Selec*vity and Atom Economy: Green Chemistry Metrics. 2 nd Principle of Green Chemistry. Types of selec*vity. Reac*on Efficiency 3/11/12

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1 Selec*vity and Atom Economy: Green Chemistry Metrics Week 4 2 nd Principle of Green Chemistry Synthe*c methods should be designed to maximize the incorpora*on of all materials used in the process into the final product. Two other principles that apply to synthe*c methods 8. Unnecessary deriva*za*on (blocking group, protec*on/deprotec*on, temporary modifica*on of physical/chemical processes) should be avoided whenever possible. 9. Cataly*c reagents (as selec*ve as possible) are superior to stoichiometric reagents. Reac*on Efficiency What do synthe*c chemists want? Higher yields Reduced use of reagents Ability to precisely form desired molecules The key to this is SELECTIVITY Types of selec*vity Chemoselec*vity reac*on at the desired func*onal group in a molecule rather than another, similar, one Regioselec*vity specific orienta*on of reac*on groups Stereoselec*vity reac*on to produce the desired enan*omer or diasteromer Trost, B. M. Selec*vity: A Key to Synthe*c Efficiency. Science, 1983, 219,

2 Chemoselec*vity Example: selec*ve reduc*on of alkenes and carbonyls Regioselec*vity Example: hydra*on of alkenes H 2, Pt/C H 3 + NaBH 4 H 2, Pt 2, PEG BH 3 -THF 2. H 2 2, Na Stereoselec*vity Percent Yield Example: dihydroxyla*on of alkenes 1. RC 3 H 2. H 3 + s 4 NM trans cis Tradi*onally, percent yield is reported as a measure of reac*on efficiency. % yield = actual yield theoretical yield theoretical yield = (moles of limiting reagent) x (MW of desired product) + NaBr + H 2S 4 Br + NaHS 4 + H 2 + NaBr + H 2S 4 Br + NaHS 4 + H 2 H 2 S bromobutane Suppose that 1.20 g of product was isolated after the reaction: % yield = 1.20 g 1.48 g = 81% theoretical yield = ( moles) x ( g/mol) = 1.48 g examples based on: Cann, M. Green Chemistry Module for rganic Chemistry. h`p://academic.scranton.edu/faculty/cannm1/organic.html Percent yield can be 100%, even if the reac*on produces a lot of waste. 2

3 Atom economy Concept introduced by Barry Trost in Describes the amount of the reactants that end up in the products. Note that cataly*c reagents are excluded from the calcula*on. % Atom economy = of utilized of all reactants used + NaBr + H 2S 4 Br + NaHS 4 + H 2 H 2 S bromobutane % Atom economy = = 49.8% Trost, B. M. The Atom Economy A Search For Synthe*c Efficiency. Science, 1991, 254, Experimental Atom Economy Takes into account the actual amounts of reagents used. Experimental atom economy = theoretical yield of product total mass of reagents used Some*mes called Reac*on Mass Efficiency + NaBr + H 2S 4 Br + NaHS 4 + H 2 H 2 S bromobutane Experimental atom economy = 1.48 g 0.80 g g g = 35.8% Percent Experimental Atom Economy Takes into account the actual amounts of reagents used and the yield of the reac*on % Experimental Atom Economy = (Experimental Atom Economy) x (% yield) + NaBr + H 2S 4 Br + NaHS 4 + H 2 % Experimental Atom Economy = 35.8% 81% = 29% Addi*onal examples of atom economy Elimina*on reac*on Br H + CH 3CH 2Na + CH 3CH 2Na + NaBr Un C 4 H 9 Br 137 4C, 8H 56 HBr 81 C 2 H 5 Na C, 5H,, Na 68 Total 205 4C, 8H 56 2C, 6H,, Br, Na 149 un This means that only 29% of the star*ng reagents end up in the isolated product. % atom economy = = 27% 3

4 Addi*onal examples of atom economy Addi*onal examples of atom economy Addi*on reac*on Rearrangement reac*on + HBr Br H H + Un C 4 H C, 8H 56 0 HBr 81 HBr 81 0 Total 137 4C, 8H, Br % atom economy = = 100% un Un C 6 H C, 12H 84 0 Total 84 6C, 12H 84 0 % atom economy = = 100% un Industrial Example Ethylene xide Ethylene oxide is an important industrial feedstock Used for produc*on of ethylene glycol, which in turn is used for: H An*freeze Polyethylene terephthalate (PET) Ether deriva*ves used as fuel addi*ves Biodegradable surfactants and cleaning products Ethylene oxide chlorohydrin route riginal route developed in 1914 (BASF) H 2 Problems: Economics: chlorine is expensive Selec*vity: difficult to prevent forma*on of dichloro compound. Health: chlorohydrin is very toxic + Ca()2 + H + Ca H 2 h`p:// Atom economy of chlorohydrin route H 2 Un C 2 H C, 4H H H 2 Ca() Ca, 4H, 2 72 Total 189 2C, 4H, 44 6H, 2, Ca, Ca()2 + H + Ca H 2 un Ethylene oxide cataly*c route Developed in 1930s Completely superseded chlorohydrin route by 1975 S*ll used for synthesis of propylene oxide + 1/2 2 Ag % atom economy = = 23% 4

5 Cataly*c synthesis + 1/2 2 Ag Un C 2 H C, 4H 28 0 ½ Total 44 2C, 4H, 44 0 % atom economy = = 100% un Environmental factor (E factor) Developed by Sheldon in the mid 1990s Very useful for industry E-factor = mass of waste mass of product Waste can be divided into different categories (i.e. aqueous and organic) Chemical outputs that are reused for other processes need not be included. Typical E factors Environmental Quo*ent Industry Annual producgon (t) Waste produced (t) E factor il refining ~ 0.1 Bulk chemicals x 10 6 <1 5 Fine chemicals x x Pharmaceu*cals x This is a good metric to account for waste, stoichiometry, and use of solvents and other auxilliary materials. Generally, E factor calcula*ons do not take into account energy use. Like E factor, but each waste is mul*plied by a hazard quo*ent (Q) based on the rela*ve hazard it poses to human health and the environment. The Environmental Assessment Tool for rganic Synthesis (EATS) is an online tool for assessing the Environmental Quo*ent. Source: Wikipedia h`p://en.wikipedia.org/wiki/green_chemistry_metrics h`p:// oldenburg.de/eatos/ EcoScale A more recent metric for smaller scale synthesis. Accounts for: reagent cost and toxicity reac*on temperature, pressure, and *me percent yield workup and purifica*on Scale from 0 (worst) to 100 (best) Van Aken, et al. EcoScale, a semi quan*ta*ve tool to select an organic prepara*on based on economical and ecological parameters. Beilstein J. rg. Chem. 2006, 2, No. 3 h`p:// EcoScale Example Using the same subs*tu*on reac*on from before: + NaBr + H 2S 4 Br + NaHS 4 + H 2 H 2 S bromobutane yield 5

6 Ecoscale calculator Manual Paper Contact Life Cycle Analysis/Assessment (LCA) s Link identifier * name MF* MW density purity* ml g mmoles equiv Bu C4H % NaBr BrNa % H2S4 H24S % Products Conditions identifier*: name: BuBr MF*: C4H9Br MW: s Name mmoles eq. Bp Hazard Price Yield Price / availability Safety Bu NaBr H2S g: 1.2 mmoles: g theor: yield: Technical setup Possible items Selected items Common set-up Instruments for controlled addition of chemicals -5 Unconventional activation technique Pressure equipment, > 1 atm Any additional special glassware Temperature / Possible items Selected items time Room temperature, < 1h Room temperature, < 24h Room temperature, < 24h -1 Heating, < 1h Heating, > 1h Cooling to 0 C Workup and Possible items Selected items purification None assical chromatography Cooling to room temperature Liquid - liquid extraction or washing -13 Adding solvent Simple filtration Removal of solvent with bp < 150 C EcoScale 57 ^ ^ ^ ^ Full analysis of a product or process, including: Raw materials extrac*on Transport and other energy requirements Manufacturing Sales Use Disposal/Recycling Focuses on economic and/or ecological variables Homework Ch. 4, #1 and 4 Read Ch. 5 in Anastas & Warner, and posted ar*cle(s) on Sustainability Come prepared to discuss sustainability in general and its applica*ons to chemistry 6