The effect of solvent on the α-effect: The MeCN-H2O solvent system

Article abstract of DOI:10.1039/b005610n

The increasing α-effect observed in MeCN-H₂O solvent mixtures, which contrasts with the previously found bell-shaped dependence on solvent composition in the DMSO-H₂O system, is attributed to the differential solvent effect on basici

Full text of DOI:10.1039/b005610n

The effect of solvent on the a-effect: the MeCN–H O solvent system†
2
a
a
b
Ik-Hwan Um, Young-Min Park and Erwin Buncel*
a
Department of Chemistry, Ewha Womans University, Seoul 120-750, Korea
Department of Chemistry, Queen’s University, Kingston, Ontario K7L 3N6, Canada.
E-mail: buncele@chem.queensu.ca; Tel: 613-533-2635; Fax: 613-533-6669
b
Received (in Corvallis, OR, USA) 10th July 2000, Accepted 23rd August 2000
First published as an Advance Article on the web 18th September 2000
The increasing a-effect observed in MeCN–H
2
O solvent
the reaction of PNPA in DMSO–H
2
O mixtures has been
mixtures, which contrasts with the previously found bell-
explained through a dissection of ground-state and transition-
7c
shaped dependence on solvent composition in the DMSO–
state contributions. In that system the basicities of the a-Nu
2
2
H
2
O system, is attributed to the differential solvent effect on
(Ox ) and normal-Nu (ClPhO ) exhibit a parallel dependence
on the DMSO–H
O composition.7
The addition of MeCN to H O could influence not only the
reaction rate but also the basicity of the anionic nucleophiles.
Although the pK values for some phenols, carboxylic acids and
amines in pure MeCN are available,
been reported for MeCN–H O mixtures. Therefore, we have
measured the relative basicity of Ox and ClPhO in MeCN–
O mixtures using piperazine as a reference base. One can
define DpK as the pK difference between the conjugate acids
basicities of the a- and normal nucleophiles in the former
2
case.
2
Among the possible causes of the a-effect, that is the enhanced
a
12a,b
reactivity of nucleophiles having an unshared pair of electrons
a
very few pK data have
1
8b
adjacent to the nucleophilic centre, the effect of solvent has
2
–9
been particularly controversial.2 As one possible approach to
2
2
the problem, in 1986 we examined the reactivities of an a-
H
2
2
nucleophile, butane-2,3-dione monoximate (Ox ), and a nor-
a
a
2
2
2
mal nucleophile, p-chlorophenoxide (ClPhO ) with p-nitro-
of the nucleophile (Ox or ClPhO ) and piperazine, i.e. DpK
a
2
phenyl acetate (PNPA) in dimethyl sulfoxide (DMSO)–H
2
O
= pK
a
of the conjugate acid of the nucleophile (Ox or
7a
2
mixtures, due to the unique properties of this solvent
system.10 Unexpectedly, we observed a bell-shaped profile for
the dependence of the a-effect on solvent composition, with a
maximum at ca. 50 mol % DMSO.7a More recently, we
observed a similar bell-shaped a-effect trend for the corre-
sponding reactions of p-nitrophenyl diphenyl phosphinate
ClPhO ) 2 pK
a
of the conjugate acid of the reference base
represents the
relative basicities of these nucleophiles. We determined DpK
(piperazine). Hence, the magnitude of DpK
a
a
a
values spectrophotometrically using the relationship: DpK =
2
2
log [HA]eq[B]eq/[A ]eq , in which [HA]eq represents the
equilibrium concentration of the conjugate acid of the nucleo-
PNPDPP).7b However, a contrary result was reported for the
phile, and [B]eq and [A ]eq represent the equilibrium concentra-
2
(
2
reaction of PNPA with O-iodosylbenzoate (IBO ) and
tion of the reference base (piperazine) and the nucleophile,
2
ClPhO : the a-effect showed no maximum but decreased
respectively. The DpK
a 2
values thus determined in MeCN–H O
steadily as the DMSO content in the reaction medium
increased.9 Clearly, more work is called for in order to
understand the effect of solvent on the a-effect.
mixtures are summarized in Table 1. As shown in the table, the
2
2
DpK
a
values of Ox and ClPhO in H
values of the conjugate acids of Ox ,
ClPhO and piperazine in H O at 25 °C, have been reported to
2
O are 20.38 and 20.44,
2
respectively. The pK
a
2
We have now extended our study to a different solvent
2
12c
be 9.44,7b 9.38 and 9.82, respectively, i.e. the DpK
determined in H O in the present study are identical to the
literature values. It is also noted that Ox and ClPhO are less
basic than piperazine in H O but appear to be more basic upon
addition of MeCN. This is consistent with the report that the
increase in pK values upon changing medium from H O to
MeCN is more significant for phenols than for amines: the pK
enhancements were reported to be 12–17 and 7–8 in pK units
for phenols and for the conjugate acids of alicyclic secondary
12c
system, acetonitrile (MeCN)–H
2
O mixtures, and have found a
a
data
new type of solvent effect on the a-effect, namely an increasing
2
2
2
a-effect. A plausible cause of this trend for the reaction of
2
2
PNPA with Ox and ClPhO (eqn. 1) in MeCN–H
2
O mixtures
2
is herein presented.
-p + Nu2
CH
?
a
2
CH
3
C(O)OC
6
H
4
NO
2
C(O)-Nu + p-NO
2
C
6
H
4
O2
a
3
Nu2 = CH
C(O)C(CH
)NNO (Ox ), an a-nucleophile
2
2
a
3
3
2
2
p-ClC
6
H
4
O
(ClPhO ), a normal nucleophile
(1)
Kinetic studies were performed spectrophotometrically under
pseudo-first-order conditions with the nucleophile in excess.
Pseudo-first-order rate constants (kobs) were obtained from
linear plots of ln (A
H
2 A
) were calculated from the slope of the linear
plot of kobs vs. nucleophile concentration. As shown in Fig. 1,
t
) vs. t. Second-order rate constants
Ox2
ClPhO2
(k
and k
Ox2 ClPhO2
the magnitude of the a-effect (k
/k
) increases as the
O to
mol % MeCN in the medium increases, from ca. 100 in H
00 in 90 mol % MeCN. Recently, we found a decreasing a-
effect trend for the reaction of PNPA with hydroxamates in
MeCN–H O mixtures, and a shift in equilibrium from an OH
acid to an NH acid upon addition of MeCN to H O was
2
5
2
2
8b
attributed as responsible for the observed a-effect trend.
Transition-state stabilization is one possible cause of the a-
effect11 and recently the bell-shaped a-effect trend observed for
†
Electronic supplementary information (ESI) is available: second-order
rate constants for the reaction of p-nitrophenyl acetate with butane-
Fig. 1 Plots showing the effect of solvent on the a-effect (ka2Nu/knormal2Nu
)
Ox2 ClPhO2
2
2
,3-dione monoximate and p-chlorophenoxide in MeCN–H
5 °C. See http://www.rsc.org/suppdata/cc/b0/b005610n/
2
O mixtures at
for the reaction of PNPA at 25.0 °C: k
/k
2
in MeCN–H O (5);
Ox2 ClPhO2
O (2); kIBO2/k
7b
ClPhO2
in DMSO–H
2
O (8).9
k
/k
in DMSO–H
2
DOI: 10.1039/b005610n
Chem. Commun., 2000, 1917–1918
This journal is © The Royal Society of Chemistry 2000
1917

Table 1 Summary of the relative basicity of the nucleophile (DpK
of the conjugate acid of the nucleophile—pK of the conjugate acid of the
O mixtures of varying composi-
a
= pK
a
propose therefore, that the differential solvent effect on the
a
basicity of these nucleophiles is the cause of the contrasting a-
reference base, piperazine) in MeCN–H
2
2
effect trends observed for the reaction of PNPA with Ox and
a
tions at 25.0 ± 0.1 °C
2
ClPhO in DMSO–H
2
O and in MeCN–H
2
O mixtures.
Furthermore, it is found that a plot of log kOx2/kClPhO2
against DDpK is linear with a slope of 0.85 (Fig. 2). This
provides evidence that the increase in the DDpK values is
Mol % MeCN
DpK
a
(Ox2)
DpK
a
(ClPhO2) DDpK b
a
a
0
20.38
0.58
1.17
1.80
2.32
2.69
3.43
3.90
4.96
5.85
20.44
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
1
2
3
4
5
6
7
8
9
0
0
0
0
0
0
0
0
0
almost fully reflected in the increase in the a-effect for the
2
2
reaction of PNPA with Ox and ClPhO upon addition of
MeCN into the reaction medium.
I. H. U. is grateful for financial support from KOSEF of
Korea (1999-2-123-003-5). E. B. thanks NSERC of Canada for
a research grant.
a
a a
The uncertainty in DpK values is estimated to be less than ±0.03 pK
Notes and references
b
2
2
units. DDpK
a
= DpK
a
a
(Ox ) 2 DpK (ClPhO ).
1
2
J. O. Edwards and R. G. Pearson, J. Am. Chem. Soc., 1962, 84, 16.
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(
(
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amines (e.g. piperidine and morpholine), respectively, upon
O to MeCN.1
2
2a,b
solvent change from H
The difference in the relative basicity between Ox and
3
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4869.
2
(
2
ClPhO can be expressed as DDpK
a
, i.e. DDpK
a
=
2
2
DpK
a
(Ox ) 2 DpK
a
(ClPhO ). As shown in Table 1, DDpK
a
4 (a) G. Moutiers, E. Guevel, L. Villien and F. Terrier, J. Chem. Soc.,
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2
increases as the mol % MeCN in the medium increases, i.e. Ox
2
a
is more basic than ClPhO by 0.06, 0.50 and 0.95 pK units in
5
(a) I. H. Um, J. S. Lee and S. M. Yuk, J. Org. Chem., 1998, 63, 9152;
b) K. R. Fountain, T. W. Dunkin and K. D. Patal, J. Org. Chem., 1997,
H
2
O, 50 and 90 mol % MeCN, respectively, which contrasts
(
6
1
with the situation, noted above, for DMSO–H O mixtures. We
2
2, 2738; (c) E. Buncel, C. Chuaqui and H. Wilson, J. Am. Chem. Soc.,
982, 104, 4896.
6
7
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8
9
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1
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1
987, 860.
1
1
0 E. Buncel and H. Wilson, Adv. Phys. Org. Chem., 1977, 14, 133.
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4
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1
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(
5
Fig. 2 Plot of log kOx2/kClPhO2 vs. DDpK
for the reaction of PNPA with
O mixtures at 25.0 ± 0.1 °C.
Selected Data for Molecular Biology, ed. H. A. Sober, The Chemical
Rubber Co., Cleveland, OH, 1968.
a
Ox and ClPhO2 in MeCN–H
2
2
1918
Chem. Commun., 2000, 1917–1918