Synthesis of Di- and Trisubstituted Azulenes Using a Danheiser Annulation as the Key Step: An Advanced Organic Laboratory Experiment

Abstract

This three-week advanced-level organic experiment provides students with an inquiry-based approach focused on learning traditional skills such as primary literature interpretation, reaction design, flash column chromatography, and NMR analysis. Additionally, students address higher-order concepts such as the origin of azulene’s blue color, the mechanism of the Danheiser annulation (step 1), identification of an unknown reaction byproduct, and rationalization of a selective electrophilic aromatic substitution reaction (step 2). Students are initially drawn in by the fascinating color of azulene and remain engaged by the intriguing questions that naturally occur during this investigation.