Micro Process Technology for Holistic Process …...D. M. Ratner, E. R. Murphy, M. Jhunjhunwala, D....
Transcript of Micro Process Technology for Holistic Process …...D. M. Ratner, E. R. Murphy, M. Jhunjhunwala, D....
March 2010
V. Hessel [email protected] Institut für Mikrotechnik Mainz GmbHDirectorate Chemical Milli and Micro Process Technologies
2 Eindhoven University of TechnologyDepartment of Chemical Engineering and Chemistry
3 Technische Universität DarmstadtTechnische Chemie / Cluster of Excellence Smart Interfaces
Limburg Horhausen Mainz Eindhoven Darmstadt
22th March 2010 – CPAC Satellite Workshop, Rome
Micro Process Technology for Holistic Process Intensification
- From Ex-Ante Cost/Eco-Efficiency Considerations via Scaling Out to Novel Process Windows
March 2010
GATEWAYS STAND FOR OPENNESSAND ENTRANCE INTO NEW WORLDS
Miyajima Torii – Miyajima Island, next to Hiroshima
Torii is commonly found at the entrance or within a Shinto shrine, where it symbolically marks the transition from the sacred to the profane
March 2010
‘SYNFLOW’
„Changing customer needs“
„More fast and flexible future production strategies“
„New, intensified process and plant concepts forspeeding up market penetration, for enhancing the
product life-cycle and improving sustainable production“
„Develop new production concepts, new start-up and shut-down strategies“
NEW HORIZONS – FUTURE FACTORY CONCEPTS
„Exploit the full potential of micro process technologies“
NMP Large ScaleEU Projects, started 2009-2010
NMP Quests – European Strategy
March 2010
FIVE PRIME DEVELOPMENT ISSUES & SUCCESS FACTORS
FABRICATIONCATALYSTS
REACTORS
PLANTS
PROCESSESOH
OH
OH
OH
COOHKHCO3 (aq)
Volume: ~17 Mio €; funding: 11.0 Mio €, 30% industry15 partners – Coordinator: IMM
Container Platforms (‚Fence-to-Fence‘)Least-Cost-Investment Plants
• Sugar oxidation hydrogenation (Abo Akademi)• Epoxidation (Mythen)• Biodiesel production (Chemtex)• Ammonia production (ITI Energy)• Polymer chemistry reaction 1 (Evonik-Degussa)• Polymer chemistry reaction 2 (Evonik-Degussa)
March 2010S. Hübschmann, D. Kralisch, V. Hessel, U. Krtschil, C. Kompter Chem. Eng. Technol. 32, 11 (2009) 1757-1765.
“Early bird" – ex-ante
EARLY BIRD MEASURING RODS –DO NOT DECIDE TOO LATE
Free
dom
of c
hoic
e, k
now
ledg
e
R & D Scale up Production
Application of decision support and optimisation tools
KnowledgeCosts & Sustainability
Degree of freedomApparatus & Processing
Stage of development
Simplified Life-Cycleand Cost Analysis(SCLA)
“Do not lock the stable door after the horse has bolted"
Process intensification: New processes & plants with step-change performance shift
March 2010
SOME PI CRITERIA- HIERARCHICALLY GROUPED
“Be holistic"
Selectivity
ProductivityEnergy
Cost (cap/op)
Price (product)
Flexibility
Footprint –Land use
Emissions
ToxicitySafety – Plant operational time
Depreciation
Society / Environmental
Company / Economy
Plant / Process
Reaction / ReactorReactivity
Transport – use of local feedstock
March 2010
“Be holistic"
V. Hessel Chem. Eng. Technol. 32, 11 (2009) 1655-1681.
BE HOLISTIC – HAND-IN-HAND DEVELOPMENT OF REACTOR DESIGN AND CHEMISTRY
Maximise transport
Maximise kinetics
Check ex-ante
Previous New, COPIRIDE
March 2010
µ-Mixing
FASTNESS OF REACTIONS
µ-Heat exchange
Met
al/h
alog
en e
xcha
nge,
G
rigna
rd k
eton
ead
ditio
n
Low
-T G
rigna
rd
Nitr
atio
ns,
pept
ide
coup
lings
SN2
reac
tions
10-2 10-1 1 10 100 1000 10,000
Proc
ess
prot
ocl
times
in o
rgan
ic
text
book
s
Man
y, m
any
reac
tions
Intrinsic chemistry * Effective chemistry
* from: Schwalbe, S., Kursawe, A., Sommer, J. Chem. Eng. Tech. 28, 4 (2005) 408-419
conv-Mixing
conv-Heat exchange
MCPT: MASS & HEAT TRANSFERNPW: KINETICS
Intensified chemistry
Mos
t rea
ctio
ns
LONZA-class A (8%) LONZA-class B (9%) ‘LONZA-class D’ (81%)
Roberge, D.M., Ducry, L., et al. Chem. Eng. Tech. 28, 3 (2005) 318-323
Time [s]
March 2010
T. Razzaq, T. N. Glasnov, C. O. Kappe, Eur. J. Org. Chem. 2009, 1321–1325.
March 2010
V. Hessel Chem. Eng. Technol. 32, 11 (2009) 1655-1681.
NOVEL PROCESS WINDOWS
German NPW Research Cluster: 7 projects
March 2010
EARLY LITERATURE REVIEWS
High temperature
High pressure
Supercritical fluids
Ultrasound
Plasma
Microwaves
March 2010
March 2010
Comparable yields were obtained for the continuous process, but with much shorter reaction times:
Reaction time reduction at best up to 2000 times; increase in space-time yield by factor 440
0
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0 20 40 60 80 100 120 140Time (min)
Yiel
d(%
)
At reflux conditions
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0 0.18 0.37 0.72 1Time (min)
Yiel
d(%
) Continuous process
Batch process
T= 180oCp= 40 bar
OH
OH
OH
OH
COOHKHCO3 (aq)
V. Hessel, C. Hofmann, P. Löb, J. Löhndorf, H. Löwe, A. Ziogas Org. Proc. Res. Dev. 9, 4 (2005) 479-489
KOLBE-SCHMITT SYNTHESIS: SPEED-UP OF REACTION BY HIGH-p,T PROCESSING
March 2010
PROCESS INTENSIFICATION: INCREASE IN SPACE-TIME YIELD BY HIGH-p,T PROCESSING
160°C, previous results200°C, previous results
140°C, previous results
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12 8Residence time (s)
Total flow rate (ml/h)
Yiel
d(%
)
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200°C, previous results
140°C, previous results
200°C, previous results
140°C, previous results
65 32 16 12 8
Residence time (s)
Total flow rate (ml/h)
Yiel
d(%
)
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0 1000 2000 3000 4000 5000Total flow rate (ml/h)
Yiel
d(%
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160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results
6532 16
12 8Residence time (s)
Total flow rate (ml/h)
Yiel
d(%
)
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Yiel
d(%
)
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50200 C, Vorversuche140 C, Vorversuche
65 32 16 12 8
Residence time (s)
5400
4
10800
10700 15400
18300 30750
560
200 C, Projekt250 C, Projekt
160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results
6532 16
12 8Residence time (s)
Total flow rate (ml/h)
Yiel
d(%
)
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0 1000 2000 3000 4000 5000
Yiel
d(%
)
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200°C, previous results
140°C, previous results
200°C, previous results
140°C, previous results
65 32 16 12 8
Residence time (s)
Total flow rate (ml/h)
Yiel
d(%
)
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0 1000 2000 3000 4000 5000Total flow rate (ml/h)
Yiel
d(%
)
0
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50
0 1000 2000 3000 4000 5000
160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results
6532 16
12 8Residence time (s)
Total flow rate (ml/h)
Yiel
d(%
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Yiel
d(%
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65 32 16 12 8
Residence time (s)
5400
4
10800
10700 15400
18300 30750
560
200 °C, Ölbad, wässrig250 °C,
6064200
Ölbad, wässrigÖlbad, BMIM-HC200 °C,
160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results
6532 16
12 8Residence time (s)
Total flow rate (ml/h)
Yiel
d(%
)
0
10
20
30
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50
0 1000 2000 3000 4000 5000
Yiel
d(%
)
0
10
20
30
40
50
200°C, previous results
140°C, previous results
200°C, previous results
140°C, previous results
65 32 16 12 8
Residence time (s)
Total flow rate (ml/h)
Yiel
d(%
)
0
10
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50
0 1000 2000 3000 4000 5000Total flow rate (ml/h)
Yiel
d(%
)
0
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50
0 1000 2000 3000 4000 5000
160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results
6532 16
12 8Residence time (s)
Total flow rate (ml/h)
Yiel
d(%
)
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10
20
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50
0 1000 2000 3000 4000 5000
Yiel
d(%
)
0
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50200 C, Vorversuche140 C, Vorversuche
65 32 16 12 8
Residence time (s)
5400
4
10800
10700 15400
18300 30750
560
200 C, Projekt250 C, Projekt
160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results
6532 16
12 8Residence time (s)
Total flow rate (ml/h)
Yiel
d(%
)
0
10
20
30
40
50
0 1000 2000 3000 4000 5000
Yiel
d(%
)
0
10
20
30
40
50
200°C, previous results
140°C, previous results
200°C, previous results
140°C, previous results
65 32 16 12 8
Residence time (s)
Total flow rate (ml/h)
Yiel
d(%
)
0
10
20
30
40
50
0 1000 2000 3000 4000 5000Total flow rate (ml/h)
Yiel
d(%
)
0
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50
0 1000 2000 3000 4000 5000
160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results160°C, previous results200°C, previous results
140°C, previous results
6532 16
12 8Residence time (s)
Total flow rate (ml/h)
Yiel
d(%
)
0
10
20
30
40
50
0 1000 2000 3000 4000 5000
Yiel
d(%
)
0
10
20
30
40
50200 °C, Vorversuche140 °C, Vorversuche
65 32 16 12 8
Residence time (s)
5400
4
10800
10700 15400
18300 30750
560
200 °C, Ölbad, wässrig250 °C,
6064200
Ölbad, wässrigÖlbad, BMIM-HC200 °C,
OH
OH
OH
OH
COOHKHCO3 (aq)
V. Hessel, C. Hofmann, P. Löb, J. Löhndorf, et al. Org. Proc. Res. Dev. 9, 4 (2005) 479-489.V. Hessel, U. Krtschil, P. Löb, A. Stark, et al. Org. Proc. Res. Dev. 13, 5 (2009) 970-982.U. Krtschil, V. Hessel, A. Stark, D. Reinhard Chem. Eng. Technol. 32, 11 (2009) 1774-1789.
Reaction time reduction at best up to 2000 times; increase in space-time yield by factor 3200
4 t / a64200 kg/(m³ h)
4 sFlow chem (9 ml)
Batch (1 l)2 h – 7200 s20 kg/(m³ h)
1 t / a
140°C, (initial)200°C, aq (initial)200°C, aq250°C, aq200°C, IL BMIM-HC
Elevated temperature
March 2010IMM Presentation 15
0
5
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35
40
45
0,0000 0,0500 0,1000 0,1500 0,2500 0,3000
Residence time [s] (reciprocal)
Yiel
d2,
4-D
HB
A [%
]
1/16 in. capillary, 200 °C, 35 bardedicated µ-reactor, 206-219 °C, 35 bardedicated µ-reactor, 200 °C, 70 bardedicated µ-reactor, 220 °C, 70 barnondedicated µ-reactor, 220 °C, 35 bar
46.5811163265130
196
34450
STY[kg/m³h]15500
200 g/h
9 g/h
20300
90 g/h
productivity
38250
225 g/h
29800
175 g/hgas formation,
intermittent flowgas formation,
intermittent flow
25-fold productivity25-fold productivity
GOOD MICROREACTORS STILL NEEDED … FOR SCALE-OUT
March 2010
INCREASE IN REACTIVITY VS. SELECTIVITY
at high temperatures and for longer residence times:
minor variation in yield
at high temperatures and for longer residence times:
minor variation in yield
substantial increase in selectivity substantial increase in selectivity
Capillary reactor, O.D. 1/8 inch 35 bar
0
5
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35
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45
0,0000 0,0100 0,0200 0,0300 0,0400 0,0500 0,0600 0,0700 0,0800 0,0900
Residence time [s] (reciprocal)
Yiel
d2,
4-D
HB
A a
nd 2
,6-D
HB
A [
%]
((
2,4-DHBA, 160°C2,4-DHBA, 180°C2,4-DHBA, 200°C
2,6-DHBA, 160°C2,6-DHBA, 180°C2,6-DHBA, 200°C
130385 33 25 20 17 1113
1
65
O OH
OH
OH
rearrangement
ΔT
O
OHOH
OHΔT
OH
OH
+ CO2
2,4-Dihydroxybenzoic acid 2,6-Dihydroxybenzoic acid Resorcinol
March 2010
HCO3- donating ionic liquids
M-IL-KSM-A-KSMicrowave
CH-IL-KSCH-A-KSConventional
Ionic liquidAqueousHeating
Solvent
BRIDGING PI TECHNOLOGIES
Faysal Benaskar (TUe)Internship at IMM
V. Hessel, U. Krtschil, P. Löb, A. Stark, et al. Org. Proc. Res. Dev. 13, 5 (2009) 970-982.
V. Hessel, D. Kralisch, U. Krtschil Energy Environ. Sci. 1, 4 (2008) 467- 478.
March 2010
‚Footprint‘ - distinct LCA (and costing) patterns; determining factors: here, energy and raw materials
Linear extrapolation to productivity 100 g 2,4-dihydroxy benzoic acid
GLOBAL WARMING POTENTIAL
Standard
IL Supercritical
S. Hübschmann, D. Kralisch, V. Hessel, U. Krtschil, C. Kompter Chem. Eng. Technol. 32, 11 (2009) 1757-1765.
Global warming potential [kg CO2/FE]
March 2010
REACTION TIME IS DETERMINING FACTOR NO. 1
Fast reaction processing has much better global warming potentialEfficient use of reactor capacities is prime issue for eco-efficient processing
Glo
bal w
arm
ing
pote
ntia
l[k
g C
O2
/ FE;
0.1
kg
prod
uct]
V. Hessel, D. Kralisch, U. Krtschil Energy Environ. Sci. 1, 4 (2008) 467- 478.
Waste waterElectrical energySolvent / ILKHCO3
Resorcinol
Reaction timereduction
Reaction timereduction
March 2010
Multi Criteria Decision Support
A. Azapagic, R. Clift, Computers and Chemical Engineering 23 (1999) 1509–1526.
Multiobjective Optimisation (MO)
BUNDLING OF PI CRITERIA INTO ONE DECISION – GREEN OR STOP LIGHT
March 2010
‘Lukewarm’ ex-cryogenico processes –MOFFAT-SWERN OXIDATION
T. Kawaguchi, H. Miyata, K. Ataka, K. Mae, J.-i. Yoshida, Angew. Chem. Int. Ed. 44 (2005) 2413 –2416.
S O + (CF3CO2)2O S+ OCOCF3
HOR'
RS+ O
R
R'
OR'
RS+
1st Step
2nd Step
3rd Stepbase
• Batch: very low temperatures (<-50°C)• Microreactor: temperatures between -20 and 20°C
• Microreactor yields >> batch yields (e.g. 95% opposed to 20%) at very short residence times of 0.01 s
Elevated temperature
March 2010
GLYCOSYLATIONS
D. M. Ratner, E. R. Murphy, M. Jhunjhunwala, D. A. Snyder, K. F. Jensen, P. H. Seeberger, Chem. Commun. 2005, 578–580.
OBnOBnO OAc
OBn
O
CCl3
NHO
OBn
OOBnO
OOO
O
OO
OBn
+OO
O OH
OO
OO
O O
OO
OOAcBnOBnO
OBn
+TMSOTfCH2Cl2
• Batch: good yields at -60°C and 213 s• Microreactor: same yield at -35°C and 25.7 s
Mannosylation of diisopropylidene galactosewith mannosyl trichloroacetimidate
Elevated temperature
March 2010
‘Scalding hot’ pressurized ex-reflux processes –BROMINATIONS
P. Löb, H. Löwe, V. Hessel, J. Fluorine Chem. 125, 11 (2004) 1677-1694.
CH3 CH3
Br
CH3
Br
CH2BrBr2
+ +
CH2
NO2
CH2Br
NO2
Br2
• High temperature: core-substitution
• 0°C: 20% side-chain bromination
•190°C: side-chain bromination• Higher conversion (40% to 95%)
with temperature and pressure
Elevated temperature
March 2010
COPPER-FREE SONOGASHIRA COUPLING
H. Kawanami, K. Matsushima, M. Sato, Y. Ikushima, Angew. Chem. Int. Ed. 46 (2007) 5129 –5132.
H
+I
RR
cat., base
rapid mixing andheating in HPHT-time: 0.012 - 4 s
H2O
• Green process: water-mediated, without organic solvents
• Copper-free process without specific ligands for Pd catalyst
• Nearly quantitative yield at 0.1–4.0 s, 250°C and 16 MPa
• Even at 0.035 s: yield was >96% yield, but decreased to 1.5% at 0.012 s
Elevated temperature
March 2010
NEWMAN-KUART REARRANGEMENT
X. Zhang, S. Stefanick, F.J. Villani, Org. Process Res. Dev. 8, 3 (2004) 455.
NO2
O
NMe2S
NO2
S
NMe2O
170°C90 %
• Scale-up prohibited in multi-purpose plants > 140°C
• Safe operation in microreactors > 200°C
• Yield near 100% at 170°C > yield by laboratory equipment (90%)
O-(2-nitrophenyl)-N,N-dimethylthiocarbamate to S-(2-nitrophenyl)- N,N-dimethylthiocarbamothioate
Elevated temperature
March 2010
Alternative solvents
Elevated temperature
March 2010
HYDROSILYLATION
A. Odedra, K. Geyer, T. Gustafsson, R. Gilmour, P. H. Seeberger, Chem. Commun. 2008, 3025–3027.
• Reduction of deoxy sugars at excellent yield (>90%)
• No toxic or chlorinated solvents such as CCl4• Process simplicity as compared to literature procedure
• Enhanced reactivity and changes in stereochemistry / cis/trans selectivities
Reduction with TTMSS, tris(trimethylsilyl)silane of various alcohol-derived thiocarbonyl derivatives in superheated toluene at 130°C with 5 min
Ph + H Si(TMS)3Ph
H Si(TMS)3
Elevated temperature
March 2010
NUCLEOPHILIC AMINATION
T. Razzaq, T. N. Glasnov, C. O. Kappe, Eur. J. Org. Chem. 2009, 1321–1325.
N Cl N
O
H
N NO
+NMP (0.04 M)
270 °C, 70 bar0.4 mL/min
Full conversion and 82% yield within 8 min at 270 °C and 70 bar as opposed to reaction times of several days in conventional equipment
Elevated temperature
March 2010
toluene thiophene
Br2 [ml/h] / Educt [ml/min]:
meta-nitrotoluene
18.6 / 42.824.5 / 49.8
18.4 / 28.4
reaction speed
formation of gaseous hydrogen bromide
CORE AND SIDE-CHAIN BROMINATIONS WITH ELEMENTAL BROMINE
Solvent-free
March 2010
S Br S Br
BrBr
BrS Br
Br
BrS BrBr
0
10
20
30
40
50
60
70
80
90
0 1 2 3 4 5Molar ratio bromine : thiophene
sele
ctiv
ity [%
]
2-BrT2,5-DiBrT2,3,5-TriBrT2,3,4,5-TetraBrT
• T = 0°C• Pure bromine
Löb, P.; Löwe, H.; Hessel, V.; Letters of Organic Chemistry 2, 8 (2005) 767-779
Löb, P.; Löwe, H.; Hessel, V. J. FluorineChem. 125, 11 (2004) 1677-16946
100
Solvent-free
THIOPHENE BROMINATION
• Figure of merit: optimum for formation of 2,5-dibromothiophenetherefore processing at molar ratios of 2
March 2010
• Large heat releases – in batch addition of reactants drop per drop over 24h – micro-reactor operation needs only some minutes (1.6 – 29 min)
S. Hubbard Master thesis, Fresenius Europa Fachhochschule Idstein/Germany (2005).
H. Löwe, V. Hessel, S. Hubbard, P. Löb Org. Proc. Res. Dev. 10, 6 (2006) 1144-1152.
• Large increases in space-time yield by micro-flow processing (8 – 652 x, based on g /ml h)-1)
Solvent-free
MICHAEL ADDITION
March 2010
Alternative solventsN
OH
scH 2O ONH
no catalyst
Sulfuric acid 383 0.1 5400 72Zeolites 623 0.1 3600 95H2O 523 40 180 0scH2O 673 40 0.63 83scH2O-HCl 648 40 0.73 99
Process T [K] p [MPa] t [s] Y [%]
Y. Ikushima, K. Hatakeda, O. Sato, M. Sato, oral presentation, ACHEMA Congress (2003)
BECKMANN REARRANGEMENT – NYLON 6 INTERMEDIATE
Process simplification: elimination of need for acid at increased reaction speed
March 2010
T. Razzaq, T. Glasnov, C. Kappe, Eur. J. Org. Chem. (2009) 1321.
Ph
O
OEtscMeOH
350°C, 180 barPh
O
OMe
Ph
O
OHscEtOH
330°C, 180 barPh
O
OEt
G. Socher et al., Fresenius J. Anal. Chem. 371 (2001) 369.
Transesterification
Esterification
Tc = 268°C; pc = 61 bar.
Tc = 239°C; pc = 81 bar.
ESTERIFICATIONS IN SUPERCRITICAL ALCOHOLS
Process simplification: no catalyst used – high ionic product of SCFs
18 min
12 min
Alternative solvents
March 2010
HAZARDOUS REACTIONSFLUORINATIONS WITH REACTIVE AGENTS
M. Baumann, I.R. Baxendale, L.J. Martin, S.V. Ley, Tetrahedron 65 2009, 6611–6625.
O
N
N
OCN
OO
O
O
N
N
OCN
O
O
FF
DAST
• DAST: volatile, reacts violently with water and readily undergoesdismutation to SF4 and (Et2N)2SF2
• Nucleophilic fluorination, electrophilic fluorination and trifluoromethylation• Purities >95% & yields up to 95%, eliminating purification• Superheated processing with rate acceleration
Dedicated fluorinations with diethyl-amino-sulfur trifluoride (DAST), (1-chloro-methyl-4-fluoro-1,4-diazo-niabicyclo-[2.2.2]octane), bis(tetra-fluoroborate) (Selectfluor®), and trimethylsilyl trifluoromethane(TMS-CF3, Ruppert’s reagent)
Hazardous reagents
March 2010
TRIMETHYLALUMINIUM MEDIATED AMIDE FORMATION
T. Gustafsson, F. Pontén, P.H. Seeberger, Chem. Commun. 2008, 1100–1102.
Cl
O
+Cl
O
CO2Et
OOEt
OEtO
O
Cl
NNCO2Et
ClCl
Cl
NN
ClCl
NH
O
N
a
b
c
• Al-catalyst highly pyrophoric and difficult to handle in larger volumes• Aluminium–amide intermediate is unstable at elevated temperatures • Batch: 16 h; combined microwave and microreactor operation at 2 min• Applied for the synthesis of rimonabant and efaproxiral at 49% yield• Rimonabant is anti-obesity drug & central cannabinoid receptor antagonist
Hazardous reagents
March 2010
AUTOCATALYTIC NITRATION OF PHENOL
L. Ducry, D. M. Roberge, Angew. Chem. 117 (2005) 8186–8189.
OHOH
NO2
OHNO2
OH
OH
OH
NO2
NO2OH
O2N NO2HNO3 + + + +
• Even at small batch scale (1 l) thermal runaway with 55 K increase• Hot-spot in microreactor only 5 K• Micro processing with largely increased purities (batch: up to 25%, micro-
flow: up to 79%), and higher yields (batch: up to 32%, micro flow: up to 77%)• Micro processing at concentrated conditions, almost solvent-free and
without H2SO4 or CH3CO2H
• Nitration of phenol: catalyzed by nitrous acid and not by the nitronium ion• Autocatalytic behaviour Hazardous reagents
March 2010
IMPROVEMENT OF PRODUCT QUALITY - IONIC LIQUID SYNTHESIS
Conventional, discontinuous manufacture• Unsufficient heat transfer in vessel -> undesired
temperature increase -> product coloration, slowing down of processing
• Large volumina of hazardous reactants
© Solvent Innovation GmbH
Conventional productionprocess
N NEtMe
Et2SO4+N NMe EtSO4
Continuous microreactor processing
Microreactor plant IMM (Laboratory scale)
• Much improved heat transfer -> faster process, no coloration
• Reduction of reactor volume(= safety gains)
March 2010
• Continuous processing• Reduction of reaction time down to minutes
Reactor tube segments with in total 7.5 ml inner volume
Mixer
Thermostated bath withembedded reactor parts
Temperature recordingsystemPumps
0
20
40
60
80
100
0 5 10 15 20
Residence time [min]
Con
vers
ion
[%]
30°C
40°C50°C
0
20
40
60
80
100
0 5 10 15 20
Residence time [min]
Con
vers
ion
[%]
30°C
40°C50°C
Initial lab rigMicromixer/tube set-up
• Optimised reactor parameters
50
60
70
80
90
100
110
0 20 40 60 80 100
in frontof mixer
50°C, 210 ml/h
1/8´´1/16´´
Flow axis [vol.-%]
Tem
pera
ture
[°C
]
1/8´´
50
60
70
80
90
100
110
0 20 40 60 80 100
in frontof mixer
50°C, 210 ml/h
1/8´´1/16´´
Flow axis [vol.-%]
Tem
pera
ture
[°C
]
1/8´´
PROCESS INTENSIFICATION BY CONTINUOUS PROCESSING
March 2010
Modular microreactor Multitubular reactorwith switchable tubes
The reactor set-up has been implemented in thedemonstration facility errected at and by RWTH Aachen
Continuous 36 h operationperformed successfully.
REACTOR SETUP FOR 100 kg/d IONIC LIQUID SYNTHESIS
March 2010
Zunächst war der 20 kg/d Reaktor des IMM integriert, späterwurde dieser und der folgende RWTH-Reaktor durch den 100 kg/d Gesamtreaktoraufbau des IMM ersetzt.
FABRICATIONCATALYSTS
REACTORS
PLANTS
PROCESSESOH
OH
OH
OH
COOHKHCO3 (aq)OH
OH
OH
OH
COOHKHCO3 (aq)
REACTORS
PILOT PLANT AT RWTH AACHEN FOR 20 AND 100 kg/d IONIC LIQUID SYNTHESIS
March 2010
x 10Labor
Pilot
Pilot
x 10Produktion
B. K. Vankayala, P. Löb, V. Hessel, G. Menges, C. Hofmann, D. Metzke, U. Krtschil, H.-J. Kost Int. J. Chem. Reactor Eng. 5 (2007) A 91
SCALE-OUT CONCEPTS FORFALLING FILM MICROREACTORS
March 2010
• Performance kept from FFMR-LARGE to STACK-1x-FFMR-LARGE• Basic reactor design thereby proved
Operation conditions: 1 M NaOH 0.5 – 1.6 (5 – 16) ml/min; CO2: 6.22 (62.2) ml/min diluted with N2 35 (350) ml/min; co-current operation mode
DO SCALED-OUT FFMRs BEHAVE THE SAME? TEST BY CO2 ABSORPTION IN ALKALINE SOLUTION
3035404550556065707580
0.02 0.04 0.06 0.08 0.1 0.12NaOH flow rate/structured area [cm/min]
NaO
Hre
acte
d[%
] StandardCylindricalLarge1-stack
March 2010
PILOT FALLING FILM MICROREACTORS IN PILOT PLANTS AT EVONIK-DEGUSSA
Ozone generator
Falling film microreactorof IMM for pilot scale
Ozone decomposition unit
Franke, R., Jucys, M., Löb, P., Rehfinger, A., Elements –Evonik Science Newsletter 2007, 22, 20.
BMBF-Projektµ.Pro.Chem
March 2010
100 xValidatednumbering-up concept
Outlook: first stepstowards even larger scalereactors have been done
ACHIEVED: THROUGHPUT INCREASE BY FACTOR 100x; FACTOR 1000 UNDERWAY
March 2010
• Be holistic – complete process development view
• Exploit fast kinetics – chemistry is not slow, but is slow made
• Process intensification - new processing – evaluation tools
• Flow chemistry: micro and milli processing tools in cascaded manner
• Scaling-out: numbering-up at micro and smart scaling-up at milli level
• Production flow chemistry is there – future factories need to be developed
CONCLUSIONS