Green Synthetic Approach to Indole-Substituted Methane Derivatives via Multi-Component Reaction

A one-pot multicomponent synthesis of unsymmetrical indole-substituted methane derivative based on two consecutive reactions of p-methylbenzaldehyde with N-methylindole and 5,5-dimethyl-1,3-cyclohexanedione is described as an experiment that was carried out by second-year undergraduate chemistry students individually in a laboratory classroom. The experiment provides an opportunity for students to carry out novel organic chemistry transformations for the synthesis of complex molecules from simple substrates, which is also the main pedagogical goal. Salient features of this teaching experiment include (a) multicomponent synthesis and good operability, (b) the absence of catalyst and any additives, (c) high yield and atomic economy, and (d) the use of inexpensive and green solvent. This laboratory experiment combines organic synthesis, TLC, NMR, and IR analysis. Several important concepts, such as green chemistry, chem- and regioselectivity, conjugated 1,4-addition, and atomic economy, are also discussed.