Green Metrics, Volume 11

Paul T. Anastas joined Yale University as Professor and iserves as the Director of the Center for Green Chemistry and Green Engineering at Yale. From 2004-2006, Paul Anastas has been the Director of the Green Chemistry Institute in Washington, D.C. Until June of 2004 he served as Assistant Director for Environment at e White House Office of Science and Technology Policy where his responsibilities included a wide range of environmental science issues including furthering international public-private cooperation in areas of Science for Sustainability such as Green Chemistry. In 1991, he established the industry-government-university partnership Green Chemistry Program, which was expanded to include basic research, and the Presidential Green Chemistry Challenge Awards. He has published and edited several books in the field of Green Chemistry and is one of the inventors of the 12 principles of Green Chemistry. David J.C. Constable is the Director the American Chemical Societys Green Chemistry Institute. From the end of September, 2011 until January, 2013 David worked as the owner and principal at Sustainability Foresights, LLC. David left Lockheed Martin as the Corporate Vice President of Energy, Environment, Safety & Health (ESH) at the end of September 2011. Prior to joining Lockheed Martin, David was the Director of Operational Sustainability in the Corporate Environment, Health, and Safety Department at GlaxoSmithKline. During Davids tenure with GlaxoSmithKline, he held positions of increasing responsibility and global reach within Corporate Environment, Health and Safety. He first joined SmithKline Beecham, a predecessor to GlaxoSmithKline, in 1991. Prior to joining SmithKline Beecham, he served as a Group Leader in the SHEA Analytical Services group of ICI Americas. Dr. Jimnez-Gonzlez is currently Director of New Product Development at Stiefel, a GlaxoSmithKline company. She has worked in GlaxoSmithKline for about 14 years in a variety of roles of increasing responsibility, most recently Director of Engagement, Planning, Analysis and Reporting and Director of Operational Sustainability leading teams responsible for the global programs to embed Sustainability into the operations, the Sustainability external reporting and the Environment, Health and Safety (EHS) strategic plan. Before joining GSK, she was program manager at the Environmental Quality Center of the Monterrey Institute of Technology and Superior Education (ITESM), and worked in several EHS and sustainability positions in Mexico. She currently also teaches Green Chemical Engineering at North Carolina State University (NCSU). In the past she was a faculty member at ITESM and visiting faculty in the Saltillo Institute of Technology, Mexico. She has a B.S. in Chemical and Industrial Eng. from the Chihuahua Institute of Technology (Mexico); a M.Sc. in Environmental Eng. from ITESM, Mexico; and a PhD in Chemical Engineering from NCSU. Her publications involve topics in the area of life cycle assessment, material selection, green chemistry, energy optimization, much of the publications as a result of GlaxoSmithKlines research.

List of Contributors XI Preface XIII 1 Green Chemistry Metrics 1 David J.C. Constable 1.1 Introduction and General Considerations 1 1.2 Feedstocks 5 1.3 Chemicals 6 1.3.1 Hazard and Risk 6 1.4 General Chemistry Considerations and Chemistry Metrics 10 1.5 Evolution of Green Chemistry Metrics 11 1.6 Andraos: Tree Analysis 14 1.7 Process Metrics 15 1.8 Product Metrics 16 1.9 Sustainability and Green Chemistry 17 1.10 Making Decisions 18 References 19 2 Expanding Rational Molecular Design beyond Pharma: Metrics to Guide Safer Chemical Design 29 Nicholas D. Anastas, John Leazer, Michael A. Gonzalez, and Stephen C. DeVito 2.1 Introduction to Safer Chemical Design 29 2.2 Life Cycle Thinking 30 2.2.1 Sustainability, Green Chemistry, and Green Engineering 30 2.2.2 Life Cycle Considerations 31 2.2.3 Life Cycle Assessment 32 2.2.4 Chemical Process Sustainability Evaluation Metrics 34 2.3 Attributes of Chemicals of Good Character 36 2.4 Tools for Characterizing the Attributes of Chemicals of Good 2.4.1 Strive to Reduce or Eliminate the Use of Chemicals 40 2.4.2 Maximize Biological and Use Potency and Efficacy 40 2.4.3 Strive for Economic Efficiency 40 2.4.4 Limited Bioavailability 41 2.4.5 Limited Environmental Mobility 41 2.4.6 Design for Selective Reactivity: Toxicity 41 2.4.7 Minimize the Incorporation of Known Hazardous Functional Groups: Toxicophores and Isosteres 42 2.4.8 Minimize the Use of Toxic Solvents 42 2.4.9 Limited Persistence and Bioaccumulation 43 2.4.10 Quick Transformation to Innocuous Products 44 2.4.11 Avoid Extremes of pH 44 2.5 A Decision Framework 44 2.5.1 A Suggested Protocol for Approaching Safer Chemical Design 45 2.5.2 Alternatives and Chemical Risk Assessment 45 2.6 The Road Ahead: Training of a Twenty-First Century Chemist 46 References 46 3 Key Metrics to Inform Chemical Synthesis Route Design 49 John Andraos and Andrei Hent 3.1 Introduction 49 3.2 Material Efficiency Analysis for Synthesis Plans 50 3.3 Case Study I: Bortezomib 56 3.3.1 Millennium Pharmaceuticals Process 59 3.3.2 Pharma-Sintez Process 62 3.3.3 Material Efficiency Local and Express 64 3.3.4 Synthesis Strategy for Future Optimization 72 3.3.5 Summary 73 3.4 Case Study II: Aspirin 74 3.4.1 Reaction Network 74 3.4.2 Material Efficiency 76 3.4.3 Environmental and SafetyHazard Impact 78 3.4.4 Input Energy 84 3.4.5 Case I 84 3.4.6 Case II 85 3.4.7 Case III 85 3.4.8 Case IV 85 3.4.9 Case V 86 3.4.10 Case VI 86 3.4.11 Concluding Remarks and Outlook for Improvements 88 References 91 4 Life Cycle Assessment 95 Concepcin Jimnez-Gonzlez 4.1 Introduction 95 4.2 The Evolution of Life Cycle Assessment 96 4.3 LCA Methodology at a Glance 97 4.3.1 Goal and Scope 98 4.3.2 Inventory Analysis 98 4.3.3 Impact Assessment 99 4.3.4 Interpretation 99 4.3.5 LCI/A Limitations 100 4.3.6 Critical Review 101 4.3.7 Streamlined Life Cycle Assessment 102 4.4 Measuring Greenness with LCI/A Applications 103 4.4.1 Probing Case Studies 103 4.4.2 Chemical Route Comparison 106 4.4.3 Material Assessment 109 4.4.4 Product LCAs 112 4.4.5 Footprinting 115 4.5 Final Remarks 117 References 118 5 Sustainable Design of Batch Processes 125 Tnia Pinto-Varela and Ana Isabel Carvalho 5.1 Introduction 125 5.2 State of the Art 126 5.2.1 Design and Retrofit of Batch Processes 127 5.2.2 Sustainability Assessment 131 5.3 Framework for Design and Retrofitting in Batch Processes 136 5.3.1 Economic Assessment 138 5.3.2 Environmental Assessment 139 5.3.3 Social Assessment 140 5.3.4 Methodologies 141 5.4 Case Studies 142 5.4.1 Retrofit Sustainable Batch Design 142 5.4.2 Design of Batch Process 147 5.5 Conclusions 150 References 152 6 Green Chemistry Metrics and Life Cycle Assessment for Microflow Continuous Processing 157 Lihua Zhang, Qi Wang, and Volker Hessel 6.1 Introduction 157 6.1.