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Multi-step chemical processes
in a modular reactor Alfa Laval Plate Reactors
Barry Johnson Alfa Laval Reactor Technology
Barry.Johnson@alfalaval.com
PIN NL, Wageningen, the Netherlands
2nd November 2011
© Alfa Laval Slide 1
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Outline
• Intro to Alfa Lavals Plate Reactors
• RedAl Reduction
– Small Scale, Increasing Scale, Production Scale
• Industrial Case Study
• TEMPO Oxidation: L/L Example
– Nozzles for mass transfer
• Summary
© Alfa Laval Slide 2
www.alfalaval.com/campaigns/stepintoart© Alfa Laval Slide 3
Alfa Laval ART® Plate Reactors
PR37
PR49
LabPlate
Design temperature:
Process pressures:
Utility pressures:
Flow rates:
Reactor Volumes:
Standard Materials:
-60°C => 200°C
FV => 20 bar
FV => 10 bar
0.15 to 500 litres/hour
Up to 14 litres
S316L, Hastelloy C22
www.alfalaval.com/campaigns/stepintoart© Alfa Laval Slide 4
Reactor PlatesProcess Pressure
Plate
Gasket
Channel Plate
Utility Channel
Utility Pressure
Plate
www.alfalaval.com/campaigns/stepintoart© Alfa Laval Slide 5
RedAl Reduction
O OHH0,6 eq RedAl
Toluene / THF 10-20 oC
2. hydrolysis & workup
Two stage reaction between Sodium bis[2-methoxyethoxy]aluminumhydride and Benzylacetone to produce 4-phenyl-2-butanol
Standard batch operation Flow Operation in Plate ReactorFill reactor with reactant & solvent, cool to 0°C Reactor Plates: 2 mm deep channel
Add RedAl over 2 hrs, T < 20°C with cooling Plate 1 – set temperature of RedAl in THF
Continue mixing and cooling for 1 hr Plate 2 – add ipure ketone, reaction & cool
Repeat for hydrolysis step Plate 3 – add in 3wt% NaOH solution,
Filter off solid waste hydrolysis and cooling
Purify product. 80 – 90 % yield QRedAl = 46 ml/min QBA = 12 ml/min
Reactor Volume = 1 m3 QNaOH = 20 ml/min
Reactor Volume = 40 ml
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RedAl Reduction: Apparatus 2mm PR37
Utility Supply
Julabo LH50
Silicon Oil at 10°C,
200 l/hr
© Alfa Laval Slide 6
Feedlines
Knauer K1800 HPLC (x2)
Lab Alliance Prep 24 (PEEK)
Swagelok & Valco Vici fittings
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RedAl Reduction: T Profiles in 2mm PR37
© Alfa Laval Slide 7
Analysis by GC – MS
Quantitative conversion
10 runs 99.0 to 99.5% alcohol
Production Run yielded
5 mol/hr (0.7 kg/hr) of
alcohol product
Incorporation of hydrolysis workup of adduct inline.
Ability to process undiluted ketone and make more viscous alcohol
Time taken to achieve maximum yield in continuous PR = 10 hrs
Operation with moisture sensitive components
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Making Larger Amounts
Assuming you have done process development in a small channel and want to increase capacity there are several options:
1. Greater Flow Rates
2. Parallelisation
3. Combining 1 & 2
4. Larger sized channels
5. Combining 1 & 4
All possible with plate reactors
© Alfa Laval
0,8 mm2
3 mm2 = 2 x 1.5
6 mm2
12 mm2 = 8 x 1.5
48 mm2 = 16 x 3
180 mm2
+ New PR49 Residence Time Plate
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Plate Characteristics on Scale Up
Micro-mixing investigated using Bourne Azo-coupling scheme
Bulk-mixing timescales in PR37& PR49 similar
© Alfa Laval Slide 9
Residence time distributions measured with optical probes
Consistent across Plate Rangeimprove with flow velocity
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RedAl Reduction in 8mm PR37
2 EX Feedlines (RedAl & BA)
– HNP mzr-11507-ex
– Coreolis Flowmeters
– Millipore Filter
Back pressure regulator
Hydrolysis Line
Outside ATEX Zones
Gear Pump / HPLC Pump
Coreolis Flowmeter
Instrumentation
Pressure Transducers
Type K Inconel Thermocouples
Huber 645w Heater Chiller
4.8 bar or 5 m3/hr, 48 kW
Slide 10
5 x 8mm
Total Volume = 240 ml
RedAlBA
Product
T = ThermocoupleUtility Flow
400 Kg/hr
TTT TT TT
TTT TT TT
TT T
NaOH
F
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RedAl Reduction: PR37 8mm Results
© Alfa Laval Slide 11
3.0 kg/hr BA
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RedAL Reduction: PR49
• Minimise Peak Temperatures
– Lower Reaction Temperature
– 2 BA Feed Points
• Determine production limitations of equipment
• Same Ex Feedlines as for PR37 trials
• Insulator Plate between reactor plates 4 & 5
© Alfa Laval Slide 12
RedAl
T
T
T
T
T
T
T
T
T
T
T
T
T
T
T
T
T
T
T
T
Quench
BA Feed 1
BA Feed 2
Product
Two Utility Feeds
Plates 1 – 4 = Huber Oil
Plate 5 = Mains Water
Total Volume= 2.3 L
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RedAL Reduction: PR49 Two T Zones & Two BA Feeds
© Alfa Laval Slide 14
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RedAl Reduction: Production Capability
PR37 (5 x 8mm Plates)
Potential (2 BA feeds)
∆P Flow Production
(bar) (L/hr) kg/hr
3.8 15 3
10 27 5.4
20 37 7.4
Utility: 400 kg/hr in series, ∆T = 6°C
PR49 (5 Plates)
Potential (2 BA feeds)
∆P Flow Production
(bar) (L/hr) kg/hr
2.3 55.5 11.1
3.2 78.3 15.4
20 200 40 (with10 Plates)
Utility: 2.5 t/hr in series, ∆T = 4°C
© Alfa Laval Slide 15
May require parallelisation of utility side in reactor
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Customer Process
Reactants are initially immiscible, but are soluble in product
Viscous system requiring good mixing throughout length of reactor and temperature control
Elevated temperatures deactivate catalyst
Batch mixing and reaction time 12 hrs
© Alfa Laval Slide 16
Substrate
200
Reactant
20
Product
1000
Catalyst+
Viscosity (mPa.s at 20°C)
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8 x 2mm
1 x 4mm1 x 8mm
Reactor Volume = 167 ml
Substrate
+
CatalystReactant
via Nozzle
Product
Customer Process: PR37 Lab Apparatus
© Alfa Laval Slide 17
S = Sample Point
T = Thermocouple
Utility Flow
150 L/hr
S
S
T
T
TT T TT TT
T TT T
Reactants fed from2 Knauer K1800 pumps
Single plate reactor as cooler
T
T
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Customer Process: PR37 Lab Trials
Total Flows = 8 – 22 ml/min
Reactor Temperatures 80 – 150°C
Vary stoichiometry and catalyst loading – determine unreacted %
⇓⇓⇓⇓
Reaction complete in 3 – 10 minutes
Channel provides sufficient liquid -liquid mixing and mass transfer
Pressure drops 4 to 14 bar
Reaction mixture rapidly reaches operating T with small overstep
© Alfa Laval Slide 18
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Customer Process: PR49 Trials
Pumps
– HNP mzr-7205 & 11507-ex
– Pneumatic Knauer K1900 for highest substrate flows (fed by diaphragm pump)
Coreolis Flowmeters
Brazed Plate Heat Exchanger as post reactor cooler
– 20 Utility / 19 Process Parallel Channels
© Alfa Laval Slide 19
Utility Flow
2 T/hr
Substrate
Substrate
+
Catalyst
Reactant
S = Sample Point
T = Thermocouple
T
PHE Product
T
T
T
T
T
T
T
T
T T
T
S S
SS
Reactor Volume = 2.3 L
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Customer Process: PR49 Results
© Alfa Laval Slide 20
1st Plate used to preheat main substrate flow
Product quality maintained on scale up of continuous process - superior to batch
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Customer Process: Plant Implementation• PR49 Unit used for 5 different products (10 – 100 tons each) of product.
• 2 shifts per day: 2 hours prep, 10 hours operation ,30 minutes cleaning.
• Demonstrated to management as success - better products, less waste, lower stocks
• Production rates to 200 kg/hr from 5 litre reactor (inlet pressure 16 – 18 bar g)
• Implementation & Scale-up
• From batch exists an understanding of the process, make some basic trials in the
PR37 (- experience from the other products) which normally takes 2 days and then
directly to the PR49. So far it has worked very well.
• Handling and Maintenance
• CIP cleaning the unit. “have not opened the unit and have no plan to open the unit”
• Waste generated when shutting down the system and changing products, but this is
still very low compare to batch
Future
• The plan is to have 3 shifts and produce 24/7.
• Want bigger -> 400 kg/hr
© Alfa Lava Slide 21
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© Alfa Laval Slide 22
Case study – TEMPO catalyzed oxidation
Feed 2
Feed 1 10 plates
cooled
by chiller
1 2 3 4 5
10 9 8 7 6
Feed 3
Product
Experimental set-up: 10 x 2mm PR37 Plates in C-22
Feed 1 = NaOCl & H2SO4 (pH adjustment) 16.1 ml/min
Feed 2 = ButoxyEthanol / TEMPO in Toluene 23.1 ml/min
Feed 3 = NaBr / NaHCO3 in Water 10.9 ml/min
www.alfalaval.com/campaigns/stepintoart© Alfa Laval Slide 23
Case study – TEMPO catalyzed oxidation
Total Flow (ml/min) T / °C Reactant Product Byproducts
12.5 No Nozzle 0 46 50 4
37.5 No Nozzle 0 3 60 37
50 + Nozzle – Plate 10 0 1 85 14
– Plate 6 0 1 88 11
– Plate 3 0 1 92 7
– Plate 2 0 1 97 2
Samples quenched with thiosulphate & analysed by GC
Conclusions
Mixing sensitive reaction. Increased flow rate gives increased yield
Use of nozzle increases main reaction rate and improves yield.
Fast reaction with nozzle, 10 plates not required.
Requires quench to prevent over-oxidation.
Peak temperature observed < 5°C
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Scale Up of Nozzles
PR37
• 1 orifice per
Injection nozzle
PR49
• Multiple orifices per Injection nozzle
• Same size Orifices
Numbering up principle
• Same flow rate
• Same velocity
• Same pressure drop
© Alfa Laval Slide 24
Same Droplet Size
Influence drop sizeindependently of
flow velocity thru reactor
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Preliminary Results: TEMPO Oxidation in PR49Feed 1 = NaOCl 16.1 L/hr Reactor = 5 Plates
Feed 2 = H2SO4 (pH adjustment) 1.8 L/hr
Feed 3 = NaBr / NaHCO3 in Water 10.9 L/hr
Feed 4 = ButoxyEthanol / TEMPO in Toluene 23.1 L/hr Nozzle = 16 x 140 µm
∆Treaction = 15°C
Plate 2
T / °C 10
Reactant 6%
Product 89%
Byproducts 5%
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Preliminary Results: TEMPO Oxidation in PR49
Initial Observation
• Scale up can produce good yields at high flow rates
– Add inline quench to stop reaction
• Principle of “numbering up” on nozzle successful
• Operation with “lower performance” pump possible where process characteristics allow and chemical corrosivity dictates
• Direct inline preparation of acidified hypochlorite
– Much easier & safer operation than batch
– Fresher and “stronger” reagent
– Formation of solid sodium sulphate (low solubility salt) at low temperature in vertical flow could lead to deposition & higher pressure drop – had to operate 10°C above PR37
© Alfa Laval Slide 26
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Summary• Demonstrated how very different flow chemistry processes (viscous / 2
phase liquid-liquid / pharma-like) can be taken from laboratory to plant scales
• Proven Plate Reactor technology a tool useful throughout chemical development and production operations
• When considering a process development remember the importance of confirming “similar” performance of equipment at different scales
© Alfa Laval Slide 27
Alfa Laval ART® Plate Reactor:
– a flexible, modular flow reactor range for accurate and controlled continuous chemistry
– adaptable to different reactions and operations
– suitable for process development in the laboratory and for production in the plant
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