Introducing Regioselectivity in Rearrangement Reactions through a Discovery Experiment Using an Improved Schmidt-Type Reaction

Abstract

Rearrangement reactions, one of the most important transformations in organic chemistry, represent an important yet difficult aspect of the discipline. However, rearrangement reactions that involve regioselectivity are rarely covered in traditional experimental textbooks. Herein, a novel organic chemistry laboratory experiment centered around a Schmidt-type rearrangement was designed and presented, aimed at elucidating the mechanism of this reaction and its regioselective nature for students. Before conducting the experiment, students are tasked with previewing the mechanism underlying the formation of the observed amide product from the reaction between 4-nitrobenzophenone and n-PrNO₂. Given the asymmetric nature of the ketone, the potential for obtaining different amide products depends on the priority of the migration of the two aryls of 4-nitrobenzophenone during rearrangement. Through this experiment, students can discover that the product arises from the migration of the more electron-rich aryl, thereby indicating a nucleophilic rearrangement with evident regioselectivity. Additionally, the concept of green chemistry was integrated into the organic chemistry curriculum, underscoring the contribution of this improved Schmidt-type reaction in reducing toxicity and enhancing safety. This approach prompts students to recognize the imperative of green chemistry in advancing sustainable societal development, emphasizing the collective responsibility of chemists to shoulder environmentally conscious practices.