1. The Twelve Principles of Green Chemistry
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2. 12 Principles of Green Chemistry
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 process into the final product.
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 methods 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. Reduce Derivatives. Unnecessary derivatization (blocking group, protection/deprotection, temporary modification of physical/chemical processes) should be avoided whenever possible .
9. Catalysis. Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.
10. Design for Degradation. Chemical products should be designed so that at the end of their function they do not persist in the environment and instead break down into innocuous degradation products.
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 should be chosen so as to minimize the potential for chemical accidents, including releases, explosions, and fires.
Anastas, P. T.; Warner, J.C. Green Chemistry: Theory and Practice, Oxford University Press,1998.
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3. 1. Prevention
It is better to prevent waste than to treat or clean up waste after it is formed.
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4. Environmental Disasters
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 then used for a new school and housing track. The chemicals leaked through a clay cap that sealed the dump. It was contaminated with at least 82 chemicals (benzene, chlorinated hydrocarbons, dioxin). Health effects of the people living there included: high birth defect incidence and siezure-inducing nervous disease among the children.
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5. Environmental Disasters
Cuyahoga River – Cleveland, Ohio
There were many things being dumped in the river such as: gasoline, oil, paint, and metals. The river was called "a rainbow of many different colors".
Fires erupted on the river several times before June 22, 1969, when a river fire captured national attention when Time Magazine reported it.
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6. 2. Atom Economy
Synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product.
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7. Organic Chemistry & Percent Yield
Epoxidation of an alkene using a peroxyacid
100% yield
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8. Percent yield:
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9. Balanced Reactions
Balanced chemical reaction of the epoxidation of styrene
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10. Atom Economy:
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Trost, Barry M., The Atom Economy-A Search for Synthetic Efficiency. Science 1991, 254,

11. Atom Economy Balanced chemical reaction of the epoxidation of styrene
Assume 100% yield.
100% of the desired epoxide product is recovered.
100% formation of the co-product: m-chlorobenzoic acid
A.E. of this reaction is 23%.
77% of the products are waste.
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12. 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.
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13. Less Hazardous Chemical Synthesis
Polycarbonate Synthesis: Phosgene Process
Materials: bisphenol A (BPA), Phosgene, CH2Cl2
Disadvantages
phosgene is highly toxic, corrosive
requires large amount of CH2Cl2
polycarbonate contaminated with Cl impurities
chemical found in hard plastics and the coatings of food and drinks cans which can behave in a similar way to estrogen and other hormones in the human body. BPA is used to make many products, including water bottles, baby bottles, dental fillings and sealants, dental devices, medical devices, eyeglass lenses, DVDs and CDs, household electronic and sports equipment. BPA can also be found in epoxy resins which is used as coatings inside food and drinks cans.
Polycarbonates (PC) are a group of thermoplastic polymers containing carbonate groups in their chemical structures. Polycarbonates used in engineering are strong, tough materials, and some grades are optically transparent.
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14. Less Hazardous Chemical Synthesis
Polycarbonate Synthesis: Solid-State Process SSP
Advantages
diphenylcarbonate synthesized without phosgene
eliminates use of CH2Cl2
higher-quality polycarbonates
Komiya et al., Asahi Chemical Industry Co.
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15. 4. Designing Safer Chemicals
Chemical products should be designed to preserve efficacy of the function while reducing toxicity.
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16. Designing Safer Chemicals Case Study: Antifoulants (Marine Pesticides)
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17. Designing Safer Chemicals: Case Study: Antifoulants
Antifoulants are generally dispersed in the paint as it is applied to the hull.  Organotin compounds have traditionally been used, particularly tributyltin oxide (TBTO). TBTO works by gradually leaching from the hull killing the fouling organisms in the surrounding area
TBTO and other Organotin 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 marine organisms to be 104 times greater than in the surrounding water).
Organotin compounds are chronically toxic to marine life and can enter food chain. They are bioaccumulative.
Bioconcentration is a term that was created for use in the field of aquatic toxicology. Bioconcentration can also be defined as the process by which a chemical concentration in an aquatic organism exceeds that in water as a result of exposure to a waterborne chemical.
Bioaccumulation refers to the accumulation of substances, such as pesticides, or other chemicals in an organism.
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18. Designing Safer Chemicals: Case Study: Antifoulants
Sea-Nine® 211
The active ingredient in Sea-Nine® 211, 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOI),  is a member of the isothiazolone family of antifoulants.
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19. Designing Safer Chemicals: Case Study: Antifoulants
Sea-Nine® 211 works by maintaining a hostile growing environment for marine organisms.
When organisms attach to the hull (treated with DCOI), proteins at the point of attachment with the hull react with the DCOI. 
This reaction with the DCOI prevents the use of these proteins for other metabolic processes.
The organism thus detaches itself and searches for a more hospitable surface on which to grow.
Only organisms attached to hull of ship are exposed to toxic levels of DCOI.(4,5-dichloro-2-n-octyl-4-isothiazolin)
Readily biodegrades once leached from ship (half-life is less than one hour in sea water).
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20. 5. Safer Solvents and Auxiliaries
The use of auxiliary substances (solvents, separation agents, etc.) should be made unnecessary whenever possible and, when used, innocuous.
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21. Safer Solvents Solvent Substitution Water as a solvent New solvents
Ionic liquids
Supercritical fluids
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22. Solvent Selection
Preferred
Useable
Undesirable
Water
Cyclohexane
Pentane
Acetone
Heptane
Hexane(s)
Ethanol
Toluene
Di-isopropyl ether
2-Propanol
Methylcyclohexane
Diethyl ether
1-Propanol
Methyl t-butyl ether
Dichloromethane
Ethyl acetate
Isooctane
Dichloroethane
Isopropyl acetate
Acetonitrile
Chloroform
Methanol
2-MethylTHF
Dimethyl formamide
Methyl ethyl ketone
Tetrahydrofuran
N-Methylpyrrolidinone
1-Butanol
Xylenes
Pyridine
t-Butanol
Dimethyl sulfoxide
Dimethyl acetate
Acetic acid
Dioxane
Ethylene glycol
Dimethoxyethane
Benzene
Carbon tetrachloride
“Green chemistry tools to influence a medicinal chemistry and research chemistry based organization”
Dunn and Perry, et. al., Green Chem., 2008, 10, 31-36
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23. 6/18/2018 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 HAP in the US.
Di-isopropyl ether
-12
Very powerful peroxide former, good alternative ethers available.
Diethyl ether
-40
Very low flash point, good alternative ethers available.
Dichloromethane
n/a
High volume use, regulated by EU solvent directive, classified as HAP in US.
Dichloroethane 15
Carcinogen, classified as a HAP in the US.
Chloroform
Dimethyl formamide 57
Toxicity, strongly regulated by EU Solvent Directive, classified as HAP in the US.
N-Methylpyrrolidinone 86
Toxicity, strongly regulated 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
Dioxane 12
CMR category 3 carcinogen, classified as HAP in US.
Dimethoxyethane
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 tetrachloride
Avoid use: CMR category 3 carcinogen, toxic, ozone depletor, banned under the Montreal protocol, not available for large-scale use, strongly regulated in the EU and the US (HAP).
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24. Solvent replacement table
Undesirable Solvent
Alternative
Pentane
Heptane
Hexane(s)
Di-isopropyl ether or diethyl ether
2-MeTHF or tert-butyl methyl ether
Dioxane or dimethoxyethane
Chloroform, dichloroethane or carbon tetrachloride
Dichloromethane
Dimethyl formamide, dimethyl acetamide or N-methylpyrrolidinone
Acetonitrile
Pyridine
Et3N (if pyridine is used as a base)
Dichloromethane (extractions)
EtOAc, MTBE, toluene, 2-MeTHF
Dichloromethane (chromatography)
EtOAc/heptane
Benzene
Toluene
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25. Pfizer’s results Use of Solvent Replacement Guide resulted in:
50% reduction in chlorinated solvent use across the whole of their research division (more than 1600 lab based synthetic organic chemists, and four scale-up facilities) during
Reduction in the use of an undesirable ether by 97% over the same two year period
Heptane used over hexane (more toxic) and pentane (much more flammable)
“Green chemistry tools to influence a medicinal chemistry and research chemistry based organization”
Dunn and Perry, et. al., Green Chem., 2008, 10, 31-36
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26. Safer solvents: Supercritical fluids
A SCF is defined as a substance above its critical temperature (TC) and critical pressure (PC). The critical point represents the highest temperature and pressure at which the substance can exist as a vapor and liquid in equilibrium.
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27.
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28. Activity-02
Study the flow sheet diagram carefully and rewrite the method
The method should not exceed 250 words
The submission date is 21st Sep
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29. 6. Design for Energy Efficiency
Energy requirements should be recognized for their environmental and economic impacts and should be minimized.
Synthetic methods should be conducted at ambient temperature and pressure.
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30. Energy in a chemical process
Thermal (electric)
Cooling (water condensers, water circulators)
Distillation
Equipment (lab hood)
Photo
Microwave
Source of energy:
Power plant – coal, oil, natural gas
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31. Alternative energy sources: Photochemical Reactions
Two commercial photochemical processes (Caprolactam process & vitamin D3)
Caprolactam process
Nitrosyl chloride NOCl  NO˙ + Cl˙ (535nm)
Vitamin D3: Photochemical electrocyclic ring opening followed by a thermal 1,7-hydride shift
no viable thermal alternative
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Chem-442

32. 7. Use of Renewable Feedstocks
A raw material or feedstock should be renewable rather than depleting whenever technically and economically practical.
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33. Polymers from Renewable Resources: Polyhydroxyalkanoates (PHAs)
Fermentation of glucose in the presence of bacteria and Propanoic acid (product contains 5-20% polyhydroxyvalerate)
Similar to polypropene and polyethene
Biodegradable (credit card)
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Chem-442

34. Polymers from Renewable Resources: Poly(lactic acid)
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35. Raw Materials from Renewable Resources: The BioFine Process
Paper mill
sludge
Agricultural
residues,
Waste wood
Levulinic acid
Green Chemistry Challenge Award 1999 Small Business Award
Municipal solid waste
and waste paper
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36. Levulinic acid as a platform chemical
butanediol
Acrylic acid
Succinic acid
MTHF
(fuel additive)
THF
Diphenolic acid
gamma
butyrolactone
DALA (-amino levulinic acid)
(non-toxic, biodegradable herbicide)
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Chem-442

37. Activity-02 Gather some ideas for Green Day
Google international celebrated days and develop a program.
Discuss the programs on 23rd Sep
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38. 8. Reduce Derivatives
Unnecessary derivatization (blocking group, protection/deprotection, temporary modification of physical/chemical processes) should be avoided whenever possible.
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39. In the first industrial synthesis Penicillin G (R=H) is first protected as its silyl ester [R = Si(Me)3] then reacted with phosphorus pentachloride at -40oC to form the chlorimidate 1 
Subsequent hydrolysis gives the desired 6-APA from which semi-synthetic penicillins are manufactured.
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40. 6/18/2018

41. This synthesis occurs in water at just above room temperature.
This synthesis has been largely replaced by a newer enzymatic process using pen-acylase.
This synthesis occurs in water at just above room temperature.
The new synthesis has many advantages from a green perspective one of which is that the Silyl protecting group is not required.
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42. Silyl ether
Silyl ethers are a group of chemical compounds which contain a silicon atom covalently bonded to an alkoxy group.
The general structure is R1R2R3Si−O−R4 where R4 is an alkyl group or an aryl group. 
Silyl ethers are usually used as protecting groups for alcohols in organic synthesis.
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43. More than 10,000 metric tons of 6-APA is made every year and much of it by the greener enzymatic process so this is a fantastic example of Green Chemistry making a real difference.
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44. 9. Catalysis
Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.
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45. Biocatalysis Enzymes or whole-cell microorganisms Benefits
Fast rxns due to correct orientations
Orientation of site gives high stereospecificity
Substrate specificity
Water soluble
Naturally occurring
Moderate conditions
Possibility for tandem rxns (one-pot)
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46. A hexokinase is an enzyme that phosphorylates hexoses (six-carbon sugars), forming hexose phosphate. In most organisms, glucose is the most important substrate of hexokinases, and glucose-6-phosphate is the most important product
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47. Biocatalysis has many attractive features in the context of green chemistry, and its impact will become continue to grow.
As biofuels companies look for more profitable ways to exploit their technology I expect bio-based routes to certain large volume specialty chemicals to be commercialized in the near future.
Examples include 1,4-butanediol, succinic acid, glucaric acid, terpenes, and even isobutene.
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48. 10. Design for Degradation
Chemical products should be designed so that at the end of their function they do not persist in the environment and instead break down into innocuous degradation products.
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49. 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 increased 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
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50. Degradation of Polymers:
Polylactic Acid
Manufactured from renewable resources
Corn or wheat; agricultural waste in future
Uses 20-50% fewer fossil fuels than conventional plastics
PLA products can be recycled or composted
Cargill Dow
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51. 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.
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52. Real time analysis for a chemist is the process of “checking the progress of chemical reactions as it happens.”
Knowing when your product is “done” can save a lot of waste, time and energy!
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53. Analyzing a Reaction
What do you need to know, how do you get this information and how long does it take to get it?
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54. 12. Inherently Safer Chemistry for Accident Prevention
Substance and the form of a substance used in a chemical process should be chosen so as to minimize the potential for chemical accidents, including releases, explosions, and fires.
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55. 12. Inherently Safer Chemistry for Accident Prevention
Tragedy in Bhopal, India
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 city of Bhopal. 15,000 people died and hundreds of thousands more were injured.
Chemists try to avoid things that explode, light on fire,
are air-sensitive, etc.
In the “real world” when these things happen, lives are lost.
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56. Bhopal, India
December 3, 1984 – poison gas leaked from a Union Carbide factory, killing thousands instantly and injuring 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 molecule
Most safety systems either failed or were inoperative
Water was released into the tank holding the methyl isocyanate
The reaction occurred and the methyl isocyanate rapidly boiled producing large quantities of toxic gas.
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57. Chemical Industry Accidents
U.S. Public Interest Research Group Reports (April 2004) find 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 accidents)
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