The origin of the α-effect: Dissection of ground-state and transition- state contributions

Article abstract of DOI:10.1021/jo9915776

The origin of the α-effect has been probed through a combination of calorimetric and kinetic studies involving butane-2,3-dione monoximate as α- nucleophile and p-chlorophenoxide as normal nucleophile in the reaction with p-nitrophenyl acetate in DMSO-H

Full text of DOI:10.1021/jo9915776

J . Org. Chem. 2000, 65, 577-582
577
Th e Or igin of th e r-Effect: Dissection of Gr ou n d -Sta te a n d
Tr a n sition -Sta te Con tr ibu tion s
1
Ik-Hwan Um and Erwin Buncel*
Department of Chemistry, Queen’s University, Kingston, Canada K7L 3N6
Received October 11, 1999
The origin of the R-effect has been probed through a combination of calorimetric and kinetic studies
involving butane-2,3-dione monoximate as R-nucleophile and p-chlorophenoxide as normal nucleo-
phile in the reaction with p-nitrophenyl acetate in DMSO-H O mixtures, which has been shown
2
to exhibit a bell-shaped profile in the R-effect with solvent composition. The study, involving
determination of enthalpies of solution and activation parameters, has allowed a dissection of
contributions to the R-effect of ground-state destabilization and transition-state stabilization in
these DMSO-H O solvent media. It has been found that over the solvent composition 0-50 mol %
2
DMSO desolvation of the R-nucleophile is the main driving factor to the increasing R-effect. However,
in solvent mixtures covering 50-90 mol % DMSO the thermodynamic activation parameters suggest
an interplay of factors that result in the bell-shaped R-effect profile. Discussion is presented that
includes possible medium-dependent nonsynchronicity of nucleophile desolvation and bond formation
for the R-nucleophile.
In tr od u ction
our work, in common with that of others, suffered from
the fundamental deficiency that no quantitative data
concerning ground-state energy levels was available. This
information is particularly important as the solvent
medium is systematically changed. In this paper, we
present the first such pertinent evidence.
The origin of the R-effect, i.e., the enhanced reactivity
of nucleophiles that have an unshared pair of electrons
on the atom adjacent to the nucleophilic center, relative
to a normal nucleophile of the same basicity, has been a
source of continuing challenge to investigators since this
phenomenon was brought to light by Edwards and
We reported in 1986 an unusual solvent effect: on
changing the DMSO-water composition, the R-effect
2
Pearson. The most popular general causes that have
R-Nu normal-Nu
(k
/k
) for the reaction of p-nitrophenyl acetate
been advanced to account for the R-effect phenomenon
are differential ground-state (GS) destabilization, transi-
tion-state (TS) stabilization, product stabilization, and
solvent effects, while other possible specific origins
include a transition state having aromatic or radicaloid
character.3 We have previously presented evidence in
(
PNPA) with oximate as the R-Nu and aryloxide as
8
normal-Nu exhibited a maximum at ca. 50 mol % DMSO.
More recently, we found a similar bell-shaped R-effect
plot for the reaction of p-nitrophenyl diphenylphosphi-
1
0
2
nate as a function of changing DMSO-H O mixtures.
-6
However, a contrary result was reported with o-iodosyl-
benzoate as the R-nucleophile and p-chlorophenoxide as
normal-nucleophile, in the reaction with PNPA, where
7
favor of TS stabilization, and we have also described an
unusual influence of solvent in R-effect systems,8 but
,9
2
no maximum in the R-effect-DMSO/H O profile was
(
1) Permanent address: Department of Chemistry, Ewha Womans
1
1
found, and in fact, the R-effect decreased steadily.
University, Seoul 120-750, Korea.
(
(
2) Edwards, J . O.; Pearson, R. G. J . Am. Chem. Soc. 1962, 84, 16.
3) Reviews: (a) Buncel, E.; Hoz, S. Isr. J . Chem. 1985, 26, 313. (b)
Clearly, more work on solvent effects was demanded.
It was shown some time ago that combining kinetic
data with heats of solution could lead to a meaningful
dissection in terms of GS versus TS stabilization/
Fina, N. J .; Edwards, J . O. Int. J . Chem. Kinet. 1973, 5, 1. (c) Grekov,
A. P.; Veselov, V. Y. Usp. Khim. 1978, 47, 1200.
(
997, 62, 2738. (b) Fountain, K. R.; Patel, K. D. J . Org. Chem. 1997,
2, 4795. (c) Fountain, K. R.; Hutchinson, L. K.; Mulhearn, D. C.; Xu,
Y. B. J . Org. Chem. 1993, 58, 7883. (d) Moutiers, G.; Guevel, E. L.;
Villien, L.; Terrier, F. J . Chem. Soc., Perkin Trans. 2 1997, 7. (e)
Terrier, F.; MacCormack, P.; Kizilian, E.; Halle, J . C.; Demerseman,
P.; Guir, F.; Lion, C. J . Chem. Soc., Perkin Trans. 2 1991, 153. (f) Hoz,
S.; Speizman, D. J . Org. Chem. 1983, 48, 2904.
4) (a) Fountain, K. R.; Dunkin, T. W.; Patel, K. D. J . Org. Chem.
1
6
12
destabilization. We report the first such results for an
R-effect system in DMSO-H
2
O, namely the determina-
) for the sodium salts
tion of enthalpies of solution (∆H
s
-
of butane-2,3-dione monoximate (Ox ) and p-chlorophen-
-
oxide (p-ClPhO ) using a calorimetric technique and the
(
5) (a) Herschlag, D.; J encks, W. P. J . Am. Chem. Soc. 1990, 112,
q
q
q
activation parameters (∆G , ∆H , and T∆S ) in the
1
1
6
951. (b) Bernasconi, C. F.; Murray, C. J . J . Am. Chem. Soc. 1986,
08, 5251. (c) Dixon, J . E.; Bruice, T. C. J . Am. Chem. Soc. 1971, 93,
592.
(10) Tarkka, R. M.; Buncel, E. J . Am. Chem. Soc. 1995, 117, 1503.
(11) Moss, R. A.; Swarup, S.; Ganguli, S. J . Chem. Soc., Chem.
Commun. 1987, 860.
(
6) (a) DePuy, C. H.; Della, E. W.; Filley, J .; Grabowski, J . J .;
Bierbaum, V. M. J . Am. Chem. Soc. 1983, 105, 2481. (b) Wolfe, S.;
Mitchell, D. J .; Schlegel, H. B. J . Am. Chem. Soc. 1981, 103, 7694.
(12) (a) Buncel, E.; Wilson, H. J . Chem. Educ. 1980, 57, 629. (b)
Buncel, E.; Wilson, H. Acc. Chem. Res. 1979, 12, 42. (c) Buncel, E.;
Symons, E. A. J . Am. Chem. Soc. 1976, 98, 656. (d) Haberfield, P.;
Friedman, J .; Pinkston, M. F. J . Am. Chem. Soc. 1972, 94, 71. (e)
Kosower, E. M. An Introduction to Physical Organic Chemistry;
Wiley: New York, 1968. (f) Reichardt, C. Solvent and Solvent Effects
in Organic Chemistry, 2nd ed.; VCH Publishers: New York, 1988. (g)
Arnett, E. M.; Bentrude, W. G.; Burke, J . J .; Duggleby, P. McC. J .
Am. Chem. Soc. 1965, 87, 1541. (h) Arnett, E. M.; McKelvey, D. R.
Rec. Chem. Prog. 1965, 26, 185.
(7) (a) Buncel, E.; Hoz, S. Tetrahedron Lett. 1983, 24, 4777. (b) Hoz,
S.; Buncel, E. Tetrahedron Lett. 1984, 25, 3411. (c) Buncel, E.; Chuaqui,
C.; Wilson, H. J . Am. Chem. Soc. 1982, 104, 4896. (d) Buncel, E.;
Chuaqui, C.; Wilson, H. J . Org. Chem. 1980, 45, 3621.
(
(
29. (b) Um, I. H.; Yoon, H. W.; Lee, J . S.; Moon, H. J .; Kwon, D. S. J .
Org. Chem. 1997, 62, 5939. (c) Um, I. H.; Oh, S. J .; Kwon, D. S.
Tetrahedron Lett. 1995, 36, 6903.
8) Buncel, E.; Um, I. H. J . Chem. Soc., Chem. Commun. 1986, 595.
9) (a) Um, I. H.; J ung, E. K.; Lee, S. M. Can. J . Chem. 1998, 76,
7
1
0.1021/jo9915776 CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/29/1999

5
78 J . Org. Chem., Vol. 65, No. 2, 2000
Um and Buncel
-
Sch em e 1
∆
∆H (p-ClPhO ) )
tr
+
∆
∆H (p-ClPhONa) - ∆∆H (Na ) (2)
tr
tr
-
+
∆
∆H (Ox ) ) ∆∆H (OxNa) - ∆∆H (Na ) (3)
tr
tr
tr
In Table 2 are presented the transfer enthalpies
∆∆Htr) from H O to DMSO-H O mixtures for the single
(
2
2
-
-
+
ions p-ClPhO , Ox , and Na .
The observed rate constants (kobs) of the reactions of
-
-
PNPA with p-ClPhO and Ox , present in exess, in
various DMSO-H O mixtures were determined spectro-
2
photometrically. All the reactions in the present system
obeyed pseudo-first-order kinetics. Generally five differ-
ent concentrations of nucleophilic solutions were used to
obtain second-order rate constants from the slope of the
plot of kobs vs concentration of nucleophile, which showed
Ta ble 1. En th a lp ies of Solu tion s (∆Hs, k ca l/m ol) for
Sod iu m Hyd r oxid e, Sod iu m p-Ch lor op h en oxid e
p-ClP h ONa ), a n d Sod iu m Bu ta n e-2,3-d ion e Mon oxim a te
(
(
OxNa ) in DMSO-H2O Mixtu r es a t 25.0 °C
-
negligible intercept indicating that the reaction with OH
∆Hs, kcal/mol
or solvent did not occur to a significant extent. The
correlation coefficient of the plot was usually higher than
0.9995 in all solvents studied. It is estimated from
replicate runs that the uncertainty in any particular
measured rate constant is less than (3%. In Tables 3
and 4 are presented the second-order rate constants for
mol % DMSO
0
NaOHa
p-ClPhONab
OxNab
-10.5
-10.4
-7.3
-5.6
-3.7
-3.4
-2.7
-2.1
-1.5
-0.8
-9.12
-7.53
-6.27
-5.98
-6.27
-6.39
-6.62
-6.67
-6.51
-6.00
-5.20
-2.98
-0.57
0.82
0.86
0.86
0.59
0.56
0.61
0.86
1
2
3
4
5
6
7
8
9
0
0
0
0
0
0
0
0
0
-
-
the reactions of PNPA with p-ClPhO and Ox in
DMSO-H
2
O mixtures at 25.0, 35.0, and 45.0 °C. The
Ox- p-ClPhO-
magnitudes of the R-effect (k /k
) values are
q
presented in Table 5, and the activation parameters (∆G ,
q
q
-
∆
H , and T∆S ) for the reactions of PNPA with p-ClPhO
a
Data taken from ref 13. b This work.
-
2
and Ox in various DMSO-H O mixtures are sum-
marized in Tables 6 and 7, respectively.
2
reaction of these nucleophiles with PNPA in DMSO-H O
mixtures, Scheme 1.
Discu ssion
Dissection of Solven t Effect on Gr ou n d -Sta te a n d
Tr a n sition -Sta te Con tr ibu tion s: Meth od ology. In
Resu lts
12
principle, a reaction pathway in a given solvent may be
represented by a qualitative two-dimensional energy
profile. Figure 1 shows such a profile for a reaction
s
The enthalpies of solution (∆H ) for the sodium salts
p-chlorophenoxide (p-ClPhONa) and oximate (OxNa)
have been measured at 25.0 ( 0.1 °C in various DMSO-
carried out in two different media, H
H O mixture. In Figure 1, the standard free energy of
2
2
O and a DMSO-
2
H O mixtures. The concentration range of the salts in a
-3
given solvent medium was 2-8 × 10 M. No dependence
of the molar enthalpy of solution on concentration was
observed within this concentration range. The precision
of the Tronac model 1250 calorimeter in typical measure-
R
the reactant, R, in H
DMSO-H
2
O is designated as G
o
and in the
R
2
O mixture as G
s
. The difference in free
R
R
energies between the two solvents (G
s
- G
o
) is termed
R
the transfer free energy δGtr
.
ment of enthalpies of solution (∆H
0.5%, while temperature control of (0.0001 °C was
maintained when a standard instrument with a 50 mL
Dewar vessel was used. In Table 1 are presented ∆H
s
) on 2 calories was
(
R
R
R
δGtr ) Gs - Go
(4)
s
Similarly, for the transition state T one obtains
values for the salts listed above together with the
literature data for NaOH.13a
T
T
T
δGtr ) Gs - Go
(5)
The transfer enthalpy for a given compound from one
solvent to another (∆∆Htr) is defined as the difference in
The difference in free energies of activation for the two
solvents is designated δ∆G , and from Figure 1 it is
q
∆
H
s
in the two solvents. Thus:
apparent that
∆
∆Htr ) ∆H (in DMSO-H O) - ∆H (in H O) (1)
s
2
s
2
q
δ∆G )
q
q
T
R
T
R
o
∆
Gs - ∆Go ) (Gs - G ) - (G - G ) (6)
The single ion transfer enthalpies from H
2
O to DMSO-
s
o
-
-
H
2
O mixtures (∆∆Htr) for p-ClPhO and Ox have been
which simplifies to
s
calculated from the measured ∆H values of sodium salts
of these anions and the known data for Na , according
to eqs 2 and 3.
+
13a
q
T
R
δ∆G ) δG
- δGtr
(7)
tr
T
δGtr can be evaluated from the measurable transfer
(
13) (a) Fuchs, R.; Hagan, C. P.; Rodewald, R. F. J . Phys. Chem.
R
free energies of reactants (δGtr ) and the kinetic activa-
1
1
974, 78, 1509. (b) Fuchs, R.; Hagan, C. P. J . Phys. Chem. 1973, 77,
797. (c) Cox, B. G. Ann. Repts. Chem. Soc. A 1973, 70, 249.
q
tion parameters (δ∆G ). The foregoing arguments apply

Origin of the R-Effect
J . Org. Chem., Vol. 65, No. 2, 2000 579
p-ClP h O-
Ta ble 2. Tr a n sfer En th a lp ies (∆∆Htr , k ca l/m ol) fr om 0 to
Ta ble 5. Ma gn itu d e of th e r-Effect (kOx-/k
) for
+
-
-
-
9
0 m ol % DMSO for Sin gle Ion s of Na , p-ClP h O , a n d
th e Rea ction of P NP A w ith Ox a n d p-ClP h O in
-
Ox a t 25.0 °C
DMSO-H2O Mixtu r es of Va r yin g Com p osition a t 25.0,
3
5.0, a n d 45.0 °C
R-effect (kOx-/kp-ClPhO-
∆∆Htr, kcal/mol
)
a
p-ClPhO- b
Ox- b
mol % DMSO
Na+
0
mol % DMSO
25.0 °C
35.0 °C
68
45.0 °C
59
0
0
0
0
0
0
0
0
0
0
0
0
1.4
5.1
8.3
1
2
3
4
5
6
7
8
9
0.8
0.8
3.3
5.4
6.7
8.0
8.6
9.0
9.5
10.2
0
10
20
30
40
50
60
70
80
96
119
183
227
264
285
283
236
181
121
-0.5
-2.3
-3.9
-5.3
-6.1
-6.6
-6.9
-7.1
136
121
9.9
11.4
11.9
12.4
12.7
13.2
217
248
186
192
203
144
83a
9
0
100a
a
Data taken from ref 13. b Calculated from calorimetric data
a
using eqs 2 and 3.
Graphically extrapolated value.
Ta ble 3. Secon d -Or d er Ra te Con sta n ts (k, M s-1) for
-
1
Ta ble 6. Activa tion P a r a m eter s (k ca l/m ol) for th e
-
-
th e Rea ction of P NP A w ith p-ClP h O in DMSO-H2O
Mixtu r es of Va r yin g Com p osition a t 25.0, 35.0, a n d 45.0
Rea ction of P NP A w ith p-ClP h O in DMSO-H2O
Mixtu r es of Va r yin g Com p osition a t 25.0 °C
°
C
kcal/mol
k, M- s-1
35.0 °C
1.50
1
mol % DMSO
∆Gq
∆Hq
T∆Sq
mol % DMSO
0
25.0 °C
45.0 °C
2.71
0
20
40
50
70
90
17.7
17.7
16.9
16.5
15.4
14.1
12.3
13.1
12.0
11.7
10.7
9.1
-5.4
-4.5
-4.9
-4.8
-4.7
-5.0
0.685a
0.653
1
2
3
4
5
6
7
8
9
0
0
0
0
0
0
0
0
0
a
0.760
1.69
3.26
1.36
2.86
5.90
a
5.77
11.1
10.7
21.7
a
13.6
34.7
Ta ble 7. Activa tion P a r a m eter s (k ca l/m ol) for th e
Rea ction of P NP A w ith Ox in DMSO-H2O Mixtu r es of
a
-
60.0
560
120
935
94.8
Va r yin g Com p osition a t 25.0 °C
a
334
kcal/mol
a
Data taken from ref 8.
∆Gq
∆Hq
T∆Sq
mol % DMSO
Ta ble 4. Secon d -Or d er Ra te Con sta n ts (k, M s-1) for
-1
0
20
40
15.0
14.6
13.6
13.1
12.2
11.2
8.0
-7.0
-5.4
-5.0
-5.4
-5.7
-5.1
-
th e Rea ction of P NP A w ith Ox in DMSO-H2O Mixtu r es
9.2
8.6
7.7
6.4
6.1
of Va r yin g Com p osition a t 25.0, 35.0, a n d 45.0 °C
5
7
0
0
k, M- s-1
1
mol % DMSO
0
25.0 °C
35.0 °C
102
45.0 °C
160
90
65.8a
77.8
1
2
3
4
5
6
7
8
9
0
0
0
0
0
0
0
0
0
a
130
230
393
309
740
1680
a
1250
2750
1990
4160
a
3850
8200
a
12 200
17 300
17 200
40 500
a
b
b
a
Data taken from ref 8. b Rates were too fast to measure.
Therfore, rate constants could not be measured at 35.0 and 45.0
°
C; instead the following values and temperatures were deter-
-
1
-1
-1 -1
mined: 28 000 M
5
s
at 15.0 °C; 34 300 M
s
at 20.0 °C;
-
1
-1
0 800 M
s
at 30.0 °C.
equally to the derived thermodynamic functions, i.e.,
R
T
equations corresponding to δGtr or δGtr can readily be
R
T
written for ∆∆Htr or ∆∆Htr
.
The purpose of this methodology is to dissect the
relative contribution of the overall solvent effect on the
GS and on the TS as the solvent composition is system-
F igu r e 1. Illustration of relationship between the transfer
free energies of reactants and the transition state and the free
energies of activation for a reaction occurring in the two
solvent systems.
2
atically changed from H O to 90 mol % DMSO and to
understand the origin of the bell-shaped R-effect versus
solvent composition plots that have frequently been
reported in this and related systems.8
sented in Table 1 together with the data for sodium
hydroxide in the literature. The enthalpies of solution
,10
13
Gr ou n d -Sta te Con tr ibu tion . The enthalpy of solu-
tion data for sodium p-chlorophenoxide (p-ClPhONa) and
sodium butane-2,3-dione monoximate (OxNa) are pre-
(∆H
exothermic, except those for OxNa beyond ca. 20 mol %
DMSO. ∆H values increase as the mol % DMSO in-
s
) of both p-ClPhONa and OxNa are negative, or
s

5
80 J . Org. Chem., Vol. 65, No. 2, 2000
Um and Buncel
F igu r e 3. Plots of transfer enthalpies (∆∆Htr) from H
DMSO-H O mixtures as a function of mol % DMSO for the
single ions Ox , p-ClPhO , and Na at 25.0 °C.
2
O to
F igu r e 2. Plots of enthalpies of solution (∆H
of mol % DMSO for the sodium salts of p-ClPhO and Ox in
DMSO-H O mixtures at 25.0 °C.
s
) as a function
2
-
-
-
-
+
2
ability interaction.19,20 Since the negative end of the dipole
in DMSO is exposed while the positive one is buried
within the molecule, DMSO is ineffective in solvating
creases in all cases. However, the increase in ∆H
pronounced for NaOH and least pronounced for p-
ClPhONa. In Figure 2 is plotted the variation of ∆H as
a function of mol % DMSO for p-ClPhONa and OxNa.
One can see that the ∆H value increases at first and
reaches maximum as the DMSO concentration increases,
close to 30 mol % DMSO, the overall increase for
p-ClPhONa and OxNa being ca. 3 and 6 kcal/mol,
s
is most
s
anions but can strongly solvate cations through ion-
dipole interactions.1 Therefore, small variations in ∆H
9,20
s
s
-
-
values for the sodium salts of p-ClPhO and Ox beyond
30 mol % DMSO likely originate from opposite influences,
i.e., an unfavorable interaction between the solvent and
the anionic solutes and a favorable one between the
respectively. Importantly, ∆H
constant beyond 30 mol % DMSO for both salts. Such a
behavior, showing a maximum ∆H value near 30 mol %
s
appears to be almost
+
solvent and the Na cation, as the mol % DMSO
increases.
s
DMSO, is not specific to the present system but, rather,
is consistent with many unusual phenomena observed
near 30-40 mol % DMSO, such as a maximum in
energy-volume coefficient,14 viscosity and density, and
The above argument gains support from the transfer
enthalpies from H
2
+
O to DMSO-H O mixtures (∆∆Htr)
2
-
-
for single ions, Na , p-ClPhO , and Ox . ∆∆Htr values
15
-
-
for p-ClPhO and Ox can be calculated using the known
1
6
a minimum in freezing point, adiabatic compress-
+ 13a
data for Na ,
via the extrathermodynamic assump-
As ) ) ∆∆Htr(Ph
ibility,17 and excess free energy of mixing of DMSO with
18
13
+
-
tion, ∆∆Htr(Ph
4
4
B ). Hence, ∆∆Htr(p-
H
2
O.
H-bonding interactions are believed to be the most
important for anionic solutes in H O. Since DMSO forms
strong H-bonding with H O, addition of DMSO to H
O mol-
and this would diminish the extent of H-
-
+
ClPhO ) ) ∆∆Htr(p-ClPhONa) - ∆∆Htr(Na ) and
-
+
∆
∆Htr(Ox ) ) ∆∆Htr(OxNa) - ∆∆Htr(Na ), as stated in
2
the Results. The ∆∆Htr values for the single ions obtained
2
2
O
in this way are summarized in Table 2 and illustrated
would decrease the concentration of free H
2
+
graphically in Figure 3. The ∆∆Htr value for Na de-
ecules,1
9,20
creases (e.g., -7.1 kcal/mol upon solvent change from
2
bonding between free H O molecules and the anions of
H O to 90 mol % DMSO), indicating that ion-dipole
2
-
-
p-ClPhO and Ox . Therefore, one can attribute the
increased ∆H values of these salts to a decrease in
H-bonding interactions over the solvent range 0-30 mol
interactions between the cation and the negative end of
the dipole in DMSO become stronger as the DMSO
content increases. The ∆∆Htr values for the anions
exhibit a steep increase as the DMSO content increases
up to near 30-40 mol %. This increase in ∆∆Htr clearly
indicates that these anions become strongly desolvated
upon the solvent change, due to reduced H-bonding
s
%
%
DMSO. When the DMSO concentration exceeds 30 mol
, the H-bonding interaction with H O molecules be-
2
comes diminished, but importantly, DMSO plays an
increasingly important role in solvent-solute interac-
tions, e.g., through charge dispersion or mutual polariz-
interaction between the anions and H
2
O molecules in the
H
2
O-rich media. However, the degree of desolvation is
(
14) Cowie, J . M. G.; Toporowski, P. M. Can. J . Chem. 1961, 39,
not so steep in the DMSO-rich media, probably due to
the combination of the increase in charge dispersion and
the decrease in H-bonding interactions. In contrast,
2
240.
(15) MacDonald, D. D.; Hyne, J . B. Can. J . Chem. 1971, 49, 611.
16) Ranky, W. O.; Nelson, D. C. In Organic Sulfur Compounds;
(
Kharasch, N., Ed.; Pergamon: New York, 1961; Vol. 1, Chapter 17.
17) Bowen, D. E.; Priesand, M. A.; Eastman, M. P. J . Phys. Chem.
974, 78, 2611.
-
-
(
∆∆Htr for OH exhibits a steeper dependence than Ox
1
-
13
or p-ClPhO in the DMSO-rich region, which is in
accord with nonpolarizable nature of the small “hard”
anion.
(
(
(
18) Lam. S. Y.; Benoit, R. L. Can. J . Chem. 1974, 52, 718.
19) Buncel, E.; Wilson, H. Adv. Phys. Org. Chem. 1977, 14, 133.
20) Parker, A. J . Chem. Rev. 1969, 69, 1.

Origin of the R-Effect
The enthalpy of solution difference between Ox and
J . Org. Chem., Vol. 65, No. 2, 2000 581
-
-
s
p-ClPhO (∆∆H ) can be calculated using the following
relationship
∆
∆H ) ∆H (OxNa) - ∆H (p-ClPhONa)
(8)
s
s
s
+
since the enthalpy of solution of Na cancels. The results
in Figure 2 show that ∆∆H increases over 3 kcal/mol
s
upon addition of DMSO up to nearly 50 mol % DMSO
and remains almost constant beyond that point: thus,
-
-
Ox experiences much greater desolvation than p-ClPhO
upon addition of DMSO to the medium.
Interestingly, the increasing trend in ∆∆H values up
s
to 50 mol % DMSO parallels the increasing R-effect trend
observed over that medium range. Thus, the greatly
-
-
increasing desolvation of Ox over p-ClPhO appears to
be the dominant factor in the increasing R-effect trend
up to 50 mol % DMSO. However, if the difference in the
GS desolvation were mainly responsible for the R-effect
2
throughout the whole range of DMSO-H O mixtures
studied, one would have expected the R-effect to remain
constant, at the maximum value, in the DMSO-rich
region. In fact, the magnitude of the R-effect decreases
F igu r e 4. Plots of the R-effect (kOx-/kp-ClPhO-) as a function of
8
,10
-
beyond 50 mol % DMSO in this and related systems.
mol % DMSO for the reaction of PNPA with p-ClPhO and
-
-
-
Ox at 25.0, 35.0, and 45.0 °C.
Since the pK
parallel manner upon addition of DMSO to the medium;
therefore, the bell-shaped R-effect cannot be due to
differential change in pK values of the two nucleophiles,
a
values of p-ClPhO and Ox change in
1
0
a
and an additional factor must be operating in the DMSO-
rich region.
Tr a n sition -Sta te Con tr ibu tion . To aid in the inves-
tigation of the effect of solvent on the TS, activation
parameters have been determined from rate constants
obtained at 25.0, 35.0, and 45.0 °C for the reactions of
-
-
2
PNPA with Ox and p-ClPhO in DMSO-H O mixtures.
In Tables 3 and 4 are summarized the rate constant data.
The effect of temperature on the reaction rates is larger
-
for the slower reaction (p-ClPhO with PNPA) than for
-
the faster one (Ox with PNPA). For example, the rate
2
accelerations in H O at 35.0 and 45.0 °C compared to
those at 25.0 °C, k(35.0 °C)/k(25.0 °C) and k(45.0 °C)/
-
k(25.0 °C), are 2.2 and 4.0 for p-ClPhO and 1.6 and 2.4
-
for Ox , respectively. This differential temperature effect
on the reaction rate is similar throughout the solvent
range studied. Consequently, the magnitude of the R-ef-
fect becomes smaller on increasing the reaction temper-
ature over the whole solvent range, which is in accord
with the reactivity-selectivity principle.21 However, the
R-effect trend obtained from the reactions run at 35.0 and
q
F igu r e 5. Comparative plots of activation parameters (∆G ,
4
5.0 °C shows the same general characteristics as that
q
q
∆
H , and T∆S ) as a function of mol % DMSO for the reaction
obtained at 25.0 °C, i.e., a bell-shaped plot with maximum
located near 50 mol % DMSO (Figure 4).
-
-
of PNPA with p-ClPhO and Ox at 25.0 °C.
exhibits an initial increase upon the solvent change from
0 to 20 mol % DMSO for both systems. However, unlike
the entropy term, ∆H decreases for both systems upon
The activation parameters for the reaction of PNPA
-
-
with Ox and p-ClPhO are summarized in Tables 6 and
and illustrated graphically in Figure 5 as a function of
q
7
further addition of DMSO, suggesting that beyond 20 mol
% DMSO the reaction rate is mainly governed by the
enthalpy term.
mol % DMSO. In accord with the rate data, the free
‡
energy of activation (∆G ) decreases as the DMSO content
-
increases, by about 4 kcal/mol for both the Ox and
q
-
A noteworthy observation is that the decrease in ∆H
for the p-ClPhO system is steeper than that for the Ox
p-ClPhO systems upon the solvent change from 0 to 90
-
-
‡
mol % DMSO. Interestingly, the entropy term (T∆S )
system in the medium range 50-90 mol % DMSO (Figure
5), which suggests that the TS for the p-ClPhO system
becomes more stabilized than the one for the Ox system
increases initially by 1-1.5 kcal/mol but remains almost
-
-
constant beyond 20 mol % DMSO, for both the Ox and
-
-
q
p-ClPhO systems. The enthalpy of activation (∆H )
in the DMSO-rich region. One possibility is that this
stabilization in the DMSO-rich region results from a
(21) (a) Buncel, E.; Wilson, H. J . Chem. Educ. 1987, 64, 475. (b)
-
-
Buncel, E.; Wilson, H.; Chuaqui, C. J . Am. Chem. Soc. 1982, 104, 4896.
greater polarizability of p-ClPhO as compared to Ox .

5
82 J . Org. Chem., Vol. 65, No. 2, 2000
Um and Buncel
q
In that case, the differential trend in ∆H between the
CaH
2
at reduced pressure (64-66 °C at 6-7 mmHg) and stored
-
-
under nitrogen. DMSO-H O mixtures of varying compositions
Ox and p-ClPhO systems beyond 50 mol % DMSO
could account for the decreasing R-effect in the DMSO-
rich region (Figure 4).
In discussion of the origin of the R-effect in the
p-nitrophenyldiphenyl phosphinate (PNPDPP) system
we found that the TS for the Ox reaction is significantly
imbalanced22 as a result of nonsynchronicity in desol-
vation and bond formation. The key point here is that
the extent of nonsynchronicity for the Ox reaction varies
as the solvent composition varies, whereas it is constant
2
2
(mol %) were prepared by adding the calculated weight of H O
to the weighed dry DMSO in a flask. The mixed solvents were
stored under nitrogen but no longer than 2 days.
Ca lor im etr ic Stu d ies. A Tronac 1250 calorimeter was
used for measurement of enthalpies of solution. Depending on
the magnitude of enthalpies of solution, generally 20- 80 mg
of an accurately weighed sample was inserted in a ca. 1.5 cm
diameter fragile glass ampule, and the ampule neck was sealed
using a micro torch. The ampule was placed in the ampule
holder, and the Dewar vessel containing 50.0 mL of solvent
was assembled to the calorimeter header. The header was
immersed in the water bath, whose temperature was controlled
at 25.000 ( 0.003 °C. The temperature of the solvent in the
dewar vessel was adjusted to equilibrate using a micro electric
heater and a mechanical stirrer provided on the header. Once
the electric heater was turned off, the temperature increased
very slowly due to the mechanical stirrer. From this point, an
electrical calibration was done to determine the initial heat
capacity of the system. When the temperature reached 25.0
1
0
-
23
-
-
10
for the p-ClPhO reaction. While a definitive analysis
of the degree of nonsynchronicity in the current system
awaits quantitative treatment2 the similarity in the bell-
3
2
shaped R-effect plot versus DMSO-H O composition, is
suggestive of having a similar origin.
In conclusion, our study has shown that differential
ground-state desolvation for the R- and the normal-
nucleophile is the main factor responsible for the increas-
°
C, the ampule was broken using the breaker located on the
ing R-effect trend in the H
%
2
O-rich media (up to ca. 50 mol
DMSO). On the other hand, differential stabilization
header and was followed by a final electrical calibration to
determine the final heat capacity of the system. The heat
of the transition state in the DMSO-rich media contrib-
utes to the decreasing R-effect over that range. Clearly,
a single factor such as GS destabilization, or even TS
stabilization, is not by itself sufficient to explain origin
of the R-effect and its variation with solvent composition
evolved by dissolution of the sample salt (Q ) was calculated
s
by multiplying the mean heat capacity (C
the temperature change (∆T) due to the sample dissolution,
) C ∆T. The enthalpy of solution (∆H ) was obtained by
dividing Q by the number of moles of sample used, i.e., ∆H
/(number of moles of sample).
Kin etics. The kinetic study was performed using a Perkin-
p
) of the system and
Q
s
p
s
s
s
)
Q
s
2
in the DMSO-H O system.
Extension of the present work to related compounds,
with different eletrophilic centers, as well as a full
analysis of potential nonsynchronicity in these systems,
is underway.
Elmer 552 spectrophotometer for the slow reactions (t1/2 > 10
s) or a Can-Tech stopped-flow spectrophotometer for the fast
reactions (t1/2 e 10 s). The temperature inside the 10 mm
quarts cells in the UV-vis spectrophotometer and the fluid
handling system of the stopped-flow apparatus could be set
anywhere between 10.0 ( 0.1 and 45.0 ( 0.1 °C.
All the kinetic studies were performed under pseudo-first-
order conditions in which the concentration of nucleophile is
generally 20-fold but at least 10-fold greater than the substrate
concentration. Nucleophile stock solutions of ca. 0.2 M were
prepared in 25.0 mL volumetric flasks in a glovebox under a
nitrogen atmosphere by adding 2 equiv of p-chlorophenol or
butane-2,3-dione monoxime to 1 equiv of base in order to
achieve self-buffered solutions. For reasons of solubility, above
Exp er im en ta l Section
Ma ter ia ls. PNPA, p-chlorophenol (p-ClPhOH), and butane-
2
,3-dione monoxime (OxH) were obtained from Aldrich and
recrystallized before use. Sodium butane-2,3-dione monoxi-
mate (OxNa) was prepared by mixing equivalent amounts of
sodium ethoxide solution and OxH. Typically, 10.51 g of OxH
(103.9 mmol) was placed in a 250 mL round-bottom flask and
1
00.0 mL of 1.039 M of sodium ethoxide solution was added.
4
4
4
0 mol % DMSO Me NOH was used as the base, while below
0 mol % NaOH could be used. The reactions were followed
The mixture was stirred for 1 h under nitrogen, the bulk
solvent removed on a rotary evaporator and the residue was
dried overnight under high vacuum (mp 234 °C dec). A similar
method was used for the preparation of sodium p-chlorophen-
oxide (p-ClPhONa, mp 305-306 °C).
by monitoring the appearance of p-nitrophenoxide ion at the
appropriate fixed wavelength (λmax: 400-432 nm). Each reac-
tion was monitored up to 10 half-lives. The pseudo-first-order
rate constants were obtained from the slopes of plots of ln(A
) versus time, where A and A represent the absorbance
∞
Doubly glass distilled water was boiled and cooled under
nitrogen just before use. DMSO was refluxed and distilled over
-
A
t
∞
t
reading at 10 half-lives and at time t (generally taken up to 3
half-lives), respectively. Other details of the kinetic method
were reported previously.24
(22) (a) J encks, W. P.; Brant, S. R.; Gandler, J . R.; Fendrich, G.;
Nakamura, C. J . Am. Chem. Soc. 1982, 104, 7045. (b) J encks, W. P.;
Haber, M. T.; Herschlag, D.; Nazaretian, K. L. J . Am. Chem. Soc. 1986,
Ack n ow led gm en t. We thank NSERC of Canada for
support of this research. I.H.U. also thanks KOSEF of
Korea for Visiting Fellowship.
1
08, 479.
23) (a) Bernasconi, C. F. Adv. Phys. Org. Chem. 1992, 27, 119. (b)
Bernasconi, C. F. Acc. Chem. Res. 1987, 20, 301.
24) Buncel, E.; Um, I. H.; Hoz, S. J . Am. Chem. Soc. 1989, 111,
71.
(
(
9
J O9915776