Scheme 2. Reaction scheme of the KS reaction carried
mass transfer effects are known for the Kolbe-Schmitt
synthesis. However, it has to be considered that the actual
temperatures (including the temperature average) in the continu-
ous processes may differ from that of the batch, even when the
set temperature (of the oil bath or from the microwave
calibration) is the same as the oil bath temperature of the batch
process. This is due to axial temperature gradients from
processing with an incoming cold solution being gradually
heated up. The motivation to use microprocess technology in
the context of this paper thus is to explore the impact of novel
process windows,6 e.g., by applying high temperatures and
pressures to considerably shorten reaction times and increase
space-time yields.
1.3. Microwave as Alternative Energy Source for Reac-
tor Heating. Microwaves are electromagnetic waves which
upon irradiation of a solvent can induce (pseudo) separated
charges in a molecule, which cause increasing heat. Microwaves
have been used for more than two decades for organic synthesis,
mainly in batch mode, as demonstrated by a large number of
successfully carried out organic reactions.18-21 Recently, re-
searchers started to investigate continuous microwave processing
in capillaries, and more rarely also with microdevices.22-26 The
potential of microwaves for solvent and support-free organic
synthesis has been outlined.27 Microwave equipment manufac-
turers meanwhile offer special tools for continuous processing,
and reports were made about microwave scale-up and mini-
plant application.28,29 It was demonstrated that the combination
of microwave heating and micro/milli process technology has
advantages over the single approaches and conventional
technology.
during this reaction
continuous process, and the process intensification by use of a
capillary reactor with a millimeter-sized diameter operated in
a novel process window,6 termed high-p,T conditions, was
demonstrated.7,8
1.2. Process Intensification by Novel Process Windows
in Milli- Or Microreactors. Milli and micro process engi-
neering9-15 facilitates operation at high pressures and temper-
atures due to the small internal volumes.7,8,16,17 This allows safe
operation in regimes that are otherwise dangerous or difficult
to reach, unless a high degree of technical expenditure is
accepted. This can, e.g., be used to massively expand the upper
operational limit for solvents, which for conventional processing
practically is often determined by the solvent boiling point
(reflux condition).7,8,16 A moderate increase in pressure can shift
the latter substantially and thus extend the temperature window.
Boiling points are for water 100 and 250 °C at 1 and 40 bar,
respectively.
Following this motivation, the solution-based Kolbe-Schmitt
reaction with resorcinol and KHCO3 giving 2,4-dihydroxyben-
zoic acid has been successfully processed in a continuous way
by making use of capillary reactors (milli process technology)7
(see Scheme 2).
Yields up to 47% were reached, which almost equals the
performance of the Kolbe-Schmitt synthesis by an aqueous
batch procedure. By virtue of the much higher temperatures
applied (up to 120 °C more), reaction times were up to 1000
times lower, i.e., coming down from hours to tens of seconds.
It was expected and proven by experiment that yields for
continuous and batch processes are roughly the same under the
same pressure and temperature, since no pronounced heat and
1.4. Solventless Processing and Ionic Liquids. Solvents
help to bring reactants together in one phase, which otherwise
would stay separate and would not or only slowly react. Solvents
may also dilute a hazardous mixture to a concentration level
which can be handled. However, solvents increase the reaction
volume and thus increase the size and cost of equipment, may
be flammable, may be poisonous, require purification (stripping,
distillation) and respective equipment, and produce additional
waste. By diluting the reactants, the presence of solvents lowers
the productivity of reactors.
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Org. Process Res. DeV. 2005, 9, 479.
For all these reasons, there is a trend in modern chemical
processing towards solvent-free processing to help keep the
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2006, 10, 1144.
(9) Geyer, K.; Codee, J. D. C.; Seeberger, P. H. Chem.sEur. J. 2006,
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Chemistry, Vol 25; Mannhold, R., Kubinyi, H., Folkers, G., Eds.;
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