The mechanism of on-water catalysis

Article abstract of DOI:10.1002/chem.201001705

Acid catalysis by interfacial water: A new mechanism is proposed for onwater catalysis, the acceleration of organic reactions when conducted in aqueous emulsions. It involves the protonation of a substrate by water, driven by the strong adsorption of hydroxide ions at aqueous interfaces with oils. This accounts for the specific role of water, and a deuterium isotope effect, at the interface, on reactions known to be acid-catalysed.

Full text of DOI:10.1002/chem.201001705

DOI: 10.1002/chem.201001705
The Mechanism of On-Water Catalysis
[a]
James K. Beattie,* Christopher S. P. McErlean,* and Christopher B. W. Phippen
[
1]
Sharpless and co-workers used the term on-water to de-
scribe the substantial rate acceleration that is observed
when some insoluble organic reactants are stirred in aque-
ous suspension. We now propose a mechanism that accounts
for the phenomenon of on-water catalysis. Three of the ob-
servations of Sharpless and co-workers are directly pertinent
to the mechanism we propose below. Firstly, the reaction
mixture must be heterogeneous, that is, there must be an in-
terface between the organic reactants and water. The pres-
ence of some methanol in the aqueous phase made little dif-
ference to the rate of the reaction, “but the rate slowed con-
siderably when enough methanol was used to make the re-
action homogeneous.” Secondly, the interface must be with
an aqueous phase. An emulsion formed with the organic re-
actants in perfluorohexane gave an only slightly enhanced
rate. Thirdly, there was a significant solvent isotope effect,
stant can be estimated from the pH dependence of the zeta
potentials of oil drops in water to be at least 10 .
8
[6]
At first this seems unlikely to account for acid catalysis at
the same interface, but a little reflection reveals that this
counterintuitive result is to be expected. Consider a sub-
strate that is activated by protonation. Reaction with water
at the interface results in the protonated activated substrate
and a hydroxide ion that is stabilised by its strong adsorp-
tion at the interface. This drives the protonation equilibrium
of the substrate [Eq. (1)] strongly to the right and accounts
for acid catalysis even in neutral solution.
S þ H O Ð SH þ OHꢀ
þ
ð1Þ
ð2Þ
2
ads
þ
SH ! products
with a noticeably slower rate in D O.
This mechanism accounts for all of the available evidence
described above. It requires water, at the interface with the
organic reactants, which provides the conditions for the pro-
tonation of the substrate, driven by the adsorption of the hy-
droxide ion product, with the associated deuterium isotope
effect, leading to acid catalysis and the enhanced rate.
We now describe additional experimental evidence consis-
tent with this mechanism. We chose to examine another
Diels–Alder reaction, that between cyclopentadiene and di-
methylfumarate (Scheme 1). In addition to having a rate
that is convenient to measure, this reaction possesses other
advantages: 1) the use of symmetric reagents removes any
endo, exo stereochemical ambiguities; 2) the ester units of
the dienophile do not react with water itself, so no back-
ground rate correction is required; and 3) the volatile diene
can be easily evaporated allowing the relative proportions
of the non-volatile fumarate and product to be measured di-
rectly by NMR spectroscopy.
2
Our proposed mechanism is supported by two additional
considerations. One is that all of the reactions that have
been described as accelerated by the on-water effect (with
the possible exception of those of metal complexes) are also
[1,2]
known to be subject to acid catalysis.
This suggests that
acid–base chemistry at the interface is responsible. Hence
the second consideration is our recently developed model
that explains the intrinsic charge that develops at the inter-
face of water with low relative permittivity (low dielectric
[3]
constant) materials. This model accounts for the numerous
observations made over many decades that the surface of
water at these interfaces, whether they are with gas, liquid
or solid, becomes negatively charged by the strong adsorp-
[4,5]
tion of hydroxide ions.
The adsorption equilibrium con-
[
a] Prof. J. K. Beattie, Dr. C. S. P. McErlean, C. B. W. Phippen
School of Chemistry
The University of Sydney
NSW, 2006 (Australia)
Fax : (+61)2-9351-3329
E-mail: james.beattie@sydney.edu.au
christopher.mcerlean@sydney.edu.au
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201001705.
Scheme 1. Diels–Alder [4+2] cycloaddition.
8972
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Chem. Eur. J. 2010, 16, 8972 – 8974

COMMUNICATION
[1,2]
Following the approaches adopted by previous authors,
we first compared the rates of reaction in different solvents
by monitoring the conversion of fumarate to product using
identical amounts of reactants for a fixed reaction time of
thirty minutes (Table 1). Because of the generally low solu-
Table 1. Solvent effect on the yield of the [4+2] cycloaddition of cyclo-
pentadiene and dimethylfumarate at room temperature after a reaction
time of 30 min.
[
a]
[b]
Solvent
on-water
on-D
at-water
neat
THF (0.1m)
THF (0.2m)
DCM (0.1m)
DCM (0.2m)
on 10 mm aq. NaCl
Conversion [%]
75
56
40
45
16
32
16
40
69
2
O
Figure 1. Plot of ꢀln [furmarate] versus time, showing first-order kinetics.
[
[
a] For standard reaction conditions see the Supporting Information.
b] Measured by H NMR analysis of the reaction mixture after evapora-
1
tion of the diene.
bility of the organic reactants in water, it is often difficult to
measure the very slow reactions of the substances fully dis-
solved in-water. We have adopted a pragmatic approach by
comparing the on-water rate of the reaction performed with
vigorous stirring to create an emulsion to what we will term
the at-water rate of the reaction performed with gentle stir-
ring so that the organic phase is not mixed with the aqueous
phase and the area of the interface between the phases is
minimised. This should approximate the rate of the neat re-
actants mixed together, a supposition supported by the data
in Table 1, with 45% conversion for the neat reaction and
Figure 2. Comparison of reaction rates at-water (ꢁ), on-water (
O (*) and on-water using a piston homogeniser (~).
&
), on-
D
2
40% conversion for the at-water conditions. By this means
we observed that the reaction was indeed accelerated by
rapid stirring to form an emulsion, with a higher yield than
under at-water conditions of gentle stirring, or dissolved in
THF, or neat. The same high conversion was found on-water
and on-water containing 1 mm, or 10 mm NaCl (see the Sup-
porting Information).
Subsequently we observed the first-order kinetics of the
reaction by measuring the disappearance of the fumarate
from replicate samples quenched at regular intervals
When the reaction mixture was passed through a four-
[9]
stage piston homogenizer to reduce the droplet size the
rate was increased significantly (Figure 3) reaching 49%
conversion in the six minutes required to homogenize the
solution. (It will be necessary to study a slower reaction to
make a quantitative determination of the effect of droplet
size on the rate.)
Up to this point, the reactions were performed in water at
its natural pH of 5.6 with no protection from air. To exclude
the possibility that the observed rate enhancements resulted
from partial dissolution of the reactants into the acidic bulk
solvent, the reactions were conducted at pH 9. As shown in
Figure 3, the rate of the on-water reaction was independent
of the pH of the aqueous medium. Indeed, the on-water re-
action was faster than the at-water reaction conducted in
1 mm, 10 mm, or 1m aqueous HCl (see the Supporting Infor-
mation). In no case was any ester hydrolysis observed.
All of these observations are consistent with the mecha-
nism proposed above. The rate-determining step of the reac-
tion occurs at the interface and increases with the surface
(
Figure 1).
The same technique was used to determine the influence
of D O on the reaction rate. As shown in Figure 2, the rate
2
is clearly faster on-water than at-water, and faster on-water
than on-D O, with a kinetic isotope effect of 1.4. A value of
2
1.2 was reported for another cycloaddition reaction accord-
ing to unpublished results cited in reference [7]. According
to our mechanism the deuterium isotope effect will be a
complex product of the effect on the autolysis of water, any
effect on the adsorption of hydroxide ion at the interface, as
well as the effect on the protonation and reaction of the
[8]
substrate.
Chem. Eur. J. 2010, 16, 8972 – 8974
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
8973

J. K. Beattie, C. S. P. McErlean, and C. B. W. Phippen
a carbocation intermediate, which is in perfect agreement
with our proposed mechanism. In the Supporting Informa-
tion we briefly describe how other reactions that do or do
not display on-water catalysis are consistent with the pro-
posed mechanism.
In summary, the on-water effect can be explained by a
simple acid-catalysis mechanism facilitated by the strong ad-
sorption of the hydroxide ion by-product at the oil–water in-
terface. With this understanding, the effect can be exploited
in a rational way for new synthetic pathways.
Acknowledgements
This work was supported by the Australia Research Council. We thank
Dr. Alex Djerdjev for assistance with the homogenisation.
Figure 3. Rate dependence on pH. (
) on pH 9 water, (*) on-water.
&
area of the interface. It does not involve dissolution of the
dieneophile into the aqueous medium, as the rate is inde-
pendent of the aqueous pH. It is not affected by the addi-
tion of mm NaCl to the water, which has the effect of releas-
ing the protons in the double layer by replacing them with
sodium ions, but these released protons are not catalytically
active. Neither are the strongly adsorbed hydroxide ions, for
they lie in a deep thermodynamic well; hence no on-water
accelerated reactions are base-catalysed. The rate-determin-
ing step is the protonation of the fumarate ester by interfa-
cial water, which accounts for the deuterium isotope effect,
and the first-order kinetics.
Keywords: biphasic catalysis
chemistry · interfaces · water chemistry
·
cycloaddition
·
green
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[7]
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Received: March 31, 2010
Published online: July 6, 2010
8974
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Chem. Eur. J. 2010, 16, 8972 – 8974