Number range CHAPTERReaction Dynamics in Supercritical Fluid Media for
Synthetic Organic Reactions

J.I. Steinfeld \[a\], R.L. Danheiser \[a\], J.W. Tester \[b\], J. Taylor
\[c\], M. Timko \[c\], and Jin Qian \[d\]

The use of supercritical fluids (SCFs) as non-toxic solvent replacements
in fine chemical synthesis is one strategy for waste minimization that
is gaining increasing attention in research and industrial applications.
Because SCF properties change significantly with relatively small
changes in pressure or density in the critical region, parameters such
as solubilities, reaction rates, and selectivities may be
\"\"tunable\"\", making SCFs particularly versatile and desirable
reaction media. However, basic data and theoretical models are lacking
for solvation of reactants and the influence of solvent density on
reaction pathways in SCFs. In the work supported by the TSE, the
reaction dynamics of model organic reactions in supercritical water
(SCW) and supercritical carbon dioxide (scCO2) have been investigated
using a variety of techniques.

The rate of methyl-t-butyl ether hydrolysis in sub-critical and SCW was
measured at 250 bar over a range of temperatures from 150 to 600 degrees
C. An assumed first-order experimental rate constant shows a local
maximum below the critical temperature of water (374 C) followed by a
local minimum just above the critical temperature. This behavior can be
attributed to changes in the properties of water as the temperature is
increased through the critical point. In particular, the ion
dissociation constant of water decreases by more than 5 orders of
magnitude from 325 to 400 degrees C at 250 bar. Therefore, an
acid-catalyzed mechanism should exhibit this local maximum and minimum
based on changes in the concentration of H+ in the system superimposed
on normal Arrhenius behavior. A rate expression was fit to the data
assuming an acid-catalyzed pathway with a first-order dependence on
\[H+\] and good agreement was achieved; furthermore, experiments
conducted with excess acid at known pH verified the rate enhancement due
to acid catalysis. Ab initio (density functional theory) calculations
validated the proposed reaction mechanism.

Our work with Diels-Alder reactions demonstrates, from a technological
standpoint, that scCO2 can accelerate reaction rates of carefully
selected synthetic transformations. Furthermore, and more importantly,
we were able to develop a mechanistic understanding of the
molecular-level solvation effects which are important to such rate
accelerations. This is the first work of this kind; previous efforts
have focused on the physicochemical properties of scCO2 (such as its
miscibility with gases such as H2) to generate technological advantages.
Although we used a specific Diels-Alder cycloaddition reaction as our
model, we expect our results to be applicable to a wide range of
synthetic transformations. The probable impact of our work is to make
scCO2 a more attractive solvent for industrial applications.

The use of power ultrasound to generate emulsions of near or
supercritical carbon dioxide and water is a powerful new tool for
developing environmentally benign processes. The motivation for this
work is the fact that scCO2 and water have complementary solvent powers,
suggesting good solubility for a wide range of compounds when the two
are used together. Power ultrasound is an efficient means of dispersing
the two phases as micron-sized droplets which, unlike similar efforts in
the field, does not rely on cosolvents or additives. Pulsed ultrasound
was used to maintain emulsions indefinitely; however, the emulsions
broke in tens of minutes upon termination of acoustic irradiation. The
limited kinetic stability of the emulsions is expected to facilitate
post-reaction separations and limit mutual phase entrainment. Using
kinetic data from a systematic study of a series of benzoyl halides, we
were able to validate models for the physical processes occurring during
carbon dioxide/water phase transfer reactions. Future applications of
this work include homogeneous catalysis, electrochemistry, and enzymatic
catalysis.

We have shown that scCO2 can be used as a delivery solvent to access the
unique catalytic properties of water. As a model, we investigated the
Diels-Alder cycloaddition of methyl vinyl ketone to cyclopentadiene, and
demonstrated that carbon dioxide/water (when stimulated using power
ultrasound) could be an efficient solvent for synthetically important
reactions. In particular, we found that the rates (conversion) and
selectivity of the reaction could be improved relative to that in pure
scCO2, while the throughput could be improved relative to that in water.
Ultrasonic agitation further improved conversion and selectivity.
Investigations are under way to expand the synthetic scope of this
technique. Based on the large number of chemical reactions which display
unusual behavior in water, we expect carbon dioxide/water emulsion
reactions to be a general methodology.

A study of partition coefficients of organic solutes between carbon
dioxide and water provided an opportunity to develop empirical
correlations to estimate partition coefficients of commercially
important reagents without measurements. This work will prove useful for
the development of water/carbon dioxide contactors and interpretation of
kinetic data in the biphasic system.

Supercritical fluids are one of a number of "green chemistry" strategies
which can reduce the use of toxic and hazardous solvents in chemical
synthesis. Unfortunately, this topic is not well represented in what we
teach our chemistry students. We are beginning to introduce these
concepts into the chemistry curriculum, in both lecture subjects such as
organic and introductory physical chemistry, and in the laboratory
subjects. The use of alternatives to hazardous solvents is a key part of
the Department-wide initative to reduce the amount of hazardous waste
generated in our research laboratories, in compliance with an EPA - MIT
consent decree.

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\[a\] Department of Chemistry and Laboratory for Energy and Environment

\[b\] Department of Chemical Engineering and Laboratory for Energy and
Environment

\[c\] Martin Family Society Graduate Fellow

\[d\] Wallenberg Foundation Postdoctoral Fellow in Environment and
Sustainability