Green Chemistry

Hermenegildo Garcia Department of Chemistry D2Q-9 96 387 7807 (ext 73441 y 78572) [email protected] www.upv.es/herme

How to pass the course?

• Attendance to class is mandatory •You can miss one class max. • To perform exercises and homework •Assignment 4 •Correct exercises •Present in due time •Public presentation (30 min) •Written exam 7 • Volonteers 10

Assignment List

• History • Examples of novel green chemistry processes • Presidential Green Chemistry Challenge award winners • Propose practical demonstrations • Renewable feedstocks • EPA grants • Search for reviews and literature reports • Search for web pages and electronic addresses • Assistance to prepare new class material

Actions aiming at Green Chemistry

Goverment Academia •Laws and regulations • Courses and training •Control • Research in new processes •Funding and promotion

Industry General public • Development of new processes • Information • Development of new products • Good practices • New renewables feedstocks • Support extra costs

• Safe operation The ACS/EPA Cooperative Agreement

• What is the EPA? • What is ACS? • EPA/ACS collaboration Propose nominations to the Presidential Green Chemistry Challenge Awards Program Highlights the concerns with current products and processes Presents a green chemistry solution Real-World Cases in Green Chemistry

ACS Activities

Earth Day Program Green chemistry in the curriculum (books) Green chemistry summer school National Chemistry Week Interactive Teaching Units

Europe and Japan

• Royal Society of Chemistry • Venice (7th Summer school in green chemistry) • Barcelona (Green Chemistry PhD course) • European Commission (Cost Actions) • York and other European Universities • Japan is developing very strong initiatives

Can the Chemistry be Dirty?

Atmospheric pollution • Green house effect and energy consumption • Ozone layer depletion • Photochemical smog • Smoke (NOx and SOx)

Aqueous pollution • Fertilizers, pesticides, insecticides Solid pollution • Industrial waste waters • Industrial soils • Solvents • Nuclear and radiactive wastes • Deter gents and urban waste waters • Chemical residues Examples of Chemical Products of the 20th Century

Thalidomide. DDT. CFCs. Endocrine disruptors. Bioaccumulating substances. Persistent/non-biodegradable materials.

Why the chemistry is dirty? • Provides energy • Provides materials (plastics, paper, etc) • Provides commodities (sprays, detergents, paints, dyes) • Provides fertilizers, insecticides, pesticides • Provides drugs and pharmaceuticals

• Social demand • Social com plain Growth of Legal Regulation

EPACT FFCA CERFA CRAA PPA AMFA PPVA ARPAA IEREA AJA AQ ANTPA 120 AS BCAA A GLCPA ES AA-AECA ABA FFRAA CZARA FEAPRA WRDA 110 IRA EDP NWPAA NAWCA OPA CODRA/NMS PAA RECA 100 FCRPA CAAA MMPAA GCRA GLFWRA HMTUS A APA RCRAA WQA 90 S WDA WLDI NEEA CERCLA CZMIA 80 COWLDA NWPA S DWAA FWLCA S ARA MPRS AA BLRA 70 CAAA ARPA ERDDAA CWA MPRS AA EAWA S MCRA NOPPA S WRCA PTS A 60 S DWAA UMTRCA ES AA BLB A QGA

FWPCA HMTA NCPA f 50 MPRS A o CZMA ES A TS CA r TAPA e 40 NCA FLPMA b FEPCA RCRA s PWS A NFMA m w MMPA FRRRPA CZMAA u a S OWA

N L 30 DPA NEPA AQA EQIA FOIA FCMHS A CAA 20 EPA WRPA EEA AFCA OS HA 10 FAWRAA FHS A NPAA NFMUA WS RA TA EA 0 FWCA AEPA FIFRA PAA NHPA RCFHS A B PA WLDA WA FWCAA NBRA NPS MB CA FAWRA IA FWA RHA AA NLRA AEA YA WPA

1870 1880 1890 1900 1910 1920 19 30 1940 1950 1960 1970 1980 1990 2000 What is Green Chemistry?

•Environmentally friendly processes Benign Disposal •Sustainability Recycle/Re-use

Chemical usage Reduce - Energy usage

Hazardous materials, processes Replace - Inefficient processes Non-sustainable components

Green Chemistry Technologies and Solutions

• What is Green Chemistry? •Chemistry to provide commodities being environmentally friendly and sustainable • How do we know what is Green? • A dip into the Clean/Green technology Pool with some examples.

How do we know what is Green? Metrics in Green Chemistry “When you can measure what you are speaking about, and express it in numbers, you know something about it; but when you cannot measure it, when you cannot express it in numbers, your knowledge is of a meagre and unsatisfactory kind; it may be the beginning of knowledge, but you have scarcely, in your thoughts, advanced to the stage of science” William Thompson, Lord Kelvin, (1891)

“If you don’t keep score then you are only practising”

Metrics in Green Chemistry

How do we know what progress we are making?

⇒ E - Factor Amount of waste/kg product: Product tonnage E Factor Bulk Chemicals 104-106 <1 - 5 Fine chemical Industry 102-104 5 - >50 Pharmaceutical Industry 10-103 25 - >100

R.A. Sheldon, Chem & Ind, 1997,12 Metrics in Green Chemistry Preparation of 2-methoxypropane-1,3-diol from glycerol

OH OH 2TrCl 2Et N HO OH + + 3 TrO OTr + 2Et3N.HCl

[92] [278.5] [101] [137.5]

OH OMe MeI Et N Et N.HI TrO OTr + + 3 TrO OTr + 3 [142] [229]

OMe OMe TrO OTr + 2AcOH HO OH + 2TrOAc [60] [106] [302]

Assuming 100% yields, no reaction or work-up solvents and no reagent excesses 1 kg glycerol produces 1.15 kg 2-methyl ether and 12.04 kg of waste!

Atom Economy

MW of desired product Atom economy = Σ MWs of all substances produced

•Diels-Alder Reaction

O O

+ 100% Atom economy

•Wittig Reaction

•O _ + C H•2 + Ph3P CH2 + Ph3 P=O

35% Atom economy Safer reactions and reagents- Renewable New Chemistry Feedstocks Catalysis Alternative Solvents Chemical Innovative recycling Membrane Engineering reactors

12 Principles of Green Chemistry

• Prevent waste: Design chemical syntheses to prevent waste, leaving no waste to treat or clean up. • Design safer chemicals and products: Design chemical products to be fully effective, yet have little or no toxicity. • Design less hazardous chemical syntheses: Design syntheses to use and generate substances with little or no toxicity to humans and the environment. • Use renewable feedstocks: Use raw materials and feedstocks that are renewable rather than depleting. Renewable feedstocks are often made from agricultural products or are the wastes of other processes; depleting feedstocks are made from fossil fuels (petroleum, natural gas, or coal) or are mined.

12 Principles of Green Chemistry

• Use catalysts, not stoichiometric reagents: Minimize waste by using catalytic reactions. Catalysts are used in small amounts and can carry out a single reaction many times. They are preferable to stoichiometric reagents, which are used in excess and work only once. • Avoid chemical derivatives: Avoid using blocking or protecting groups or any temporary modifications if possible. Derivatives use additional reagents and generate waste. • Maximize atom economy: Design syntheses so that the final product contains the maximum proportion of the starting materials. There should be few, if any, wasted atoms. • Use safer solvents and reaction conditions: Avoid using solvents, separation agents, or other auxiliary chemicals. If these chemicals are necessary, use innocuous chemicals.

12 Principles of Green Chemistry

• Increase energy efficiency: Run chemical reactions at ambient temperature and pressure whenever possible. • Design chemicals and products to degrade after use: Design chemical products to break down to innocuous substances after use so that they do not accumulate in the environment. • Analyze in real time to prevent pollution: Include in- process real-time monitoring and control during syntheses to minimize or eliminate the formation of byproducts. • Minimize the potential for accidents: Design chemicals and their forms (solid, liquid, or gas) to minimize the potential for chemical accidents including explosions, fires, and releases to the environment.

Pharmaceutical Applications Traditional synthesis of ibuprofen

O O CHCO2C2H5 ClCH CO C H (CH3CO)2O 2 2 2 5 NaOC H AlCl3 2 5

CHO HC NOH

H+ H2NOH H2O

CN CO2H

Ibuprofen Pharmaceutical Applications

Alternative synthesis of ibuprofen

O

(CH3CO2)O H2 HF catalyst

OH CO2H

CO, Pd

Ibuprofen B HC Company Redesign of the Sertraline Process NMe NMe NMe NMe

TiCl / MeNH Pd/C, H2 (D)-mandelic acid EtOAc 4 2 EtOH HCl toluene/hexanes THF Cl Cl O Cl Cl Cl Cl Cl Cl + TiO 2 Sertraline Mandelate Sertraline + MeNH4Cl racemis mixture isolated "imine" cis and trans isomers isolated isolated final product

Cl Cl NMe NMe NMe NMe

MeNH2 PdC/CaCO3 (D)-mandelic EtOAc EtOH + H2O acid H2/EtOH HCl EtOH MeOH rex Cl Cl Cl Cl Cl Cl Cl Cl

Sertraline "imine" racemic mixture Sertraline Mandelate isolated not isolated not isolated isolated final product

Alternative Synthetic Pathways Sodium iminodisuccinate  Biodegradable, environmentally friendly chelating agent  Synthesized in a waste-free process  Eliminates use of hydrogen cyanide Bayer Corporation and Bayer AG 2001 Alternative Synthetic Pathways Award Winner

O O O

NaOH NaO ONa O NH3 NaO ONa N O O H O New Chemistry: Synthesis of 4-ADPA Monsanto’s new route: rubber antidegradant 130,000 M tonnes/annum Starting Material: Aniline

NH2

Green Chemistry Traditional Chemistry Safer. Organo-halogens used. No Organo-halogens. Waste Minimised -74% less Hazardous Solvent used. organic, 99% less water. High Waste levels. Reusable catalyst employed. Reduced Cost.

N NH H 2 Product : 4-ADPA Catalysis

Zeolites as Alternatives to Classical Routes

• Alumino-silicates • 3D crystalline structure • Uniform pore size • Green applications in > Catalysis > Water treatment > Remediation > Odour control

Zeolites: Chemical Composition

PRIMARY STRUCTURE

Organic or inorganic Exchangeable Acid Zeolites H+

Control: x+ x- • during synthesis M [Al Si O ] z H O • after synthesis x/n x y 2 (x + y ) 2

y/x between 1 and ∞ number of countercations Variable hydrophylicity Thermally reversible

Zeolites:Microporous Solids • More than 30 natural zeolites • More than 300 synthetic zeolites

30 Mesoporous SUPRAMOLECULAR CHEMISTRY

Molecular Sieves ) Å

( 20

r 18 Ox Microscopic Reactor e t e

m Reaction Cavity a MCM-41 Di 12 Ox Molecular Pockets e r

Po 10 10 Ox 8 Ox VPI-5

ß, Y, ž Erionita ZSM-5

small medium large extra large

Pore size SOME COMMON TOPOLOGIES

BEA Faujasite (zeolite Beta): (zeolites X and Y): tridirectional, tridirectional, large pore (12 Å) large pore (13 Å)

Pentasil (silicalite and ZSM-5): bidirectional, medium pore (5.4X5.62) Å

MCM-41: unidirectional, mesoporous (20 Å)

Zeolite Particles by SEM

ADVANTAGES OF ZEOLITES AS HOSTS

• WELL DEFINED SOLIDS • SYNTHETIC MATERIALS – REPRODUCIBILITY BETWEEN BATCHES – CONTROL OF CHEMICAL COMPOSITION – LARGE AMOUNTS g ⇒ Ton • THERMAL AND CHEMICAL STABILITY • LARGE VARIETY – SIZE AND GEOMETRY OF MICROPORES • OTHERS: – ACTIVE SITES – TRANSPARENT TO UV RADIATIONS

ACID ZEOLITES: H+ AS CHARGE BALANCING CATION

• CASE OF ZEOLITE Y (POST-SYNTHETIC EXCHANGE) + NH 4 o >500 HY NaY NH4 Y + Na NH3 • CASE OF ZSM-5 (AS-SYNTHESIZED SAMPLES) H O O - O o O Si + Al O >500 O O NPr ZSM-5 HZSM-5 4 NPr + CH =CH 3 2 CH3

PROPERTIES: •CONTROL OF THE POPULATION OF ACID SITES: ONE SITE EACH FRAMEWORK Al •ACID STRENGTH DISTRIBUTION •SUPERACIDIC BEHAVIOR AT HIGH TEMPERATURES •ALSO LEWIS SITES Zeolites and Petrochemistry

• Fluid Catalytic Cracking – Conversion of Gas Oil into Gasoline • Reforming – Increase of octane number (Quality of gasoline) • Alkene Alkylation – Gasoline with high octane number

Catalysis: Zeolites

Disproportionation of Toluene Using HZSM5

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+

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Shape selectivity allows only p-xylene to pass through

Solvent Replacement in Green Chemistry

• Volatile organic solvents are the normal media for carrying out organic syntheses and extractions - usage £4,000,000,000 p.a.

• Also used in products- paints, varnishes, cleaning agents, adhesives

• VOC’s causing considerable environmental concern! (Global warming/Ozone Depletion)

Solvent Replacement in Green Chemistry Benzene

• Excellent solvent but it is a Genotoxic

human carcinogen • Limit in drinking water of 5ppb(US EPA) • In 1990 Perrier water found to have 12- 20ppb (cigarette smoke has 2000 times

more benzene than this) - 160 million bottles withdrawn • EU limit in petrol 5% before 2000, now <1% Solvent Replacement in Green Chemistry Halogenated Solvents

Dichloromethane CH2Cl2: • a suspected human carcinogen • widely used in synthesis and extractions • extraction of caffeine from coffee (<10ppm residue)

Perchoroethylene CCl2CCl2: • a suspected human carcinogen • main use in dry cleaning(85% of all solvents) • also found in printing inks, typewriter correction fluid and shoe polish

Solvent Replacement in Green Chemistry Carbon Dioxide

Compound Critical temperature Critical pressure (oC) (Bar) Carbon dioxide 31 73.8 Ethane 32.3 48.8 Water 374.0 220.6

scCO2 is inexpensive, non-flammable and non-toxic.

Current applications include: • Decaffeination of coffee -replacing dichloromethane • Dr y Cleaning -replacing perchloroethylene. CO2 for Dry Cleaning

Dry Cleaning  current process uses perc (perchloroethylene), a suspected carcinogen and groundwater contaminant  new process uses liquid carbon dioxide, a nonflammable, nontoxic, and renewable substance

Other solvents

• Perfluorinated solvent – Fluorous media • Ionic Liquids • Water • Solventless reactions – High conversions are needed

Perfluorinated solvents

R1 R1 F C R2 Si P Si R2 (2n+1) CnF(2n+1) 3 N N R3 R N N F(2n+1)C CnF(2 ) Si n+1 R1 R3 R2

R1, R2, R3: CH or -CH CH C F 3 2 2 n 2n+1 fluorinated cyclam

fluorinated triarylphosphines Ionic Liquids

+ - - - - N N R + An : PF6 , BF4 , Cl , etc. R N An- R An-

N,N'-dialkylimidazoliums N-alkylpyridinium AlCl - 3 - AlCl3 - Cl AlCl4 Al2Cl7

Real-World Cases: Microbes as Catalysts

Synthesis of adipic acid and catechol from renewable feedstocks using genetically modified E. coli Applications  Catalysis/biocatalysis  Renewable feedstocks  Waste water remediation

Catalysis

Activity + selectivity, higher throughput with less waste, less energy Propeneamide is the first bulk chemical manufactured using an industrial biotransformation: O N 5 degrees C NH2 pH 7.5 99.99% Yield

The active enzyme is nitrile hydralase in whole cells of Rhodococcus rhodochrous, immobilised on poly(propeneamide) gel Catalysis

Membrane Technology Extractive Membrane Bioreactor

Biomedium M Wastewater Detachment B E I M Dissolved Oxygen O B Nutrients F R Pollutants I A L N Attachment M E

Membrane Technology Extractive Membrane Bioreactor

New Stripper-BioScrubber plant on site at Atofina Widnes

(Project initiated in March 2000)

Removals of benzene or toluene from 500-1000 mg L-1 to less than 1ppm from point source waste stream

Membrane Separations in Green Chemical Technology Biotransformations

Membrane Bioreactor for Biotransformations

Aqueous Phase Organic Phase R R Whole cells or R = Reactant enzymes as C P = Product biocatalysts Nonporous P P membrane

Nanoporous membranes • Is it possible to filtrate molecules?

a) No-crosslinked PDMS polymer

Me Me Me Me Me Me Me Me Si O Si O Si O Si + H Si O Si O Si O Si H Me Me Me Me Me Me Me Me n m

A H B H

catalyst

A CH2CH2 B H

(linear PDMS)

b) Crosslinked PDMS polymer

Me Me Me Me Me Me Me Me Me H Me Me Me Si O Si O Si O Si O Si O Si O Si + H Si O Si O Si O Si O Si O Si O Si H Me Me Me Me Me Me Me Me Me Me Me Me Me Me n n' n n'

catalyst

H

B H

CH2CH2

A CH2CH2 B H

CH2CH2 A (crosslinke d PDMS) Nanoporous membranes to filtrate molecules

PDMS membrane Hydrophilic phase

H2O

H2O2

H2O2

H2O

H O 2 2 Hydrophobic phase Nanoporous membranes to filtrate molecules

HO OH

* R Aqueous phase H2O

O O Organic phase * * R R (R and S)

Aqueous phase H2O HO OH

* R

Nanoporous membranes to filtrate molecules

N N Co t But O Bu OAc t tBu Bu

Nanopores of Anodisk

ZSM-5 continuous film

Renewable Resources

• Biodiesel – Synthesis of biodiesel from vegetable oil – Properties of biodiesel – Potential of biofuels

Polylactic Acid

. Manufactured from renewable resources . Corn or wheat; agricultural waste in future . A new thermoplastic polymer family based on polylactic acid developed by Cargill Dow . 144,000 tpa plant built in Nebraska USA . Potential market approaching 500,000 metric tons per year. . Uses 20-50% fewer fossil fuels than conventional plastics . PLA products can be recycled or composted

Cargill Dow

Designing Safer Chemicals

Cationic electrodeposition coatings containing yttrium  Provides corrosion resistance to automobiles  Replaces lead in electrocoat primers  Less toxic than lead and twice as effective on a weight basis

PPG Industries 2001 Designing Safer Chemicals Award Winner

Alternative Reagents  Chlorine-free wood pulp bleaching  TAML catalysts activate hydrogen peroxide  Eliminates formation of chlorinated organics

Collins, Carnegie Mellon University

_ H H O O O X N N + III Cat Fe + + + + + Cat = Li , [Me4N] , [Et4N] , [PPh4] X N N X = Cl, H, OCH O 3 O

Agrochemicals

Pesticides • Insecticides (wide spectrum, juvenile and sexual hormones traps) • Fungicides • Herbicides (natural defense) • Rodenticides

Cl O Cl Cl + Cl C H + H Cl Cl Cl Cl Cl

-HCl

Cl Cl

Cl Cl Pesticide generation

1. First Generation Pesticides: toxic metals. 2. Second Generation Pesticides: synthetic organic pesticides e.g. chlorinated hydrocarbons such as persistent DDT. 3. Nonpersistent pesticides (e.g. malathion, aldicarb). 4. Pheromones and insect hormones

4.- PESTICIDAS CLORADOS

H Cl Cl Cl Cl C C Cl Cl Cl Cl Cl Cl Cl DDT LINDANO

Cl Cl Cl Cl Cl Cl Cl Cl O Cl Cl Cl Cl ALDRIN DIELDRIN Cl Cl Cl Cl Cl •Activity against carbonic anhydrase Cl enzyme Cl CLORDANO

Pest resistance and Biomagnification

• Total impact of a pesticide depends on 1) toxicity, 2) dosage, 3) location • Pests develop resistance, may have far reaching effects, and desirable insects also impacted. • Resurgences – pest population recovers and explodes • Secondary Pest Outbreaks – non-pests become pests as loose natural enemies, gain resistance to pesticides • Biomagnification: multiplying effect of bioaccumulation through the food chain. Chemicals accumulate in lipids

Alternative Pest Control Methods i. Control by natural enemies: lady bugs

v. Cultural control: non-chemical alteration of environmental factors e.g. hygiene, crop rotation vi. Natural Chemical Control (isolate, ID, synthesize then use insects own hormones or pheromones to disrupt its life cycle. Non-toxic and specific. Sex pheromones can be used to lead insects into traps, or confuse them. vii. Genetic Control: breed resistance crops using chemical (e.g. Hessian fly on wheat) or physical barriers (e.g. hooked hairs), sterile males (e.g. tsetse fly), biotechnology – genetic engineering for transgenic crops (e.g. resistance to pest, or resistance to broad-spectrum herbicide). Insect Metamorphosis Egg Larva Pupa Adult

Changes are controlled by juvenile hormones

What are pheromones

• Pheromones are chemicals emitted by an animal that signals another animal of the same species. • Example: female gypsy moths emit a pheromone to attract a male

Pheromones and Pest Control

• Pheromones can be utilized to catch or deter insects • Example: Pheromone “traps”, which contain the pheromone emitted by the female gypsy moth can be set to catch male moths

Examples of some Pheromones

CH OH 2 (E)10, (Z)12-Hexadecadienol

Sexual pheromone of silk butterfly female (Bombyx mori)

CH2 CH2 OH

(+)(z)2-Isopropenyl-1-methylcyclobutan-ethanol

Sexual pheromone of cotton worm

Green Chemistry Technologies and Solutions Conclusions: Much still to do but Green Chemistry provides a focus for:

• A pro-active approach to the increase in legislation (e.g. emissions, Green House Gases taxes,restricted chemicals

list) • A competitive advantage: beneficial in reducing costs/risks and provide greater manufacturing flexibility • An improvement in public image