Chemistry Reference
In-Depth Information
systems. Increases in boiling points of many com-
monly used solvents are significant with modest rises
in pressure [69], and at 2-3 MPa relatively high
temperatures can be attained safely for a variety of
solvents. Such conditions can be obtained with the
microwave reactors but not readily with typical
glassware. Higher temperatures have led to reaction
times up to three orders of magnitude shorter than
those for the same preparations carried out conven-
tionally [9,65,68].
Benefits of high temperature also can be gained
with traditional autoclaves but the energy usually
is applied to the reaction mixture conductively, by
external heating. Consequently, the rate of temper-
ature increase usually is low, thermal gradients
develop and even by stirring batch reactions not all
of the sample will be at the temperature of the
applied heat. With microwaves, the whole sample
can be irradiated and the energy input can be
adjusted readily to match that required. Bulk heating
combined with efficient stirring diminishes the tem-
perature gradients.
Scheme 17.5
Pathway for catalytic ether synthesis [71].
tively constant. Although HX and RX are stoichio-
metric reactants or products in Equations 1 and 2,
they do not appear in the sum (Equation 3). The net
procedure involves condensation of two molecules
of ROH to give R
2
O plus water. The process has been
demonstrated with primary and secondary alcohols,
including base- and acid-labile compounds. Advan-
tages for clean production are the high atom econ-
omy, salts are not formed, RX often is recoverable,
the reaction does not require the addition of strong
acids or bases and water is the major by-product.
Etherification
6.2 Rapid heating, cooling and ease of use
for high-temperature reactions
Conditions employing elevated temperatures with
less catalyst, a milder catalyst or without the addi-
tion of catalyst can be an attractive alternative to
those utilising aggressive reagents at lower tempera-
tures. A recent example concerns a catalytic, thermal
etherification that produces minimal waste and can
be carried out near neutrality [70]. This represents a
cleaner alternative to the 150-year-old Williamson
procedure, in which the ether is produced through
substitution of an alkyl halide by a strongly basic
alkoxide or phenoxide. The Williamson synthesis
generates a stoichiometric amount of waste salt, and
sometimes base-catalysed elimination of hydrogen
halide can compete.
The new process is suited to production by MBR
or CMR and is shown in Scheme 17.5 for a sym-
metrical ether. An excess of alcohol (ROH) and a
catalytic amount of RX are heated. A solvolytic dis-
placement reaction between RX and ROH affords
R
2
O along with HX or its elements (hereafter referred
to as HX; Equation 1). The liberated HX attacks
another molecule of ROH to form water and to
regenerate RX (Equation 2). If the rates of both reac-
tions are comparable, the concentration of HX will
be low throughout and that of RX will remain rela-
Vessels for microwave-assisted chemistry usually are
made from thermal insulators and, as indicated by a
temperature profile communicated recently [71], the
benefits of rapid heating can be diminished if the
opportunity for work-up is delayed by slow cooling.
Decomposition of thermally unstable products also
can occur.
In the CMR, rapid cooling takes place through an
in-line heat exchanger adjacent to the microwave
heating zone [65]. Mixtures can be cooled immedi-
ately, while still under pressure, to prevent losses of
volatiles and to minimise decomposition of thermally
labile products.
The MBR has an incorporated cold-finger that
offers advantages for cooling microwave reactions in
pressure vessels [68]. Because the cold-finger con-
tacts the reaction mixture directly, cooling can be ini-
tiated at any time during operation and is efficient
because it is not
via
the container. Temperature and
pressure monitoring, as well as stirring, can be main-
tained during the cooling process, allowing access to
the vessel at the earliest opportunity.
As discussed for the following four examples, the
CMR and MBR have been useful for reactions that
