Blue light mediated C-H arylation of heteroarenes using TiO2 as an immobilized photocatalyst in a continuous-flow microreactor

Article abstract of DOI:10.1039/c7gc00497d

Titanium dioxide was applied as an immobilized photocatalyst in a microstructured falling film reactor for the continuous-flow C-H arylation of heteroarenes with aryldiazonium salts as the starting material. Detailed investigations of the catalyst and a successful long-term run proved its excellent usability for this process. Very good yields up to 99% were achieved with broad substrate scope and were compared with batch synthesis. The transfer to the continuous-flow mode revealed an impressive boost in reactor performance solely resulting from the improved irradiation and contact of the catalyst, substrate and light.

Full text of DOI:10.1039/c7gc00497d

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PAPER
Blue light mediated C–H arylation of heteroarenes
using TiO as an immobilized photocatalyst in a
2
Cite this: DOI: 10.1039/c7gc00497d
continuous-flow microreactor†
a
a
b
c
c
David C. Fabry, Yee Ann Ho, Ralf Zapf, Wolfgang Tremel, Martin Panthöfer,
a
b
Magnus Rueping* and Thomas H. Rehm*
Titanium dioxide was applied as an immobilized photocatalyst in a microstructured falling film reactor for
the continuous-flow C–H arylation of heteroarenes with aryldiazonium salts as the starting material.
Detailed investigations of the catalyst and a successful long-term run proved its excellent usability for this
process. Very good yields up to 99% were achieved with broad substrate scope and were compared with
batch synthesis. The transfer to the continuous-flow mode revealed an impressive boost in reactor per-
formance solely resulting from the improved irradiation and contact of the catalyst, substrate and light.
Received 15th February 2017,
Accepted 16th March 2017
DOI: 10.1039/c7gc00497d
rsc.li/greenchem
1
2–15
thetic photo-process.
The in situ surface modification of
Introduction
TiO is another possibility to enhance the absorption range of
2
Titanium dioxide has proved its potential as a heterogeneous the photocatalyst. As recently shown by Rueping et al., the
1
photocatalyst for various applications in chemical synthesis.
TiO surface catalysed formation of a TiO azoether from aro-
2 2
The outstanding chemical and photochemical stabilities of matic diazonium salts results in a strong light absorption in
1
6
2
TiO allow, in combination with its high availability, low cost the blue region with a maximum of approx. 450 nm.
and non-toxicity, its use in advanced oxidation processes (AOP) Irradiating this substrate–catalyst combination results in the
2
for the mineralization of toxic compounds in wastewater. In formation of aryl radicals, which efficiently add to heteroarenes
contrast to degradation processes TiO
2
has also attracted con- like furan or thiophene available in the reaction solution.
In parallel to the development of photochemically catalysed
eses. Alcohol, amine and thiol oxidation to aldehydes, reactions with visible light, continuous-flow technology has
siderable interest as a photocatalyst for fine chemical synth-
3
4
5
6
1
7–19
imines and disulfides, respectively, are known as well as become one important tool for photochemists.
Micro-
7
8,9
various methods for C–C and C–heteroatom bond forming tubular-based reactors are a commonly used reactor type for
2
0–22
reactions. Hydrogenation reactions, of e.g. nitro arenes to photochemical transformations.
They are equipped with
1
0
the respective amines,
or the cyclisation of L-lysine to thin light transparent capillaries having an inner diameter of
1
1
L-pipecolinic acid, have been performed with pure TiO or less than a millimetre. Energy-efficient light emitting diodes
2
with Pt nanoparticles as a co-catalyst attached to the TiO2 are recommended for the wavelength-selective irradiation of
particle surface. Particularly the use of co-catalysts with TiO
has been explored in recent times in order to overcome the lary.
2
the liquid thin film of the reaction solution inside the capil-
2
3,24
In contrast to batch photo-reactions continuous-flow
limiting UV absorption range of pure TiO2 and enter the reactors allow the exact control of the irradiation time by the
visible light region for a milder and even more sustainable syn- flow rate of the reaction solution being pumped through the
capillary. This advantage minimizes detrimental effects on the
product formation due to over-irradiation. Besides these
advantages microstructured reactors also allow an intense
mixing of liquid or gas–liquid phases inside the micro-sized
a
RWTH Aachen University, Institute of Organic Chemistry, Landoltweg 1, 52074
Aachen, Germany. E-mail: magnus.rueping@rwth-aachen.de; Fax: +49 241 8092665
b
Fraunhofer ICT-IMM, Carl-Zeiss-Straße 18-20, 55129 Mainz, Germany.
channels yielding efficient mass transfer and accelerated
E-mail: thomas.rehm@imm.fraunhofer.de; Tel: +49 6131 990 195
c
2
5–28
Johannes Gutenberg University Mainz, Institute of Inorganic Chemistry and
Analytical Chemistry, Duesbergweg 10-14, 55128 Mainz, Germany
Electronic supplementary information (ESI) available: Catalyst preparation and
immobilisation, surface roughness, TEM, nitrogen physisorption, XRD, SEM,
reactions.
The use of solid phases like heterogeneous
photocatalysts needs another reactor design. Flexible capil-
laries are replaced by stiff microchannels made of inert poly-
mers or glass. A heterogeneous catalyst material can be then
†
19
EDX, lab plant description and flow chart, synthesis of aryldiazonium salts,
F
29
1
13
coated to the walls of the microchannels. This approach is
usually used for reaction screening and synthesis development
NMR analysis during long-term run, and product characterization: H-, C-, and
1
9
F-NMR spectroscopy. See DOI: 10.1039/c7gc00497d
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Fig. 2 FFMR reaction plate with TiO
2
immobilized in 32 microchannels
(
(
left) and the roughness of the catalyst material inside a microchannel
right).
Fig. 1 FFMR as the key element of the lab plant with a royal blue LED
array in a heat sink magnetically fixed to the top plate of the micro-
reactor (© Fraunhofer ICT-IMM).
4
1
surface. The applied method allows the immobilisation of a
thin TiO layer solely in the microchannels of the reaction
2
plate. The surface roughness of the calcined catalyst material
was investigated for five measuring lengths of 4 mm along the
bottom of one microchannel. The arithmetical mean deviation
of the roughness profile is Ra = 1.84 µm, and the average
in chip reactors with a small internal volume and low flow rate
on the µL min− scale.
1
30–32
For scale-up of a well-explored batch photo-reaction and its
transfer into continuous-flow mode a larger reactor type is
necessary, like the microstructured falling film reactor (FFMR)
z
surface roughness is R = 13.71 µm (Fig. 2, right and ESI†). The
data from these experiments indicate a constant roughness
with an equal distribution of catalyst material on the wall of
the surveyed microchannel. The surface roughness allows the
generation of turbulence in the liquid thin film for efficient
contact of the liquid stream with the catalyst surface.
(
Fig. 1). The design and working principle of the FFMR allows
the formation of liquid thin films in open stainless steel
microchannels with a thin film thickness below 100 µm and
flow rates of 1 mL min for the standard reactor version and
up to 10 mL min for the large reactor version (for more details,
see the ESI†).
mical reactions like photochlorinations and dye-sensitized
singlet oxygen formation.
ated in detail for the dye-sensitized photooxygenation of 1,5-dihy-
droxynaphthalene to Juglone.
In the work presented here the FFMR technology is used
for the first time with a heterogeneous photocatalyst immobi-
lized inside the microchannels. Based on previous work by
Rueping et al. on the TiO catalyzed C–H arylation of hetero-
arenes with diazonium salts as the starting material, this reac-
tion is transferred from small scale batch to continuous-flow
−
1
−1
33–36
The specific surface area and the pore diameter of the cata-
lyst material were analysed before and after calcination (see
The FFMR has already been used for photoche-
37
38,39
the ESI† for details). Prior to the thermal treatment TiO
2
Very recently the FFMR was evalu-
2
−1
powder had a specific surface area of 157.11 m g with a
median pore diameter of 6.6 nm. After wet catalyst preparation
and calcination at 450 °C the specific surface area was reduced
40
2
−1
to 118.93 m
g , whereas the median pore diameter had
increased to 8.7 nm. These values obtained with the BET and
BJH methods show a typical trend of mesoporous TiO upon
2
2
42
thermal treatment. Transmission electron microscopy (TEM)
was used to visualize the particle size of TiO before and after
calcination. Large agglomerates are observed in both cases.
Before temperature treatment TiO particles show a regular
2
mode in the FFMR with TiO as an immobilized photocatalyst
2
2
in stainless steel microchannels. Besides catalyst analysis a
wide range of aryldiazonium salts are investigated with furan,
thiophene and pyridine as heteroarenes including a long-term
run. Calculation of the specific reactor performance proves a
considerable boost in the performance and superiority of con-
tinuous-flow synthesis in the FFMR against batch synthesis.
dimension within the larger agglomerates (Fig. 3, left). After
thermal treatment TiO particles tend to stick together to larger
2
structures within the agglomerates (Fig. 3, right). This appear-
ance can be attributed to the adhesion between the particles
upon interaction with the binder from catalyst preparation.
Results and discussion
Catalyst immobilisation and analysis
For all experiments reaction plates were used with 32 micro-
channels and a channel architecture of 600 µm in width,
2
00 µm in depth and 78 mm in length (Fig. 2, left). TiO2
(24 mg, anatase modification) was immobilized as a catalyti-
cally active metal oxide as described in the Experimental
section (vide infra). Cleaning of the reaction plate with citric
acid and heat treatment at 800 °C prior to the immobilization
of the metal oxide with poly-vinyl alcohol as a binder enables
2
Fig. 3 TEM images of TiO particles before (left) and after (right) calci-
strong adhesion of the catalyst material to the stainless steel nation at 450 °C (length scale: 100 nm).
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Further analysis of TiO
2
was carried out using X-ray diffrac-
Scanning electron microscopy was carried out to investigate
tion (XRD) in order to gain insight into the crystal modifi- the surface structure of immobilized TiO before and after its
2
2
cation of nano-powderous TiO before and after thermal treat- use in the microreactor (Fig. 5). Despite a little change in
ment. All patterns exhibit reflections due to the anatase as well colour from off-white to slightly yellowish, neither on the sub-
as the rutile modification of TiO , the latter being the minor micrometre scale nor on a larger scale any changes of the
2
component (Fig. 4). The reflection profiles of the anatase surface structure have been observed after intense use of the
2
phase are broad as expected for nanoscale materials, yet the TiO coated plate for all runs (see the ESI† for images with
tips of the reflections are too sharp. Thus the anatase com- lower magnification).
ponent was modelled using two phases of identical crystallo-
In conjunction with SEM analysis energy dispersive X-ray
graphic data, but with different crystallite sizes and mass (EDX) analysis was performed as well to check the composition
ratios. In this model the sharp tips of the reflection profiles of the catalyst material in the microchannels before and after
are due to a minor component of approx. 5 wt% with a crystal- its use in flow synthesis (Table 1 and ESI†). In both cases tita-
lite size larger than 100 nm. In this crystallite size regime nium and oxygen represent the major share of the detected
reflection broadening due to the crystallite size and the broad- elements in the correct ratio for TiO , whereas the oxygen
2
ening due to the diffractometer technical limits become com- share is slightly higher in the unused sample. This portion as
parable, thus a more precise value of the crystallite size of the well as the carbon content of 2.55 atom% can be attributed to
minor phase cannot be determined from laboratory diffrac- residues of the binder poly(vinyl alcohol) from catalyst prepa-
2
tometer data. Importantly, calcination changes the TiO catalyst ration. The used sample shows a significant carbon and fluo-
only negligibly, but the composition and crystallite size before rine content of 3.41 atom% and 3.20 atom%, respectively.
and after calcination are virtually the same.
Both elements result from the last experiments performed
with trifluoromethylated benzenediazonium salts (vide infra).
A low content of iron with 0.62 atom% and 1.05 atom%,
respectively, most likely results from the stainless steel reac-
tion plate as a catalyst carrier.
Lab plant design and reactor integration
The FFMR is part of an integrated multi-purpose lab plant for
different reactor types (FFMR and tube-in-tube flow reactor)
(
Fig. 6). The heat exchanger of the FFMR is connected to a
water-filled thermostat for maintaining the temperature of the
reaction plate at 20 °C (see the ESI† for details of the flow
Fig. 5 SEM images of the TiO
2
surface in the microchannels before
(left) and after (right) use in the FFMR (length scale: 1 µm).
Table 1 Element composition of catalyst material inside the micro-
channels as analysed by EDX
Element
Before use in FFMR, atom%
After use in FFMR, atom%
C
O
F
P
S
2.55
70.06
—
0.35
0.12
26.30
—
3.41
65.30
3.20
0.23
—
26.67
0.13
1.05
2
Fig. 4 X-ray powder diffraction patterns of the TiO before (bottom)
and after (top) calcination (red dots: experimental data, black line: fit,
red line: difference curve; ticks indicate the reflection positions of the Cr
anatase (black) and rutile (red) phases, respectively).
Ti
Fe
0.62
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Table 2 Evaluation of the reaction conditions and substrate scope for
a
furan series
Metal Light c
Yield: flow
synthesis (%) synthesis (%)
Yield: batch
e
b
d
Entry Substrate oxide source
1
2
3
4
5
6
7
8
9
1
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
TiO
ZnO
Bi
2
Royal blue
Royal blue
Royal blue
Royal blue
Cold-white <10
Actinic blue <10
79
<10
<10
0
96
—
—
—
—
—
—
94
90
—
2
O
3
Fig. 6 FFMR lab plant with a HPLC pump, thermostat, nitrogen gas
supply and power supply of the LED array.
—
TiO
TiO
TiO
TiO
2
2
2
2
—
0
99
87
91
Royal blue
Royal blue
Royal blue
chart). This external cooling is necessary since prolonged LED
irradiation can lead to heating of the reaction plate and
solvent evaporation in the microchannels which results in fal-
TiO2
TiO
0
2
a
Reaction conditions: 5 mmol 1a–d in 100 mL EtOH/furan (1 : 1, v/v);
sification of the residence time of the reaction solution in the T = 20 °C; fliq = 0.5 ml min−
1
. Amount of immobilized metal oxide:
b
c
m(TiO
P
2
) = 24 mg, m(ZnO) = 24 mg, m(Bi O ) = 27 mg. Electrical power
2
3
microreactor. The starting material solution is pumped with a
d
e
ele ≈ 2.4 W. Yield after chromatographic purification. See ref. 16.
HPLC pump into the reactor at a flow rate fliq = 0.5 mL min−
1
.
A nitrogen gas stream is fed in counter-flow to the liquid
stream into the FFMR. This inert gas flow of approx. 10 mL
the same yield of 72% was obtained by flow and batch syn-
thesis. The nitro derivative 6c, however, gave a considerably
lower yield of 42% compared to 83% in the batch synthesis. A
moderate yield of 45% was achieved for the trifluoromethyl-
ated compound 6d (Table 3). Pyridine was used as the last het-
erocycle. Surprisingly, the pyridine series yielded in continu-
ous-flow far better results than via the batch synthesis. In the
case of 7b 99% yield was obtained compared to 79% in batch.
The same trend was observed for 7c with 85% yield in flow syn-
thesis compared to 53% in batch. Therefore, a broader sub-
−
1
min was used to support the self-draining of the reactor. All
LEDs (actinic blue, royal blue, cold-white) used for the experi-
ments are installed on an aluminium heat sink, which can be
fixed magnetically in front of the inspection window of the
FFMR (Fig. 1).
Reaction evaluation and substrate scope
The first set of experiments was performed with 4-fluorobenzene-
diazonium salt 1a and furan as a heterocycle. In order to
investigate the necessity and type of photocatalyst several runs
were performed with different metal oxides using royal blue
3
strate scope was investigated. Except for 7e (p-CF ) with 75%
yield excellent yields of up to 99% were obtained for all other
pyridine compounds (Table 3). To complete the substrate
scope, the precursor of dantrolene, an API for muscle relax-
ation, was synthesized as well in continuous-flow mode
−
1
light (455 nm) at a flow rate fliq = 0.5 mL min (Table 2). In
the case of TiO a yield of 79% was obtained (entry 1), whereas
for ZnO and Bi only low yields could be achieved (entries 2
3). In the case of a blank reaction plate without metal
2
2 3
O
43
&
(
1
Table 3, framed). Furfural (8) was used as a heterocycle with
c as a diazonium salt under standard reaction conditions
oxide no reaction took place (entry 4). The impact of the light
source was investigated as well with the reaction plate carrying
−1
with fliq = 0.5 mL min , T = 20 °C and royal blue light with
TiO2 as a photocatalyst. A slightly lower yield of 65% was
achieved for 9 in continuous-flow mode compared to 68%
TiO . The use of cold-white light (6500 K, entry 5) and actinic
2
blue (410 nm, entry 6) as well as the absence of light as the
blank test (entry 7) was ineffective compared to royal blue
light, which provided a maximum light intensity at the absorp-
in batch. The conversion of
hydrochloride provided dantrolene in an excellent yield of
2% (see the ESI†).
9 with 1-aminohydantoin
tion range of the photoactive TiO
2
azoether at approx.
9
1
6
4
50 nm. Therefore, all further experiments were performed
with royal blue light for irradiation and TiO as the catalyst
material. Under these conditions the furan series was com-
2
Long-term run
pleted with three more diazonium salt derivatives showing The long-term run was performed with 4-trifluoromethyl-
approximately the same or better yields compared to the batch benzene diazonium salt (1e) in EtOH and pyridine as hetero-
synthesis (entries 8–10, Table 2).
arenes. Standard reaction conditions were applied as well in
The next set of experiments was performed with thiophene this experiment with T = 20 °C, fliq = 0.5 mL min− , royal blue
1
as the heterocycle for C–H arylation (Table 3). In the case of 6b light and TiO immobilized in the microchannels. During the
2
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Table 3 Reaction conditions and substrate scope for thiophene and
a
pyridine series
Fig. 7 Constant yields for 1d during long-term run over 180 minutes
19
(
left) and part of the F NMR spectra of the sample taken after
30 minutes (right).
reactor systems. In the case of a batch reactor system the
4
4
specific reactor performance Lbatch is usually described by:
cstarting material ꢀ Yproduct
½mol Lꢁ minꢁ1ꢂ
1
ð1Þ
Lbatch ¼
tR þ tD
with cstarting material as the molar concentration of the starting
material, Yproduct as the yield of the desired product and t as
R
the reaction time. The dead time t can be assumed for filling
D
the reaction vial, starting the reaction and quenching the reac-
tion afterwards. The specific reactor performance of the FFMR
4
4
LFFMR can be calculated by:
cstarting material ꢀ Yproduct
½mol Lꢁ minꢁ1ꢂ
1
ð2Þ
LFFMR ¼
τ
with τ as the residence time of the reaction solution in contact
with the catalyst material. The residence time τ can be calcu-
lated by:
a
Reaction conditions: 5 mmol 1b–h in 100 mL EtOH/thiophene or pyr-
4
5
idine (1 : 1, v/v); T = 20 °C; fliq = 0.5 ml min− ; amount of immobilized
1
2
metal oxide: m(TiO ) = 24 mg; yield of continuous-flow synthesis after
chromatographic purification; yield of batch synthesis, see ref. 16.
N ꢀ Vc N ꢀ W ꢀ L ꢀ δ
τ ¼
¼
½sꢂ
ð3Þ
fliq
fliq
with N as the number of microchannels on the reaction plate,
Vc as the irradiated volume of the reaction solution in one
microchannel, W as the width of a microchannel, L as the
microchannel length, δ as the liquid thin film thickness and
fliq as the flow rate of the reaction solution. The liquid thin
complete run time of 180 min nine samples were taken from
the reactor outlet and mixed with 4-trifluoromethylbenzyl
1
9
alcohol as the internal standard ( F NMR (56 MHz) δ =
65.99; s, 3F) in DMSO-d . Over the complete run time the
process was performing constant with a mean conversion of
7%, which is in good agreement with the yield of 75%
achieved with the synthesis during substrate scope evaluation
−
6
4
5,46
film thickness δ can be expressed by the Nusselt equation:
7
sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
3
ꢀ fliq ꢀ μ
liq
3
liq
(
(
Fig. 7). The NMR spectra revealed only the product 7e
F NMR (56 MHz) δ = −66.44) and the diazoether of 1e with
δ ¼
½μmꢂ
ð4Þ
N ꢀ ρ ꢀ W ꢀ g
1
9
ethanol being the intermediate compound of the synthesis
with μliq as the dynamic viscosity of the reaction solution, ρliq
as the density of the reaction solution and g as the gravitational
constant. The conversion of 4-chlorobenzenediazonium salt (1b)
with pyridine to 2-(4-chlorophenyl)pyridine (7b) was chosen for
comparing batch and continuous-flow synthesis. In Table 4 all
necessary data are compiled for the calculation of the specific
reactor performance of the batch system and the continuous-flow
1
9
(
F NMR (56 MHz) δ = −66.28). It has to be pointed out that
reaction evaluation and long-term run has been performed
with solely one plate with immobilized TiO . This fact proves
2
the exceptional durability and reusability of the immobilized
catalyst.
Flow reactor performance
reactor. In the case of the batch synthesis
a specific
The specific reactor performance L is an important parameter reactor performance of Lbatch = 5.4 × 10− mol L min was cal-
5
−1
−1
to characterize chemical processes performed using different culated. For the continuous-flow synthesis in the FFMR a specific
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Table 4 Data for and results of the calculation of the specific reactor boost in the specific reactor performance up to a factor of
performance L
6000. This strong increase can be attributed to the improved
irradiation and substrate–catalyst–light interaction on the
microstructured surface of the continuous-flow reactor. These
results clearly show the major advantages for photochemistry
when performed in a microstructured environment.
a
Batch
Flow
0.05
Unit
mol L−
1
Molar concentration
0.05
c
starting material
Yield Yproduct
79%
—
—
—
—
—
—
—
99%
32
—
—
Number N of microchannels
Microchannel width, W
Channel length, L
Gravitational constant, g
Liquid flow rate, fliq
Dynamic viscosity, μ
Density, ρ
600
µm
mm
c
78
−
2
9.81
0.5
0.8839
0.8910
—
—
50.9
9.1
m s
Experimental
Catalyst preparation and immobilization
−
1
mL min
g mL
mPa s
min
min
µm
d
d
−1
Reaction time, t
Dead time, t
R
720
A slurry-washcoat process was used for the immobilization of
catalyst material on the FFMR reaction plate. The preparation
b
D
15
Liquid thin film thickness, δ
Residence time, τ
—
—
2 2 3
of TiO , ZnO and Bi O washcoats was carried out according to
s
Specific reactor performance, L 5.4 × 10−
5
0.32
mol L min−1 literature procedures.
−1
41,48
The method is exemplified here for
TiO . 2.5 g of poly(vinyl alcohol) (PVA) used as a binder (Sigma
Aldrich, Mowiol 40–88) were mixed with 42.5 mL of distilled
(diazoether formation and photocatalysis) is not only limited to water and stirred at 65 °C until PVA had completely dissolved
a
b
c
2
Data extracted from ref. 16. Estimated dead time. The full length
of a microchannel is used for the calculation, since the dual role of
TiO
2
d
the directly and fully irradiated length of 54 mm. Data extracted
from ref. 47.
(
approx. 2–3 h). 5 g of TiO (Alfa Aesar, 45603, anatase modifi-
2
cation) and 0.375 g concentrated acetic acid were added to the
solution and stirred for 3 h at 65 °C, and finally at room temp-
erature for 2–3 days, until the suspension became homo-
geneous and dense.
reactor performance of LFFMR = 0.32 mol L− min−1 was
calculated. The extreme performance increase by a factor of
approx. 6000, solely by switching from batch to continuous-flow
mode, can be attributed to the following reasons. The FFMR
1
All reaction plates were cleaned with citric acid solution
(
10 wt% in water) under ultrasound treatment. After rinsing
the cleaned plates with distilled water, they were heated in an
oven at 800 °C. Prior to the deposition of the washcoat in the
microchannels, the area on the reaction plate not to be coated
with a catalyst was covered with an adhesive tape. Afterwards
the microchannels were completely filled with the prepared
suspension and the excess of the suspension was wiped off.
After drying at room temperature in air, the coated plates were
calcined at 450 °C for 6 h.
offers
a
strongly improved irradiation of the reaction
solution compared to the batch synthesis. The royal blue LED
array provides solely the light exactly matching to the
absorption range of the TiO diazoether. During the process the
2
volume of the reaction solution inside the microchannels is
quite small (approx. 0.08 mL) and in intense contact with the
fully irradiated catalyst surface. This efficient combination is in
clear contrast to the batch synthesis where the complete catalyst
suspension volume is irradiated by a rather unspecific light
source.
Catalyst analysis
The surface roughness of the catalyst layer inside the micro-
channels was measured with a NanoFocus AF 2000. The
surface area and the pore diameter of the catalyst material
were determined before and after calcination. Low temperature
Conclusions
For the first time the falling film microreactor technology was nitrogen physisorption was performed with Sorptomatic 1990
successfully applied to a photochemically catalysed reaction (Carlo Erba Instruments) automatic apparatus. The obtained
with TiO as an immobilized photocatalyst in the microchan- information was used for the calculations of the surface area
2
nels of a continuous-flow reactor. A wide variety of arenediazo- and the pore diameter by applying the BET and BJH methods.
nium salts were used as the starting material for blue light Transmission electron microscopy (TEM) images were
mediated C–H arylation of heteroarenes in continuous-flow recorded with a Zeiss Libra® 120 on copper grids with a
mode. Furan, thiophene and pyridine as well as furfural were carbon thin film (CF300-CU, EM Science). X-ray powder diffrac-
converted into the desired products with good to excellent tion (XRD) patterns were recorded from powders prepared
yields up to 99%. A long-term run over 180 min was success- between two stripes of 3 M Scotch tape using a Siemens D5000
fully performed as well in order to demonstrate the catalyst equipped with a Ge (111) monochromator (Huber 611 Guinier
performance. Detailed XRD, SEM and EDX analyses of the monochromator) and a Braun M50 position sensitive detector
catalyst material before and after calcination and its use in the in transmission mode. Scanning electron microscopy (SEM)
microreactor, respectively, proved the excellent stability and images were taken with a Zeiss Leo 1550 VP Field Emission
usability of TiO
ous-flow microreactor. The transfer of the C–H arylation of TiO
heteroarenes from batch mode to continuous-flow revealed a eration voltage was 5.00 kV, and the working distance was
2
as an immobilized photocatalyst in a continu- Scanning Electron Microscope. The reaction plates containing
2
were scanned without any sample preparation. The accel-
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between 7.7 and 8.0 mm. Energy Dispersive X-ray (EDX) ana- 11 B. Pal, S. Ikeda, H. Kominami, Y. Kera and B. Ohtani,
lysis was performed with an Oxford INCA II setup.
J. Catal., 2003, 217, 152–159.
12 S. Füldner, R. Mild, H. Siegmund, J. Schroeder, M. Gruber
General procedure for the TiO catalyzed arylation in continu-
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2
ous-flow
13 M. Cherevatskaya, M. Neumann, S. Füldner, C. Harlander,
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Aryldiazonium tetrafluoroborates 1a–h were synthesized
according to literature procedures (for details, see the ESI†).
The appropriate salt was dissolved in a solvent mixture of
EtOH and the corresponding heterocycle (furan, thiophene,
pyridine or furfural, v : v 1 : 1, 50 mM). The resulting mixture
was stirred until complete solvation of the diazonium salt.
Then, the mixture was pumped into the falling film microreac-
tor for collapsing down into the microchannels. As soon as the
reaction solution equally rinsed all microchannels irradiation
was started by switching on the LED array connected to the
FFMR. The crude reaction mixture was collected and filtered
over a short plug of silica and flushed with ethyl acetate. If
necessary, the final products were further purified using flash
column chromatography on silica gel (eluent cyclohexane/ethyl
acetate).
1
1
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T. H. R. would like to thank Dr Raphael Thiermann for TEM
analysis, Anja Himmelsbach for SEM and EDX analysis and
Gitta Hasert for nitrogen physisorption analysis (all 22 J. Schachtner, P. Bayer and A. Jacobi von Wangelin,
Fraunhofer ICT-IMM). This research has received funding
Beilstein J. Org. Chem., 2016, 12, 1798–1811.
from the European Research Council under the European 23 G. Kreisel, S. Meyer, D. Tietze, T. Fidler, G. Gorges,
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