Solvent effect on the α-effect for the reactions of aryl acetates with butane-2,3-dione monoximate and p-chlorophenoxide in MeCN-H2O mixtures

Article abstract of DOI:10.1021/jo0156114

Second-order rate constants have been measured spectrophotometrically for the nucleophilic reactions of three substituted phenyl acetates with butane-2,3-dione monoximate (Ox^-) as an α-nucleophile and p-chlorophenoxide (ClPhO^-) as co

Full text of DOI:10.1021/jo0156114

J . Org. Chem. 2001, 66, 4859-4864
4859
Solven t Effect on th e r-Effect for th e Rea ction s of Ar yl Aceta tes
w ith Bu ta n e-2,3-d ion e Mon oxim a te a n d p-Ch lor op h en oxid e in
MeCN-H2O Mixtu r es
Ik-Hwan Um,* Eun-J u Lee, 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
Received March 2, 2001
Second-order rate constants have been measured spectrophotometrically for the nucleophilic
reactions of three substituted phenyl acetates with butane-2,3-dione monoximate (Ox-) as an
R-nucleophile and p-chlorophenoxide (ClPhO-) as corresponding normal nucleophile, in MeCN-
H2O mixtures of varying compositions at 25.0 ( 0.1 °C. The reactivity of Ox- toward the aryl acetates
decreases upon addition of MeCN to the reaction medium up to ca. 30 mol % MeCN, followed by a
gradual increase in rate upon further addition of MeCN. A similar result has been obtained for the
reaction of ClPhO- with the aryl acetates. However, the decrease in rate is more significant for the
less reactive ClPhO- than for the more reactive Ox-. Thus, for all the aryl acetates studied, Ox-
-
-
exhibits a sizable R-effect (kOx /kClPhO ) whose magnitude increases as the mol % MeCN in the
reaction medium increases. The relative basicities (∆pKa) of Ox- and ClPhO- have been determined
spectrophotometrically using piperazine as a reference base. The ∆pKa values increase on increasing
the mol % MeCN in the medium for both Ox- and ClPhO-. The difference in the relative basicities
-
of these nucleophiles (∆∆pKa) becomes larger with increasing mol % MeCN. The plots of log kOx
/
-
kClPhO vs ∆∆pKa for the three substrates are linear with near-unit slope, indicating that the
difference in the relative basicity of the nucleophiles is largely responsible for the increasing R-effect
with medium composition in this system.
In tr od u ction
Particularly, the effect of solvent on the R-effect has been
controversial.6-9 While the effect of solvent on the R-effect
has been suggested to be unimportant on the basis of the
similar magnitude of the R-effect for reactions performed
in H2O and in neat organic solvents,6 gas-phase studies
and theoretical calculations indicate a significant solvent
effect on the R-effect.7
The term R-effect was given to describe the abnormally
enhanced nucleophilicity exhibited by nucleophiles hav-
ing one or more nonbonding electron pairs at the position
adjacent to the nucleophilic center relative to a nucleo-
phile of the same basicity.1 Numerous studies have been
performed to account for the R-effect phenomenon.2
Theories suggested for the origin of the R-effect include
reactant destabilization through electronic repulsion
between nonbonding electron pairs, transition-state sta-
bilization, enhanced stability of the R-product, solvent
effect, as well as a transition state having aromatic or
radicaloid character.2-10 However, none of these factors
alone can fully account for the R-effect phenomenon.
To obtain more conclusive information on the role of
solvent, we initiated a systematic study for the reactions
(6) (a) Moss, R. A.; Swarup, S.; Ganguli, S. J . Chem. Soc,. Chem.
Commun. 1987, 860-861. (b) Curci, R.; Di Furia, F. Int. J . Chem. Kinet.
1975, 7, 341-345. (c) Gregory, M.; Bruice, T. C. J . Am. Chem. Soc.
1967, 89, 4400-4402.
(7) (a) DePuy, C. H.; Della, E. W.; Filley, J .; Grabowski, J . J .;
Bierbaum, V. M. J . Am. Chem. Soc. 1983, 105, 2481-2482. (b) Wolfe,
S.; Mitchell, D. J .; Schlegel, H. B.; Minot, C.; Eisenstein, O. Tetrahedron
Lett. 1982, 23, 615-618. (c) Evanseck, J . D.; Blake, J . F.; J orgensen,
W. L. J . Am. Chem. Soc. 1987, 109, 2349-2353. (d) Fountain, K. R.;
Dunkin, T. W.; Parel, K. D. J . Org. Chem. 1997, 62, 2738-2741. (e)
Fountain, K. R.; Hutchinson, L. K.; Mulhearn, D. C.; Xu, Y. B. J . Org.
Chem. 1993, 58, 7883-7890.
* To whom correspondence should be addressed. Tel: (822) 3277-
2349. Fax: (822) 3277-2844.
† Queen’s University.
(1) Edwards, J . O.; Pearson, R. G. J . Am. Chem. Soc. 1962, 84, 16-
24.
(2) Reviews: (a) Buncel, E.; Hoz, S. Isr. J . Chem. 1985, 26, 313-
319. (b) Grekov, A. P.; Veselor, V. Y. Usp. Khim. 1978, 47, 1200-1230.
(c) Fina, N. J .; Edwards, J . O. Int. J . Chem. Kinet. 1973, 5, 1-26.
(3) (a) Bernasconi, C. F.; Murray, C. J . Am. Chem. Soc. 1986, 108,
5251-5257. (b) Palling, D. J .; J encks, W. P. J . Am. Chem. Soc. 1984,
106, 4869-4876.
(4) (a) Terrier, F.; Moutiers, G.; Xiao, L.; Guevel, E.; Guir, F. J . Org.
Chem. 1995, 60, 1748-1754. (b) Moutiers, G.; Guevel, E.; Villien, L.;
Terrier, F. J . Chem. Soc., Perkin Trans. 2 1997, 7-10. (c) Laloi-Diard,
M.; Verchere, J . F.; Gosselin, P.; Terrier, F. Tetrahedron Lett. 1984,
25, 1267-1268.
(5) (a) Um, I. H.; Lee, J . S.; Yuk, S. M. J . Org. Chem. 1998, 63, 9152-
9153. (b) Fountain, K. R.; Dunkin, T. W.; Patal, K. D. J . Org. Chem.
1997, 62, 2738-2741. (c) Buncel, E.; Chuaqui, C.; Wilson. H. J . Am.
Chem. Soc. 1982, 104, 4896-4900. (d) Mclsaac, J . E., J r.; Subbaraman,
J .; Mulhausen, H. A.; Behrman, E. J . J . Org. Chem. 1972, 37, 1037-
1041. (e) Wiberg, K. B. J . Am. Chem. Soc. 1955, 77, 2519-2522.
(8) (a) Buncel, E.; Um, I. H. J . Chem. Soc., Chem. Commun. 1986,
595. (b) Um, I. H.; Buncel, E. J . Org. Chem. 2000, 65, 577-581. (c)
Um, I. H.; Hong, J . Y.; Buncel, E. Chem. Commun. 2001, 27-28.
(9) (a) Um, I. H.; Kwon, D. S.; Lee, G. J . Bull. Korean Chem. Soc.
1989, 10, 620-621. (b) Um, I. H.; Oh, S. J .; Kwon, D. S. Tetrahedron
Lett. 1995, 36, 6903-6906. (c) Um, I. H.; Yoon, H. W.; Lee, J . S.; Moon,
H. J .; Kwon, D. S. J . Org. Chem. 1997, 62, 5939-5944. (d) Um, I. H.;
Chung, E. K.; Lee, S. M. Can. J . Chem. 1998, 76, 729-737. (e) Um, I.
H.; Park, Y. M.; Buncel, E. Chem. Commun. 2000, 1917-1918.
(10) (a) Buncel, E.; Hoz, S. Tetrahedron Lett. 1983, 24, 4777-4780.
(b) Hoz, S.; Buncel, E. Tetrahedron Lett. 1984, 25, 3411-3414. (c)
Fountain, K. R.; Tad-y, D. B.; Paul, T. W.; Golynskiy, M. V. J . Org.
Chem. 1999, 64, 6547-6553. (d) Fountain, K. R.; Patel, K. D. J . Org.
Chem. 1997, 62, 4795-4797. (e) Fountain, K. R.; Dunkin, T. W.; Patel,
K. D. J . Org. Chem. 1997, 62, 3711-3714. (f) Fountain, K. R.; White,
R. D.; Patel, K. D.; Xu, Y.; New, D. G.; Cassely, A. J . J . Org. Chem.
1996, 61, 9343-9436.
10.1021/jo0156114 CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/09/2001

4860 J . Org. Chem., Vol. 66, No. 14, 2001
Um et al.
of p-nitrophenyl acetate (PNPA) with butane-2,3-dione
monoximate (Ox-) and p-chlorophenoxide (ClPhO-), as
an R-effect nucleophile and a corresponding normal
nucleophile, respectively, in dimethyl sulfoxide (DMSO)-
H2O mixtures of varying compositions, owing to the
unique properties of this solvent system.11b Unexpectedly,
-
-
the magnitude of the R-effect (kOx /kClPhO ) increased upon
addition of DMSO in the reaction medium up to ca. 50
mol % DMSO and then decreased beyond that point,
resulting in a bell-shaped dependence on solvent composi-
tion.8a,b A similar bell-shaped R-effect profile with a
maximum R-effect at ca. 50 mol % DMSO was observed
for the corresponding reactions of p-nitrophenyl diphe-
nylphosphinate (PNPDPP) and p-nitrophenyl benzene-
sulfonate (PNPBS),8c,13 suggesting that the bell-shaped
R-effect trend is general for the reactions of the carbonyl,
phosphinyl, and sulfonyl esters with Ox- and ClPhO- in
DMSO-H2O mixtures. However, Moss reported that the
magnitude of the R-effect for the reaction of PNPA with
O-iodosylbenzoate (IBO-) and ClPhO- in DMSO-H2O
mixtures shows no maximum but decreases steadily as
the DMSO content in the reaction medium increases.6a
Terrier and co-workers reported that the R-effect for the
reaction of PNPA with R,R,R-trifluoroacetophenone oxi-
mate (TAOx-) and ClPhO- increases with DMSO content
up to 70 vol %.4c Clearly, more work on solvent effects
on the R-effect is demanded.
In view of the above, we have extended our studies to
a different solvent system, namely acetonitrile (MeCN)-
H2O mixtures, instead of DMSO-H2O mixtures.9 Inter-
estingly, we have found that the magnitude of the R-effect
increases as the mol % MeCN in the reaction medium
increases.9e In the present paper, we report our results
for the reactions of Ox- and ClPhO- with three aryl
acetates, together with an analysis of the cause of this
contrasting R-effect profile in MeCN-H2O mixtures.
-
F igu r e 1. Plots of log kOx vs mol % MeCN for the reactions
of aryl acetates (1a -c) with Ox- in MeCN-H2O mixtures at
25.0 ( 0.1 °C: b (1a ), X (1b), O (1c).
slope of the plot of kobs vs nucleophile concentration,
which showed near-zero intercepts indicating that reac-
tion with solvent was negligible. The correlation coef-
ficients of the plots were usually higher than 0.9995 in
all the solvent compositions studied. It is estimated from
replicate runs that the uncertainty in the rate constants
is less than (3%. The second-order rate constants
determined in this way are presented graphically in
Figures 1 and 2 as a function of medium composition.
Relative basicities of the present nucleophiles (∆pKa
) pKa of the conjugate acid of nucleophiles - pKa of the
conjugate acid of the reference base) were determined
spectrophotometrically with respect to piperazine as the
reference base. This was done using the relationship in
eq 2
2
∆pKa ) log[HA]eq[B]eq/[A]eq
(2)
in which [HA]eq represents the equilibrium concentration
of the conjugate acid of the nucleophile and [B]eq and
[A-]eq represent the equilibrium concentration of the
reference base (piperazine) and the nucleophile, respec-
tively. The equilibrium concentration of the nucleophile
was determined from the relationship [A-]eq ) A/ꢀ, in
which A and ꢀ represent the absorbance and molar
absorptivity of the nucleophile at 290 nm for Ox- and
299 nm for ClPhO-, respectively. The advantages of
piperazine as a reference base are as follows: (1) the
basicity of piperazine is similar to that of Ox- and
ClPhO- in H2O; (2) piperazine is stable under the
experimental conditions and does not absorb in the UV
light in the region of interest. The ∆pKa values deter-
mined in this way are summarized in Table 2.
Resu lts
Kinetic studies were performed under pseudo-first-
order conditions with the nucleophile in excess. Pseudo-
first-order rate constants (kobs) were obtained from linear
plots of ln(A∞ - At) vs t, where A∞ and At are absorbances
at infinite time and at time t, respectively. Generally, five
different concentrations of nucleophile solutions were
used to determine second-order rate constant from the
(11) (a) Parker, A. J . Chem. Rev. 1969, 69, 1-32. (b) Buncel, E.;
Wilson, H. Adv. Phys. Org. Chem. 1977, 14, 133-202.
(12) Lowry, T. H.; Richardson, K. S. Mechanism and Theory in
Organic Chemistry, 2 nd ed.; Harper and Row: New York, 1981.
(13) Tarkka, R. M.; Buncel, E. J . Am. Chem. Soc. 1995, 117, 1503-
1507.
Discu ssion
Solven t Effect on Ra te. As shown in Figure 1, the
reactivity of Ox- decreases upon the initial addition of

R-Effect for the Reactions of Aryl Acetates
J . Org. Chem., Vol. 66, No. 14, 2001 4861
increases to 80.8 M-1 s-1 on going to 90 mol % MeCN
(see Table S1 in the Supporting Information). Similar
rate behavior is obtained for the reactions of 1b and 1c
with Ox-. In all cases, the second-order rate constants
exhibit a minimum at ca. 30 mol % MeCN. The reactivity
of ClPhO- exhibits a similar pattern, as shown in Figure
2. However, the rate decrease is more significant for the
reaction of ClPhO- than for Ox-; the second-order rate
constant for the reaction of 1a with ClPhO- decreases
from 0.171 M-1 s-1 in H2O to 0.0232 M-1 s-1 in 40 mol %
MeCN, and then increases to 0.0580 M-1 s-1 (see Table
S2 in the Supporting Information).
It is well-known that the negative end of the dipole in
dipolar aprotic solvents such as MeCN and DMSO is
exposed, whereas the positive end is buried within the
molecule.11 Since anions would be strongly destabilized
in such dipolar aprotic solvents, one might expect a
significant rate acceleration for the reactions of anionic
nucleophiles upon addition of MeCN or DMSO to the
reaction medium. In fact, in the latter case, the reactivi-
ties of Ox- and ClPhO- toward 1b increase significantly
as the mol % DMSO in the reaction medium increases,
except for ClPhO- from 0 to 10 mol % DMSO.8 Therefore,
the initial rate decrease upon addition of MeCN to the
reaction medium up to ca. 30 mol % in the present system
is an unexpected result based on the Hughes-Ingold
rules of solvent effects.11,12
However, whereas DMSO is a highly polarizable
solvent, MeCN is not so. Accordingly, DMSO can strongly
stabilize polarizable anions (e.g., picrate) or anionic
transition states that are expected to be highly polariz-
able through polarizability or charge dispersion interac-
tion, while MeCN does not exert such strong interac-
tions.11 This difference in solvent property between
MeCN and DMSO is likely largely responsible for the
difference in the rate behavior between the reaction run
in MeCN-H2O and that in DMSO-H2O mixtures (how-
ever, other difference may also contribute, e.g., H-
bonding).11 This argument can be further supported by
similar results obtained for other reactions run in
MeCN-H2O and in DMSO-H2O mixtures; the second-
order rate constant for the reaction of 1b with OH- and
benzohydroxamate anions in MeCN-H2O mixtures
showed a minimum at ca. 30 mol % MeCN,9c while in
DMSO-H2O mixtures the reactions of p-nitrophenyl
diphenylphosphinate (PNPDPP) and p-nitrophenyl ben-
zenesulfonate (PNPBS) with Ox- and ClPhO- exhibited
increasing rate trends upon addition of DMSO to the
reaction medium.8c,13
Solven t Effect on th e r-Effect. As shown in Table
1, for the reactions of 1a with Ox- and ClPhO-, the
magnitude of the R-effect (kOx-/kClPhO-) increases as the
mol % MeCN in the reaction medium increases from 138
in H2O to 375 and 1390 in 50 and 90 mol % MeCN,
respectively. A similar result is obtained for the reactions
of 1b and 1c, indicating that the effect of solvent on the
R-effect is general to this series. The effect of solvent on
the R-effect is graphically demonstrated in Figure 3. One
can see that the plot of the R-effect vs mol % MeCN
exhibits upward curvature regardless of the substrate.
The increasing R-effect profile obtained in the present
reaction is in contrast to the one obtained in the corre-
sponding reactions run in DMSO-H2O mixtures. The
magnitude of the R-effect for the reaction of 1b, PNPDPP
and PNPBS with Ox- and ClPhO- in DMSO-H2O
mixtures was found to increase upon addition of DMSO
F igu r e 2. Plots of log kClPhO- vs mol % MeCN for the reactions
of aryl acetates (1a -c) with ClPhO- in MeCN-H2O mixtures
at 25.0 ( 0.1 °C: b (1a ), X (1b), O (1c).
-
-
Ta ble 1. Ma gn itu d e of r-Effect (kOx /kClP h O ) for th e
Rea ction s of Ar yl Aceta tes (1a -c) w ith Ox- a n d ClP h O-
in MeCN-H2O Mixtu r es a t 25.0 ( 0.1 °C
Ox- ClPhO-
k
/k
MeCN (mol %)
1a
1b
1c
0
10
20
30
40
50
60
70
80
90
138
166
208
266
314
375
484
665
868
1390
96.1
96.6
116
148
180
210
254
312
369
505
52.5
66.2
73.3
82.8
96.9
117
144
165
202
268
Ta ble 2. Su m m a r y of th e Rela tive Ba sicity of th e
Nu cleop h ile (∆p Ka ) p Ka of th e Con ju ga te Acid of th e
Nu cleop h ile - p Ka of th e Con ju ga te Acid of th e
Refer en ce Ba se, P ip er a zin e) in MeCN-H2O Mixtu r es of
Va r yin g Com p osition s a t 25.0 ( 0.1 °Ca
b
MeCN (mol %)
∆pKa (Ox-)
∆pKa (ClPhO-)
∆∆pKa
0
10
20
30
40
50
60
70
80
90
-0.38
0.58
1.17
1.80
2.32
2.69
3.43
3.90
4.96
5.85
-0.44
0.43
0.90
1.44
1.89
2.19
2.84
3.20
4.18
4.90
0.06
0.15
0.27
0.36
0.43
0.50
0.59
0.70
0.78
0.95
a
The uncertainty in ∆pKa values is estimated to be less than
(0.03 pKa units. ∆∆pKa ) ∆pKa (Ox-) - ∆pKa (ClPhO-).
b
MeCN into the reaction medium and then increases upon
further addition of MeCN; the second-order rate constant
for the reaction of 1a with Ox- decreases from 23.6 M-1
s-1 in H2O to 6.46 M-1 s-1 in 30 mol % MeCN and then

4862 J . Org. Chem., Vol. 66, No. 14, 2001
Um et al.
oximates) is mainly responsible for the cause of the
vanishing R-effect with increasing oximate basicity.4,17
The GS of Ox- and ClPhO- would be also destabilized
upon the addition of MeCN in the medium, consequent
to the repulsion between the negative dipole end of MeCN
and the anionic species. However, the difference in the
GS solvation energy between Ox- and ClPhO- in MeCN-
H2O mixtures will be practically constant for the reac-
tions of 1a , 1b, and 1c. Therefore, if the difference in the
GS solvation energy were mainly responsible for the
R-effect, the magnitude of the R-effect should be about
the same, regardless of the substrate. In fact, the
magnitude of the R-effect is strongly dependent on
substrate, as shown in Table 1 and Figure 3. Therefore,
the present results clearly suggest that while the solvent
effect on the R-effect is significant, the difference in the
GS energy of Ox- and ClPhO- cannot be solely respon-
sible for the R-effect in the present system. This argu-
ment is consistent with our recent report which found
Ox- to be 3.92 kcal/mol less solvated than ClPhO- in
H2O,8b equivalent to an R-effect of 750. However, the
R-effect observed in the present system in H2O is found
to be only 138, 96, and 52 for the reaction of 1a , 1b, and
1c, respectively, indicating that the differential GS
energy is not fully reflected in the R-effect.
Many factors have been suggested to influence the
magnitude of the R-effect, e.g., basicity of nucleophile,4
hybridization type of electrophilic center,5 solvent,6 and
-
F igu r e 3. Plots of R-effect (kOx /kClPhO-) vs mol % MeCN for
the reactions of aryl acetates (1a -c) with Ox- and ClPhO- in
MeCN-H2O mixtures at 25.0 ( 0.1 °C: b (1a ), X (1b), O (1c).
â
nuc value.3,8c,15 The importance of ânuc in influencing the
R-effect can be demonstrated as follows.
to the medium up to ca. 50 mol % DMSO, and then
decrease beyond that point, resulting in a bell-shaped
R-effect profile.8,13 Therefore, the increasing R-effect
profile obtained in the MeCN-H2O mixtures in the
present study is a noteworthy finding and suggests that
the role of solvent on the R-effect is significant.
Bruice showed that the magnitude of the R-effect
decreases as the ânuc value decreases for reactions of a
variety of substrates with hydrazine and glycylglycine.15
We found that the reaction of an sp-hybridized carbon
center in which the ânuc value is 0.32 exhibits an
unexpectedly small R-effect.5a Furthermore, Bernasconi
observed no R-effect for the addition reaction of a series
of primary amines to Meldrum’s acid, a system for which
ânuc ) 0.22.3 For nucleophilic substitution reactions of a
series of aryloxides with 1a , 1b, and 1c, the ânuc values
have been reported to be 0.89, 0.79, and 0.38, respec-
tively.18 Hence, in the present reactions of 1a -c, the ânuc
value follows the same order as the R-effect in magnitude.
Similarly, we recently found that the magnitude of the
R-effect is strongly dependent on the ânuc value for
reactions of Ox- and ClPhO- at three different electro-
philic centers (i.e., 1b, PNPBS and PNPDPP) in 50 mol
% DMSO-H2O mixture: the R-effects were ca. 300, 200,
and 40 while the ânuc values were 0.64, 0.54, and 0.21
for the carbonyl, sulfonyl, and phosphinyl ester, respec-
tively.8c
Since the magnitude of the ânuc value has been under-
stood as a measure of bond formation between the
nucleophile and the substrate in the TS of the rate-
determining step, the TS structure of 1a , 1b , and 1c
systems would vary according to the different ânuc values.
One can expect that the TS stabilizing effect would be
proportional to the degree of bond formation at the TS.
It follows that the TS stabilizing effect would be most
significant for the reaction of 1a and least significant for
The enhanced reactivity of an R-effect nucleophile
compared to that of a corresponding normal nucleophile
can result from destabilizing the ground-state (GS) and/
or by stabilizing the transition state (TS) of the R-effect
nucleophile system. The R-nucleophile HOO- was re-
ported to be 12 kcal/mol less solvated than OH- in H2O14
and up to 102-104 times more reactive than HO- in
various addition reactions, although HOO- is less basic
than HO- by over 4 pKa units.5,15,16 However, DePuy et
al. found that HOO- shows no enhanced nucleophilicity
in the gas-phase reaction with methyl formate.7a Fur-
thermore, Wolfe et al. in an extensive ab initio study
found no unusual geometrical or energetic effect for the
transition state in gas-phase SN2 reactions with HOO-
and FO-.7b J orgensen et al. obtained a similar result
through ab initio study of SN2 reactions of HOO- and
HO- with CH3Cl.7c Therefore, it has been suggested that
HOO- is not intrinsically more reactive than HO- , but
that the enhanced reactivity of HOO- in solution is
mostly due to a solvation effect.7 A similar conclusion has
been drawn by Terrier et al. who found that highly basic
oximates of various structures show small or no R-effect
for the reactions with 1b, and suggested that differential
solvation (i.e., solvational imbalance for highly basic
(17) Terrier, F.; MacCormack, P.; Kizilian, E.; Halle, J . C.; Dem-
erseman, P.; Guir, F.; Lion, M. J . Chem. Soc., Perkin Trans. 2 1991,
153-158.
(18) (a) Kwon, D. S.; Lee, G. J . L.; Um, I. H. Bull. Korean Chem.
Soc. 1990, 11, 262-264. (b) J encks, W. P.; Gilchrist, M. J . Am. Chem.
Soc. 1968, 90, 2622-2644.
(14) Ritchie, C. D. J . Am. Chem. Soc. 1983, 105, 7313-7318.
(15) Dixon, J . E.; Bruice, T. C. J . Am. Chem. Soc. 1971, 93, 6592-
6597.
(16) Buncel, E.; Wilson, H.; Chuaqui, C. J . Am. Chem. Soc. 1982,
104, 4896-4900.

R-Effect for the Reactions of Aryl Acetates
J . Org. Chem., Vol. 66, No. 14, 2001 4863
the reaction of 1c, based on their ânuc values. This would
explain the finding that the magnitude of the R-effect and
the ânuc value follow a direct relationship in the present
and other systems as mentioned above.
Solven t Effect on Ba sicity. The addition of MeCN
to H2O would also influence the basicity of the present
anionic nucleophiles. It is well-known that carboxylic
acids and phenols become significantly weaker acids in
MeCN than in H2O.19 Although the pKa values for some
phenols and carboxylic acids in pure MeCN are avail-
able,19 very few pKa data have been reported for MeCN-
H2O mixtures.9c As part of the present study, we have
measured the relative basicity of Ox- and ClPhO- in
MeCN-H2O mixtures using piperazine as a reference
base. One can define ∆pKa as the pKa difference between
the conjugate acids of the nucleophile (Ox- or ClPhO-)
and piperazine, i.e., ∆pKa ) pKa of the conjugate acid of
the nucleophile (Ox- or ClPhO-) - pKa of the conjugate
acid of the reference base (piperazine). Therefore, the
magnitude of ∆pKa values represents the relative basici-
ties of these nucleophiles. The ∆pKa values determined
spectrophotometrically in MeCN-H2O mixtures of vary-
ing compositions (see the Results) are summarized in
Table 2.
As shown in Table 2, the ∆pKa values of Ox- and
ClPhO- in H2O are -0.38 and -0.44, respectively. The
pKa values of the conjugate acids of Ox-, ClPhO-, and
piperazine have been reported as 9.44,13 9.38,20 and
9.82,20 respectively; i.e., the ∆pKa data determined in H2O
in the present study are identical to the literature values.
It is also noted that Ox- and ClPhO- are less basic than
piperazine in H2O but appear to be more basic upon
addition of MeCN to H2O. This is consistent with the
reports that the increase in pKa values upon changing
the medium from H2O to MeCN is more significant for
phenols than for amines. Thus, the pKa enhancements
were reported to be 12-17 and 7-8 pKa units for phenols
and the conjugate acids of alicyclic secondary amines
(e.g., piperidine and morpholine), respectively, upon
solvent change from H2O to MeCN.19
-
F igu r e 4. Plots of log kOx /kClPhO- vs ∆∆pKa for the reactions
of aryl acetates with Ox- and ClPhO- in MeCN-H2O mixtures
at 25.0 ( 0.1 °C. b (1a ), X (1b), O (1c).
To confirm the above argument, we have correlated
-
-
∆∆pKa values with log kOx /kClPhO values obtained in the
-
-
present study. As shown in Figure 4, the log kOx /kClPhO
value increases linearly with ∆∆pKa, indicating that the
increasing ∆∆pKa value is responsible for the increasing
R-effect profile upon addition of MeCN in the medium.
The slope of the linear plots in Figure 4 is near unity,
which indicates that the increase in the ∆∆pKa values is
fully reflected in the increasing R-effect profile for the
reactions of 1a -c with Ox- and ClPhO- in MeCN-H2O
mixtures
The difference in the relative basicity between Ox- and
ClPhO- can be expressed as ∆∆pKa , i.e., ∆∆pKa ) ∆pKa
(Ox-) - ∆pKa (ClPhO-). As shown in Table 2, ∆∆pKa
increases as the mol % MeCN increases in the medium;
i.e., Ox- is more basic than ClPhO- by 0.06, 0.50, and
0.95 in pKa units in H2O, 50 and 90 mol % MeCN,
respectively. However, interestingly, the ∆∆pKa trend
determined in MeCN-H2O mixtures in the present study
is in contrast to that determined in DMSO-H2O mix-
tures. The ∆pKa values of the conjugate acids of Ox- and
ClPhO- increase in a parallel manner as the mol %
DMSO in the medium increases, while ∆∆pKa remains
nearly constant upon the change in medium from H2O
to 90 mol % DMSO.8b,13,21 Therefore, we propose that the
differential solvent effect on the relative basicity is the
cause of the contrasting R-effect profile for the reaction
run in MeCN-H2O, compared with DMSO-H2O mix-
tures.
Con cu lsion s
The results of the kinetic study for the reaction of aryl
acetates (1a -c) with Ox- and ClPhO- and of the relative
basicity measurements of these nucleophiles in various
MeCN-H2O mixtures, have allowed us to conclude the
following. (1) The reactivity of Ox- and ClPhO- toward
1a -c decreases upon addition of MeCN up to ca. 30 mol
% MeCN and then increases upon further addition of
MeCN to the reaction medium. (2) The magnitude of the
-
-
R-effect (kOx /kClPhO ) increases as the mol % MeCN in the
reaction medium increases, indicating a significant sol-
vent effect on the R-effect. (3) Differential GS solvation
between Ox- and ClPhO- cannot be solely responsible
for the R-effect in the present system. (4) ânuc values in
the present system are in the same order as the R-effect
in magnitude, indicating that TS stabilization is a
significant contributor to the R-effect. (5) The relative
basicity (∆pKa) of Ox- and ClPhO- with respect to
piperazine as reference base increases as the mol %
MeCN increases, and the difference in the relative
basicity between Ox- and ClPhO- (∆∆pKa) becomes
larger with increasing mol % MeCN in the medium. (6)
(19) (a) Chantooni, M. K.; Kolthoff, I. M. J . Phys. Chem. 1976, 80,
1306-1310. (b) Coetzee, J . F.; Padmanabhan, G. R. J . Am. Chem. Soc.
1965, 87, 5005-5010.
(20) J encks. W. P.; Regenstein, J . In Handbook of Biochemistry.
Selected Data for Molecular Biology; Sober, H. A., Ed.; The Chemical
Rubber Co.: Cleaveland, OH, 1968.
-
-
Plots of log kOx /kClPhO vs ∆∆pKa are linear with near
unit slope, indicating that the increasing ∆∆pKa values
(21) Laloi-Diard, M.; Verchere, J . F.; Gosselin, P.; Terrier, F.
Tetrahedron Lett. 1984, 25, 1267-1270.

4864 J . Org. Chem., Vol. 66, No. 14, 2001
Um et al.
(solvent composition g50 mol % MeCN) was used as the base.
The reactions were followed by monitoring the appearance of
the leaving aryloxide ion (e.g., p-nitrophenoxide ion at 400 nm).
Each reaction was monitored up to 10 half-lives. The pseudo-
first-order rate constants were obtained from the slopes of plots
of ln(A∞ - At) versus time, where A∞ and At represent the
absorbance reading at 10 half-lives and at time t (generally
taken up to 3 half-lives), respectively. Other details of kinetic
methods were reported previously.22
is largely responsible for the increasing R-effect trend
observed in the present system.
Exp er im en ta l Section
Ma ter ia ls. PNPA, butane-2,3-dione monoxime, p-chlorophe-
nol, and other chemicals used were obtained from Aldrich and
recrystallized before use. MeCN was distilled over P2O5 under
a
nitrogen atmosphere. Doubly glass-distilled water was
Rela tive Ba sicity Mea su r em en ts. Relative basicities of
Ox- and ClPhO- were determined spectrophotometrically.
Piperazine was chosen as reference base. Determinations of
relative basicity were done by measuring the absorbance of
Ox- or ClPhO- which is at equilibrium with the conjugate acid
of the base, i.e., piperazinium ion, using the same UV-vis
spectrophotometer as used for the kinetic study at the ap-
propriate fixed wavelength. Standard 1.0 cm quartz cells
(Hellma) closed on top with a rubber septum were used.
Hamilton gastight syringes were used to transfer solutions.
All the solutions were prepared in 25.0 mL volumetric flasks
sealed with a rubber septum just before use under a nitrogen
atmosphere. Other details of relative basicity measurements
are similar to the those in the literature.9c,23
further boiled and cooled under nitrogen just before use.
MeCN-H2O mixtures of varying compositions (mol %) were
prepared by adding the calculated weight of H2O to the
weighed, dry MeCN in a flask. The mixed solvents were stored
under nitrogen but no longer than 2 days.
P r od u ct An a lysis. 4-Acetylphenoxide, 4-nitrophenoxide,
and 2,4-dinitrophenoxide were identified as one of the final
products of the corresponding reactions by comparison of the
UV-vis spectra after completion of the reactions with those
of authentic samples at the same experimental conditions. The
other products, 4-chlorophenyl acetate and 2,3-butanedione
mono-(O-acetyl oxime), were indentified by HPLC using a
Waters 600 liquid chromatograph equipped with a Waters 996
photodiode array detector, a Rheodyne 7725i manual injector,
and a column of Nova-Pak C18 60 Å (4 µm) (3.9 i.d. × 150
mm length). The flow rate was 1 mL/min, and the eluent was
50% MeCN in MeOH (v/v). Quantitative analysis was per-
formed by comparison of the HPLC peak area of the reaction
mixture with that of the authentic sample.
Ack n ow led gm en t. I.H.U. is grateful for the finan-
cial support from KOSEF (1999-2-123-003-5) of Korea.
E.B. thanks NSERC of Canada for a research grant.
Kin etics. Kinetic studies were performed with a Scinco
Su p p or tin g In for m a tion Ava ila ble: Second-order rate
constants for the reactions of aryl acetates (1a -c) with Ox-
in MeCN-H2O mixtures at 25.0 ( 0.1 °C (Table S1) and the
rate constants for the corresponding reactions with ClPhO-
(Table S2). This material is available free of charge via the
Internet at http://pubs.acs.org.
S-2100 UV-vis spectrophotometer for slow reactions (t1/2
>
10 s) or for fast reactions (t1/2 e 10 s), with an Applied
Photophysics SX-17MV stopped-flow spectrophotometer, equip-
ped with a Neslab RTE-110 constant temperature circulating
bath to keep the temperature in the reaction chamber at 25.0
( 0.1 °C. All the reactions were carried out under pseudo-
first-order conditions in which the concentrations of nucleo-
philes were generally over 20 times, but at least 10 times,
greater than that of the substrate. Nucleophile stock solutions
of ca. 0.2 M were prepared in 25.0 mL volumetric flasks by
adding 0.5 equiv of base in order to achieve self-buffered
solutions. For reasons of solubility, standardized NaOH solu-
tion (solvent composition e40 mol % MeCN) or Me4NOH‚5H2O
J O0156114
(22) Buncel, E.; Um, I. H.; Hoz, S. J . Am. Chem. Soc. 1989, 111,
971-975.
(23) Mathews, W. S.; Bares, J . E.; Bartmess, J . E.; Bordwell, F. G.;
Cornforth, F. J .; Drucker, G. E.; Margolin, Z.; McCallum, R. J .;
McCallum, G. J .; Vanier, N. R. J . Am. Chem. Soc. 1975, 97, 7006-
7013.