Green Engineering using Commercial Flow Reaction & Process Intensification Platforms Vijay Kirpalani CEO Pi Process Intensification Mumbai 08-12-2013 Copyright Pi-Process Intensification Experts LLP 1
Twelve Principles of Green Chemistry 1. Prevent waste rather than treat/clean it up later 2. Invoke atom economy 3. Design safer chemicals 4. Use & generate less toxic substances 5. Massively reduce quantities of solvents used 6. Design syntheses for energy efficiency 7. Renewable feedstock for large scale processes 8. Minimize steps in synthesis 9. Use of highly-selective catalytic reagents 10. Design materials that innocuously degrade 11. Real-time monitoring for pollution prevention 12. Minimise potential for accidents P.T. Anastas and J.C. Warner, Green Chemistry: Theory and Practice, Oxford University Press: New York, 1998, p.30 8 out of 12 can be achieved through intensification of processes & flow chemistry. 08-12-2013 Copyright Pi-Process Intensification Experts LLP 2
Process Intensification Reactions Flow Chemistry Other Platforms Process Intensification Extraction Distillation Crystallization Unit Operations Filtration Drying Air Pollution Control - Absorption Effluent Treatment Cavitation Reactors 08-12-2013 Copyright Pi-Process Intensification Experts LLP 3
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Pi Benefits 08-12-2013 Copyright Pi-Process Intensification Experts LLP 5
FLOW Chemistry An established technique for performing reactions under conditions where : Mixing Temperature Pressure and Reaction Time are precisely controlled and safely done. Variables : stoichiometry, concentration, residence-time, temperature and pressure are easily adjusted and reactions optimized quickly. Scale-up : nearly linear and usually done by numbering-up 08-12-2013 Copyright Pi-Process Intensification Experts LLP 6
FLOW Reactors Fast Track to Optimized Processes Though the use of Continuous processes is widespread for chemical product, the development of processes for Fine chemicals & APIs has historically been restricted to the centuries-old technique of iterative-batch-reactions. The increasing pressure to quickly discover & deliver compounds using scalable processes has compelled the synthetic chemists to harness Flow Chemistry techniques. Commercial FLOW REACTORS are now an easily available & common enabling technology for performing synthesis in the laboratory & plant scale. Cost benefits ( size / safety / energy efficiency / yield / purity) of flow reactors are so compelling, that the cost of the reactor is of subordinate interest. 08-12-2013 Copyright Pi-Process Intensification Experts LLP 7
FLOW Reactors TECHNOLOGY Selection of apt reactor technology platform is most important for better cost benefit realization :- a) HEAT Transfer Area cost for Heat Transfer limited process b) Reactor Volume cost for Mass Transfer & slow kinetically limited process Key types : Micro-reactors / Microchannel reactors Falling-film micro-reactors Tubular flow reactors Spinning Tube-in-Tube reactors Spinning Disk reactors Spinning Disk FUMI reactors Oscillatory Tube/Baffled flow reactors Microwave assisted flow reactors Sonication-assisted flow reactors Multi-cell flow reactors Aspirator flow reactors 08-12-2013 Copyright Pi-Process Intensification Experts LLP 8
History of Chemical Manufacture Nothing has changed in nearly 500 years Steven Ley, et al 08-12-2013 Copyright Pi-Process Intensification Experts LLP 9
Industry Appeal Higher reaction control translates into : ability to safely handle : hazardous reactions / reagents / unstable-intermediates and highly exothermic reactions consistent good quality & high yields / selectivity Scalability with FLOW Reactors : Numbering-up -- Running multiple reactors in parallel is advantageous there is no theoretical limit to the number of reactors that can be used physical conditions are identical whether using 10 or 10,000 reactors Modular, plug-&-play, quick-fit / release designs 08-12-2013 Copyright Pi-Process Intensification Experts LLP 10
Scalable Development Platforms A few of the scalable Flow Chemistry platforms available to synthesis development chemists today A) Versatile : Limitation : high solid slurries R-series E-series for suspensions 08-12-2013 Copyright Pi-Process Intensification Experts LLP 11
Scalable Development Platforms A) Versatile : Limitation : high solid slurries (cont d) Flow-Syn Asia series 08-12-2013 Copyright Pi-Process Intensification Experts LLP 12
Scalable Development Platforms A) Versatile : Limitation : high solid slurries (cont d) Advanced Flow Reactors Labtrix 08-12-2013 Copyright Pi-Process Intensification Experts LLP 13
Scalable Development Platforms A) Versatile : Limitation : high solid slurries (cont d) MMRS from 08-12-2013 Copyright Pi-Process Intensification Experts LLP 14
Scalable Development Platforms B) Versatile : Can handle solids in a slurry! 30% to 50% solids in slurry! ACR - Coflore COBR Oscillatory Baffled Reactor 08-12-2013 Copyright Pi-Process Intensification Experts LLP 15
Scalable Development Platforms C) Reaction specific : H-Cube for Hydrogenation O-Cube for Ozonolysis 08-12-2013 Copyright Pi-Process Intensification Experts LLP 16
Industrial Scale FLOW Reactors Ehrfeld Lonza Flow Plate Micro Reactor from 08-12-2013 Copyright Pi-Process Intensification Experts LLP 17
Industrial Scale FLOW Reactors KiloFlow & PlantriX KiloFlow & Plantrix (SiC) from 08-12-2013 Copyright Pi-Process Intensification Experts LLP 18
Industrial Scale FLOW Reactors Advanced Flow Reactors Alfa Laval ART Plate Reactor 08-12-2013 Copyright Pi-Process Intensification Experts LLP 19
Industrial Scale FLOW Reactors Coflore ATR : Dynamic Agitated Tubular Reactor 08-12-2013 Copyright Pi-Process Intensification Experts LLP 20
Industrial Scale FLOW Reactors Spinning Tube-in-Tube Hydrodynamic CAVITATION Reactor Kreido Hydrodynamics 08-12-2013 Copyright Pi-Process Intensification Experts LLP 21
Industrial Scale FLOW Reactors FUMI Spin Disk Spinning Disk Reactor SpinPro-300 Volume : 300 ml Output : 10 T / day + 08-12-2013 Copyright Pi-Process Intensification Experts LLP 22
Industrial Scale FLOW Reactors Oscillatory Tube Reactor Oscillatory Baffled Reactor 08-12-2013 Copyright Pi-Process Intensification Experts LLP 23
Industrial Scale FLOW Reactors Continuous Flow Microwave-assisted Reactors CaMWave 08-12-2013 Copyright Pi-Process Intensification Experts LLP 24
Industrial Applications Reactions GRIGNARD Reactions uses ChemtriX PLANTRIX Micro Reactors made of EKasic (SiC) in a pharma API production plant Grignard Reactions 08-12-2013 Copyright Pi-Process Intensification Experts LLP 25
Industrial Applications Reactions Hydroformylation - Evonik example Evonik s container for hydroformylation at the backbone facility of the INVITE GmbH at Leverkusen, Germany jetloop reactor with integrated membrane separation The hydroformylation process in a jetloop with an integrated membrane separation was successfully demonstrated at the INVITE facility in Leverkusen from February to March 2013. 08-12-2013 Copyright Pi-Process Intensification Experts LLP 26
Hydroformylation - Evonik example (cont d) Benefits reduced investment costs through standardized & easily scalable reactor equipment, reduced operating costs due to maximized space-time, yield & integrated heat management, high selectivities due to low heat gradients & ideal mixing improved catalyst lifespan due to separation under process conditions. 08-12-2013 Copyright Pi-Process Intensification Experts LLP 27
Halogen /Lithium Exchange 1.75 T / month on a 2.5 Ø Disk // 7T / month on a 5 Ø Disk 08-12-2013 Copyright Pi-Process Intensification Experts LLP 28
Halogen /Lithium Exchange 1.23 T / month on a 2.5 Ø Disk // 5 T / month on a 5 Ø Disk 08-12-2013 Copyright Pi-Process Intensification Experts LLP 29
Nitration Example (Novartis) Highly Exothermic Batch synthesis delayed 2 months for DSC information Batch scaleup problematic Yield not reproducible Increased formation of by-product led to formation of a gum which was difficult to purify Batch synthesis required significantly more time than expected STRONG EXOTHERM onset at 130 ºC (1373 J/g) http://dx.doi.org/10.1021/op200055r
Unit-Ops -- Extraction SpinPro SDE-300 + Volume : 300 ml Throughput : 10,000 L / day 08-12-2013 Copyright Pi-Process Intensification Experts LLP 31
Unit-Ops -- Distillation Acetic Acid Methanol Catalyst Reactive Distillation Methyl Acetate Methyl Acetate Reactor Solvent Recovery Methanol Recovery Acetic Acid Splitter Extractive Distillaton Water Sulfuric Acid Methanol Extractor Azeo Column Decanter Flash Column Color Column Reactor Column Impurity Removal Columns Heavies Heavies Water Flash Column Eastman Chemicals Water Water 08-12-2013 Copyright Pi-Process Intensification Experts LLP 32
Unit-Ops -- Intensified Distillation 30 mt column replaced by a 1.5 mt column for MeOH Distn. HiGee Distillation 08-12-2013 Copyright Pi-Process Intensification Experts LLP 33
Unit-Ops -- Crystallization Oscillatory Tube Crystallizer 08-12-2013 Copyright Pi-Process Intensification Experts LLP 34
Unit-Ops -- Filtration Modular Spin Disk Filter Dynamic Membrane 08-12-2013 Copyright Pi-Process Intensification Experts LLP 35
Unit-Ops -- Absorption Pulsed-Jet Dynamic Waveform Absorber 08-12-2013 Copyright Pi-Process Intensification Experts LLP 36
Major Route Design Factors and Their Interactions Safety Quality Durability / Robustness Synthesis Process Cost Environmental Impact T.Y.Zhang, Cem.Rev., 2006, 106, 2583. 08-12-2013 Copyright Pi-Process Intensification Experts LLP 37
QUESTIONS? 08-12-2013 Copyright Pi-Process Intensification Experts LLP 38
WISH YOU A GREENER TOMORROW THANK YOU 08-12-2013 Copyright Pi-Process Intensification Experts LLP 39