Organic Process Research & Development
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260 mg) was dissolved in toluene (10 mL) and placed in
Self metathesis - but-2-ene-1,4-diol 8. A flow
chemistry protocol leading to 8 was elaborated on the
basis of a previously disclosed batch protocol.17 The
substrate propꢀ2ꢀenꢀ1ꢀol 7 (20 µL, 0.30 mmol) and
the HoveydaꢀGrubbs 2nd generation catalyst (19 mg,
0.030 mmol, 10 molꢀ%) were dissolved in acetone
(2.00 mL). The mixture was transferred to a reservoir
and pumped into the MJOD reactor at a rate of r = 0.40
mL min.ꢀ1 When the reactant/catalyst reservoir was
emptied, pure solvent (acetone) was pumped into the
MJOD reactor body at a rate r = 0.85 mL min.ꢀ1 to
provide a total residence time of 60 min. The
temperature of the MJOD reactor body was controlled
the reservoir R2. The reservoir R3 was filled with pure
toluene (V≈250 mL). The pump R3 was used to fill the
MJOD flow reactor with toluene. The reactor tubeo was
heated by passing temperatureꢀcontrolled water (30 C or
45 oC) through the reactor jacket using a circulating pump.
Two precision feeding pumps, P1 and P2, were utilized to
feed the substrate 1 and the Ruꢀcatalyst from the reservoirs
R1 and R2 and dispense accurately volumes/quantities at
the input section of the MJOD flow reactor body. The
substrate 1 solution was pumped using a rate of r = 3.33
mL min.ꢀ1 The HoveydaꢀGrubbs 2nd generation catalyst
solution was pumped with a rate r = 0.67 mL min.ꢀ1 The
overall reactor volumeꢀtime flow corresponded to 4 mL
minꢀ1 and provided a reactor residence time of 15 min. The
reaction experiments were conducted at temperatures of
30 oC or 45 oC.
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at a temperature of 25 C using the heat exchanger
(circulator) throughout the whole reaction experiment.
1-Tosyl-2,5-dihydro-1H-pyrrole 4. N,Nꢀdiallylꢀ4ꢀmethylꢀ
benzenesulfonamide 3 (0.261 g, 1.04 mmol) was dissolved
in methylenechloride (5 mL) that was added the Hoveydaꢀ
Grubbs 2nd generation catalyst (31 mg), that corresponded
to 5 molꢀ% of the catalyst. This mixture was transferred to
the reagent reservoir R1. The reservoir R3 was filled with
toluene (≈250 mL). The pump R3 was used to fill the
MJOD reactor with toluene. The jacketed reactor tube of
Conclusion
We have assembled a MJOD flow reactor platform
to successfully conduct various olefin metathesis
experiments. The achieved results were benchmarked
with other reaction platforms, revealing the MJOD
flow reactor to be better or at least equivalent in
productivity when compared to the other approaches.
Moreover, the investigation revealed that the MJOD
flow reactor platform can operate satisfactorily even
when the volume of the reaction mixture is only a
fraction of the net reactor volume, which
demonstrates that the MJOD flow reactor may be
operated as a plug flow reactor.
the MJOD reactor was heated by circulating water at a
o
temperature of 40 C by means of a circulator pump. The
reaction was conducted switching on the pump P1 that
furnished the MJOD flow reactor with reaction mixture at a
flow rate of r = 1.00 mL min.−1 When reservoir R1 was
emptied, the feeding pump P3 was switched on to provide
an pure solvent plug at a rate of r=0.85 mL min.−1 This
configuration provided a reactor residence time of 60 min.
1,4-dibromobut-2-ene 6. The substrate 5 (26 µL, 0.30
mmol) and the HoveydaꢀGrubbs 2nd generation catalyst (19
mg, 0.030 mmol, 10 molꢀ%) was dissolved in acetone
(2.00 mL) and transferred to reservoir R1. The mixture
was pumped (P1) into the MJOD reactor at a rate r = 0.40
mL min.ꢀ1 When the reservoir of the reaction mixture (R1)
was emptied, pure solvent (R3) was pumped (P3) into the
MJOD flow reactor with a rate of r = 0.85 mL min.ꢀ1 to
provide a total residence time of 60 min. The reactor heat
exchanger was maintained at a temperature of 25 oC.
Exerimental Section
General methods. Starting materials, reagents, catalyst and
solvents were purchased commercially and used without
further purification.
GLC analyses were performed on a capillary gas
chromatograph equipped with a fused silica column (L 25
m, 0.20 mm i.d., 0.33 ꢀm film thickness) at helium
pressure of 200 kPa, split less /split injector and flame
ionization detector.
But-2-ene-1,4-diol 8. Propꢀ2ꢀenꢀ1ꢀol 7 (20 µL, 0.30 mmol)
and the HoveydaꢀGrubbs 2nd generation catalyst (19 mg,
0.030 mmol, 10 molꢀ%) was dissolved in acetone (2.00
mL). The mixture was transferred to reservoir R1 (see
Figure 2) and pumped (P1) into the MJOD flow at a rate of
r = 0.40 mL min.ꢀ1 When reservoir R1 of the reaction
mixture was emptied, pure solvent (acetone) that was
placed in reservoir R3 was pumped (P3) into the MJOD
flow reactor body with a rate r = 0.85 mL min.ꢀ1 that
provide a total residence time of 60 min. The temperature
of the MJOD reactor body was controlled at T=25 oC using
the heat exchanger (circulator) throughout the whole
reaction experiment.
Mass spectra were obtained on a GCꢀMS instrument, using
a gas chromatograph equipped with fused silica column (L
30 m, 0.25 mm i.d., 0.25ꢀm film thickness) and He as
carrier gas.
1
Structure control by using HꢀNMR spectra were recorded
on a NMR spectrometer operating at 400 MHz. Chemical
shifts was referenced to internal TMS. The obtained
synthesis products were compared with authentic samples.
The flow reactor. A multiꢀjet oscillating disk (MJOD) flow
reactor system with a net volume Vnet≈50 mL (L = 1000
mm, di=10 mm) furnished with N=80 pcs. of 4ꢀjets disks
was used for all experiments in the present study. The
input section is furnished with four inlet points, whereof
two or three were connected to precision feeding pumps.
The nonꢀused inputꢀlines were plugged during the reaction
experiments. See the process flow diagram in Figure 2 and
a 3D drawing of the MJOD flow reactor in Figure 1. The
tubular volume (reactor jacket) surrounding the reactor
tube was used for circulating temperature controlled water
in order to keep the reaction temperature at the desired
level (selected in the temperature range T=20−60oC). The
oscillator was adjusted to provide oscillations on the MJOD
unit with an amplitude of A=5 mm at a frequency of
f ≈ 1.6Hz.
Author Information
Corresponding Author
* Phone: +47 55 58 34 52. Fax: +47 55 58 94 90.
Eꢀmail: Hans.Bjorsvik@kj.uib.no
Present address
#Nordahl Griegs secondary high school, Bergen,
Norway
Notes
The Authors declare no competing financial interest.
Acknowledgements
Fluens Synthesis are gratefully acknowledged for
placing the MJOD flow reactor rig at our disposal.
Synthesis of diethyl cyclopent-3-ene-1,1-dicarboxylate 2.
Diethyl 2,2ꢀdiallylmalonate 1 (1 g, 4.16 mmol) was
dissolved in toluene (50 mL) and placed in reservoir R1.
The HoveydaꢀGrubbs 2nd generation catalyst (52 mg or
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