Multi-step chemical processes in a modular reactor · Multi-step chemical processes in a modular reactor Alfa Laval Plate Reactors ... Feed 1 = NaOCl & H 2SO 4 (pH adjustment) 16.1

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Multi-step chemical processes

in a modular reactor Alfa Laval Plate Reactors

Barry Johnson Alfa Laval Reactor Technology

[email protected]

PIN NL, Wageningen, the Netherlands

2nd November 2011

© Alfa Laval Slide 1


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


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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


Reactor PlatesProcess Pressure

Plate

Gasket

Channel Plate

Utility Channel

Utility Pressure

Plate


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


RedAl Reduction: Apparatus 2mm PR37

Utility Supply

Julabo LH50

Silicon Oil at 10°C,

200 l/hr


Feedlines

Knauer K1800 HPLC (x2)

Lab Alliance Prep 24 (PEEK)

Swagelok & Valco Vici fittings


RedAl Reduction: T Profiles in 2mm PR37


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


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


Plate Characteristics on Scale Up

Micro-mixing investigated using Bourne Azo-coupling scheme

Bulk-mixing timescales in PR37& PR49 similar


Residence time distributions measured with optical probes

Consistent across Plate Rangeimprove with flow velocity


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


RedAl Reduction: PR37 8mm Results


3.0 kg/hr BA


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


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


RedAL Reduction: PR49 Two T Zones



RedAL Reduction: PR49 Two T Zones & Two BA Feeds



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


May require parallelisation of utility side in reactor


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


Substrate

200

Reactant

20

Product

1000

Catalyst+

Viscosity (mPa.s at 20°C)


8 x 2mm

1 x 4mm1 x 8mm

Reactor Volume = 167 ml

Substrate

+

CatalystReactant

via Nozzle

Product

Customer Process: PR37 Lab Apparatus


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


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



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


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


Customer Process: PR49 Results


1st Plate used to preheat main substrate flow

Product quality maintained on scale up of continuous process - superior to batch


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



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


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


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


Same Droplet Size

Influence drop sizeindependently of

flow velocity thru reactor


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%


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



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 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


Acknowledgements

• Daniel Unge

• Linus Helming

• Ian Reynolds

• Bjorn Elman

• Kasper Hoglund

• Magnus Lingvall

• Magnus Petersson

• Zolo Ostlund


Thank you for your attention

Documents

Multi-step chemical processes in a modular reactor · Multi-step chemical processes in a modular reactor Alfa Laval Plate Reactors ... Feed 1 = NaOCl & H 2SO 4 (pH adjustment) 16.1