Scalable Green Chemistry: Case Studies from the Pharmaceutical Industry, 1st Edition (Hardback) book cover

Scalable Green Chemistry

Case Studies from the Pharmaceutical Industry, 1st Edition

Edited by Stefan Koenig

Jenny Stanford Publishing

350 pages | 187 B/W Illus.

Purchasing Options:$ = USD
Hardback: 9789814316491
pub: 2013-09-11
SAVE ~$32.00
eBook (VitalSource) : 9780429099953
pub: 2013-09-11
from $28.98

FREE Standard Shipping!


Packed with real-world examples, this book illustrates the 12 principles of green chemistry. These diverse case studies demonstrate to scientists and students that beyond the theory, the challenges of green chemistry in pharmaceutical discovery and development remain an ongoing endeavor. By informing and welcoming additional practitioners to this mission, the negative environmental impact of pharmaceutical products will continue to be minimized. Green chemistry is the methodology by which chemical production in this industry can become more efficient, adding environmental stewardship to the noble mission of treating human disease.


"At last! A book which provides a discussion of green chemistry from a process chemistry/engineering viewpoint. The case studies on individual pharmaceuticals in the various chapters are supplemented by a great general introductory chapter and a final concluding chapter by the editor."

--Dr. Trevor Laird, Editor, Organic Process Research & Development

"This monograph is a tutorial featuring not only an impressive overview of the virtues of green chemistry, but also real-world cases that illustrate how this emerging field can be applied within the pharma arena to great economic, as well as environmental, advantage."

--Prof. Bruce H. Lipshutz, University of California, Santa Barbara, USA

"This thirteen-chapter book summarizes the most recent green chemistry and engineering achievements in the pharmaceutical industry. It provides good examples that illustrate the concept of green-by-design, the practice of green metrics, and the advancement of green technologies in drug design, development and production."

--Prof. Wei Zhang, University of Massachusetts Boston, USA

"Scalable Green Chemistry represents an important and timely contribution to the armamentarium of the pharmaceutical green chemist. This book’s case studies, contributed by well-known and highly respected authors from this field, will be catalysts for the progression and broader adoption of a more sustainable way to do drug synthesis and manufacture."

--Dr. Berkeley W. Cue, Jr.,BWC Pharma Consulting LLC, USA

"This timely book illustrates the application of green chemistry principles to several prominent cases in greener pharmaceutical manufacturing. It showcases excellent examples of the impact of green chemistry on the pharmaceutical industry."

--Prof. Chao-Jun Li, McGill University, Canada

Table of Contents

Introduction to Green Pharmaceutical Science: Fact, Fiction, and Future, Julie B. Manley

Green Chemistry in Drug Development, Apurba Bhattacharya, Siddhartha Akasapu, and Rakeshwar Bandichhor







Development of Green-by-Design, Practical Biocatalytic Processes, Gjalt W. Huisman and Steven J. Collier


Introduction on Biocatalysis and Directed Evolution

Biocatalysis and Green Chemistry

Ketoreductase Processes for Chiral Alcohols

Transaminase Processes to Chiral Primary Amines

Acyltransferase Approach to Simvastatin

Integrated Biocatalytic Processes

Conclusions and Outlook

Application of Green Metrics to Scalable Industrial Synthesis Plans: Approaches to Oseltamivir Phosphate (Tamiflu R _), John Andraos


Green Metrics Essentials for Industrial Chemists

Oseltamivir Approaches: Synthesis Strategies

Oseltamivir Syntheses: Material Efficiencies

Concluding Remarks

The Road to Becoming Green: Process Development of AR-A2, an Active Pharmaceutical Ingredient with Antidepressant Activity, Hans-J¨urgen Federsel, Martin Hedberg, Fredrik R. Qvarnstr¨om, and Wei Tian

The Green Agenda

Starting the New Project

Time for Change: The Road Map to Better Synthesis

Homing in on Safety, Health, and Environment (SHE) Improvements

Focusing the Morpholinobenzoic Acid Side Chain: Design of the Ultimate Process

Reaching the End Product: SHE Perspective on the Final Stages

Summary: Improvements in Environmental Impact of the AR-A2 × HBr Process

Improved and Greener Process for Pioglitazone and Its Pharmaceutically Acceptable Salts, Apurba Bhattacharya, Rakeshwar Bandichhor, and Lokeswara Rao Madivada


A Green Attitude

Synthesis of Pioglitazone

Development of a Greener Process: Improved Process for Pioglitazone

Process Optimization


The Development of a Convergent Green Synthesis of Linezolid, an Oxazolidinone Antibacterial Agent, William R. Perrault, James B. Keeler, William C. Snyder, Christian L. Clark, Michael R. Reeder, Richard J. Imbordino, Rebecca M. Anderson, Nabil Ghazal, Stephen L. Secreast, and Bruce A. Pearlman


Green Linezolid Process


Development of a Nonaqueous Process for the Synthesis of 3-Amino-pentan-1,5-diol, Thimma Rawalpally and Thomas Cleary


IND Synthesis

First-Generation Aminodiol Synthesis

Second-Generation Synthesis

Environmental Assessment of the Synthetic Routes

Development of a Robust, Environmentally Responsible Process for the Manufacture of Tofacitinib Citrate, Rajappa Vaidyanathan


Retrosynthetic Strategy

Approaches to Piperidine 6

Choice and Synthesis of the Coupling Partner

The Debenzylation Step

Amidation, Salt Formation, and Isolation


Selective Nitration under cGMP Conditions, Peter Poechlauer, Sascha Braune, and Roland Oberm¨uller

Introduction: Pharmaceuticals—Successful Products, Inefficient Manufacture?

Pharmaceutical Production

Process Intensification

Process Intensification in Practice

Safety First: A thorough Analysis

Consequences for Plant Design


Continuous Improvement and Its Consequences on the Environmental Impact of a Plant


Going Green Using Combined Real-Time Analytics and Process Automation, Dominique Hebrault and Terry Redman


Case Studies

General Conclusions

Approaches to the Scale-Up of Organic Chemistry Using Microwave Heating, Nicholas E. Leadbeater


Scale-Up of Chemistry Performed Using Microwave Heating

Concluding Remarks

Challenges Faced and Future Directions, Stefan G. Koenig


Successful Beginnings

The Future of Green Chemistry

Conclusions Index 357

About the Editor

Stefan Koenig received his PhD from Yale University before conducting postdoctoral research at the ETH (Swiss Federal Institute) in Zurich, Switzerland. He embarked on his professional career in the pharmaceutical industry at Sepracor (now Sunovion Pharmaceuticals). Currently, he is a scientist at Genentech and chair of Roche/Genentech’s global Green Chemistry Technical Working Group.

Subject Categories

BISAC Subject Codes/Headings:
MEDICAL / Pharmacology
SCIENCE / Chemistry / Organic
TECHNOLOGY & ENGINEERING / Environmental / General