The chlorination reaction of aromatic compounds is highly important for the synthesis of pharmaceutical products. As the most common chlorination reagent, chlorine is restricted from undergraduate laboratory experiment training due to its toxicity. To circumvent this disadvantage, a myriad of chlorination reagents have been developed to fulfill the same task. Among these reagents, NCS is widely available and readily available for storage. However, NCS is less reactive than chlorine in the chlorination reaction and requires a prolonged reaction time, which limits its adaptation to laboratory teaching. Regarding the significance of chlorination reactions, it is highly desirable to introduce a safe and speedy experiment showing the chlorination of aromatic compounds into an undergraduate laboratory.
In recent years, electrochemical synthesis has experienced a new tide of growth. By utilizing electrons with high potential at the anode and cathode, electrochemical reactions drive the inert substrate and reagents to reactive intermediates, forming challenging bonds with step and atom economy. Featuring the concept of electron catalysis, electrochemical transformation justifies its importance in the area of green chemistry of the new version. Recently, there has been progress in electrochemistry in chemical education. In particular, the undergraduate laboratory course focusing on electrochemical synthesis has received increasing attention since it can convey the classic and state-of-the-art concept of green chemistry driven by electrons to undergraduate students directly. With these efforts, however, electrochemical chlorination is still unexplored in chemical education.
Figure 1. Experimental setup for Undergraduate Laboratory Course
Herein, we report the first electrochemical chlorination experiment of aromatic compounds designed for undergraduate laboratory teaching (Figure 1). This reaction could convey several features to students: (1) using electricity as a driving force to achieve highly efficient transformation (Figure 2); (2) utilizing mild and safe NCS as a reagent; and (3) using inexpensive carbon material as an electrode. Additionally, (4) the reaction generates chlorine in situ and on demand, avoiding side reactions due to excess chlorine.
Figure 2. Proposed Reaction Pathway
This research has been published online in Journal of Chemical Education entitled “Application of Electrochemical Chlorination Reaction in Organic Laboratory Course” (Paper link: https://doi.org/10.1021/acs.jchemed.2c01088). Prof. Xu Cheng and Prof. Jie Dai are cocorresponding authors. 2018 undergraduate students, Jinkun Fan (now 2022 Ph. student @NJU), Yujie Li (now Ph.D. student @NTU), Yiting Wei (now Ph.D. student @PKU) were the first, second, and third authors, respectively. This work was supported by National Basic Subject Talent Training Plan 2.0 (20221021) and the 2021 Jiangsu Province Higher Education Reform Research Project (2021JSJG027).