Abstract
Inductively heated copper wire inside a flow microreactor can
serve as a source for a catalytic copper species that promotes 1,3-dipolar
cycloadditions of alkynes with in situ formed azides to yield 1,2,3-triazoles.
The same setup was used to carry out decarboxylations of 2-alkynoic
acids and for the intramolecular C-O coupling of 2′-bromobiphenyl-2-carboxylic
acid.
Key words
click chemistry - copper - heterogeneous catalysis - microreactors - inductive heating
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19 Hazard warning: Aliphatic azides are
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data are available in the literature. We never encountered any hazards during
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of explosions.
20
Typical Procedure
for Triazole Syntheses
TM TU. The
collection vial was placed behind the scavenger cartridge. The system
was flushed with a DMF-H2 O mixture (5:1), and
the temperature was adjusted to 100 ˚C. After
the flow (flow rate 0.2 mL/min) and temperature values
reached a steady state a solution of bromide 4 (0.25
M), phenylacetylene (1 , 0.125), and sodium
azide (0.25 M, higher concentrations led to blockage of the system
due to precipitation) in DMF-H2 O was pumped
through the system (residence time approx. 10 min). After collection
of the crude product, the mixture was diluted with H2 O,
extracted with EtOAc, and dried (MgSO4 ). After evaporation
of the solvent the crude product was purified by flash chromatography
on silica gel to yield compound 5 in quantitative
yield as a slightly yellow solid.
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Typical Procedure
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TM TU.
The collection vial was placed behind the scavenger cartridge. The
system was flushed with MeCN, and the temperature was adjusted to 60 ˚C.
After the flow (flow rate 0.1 mL/min) and temperature values
reached a steady state a solution of 2-alkynoic acid 13 (0.1
M) in MeCN was pumped through the system (residence time approx.
20 min). After collection of the crude product, the solvent was
evaporated in vacuo, and the crude material was purified by flash
chromatography on silica gel to yield compound 14 in
93% yield as a yellow oil.
26
Synthesis of Benozopyranone
18
TM TU.
Behind the scavenger cartridge the collection vial was placed. The system
was flushed with DMF, and the temperature was adjusted to 200 ˚C.
After the flow (flow rate 0.1 mL/min) and temperature values
reached a steady state a solution of bromo acid 17 (0.04
M) in DMF was pumped through the system (residence time approx.
20 min). After collection of the crude product, the mixture was
diluted with H2 O, extracted with EtOAc, and dried (MgSO4 ).
After evaporation of the solvent in vacuo the crude product was purified
by flushing through a short pad of silica to yield compound 18 in 95% yield as a pale brownish
solid.
