Solvent effect on the α-effect: Ground-state versus transition-state effects; a combined calorimetric and kinetic investigation

Article abstract of DOI:10.1021/jo051823f

In a study of the solvent effect on the α-effect, second-order rate constants (k_Nu-) have been determined spectrophotometrically for reactions of a series of substituted phenyl acetates with butan-2,3-dione monoximate (Ox^-, α-nucleop

Full text of DOI:10.1021/jo051823f

Solvent Effect on the r-Effect: Ground-State versus
Transition-State Effects; a Combined Calorimetric and Kinetic
Investigation
Ik-Hwan Um,*,† So-Jeong Hwang,† and Erwin Buncel*,‡
Department of Chemistry, Ewha Womans UniVersity, Seoul 120-750, Korea, and
Department of Chemistry, Queen’s UniVersity, Kingston, Ontario K7L 3N6, Canada
ihum@mm.ewha.ac.kr; buncele@chem.queensu.ca
ReceiVed August 30, 2005
-
In a study of the solvent effect on the R-effect, second-order rate constants (kNu ) have been determined
spectrophotometrically for reactions of a series of substituted phenyl acetates with butan-2,3-dione
monoximate (Ox-, R-nucleophile) and p-chlorophenoxide (p-ClPhO-, reference nucleophile) in DMSO-
H2O (DMSO ) dimethyl sulfoxide) mixtures of varying compositions at 25.0 ( 0.1 °C. The magnitude
-
-
of the R-effect, kOx /kp-ClPhO , increases as the DMSO content in the medium increases up to 40-50 mol
%, reaching 500, one of the largest R-effect values, and then decreases on further addition of DMSO,
resulting in a bell-shaped R-effect profile regardless of the nature of the substrates. The magnitude of the
R-effect is found to be significantly dependent on the substrates (or, more quantitatively, on ânuc). Thus,
â
nuc is an important predictor of the magnitude of the R-effect. The bell-shaped R-effect profile found in
the present system is attributed to the differential change in the sensitivity of the medium effect on the
Ox- and p-ClPhO- systems but not due to a change in the reaction mechanism or to a drastic change in
the basicity of the two nucleophiles on addition of DMSO to the medium. Through application of
calorimetric measurements of ground-state solvation combined with the diagnostic ânuc values, it is shown
that the transition-state effect is more dominant than the ground-state effect as the origin of the R-effect
in the present system.
Introduction
in the development of protocols for environmental decontamina-
tion of sites polluted with organophosphorus insecticides,
R-nucleophiles such as oximates have been demonstrated to be
highly effective.4 The needs to develop efficient means to
destroy stockpiles of organophophorus nerve agents have led a
number of groups to investigate different approaches toward
enhancing decomposition of these agents; R-nucleophiles can
Nucleophiles which bear one or more nonbonding electron
pairs at the position R to the nucleophilic center have been
termed R-nucleophiles and exhibit enhanced reactivity compared
with normal nucleophiles of similar basicity (the R-effect).1,2
Current interest in studying the reaction of R-nucleophiles has
received major new impetus from the importance of the many
applications of these highly reactive species.3-7 For example,
(3) (a) Balakrishnan, V. K.; Han, X.; VanLoon, G. W.; Dust, J. M.;
Toullec, J.; Buncel, E. Langmuir 2004, 20, 6586-6593. (b) Couderc, S.;
Toullec, J. Langmuir 2001, 17, 3819-3828. (c) Toullec, J.; Moukawin, M.
Chem. Commun. 1996, 221-222.
(4) (a) Terrier, F.; Degorre, F.; Kiffer, D.; Laloi, M. Bull. Soc. Chim.
Fr. 1988, 31, 415-419. (b) Terrier, F.; Le Gue’vel, E.; Chatrousse, A. P.;
Moutiers, G.; Buncel, E. Chem. Commun. (Cambridge) 2003, 600-601.
(c) Ashani, Y.; Cohen, S. J. Med. Chem. 1971, 14, 621-626.
(5) (a) 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-
7905. (b) Moss, R. A.; Kanamathareddy, S.; Vijayaraghavan, S. Langmuir
2001, 17, 6108-6112.
* To whom correspondence should be addressed. Tel.: 82-2-3277-2349
(I.-H.U.); 1-613-533-2653 (E.B.). Fax: 82-2-3277-2844 (I.-H.U.); 1-613-533-
6669 (E.B.).
† Ewha Womans University.
‡ Queen’s University.
(1) Pure Appl. Chem. 1979, 51, 1731.
(2) Reviews: (a) Buncel, E.; Um, I. H. Tetrahedron 2004, 60, 7801-
7825. (b) Hoz, S.; Buncel, E. Isr. J. Chem. 1985, 26, 313-319. (c) Curci,
R.; Di Furia, F. Int. J. Chem. Kinet. 1975, 7, 341-349. (d) Grekov, A. P.;
Veselov, V. Ya. Russ. Chem. ReV. 1978, 47, 631-648.
10.1021/jo051823f CCC: $33.50 © 2006 American Chemical Society
Published on Web 01/05/2006
J. Org. Chem. 2006, 71, 915-920
915

Um et al.
accelerate these decompositions.5,6 In cases of poisoning by
organophosphorus toxicants, standard medical procedure in-
cludes injection of oximate nucleophiles into the poisoned
person.7 No doubt the high reactivity of R-nucleophiles will
also find uses in synthetic organic chemistry. In this regard,
mildly basic R-nucleophiles could be used in deprotection steps
in synthetic sequences, e.g., deprotection of alcohols by remov-
ing the protecting group.
SCHEME 1
our analysis of ground-state and transition-state contributions
to the R-effect.
Investigations of solvent effects, through enthalpies of solution
and structural modification, have all formed part of an ongoing
program of research into the reactivity of these versatile
R-nucleophiles.8-12 In 1986, we showed that there is a signifi-
cant medium effect on the R-effect for the reactions of
Results
All the reactions in this study obeyed pseudo-first-order
kinetics in the presence of a large excess of nucleophile. Pseudo-
first-order rate constants (kobsd) were obtained from the plots of
ln(A∞ - At) vs t, which were linear over 90% of the reaction.
p-nitrophenyl acetate (1a) with butan-2,3-dione monoximate
(Ox-, pKa
) 9.44 in H2O) as an R-nucleophile and
OxH
p-chlorophenoxide (p-ClPhO-, pKap-ClPhOH ) 9.38 in H2O) as
reference nucleophile in DMSO-H2O (DMSO ) dimethyl
-
Second-order rate constants (kNu ) were determined from the
-
/
sulfoxide) mixtures of varying compositions. The R-effect, kOx
slopes of the linear plots of kobsd vs the nucleophile concentra-
tion. These plots had only small intercept values, indicating that
the contribution of hydroxide and/or water to kobsd was negligible
-
kp-ClPhO , was found to increase with increasing DMSO content
in the medium up to 50 mol % DMSO and then to decrease on
further addition of DMSO, resulting in a bell-shaped R-effect
profile.8 The medium effect on the R-effect has recently been
dissected into ground-state and transition-state effects from
combination of the calorimetrically measured enthalpies of
solution (∆Hs) and the kinetically determined activation pa-
rameters (∆Gq, ∆Hq, and ∆Sq).9 The effect of medium on the
R-effect has also been studied by changing the medium from
DMSO-H2O to MeCN-H2O mixtures,10 the electrophilic
center from CdO (1a) to PdO (2) and SO2 (3),11 and the leaving
group from p-nitrophenoxide in 1a to p-nitrothiophenoxide.12
In all cases, the effect of medium on the R-effect has been found
to be significant.
-
(see Supporting Information). The kNu values determined are
summarized in Table 1 and illustrated graphically in Figure 1
for the reactions of 1a-e with Ox- and p-ClPhO- in DMSO-
H2O mixtures of varying compositions.
Discussion
Medium Effect on Rate. In this section, the effect of added
DMSO on the reaction rate will be analyzed in terms of
H-bonding and polarizability interactions. The results given in
Table 1 and illustrated in Figure 1A show clearly a significant
increase in the second-order rate constant for the reaction of
1a-e with Ox- as the DMSO content in the medium increases.
The rate enhancement is more significant in the DMSO-rich
region; the second-order rate constant increases from 65.8 M-1
s-1 to 1680 and 40500 M-1 s-1 as the medium changes from
pure water to 50 and 90 mol % DMSO, respectively for the
reaction of 1a with Ox-. The least reactive substrate (1e)
exhibits a small rate decrease as the medium changes from pure
water to 10 mol % DMSO.
An initial decrease in rate upon addition of DMSO has also
been observed for the corresponding reactions with p-ClPhO-,
as shown in Table 1 and Figure 1B. This decrease in rate
constants persists into higher DMSO contents for the less
reactive substrates. For example, the second-order rate constant
for the reaction of 1a with p-ClPhO- decreases from 0.685 M-1
s-1 in H2O to 0.653 M-1 s-1 in 10 mol % DMSO, and the rate
constants above 20 mol % DMSO exceed the value in H2O.
On the other hand, the second-order rate constant for the least
reactive 1e decreases from 0.091 M-1 s-1 in H2O to 0.038 M-1
s-1 in 20 mol % DMSO, and the rate constant in 50 mol %
DMSO (0.085 M-1 s-1) is still smaller than that in H2O.
Significant rate enhancements have often been observed for
reactions with anionic nucleophiles on addition of DMSO to
the reaction medium since anionic nucleophiles become des-
olvated in the aprotic solvent.13 In fact, we have recently
reported that p-ClPhO- and Ox- become desolvated to the
extent of 10.2 and 13.2 kcal/mol as the medium changes from
pure water to 90 mol % DMSO.9 The decrease in the rate
In the present study we have extended our investigation to
the nucleophilic substitution reactions of 1b-e with Ox- and
p-ClPhO- in DMSO-H2O mixtures of varying compositions
(Scheme 1). Our systematic investigation provides important
clues rationalizing the bell-shaped R-effect profile and of the
factors determining the magnitude of the R-effect and supports
(6) (a) Um, I. H.; Jeon, S. E.; Baek, M. H.; Park, H. R. Chem. Commun.
(Cambridge) 2003, 3016-3017. (b) Nagelkerke, R.; Thatcher, G. R. J.;
Buncel, E. Org. Biomol. Chem. 2003, 1, 163-167. (c) Buncel, E.;
Nagelkerke, R.; Thatcher, G. R. J. Can. J. Chem. 2003, 81, 53-63. (d)
Tsang, J. S. W.; Neverov, A. A.; Brown, R. S. J. Am. Chem. Soc. 2003,
125, 1559-1566.
(7) Wilson, I. B.; Ginsburg, S. Arch. Biochem. Biophys. 1995, 54, 569.
(8) Buncel, E.; Um, I. H. J. Chem. Soc., Chem. Commun. 1986, 595.
(9) Um, I. H.; Buncel, E. J. Org. Chem. 2000, 65, 577-582.
(10) (a) Um, I. H.; Park, Y. M.; Buncel, E. Chem. Commun. (Cambridge)
2000, 19, 1917-1918. (b) Um, I. H.; Lee, E. J.; Buncel, E. J. Org. Chem.
2001, 66, 4859-4864.
(11) Um, I. H.; Hong, J. Y.; Buncel, E. Chem. Commun. (Cambridge)
2001, 27-28.
(12) Um, I. H.; Buncel, E. J. Am. Chem. Soc. 2001, 123, 11111-11112.
(13) (a) Parker, A. J. Chem. ReV. 1969, 69, 1-32. (b) Buncel, E.; Wilson,
H. AdV. Phys. Org. Chem. 1977, 14, 133-202. (c) Buncel, E.; Wilson, H.
Acc. Chem. Res. 1979, 12, 42-48.
916 J. Org. Chem., Vol. 71, No. 3, 2006

SolVent Effect on the R-Effect
-
TABLE 1. Summary of the Second-Order Rate Constants (kNu ) for the Reaction of 1a-e with Ox (and p-ClPhO- in Parentheses) in
-
Various DMSO-H2O Mixtures at 25.0 °C
-/(M-1 s-1)
kNu
mol % DMSO
1aa
1b
1c
1d
1e
0
10
20
40
50
70
90
65.8 (0.685)b
77.8 (0.653)
131 (0.76)
41.5 (0.320)
47.3 (0.230)
72.0 (0.241)
275 (0.562)
499 (1.09)
31.6 (0.302)
34.2 (0.224)
56.9 (0.232)
208 (0.465)
399 (0.922)
1530 (4.72)
5920 (36.4)
21.7 (0.171)
23.6 (0.127)
29.6 (0.117)
89.0 (0.191)
160 (0.353)
541 (1.47)
15.4 (0.0910)
13.9 (0.0500)
14.0 (0.0380)
26.2 (0.0520)
37.5 (0.0850)
104 (0.312)
746 (2.80)
1680 (5.90)
8200 (34.7)
40500 (335)
1920 (4.88)
6460 (38.8)
1620 (10.3)
330 (1.97)
a Data for the reactions of 1a taken from ref 8. b The data in the parentheses are the second-order rate constants for the corresponding reactions with
p-ClPhO-. Data taken from ref 22.
FIGURE 1. Plots of the logarithmic second-order rate constants vs mole percent DMSO for the reactions of 1a-e with Ox- (A) and p-ClPhO-
(B) at 25.0 ( 0.1 °C.
-
-
constant in the water-rich region found in the present system is
hence unexpected.
in Figure 2, the R-effect (kOx /kp-ClPhO ) increases as the solvent
is changed up to ca. 40-50 mol % DMSO, in which the
maximum R-effect is observed, and then it decreases upon
further additions of DMSO, resulting in a bell-shaped R-effect
profile. It is noted that the magnitude of the R-effect in pure
water is similar to that in pure DMSO in all cases. Thus, if the
reaction were performed solely in the two pure solvents, one
would not have found the medium-dependent R-effect profile.
Clearly, the present result shows that the effect of medium on
the R-effect is significant and supports the argument that a two-
point analysis of the R-effect could be misleading.14
Various changes are attendant upon addition of anionic solutes
to a bulk solvent, whether pure water or DMSO-H2O mix-
tures.9,13 H-bonding is an important interaction between solvent
molecules and anionic solutes in the H2O-rich region. Thus,
addition of DMSO to the reaction medium would destabilize
anionic solutes (both anionic nucleophiles and anionic transition
states) due to decreased H-bonding interaction. The fact that
Ox- exhibits decreased reactivity toward the least reactive 1e
in 10 mol % DMSO suggests that the transition state becomes
more desolvated than the ground state. On the contrary, in the
DMSO-rich region, free H2O molecules for H-bonding become
limited;9,13 accordingly, H-bonding is diminished in importance.
Instead, polarizability interaction becomes dominant in the
DMSO-rich region.9,13 Since DMSO is highly polarizable, it
can stabilize a polarizable transition state through the polariz-
ability interaction. This argument is consistent with the large
rate enhancement observed in the DMSO-rich region. It follows
from the evidence presented here that decreased H-bonding and
enhanced polarizability interactions are responsible for the initial
rate retardation in the H2O-rich region and the major rate
enhancement in the DMSO-rich region, respectively.
It is shown in Figure 2 that the reactions of 1a-e and 2 with
Ox- and p-ClPhO- exhibit a maximum R-effect at 40 or 50
mol % DMSO in all cases. However, the magnitude of the
R-effect is dependent on the substrate; in the phenyl acetate
series the maximum R-effect found at 40 mol % DMSO is ca.
500 for the reaction of 1e, but only ca. 40 for the diphenylphos-
phinate 2, i.e., over 1 order of magnitude smaller.
Many factors have been suggested to influence the magnitude
of the R-effect: the basicity of R-nucleophiles, the type of
hybridization of the electrophilic centers, and the magnitude of
â
nuc, among them.4,15-19 Aubort and Hudson have reported that
highly basic R-nucleophiles (e.g., acetone oximate anion) do
(14) Hoz, S.; Buncel, E. Tetrahedron Lett. 1984, 25, 3411-3414.
J. Org. Chem, Vol. 71, No. 3, 2006 917
Medium Effect on the R-Effect. Factors influencing the
magnitude of the R-effect will be discussed here. As illustrated

Um et al.
TABLE 2. Hammett G Values and Correlation Coefficients (R2)
with Various σ Constants for the Reactions of 1a-e with Ox- in
DMSO-H2O Mixtures at 25.0 °C
F
mol % DMSO
σ
σ°
σ-
0
10
20
40
50
70
90
1.26 (0.909)a
1.43 (0.906)
1.89 (0.876)
2.70 (0.873)
3.03 (0.867)
3.33 (0.846)
3.67 (0.847)
1.26 (0.968)
1.46 (0.964)
1.88 (0.933)
2.68 (0.925)
3.00 (0.918)
3.33 (0.903)
3.77 (0.915)
0.52 (0.763)
0.62 (0.782)
0.87 (0.822)
1.28 (0.842)
1.48 (0.859)
1.72 (0.887)
2.19 (0.912)
a The data in the parentheses are correlation coefficients in the plot log
k vs σ (σ° or σ-).
magnitude of the ânuc values and the magnitude of the R-effect
can be also found in the present system. As shown in Figure 2,
the magnitude of the R-effect is very small for the reaction of
2, while that for 1b-e is much larger. Now, the ânuc value of
0.90 ( 0.03 is close to unity; hence, the R-effect of ca. 500
found for 1e represents the maximum R-effect found so far for
the reaction of an sp2 carbon. It follows from the evidence
presented here that ânuc is an important predictor to determine
the magnitude of the R-effect.
Origin of Bell-Shaped R-Effect. Possible causes for the bell-
shaped R-effect profile will be examined in this section. One
possibility is that a change in the reaction mechanism on addition
of DMSO to the reaction medium might be responsible for the
bell-shaped R-effect. In fact, change of solvent from water to
an aprotic solvent such as MeCN has often been suggested to
result in a change in the reaction mechanism.21 For example,
Lee et al. have concluded that the change of solvent from water
to MeCN causes a mechanistic change in the aminolysis of aryl
chloroformates and chlorothionoformates, from stepwise to
concerted.21
Hammett correlations have been performed to examine
whether addition of DMSO to the reaction medium causes a
change in the reaction mechanism or not. As shown in Table 2,
σ- constants give the poorest Hammett correlation, while σ°
results in the best correlation for the reactions of 1a-e with
Ox- in all DMSO-H2O mixtures. A similar result is seen in
Table S29 in the Supporting Information for the corresponding
reactions with p-ClPhO-.
If leaving group departure is involved in the rate-determining
step (RDS), whether the reaction proceeds through a stepwise
or concerted mechanism, a partial negative charge would
develop on the oxygen atom of the leaving aryl oxides. Since
negative charge can be delocalized on the substituent in the
leaving group through resonance, one would expect σ- constants
to give the best Hammett correlation. The fact that σ- constants
result in the poorest Hammett correlation suggests that leaving
group departure is not involved in the rate-determining step in
the DMSO-H2O mixtures studied. This argument is consistent
with our previous proposal that the reactions of 1a with
substituted phenoxides in DMSO-H2O mixtures proceed
through a tetrahedral intermediate with its formation as the
RDS.22 Addition of DMSO to the reaction medium does not
FIGURE 2. Plots showing solvent effect on the R-effect for the
reactions of 1a-e and 2 with Ox- and p-ClPhO- in DMSO-H2O
mixtures of varying compositions at 25.0 °C.
not exhibit the R-effect in the reaction with 1a.15 A similar result
has recently been reported for the reaction of 1a with a series
of substituted oximate anions.4,16 Terrier et al. observed that
the Brønsted-type plot is linear for low basic oximates (pKa <
8) but levels off for the more basic oximates (pKa g 8).4,16 The
hybridization type of the electrophilic center was proposed to
be an important factor in determining the magnitude of the
R-effect, based on the observation of a large rate constant ratio
17
(kHOO /kHO ). For example, Wiberg reported that HOO- is
22 000 to 66 000 times more reactive than HO- toward the sp-
hybridized carbon of benzonitriles in 50% aqueous acetone.17a
-
-
However, we have recently found an R-effect (kNH NH /kglycylg
-
2
2
lycine) of only 7-10 with ânuc ) 0.32 for the reactions at the
sp-hybridized carbon atom of 3-butyn-2-one with primary
amines including hydrazine and methoxylamine. This result
suggests that the R-effect is not necessarily large for the reactions
at an sp-hybridized carbon when ânuc is small,18 indicating that
the magnitude of ânuc is a more important predictor of the
magnitude of the R-effect. This is consistent with the finding
by Bruice and Dixon that the magnitude of the R-effect increases
with increasing ânuc value for the reactions of 17 substrates with
hydrazine as R-nucleophile and glycylglycine or glycinamide
as the corresponding reference nucleophile.19
While the reactions of 2 with aryloxides proceed with ânuc
) 0.21,11 much larger ânuc values have been reported for the
reactions of the aryl acetates with aryloxides, being 0.78 for 1a
and 0.90 ( 0.03 for 1b-e.20 The correlation between the
(15) (a) Aubort, J. D.; Hudson, R. F. J. Chem. Soc. D 1970, 938-939.
(b) Aubort, J. D.; Hudson, R. F. J. Chem. Soc. D 1970, 1378-1379.
(16) (a) Buncel, E.; Cannes, C.; Chatrousse, A. P.; Terrier, F. J. Am.
Chem. Soc. 2002, 124, 8766-8767. (b) Moutiers, G.; Le Guevel, E.; Cannes,
C.; Terrier, F.; Buncel, E. Eur. J. Org. Chem. 2001, 17, 3279-3284.
(17) (a) Wiberg, K. B. J. Am. Chem. Soc. 1955, 77, 2519-2522. (b)
Mclssac, J. E., Jr.; Subbaraman, J.; Mulhausen, H. A.; Behrman, E. J. J.
Org. Chem. 1972, 37, 1037-1041.
(18) Um, I. H.; Lee, J. S.; Yuk, S. M. J. Org. Chem. 1998, 63, 9152-
9153.
(19) Dixon, J. E.; Bruice, T. C. J. Am. Chem. Soc. 1971, 93, 6592-
6597.
(20) Kwon, D. S.; Lee, G. J.; Um, I. H. Bull. Korean Chem. Soc. 1990,
11, 262-264.
(21) Oh, H. K.; Ha, J. S.; Sung, D. D.; Lee, I. J. Org. Chem. 2004, 69,
8219-8223.
(22) Buncel, E.; Um, I. H.; Hoz, S. J. Am. Chem. Soc. 1989, 111, 971-
975.
918 J. Org. Chem., Vol. 71, No. 3, 2006

SolVent Effect on the R-Effect
nonperfect syncronization in the transition state (PNS).23,24 In
contrast, the lack of such curvature for the current system
suggests that no such imbalance exists here, indicating that the
origin of the R-effect is likely to be different for the reactions
of 1a-e and 2. Interestingly, a common feature exhibited in
the novel Brønsted-type plots is that Ox- shows higher
sensitivity of the medium effect than p-ClPhO- in the H2O-
rich region, but the reverse is true in the DMSO-rich region
regardless of the nature of substrates. It follows from the
evidence presented here, that the origin of the bell-shaped
R-effect is the differential sensitivity of the medium effect on
the Ox- and p-ClPhO- systems but not a change in reaction
mechanism or a drastic change in the basicity of the two
nucleophiles on addition of DMSO to the medium.
Ground-State vs Transition-State Effect: Evidence from
Enthalpies of Solution. Finally, the effect of medium on the
R-effect will be dissected into ground-state and transition-state
contributions. We have recently shown through measurements
of heats of solution that both Ox- and p-ClPhO- are desolvated
upon addition of DMSO and the former experiences higher
desolvation than the latter.9 The difference in the desolvation
energy between Ox- and p-ClPhO- (∆∆Hs) has been found to
increase up to ca. 40 mol % DMSO but to remain nearly
constant beyond that point. Thus, ∆∆Hs increases 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 remains
nearly constant upon further addition of DMSO.9
If the ground-state energy difference between Ox- and
p-ClPhO- (e.g., ∆∆Hs) were responsible for the R-effect, then
the magnitude of the R-effect should have remained constant
at the maximum beyond 40 mol % DMSO. The fact that the
R-effect decreases in the DMSO-rich region suggests that the
ground-state effect cannot be responsible for the R-effect in this
region. In our previous report for the reactions of 1a with Ox-
and p-ClPhO-, we have shown through a kinetic study and
dissection of rate data, that the transition-state for the reaction
with Ox- becomes less solvated than the one for reaction with
p-ClPhO- in the DMSO-rich region, and that the differential
solvation of the two transition-states is responsible for the
decreasing R-effect trend beyond the break point of 40-50 mol
% DMSO.9
The above argument can be further supported from the
substrate dependent R-effect shown in Figure 2. Since Ox- and
p-ClPhO- were employed as the common nucleophiles for all
the reactions of 1a-e and 2, the ground-state effect will be
constant for the nucleophiles. Besides, the ground-state effect
for the substrates is plausibly expected to be similar. Therefore,
one would expect similar magnitudes of the R-effect if the
ground-state effect governs the R-effect in these systems. Thus,
the fact that the R-effect is significantly dependent on the
substrates (or, more quantitatively, on the ânuc value), clearly
leads to the conclusion that the transition-state effect is more
important than the ground-state effect for the R-effect in the
present system.
FIGURE 3. Novel Brønsted-type plots for the reactions of 1a-e and
2 (inset) with Ox- and p-ClPhO- in DMSO-H2O mixtures of varying
compositions at 25 ( 0.1 °C.
cause a mechanism change since the novel Brønsted-type plot,
in which the pKa change of phenols is brought about by changes
in the reaction medium, is linear over the whole range of
DMSO-H2O composition.22 Accordingly, the evidence tends
to rule out the bell-shaped R-effect profile being due to a change
in reaction mechanism.
One might further suggest that a drastic change in pKa of the
conjugate acid of Ox- and p-ClPhO- is responsible for the bell-
shaped R-effect, since nucleophilicity is strongly influenced by
the basicity of nucleophiles. In fact, we have recently reported
that the R-effect for the reactions of aryl acetates (including 1a
and 1d) with Ox- and p-ClPhO- in MeCN-H2O mixtures
increases as the MeCN content in the medium increases.10 The
pKa values of the conjugate acids of Ox- and p-ClPhO- have
been found to increase as the MeCN content in the medium
increases. However, Ox- has been shown to be more basic than
p-ClPhO- in media of higher MeCN content and the increasing
pKa difference between the conjugate acid of Ox- and p-ClPhO-
has been attributed to be responsible for the increasing R-effect
profile in this case.10 In contrast, the pKa’s of the conjugate
acids of Ox- and p-ClPhO- have been found to increase in a
parallel manner upon addition of DMSO.9,23
-
Novel Brønsted-type plots, log kNu vs pKa, where pKa
changes are brought about by change in solvent composition,
have been constructed for the present system. As shown in
Figure 3, the Ox- system exhibits linear correlations beyond
10 mol % DMSO. On the contrary, the p-ClPhO- system
exhibits an initial decrease on addition of DMSO followed by
steep upward curvature. We have recently reported contrasting
novel Brønsted-type plots for the corresponding reactions of
2.23 As shown in the inset of Figure 3, the novel Brønsted-type
plot for the reaction with Ox- exhibits downward curvature
while that for the reaction with p-ClPhO- gives rise to a linear
plot. This downward curvature was taken to be indicative of
The magnitude of the ânuc value has been understood as a
measure of bond formation between the nucleophile and the
substrate in the transition state of the RDS;22,25 hence the
transition-state structure for the reactions of 1a-e and 2 would
vary according to the different ânuc values. One can expect that
(24) Bernasconi, C. F. AdV. Phys. Org. Chem. 1992, 27, 119-238.
(25) Jencks, W. P. Catalysis in Chemistry and Enzymology; McGraw-
Hill: New York, 1969; pp 107-111.
(23) Tarkka, R. M.; Buncel, E. J. Am. Chem. Soc. 1995, 117, 1503-
1507.
J. Org. Chem, Vol. 71, No. 3, 2006 919

Um et al.
chloride in anhydrous ether in the presence of triethylamine. Their
purity was checked by their melting points and H NMR spectra.
the transition-state stabilizing effect would be more significant
for the reaction system in which the degree of bond formation
between nucleophile and substrate in the transition state is more
advanced and vice versa. Accordingly, it is plausible that the
transition-state stabilizing effect would be larger for the reactions
of 1b-e (ânuc ) 0.90 ( 0.03) compared with the corresponding
reactions of 1a (ânuc ) 0.78) or 2 (ânuc ) 0.21), on the basis of
their ânuc values. This would account for the large R-effect found
for the reactions of 1b-e and the small R-effect observed for
2, consistent with the preceding conclusion that transition-state
effect is more dominant than the ground-state effect as the origin
of the R-effect.
1
Butan-2,3-dione monoxime (OxH) and the 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 mmHg), and stored under nitrogen. 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 g 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 M 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 reaction medium and an aliquot of the nucleophile stock
solution. The nucleophile stock solution of ca. 0.2 M was prepared
by dissolving 2 equiv of OxH and 1 equiv of standardized NaOH
solution to make a self-buffered solution. Generally, the nucleophile
concentration was varied over the range (1-100) × 10-3 M, while
the substrate concentration was 4 × 10-5 M. All the solutions were
transferred by gastight syringes under nitrogen. The reactions were
followed by monitoring the appearance of Y-substituted phenoxide
Conclusions
The results of the kinetic study for the reactions of 1a-e
and 2 with Ox- and p-ClPhO- as the R and normal nucleophiles,
respectively, have allowed us to conclude the following. (1)
The bell-shaped R-effect profile obtained for the reactions of
1a-e and 2 suggests that the effect of medium on the R-effect
is significant and a two-point analysis could be misleading. (2)
The reactions of 1a-e with Ox- and p-ClPhO- proceed through
a tetrahedral intermediate with its formation being the RDS in
all the DMSO-H2O mixtures studied. (3) The contrasting novel
Brønsted-type plots for the reactions of 1a-e and 2 suggest
that the origin of the R-effect is likely to be different for these
systems. (4) Differential change in the sensitivity of the medium
effect on the Ox- and p-ClPhO- systems is responsible for the
bell-shaped R-effect profile found for the reactions of 1a-e and
2. (5) The magnitude of the R-effect is significantly dependent
on ânuc values. (6) Through application of calorimetric measure-
ments of ground-state solvation combined with the diagnostic
ions at a fixed wavelength corresponding to the λmax
.
Product Analysis. Y-substituted phenoxide ion was liberated
quantitatively and identified as one of the reaction products in the
reactions of 1a-e with Ox- by comparison of the UV-vis spectra
after completion of the reactions with those of the authentic samples
under the same reaction conditions.
Acknowledgment. The authors are grateful for the financial
support from the Korea Science and Engineering Foundation
(Grant KOSEF-F01-2005-000-10033-0) and NSERC of Canada
(E.B.).
ânuc values, it is proposed that the transition-state effect is more
dominant than the ground-state effect for the R-effect in the
present system.
Supporting Information Available: Tables of kinetic data for
the reactions of 1a-e with Ox- in DMSO-H2O mixtures. This
material is available free of charge via the Internet at http://
pubs.acs.org.
Experimental Section
Materials. Y-substituted phenyl acetates (1a-e) were readily
prepared from the reactions of the Y-substituted phenol and acetyl
JO051823F
920 J. Org. Chem., Vol. 71, No. 3, 2006