Principlr of green Chemistry 12th principle

process intensification

1. The Twelve Prin ciples o f Green Chemistr y

2. 1. Prevention . It is better to prevent waste than to treat or clean up waste after it is formed . 2. Atom Economy . Synthetic methods should be designed to maximize the incorporation of all materials used in the 3. Less Hazardous Chemical Synthesis . Whenever practicable , synthetic methodologies should be designed to use and generate substances that possess little or no toxicity to human health and the environment . 4. Designing Safer Chemicals . Chemical products should be designed to preserve efficacy of the function while reducing toxicity. 5. Safer Solvents and Auxiliaries . The use of auxiliary substances ( solvents , separation agents , etc .) should be made unnecessary whenever possible and , when used , innocuous . 6. Design for Energy Efficiency . Energy requirements should be recognized for their environmental and economic impacts and should be minimized.Synthetic m ethods should be conducted at ambient temperature and pressure. 7. Use of Renewable Feedstocks . A raw material or feedstock should be renewable rather than depleting whenever technically and economically practical . 8. ReduceDerivatives .Unnecessary derivatization (blocking group,protection/deprotection ,temporary modification of 9. Catalysis . Catalytic reagents ( as selective as possible ) are superior to stoichiometric reagents . 10. Desig i t n e v g i . apdr l i i t eir function they do not persist 11. Real-time Analysis for Pollution Prevention .Analytical 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 Prevention . Substance and the form of a substance used in a chemical process Anastas,P.T.;Warner,J.C.Green Chemistry:Theory and Practice,Oxford Uni versity Press,1998. s th c f u o d d on pro the en t t a a d t a a degr so th o s nn de to be in d n u ow ho k ts a c e u br od te al d ins emic n h a C ent ion nm dat o a r r e D he for n n 12 Pri ncipl es of Green Chemistr y should be chosen so as to minimize the potential for chemical accidents , including releases , explosions , and fires . physical / chemical processes ) should be avoided whenever possible . process into the final product .

3. 1.Prevention I t is better to pre vent waste t han to treat o r clean up wa ste after it is formed.

4. ecumenical task force of the niagara frontier LARDOUS CHEMICALS UNA IZED PRQHIBITED Love Canal Colleetio n ◎ 1998 University Achives,Uriversity Librares,State University of New York at Buff alo http://ublib.buffalo.edu/librarie s/projects/lovecanal/ ENTRY UTHOR Environmental Disast ers Love Canal -in Niagara Falls,NY a chemical and plastics company had used an old canal bed as a chemical dump from 1930s to 1950s.The land was t hen used for a new school and ho using track.The chemicals leaked through a clay cap that sealed the dump.It was contaminated with at least 82 chemicals(benzene, chlorinated hydro carbons,dioxin).Health effects of the people living there included:high birth defect incidence and siezure-inducing ner vous disease among the children . ●

5. · Cuyahoga River-Cleve land,Ohio - There were many things being dumped in the river such as:gasoline,oil,paint,an d metals.The river was called " a rainbow of many d ifferent colors ". - Fires erupted on the river several times before June 22,1969,when a river fire captured national attention when Time Magaz ine reported it. Some river!Chocolate-brown,oily,bubbling with subsurface gases,it oozes rather than flows."Anyone who falls into the Cuyahoga does not dro wn,"Cleveland's citizens joke grimly. "He decays." Time Magazin e,August 1969 Environmental Disasters

6. 2.Atom Economy Synthetic methods should be designed to maximize the incorporation of all m aterials used in the process into the final product .

7. Organic Chemistry &Percent Yie ld Epoxidation of an alkene using a peroxyacid 100%yield

8. Percent yield: What is missin g? What co-products are made? How much waste is generated? Is the waste benign waste? Are the co-products benign and/or useable? How much energy is requi red? Are purifica tion steps needed? What solvents are used?(are they benign and/or reusable? Is the“catalyst”truly a catalyst?(stoichiometric vs.catalytic?) Percent yield:

9. Balanced chemical reaction of the epoxidation o f styrene Balanced Reacti ons

10. Balanced Equations Focuses on the reagen ts Stoichiometry? How efficient is the r eaction in practice? Solvents? Energy? Atom Economy: Atom Economy Trost,Barry M.,The Atom Economy-A Search fo r Synthetic Efficiency.Science 1991,254,1471-1477 .

11. Assume 100% yield . 100% of the desired epoxide product is recovered . 100% formation of the co - product :m- chlorobenzoic acid A.E.of this reacti on is 23%. 77% of the products are waste . Balanced chemical reaction of the epoxidation of styrene Atom Econ om y

12. 3.Less Hazardous Chemical Synthesis Whenever practicable,synthetic methodologies should be desi gned to use and generate substances that possess little or no toxicity to human health and the envir onment .

13. ◆ Disadvant ages a phosgene is highly t oxic,corrosive a requires large amount of CH ₂ Cl ₂ m polycarbonate contaminated with Cl impurities Less Hazardous Chemical Synth esis Polycarbona te Synthesis:Phosgene Process HO -OH + C l C NaOH

14. ◆ Advantage s ■ diphenylcarbonate synthesized without phosgene ■ eliminates use of CH ₂ Cl ₂ m higher-quali ty polycarbonates Komiya et al.,Asahi Chemical Industry Co. Less Hazardous Chemical Synthesis Polycarbonate Synthesis:Sol id-State Process

15. 4.Designing Safer Chemicals Chemical products should be designed to preserve efficacy of the function while reducing toxicity .

16. Designing Safer C hemicals Case Study:Antifoulants (Marine Pesticid es) http://academic.s cranton.edu/faculty/CANNM1/environmentalmodule.htm l

17. Antifoulants are generally dispersed in the paint as it is applied to the hull.Organotin co mpounds have traditionally been used , particularly tributyltin oxide ( TBTO ). TBTO works by gradually leaching from the hull killing the fouling organisms in the surroun ding area TBTO and other organot in antifoulants have long half- lives in the environment ( half - life of TBTO in seawater is >6 months ). They also bioconcentrate in marine organisms(the concentration of TBTO in m arine organisms to be 104 times greater than in the surrounding water). Organotin compounds are chronically toxi c to marine life and can enter food chain . They are Designing Safer Chemicals: Case Study:Antifoul ants bioaccumulative . http :// academic . scranton . edu / faculty / CANNM 1/ environmentalmodule . html Tributyltin Oxide

18. Designing Safer Chemicals: Case Study:Antifoul ants Sea - NineR 211 http://www.rohmhaas.com/seanine/index .html Rohm and Haas Pr esidential Green Chemistry Challenge Award ,1996 The active ingredient in Sea - Nine ⑧ 211,4,5- dichloro -2-n- octyl -4- isothiazolin -3- one ( DCOl ), is a member of the isothiazolone family of antifoulants . 4,5-dichloro-2-n-oct yl-4-isothiazolin-3-one DCO| http://academic.scranton.edu/faculty/CANNM1/environmental module.html

19. Designing Safer Chemicals: Case Study:Antifoul ants Sea-Nine ⑧ 211 works by maintaining a hostile growing environment for marine organisms.When organisms attac h to the hull (treated with DCOI),pro teins at the point of attachment with the hull react with the DCOI.This r eaction with the DCOl prevents the use of these proteins for other metabolic processes.The organi sm thus detaches itself and searches for a more hosp itable surface on which to grow. Only organisms attached to hull of ship are exposed to toxic levels of DCOI . Readily biodegrades once leached from ship (half- life is less than one hour in sea water ). http://academic.scranton.edu/faculty/CANNM1/environmental module.html

20. 5. Safer Solvents and Auxiliarie s The use of auxiliary su bstances (solvents, separation agents,e tc.)should be made unnecessary whenever possible and , when used,inno cuous.

21. Safer Solvents · Solvent Substitution · Water as a solvent · New solvents -lonic liquids -Supercritical fluids

22. Preferred Useable Undesirable Water Cyclohexane Pentane Acetone Heptane Hexane(s) Ethanol Toluene Di-isopropyl eth er 2-Propanol MethyIcyclohex ane Diethyl ether 1-Propanol Methyl t-butyl ether Dichloromet hane Ethyl acet ate lsooctane Dichloroet hane lsopropyl ace tate Acetonitr ile Chloroform Methanol 2-MethyITHF Dimethyl formam ide Methyl ethyl k etone Tetrahydro furan N-Methylpyrrolidin one 1-Butanol Xylenes Pyridine t-Butanol Dimethyl sulfoxide Dimethyl aceta te Acetic acid Djoxane Ethylene glycol Dimethoxyet hane Benzene Carbon tetrachlo ride Solvent Selection “Green chemistry tools to influence a medicinal chemi stry and research chemistry based organization” Dunn and Perry,et.al.,Green Chem.,2008,10,31-36

23. Red Solvent Flash point (° C) Reason Pentane -49 Very low flash point,good alternative available. Hexane (s) -23 More toxic than the alternative heptane,classified as a H AP in th e US Di-isopropyl eth er -12 Very powerful per oxide former,good alternative ethers available. Diethyl ether -40 Very low flash point,good alternative ethers available Dichloromethane n/a High volume us e,regulated by EU solvent directive,classified as HAP in US . Dichloroethane 15 Carcinogen,classified as a HAP i n the US. Chloroform n/a Carcinogen,classified as a HAP i n the US. Dimethyl formamide 57 Toxicity , strongly regulated by EU Solvent Directive , classified as HAP in the US N-Methylpyrrolidinone 86 Toxicity,strongly reg ulated by EU Solvent Directive Pyridine 20 Carcinogenic/mutagenic/reprotoxic (CMR)category 3 carcinogen,toxicity very low threshold limit value (TLV )for worker exposures. Dimethyl acetate 70 Toxicity,strongly regulat ed by EU Solvent Directive. Dioxane 12 CMR category 3 carcinogen,classified as HAP in US . Dimethoxyet hane CMR category 2 carcinogen,toxicity Benzene -11 Avoid use : CMR category 1 carcinogen , toxic to humans and environment , very low TLV (0.5 ppm ), strongly regulated in EU and the US ( HAP ) Carbon tetrachlo ride n/a Avoid use:CMR category 3 carcinogen,toxic,ozone depletor,banned under the Montreal p rotocol,not available for large-scale use,strongly regulated in the EU and the US ( HAP ) “Green chemistr y tools to influence a medicinal chemistry and research chemistry based organization” Dunn and Perry,et.al.,Green Chem.,2008,10,31-36

24. Undesirable Solve nt Alternati ve Pentane Heptane Hexane(s) Heptane Di-isopropyl et her or diethyl ether 2-MeTHF or tert-butyl methyl ether Dioxane or dimethox yethane 2-MeTHF or tert- butyl methyl ether Chloroform,dichloroethane or carbon tetrachloride Dichloromet hane Dimethyl formamide,dimethyl acet amide or N-methylpyrr olidinone Acetonitri le Pyridine Et ₃ N (if pyridine is used as a base) Dichloromethane (extraction s) EtOAc,MTBE,toluene,2- MeTHF Dichloromethane(chromatogra phy) EtOAc/heptane Benzene Toluene “ Green chemistry tools to influence a medicinal chemistry and research chemistry based organization ” Dunn and Perry , et . al ., Green Chem .,2008,10,31-36 Solvent replacement table

25. Use of Solvent Replacement Guide resulted in: · 50%reduction in chlorinated sol vent use across the whole of their research division (more than 1600 lab b ased synthetic organic chemists,and four scale-up facilities)du ring 2004-2006. · Reduction in the use of an undesirable ether by 97%over the same two year period · Heptane used over hexane (more toxic)and pen tane (much more flammable) “Green che mistry tools to influence a medicinal chemistry and research chemistry based organization” Dunn and Perry,et.al.,Green Chem.,2008,10,31-36 Pfizer's results

26. A SCF is defined as a substance above its critical temperature ( Tc ) and critical pressure ( Pc ). The critical point represents the highe st temperature and pressure at which the substance can exist as a vapor and liquid in equilibrium. http :// www . chem . leeds . ac . uk / People / CMR / whatarescf . html Liquid Solid Gas Triple point Safer solvents:Superc ritical fluids Critical p oint Tc =31.1℃ Pc=73. 8 bar Supercritical region Temperature ,T pressure,p

27. pre-soaked beans bksh pressue eXtaction vess e caffeine dissolves in water caffeine caffeine water Coffee bean us d i ne gc asf epi en ract oit inc al carbon dioxid e http://www.uyseg.org /greener _industry/pages/superCO2/3superCO2_coffee.htm recovery 山 scCO ₂ + caffeine caffeine dissolves in scCO ² coffee beans decaffeinated caffeine and water ( recycled ) caffeine beans scCO ₂ water

28. 6.Design for En ergy Efficiency Energy requi rements should be recognized for their environmenta l and economic impacts and should be minimized.Synthetic method s should be conducted at ambient temperature and pressure.

29. · Thermal (electric) · Cooling(water condensers,water ci rculators) · Distillation · Equipment (lab hood) · Photo · Microwave Source of energy: · Power plant-coal,oil,natural ga s Energy in a chem ical process

30. Energy usage Chemicals and petroleum industries account for 50% of industrial energy usag e. ~1/4 of the energy used is consumed in distillation and drying processes.

31. Alternative energy sou rces: Photochem ical Reactions Two commercial photoc hemical processes (Caprolactam process &vitamin D3) 1. Caprolactam p rocess NOCl→ NO*+CI( 535nm) (c)2010 Beyond Benign - All Rights Reserved . O .N~ . NOH .2 HCl

32. Alternative Energy Sources: Microwave chemistry · Wavelengths between 1 mm and 1 m - Frequency fixed at 2.45 GHz · More directed source of ene rgy · Heating rate of 10°C per second is achievable · Possibility of overheating (explosio ns) · Solvent-free condit ions are possible · Interaction with matter characterized by penetration depth

33. 7.Use of Renewabl e Feedstocks A raw material or feedstock should be renewable rather than depleting whenever t echnically and economically practical .

34. Biomaterials [Carbohydrates,Proteins,Lipids ] Highly Functionaliz ed Molecules Petroleum Products [ Hydrocarbons ] Singly Functionalized Compounds [ Olefins , Alkylchlorides ] Highly Fu nctionalized Molecules

35. Polymers from Renewable Resources: Polyhydroxyalkan oates (PHAs) · Fe rmentation of glucose in the presence of bacteria and propanoic acid (product contains 5-20%polyhydroxyvalerate) · Similar to polypropene and polyethene · Biodegradable (credit card) OH O 、 ∠ OH Alcaligenes eutrophus HO' OH pro panoic acid R=Me,polydroxybutyrate OH R = Et , polyhydroxyvalerate (c)2010 Beyond Benign -All Rights Reserved.

36. Polуmers from RenемаЫе В езоигсеs: Pоlу(laсtiс асіа ) Beverages find a natural fit with NatureWo rks PLA packaging. Beverages are enhanced with contalners and labels made from Na tureWorks PLA . Showcase your brand whlle allowing consumers to see and taste pure produet Even more refreshing is co nsumer reaction to the Nature Works brand story Market research clearly shows that consumers bellevehat beverages packaged in co ntairers made from nature are fresher and more wholesome , Performance and the envronmental atiributes of botfies and labels made from PLA can provide you with a strong point ol differentiation. http:lvvww.natureworksllc.com/corporate/nw_pack_home.asp

37. Green Chemistry Challenge Award 1999 Small Business Awa rd Municipal solid wast e and waste paper Raw Materials from Renewable Resou r ces: The BioFine Process Agricultural residues, Waste wood Paper mill sludge Levulinic acid

38. Levulinic acid as a platform chemical

39. 8.Reduce Derivatives Unnecessary derivatization ( blocking group , protection / deprotection , temporary modificati on of physical / chemical processes ) should be avoided whenever pos sible.

40. Protecting Grou ps 2 synthetic steps are added each t ime one is used Overall yield and atom e conomy will decrease “Protecting groups are used because there is no direct way to sol ve the problem without them .”

41. Publication s “Noncovalent Derivatives of Hydroquinone:Complexes wi th Trigonal Planar Tris-(N,N- Dialkyl)trimesamides"Cannon,Amy S.;Foxman ,Bruce M.;Guarrera,Donna J.;Warner,John C. Crystal Growth and Design 2005, 5(2),407-411. "Synthesis of Tetrahed ral Carboxamide Hydrogen Bond Acceptors"Cannon,Amy S.;Jian,Tian Ying,Wang,Jun;Warner,John C.Organic Prep.And Proc.Int. 2004 36(4),353-359. “Synthesis of Phenylenebis(methylene)-3-carbamoylpyridinium Bromides”Zh ou,Feng;Wang,Chi- Hua ; Warner , John C . Organic Prep . And Proc . Int . 2004 , 36(2),173-177. "Noncovalent Derivatization:Green Chemistry Appli cations of Crystal Engineering."Cannon,Amy S.;Warner,John C.Crystal Growth and Design 2002 ,2(4)255-257. “Non-Covalent Derivatives of Hydroquinone:Bis-(N,N-Dialkyl)B icyclo[2.2.2]octane-1,4- dicarboxamide Complexes.”Foxman,Bruce M.;Guarrera,Pai,Ramdas;Tassa,Carlos;Don na J.; Warner,John C.Crystal Enginerer ing 1999 2(1),55. “Environmentally Benign Synthesis Using Cryst al Engineering:Steric Accommodation in Non- Covalent Derivatives of Hydroquinones.”Foxman,Bruce M.;Guarrera,Donna J.;Taylor,Lloyd D.; Wamer,John C.Cryst al Engineering. 1998 ,1,109. “Pollution Prevention via Molecular Reco gnition and Self Assembly:Non-Covalent Derivatization.” Wamer,John C.,in “Green Chemistry:Front iers in Benign Chemical Synthesis and Processes.” Anastas,P.and Williamson,T.Eds.,Oxford University Press,Lond on.pp 336-346. 1998. "Non-Covalent Derivatization:Diffusion Control via M olecular Recognition and Self Assembly". Guarrera,D.J.;Kingsley,E.;Taylor,L.D.;Warner,Jo hn C.Proceedings of the IS&Ts 50th Annual Conference. The Physics and Chemistry of lmagi ng Systems,537, 1997. "Molecular Self-Assembly in the Solid State.The Combined Use of Solid State NMR and Differential Scanning Calorimetry f or the Determination of Phase Constitution."Guarrera,D.; Taylor,L.D.;Warner,John.C.Ch emistry of Materials 1994 ,6,1293. "Process and Composition for Use in Photographic Materials Containing Hydroquinones. Continuatio n in Part."Taylor,Lloyd D.;Warner,John.C.,US Patent 5,338,644.August 16, 1994. "Process and Composition for Us e in Photographic Materials Containing Hydroquinones."Taylor, Lloyd D.;Warner,John.C.,US Patent 5,177,262.January 5, 1993. "Structural Elucidation of Solid State Pheno l-Amide Complexes."Guarrera,Donna.J.,Taylor, Lloyd D., Warner,John C.,Proceedings of t he 22nd NATAS Conference,496 1993. "Aromatic-Aromatic Interactions in Molecu lar Recognition:A Family of Artificial Receptors for Thymine that Shows Both Face-To-Face and Edge-To-Face Orientations."Muehldorf,A.V.;Van Engen,D.;Warner,J.C.;Hamilton,A.D.,J.Am.Chem.Soc., 1988, 110,6561. NonCovalent Der ivatization Entropic Control in Material s Design Crystat Engineeri ng Supplement t o Malerials Hesea rch Bulletin AL

42. 9.Catalys is Catalytic reagents (a s selective as possible)are superior to stoichiometric reagents.

43. · Same phase as rxn medium · Difficult to separate · Expensive and/or difficult to separate · Very high ra tes · Not diffusion co ntrolled · Robust to poisons · High selectivity · Short service life · Mild conditions · Mechanisms well understood · Distinct solid phase · Readily separated · Readily regenerated & recycled · Rates not as fast · Diffusion limited · Sensitive to pois ons · Lower select ivity · Long serv ice life · High energy proc ess · Poor mechanis tic understan ding Heterogeneous vs Homoge nous

44. · Distinct solid phase · Readily sep arated · Readily regenerate d & recycled Green · Rat es not as f ast catalys t · Diffusion limited · Sensitive to poison s · Lower select ivity · Long ser vice life · High energy proces s · Poor mechanis tic understan ding · Same phase as rxn med ium · Difficult to separate · Expensive and/or dif ficult to separate Very high r ates ● Not diffusion controlled Robust to pois ons ·\ High sel ectivity Short service life ·\ Mild condi tions · Mechanisms well understood Heterogeneous vs Homoge nous

45. · Enzymes or whole-cell microorganisms · Benefits -Fast rxns due to corr ect orientations -Orientation of site giv es high stereospecificity -Substrate specificity - Water soluble -Naturally occurring -Moderate condition s -P ossibility for tandem rxns ( one - pot) Biocataly sis bindingsi te illustratingind wed ht Hexokinasewith Glucose substrate Binding empty

46. 10.Design for Degradation Chemical products should be designed so that at the e nd of their function they do not persist in the env ironment and i nstead break down int o innocuous degradati on products.

47. Persistence ·Early examples: · Sulfonated detergents — Alkylbenzene sulfonates -1950's &60's - Foam in sewage plants , rivers and streams - Persistence was due to long alkyl chain -Introduction of alkene group into the chain incr eased degradation · Chlorofluorocarbons ( CFCs ) - Do not break down , persist in atmosphere and contribute to destruction of ozone layer · DDT - Bioaccumulate and cause thinning of egg shells

48. Degradation of Polymers: Polylactic Acid ◆ Manufactured from ren ewable resources a Corn or wheat ; agricultural waste in future ◆ Uses 20-50% fewer fossil fuels than conventional plastics ◆ PLA products ca n be recycled or composted C argill Do w

49. 11.Real-time Analysis for Pollution Prevention Analytical methodologies need to be further developed to allow for real - time in-process monitori ng and control prior to the formation of hazardous substa nces .

50. Real time ana lysis for a chemist is the process of “checking the progress of chemical reactions as i t happens." Knowing when your pr oduct is “done”can save a lot of waste, time and energy!

51. Analyzing a Reaction What do you need t o know,ho w do you get this i nformation and how long does it take to get it?

52. 12.Inherently Safer Ch emistry for Accident Prevention Substance and the form of a substance used in a chemic al process should be chosen so as to minimize the pote ntial for chemical accidents,including releases , explosions , and fires .

53. 12.Inherently Safer Chemistry for Accident Prevention Tragedy in Bhopal,India -198 4 In arguably the worst industrial accident in history,40 tons of methyl isocyanate were accidentally released when a holding tank overheated at a Union Carbide pesticide plant,located in the heart of the ci ty of Bhopal. 15,000 people died and hundreds of thousands more were in jured. Chemists try to avoid things that e xplode,light on fire, are air-sensitive,etc. In the"real world"when these things happen,lives are lost.

54. · December 3,1984-poison gas l eaked from a Union Carbide factory,killing thousands instantly and inju ring many more (many of who died later of exposure) .Up to 20,000 people have died as a result of exposure (3-8,000 instantly).More than 120,000 still suffer from ailments caused by exposure What happened? · Methyl isocyanate -used to make pesticides was being stored in large quantities on-site at the plant · Methyl isocyanate is highly reactive,exothermic m olecule · Most safety systems either faile d or were inoperative · Water was released into the tank holding t he methyl isocyanate · The reaction occurred and the methyl i socyanate rapidly boiled producing large quantities of toxic gas. Bhopal,India

55. · U.S.Public Interest Research Group Reports(April 2004)f ind that chemical industry has had more than 25,000 chemical accidents since 1990 · More than 1,800 accidents a year or 5 a day · Top 3:BP,Dow,DuPont(1/3 of the accide nts) http://uspirg.org/uspirgn ewsroom.asp?id2=12864&id3=USPIRGnewsroom& Chemical Industry Accidents