What is Green ? Why it is required? Se Nee Boe eR Rem Ua ec Laake me Rr + Environmental disasters: DDT, CFC, Bhopal Gas Tragedy (4K killed, 3.9K disabled, 5.6L injured), Flixborough, Seveso disasters. * Ozone layer depletion, water resources polluted, toxicity of common chemicals ee ice keclemirL e Oe anal tec Ima IA ela * No or less pollution is better than treating pollution related problems. * Green Chemistry: Natural evolution of pollution prevention initiatives taken by LCI Cln Aor ooe (ie UN Rca ee Rn heed Cael Ra eC) Rod formalized statements, policies and principles. Ren Cao acne ey ieee ee ura cen eee een kas ete RA Ror asi ad oa Aer tert eek Peele uRe util da mele ad go . See ie acs.org/content/acs/en/greenchemistry/what-is-green-chemistry.html(elcer-TamOnlslan aay Cee Rea a NACE) ceed ee) VA ee RE eee Tae) oe le when used in the design, development and implementation of chemical products and processes, enables scientists to protect and benefit the elcome Cae * Green Chemistry uses renewable, biodegradable materials which do not eam ene * Green Chemistry is using catalysis and biocatalysis to improve efficiency and conduct reactions at low or ambient temperatures. * Green Chemistry reduces the use and generation of hazardous substances. * Green Chemistry is a proven systems approach. * Green Chemistry offers a strategic pathway to build a sustainable future.Principles of Green Chemistry fete me uicny Everyone's Doing It! ‘The 12 Principles of Green Chemistry Prevent Waste stom Econom Design Benign Benign Solvents & Auxiliaries n for Energy Efficiency ‘Prevention Inherently Benign Chemistry for Accident Prevention Deter encedse ac-\Z—1a1 eel] * It is better to prevent waste than to treat or clean up waste after it has Lumet * For 1 Kg of API a process generates 100 Kg of waste, is it a green process? * How much weight/Kg of API will you accept for a good, Se Marlee let oR ORR Trg Pme]e-f 1a) omcve) oa) Paci SBS clad M ulead * Catalyst * Energy consumption inefficiency - CO2 burden Mate ah Tee CEC PdE-factor and PMI eR RR ee WEE m ee eck Ct) Total mass of materials used in a process,Kg Mass of the API (product,Kg) cea [ol id * Process Mass Intensity (PMI) = * PMI is usually between 25 to 1000 for pharmaceuticals. RTT UN RSPAS Le Re dct Pe htt hcl had 2 a el Ma cea) YT Dome gL en ts * Ideally PMI = 1, all input is incorporated in the product. * How to achieve this? * Reduce the use of organic solvents, and water. * PMI is equally useful as “Life Cycle Inventory and Assessment” * An efficient process will reduce CO2 burden by 5.5-6.5 Kg CO2/Kg product.sme Solerale Prowess (Pfizer’s Antidepressant) is Greener ° NCH, NHCHy NHCH, He CHsNH, PaiCaco, [D.Mandelic aci, EtOH +H,0| EtOH EtOH ci ct cl <1 ce a Cc Three step process Ethylacetate jw Introduction of EtOH as solvent Replacement of Pd/C with Pd/CaCO, - higher yields aie Elimination of titanium chloride, toluene, THF, CH2Cl,, and hexane “HCI Reduction of solvents from 60,000 to 6,000 gal/ton Elimination of 440 tons of titanium dioxide, 150 tons of 35% HCI, and 100 tons of 50% NaOH ‘Sertraline - HCI2. Atom economy (AE) Synthetic methods should be designed to maximize incorporation of all materials used in the process into the final product. what atoms of the reactants are incorporated into the final desired product(s) and what atoms are wasted?” Barry Trost Peers Maite e Role Madu) Aleit 101) mole Peele imi arate on irr Pe Br se) 7 Peery eC) * It has 100 % yield w.rt. n-butanol i.e. all of it is converted to product. * But for the overall process what is the efficiency in terms of cele eg2. Atom economy (AE) cont... * Ignoring other input (compounds & energy) is not the best choice. MolWt. of the desired product a Rae eee * Thus Atom economy(AE) = Patt) Ce oy or a Da ope Pome De tae anne Penne * Atom economy (AE) = 137.02/(74.12+102.89+98.07)*100 * AE=49.81~50% * Only half of the input material is incorporated in the product. * In AE calculations stoichiometric reagents are included, catalysts are ignored.2. Atom economy (AE) * Addition and rearrangement ersten eat aie % Atom Economy = SR earTaet eee tole lm tual ial lela 1.3.€q. CH! 3x 141.93 + 18.01 70.13 % Atom Economy = 73.14 + 3% 141.93 + 18.013. Less Hazardous chemical synthesis ATi De Tadte-)ol Me mht Rael Mele Cil-Ut te RoR ELL generate substances that possess little or no hazard/toxicity to human health PUT Rea * This principle says that discover new things with environment and health in Afole on . P| onl (elateahy ees i erences ees ite elas ani ele See en IRE tect Regie * Toluene, pyridine are flammable, carcinogenic,3. Less Hazardous chemical synthesis: example a co a Paar eM Ue Mela lat reer Peace RES im) ae Rll ele * Reduced reaction (2 hr) and workup time. * ZnO (side product) relatively non-toxic (but toxic to aquatic life).4. Designing safer chemicals Cee eee eee MMe Tu R mea Ream Ly ireland a Ne) od RCS Lat Men L Ua Pele) eee) amor) > C(out). * Thus if we fix C more than we release C, global temps will gradually stabilize or J. Ba iCele [Tt celta See ae uence yeni ccene) Sie eee eee Rue una en Eee] Been een cur eee un cen can cs8. Reduce Derivatives Tee Cc Ce out a ray Cc CIC modification of physical/chemical processes) should be minimized or avoided einem tit nie cei enr ca cence * Reduce use of protecting groups in synthetic schemes. > Enzymes help here (not always!) See a eae ere a UR eee age BU el tata ec eae Ct} rea ea ae ea) i) TMSCI, then PCIS, PhNMe2, DCM, -40°C ii) n-BuOH -40°C ane eC Tg Vee RUCU BOR ata Str eR anemia mates Se ee eRe Reece eemer Caen emul ae Ee rice9. Catalysis Cee Cust ee a eee eS Rice uae Cie cuss eC ane Sic e Ck Cn nates irae eC Cra eRe aS ue OM ees Serer Cue Coste atc cl We can reduce ketones with H2, but DR oe cea eu a ee oe SNe eR re Uren else eR Ue Cet eee ease Ree eu Mra as SU MCR eet a Te eas RCAC Ce CR ACCe Rai cunoteeet Saco ROMS mates eek rie Organic and bio catalysts need to be developed. (These are renewable as well).10. Design for degradation Chemical products should be designed so that at the end of their function they break down into innocuous degradation products and do not persist in the environment. * Principle 3, 4, 5 and 12 guide chemists/pharmacists to reduce hazards. * Principle 10 guides towards a design that favors degradation after end use. * This reduces exposure. Remember! Risk = hazard * exposure. * Properties: lipophilicity, volatility, water solubility, t1/2 in water, soil and air. * Using this chemicals defined: PBT (Persistent, bioaccumulative, and/or toxic). * Design out molecular features leading to hazard and/or toxicity. * Design for degradation can be driven by SNM acai attack10. Design for degradation... * Mechanistic understanding is required to design out hazard and toxicity. * Many persistent comps contain Halogens (Cl). * Clis electronegative and withdraws electrons from atoms attached to it. * Enzymatic biodegradation (oxygenation) mostly targets electron rich centers. Se ORE one eo * Thus organochlorines tend to persist in the env due to low degradation rates. * Prediction methods, rule of thumb, databases, guidelines help in design for degradation. * Design should consider release, transport mechanism and end env conditions. * * Foaming, chocking of public water systems in 1960s led to design of degradable surfactants (from branched to straight chain fatty acids).10. Design for Degradation: rules of thumb * Aromatic compounds with = 3 rings biodegrade easily, those with > 3 rings tend to persist. + Ortho or para Cl derivatives biodegrade easily, meta Cl tend to persist. * Primary, secondary amines are more degradable than tertiary. cen 5 period cen Persat nthe Env cv Boethiling et al. Designing Small Molecules for Biodegradability. Chem. Rev. 2007, 107. 2207.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 Tet Ula fella Melati eee emo Meee eam Oeics control and efficiency. * Reaction monitoring routine on lab scale (HPLC, MS, UV-visible, FT-IR, NMR). * On industrial scale (large reactors, high vol. solvents, bulk material) challenge * Sampling, safety, process susceptibility to moisture, 02, temp, press As. * Online, in-line, at-line process monitoring now possible for many processes. * Similar approach for waste, hazard and toxicity management is required. SNS es Rema ee Ree) LC LT12. Inherently Safer Chemistry for Accident Prevention Substances and the form of a substance used in a chemical process should be Cee MU Re eu Rm lela me aoe explosions, and fires. * Safety principle can be defined as the control of recognized hazards to achieve an acceptable level of risk. iN * Principle 12 in combination with others ensures safer working place. * Workers, operators, MS, PhD students are benefited by application of green Coat lea melee ol oe12. Safety principle jerarchy | of Safety j Controls