Multistep Synthesis of Diphenhydramine: A Modular Laboratory for First-Semester Organic Chemistry Students

A straightforward synthesis of diphenhydramine, a common medication known to most undergraduate students, is described for implementation as a capstone into the first-semester organic chemistry laboratory curriculum. This multistep synthesis converts benzophenone to the bromide salt of diphenhydramine using first-semester reactions including reduction and substitution. This rigorously developed procedure was undertaken independently by the three coauthors and verification was conducted externally to the home institution. Assessment of two major learning objectives indicates general success, but also points to places where students can improve. In developing this synthetic procedure, the concept of a modular approach was developed for an organic chemistry laboratory to allow application at a broad array of institutions; individualized adaptation of this procedure can fit a variety of learning objectives as needed. A detailed supplementary section is included to support instructors who may wish to implement elements of this procedure or the modules into their laboratory curriculum.