Going Green in Process Chemistry: Optimizing an Asymmetric Oxidation Reaction To Synthesize the Antiulcer Drug Esomeprazole.

Graeme D Mcallister,Andrew F Parsons

doi:10.1021/acs.jchemed.9b00350

Abstract

Sustainable practices in process chemistry are highlighted by a novel, 9 week team project of 8–12 students, in collaboration with AstraZeneca chemists, in an organic chemistry laboratory. Students synthesize the antiulcer medicine esomeprazole, which involves the asymmetric oxidation of pyrmetazole. To provide insight into the modern process chemistry industry, they propose environmentally friendly modifications to the asymmetric oxidation. Students first synthesize pyrmetazole and then follow a standard oxidation procedure and carry out modified, greener reactions of their choice. They investigate how a change in reaction conditions affects both the yield and enantioselectivity of esomeprazole. Positive student feedback was received and student postlab reports were analyzed over a 4 year period (2015–2018). Results consistently showed that the project provided students with the key tools to develop greener syntheses. This contextual approach not only offers the opportunity to develop valuable communication and team-working skills, but it also gives students creative input into their experimental work. It teaches the important research skills involved in sustainable process chemistry, from reproducing and modifying a literature procedure to identifying green metrics.

Highlights

Process chemistry involves the development and optimization of production processes, in the pharmaceutical sector
To give a flavor of practical process chemistry in our undergraduate course, around 10 years ago, in collaboration with AstraZeneca chemists, we developed a new mini-project for third-year students.[8]
The feedback from 2015 from the first cohort to explore the greener synthesis of esomeprazole was positive (Table 1)

Summary

■ INTRODUCTION

Process chemistry involves the development and optimization of production processes, in the pharmaceutical sector. In 2015, we decided to challenge students further by focusing the project on the development of a greener, more sustainable synthesis of esomeprazole, by evaluating variations in the oxidation reaction according to the 12 principles of green chemistry This provided a practical application of lecture course material, taught from year 2 onward, on the practice of clean and sustainable production by faculty in our Green Chemistry Centre of Excellence. Students were encouraged to look at the chemical literature to help inform their decisions This typically involved using green solvent selection guides.[18,19] Students could investigate changes outside of the indicative variations (e.g., an alternative oxidant) provided they had good reasons for doing this, including sound literature precedent (perhaps based on mechanistic considerations20), and the reagents were commercially available. All chemicals should be disposed of properly in appropriate waste containers

■ RESULTS AND PEDAGOGICAL OUTCOMES

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES