Rapid and Convenient Synthesis of the 1,4-Dihydropyridine Privileged Structure

A short, semi-microscale synthesis of two 1,4-dihydropyridine drug analogues via a Hantzsch reaction is described, which is appropriate for a second-year undergraduate organic laboratory. Products are specifically chosen to highlight the biological relevance of this compound type while introducing the notion of a privileged structure. 1,4-Dihydropyridines are bioactive as calcium channel blockers and antioxidants and are lead candidates in the treatment of various medical conditions. Students generate one substituted 1,4-dihydropyridine by an operationally simple process and characterize it by melting point measurements, IR spectroscopy, and 1H and 13C NMR spectroscopy. This provides a springboard to discuss concepts of green chemistry, structure-activity relationships, conformational analysis, and related synthetic approaches. © 2010 The American Chemical Society and Division of Chemical Education, Inc.