integrated continuous-flow photoreactors · integrated continuous-flow photoreactors :...
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Integrated Continuous-flow Photoreactors :
Photooxidation with singlet oxygen
N. Emmanuel - J-C. M. Monbaliu
CiTOS – ULiège
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Introduction
2N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
Overview of the project
Examples of model sulfoxides
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Introduction
2N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
Overview of the project
LansoprazoleModafinileOmeprazole
Examples of model sulfoxides Examples of pharmaceuticals sulfoxides high-added value
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1O2
Introduction
2N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
Overview of the project
LansoprazoleModafinileOmeprazole
Examples of model sulfoxides Examples of pharmaceuticals sulfoxides high-added value
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1O2
Introduction
2N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
Overview of the project
LansoprazoleModafinileOmeprazole
Examples of model sulfoxides Examples of pharmaceuticals sulfoxides high-added value
Seamless scale-upPRODUCTIVITY
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1O2
Introduction
2N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
Overview of the project
LansoprazoleModafinileOmeprazole
Examples of model sulfoxides Examples of pharmaceuticals sulfoxides high-added value
Seamless scale-upPRODUCTIVITY Continuous-Flow Chemistry
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Introduction
3N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
What is continuous-flow chemistry?
Batch reactorsContinuous-Flow
micro/mesofluidic reactors
3D internal structure >> 104 µmmL < internal volume < kL
Finite volume of chemicals
3D internal structure < 103 µmµL < internal volume < mL
Infinite volume (flow) of chemicals
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Introduction
3
What is continuous-flow chemistry?
Batch reactorsContinuous-Flow
micro/mesofluidic reactors
3D internal structure >> 104 µmmL < internal volume < kL
Finite volume of chemicals
3D internal structure < 103 µmµL < internal volume < mL
Infinite volume (flow) of chemicals
Reactor TypeSurface/Volume
Ratio (cm²/cm³)
1 m³ reactor 0.06
100 mL reaction bulb 1
microchannel 100 µm 200
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
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Introduction
4
Batch photochemistry
logI0I= ε C l
IA
IB
I0
I0
wA
wB
IA IB>
wA wB<• Lack of uniformity in irradiation
Control of exposure time? Mixing efficiency ? Thickness of solution ? Concentration ?
• Only for low concentrations• Tricky scale-up
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
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Introduction
5
Flow photochemistry
IAI0
I0
wA
wB
IA IB ≈ I0<
wA wB>• Uniform irradiation
Precise controle of exposure time(residence time)
High or low concentrations Thin layer of solution
• Easy scale-up
IB ≈ I0
Ø 750 µm
logI0I= ε C l
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
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Introduction
6
Our project : First step model reaction
Rose Bengal(photosensitizer)
×
hν
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
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Introduction
6
Our project : First step model reaction
Rose Bengal(photosensitizer)
×
Avoided thanks to flow photochemistry
hν
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
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Introduction
6
Our project : First step model reaction
Rose Bengal(photosensitizer)
×
Avoided thanks to flow photochemistry
hν
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
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Photooxidation of (L)-methionine
7N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULg)
Results in batch
0.1 M2h
MethionineRose Bengal
water
Oxidation
2.552.05 2.65 2.95
2.55 2.052.95 2.653.08
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Photooxidation of (L)-methionine
8
Results in a home-made microreactor
0.1 M< 1 min
Segmented flow for an excellent exchange
between liquid and gas
(Discovering the Future of Molecular Sciences, 2014)
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
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Corning Photoreactor
9
Corning© Photoreactors : Laboratory to industrial scale
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
Low-flowLab scale
G1 Pilote (transition)
G3 Industrial scale
1 plate : 155 x 125 mm 5 plates : 155 x 125 mm 5 plates : 310 x 250 mm
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10
Results in a Corning© Advanced-Flow™ Lab Photo Reactor
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
N. Emmanuel, C. Mendoza, M. Winter, C. R. Horn, A. Vizza, L. Dreesen, B. Heinrichs, J-C. M. Monbaliu, Org. Process Res. Dev., 21 (2017) 1435–1438.
1.2 min residence time1.1 O2 equivalent>99%conversion
Corning Photoreactor
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11N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
Low-flowLab scale
G1 Pilote (Transition)
G3 Industrial scale
Corning Photoreactor
0.13 Kg day-1
5.1 Kg day-1
16.5 Kg day-1
productivity
Corning© Photoreactors : Laboratory to industrial scale
1 plate : 155 x 125 mm 5 plates : 155 x 125 mm 5 plates : 310 x 250 mm
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Corning Photoreactor
12
Test of 3 water-soluble photosensitizers
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
Rose Bengal tetrakis(4-carboxyphenyl)porphyrinMethylene blue
λmax : 410 to 420 nm λmax : ~ 670 nm λmax : ~ 540 nm
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Corning Photoreactor
12N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
Rose Bengal tetrakis(4-carboxyphenyl)porphyrinMethylene blue
λmax : 410 to 420 nm λmax : ~ 670 nm λmax : ~ 540 nm
Test of 3 water-soluble photosensitizers
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Corning Photoreactor
12N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
Rose Bengal tetrakis(4-carboxyphenyl)porphyrinMethylene blue
λmax : 410 to 420 nm λmax : ~ 670 nm λmax : ~ 540 nm
Test of 3 water-soluble photosensitizers
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Corning Photoreactor
13
Transposition to other compounds
MeOH
MeOH
α-terpinene Ascaridole
Citronellol
Na2SO4 HCl
Rose oxide
Quantitative conversion in 2 min
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
N. Emmanuel, C. Mendoza, M. Winter, C. R. Horn, A. Vizza, L. Dreesen, B. Heinrichs, J-C. M. Monbaliu, Org. Process Res. Dev., 21 (2017) 1435–1438.
Quantitative conversion in 1 min
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Recovery of photosentizer
14
Rose Bengal in silica nanoparticles
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
45 nm
Pore size : 2.96 nmwt% of RB : 8%Produced by C. Mendoza
Protection against photobleaching
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Recovery of photosentizer
14
Rose Bengal in silica nanoparticles
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
RB-Si
45 nm
Protection against photobleaching
Free RB
Pore size : 2.96 nmwt% of RB : 8%Produced by C. Mendoza
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Recovery of photosentizer
14
Rose Bengal in silica nanoparticles
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
45 nm
Protection against photobleaching
RB-Si Free RB
47%
90%
34%
Quantitative
Quantitative
Quantitative
Pore size : 2.96 nmwt% of RB : 8%Produced by C. Mendoza
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Recovery of photosensitizer
15
Rose Bengal in silica nanoparticles
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
CentrifugationRB-Si NPs recovery
… …
α-terpinene
1st use of
CentrifugationRB-Si NPs recovery
2nd use of 3rd use of
ascaridole
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Recovery of photosensitizer
15
Rose Bengal in silica nanoparticles
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
CentrifugationRB-Si NPs recovery
… …
90%
α-terpinene
1st use of
CentrifugationRB-Si NPs recovery
2nd use of 3rd use of
ascaridole
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Recovery of photosensitizer
15
Rose Bengal in silica nanoparticles
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
CentrifugationRB-Si NPs recovery
… …
90% 86%
α-terpinene
1st use of
CentrifugationRB-Si NPs recovery
2nd use of 3rd use of
ascaridole
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Recovery of photosensitizer
15
Rose Bengal in silica nanoparticles
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
CentrifugationRB-Si NPs recovery
… …
90% 86% 62%
α-terpinene
1st use of
CentrifugationRB-Si NPs recovery
2nd use of 3rd use of
ascaridole
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Recovery of photosensitizer
16
In-line liquid-liquid separation
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
• Multi-phasic system : aqueous phase, organic phase, gas phase, solid phase (NPs)• Higher affinity of free RB (or RB-Si NPs) for aqueous vs organic phase• In-line separation could allow successive uses of photosensitizer
Free RB or RB-Si NPs(Water)
α-terpinene(Toluene)
RB or RB-Si NPS(Water)
ascaridole(Toluene)
Zaiput© SEP-10 Liquid-liquid separator
Total conversion
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Conclusion
17
Photooxidation in continuous-flow reactor
• Benefits from microreactor’s assets Control of irradiation, residence time,
temperature, pressure, …
• Total conversion in short times (min)
• Green conditions : Rose Bengal, Water, light, oxygen, …
• Highly eased scale-up
• Versatility Substrate, photosensitizer, conditions, …
• Opens to plenty of possibilities
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
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Acknowledgments
18
CiTOS:
Dr. J-C. M. Monbaliu
R. GérardyN. TshibalonzaV-E. KassinT. ToupyM-M. SchmitzM. ClavierR. Morodo-Martinez
Corning S.A.S. :
Dr. Y. Jiang
Eng. M. WinterDr. C. HornA. Vizza
+ the team
This research was supported by the French Community (Belgium) and the Joint Research
Actions (ARC 15/19-05 icFlow)
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
ARC team:
C. MendozaC. PaezB. HeinrichsL. DreesenM. Lisemont
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Thank you for your kind attention
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Photooxidation of (L)-methionineThermolysis to vinylglycine
270°C
1.7 minTolueneDMAD
x2
x2
Cbz-Met-OH
Cbz-Met-OMe
Pump
Coolingbath
oven
Thermolysis setup
vinylgycine
N. Emmanuel - J-C. M. Monbaliu (CiTOS - ULiège)
1 N. Lamborelle, J. F. Simon, A. Luxen, J-C. M. Monbaliu, Org. Biomol. Chem., 2015, 13, 11602