<p>List of Contributors xvii</p> <p>Foreword xxi</p> <p>Preface xxiii</p> <p><b>Part I General Topics in Green Chemistry 1</b></p> <p><b>Green ChemistryMetrics 3<br /></b><i>Frank Roschangar and Juan Colberg</i></p> <p>1.1 Business Case 3</p> <p>1.2 Historical Context 3</p> <p>1.3 Metrics, Awards, and Barriers 4</p> <p>1.4 Metrics Unification Via Green Aspiration Level 9</p> <p>1.5 Green Scorecard 12</p> <p>1.6 Supply Chain 14</p> <p>1.7 Outlook and Opportunities 15</p> <p>References 17</p> <p><b>Green Solvents 21<br /></b><i>Janet L. Scott and Helen F. Sneddon</i></p> <p>2.1 Introduction 21</p> <p>2.2 Solvent Selection Guides and Tools 23</p> <p>2.3 Greener Molecular Solvents 24</p> <p>2.4 Opportunities, Challenges, and Future Developments 34</p> <p>References 34</p> <p><b>Green Analytical Chemistry 43<br /></b><i>Paul Ferguson and Douglas Raynie</i></p> <p>3.1 Introduction 43</p> <p>3.2 Sample Preparation 47</p> <p>3.3 Techniques and Methods 50</p> <p>3.4 Process Analytical Technology 60</p> <p>3.5 Biopharmaceutical Analysis 62</p> <p>3.6 Conclusions 65</p> <p>Acknowledgments 66</p> <p>References 66</p> <p><b>Green Engineering 71<br /></b><i>Christopher L. Kitchens and Lindsay Soh</i></p> <p>4.1 Introduction: Green Engineering Misconceptions and Realizations 71</p> <p>4.2 12 Principles of Green Engineering 72</p> <p>4.3 Green Chemistry Metrics Applied to Engineering 73</p> <p>4.4 Use of Green Solvents in the Chemical Industry 80</p> <p>4.5 Presidential Green Chemistry Awards 86</p> <p>4.6 Opportunities and Outlook 87</p> <p>References 87</p> <p><b>Greening of Consumer Cleaning Products 91<br /></b><i>David C. Long</i></p> <p>5.1 History of Green Consumer Cleaning Products 91</p> <p>5.2 Drivers for Greener Products 94</p> <p>5.3 Development of Green Cleaning Criteria and Eco-Labeling 98</p> <p>5.4 Development of Greener Ingredients for Cleaners 102</p> <p>5.5 The Future of Green Cleaning 111</p> <p>Acknowledgments 112</p> <p>References 112</p> <p><b>Innovation with Non-Covalent Derivatization 117<br /></b><i>John C.Warner and Emily Stoler</i></p> <p>6.1 Introduction 117</p> <p>6.2 NCD Overview 118</p> <p>6.3 Pharmaceutical NCDs 121</p> <p>6.4 Environmental and Green Chemistry Benefits 123</p> <p>References 123</p> <p><b>Part II Green Catalysts 131</b></p> <p><b>Catalytic C-H Bond Cleavage for Heterocyclic Compounds 133<br /></b><i>Zhanxiang Liu and Yuhong Zhang</i></p> <p>7.1 Introduction 133</p> <p>7.2 Synthesis of Nitrogen Heterocycles 133</p> <p>7.3 Synthesis of Oxygen-Containing Heterocycles 144</p> <p>7.4 Synthesis of Sulfur-Containing Heterocycles 148</p> <p>7.5 Medium-Sized Heterocyclic Compounds 150</p> <p>7.6 Conclusion 152</p> <p>References 152</p> <p><b>Biocatalysis 161<br /></b><i>James Lalonde</i></p> <p>8.1 Introduction 161</p> <p>8.2 Enzymes for Biocatalysis 162</p> <p>8.3 Advances in Enzyme Engineering and Directed Evolution 164</p> <p>8.4 Biocatalytic Synthesis of Pharmaceuticals: Case Studies of Highly Efficient Pharmaceutical Syntheses 165</p> <p>8.5 Summary and Future Outlook 178</p> <p>References 180</p> <p><b>Practical Asymmetric Organocatalysis 185<br /></b><i>Wen-Zhao Zhang, Samik Nanda, and Sanzhong Luo</i></p> <p>9.1 Introduction 185</p> <p>9.2 Aminocatalysis 185</p> <p>9.3 Brønsted Acid Catalysis 191</p> <p>9.4 Brønsted Base Catalysis 193</p> <p>9.5 Hydrogen-Bonding Catalysis 197</p> <p>9.6 Phase-Transfer Catalysis 202</p> <p>9.7 Lewis Acid, Lewis Base, and N-Heterocyclic Carbene Catalysis 204</p> <p>9.8 Large-Scale Reaction (>100-Gram Reaction) 207</p> <p>9.9 Conclusion 209</p> <p>References 209</p> <p><b>Fluorous Catalysis 219<br /></b><i>L´aszl´o T. Mika and Istv´an T. Horv´ath</i></p> <p>10.1 Introduction and the Principles of Fluorous Catalysis 219</p> <p>10.2 Ligands for Fluorous Transition Metal Catalysts 224</p> <p>10.3 Synthetic Application of Fluorous Catalysis 225</p> <p>10.4 Fluorous Organocatalysis 256</p> <p>10.5 Other Applications of Fluorous Catalysis 259</p> <p>References 259</p> <p><b>Solid-Supported Catalysis 269<br /></b><i>Sukanta Bhattacharyya and Basudeb Basu</i></p> <p>11.1 Introduction 269</p> <p>11.2 Immobilized Palladium Catalysts 270</p> <p>11.3 Immobilized Rhodium Catalysts 276</p> <p>11.4 Immobilized Ruthenium Catalysts 279</p> <p>11.5 Other Immobilized Catalysts 284</p> <p>11.6 Conclusions 286</p> <p>References 287</p> <p><b>Asymmetric Organocatalysis in Aqueous Media 291<br /></b><i>Kartick C. Bhowmick and Tanmoy Chanda</i></p> <p>12.1 Introduction 291</p> <p>12.2 Carbon-Carbon Bond-Formation Reactions 292</p> <p>12.3 Reactions Other than C-C Bond Formation 313</p> <p>12.4 Conclusion 314</p> <p>References 314</p> <p><b>Part III Green Synthetic Techniques 325</b></p> <p><b>Solvent-Free Synthesis 327<br /></b><i>Kendra Leahy Denlinger and JamesMack</i></p> <p>13.1 Introduction 327</p> <p>13.2 Ball Milling 328</p> <p>References 339</p> <p><b>Ultrasonic Reactions 343<br /></b><i>Rodrigo Cella and H´elio A. Stefani</i></p> <p>14.1 Introduction 343</p> <p>14.2 How Does CavitationWork? 343</p> <p>14.3 Aldol/Condensation Reactions 345</p> <p>14.4 1,4-Addition 351</p> <p>14.5 Heterocycles Synthesis 353</p> <p>14.6 Coupling Reactions 356</p> <p>14.7 Wittig Reaction 361</p> <p>14.8 Diels-Alder Reaction 362</p> <p>14.9 Miscellaneous 365</p> <p>14.10 Conclusions 366</p> <p>References 366</p> <p><b>Photochemical Synthesis 373<br /></b><i>Stefano Protti,Maurizio Fagnoni, and Angelo Albini</i></p> <p>15.1 Introduction 373</p> <p>15.2 Synthesis and Rearrangement of Open-Chain Compounds 376</p> <p>15.3 Synthesis of Three- and Four-Membered Rings 382</p> <p>15.4 Synthesis of Five-, Six- (and Larger)-Membered Rings 391</p> <p>15.5 Oxygenation and Oxidation 398</p> <p>15.6 Conclusions 400</p> <p>Acknowledgments 401</p> <p>References 401</p> <p><b>Pot Economy Synthesis 407<br /></b><i>Wenbin Yi, Xin Zeng, and Song Gao</i></p> <p>16.1 Introduction 407</p> <p>16.2 Multicomponent Reactions 407</p> <p>16.3 One-Pot and Multi-Step Reactions 415</p> <p>16.4 One-Pot Asymmetric Synthesis 424</p> <p>16.5 Outlook 434</p> <p>References 434</p> <p><b>Microwave-Assisted Organic Synthesis: Overview of Recent Applications 441<br /></b><i>Nandini Sharma, Upendra K. Sharma, and Erik V. Van der Eycken</i></p> <p>17.1 Introduction 441</p> <p>17.2 C-H Functionalization 449</p> <p>17.3 Insertion Reactions 452</p> <p>17.4 Reduction 453</p> <p>17.5 Synthesis of Peptides and Related Fine Chemicals 455</p> <p>17.6 Newer Developments 459</p> <p>17.7 Summary 461</p> <p>References 461</p> <p><b>Solid-Supported Synthesis 469<br /></b><i>Indrajeet J. Barve and Chung-Ming Sun</i></p> <p>Abbreviations 469</p> <p>18.1 Introduction 471</p> <p>18.2 Techniques of Solid-Phase Supported Synthesis 472</p> <p>18.3 Solid-Phase Supported Heterocyclic Chemistry 476</p> <p>18.4 Solid-Supported Synthesis of Natural Products 486</p> <p>18.5 Solid-Supported Organometallic Chemistry 491</p> <p>18.6 Solid-Phase Synthesis of Peptides 493</p> <p>18.7 Solid-Phase Supported Stereoselective Synthesis 494</p> <p>18.8 Interdisciplinary Solid-Supported Synthesis 499</p> <p>References 505</p> <p><b>Light Fluorous Synthesis 509<br /></b><i>Wei Zhang</i></p> <p>19.1 Introduction 509</p> <p>19.2 “Heavy” Versus “Light” Fluorous Chemistry 509</p> <p>19.3 The Green Chemistry Aspects of Fluorous Synthesis 510</p> <p>19.4 Fluorous Techniques for Discovery Chemistry 511</p> <p>19.5 Conclusions 533</p> <p>References 533</p> <p><b>Part IV Green Techniques and Strategies in the Pharmaceutical Industry 539</b></p> <p><b>Ionic Liquids in Pharmaceutical Industry 541<br /></b><i>Julia L. Shamshina, Paula Berton, HuiWang, Xiaosi Zhou, Gabriela Gurau, and Robin D. Rogers</i></p> <p>Abbreviations 541</p> <p>20.1 Introduction 543</p> <p>20.2 Finding the Right Role for ILs in the Pharmaceutical Industry 544</p> <p>20.3 Conclusions and Prospects 567</p> <p>References 568</p> <p><b>Green Technologies and Approaches in theManufacture of Biologics 579<br /></b><i>Sa V. Ho and Kristi L. Budzinski</i></p> <p>21.1 Introduction 579</p> <p>21.2 Characteristics of Biologics 580</p> <p>21.3 Manufacture of Therapeutic Biologics 581</p> <p>21.4 Environmental Metrics Development and Impact Analysis 587</p> <p>21.5 Some Future Directions 592</p> <p>21.6 Conclusions 594</p> <p>Acknowledgments 594</p> <p>References 594</p> <p><b>Benchmarking Green Chemistry Adoption by “Big Pharma”and Generics Manufacturers 601<br /></b><i>Vesela R. Veleva and BerkeleyW. Cue</i></p> <p>22.1 Introduction 601</p> <p>22.2 Literature Review 602</p> <p>22.3 Pharmaceutical Industry Overview and Green Chemistry Drivers 604</p> <p>22.4 Benchmarking Industry Adoption of Green Chemistry 607</p> <p>22.5 Results and Discussion 610</p> <p>22.6 Conclusion 616</p> <p>References 616</p> <p><b>Green Process Chemistry in the Pharmaceutical Industry: Case Studies Update 621<br /></b><i>Joseph M. Fortunak, Ji Zhang, Frederick E. Nytko III, and Tiffany N. Ellison</i></p> <p>23.1 Introduction 621</p> <p>23.2 Pharmaceutical Patents Driving Innovation 622</p> <p>23.3 A Caution About Drug Manufacturing Costs 623</p> <p>23.4 Process Evolution by Multiple Route Discovery Efforts—Dolutegravir 624</p> <p>23.5 The Impact of Competition on Process Evolution—Tenofovir Disoproxil Fumarate 628</p> <p>23.6 Simeprevir (Olysio/Sovriad) and Analogues: Chiral Phase-Transfer Catalyst-Promoted Optical Alpha-Amino Acid Synthesis: A Metal-free Process 633</p> <p>23.7 Vaniprevir (MK 7009), Simeprevir (TMC435), and Danoprevir: Ring-Closing Metathesis (RCM) for Macrocyclic Lactam Synthesis: Now a Commercial Reality 635</p> <p>23.8 Daclatasvir (BMS-790052, Daklinza), and Ledipasvir (GS-5885): Palladium Catalyzed Cross-Coupling for Greening a Process 638</p> <p>23.9 Sitagliptin (Januvia) and Ponatinib (Iclusig): Greening the Process by Telescoping Multiple Steps Together 639</p> <p>23.10 Febuxostat (Uloric): Greening the Process via Metal Catalyzed C-H Activation: A Prospect 641</p> <p>23.11 Conclusions 644</p> <p>References 644</p> <p><b>Greener Pharmaceutical Science Through Collaboration: The ACS GCI Pharmaceutical Roundtable 649<br /></b><i>Julie B. Manley andMichael E. Kopach</i></p> <p>24.1 Introduction 649</p> <p>24.2 Establishing Pre-Competitive Collaborations 650</p> <p>24.3 Informing and Influencing the Research Agenda 654</p> <p>24.4 Developing Tools 661</p> <p>24.5 Educating Leaders 666</p> <p>24.6 Collaborating Globally 668</p> <p>24.7 Future Opportunities 669</p> <p>24.8 Success Factors 671</p> <p>References 673</p> <p>Index 675</p>