Corning Advance Flow Reactor Tool for laboratory, process ......Plant view Economics ... DETAIL DESIGN BASIC DESIGN BATCH CONTINUOUS 0,00 5,00 10,00 15,00 20,00 25,00 30,00 35,00 40,00

Corning Advance Flow ReactorTool for laboratory, process development and production

CPAC Rome, March 2011

Dr. Sergio PissaviniBusiness Director

Dr. Pierre WoehlBusiness Development

2© Corning Incorporated 2010

Outline

Reactor Designs Superior Mass, Heat Transfers & Integration with Reactions

Process Intensification Right Process Development Tool & Methodology

Reactions examples Mixing, Integrated Mass/Heat Transports (Immiscible L-L) G-L-S

Engineering Approach Scale up Criteria for application Plant view

Economics Nitration plant Organometallic plant Pantoprazole example

Concluding remarks

Q&A


Mixing & Mass Transfer “Fine” Design

Immiscible liquid-liquid mixing

Gas-Liquid two phase mixing

Computational Fluid Dynamics (CFD)Reactor Design & Flow Hydrodynamics Quantification

Courtesy of Fluent


Efficient Mixing for Multiphase Reaction Systems

• Superior mixing quality for L-L, G-L, G-L-S• Optimized designs for multiphase reactions• High resistance to fouling• Smooth surface for easy clean

Mixing Zones Gas/Liquid


Heat Transfer “Fine” Design & Control

T, 0C8020 140

Model Prediction Accuracy:T < 3 C; HT Coefficient < 8%

Advanced thermal & mechanical designs became possible at fine dimensional scale

(500 m – few millimeters)

Corning Advanced-Flow™ Glass Fluidic ModulesCourtesy of Fluent


Outline Reactor Designs

Superior Mass, Heat Transfers & Integration with Reactions



Engineering Approach Scale up Criteria for application Plant view


Concluding remarks

Q&A


Fluidic modules: concept and library

Reaction layerHeat exchange layer

Heat exchange layer

Mixing 300 microns

Pressure drop1 millimeter Reactants

700 microns

4 mm

Heat transfer

Reactants

Heat exchange fluid

700 microns


1

10

100

1 000

10 000

100 000

1 000 000

10 000 000

100 000 000

0,01 0,1 1 10 100 10001 cm1 mm 1 m

The Impact of Dimensions

100 m

Heat transfer U x (S/V)

(kW/m3.K)

Pressure dropSimple tube

(bar)4128

dQ

LP

Laminar flow

Mixing QualityVillermaux

(%)

100

90

80

450 m

20 bar

6 mm

80 %


Reaction with highMass/Heat transfer resistances

Reaction with highMass/Heat transferResistances

Understand Interactions of Transports & Reaction ‐Essential

AFR can intensify reaction with very short residence time (seconds to few minutes) with similar temperature as batch! –”Transport controlled process”

FastReactionKinetics

Mediate/Slow

Reaction Kinetics

AFR can intensify reaction with short residence time (few minutes) but with higher temperature and/or concentration as batch! (+ 30 ~ 100C)

AFR allows elevated temperature without leading tohigh impurity due to short residence time/better heat transfer

Good mixing of multiphase is essential

Elevated T and/or C & good mixing are essential






Engineering Approach

Scale up Criteria for application Plant view


Concluding remarks

Q&A


Nitration Reactions in Corning® AFRReduced solvent usage, higher yield of safer operation

• Shortening of Development Cycle• Value generated from: reduced solvent usage,

higher yield & significant improvement in safety

Ref: Chemistry Today, 26 (5), 1-4, Sept~Oct (2008)

HOR OH + HNO3

HOR ONO2

O2NOR ONO2X

Product By-ProductCaused Safety Issue

Excellent Mixing of immiscible liquids

Commercial scale demonstration


Large-scale microreactors in production plant B700

Peter Poechlauer; Sascha Brune (DSM), Process intensification in development and efficient production of pharmaceuticals, “2nd symposium on Continuous Flow Reactor Technology for Industrial Applications”, Oct 4‐5, 2010


Green Process: Glycerol to Fuel Additives (STBE) in Corning® AFR: Successful feasibility for large scale production (1)

• 10% biofuels for transports by 2020 in EU• 276 biodiesel plants• 20 millions tons biodiesel capacity in 2009 (EU)• ~1 million Glycerine (50% of capacity, 10% => Glycerine)

Convert Glycerol to STBE(Solketal TertButyl Ether) via Solketal

11-12 kg/hr STBE (90 tons/Year)

Short process development cycle: ~4 months

acetone isobutent

STBESolkertalGlycerine

Ref: Chemistry Today Vol 28 n 4 July/August 2010


Particle Handling in Corning® AFREnable S/L, S/G/L slurry reaction

• Evl Kit (Gen 1) has no problem to handle the solid with variety of particle sizes (up to 200 m) and solid loading up to 2.0%

Particle size(m)

Solid loading(g/L)

Slurry Hydrodynamics

A: 30 2.5 OK

B: 40-75 2.5 Ok

C: 63-200 5.0-20 OK

No clogging all timeA: noble metal catalystB: Silica 200-400 meshC: Silica 65-250 mesh

A1

A2

A3

A4A1

A2

A3

A4

A’2 A’3 A’4A’2 A’3 A’4







Scale up Distribution Criteria for application


Concluding remarks

Q&A


Reactor Kits for Effective Continuous‐Flow Feasibility & Process Development (1/2)

Low internal volume

High flexibility

Metal-free reaction path

Heat transfer and mixing performance consistent with Corning larger-scale reactors (Type 1X, Type 2X, Type 4X)

Standard Reactor Module BStandard Reactor Module A

1~10 ml/min

Low‐Flow Evaluation Reactor Kit

Meeting Customer Need for less chemicals consumption

in R/D


Reactor Kits for Effective Continuous‐Flow Feasibility & Process Development (2/2)

A’2 A’3 A’4

A1

A2

A3

A4

Operating Window: T: ‐60C ~ 230C; P up to 18 bars; 15‐300 ml/min


4X Reactor

Quick Response to Market Demands with Flexible & Scalable Production Capacity

1X Reactor 80 t/yr (process-flow)

2X Reactor

Temperature: -60°C ~ 230°CPressure: up to 18 bars (1.8MPa)

Numbering-up several identical reactors to meet required production capacity from few tons/yr to many thousands tons/yr

g/min 30 160 400 660 1600 3200kg/hour 1.8 10 25 40 100 200T/Yr (8000hr) 14.4 72 180 288 720 1440

720 t/yr

240 t/yr

3 time increased


Numbering‐up Instead of Scaling‐up for ProductionFUNCTIONAL

FLUIDIC MODULESProduction Bank

Scale-Up EffectYes NO Fluidic Modules

Lab scale

Pilot scale

Production Batch

Reactor


Fluid distribution can be internal,…

Typical internal fluid distribution in a plate heat

exchanger

Doc Schmidt (www.apiheattransfer.com/)


…external and passive,…

bifurcation

consecutive


…external and active,…


…each solution having its pros and cons.

MANIFOLD TYPEINTERNAL EXTERNAL

PASSIVE ACTIVE

COMPLEXITY

APPEARS SIMPLE APPEARS COMPLEX

COMPLEXITY HIDDEN AND REAL ACTUALLY SIMPLER THAN IT APPEARS

DIRECT MEASUREMENT NOT POSSIBLE EASY

FLOW ADJUSTMENT NOT POSSIBLE POSSIBLE YES

COST LOW LOW HIGH


Corning’s approach relies on an internal numbering-up..

Conventional internal numbering-up: no way to

correct a wrong distribution

Corning approach with connecting paths between channels (EP 2 172 260 A1)


…together with an adapted external fluid distribution.

Taking into account actual process needs and chemical engineering know-how

A combination of passive and active distribution system. (EP 2 193 839 A1).







Scale up Criteria for application Plant view


Concluding remarks

Q&A


Not to forget cost and scale up risk in process defintion


Case 1: Plant design Comparison – Batch vs. ContinuousSelective Nitration

0

50

100

150

200

250

300

350

400

450

500

550

Am

ount

CONTROLLERS LOCAL INDICATOR DCS INDICATORS

Comparison between Continuous and Discontinuous Plants - INSTRUMENTATION AND CONTROL - TOTAL

CONTINUOUS BATCH

300.000 kfrig/h

100.000kfrig/h

1.000kg/h 500

kg/h

5.000m3/h

1.000m3/h

500Nm3/h

50Nm3/h

10tons/h 4

tons/h

3.000kg/h 2.500

kg/h

800m3/d

500m3/d

BRINE PROCESS WATER SCRUBBER NITROGEN STEAM ACQUEOUSWASTE

CONCENTRATOR

WASTE WATERTREATMENT

Comparison between Continuous and Discontinuous Plants -UTILITIES CONSUMPTION

BATCH CONTINUOUS

Comparison between Continuous and Discontinuous Plants -ESTIMATED TIME FOR REALIZATION

0 5 10 15 20 25 30 35

TOTAL WITHOUT OVERLAP

TOTAL WITH OVERLAP

VALIDATION

COMMISSIONING

AUTOMATION

WIRING

MECHANICAL ASSEMBLING

CARPENTRY

BUILDING CONSTRUCTION

DETAIL DESIGN

BASIC DESIGN

BATCH CONTINUOUS

0,00

5,00

10,00

15,00

20,00

25,00

30,00

35,00

40,00

€/kg

RAWMATERIAL

JOB WASTES PLANT COST(5Y)

BUILDINGS(10Y)

TOTAL

Comparison between Continuous and Discontinuous Plants -PRODUCT DIRECT COST

CONTINUOUS BATCH

0

20

40

60

80

100

120

140

160

180

200

220

Am

ount

FLOW RATE PRESSURE pH TOTAL

Comparison between Continuous and Discontinuous Plants - REGULATION LOOP

CONTINUOUS BATCH

0

5 000 000

10 000 000

15 000 000

20 000 000

25 000 000

€

PROCESS STORAGE UTILITIES GENERAL TOTAL

Comparison between Continuous and Discontinuous Plants -INVESTMENT COST

CONTINUOUS BATCH


NITRATION PLANT – BATCH 400 ton/yr

22.8

0 m

eter

s

42.80 meters 42.80 meters42.80 meters

22.8

0 m

t

22.8

0 m

t

14.8

0 m

eter

s

30.80 meters

Case 1: Plant Footprint Comparison – Batch vs. ContinuousSelective Nitration

NITRATION PLANT – CONTINUOUS 400 ton/yr


Advanced Flow Reactors: Greener and More Economical

-2,5-2,1-1,7-1,3-0,9-0,5-0,10,30,71,11,51,92,32,73,13,53,94,34,75,15,55,96,3

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Greener Index

Econ

omic

Inde

x (E

1/E0)

-1-1


Concluding Remarks

• Superior mass & heat transfers of Corning® AFR offer broad opportunity for multiphase reaction process intensifications

• Right process development tools & methodology are essential to effective development of production technology

• Fundamental understanding of hydrodynamics are critic to multiphase reaction application development

• Tested cases demonstrated promising benefits of using AFR in pharma and fine chemical applications

• Process Intensification in combination with PAT will enable the transition from batch to continuous

• Shorter development time• Minimizing scale-up risk• Open new chemistry routes• Green impact on chemical production

Documents

Corning Advance Flow Reactor Tool for laboratory, process ......Plant view Economics ... DETAIL DESIGN BASIC DESIGN BATCH CONTINUOUS 0,00 5,00 10,00 15,00 20,00 25,00 30,00 35,00 40,00