The E factor at 21
Roger A. Sheldon Delft University of Technology
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Outline
The E factor at 21
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1. Origins of the E factor 2. Green chemistry, catalysis & sustainability 3. Suspect solvents 4. Biocatalysis 5. The bio-based economy 6. The metrics of sustainability 7. Conclusions & prospects
Phloroglucinol Synthesis anno 1980
Ca. 40kg of solid waste per kg phloroglucinol
Atom Utilisation = 126/2282 = ca. 5 %
E Factor = ca. 40
MW = 126
HO OH
O H
product
O2N NO2
CH3
NO2
K2Cr2O7
H2SO4 / SO3
O2N NO2
COOH
NO2
Fe/HCl
- CO2
H2N NH2
NH2
aq.HCl
ΔT
TNT phloroglucinol
HO OH
O H
“ To measure is to know ” Lord Kelvin
byproducts
+ Cr2 (SO4)3 + 2KHSO4 + 9FeCl2 + 3NH4Cl + CO2 + 8H2O
392 272 1143 160 44 144
> 90 % yield Selective? Efficient?
TNT
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Reaction Stoichiometry and Atom Economy
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Conclusion?
From the traditional one of chemical yield to one that assigns value to waste elimination and avoiding toxic/hazardous materials An environmental factor was missing
A new paradigm was needed for efficiency in organic synthesis
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Green chemistry efficiently utilises
(preferably renewable) raw materials,
eliminates waste and avoids the use
of toxic and/or hazardous solvents
and reagents in the manufacture and
application of chemical products.
Green (Clean) Chemistry
Sheldon, Arends and Hanefeld , Green Chemistry
and Catalysis, Wiley, New York, 2007
Anastas & Warner, Green Chemistry : Theory
& Practice ,Oxford Univ. Press,New York,1998
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Green (Clean) Chemistry
Green chemistry is pollution prevention not end-of-pipe remediation
“Environmental pollution is an incurable disease. It can only be prevented”.
Barry Commoner “The Closing Circle” , 1971
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Meeting the needs of the present generation
without compromising the needs of future
generations to meet their own needs
What is Sustainability?
Brundtland Report, ‘Our Common Future’, 1987
Profit
People
Planet
Making every decision with the future in mind
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Sustainable
Economic (Profit)
Environment (Planet)
Social (People)
Viable
Equitable
Bearable
The Sustainability Venn Diagram
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Green Chemistry
• Waste minimization
• Environmentally acceptable solvents, reagents and end-products
• Renewable feedstocks
• Products & processes
The Bio-Based Economy
- Biomass as feedstock - Biodegradable products - (Bio)catalytic conversions
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Tonnage E Factor
Oil Refining 106-108 <0.1
Bulk Chemicals 104-106 <1 - 5
Fine chemical Industry 102-104 5 - >50
Pharmaceutical Industry 10-103 25 - >100
R.A.Sheldon, Chem & Ind, 1992, 903 ; 1997, 12
E Factor = kg waste/kg product
[i]
“Another aspect of process development mentioned by all pharmaceutical process chemists who spoke with C&EN is the need for determining an E Factor”. A. N. Thayer, C&EN, August 6, 2007, pp. 11-19
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The E factor
• Is the actual amount of all waste formed in the process, including solvent losses and waste from energy production (c.f. atom utilisation is a theoretical nr.) • E = [kgs raw materials- kgs product]/[kgs product] • A good way to quickly show (e.g. to students) the enormity of the waste problem
(E)verything but the Product
What about the process water? Only if it needs to be treated
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E = Total mass of waste Mass of final product
AE (%) = m.w of product x 100 Σ m.w. of reactants
Reaction mass efficiency (RME)
Mass of product C x 100 Mass of A + Mass of B
E factor Atom efficiency (AE)
RME(%) =
Mass intensity (MI)
MI = Total mass in process Mass of product
CE(%) =
Carbon efficiency (CE)
Carbon in product x 100 Total carbon in reactants
Effective mass yield (EMY)
EMY(%) = Mass of product x 100 Mass of hazardous reagents
Mass Productivity (MP)
Mass of product Total mass in process
MP =
Metrics of Green Chemistry
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E-factor M&M model Industry segment
0.1 Oil refining
1 Bulk Chemicals &
Polymers 10
100 Fine Chemicals
250 Pharmaceuticals &
Electronics
The Goal Is Zero
E-factor as a green chemistry metric
Irvin J. Levy Professor of Chemistry Gordon College, Wenham, MA 01984
http://www.cs.gordon.edu/~ijl/visualizingWaste/
E-factor = mass of waste ÷ mass of product
E-factor = (mass of inputs - mass of outputs) ÷ mass of product
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On the Way Towards Greener Processes, as Quantified by E Factors
B. H. Lipshutz, N. A. Isley, J. C. Fennewald, E. D. Slack 15
The Environmental Impact EQ
EQ = E(kg waste) × Q
Q = Unfriendliness Multiplier
e.g. NaCl : Q = 1 ( arbitrary)
Cr salts : Q = 1000?
R.A.Sheldon, Chem & Ind, 1992, 903 ; 1997, 12
There are many shades of green!
Quantification of Q
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http://www.metzger.chemie.uni-oldenburg.de/eatos/eatosmanual.pdf
Environmental Assessment Tool for Organic Syntheses
EATOS
- Mass and Energy Flow - Environment, Health and Safety - Persistence, bioaccumulation and toxicity (PBT) - Costs
Combines raw material efficiency with LCA and economic indicators
J. O. Metzger and M. Eissen, Chem. Eur. J. 8, 3580-3585 (2002)
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http://www.metzger.chemie.uni-oldenburg.de/eatos/eatosmanual.pdf
Environmental Assessment Tool for Organic Syntheses
EATOS
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Major Sources of Waste
• Stoichiometric Reagents
- Acids & Bases
- Oxidants & reductants
- Na2Cr2O7, KMnO4, MnO2
- LiAlH4, NaBH4, Zn, Fe/HCl
• Solvent losses ( 85% of non-aqueous mass)
The Solution : Atom & step economic catalytic processes
in alternative reaction media
(the best solvent is no solvent) 19
J. J. Berzelius 1779-1848
Organic Chemistry (1807) Catalysis (1835)
Urea synthesis 1828 ( Wöhler ) First synthetic dye 1856 Aniline purple (Perkin)
Dyestuffs Industry (based on coal-tar)
Fine Chemicals
Catalysis in Organic Synthesis
ca. 1900 Catalysis definition (Ostwald) Catalytic Hydrogenation (Sabatier) ca. 1920 Petrochemicals
1936 Catalytic cracking 1949 Catalytic reforming 1955 Ziegler-Natta catalysis
Bulk Chemicals & Polymers
Bridging the Gap
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The Ideal Synthesis 100% Yield
One Step
Simple & Safe
Economical in Time & Waste
Environmentally Acceptable
- atom economy
- step economy
- human economy
Urea Taxol Apoptolidine 1828 1990’s 2005 #Steps 1 37 98
Shorten the synthesis or change the target
1. Ni cat.
2. H2 / cat.
+ N
O
13 steps
Wilstatter
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"The ideal chemical process is that which a one-armed operator can perform by pouring the reactants into a bath tub and collecting pure product from the drain hole"
Sir John Cornforth (Nobel Prize 1975)
The Ideal Process
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Catalysis
Biocatalysis
Heterogeneous Homogeneous
Sheldon, Arends and Hanefeld , Green Chemistry And Catalysis, Wiley, New York, 2007
Organocatalysis
Catalysis & Green Chemistry
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The Solvent Problem : Catalysis in Non-conventional Reaction Media
• Toxicity and/or hazards of atmospheric and
ground water pollution by conventional solvents
• Separation/recycling of homogeneous catalysts
“The best solvent is no solvent”
• (Biphasic) catalysis in non-conventional media
- water
- supercritical carbon dioxide
- ionic liquids
Two challenges :
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Solvent Selection Guide
Water scCO2 Acetone Ethanol 2-Propanol 1-Propanol Heptane Ethyl Acetate Isopropyl acetate Methanol MEK 1-Butanol t-Butanol
Cyclohexane Toluene Methylcyclohexane TBME Isooctane Acetonitrile 2-MeTHF THF Xylenes DMSO Acetic Acid Ethylene Glycol
Pentane Hexane(s) Di-isopropyl ether Diethyl ether Dichloromethane Dichloroethane Chloroform NMP DMF Pyridine DMAc Dioxane Dimethoxyethane Benzene Carbon Tetrachloride
P. Dunn et al, Green Chem. 2008, 10, 31-36 25
Biocatalysis is Green & Sustainable • Enzymes are derived from renewable resources and are biodegradable (even edible sometimes) • Avoids use of (and product contamination by)
scarce precious metals • Mild conditions: ambient T & P in water
• High rates & highly specific : substrate, chemo-, regio-, and enantiospecific • Higher quality product • No special equipment needed
Reduced environmental footprint 26
Historically: Adapt Process to fit Catalyst
Available
Catalyst
Dream Process
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Nightmare Process
Catalyst
Compromise process to accommodate catalyst
Adapt catalyst to
optimum process
EVOLVE
Dream Process
Adapted
Catalyst
Future: Adapt Catalyst to fit Ideal Process
Directed Evolution 28
The Challenge
Disadvantages of Enzymes
Low operational stability & shelf life
Cumbersome recovery & re-use
Product contamination
Allergic reactions to proteins
Non viable biocatalytic applications
Costs are too high
Not practical
The Solution: Immobilization 29
Heterogeneous Catalysis with Enzymes
• Available Technologies – Proprietary CLEA (Cross-Linked Enzyme Aggregate)
Technology – On various carriers – Encapsulation – Combinations
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“In an ideal chemical factory there is, strictly speaking, no waste but only products. The better a real factory makes use of its waste, the closer it gets to its ideal, the bigger is the profit.“ A. W. von Hofmann (1884)
Conclusions & Take Home Message
1. There is not one winner. 2. There are many chemo- and bio-catalytic methods 3. There are many shades of green.
Waste Valorisation: The New Frontier
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Remediation
Prevention
Utilisation
Valorisation
Green Chemistry
Sustainable Development
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The Size of the Opportunity
• Lignocellulosic biomass residues: 220 X 109 tonnes /annum • Rice husks: 120 X 106 tonnes / annum
• Sugar cane bagasse: 220 X 106 tonnes / annum
• Waste straw in China: 600 X 106 tonnes / annum
• Orange peel in Brazil: 8 X 106 tonnes / annum
C. O. Tuck, E. Perez, I. T. Horvath, R. A. Sheldon, M Poliakoff, Science, 2012, 337 , 695-699
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Product €/ton
Average Bulk Chemical 1000
Transportation Fuel 200-400
Fermentation Feedstock 100-300
Animal Feed 70-120
Electricity Generation 60-150
Landfill -/- 400
The Valorisation Scale
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Product €/GJ
Epichlorohydrin 30 - 40
Transport fuel 10
Electricity 3
Valorisation of glycerol ( 25.3 GJ/tonne)
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Meaningful Metrics for Biomass Valorisation
• Boundary conditions?
(Cradle-Gate-Gate-Grave-Cradle)
• Land & Water Usage
• Economics
kgs product(s) kgs product(s)+ kgs waste
Meff = energy out energy in
Eeff =
A concise set of metrics for quick evaluation of petrochemical vs bio-based processes
“To measure is to know” Lord Kelvin
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Sustainability metrics of
chemicals from biomass
List of selected metrics:
- material efficiency
- total energy efficiency
- land use
- economic added value
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www.ubiochem.org
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Sustainability metrics of chemicals from biomass
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Lignocellulosic biomass to
sustainable fuels & chemicals
The stone age didn’t end when there were no more stones left
Y.Cao, X. Jiang, R. Zhang & M. Xian, Appl Microbiol Biotechnol (2011) 91:1545
Metabolically engineered E. coli
Production of Phloroglucinol by Fermentation
3.8 g/L in 12 h
Not (yet) commercially viable
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and Sustainable
Thank you, any questions? 41