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

Abstract

This three-part laboratory experiment investigates key aspects of the Buchwald−Hartwig amination cross-coupling reaction through guided-inquiry learning strategies. The first part of this experiment utilizes high-throughput experimentation techniques to reinforce, explore, and extend fundamental concepts that are represented in the classroom, including the use of air-free Schlenk techniques and heteronuclear NMR analysis. The second component challenges students to evaluate their results to design, set up, and perform a preparative-scale Buchwald−Hartwig amination. Finally, students purify and isolate their products using column chromatography allowing them to fully characterize their target molecules through a variety of analytical techniques. This experiment represents one of the final experiments performed in the fourth-year undergraduate chemistry curriculum and serves as a capstone learning experience for students.

Training Undergraduate Sophomore or Junior Students in Air- and Moisture-Sensitive Reaction Techniques through a Multistep Synthesis of the Tripodal Bis[2-(2,3-dihydroxyphenyl)-6-pyridylmethyl](2-pyridylmethyl)amine (BCATTPA) Compound

“…The Schlenk Line Survival Guide is an invaluable education resource filled with illustrated step by step guides on how to perform these air- and moisture-free techniques . There have also been published video demonstrations on the use of a Schlenk line for degassing liquids and handling and transferring sensitive reagents, − which have been referenced and used in other educational video demonstrations. − Select papers have been published reporting laboratory experiments that incorporate these techniques, − and in 2021, a call for papers was issued for a special issue on Chemical Safety Education: Methods, Culture, and Green Chemistry where one article dealt with the subject of using syringes to handle air- and moisture-sensitive reagents . A 2022 paper addresses how to safely handle cannulas and needles in the laboratory and common inorganic and organometallic synthesis manuals also cover these reaction techniques in detail. − …”

A Modern Twist on an Old Measurement: Using Laboratory Automation and Data Science to Determine the Solubility Product of Lead Iodide

“…Data science and laboratory automation are rapidly becoming essential tools in modern experimental chemistry. , As such, it is important that we teach these skills throughout the chemistry curriculum, but efforts to date have primarily been in upper-level courses. Recent articles in this Journal have discussed training machine learning for spectroscopy-related problems in physical and analytical chemistry. − High-throughput experimentation has been discussed in the context of second-year organic chemistry and upper-level biochemistry courses. − The closely related idea of autonomous experimentation  colloquially known as “self-driving labs”  has been discussed in the context instrumental analysis or advanced elective courses. − …”

Catalysis in Modern Drug Discovery: Insights from a Graduate Student-Taught Undergraduate Course

“…In spite of the dramatic impact and evolution of transition-metal catalysis in drug development, it often receives less attention than “classical” reactions (e.g., S N 2, Diels–Alder, etc.) and their fundamental principles in undergraduate lecture courses . As such, students may not have the opportunity to learn fundamental concepts in catalysis, or perhaps more importantly, understand the applications of these concepts in important areas such as pharmaceutical development.…”