Photosensitized addition of isopropanol to furanones in a continuous-flow dual capillary microreactor

Article abstract of DOI:10.1016/j.tetlet.2010.11.018

A novel continuous-flow photoreactor with parallel capillaries was constructed and successfully tested for the DMBP-sensitized addition of isopropanol to furanones. Complete conversions were achieved after a maximum of 10 min of irradiation with a single

Full text of DOI:10.1016/j.tetlet.2010.11.018

Tetrahedron Letters 52 (2011) 278–280
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Photosensitized addition of isopropanol to furanones in a continuous-flow
dual capillary microreactor
Alexander Yavorskyy a, Oksana Shvydkiv a, Kieran Nolan a, Norbert Hoffmann b, Michael Oelgemöller c,
⇑
a Dublin City University, School of Chemical Sciences, Glasnevin, Dublin 9, Ireland
b Institut de Chimie Moléculaire de Reims, UMR 6229 CNRS et Université de Reims Champagne-Ardenne, Equipe de Photochimie, UFR Sciences, B.P. 1039, 51687 Reims,
Cedex 02, France
c James Cook University, School of Pharmacy and Molecular Sciences, Townsville, Queensland 4811, Australia
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel continuous-flow photoreactor with parallel capillaries was constructed and successfully tested
for the DMBP-sensitized addition of isopropanol to furanones. Complete conversions were achieved after
a maximum of 10 min of irradiation with a single 350 nm lamp. The results were compared to analogous
batch experiments using a conventional Rayonet chamber reactor equipped with 16 UVA lamps. The cap-
illary tower generally showed higher space-time yields.
Received 24 September 2010
Revised 25 October 2010
Accepted 5 November 2010
Available online 11 November 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Photoaddition
Furanones
Photochemistry
Microreactor
Microcapillary
Continuous-flow synthesis
Organic synthesis in microreactors has recently emerged as a
promising new methodology.1 The small dimensions of microreac-
tors make them especially advantageous for photochemical appli-
cations and numerous photochemical transformations have been
reported so far.2 In particular, the narrow reaction channels of mic-
roreactors allow efficient penetration of light even at high chromo-
phore concentrations. Their continuous flow operation also
minimizes follow-up reactions of target products as often encoun-
tered in batch processes. Microphotochemistry has also been suc-
cessfully adopted by the chemical industry.3
OH
OH
hν (365 nm)
+
R
R
O
O
DMBP
O
1a-c
O
2a-c
Scheme 1. DMBP-sensitized isopropanol addition to furanones.
DMBP is the necessity for its removal, but it has been applied suc-
Major disadvantages of conventional (commercially available)
microreactors are, however, the fixed length of the reaction chan-
nel and the single-channel design. Although numbering-up can be
achieved using an array of microreactors,4 this strategy causes sig-
nificant investment costs. Flexible capillaries represent a cost-effi-
cient alternative and isolated examples have been reported in
macro- as well as micro-formats.5,6
cessfully to the isopropanol addition in
a 365 nm UV-LED
microchip.9
The experimental set-up is shown in Figure 1. To allow for the
synthesis of larger amounts of product material in a single run, a
dual syringe pump was implemented. The pump was connected
to two parallel UV-transparent polytetrafluoroethylene (PTFE) cap-
illaries of 460 cm length and 558 lm inner diameter (each, internal
For the present study the diastereoselective addition of isopro-
panol to furanones was selected as a model transformation in a no-
vel microcapillary photoreactor (Scheme 1).7 The original protocol
used acetone as a sensitizer, however, the limited chemical
stability of some connections and fittings made a replacement nec-
essary. Related photoadditions of amines used 4,40-dimethoxyben-
zophenone (DMBP) as an efficient sensitizer.8 A disadvantage of
volume per capillary: 1.12 mL). The capillary pair was tightly
wrapped around a Pyrex glass cylinder (transmission: k P 300 nm)
of 6.5 cm diameter and 20 cm height (22 windings covering
14 cm). A single UVA (RPR-3500 Å, 8 W, k = 350 25 nm) lamp
was placed in the centre of this dual-microcapillary tower. A small
cooling fan was mounted on the bottom of the tower encapsulated
in the base.
A series of reactions were examined in continuous-flow mode
using this dual microcapillary reactor. The irradiation time was
controlled simply by changing the flow rate. The results obtained
⇑
Corresponding author. Tel.: +61 07 4781 4543; fax: +61 07 4781 6078.
E-mail address: michael.oelgemoeller@jcu.edu.au (M. Oelgemöller).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.11.018

A. Yavorskyy et al. / Tetrahedron Letters 52 (2011) 278–280
279
100000
1500
1000
500
0
10000
1000
DMBP in MeCN
Power (lamp)
100
200
250
300
350
400
450
Wavelength [nm]
Figure 2. UV-spectrum of DMBP (in MeCN) vs the emission spectrum of the UVA
lamp. The vertical dotted line represents the cut-off wavelength of Pyrex at 300 nm.
Figure 1. Experimental set-up. Inset shows a close-up of the double capillary.
100
were compared to reactions in a conventional chamber (Rayonet)
reactor under batch conditions.7b
c = 6.67 mM
ε350 nm = 496 L mol-1cm-1
80
Initially, the performance of the capillary microreactor in terms
of conversion rates was evaluated. A previously degassed solution
of furanone 1a–c and catalytic amounts of DMBP in isopropanol
were irradiated while passing through the microcapillaries at var-
ious flow rates. The reaction mixture was collected in separate
flasks (protected from light) outside the irradiated area. The con-
version rates were subsequently determined by 1H-NMR spectros-
copy (Table 1).10 Three furanone derivatives were investigated and
complete conversions were achieved after just 7.5 (1c) and 10 (1a
and 1b) minutes of irradiation, respectively.
60
40
20
0
0
1
2
3
4
5
6
7
Pathlength [mm]
Next, a comparison study (continuous-flow versus batch) was
conducted using a fixed reaction time of 5 min. The microcapillary
reactor gave conversion rates of 75% (1a), 96% (1b) and 99% (1c),
respectively. The same experiments were repeated under batch
conditions in a much larger Rayonet chamber reactor. After irradi-
ation with a set of 16 UVA lamps, incomplete conversion rates of
90% (1a), 90% (1b) and 87% (1c) were achieved.11
With the exception of the parent furanone 1a, the microcapil-
lary reactor gave higher conversion rates compared to the batch
process. To explain this trend we have recorded the UV-spectrum
Figure 3. Light-penetration profile for a 6.67 mM solution of DMBP at 350 nm. The
vertical lines represent the inner diameter of the microcapillary (dashed) vs the
effective pathlength of the Pyrex test tube (dotted).
(558 l
m) and the Rayonet Pyrex test tube (9 mm), respectively.12
Due to the circular arrangement of the lamps around the reaction
vessel in the Rayonet (batch) reaction, its effective pathlength
was reduced to 4.5 mm. At the chosen concentration of DMBP, both
set-ups allowed for complete penetration of light (Fig. 3). Whereas
the batch reactor had reached its optimum in terms of the concen-
tration of DMBP, the microcapillary reactor set-up allows for much
higher sensitizer concentrations to be used. This may ultimately
give higher conversions (and yields).
of DMBP and matched it to the emission spectrum of the UVA lamp
*
(Fig. 2). The crucial n
p absorption band of DMBP showed a good
overlap with the emission band of the light source. At its emission
maximum at 350 nm in acetonitrile, DMBP showed an extinction
coefficient (e .
350nm) of 496 L molꢀ1 cmꢀ1
Due to its much larger surface-to-volume ratio,1 in combination
with a superior light penetration within the microcapillaries, the
continuous-flow system resulted in significantly higher space-time
yields (STY).13 For the 5 min irradiations the reactor performance
data are summarized in Table 2. For compound 1a, the larger num-
ber of lamps fitted in the Rayonet reactor resulted in a somewhat
higher conversion rate.
Based on these data, the light penetration was calculated at
350 nm and matched with the inner diameters of the capillary
Table 1
Experimental details
Residence time
(min)
Flow rate
l/min)
Conversion (%)a
In conclusion, isopropanol additions to furanones have been
realized in a novel dual-capillary microreactor. The easy design
(
l
R = H (2a)
R = OEt (2b)b
R = OMent (2c)
2.5
5
7.5
10
15
20
460
230
153.3
115
76.7
57.5
35
50
64
75 (90c)
95
96 (90c)
99
99 (87c)
100
Table 2
Reactor performance data for 5 min reactions
100
100
100
100
100
n.d.d
100
n.d.d
100
Reactor
Surface-to-volume
ratio (m2/m3)a
STY (mmol Lꢀ1 minꢀ1
)
1a
1b
1c
a
b
c
Determined by 1H NMR spectroscopy.
Used as racemate.
Conversion under batch conditions in a chamber reactor.
Not determined.
Microcapillary
Batch (test tube)
7,169
466
22.4
6.0
28.6
6.0
29.5
5.8
d
a
Assuming a cylindrical geometry for both, capillary and test tube.

280
A. Yavorskyy et al. / Tetrahedron Letters 52 (2011) 278–280
8. (a) Harakat, D.; Pesch, J.; Marinkovic´, S.; Hoffmann, N. Org. Biomol. Chem. 2006,
4, 1202; (b) Bertrand, S.; Hoffmann, N.; Humbel, S.; Pete, J. P. J. Org. Chem. 2000,
65, 8690; (c) Bertrand, S.; Glapski, C.; Hoffmann, N.; Pete, J. P. Tetrahedron Lett.
1999, 40, 3169.
of the reactor makes it an interesting synthetic tool for chemical
research and development (rather than production).14 The gener-
ally small volumes additionally help to reduce the amounts of
chemicals and solvents, thus contributing to Green Chemistry.15,16
The set-up also allows for parallel synthesis using multiple capil-
laries and this modification is currently being investigated using
an improved reactor with up to 10 microcapillaries.17 This modi-
fied design will also increase the overall aperture of the microcap-
illary with a tighter wrapping around the central glass column.
9. Shvydkiv, O.; Yavorskyy, A.; Nolan, K.; Youssef, A.; Riguet, E.; Hoffmann, N.;
Oelgemöller, M. Photochem. Photobiol. Sci. 2010, 9, doi: 10.1039/c0pp00223b.
10. General procedure for irradiation in the capillary microreactor: A solution of the
furanone (0.334 mmol) and DMBP (0.066 mmol) in isopropanol (10 mL) was
purged with nitrogen and loaded into a dual syringe pump. The reaction
mixture was pumped through the microcapillaries while being irradiated by a
single UVA lamp (RPR-3500 Å, k = 365 25 nm, 8 W). After evaporation of the
solvent, the conversion was determined by 1H NMR spectroscopy of the crude
product. The signal integration for the proton at the b-position of 1a–c was
compared to the signal integration for the acetal proton of 2a–c. Pure products
were isolated by column chromatography.9
Acknowledgements
11. General procedure for irradiation under batch conditions: A solution of the
furanone (0.5 mmol) and DMBP (0.1 mmol) in isopropanol (15 mL) was added
to a Pyrex glass tube (inner diameter: 9 mm) and purged with argon. The tube
was stoppered and the reaction mixture was irradiated for 5 min at
350 25 nm (Rayonet RPR-100, equipped with 16 ꢁ RPR-3500 Å lamps,
16 ꢁ 8 W). After evaporation of the solvent, the conversion was determined
by 1H NMR spectroscopy of the crude product. Pure products were isolated by
column chromatography.9
This work was financially supported by Science Foundation Ire-
land (SFI, 07/RFP/CHEF817), the Environmental Protection Agency
(EPA, 2008-ET-MS-2-S2), the Department of Environment, Heritage
and Local Government (DEHLG, 2008-S-ET-2) and the Région
Champagne-Ardenne. The authors thank Dr. J. C. Scaiano (Luz-
chem) for providing technical information on the UVA lamp.
12. Braun, A. M.; Maurette, M.; Oliveros, E. Photochemical Technology; Wiley:
Chichester, 1991.
13. Space-time yields (STY) are dependent on the reactor geometry and were
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