Micro Process Technology and Novel Process Windows –Three Intensification Fields Svetlana Borukhova and Volker Hessel - Process Intensification for Green Chemistry - page 136

performed in a microcapillary reactor. A temperature increase from 453 to 533 K sped up
the reaction by a factor of 30, allowing a reduction of the inner reactor hold-up from 500 to
8m 3 and a decrease in the power of the explosion by factor of 6.3 [291].
Process simplification was achieved for the core bromination of toluene and for
photoirradiation in the side-chain bromination of toluene and m-nitro toluene through
avoidance of the need for Lewis acid catalysts in core substitution and in photointiation
for side-chain substitution, respectively. Catalyst-free Toluene bromination was com-
pleted by Loeb et al. within 2.0-3.9 minutes, and at high Ts practically all brominated
species were core-substituted. The photoinitiation-free bromination of m-nitrotoluene in
the side-chain position was performed at elevated temperatures (170-230 C). The
space-time yield was multiplied by a factor of 18 and the turnover of nitrotoluene
increased from 40 to 95% [292].
The click chemistry synthesis of 5-substituted tetrazoles from cyanides and NaN 3 in a
microreactor was performed safely and efficiently and with a broad substrate scope [293].
Process simplification was achieved, since no metal promoter was needed and a near-
equimolar amount of NaN 3 was sufficient, with no need for an excess. The synthesis was
also safer because shock-sensitive metal azides such as Zn(N 3 ) 2 are avoided (as HN 3 is
formed in situ) and unreacted NaN 3 is quenched in line with NaNO 2 . High-T (190 C)
processing leads to high reaction rates and short reaction times. Moreover, compared to
batch processing, the flow synthesis is scaleable.
High p is currently being investigated as a candidate for Cu-catalyst replacement in
1,3-dipolar cycloaddition with preservation of regioselectivity under continuous
flow conditions. Hessel and coworkers developed a home-built high-p,T setup (see
Figure 4.20) with limits of 300 C and 400 bar [193,194]. Multistep synthesis of the
anticonvulsant drug Rufinamide (see Scheme 4.11) is to be speeded up and brought to a
commercial scale.
Figure 4.20 High-p,T setup built by Hessel et al. , consisting of two HPLC pumps, high-T
reaction followed by quenching zone, sample loop and back-pressure regulator [193,194].