Angled Vortex Fluidic Mediated Multicomponent Photocatalytic and Transition Metal-Catalyzed Reactions

Article abstract of DOI:10.1002/chem.201801109

The dynamic thin film formed in an angled rapidly rotating tube in a vortex fluidic device (VFD) is effective in facilitating multicomponent reactions (MCRs) as photocatalytic or metal-mediated processes. Here, we demonstrate the utility of the VFD by using two known MCRs, an Ugi-type three component reaction and an A³-coupling reaction. The Ugi-type reaction can be done in either confined or continuous-flow modes of operation of the microfluidic platform whereas the A³-coupling reaction was optimized for the confined mode of operation. The examples tested gave excellent yields with short reaction times.

Full text of DOI:10.1002/chem.201801109

A Journal of
Accepted Article
Title: Angled vortex fluidic mediated multicomponent photocatalytic and
transition metal-catalysed reactions
Authors: Keith A Stubbs, Colin Raston, and Louisa Ho
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To be cited as: Chem. Eur. J. 10.1002/chem.201801109
Link to VoR: http://dx.doi.org/10.1002/chem.201801109
Supported by

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Angled vortex fluidic mediated multicomponent photocatalytic
and transition metal-catalysed reactions
Louisa A. Ho,[a] Colin L. Raston[b] and Keith A. Stubbs*[a]
Abstract: The dynamic thin film which is formed in an angled
rapidly rotating tube in a vortex fluidic device (VFD) is effective
in facilitating multicomponent reactions (MCRs)
as
photocatalytic or metal-mediated processes. Here we
demonstrate the utility of the VFD using two known MCRs, an
Ugi-type three component and A3-coupling reactions. The Ugi-
type reaction can be done in either confined or continuous flow
modes of operation of the microfluidic platform whereas the A3-
coupling reaction was optimised for the confined mode of
operation. The examples tested gave excellent yields with short
reaction times
.
Introduction
At the heart of organic chemistry is the development of new
methodologies to prepare molecules, not only new bond-forming
reactions but also developing more efficient and scalable
preparation techniques. Two aspects of these concepts, which
are receiving increasing attention, are the use of
mulitcomponent reactions (MCRs)[1-6] and flow chemistry[7-14] to
gain access to new molecules and facilitate chemical
transformations, respectively.
MCRs are a useful method of preparing new synthetic
molecules where typically three or more components are
combined in a single pot and through a series of chemical
reactions new compounds can be produced which are
dependent only on the starting materials used.[15] Flow chemistry
on the other hand has seen a rapid increase in its use to prepare
a wide variety of molecules both in academia and industry.[7-14]
The advancement of flow chemistry in the literature has been
greatly aided by the development of smaller-sized reactors that
allow for their use in laboratory settings[16-18] and to this end the
Figure 1. (A) Photograph of a VFD shown operating in the confined mode
(heating block/ photochemical apparatus removed for clarity). The device
features a tube, being rotated at a specific angle at high speed to generate a
thin film. (B) Overall utility of the VFD in terms of applications noting that
MCRs are well suited for this microfluidic platform. (C) Examples of the MCRs
and those being studied here.
chemical reaction, for example reagent quantities, surface area
of reaction and temperature.[18] Of interest is that the flow device
based on angled vortex driven dynamic thin films, called the
vortex fluidic device (VFD) (Figure 1A),[25] has not been
rigorously investigated in regards to its ability to be used as a
processing platform for MCRs, even though its design
characteristics,[25] which have been reviewed recently,[31] are
favoured as such.[25]
use of
a number of microfluidic platforms with synthetic
capabilities have been discussed.[19-30] The increased interest in
flow chemistry stems from the ability to use it to efficiently
control a variety of factors important to the success of a
An important advantage of the VFD over other microfluidic
platforms is the ability of the device to form a dynamic thin film,
where the chemistry of interest takes place. The film is formed
by the rapid rotation of a tube with the thickness of the film
controlled by varying the speed of rotation and the tilt angle.[25, 31]
Using a film confers a number of advantages in synthesis
including rapid heat transfer and uniform mixing with no
concentration gradients. Numerous applications have been
studied utilizing these features (Figure 1B)[31] with optimizing
rotational speeds enhancement of both organic and enzymatic
reactions arising from pressure waves being achieved.[32] In
addition, the VFD works in two modes of operation, depending
on the chemistry being conducted, the confined mode for a finite
[a]
[b]
Dr. L. A. Ho, Dr. K. A. Stubbs
School of Molecular Sciences
University of Western Australia
35 Stirling Highway, Crawley, WA 6009 (Australia)
E-mail: keith.stubbs@uwa.edu.au
Prof. C. L. Raston
Centre for Nanoscale Science and Technology, College of Science
and Engineering
Flinders University
Sturt Road, Bedford Park, SA 5042 (Australia)
E-mail: colin.raston@flinders.edu.au
Supporting information for this article is given via a link at the end of
the document.
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volume of liquid and the continuous flow mode, where the
reaction is conducted within the tube and the mixture collected
as it leaves the system.[25, 31]
To explore the utility of the VFD as a device to mediate
MCRs we chose two examples of MCRs, the Ugi-type three-
component and the A3-coupling reactions. Classically the Ugi
reaction employs an aldehyde, amine, a carboxylic acid and an
isocyanide[33] (Figure 1C) but recent advances have shown that
variations of reaction are possible to give Ugi-type reaction
processes where the iminium ion intermediate needed for a
successful reaction is generated in situ from non-classical
precursors using, for example, chemical oxidative[34-36] or
photochemical processes,[37] allowing for the formation of a
38-40]
variety of different types of molecules.[1,
The A3-coupling
reaction involves the coupling of an aldehyde, alkyne and amine
through C-H bond activation.[41] This type of reaction has gained
wide attention as the propargylamine products formed in these
reactions have been used in the preparation of a wide variety of
nitrogen containing heterocycles.[42] Typically the reaction is
catalysed by metals and these materials include ionic salts and
ligand-based compounds, in high yields and in reasonable
reaction times.[41, 43, 44]
Overall, here we demonstrate the potential utility of the
VFD as a simple flow reactor in being able to mediate MCRs as
part of developing new efficient synthetic protocols for organic
reactions, which can be translated easily between laboratories.
Figure 2. Variation in isolated yield for the test MCR reaction between N-
phenyltetrahydroisoquinoline, acetic acid and cyclohexyl isocyanide as
a
function of rotational speed and tilt angle of the VFD tube, as factors which
affect the film thickness. The optimisation procedure used acetonitrile with
Rose Bengal (1 mol%) for 30 minutes. All reactions were conducted in
triplicate with the average Errors were within ±2%.
for the preparation of this molecule where reactions are typically
conducted for many hours with lower yields. We established that
under similar reaction conditions that Eosin Y, another
commonly used organic dye in photocatalytic reactions, gave a
lower yield (60%).
Results and Discussion
The type of MCR we first investigated with the VFD was a
specific Ugi-type three-component reaction involving sp3 C-H
bond activation of a tetrahydroisoquinoline with a carboxylic acid
and an isocyanide which can be photocatalytically-mediated
through the use of metals,[45] and more recently using diethyl
diazodicarboxylate[46] (Figure 1C). Organic dyes represent an
excellent substitute for the use of metal-based systems in
photocatalytic reactions with many examples of reactions
involving such dyes reviewed in the literature.[47-51] We
hypothesised that the dynamic thin film in the VFD with tuneable
fluid dynamics could facilitate the use of organic dyes in
simplifying the application of MCRs in synthesis.
Initially, we used the confined mode of operation of the
VFD, a strategy which has served well in studying a number of
processes before taking them to continuous flow processing.[31]
This involves optimising the unique operational parameters of
the device, namely the rotational speed of the tube and its tilt
angle. Studies were conducted using a 10 mm OD borosilicate
glass tube (NMR grade) for N-phenyltetrahydroisoquinoline,
acetic acid and cyclohexyl isocyanide in the presence of an
amount of Rose Bengal and solvent. The choice of solvent and
Further investigation into the amount of Rose Bengal required to
facilitate the process also demonstrated the utility of the VFD of
being able to establish a thin film (ca 250 nm at 5000 rpm and
45° tilt angle)[25] which is important in generating a large surface
area for the reaction. This allows for more uniform irradiation as
the liquid moves along the tube, in moving towards all molecules
being treated in the same way, and thus more effective and
homogenous reaction conditions. Interestingly the amount of
Rose Bengal needed to complete the reaction within the same
time frame could be reduced significantly (See Supporting
Figure 1). Of particular note is a ~10-fold reduction in the
amount of organic dye that is normally used to facilitate
photocatalytic reactions reported in the literature. In addition, the
optimal 5000 rpm speed and 45° tilt has been established for a
number of reactions and processes for the 10 mm OD tube,
including protein folding,[56] highlighting special fluid dynamic
effects which are currently under investigation in a number of
research laboratories.
With suitable reaction conditions established for the
confined mode of operation of the VFD, we expanded the set of
substrates to demonstrate that the reaction has general utility
(Table 1). In all cases the yields were comparable to literature
preparations of the respective compounds but they are achieved
in a considerably shorter time, as well as with greatly reduced
catalytic loading. We then expanded the method to using
continuous flow operation of the VFD, noting that a 30 minute
reaction time in the confined mode is highly commensurate with
organic dye loading was based on successful literature
52-55]
photocatalytic reactions.[45,
Interestingly, the reaction
proceeded smoothly and was deemed complete after only 30
minutes across all parameters, but 5000 rpm rotational speed
and 45° tilt angle produced the highest conversion, at 88% yield
(Figure 2). This is highly commensurate with literature reactions
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Table 1. Synthesis of various compounds using the VFD operating at 5000
rpm rotational speed and 45° tilt angle in confined mode at room temperature
for 30 minutes, in the presence of Rose Bengal (0.1 mol%). All reactions
were conducted in triplicate with the average shown. Errors were within ±2%.
Literature yields for known compounds are shown in brackets.
Figure
3.
Synthesis
of
N-acetyl-N-cyclohexyl-2-phenyl-1,2,3,4-
Entry
Substrate 1
Substrate 2
Substrate 3[a]
Product Yield
(Lit. Yield)
tetrahydroisoquinoline-1-carboxamide (Table 1, Entry 1) using the VFD in the
continuous flow mode. The parameters used were those that were optimised
in the confined mode (5000 rpm and 45° tilt angle) at room temperature.
Fractions (2 mL) were collected in a continuous fashion from when the
reaction mixture begun to elute from the device. The components of all
materials in the reaction mixture were as for the optimised confined mode
reactions. All reactions were conducted in triplicate with the average
conversion shown (errors within ±3%) as determined using 1H NMR.
R1
H
R2
C6H11
R3
CH3
88(86)[45]
79(60)[46]
73
1
2
H
CH2Ph
C4H9
CH3
3
H
CH3
79
4
H
CH2CO2Me
CH2Ts
MeOPh
C6H11
CH3
the residence time for liquid entering the tube and exiting
at the top for a flow rate of 0.1 mL/min.[25, 31] Again we used a
working solution of phenyltetrahydroisoquinoline, acetic acid and
cyclohexyl isocyanide to investigate the utility of the continuous
flow mode in the preparation of the targeted coupled product
(Table 1, Entry 1) and found that fractions collected contained
an excellent conversion of product (Figure 3). Consistent with
71(85)[46]
71
5
H
CH3
6
H
CH3
93(95)[45]
79(92)[45]
83
7
OMe
OMe
OMe
OMe
OMe
Br
CH3
8
CH2Ph
C4H9
CH3
that observed previously[57] initial fractions had
a higher
9
CH3
conversion than fractions collected later, implying steady state
conversion needs to be achieved during the processing. Higher
than optimal flow rates reduced the conversion, which is
consistent with a reduction in residence time for the reaction
under continuous flow.
With these successful results in hand we next turned our
attention to the other model MCR reaction, the A3-coupling
reaction. We felt that the VFD was well suited to using this
73
10
11
12
13
14
15
16
17
18
19
20
21
22
CH2CO2Me
MeOPh
C6H11
CH3
80(80)[45]
CH3
84(91)[45]
81
CH3
Br
CH2Ph
C4H9
CH3
78
Br
CH3
83
Br
CH2CO2Me
MeOPh
C6H11
CH3
74
Br
CH3
71
H
MCA
C6H4OCH2
Ph
81
H
C6H11
78
H
C6H11
79
H
C6H11
C3H7
3-BrPh
4-NO2Ph
79
H
C6H11
83
H
C6H11
Figure 4. (A) Variation in isolated yield for the MCR reaction between
morpholine, benzaldehyde and phenylacetylene in water at 100°C with AuBr3
(1 mol%) for 2 hours. (B) Variation in isolated yield for the MCR reaction
between morpholine, benzaldehyde and phenylacetylene in water with varying
catalyst loading and temperature using optimised VFD parameters (9000 rpm,
maximum capability of the VFD, 45° tilt angle) for 2 hours. All reactions were
conducted in triplicate with the average shown. Errors were within ±2%.
[a] MCA = 4-MeOC6H4CHCH
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Table 2. Synthesis of various A3-coupling products using the VFD operating
at 9000 rpm (maximum rotational speed) and 45° tilt angle in confined mode
at 80°C with AuBr3 (1.0 mol%) for 2 hours. All reactions were conducted in
triplicate with the average shown. Errors were within ±2%. Literature yields
for known compounds are shown in brackets.
without a significant loss of yield (0.5 mol%, 63% yield). On the
other hand, the temperature could be reduced to 80°C without a
reduction in yield.
With suitable reaction conditions established, we
expanded the set of substrates to demonstrate general utility
(Table 2). In all cases the yields were comparable to literature
preparations of the respective compound but nevertheless, they
were also achieved in a considerably shorter time. We note that
the tilt angle is optimal at 45° (Figure 4A), with the optimal speed
≥ 9000 rpm, which is limited by the operational limits of the in-
house constructed VFD.[25] Clearly the 45° tilt angle is a common
thread for all reactions herein, and for a number of other
Entry
Amine
Aldehyde
Alkyne
Product Yield
(Lit. Yield)
31]
reactions and processes studied in the VFD.[25,
While the
reactions studied herein are in a 10 mm OD tube in the VFD, in
recent studies a 20 mm OD tube has been utilised, but the
optimal tilt remains at 45°, and thus the choice of tube diameter
is not a limiting design feature of the VFD.
R1
R2
R3
Ph
R4
Ph
94(59)[58]
83(75)[59]
85(88)[60]
82
-(CH2)2O(CH2)2-
-(CH2)5-
1
2
Ph
Ph
-(CH2)4-
Ph
Ph
3
Conclusions
-(CH2)6-
Ph
Ph
4
We have demonstrated that the VFD, a user-friendly plug-and-
play device (relative to most other microfluidic flow devices), can
be used efficiently to facilitate MCRs in high yield. The MCRs
demonstrated are photocatalytic and metal-mediated in nature
which demonstrates the overall flexibility of chemical reactions
72(61)[61]
88(90)[62]
C4H9
C4H9
Ph
Ph
5
-(CH2)2O(CH2)2-
-(CH2)5-
4-MeOPh
4-MeOPh
4-MeOPh
C6H11
C6H11
C6H11
4-MePh
4-MePh
4-MePh
Ph
Ph
6
81(61)[63]
84(87)[60]
90(90)[60]
92(99)[63]
92(98)[58]
87
Ph
7
which are able to be conducted in the VFD. As has been
-(CH2)4-
Ph
8
31]
previously described[25,
the rotational speed and tilt can be
optimised for a particular reaction, akin to optimising reagents,
solvents and temperature when finding ideal conditions for a
new chemical transformation using traditional batch processing.
The optimised tilt angle of 45° is noteworthy, where the effect of
gravity on the dynamic thin film is the greatest, at least judged
as the maximum cross vector of gravity with centrifugal force.
The utility of the VFD lies in this point as two more parameters
can be added to the optimisation protocol. The thin films
generated by the VFD allow for efficient heat and mass transfer,
uniform mixing and no concentration gradients which are
important considerations in chemical synthesis. The presence of
rotational speed dependent introduced pressure waves,[31, 32] is
likely to be in play for the optimal 5000 rpm for the MCR reaction
between N-phenyltetrahydroisoquinoline, acetic acid and
cyclohexyl isocyanide. This speed is optimal for a number of
other reactions using 10 mm diameter glass tubes in the VFD, in
contrast to close to 7000 rpm for a number of reactions in 20
mm glass tubes.[31, 32] Radial dependent processing in the VFD is
now a major current research program underway. We note that
the VFD has two different operating methodologies, namely
confined and continuous flow, reactions for which the conditions
are appropriate can be easily upscaled for increased output. We
envisage that the VFD can be readily adapted to other MCRs
which will add to the utility of the VFD as a device which controls
chemical reactivity and selectivity.
-(CH2)2O(CH2)2-
-(CH2)5-
Ph
9
Ph
10
11
12
13
14
15
-(CH2)4-
Ph
-(CH2)2O(CH2)2-
-(CH2)5-
Ph
Ph
82
84(86)[60]
88
-(CH2)4-
Ph
-(CH2)2O(CH2)2-
3-MeOPh
strategy that allowed for the application of this reaction. Again, to
demonstrate whether the VFD could be used in conjunction with
a suitable transition metal salt for such MCRs we used the
confined mode of operation. AuBr3 was the choice of metal salt,
which is simple and has been demonstrated to be useful in
mediating A3-couplings.[64]
Studies were conducted using morpholine, benzaldehyde
and phenylacetylene in water with dissolved AuBr3 (1 mol%) at
5000 rpm rotational speed and 45° tilt angle (VFD parameters
used in the initial MCR, Figure 4A). Interestingly, the reaction
proceeded smoothly and was deemed complete after only 2
hours at 100°C (yield 80%). With a basis for optimisation in hand
we varied the speed and found the yield was increased at higher
speeds with 9000 rpm being optimal (94%). After optimising the
VFD operating parameters, we investigated the loading of the
catalyst and the temperature of the reaction (Figure 3B).
Disappointingly, the catalyst loading could not be reduced
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Experimental details for the other compounds listed in Table 1 are
provided in the Supporting Information.
Experimental Section
General
Optimisation of reaction conditions for the coupling of morpholine,
benzaldehyde and phenylacetylene with AuBr3
Details of the in-house construction of the 10 mm VFD powered by a
Faulhaber 4490 H 024 B motor have been previously reported.[25] 1H and
13C nuclear magnetic resonance (NMR) spectra were obtained on a
Bruker Avance IIIHD 500 (500 MHz for 1H and 125.8 MHz for 13C) or
Bruker Avance IIIHD 600 spectrometer (600 MHz for 1H and 150.9 MHz
for 13C). The solvent used for NMR was deuteriochloroform (CDCl3) and
were calibrated for 1H at  7.26 ppm and 13C at  77.16 ppm. High
resolution mass spectra (HR-MS) were obtained on a Waters LCT
Premier XE spectrometer, run in W-mode, using the electrospray
ionisation (ESI) or atmospheric pressure chemical ionisation (APCI)
method with CH3CN:0.1% HCOOH (9:1) as a matrix. Infrared spectra
were obtained on a PerkinElmer spectrum one FTIR spectrometer fitted
with a PerkinElmer Universal ATR sampling accessory. Samples were
analysed as neat samples and recorded in wave numbers (cm-1). Flash
chromatography was performed on Merck silica gel using the specified
solvents. Thin layer chromatography (TLC) was effected on Merck silica
gel 60 F254 aluminium-backed plates that were visualised using a UV
lamp.
A 10 mm NMR tube was charged with morpholine (100 l, 1.1 mmol),
benzaldehyde (100 l, 1.0 mmol) and phenylacetylene (160 l, 1.5 mmol),
AuBr3 (4 mg, 1 mol%) in water (1 mL). The tube was capped tightly and
then rotated in the VFD at 3000, 5000, 7000 or 9000 rpm at a tilt angle of
15, 45 or 75° for 2 hours at 100°C. The mixture was then transferred to a
round bottom flask and evaporated to dryness. The residue was then
then redissolved in EtOAc and adsorbed onto silica gel and subsequent
flash chromatography (EtOAc:hexanes) gave the desired compound.
Optimisation of reaction conditions (catalyst loading and
temperature) for the coupling of morpholine, benzaldehyde and
phenylacetylene with AuBr3
A 10 mm NMR tube was charged with morpholine (100 L, 1.1 mmol),
benzaldehyde (100 L, 1.0 mmol) and phenylacetylene (160 L, 1.5
mmol), AuBr3 (0.25-1 mol%) in water (1 mL). The tube was capped tightly
then rotated in the VFD at 9000 rpm at a tilt angle of 45° for 2 hours at
60, 80 and 100°C. The mixture was then transferred to a round bottom
flask and evaporated to dryness. The residue was then redissolved in
EtOAc and adsorbed onto silica gel and subsequent flash
chromatography (EtOAc:hexanes) gave the desired compound.
Optimisation of VFD reaction conditions for the coupling of N-
phenyltetrahydroisoquinoline,
isocyanide with Rose Bengal
acetic
acid
and
cyclohexyl
A 10 mm NMR tube was charged with N-phenyltetrahydroisoquinoline
(52 mg, 0.25 mmol), acetic acid (17 L, 0.3 mmol), cyclohexyl isocyanide
(37 L, 0.3 mmol) Rose Bengal (2 mg, 1 mol%) and acetonitrile (2 mL).
The tube was then capped tightly then rotated in the VFD at 3000, 5000
or 7000 rpm with a tilt angle of 15, 45 or 75° for 30 minutes in the
presence of green LEDs (~530 nm - 2.7 mW/cm2) at a distance of 3 cm.
The mixture was then diluted with EtOAc (2-3 mL) transferred to a round
bottom flask and evaporated to dryness. The residue was then
redissolved in EtOAc and adsorbed onto silica gel and subsequent flash
chromatography (EtOAc:hexanes, 1:9) was conducted and gave the
desired compound.
General procedure for A3-coupling of an amine, aldehyde and
alkyne with AuBr3
A 10 mm NMR tube was charged with the appropriate amine (1.1 mmol)
aldehyde (1.0 mmol) and acetylene (1.5 mmol), AuBr3 (1 mol%) in water
(1 mL). The tube was capped tightly then rotated in the VFD at 9000 rpm
with a tilt angle of 45° for 2 hours at 80°C. The mixture was then
transferred to a round bottom flask and evaporated to dryness. The
residue was then redissolved in EtOAc and adsorbed onto silica gel and
subsequent flash chromatography (EtOAc:hexanes) gave the desired
compound.
4-(1,3-Diphenylprop-2-yn-1-yl)morpholine (Table 2, Entry 1)
General
procedure
for
photoredox
coupling
of
N-
aryltetrahydroisoquinoline, carboxylic acids and isocyanides with
Rose Bengal
Morpholine (100 L), benzaldehyde (100 L) and phenylacetylene (160
L) was used to obtain the title compound (260 mg, 94%). Rf 0.24
(EtOAc:hexanes 1:9). 1H NMR and 13C NMR were consistent with
literature values.[58] 1H NMR (500 MHz, CDCl3): δ = 7.68-7.63 (m, [app d],
2H), 7.56-7.50 (m, 2H), 7.42-7.29 (m, 6H), 4.80 (s, 1H), 3.80-3.70 (m,
4H), 2.70-2.60(m, 4H). 13C NMR (125 MHz, CDCl3): δ = 137.8, 131.8,
128.5, 128.3, 128.2, 128.2, 127.7, 122.9, 88.4, 85.0, 67.1, 62.0, 49.9.
A
10 mm NMR tube was charged with the appropriate
tetrahydroisoquinoline (0.25 mmol), carboxylic acid (0.3 mmol),
isocyanide (0.3 mmol), Rose Bengal (0.2 mg, 0.1 mol%) and acetonitrile
(2 mL). The tube was capped tightly and then rotated in the VFD at 5000
rpm with a tilt angle of 45° for 30 minutes in the presence of green LEDs
(~530 nm - 2.7 mW/cm2) at a distance of 3 cm. The mixture was then
diluted with EtOAc (2-3 mL) and transferred to a round bottom flask and
evaporated to dryness. The residue was then redissolved in EtOAc and
adsorbed onto silica gel and subsequent flash chromatography
(EtOAc:hexanes, 1:9-1:4) gave the desired compounds.
Experimental details for the other compounds listed in Table 2 are
provided in the Supporting Information.
Acknowledgements
N-acetyl-N-cyclohexyl-2-phenyl-1,2,3,4-tetrahydroisoquinoline-1-
carboxamide (Table 1, Entry 1)
N-Phenyltetrahydroisoquinoline[65] (50 mg), acetic acid (17 L) and
cyclohexyl isocyanide (37 L) was used to obtain the title compound (82
mg, 88%). Rf 0.28 (EtOAc:hexanes 1:9). 1H NMR and 13C NMR were
consistent with literature values.[45] 1H NMR (500 MHz, CDCl3): δ = 7.38-
7.33 (m,1H), 7.30-7.20 (m, 4H), 7.17-7.14 (m, 1H), 7.00-6.95 (m, [app d],
2H), 6.86-6.83 (m, [app t], 1H), 6.16 (s, 1H), 3.71-3.64 (m, 1H), 3.59-3.51
(m, 2H), 3.03-2.95 (m, 1H), 2.94-2.86 m, 1H), 2.18 (s, 3H), 2.01-1.89 (m,
1H), 1.84-1.65 (m, 3H), 1.57-1.43 (m, 2H), 1.20-0.95 (m, 4H). 13C NMR
(125 MHz, CDCl3): δ = 177.2, 174.5, 148.6, 135.5, 132.5, 129.2, 128.4,
127.7, 126.3, 119.1, 115.3, 63.3, 59.1, 44.7, 30.7, 29.4, 27.4, 26.4, 25.6,
25.0.
The authors wish to thank the Centre for Microscopy,
Characterisation and Analysis at The University of Western
Australia, which is supported by University, State and Federal
Government funding. CLR thanks Flinders University, the
Government of South Australia and both KAS and CLR also
thank the Australian Research Council for funding
(DP170100452).
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[33] I. Ugi, C. Steinbrückner, Angew. Chem. Int. Ed. 1960, 72, 267.
Keywords: Thin film microfluidics • photocatalysis • vortex
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10.1002/chem.201801109
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Louisa A. Ho., Colin. L. Raston, Keith. A.
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Page No. – Page No.
Angled vortex fluidic mediated
multicomponent photocatalytic and
transition metal-catalysed reactions
The VFD microfluidic device, has been used in multicomponent reactions (MCRs)
involving photocatalytic or metal-mediated processes. These reactions give
excellent yields with short reaction times.
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