cross over those for the
corresponding reactions for Ox– at ∆∆Htr = 6–7 kcal/mol.
The points for the reactions of p-ClPhO– lie below those for
the reactions with Ox– up to ∆∆Htr = ~6 kcal/mol but exceed
them beyond that point. Such a crossover indicates that in
the DMSO-rich region the reactions with p-ClPhO– attain al-
most the same rate enhancements as those with Ox– but with
smaller ∆∆Htr values.
Conclusions
Through the combination of kinetic data with calorimetri-
cally determined GS solvation of Ox– and p-ClPhO–, which
allowed dissection of the medium effect on TS and GS con-
Interestingly, further scrutiny of Fig. 4 reveals that
the points for the reactions of PNPA with Ox– fall above
© 2006 NRC Canada

Um et al.
1555
tributions, the present study leads to the following conclu-
sions. (i) The bell-shaped α-effect profile obtained for the
reaction of PNPB with Ox– and p-ClPhO– is similar to that
previously found for the corresponding reaction with PNPA,
differing notably however, in the magnitude of the α-effect
beyond 40 mol% DMSO; the PNPB system exhibits a much
smaller α-effect than the PNPA system in this DMSO-rich
region. (ii) The dominant GS effect in the H2O-rich region
and TS effect in the DMSO-rich region are proposed to be
responsible for the origin of the increasing and decreasing α-
effect trends, respectively. (iii) The effect of medium change
on reactivity is more significant for the reaction with p-
ClPhO– than for that with Ox– in DMSO-rich region.
(iv) The reaction of PNPB with p-ClPhO– gains greater rate
enhancements than the corresponding reaction of PNPA in
DMSO-rich region, which is responsible for the smaller α-
effect found for the reaction of PNPB beyond 40 mol%
DMSO. (v) Concordant with the increased polarizability ef-
fected on going from PNPA to PNPB with the change Me →
Ph, is the advent of the maximum in the bell-shaped α-effect
profile (Fig. 2) at a lower DMSO content with PNPB than
with PNPA (40 vs. 50 mol% DMSO) and similarly the
smaller magnitude of the α-effect (230 vs. 285).
tion of the reactions with those of the authentic samples
under the same reaction conditions.
Acknowledgement
The authors are grateful for the financial support from Ko-
rea Science and Engineering Foundation (KOSEF-F01–
2005–000–10033–0) and Natural Sciences and Engineering
Research Council of Canada (NSERC) (EB). Y.H. Kim is
also grateful for the BK 21 Fellowship.
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Experimental section
Materials
PNPB was readily prepared from the reaction of benzoyl
chloride with p-nitrophenol in the presence of triethyl amine
in anhydrous ether. Butan-2,3-dione monoxime and phenols
used are of the highest quality available and were
recrystallized before use. DMSO was refluxed over calcium
hydride, distilled, collecting the fraction of bp 64–66 °C (6–
7 mm Hg, 1 mm Hg = 133.322 4 Pa) and stored under nitro-
gen. Doubly glass distilled water was further boiled and
cooled under nitrogen just before use.
Kinetics
Kinetic studies were performed with
a
UV–vis
spectrophotometer for slow reactions (t1/2 ≥ 10 s) and a
stopped-flow spectrophotometer for fast reactions (t1/2
<
10 s) with a constant temperature circulating bath at 25.0
0.1 °C. Typically, the reaction was initiated by adding 5 µL
of ca. 0.02 mol/L of substrate solution in MeCN by 10 µL
gastight syringe to a 10 mm quartz UV cell containing
2.50 mL of the thermostated reaction mixture made up of re-
action medium and an aliquot of the nucleophile stock solu-
tion. The nucleophile stock solution of ca. 0.2 mol/L was
prepared by dissolving 2 equiv. of oxime (or phenol) and 1
equiv. of standardized NaOH solution to make a self buf-
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varied over the range, 1–100 × 10–3 mol/L, while the sub-
strate concentration was 4 × 10–5 mol/L. All the solutions
were transferred by gastight syringes under nitrogen. The re-
actions were followed by monitoring the appearance of p-
nitrophenoxide ions at 410 nm.
Product analysis
p-Nitrophenoxide ion was liberated quantitatively and
identified as one of the reaction products in the reactions of
PNPB by comparison of the UV–vis spectra after comple-
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