Comparing Industrial Amination Reactions in a Combined Class and Laboratory Green Chemistry Assignment

Abstract

This article describes a comparative assignment developed for a third-year undergraduate organic synthesis course involving a combined laboratory experiment and class exercise. In this assignment, students compare the sustainability of two industrial amination reactions to form the same target molecule (4-(n-hexylamino)benzonitrile): a nucleophilic aromatic substitution procedure (S N Ar) provided in the class exercise, and a Buchwald−Hartwig (B−H) amination procedure completed in the laboratory. The assignment is structured using a "case-study" format to provide appropriate context. Students use industrial solvent and reagent substitution guides, complete process mass intensity calculations, and apply the Twelve Principles of Green Chemistry to compare and contrast the S N Ar and B−H reactions. They finally recommend a preferred reaction procedure after considering multiple sustainability concepts in their analyses. The assignment is highly adaptable as different industry guides may be used and the S N Ar reaction procedure is easily modified. Ultimately, students learn to apply sustainable chemistry principles to industrially relevant reactions, an important skill for their future careers.

Evaluating Feedstocks, Processes, and Products in the Teaching Laboratory: A Framework for Students To Use Metrics to Design Greener Chemistry Experiments

“…15,16,24,168 Rather than comparing different techniques as we have done, individual laboratories and activities have been developed specifically to explore sustainability metrics. Dicks 169,170 designed laboratories focused on considering E-factor and reaction mass efficiency of an aza-Baylis-Hilman reaction 171 and the synthesis of benzodiazepines. 17, 172 Fennie meanwhile developed similar green metric explorations of amine-forming reactions.…”

“…To consider the amount of waste students can compare the reaction mass efficiency as detailed by Jessop and considered herein for biodiesel production, extractions, and catalyst synthesis. ,,, Rather than comparing different techniques as we have done, individual laboratories and activities have been developed specifically to explore sustainability metrics. Dicks , designed laboratories focused on considering E-factor and reaction mass efficiency of an aza -Baylis-Hilman reaction and the synthesis of benzodiazepines. , Fennie meanwhile developed similar green metric explorations of amine-forming reactions . Most of these examples accompany a laboratory component, but for those in search of an in-class tool, we developed an activity that uses LEGOs as molecular models.…”

The Green Chemistry Initiative’s contributions to education at the University of Toronto and beyond

“…Based on the success of these two activities, a third CHM 343H assignment was devised in 2017 via the CTFP which connects practical and theoretical aspects of the course. Students are required to undertake a Buchwald-Hartwig amination laboratory reaction to generate an aromatic amine, and compare the sustainability of their method with the sustainability of a nucleophilic aromatic substitution reaction that forms the same product (16). Feedback regarding the impact of all three assignments has been exceptionally positive, with many students appreciating the "real-world" application of green chemistry tools.…”

Buchwald–Hartwig Amination, High-Throughput Experimentation, and Process Chemistry: An Introduction via Undergraduate Laboratory Experimentation

“…16 While Pdcatalyzed reactions that from C−C bonds have been introduced as undergraduate laboratory experiments, such as Suzuki−Miyaura cross-coupling, 3 limited examples exist that incorporate this widespread C−N bond-forming reaction. 17 In addition, even fewer of these examples introduce the concept of high-throughput experimentation to undergraduates, a particularly useful chemical application in catalysis and process chemistry, 18,19 research. Recently, high-throughput experimentation has also been introduced for undergraduate laboratories utilizing the Suzuki−Miyaura reaction.…”