Presentation on theme: "Principles and Practices of Green Chemistry"— Presentation transcript:
1 Principles and Practices of Green Chemistry Prepared by:Milton Perez, P.E.Associate Director,Env. AffairsPfizer La Jolla LaboratoriesIEA Biotech CommitteeApril 19, 2006
2 Agenda Introduction to Green Chemistry Safety Aspects of Green ChemistrySome Practical ConsiderationsExample of Green Chemistry Screening Tools
3 What is green chemistry? “…the utilization of a set of principles that reduces or eliminates the use or generation of hazardous substances in the design, manufacture and application of chemical products.”*Source: Paul T. Anastas and John C. Warner, Green Chemistry: Theory and Practice (New York, NY: Oxford University Press Inc., 1998).ISBN
4 Why Green Chemistry?Green Chemistry Describes Technologies, Techniques, and Philosophies, that Enable Efficient Discovery, Development and Manufacturing of new Pharmaceuticals.As our Industry Becomes Increasingly Competitive, It is Incumbent that We Incorporate the Most Efficient, Economical, and Environmentally Sound Practices Possible in Our Daily Operations
5 12 Principles of Green Chemistry (Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice, Oxford UniversityPress: New York, 1998, p.30. By permission of Oxford University Press)1. PreventionIt is better to prevent waste than to treat or clean up waste after it has been created.2. Atom EconomySynthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product.3. Less Hazardous Chemical SynthesesWherever practicable, synthetic methods should be designed to use and generate substances that possess little or no toxicity to human health and the environment.4. Designing Safer ChemicalsChemical products should be designed to effect their desired function while minimizing their toxicity.
6 5. Safer Solvents and Auxiliaries The use of auxiliary substances (e.g., solvents, separation agents, etc.) should be made unnecessary wherever possible and innocuous when used.6. Design for Energy EfficiencyEnergy requirements of chemical processes should be recognized for theirenvironmental and economic impacts and should be minimized. If possible, synthetic methods should be conducted at ambient temperature and pressure.7. Use of Renewable FeedstocksA raw material or feedstock should be renewable rather than depleting whenever technically and economically practicable.8. Reduce DerivativesUnnecessary derivatization (use of blocking groups, protection/ deprotection, temporary modification of physical/chemical processes) should be minimized or avoided if possible, because such steps require additional reagents and can generate waste.
7 12 Principles of Green Chemistry 9. CatalysisCatalytic reagents (as selective as possible) are superior to stoichiometric reagents.10. Design for DegradationChemical products should be designed so that at the end of their function they break down into innocuous degradation products and do not persist in the environment.11. Real-time analysis for Pollution PreventionAnalytical methodologies need to be further developed to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances.12. Inherently Safer Chemistry for Accident PreventionSubstances and the form of a substance used in a chemical process should be chosen to minimize the potential for chemical accidents, including releases, explosions, and fires.
8 Sildenafil (Viagra) Case Study Early Development RouteFinal Process Route
9 Green Chemistry and the Synthesis of Viagra (Sildenafil) 1300 L/kgMedicinal Chemistry1990100 L/kgOptimisedMed. Chemistry199422 L/kgCommercial Route(1997)7 L/kgfollowing solventrecoveryCH2CL2AcetoneEthanolMethanolEtherEthyl Acetate2-ButanoneToluenePyridinet-Butanol4 L/kgFuture TargetNew solvent
10 Safety Aspects of Green Chemistry 1) PreventionLess volume >>> less chance for unplanned events.If hazardous waste is not generated, the infrastructure to manage it will not be required, or if required, to a lesser degree.Fewer hazardous waste storage areas, or smaller ones, means less time spent on weekly inspections and therefore less time in direct contact with containers.
11 Safety Aspects of Green Chemistry 2) Atom EfficiencyThe more efficient the transformation of raw materials into product, the fewer waste streams that will be generated and the less risk of hazardous substances being generated and therefore handled.
12 Safety Aspects of Green Chemistry 3) Less Hazardous Chemical SynthesisWith less hazardous chemical processes, the result will be less risk of unplanned events.Process safety requirements will decrease.Less risk related to storage of hazardous materials due to decreased raw material needs; therefore potentially less need for fire/life safety infrastructure, segregated storage areas.
13 Safety Aspects of Green Chemistry 4) Design Safer ChemicalsThe more inherently safer a product is, the safer they will be to manufacture. Pesticides are a good example.5) Safer Solvents and AuxiliariesHow much time and resources are spent assessing and managing solvent exposures?Many halogenated solvents >>> suspected carcinogens.Spark hazards?
14 Safety Aspects of Green Chemistry 6) Design for Energy EfficiencyWith less heat and pressure, there is less risk of injury due to unplanned release or venting.Cryogenic systems can also cause injury due to extreme cold.7) Use Renewable FeedstocksSustainability aspect of Green Chemistry
15 Safety Aspects of Green Chemistry 8) Reduce DerivativesFewer steps >>> fewer hazardous materials >>> less risk of exposure to employees.10) Design For DegradationAnother principle relating sustainability to green chemistry.11) Real Time Analysis for Pollution PreventionReal-time monitoring allows for assurance of proper reaction conditions which leads to a more controlled situation. More control >>> less risk of generating unwanted products and less risk of upsets.If sampling is done manually, this method would avoid potential employee exposures and the need for personal protective equipment.
16 Safety Aspects of Green Chemistry 12) Inherently Safer Chemistry for Accident PreventionIndustry has experienced many notable chemical accidents; some through carelessness, others accidental, even others unpredictable, and few intentional. On the whole, if you minimized the amount of chemicals used, and select less hazardous materials, the risk decreases.Be careful not to increase accident potential inadvertently while minimizing waste generation; need to consider the whole situation.
17 Some Practical Considerations: Reducing MeCl Usage ExtractionsIf you need to use MeCl measure it, don’t just fill up the separating funnel ?Can Ethyl acetate, t-butyl methyl ether or toluene be used instead ?ChromatographyCan Ethyl Acetate : Heptane mixtures be used (similar polarity) ?EtOH/EtOAc mixtures are an alternative to MeCl/MeOHCan Reverse Phase Chromatography be used ?ReactionsCan you reduce the concentration, CRD suggest 1g in 5ml.EvaporationWhen stripping down MeCl on a rotary evaporator. Transfer the evaporated solvent to the waste container periodically
18 Some Practical Considerations: Reducing MeCl Usage Consider using 2-MeTHF as a replacement for DCM in extractions2-MeTHF avoids the emulsions associated with DCM and has low water solubility making it excellent for extractions.Consider using isopropyl acetate for extractionsMore stable to base than EtOAc and has lower water solubility.Trifluorotoluene (benzotrifluoride) is heavier than water and immiscible with water.A potential bottom level replacement for DCM though significantly more expensive.Note multiple extractions are often not requiredAll of the product is often in the first extraction (especially when extraction solvents with low water solubility are used
19 Green Chemistry Screening Tools: Solvent Replacement Table Non-Green SolventsAlternativePentaneHeptaneHexane(s)Di-isopropyl ether or ether2-MeTHF or t-Butyl methyl etherDioxane or dimethoxyethaneChloroform, dichloroethane or carbon tetrachlorideDCMDMF or DMAcAcetonitrile or NMPPyridineEt3N (if pyridine used as base)DCM (extractions)EtAc, MTBE, toluene, 2-MeTHFDCM (chromatography)EtAc / HeptanesBenzeneToluene
20 Side by Side Comparisons MeCl / Ethyl Acetate MethyleneChlorideEthylAcetateExtraction solventReaction solventChromatography eluantPurchase Cost (4L ACS) $ 3.03 / L $ 3.52 / LHazardous Air Pollutant*? Yes NoOzone Depleting Compound*? No NoOccupational Exposure Limit (PEL)? ppm ppmCarcinogen**? Anticipated Not AnticipatedFlammable? No YesEstimated Disposal Cost $ /liter $ /liter
21 Side by Side Comparisons 2-Methyl THF / THF 2 Me THFTHFExtraction solventReaction solventGreen solventPurchase Cost $ / L $ / LSource Corn starch Oil“Peroxide forming Potential” Lower than THF Present.Miscibility with H2O No YesGlobal warming Potential No NoOccupational Exposure Limit (PEL) Not established ppmCarcinogen? Not established NoFlammable? Yes YesBoiling Point oC oC
22 Side by Side Comparisons Hexane / Heptane HexanesHeptaneChromatography eluantPurchase Cost (HPLC Grade) $2.20/liter $5.25/literHazardous Air Pollutant*? Yes NoVOC*? Yes YesOzone Depleting Compound*? No NoOccupational Exposure Limit(TLV)? ppm (n-hexane) ppmCarcinogen**? Not Anticipated Not AnticipatedBoiling Point oC oCFlash PointHazardous waste cost??? oC oC
23 Green Chemistry Screening Tools: Solvent Selection Spreadsheet