Beilstein Journal of Organic Chemistry 2009, 5, No. 34.
3
4
5
.
.
.
cipated that the combination of low pressure CO/V-65 could be
successfully applied to the TTMSS-mediated three component
carbonylative-coupling reaction of 1-iodooctane (9) [26,27] in a
microflow system using methyl vinyl ketone and acrylonitrile as
acyl radical traps (entries 6 and 7 ). Gratifyingly, in both cases,
good yields of the three-component coupling products were
formed by using reduced CO pressure.
7.
Usutani, H.; Tomida, Y.; Nagaki, A.; Okamoto, H.; Nokami, T.;
Conclusion
We have developed a facile platform to conduct radical
carbonylation under CO pressure in a flow system comprised of
a T-shaped mixer and a tabular residence time unit. Using V-65
as a radical initiator, we were able to carry out typical tin- or
silicon-based radical carbonylation reactions leading to alde-
hydes, unsymmetrical ketones, and a lactam, in a continuous
microflow system.
8
9
1
1
.
.
2
1.Bogdan, A. R.; Mason, B. P.; Sylvester, K. T.; McQuade, D. T.
1
1
1
Experimental
Typical procedure for radical carbonylation in a microflow
system. The radical formylation of 1-bromododecane (1).
1
2
-Bromododecane (1, 1 mmol, 249.5 mg), V-65 (0.1 mmol,
4.8 mg), Bu3SnH (1.2 mmol, 352.9 mg), and decane (59 mg)
9
as an internal standard were dissolved in toluene (50 mL). The
toluene solution was placed in a syringe (17 mL), which was
then attached to a syringe pump. The system was pressurized
with CO (83 atm) by means of the pressure control valve. The
flow rate of CO was controlled at 0.14 mL/min by the mass
flow controller. The toluene solution was introduced at a flow
rate of 0.37 mL/min, then was mixed with CO in the T-shaped
micromixer (i.d. = 1000 μm). The reaction was then fed into the
residence time unit, which was immersed in an oil bath and
heated at 80 °C. The time needed for the reaction mixture to
travel through the residence time unit was expressed as the
residence time (12 min). The mixture of products was collected
at the outlet. The initial effluent exiting the microflow reactor
was discarded (ca. 20 min) until a stable gas-liquid mixing was
achieved, and the following portion was collected for a 10 min
period. The yield was determined by GC analysis, and the
product was identified by comparison of 1H NMR spectrum and
a retention time for GC analysis with those of authentic sample.
1
1
1
0.Murphy, E. R.; Martinelli, J. R.; Zaborenko, N.; Buchwald, S. L.;
2
22.Ryu, I.; Miyazato, H.; Kuriyama, H.; Matsu, K.; Tojino, M.;
2
3.Tojino, M.; Otsuka, N.; Fukuyama, T.; Matsubara, H.; Schiesser, C. H.;
2
2
2
2
Acknowledgments
We thank JSPS/MEXT Japan and MCPT/NEDO for their finan-
cial support of this work.
References
1.
2.
Hessel, V.; Renken, A.; Schouten, J. C.; Yoshida, J., Eds. Micro
Process Engineering; Wiley-VCH: Verlag, 2009.
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