Madhav Sapre CTO Pi Process Intensification Mumbai

Transcription

1 GREEN ENGINEERING & PROCESS OPTIMIZATION using Process Intensification Platforms Madhav Sapre CTO Pi Process Intensification Mumbai Copyright Pi-Process Intensification Experts LLP 1

2 Sustainable Development Development that meets the needs of the present without compromising the ability of future generations to meet their own needs. World Commission on Environment and Development (1987) 2

3 12 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. 3

4 12 Design Principles of Green Engineering 1. Prevention instead of treatment(of wastes) 2. Maximize Efficiency (of mass, energy, space & time) 3. Design separation & purification for materials & energy 4. Inherent v/s circumstantial use of non-hazardous inputs 5. Output-Pulled v/s Input-Pushed use of inputs 6. Keep-it-Simple ( complexity is an life-long cost attribute!) 7. Design GOAL targeted durability (not immortality) 8. Target the need (not unnecessary capacity/capability) ( one-size-fits-all solutions are a design flaw! ) 9. Minimize material diversity (in multicomponent/multiproduct campaigns) 10. Integrate material & energy flows 11. Design for commercial after-life 12. Renewable rather than Depleting material & energy inputs 12 out of 12 can be achieved through intensification of processes & flow chemistry. 4

5 Process Intensification Reactions Flow Chemistry Other Platforms Process Intensification Extraction Distillation Crystallization Unit Operations Filtration Drying Air Pollution Control - Absorption Effluent Treatment 5

6 Copyright Pi-Process Intensification Experts LLP 6

7 Pi Benefits 7

8 Optimization Innovation 8

9 Optimization - Principles 9

10 Path to Optimization 10

11 An established technique for performing reactions under conditions where : Mixing Temperature Pressure & 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 11

12 Flow Chemistry enables GREEN Engineering 12

13 FLOW Reactors -Fast Track to Optimized Processes Inspite of continuous processes being widespread in the chemical industry, the development of processes for Fine chemicals & APIs has historically been restricted to the centuries-old technique of iterative-batch-reactions. 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. 13

14 FLOW Reactors TECHNOLOGY PLATFORMS 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 : Pi offers Micro-reactors / Microchannel reactors Falling-film micro-reactors - Tubular & Dynamic-Tubular flow reactors Spinning Tube-in-Tube reactors Spinning Disk reactors Spinning Disk FUMI reactors Oscillatory Tube/Baffled flow reactors (OBRs) Microwave assisted flow reactors Sonication-assisted flow reactors Multi-cell flow reactors Aspirator flow reactors, etc. - 14

15 Industrial Scale Slurry FLOW Reactors from Pi Coflore ATR : Dynamic Agitated Tubular Reactor 10 L ATR replaces a L batch reactor with high solids-slurry 10 Litre Ideal for Hydrogenations & Bio-Catalysis, etc Copyright Pi-Process Intensification Experts LLP 15

16 Biocatalysis in Coflore 16

17 Biocatalysis in Coflore Biocatalytic RESOLUTION of DL-Alanine Comparison Batch v/s ATR (continuous) Gilda Gasparini (AM Technology, UK) 17

18 HYDROGENATION in Coflore 18

19 EPOXIDATION in Coflore Drivers: High atom efficiency, Tims & Energy conservation, high selectivity and virtually no degradation products (impurities) 19

20 Industrial Scale Spinning-Disk FLOW Reactors FUMI Spin Disk Spinning Disk Reactor Forced Uniform Molecular Interdiffusion SpinPro-300 Volume : ml Output : 10 T / day + 20

21 Spinning Disk Reactor - Principle FUMI (Forced Uniform Molecular Interdiffusion) 21

22 Industrial Spinning Disk Reactor LAB / Small PLANT REACTOR 1000s Tonnes/Yr PLANT REACTOR 22

23 Industrial Applications Reactions in Spinning Disk Reactors GRIGNARD Reaction Safe, Atom Efficient, v-low Impurities & Work-up Copyright Pi-Process Intensification Experts LLP 23

24 Reactions in Spinning Disk Reactors Halogen /Lithium Exchange Safe, Atom Efficient, v-high selectivity & No Work-up 21 T/yr on a 2.5 Ø (0.2 ml) Disk // 84 T/yr on a 5 Ø (0.8 ml) Disk Copyright Pi-Process Intensification Experts LLP 24

25 Reactions in Spinning Disk Reactors Halogen /Lithium Exchange (cascade) Safe, Atom & Time Efficient, v-low Impurities & Work-up T/yr on a 2.5 Ø (0.2ml) Disk // 60 T/yr on a 5 Ø (0.8ml) Disk Copyright Pi-Process Intensification Experts LLP 25

26 Industrial Scale FLOW Reactors from Pi PlantriX (Micro-Channel Reactors) 50 to 275 Tonne/Yr Plantrix (SiC) (cgmp) from 300 to 1500 Tonne/Yr the Netherlands High Corrosion-Resistant Grade SiC (EKasiC from ESK) Very few & secure connections safer operations & maintenance non-leachable & diffusion-bonded SiC (not brazed or bolted!) Copyright Pi-Process Intensification Experts LLP 26

27 Reactions GRIGNARD Reaction in PlantriX SiC Micro-Channel Reactor uses ChemtriX PLANTRIX Micro Reactors made of EKasic (SiC) in a pharma API production plant Grignard Reactions 27

28 NITRATION DSM selected ChemtriX v/s Corning. Reasons: very few and secure connections, non-leachable & diffusion-bonded SiC (ChemtriX) v/s Glass or brazed SiC (Corning) Drivers: Control reaction exotherm (runaway, explosive ) for process safety High mono- nitro selectivity, high-productivity & GMP production Copyright Pi-Process Intensification Experts LLP 28

29 Reactions :Nitration (Novartis) Highly Exothermic Batch synthesis delayed 2 months for DSC information Batch scale-up 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) Copyright Pi-Process Intensification Experts LLP

30 Process Intensification of UNIT OPERATIONS 30

31 Unit-Ops -- Extraction SpinPro SDE-300 Volume : 300 ml Throughput : 10,000 L / day + Extremely High Extraction Efficiency Drivers: Complete product extraction, ideal for recovery of solvents/organics from waste water, high-productivity & GMP equipment 31

32 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 32

33 Unit-Ops -- Intensified Distillation 30 mt column replaced by a 1.5 mt column for MeOH Distn. Drivers: v. high vapour-liquid contact surfaces // v. Low reflux ratios // v. Low energy consumption, v. low space requirements HiGee Distillation 33

34 Unit-Ops -- Absorption Pulsed-Jet Dynamic Waveform Absorber Drivers: v. high gas-liquid contact surfaces // v. high efficiency // v. low space requirements 34

35 SUMMARIZING Process Intensified & Optimized Reaction & Operation Platforms 1. small footprint & low CAPEX ( a major advantage for sterile-processing & clean-room projects at a fraction of the CAPEX usually required) 2. v. small (and so low cost) Utility CAPEX -- due to v low peak-loads 3. v. high heat transfer area/volume ratios 4. discernable design-space -- QbD built-in 5. reproducible consistent quality & yields (impurity profile is more precise) 6. genuine feasibility for application of PAT (Process Analytical Tools) 7. highly flexible ( key equipments can be plug-&-produce ) 8. v. high turn-down ratios ( 1000 : 1 times production capacities) 9. High intrinsic safety due to extremely low reaction volumes, low residence times and high degree of temp/pressure control. 10. easy Lab to Plant scalability We now see equipments giving 10,000 MT/yr at 1 Litre reaction volume! It will be interesting to see how the scene unfolds in INDIA Copyright Pi-Process Intensification Experts LLP 35

36 Major Route Design Factors and Their Interactions Safety Quality Synthesis Process Durability / Robustness Cost Environmental Impact T.Y.Zhang, Cem.Rev., 2006, 106,

37 Questions? WISH YOU A GREENER TOMORROW THANK YOU Madhav Sapre ms@pi-inc.co 37