Unexpected One‐Step Formation of Iodo[1,3]dioxolo[4,5‐c]pyridine Derivatives by a Hofmann–Löffler–Freytag Reaction: Studies on the Synthesis of a Pyridine‐Containing Macrocycle

Abstract During attempts to prepare functionalized 5‐iodopyridine derivatives the unexpected formation of iodo[1,3]dioxolo[4,5‐ c ]pyridines was discovered. The conversion of 3‐alkoxypyridin‐4‐ols into the corresponding 5‐iodo compounds was achieved by reaction with one equivalent of iodine or tetramethylammonium dichloroiodate under basic conditions. When three equivalents of iodine were used in chlorinated solvents, after 5‐iodination, subsequent reaction of the 3‐alkoxy group took place to form a 1,3‐dioxolane ring with the 4‐hydroxyl group. Generation of the resulting iodo[1,3]dioxolo[4,5‐ c ]pyridines is explained by a radical process known as the Hofmann–Löffler–Freytag reaction. Two 6‐ethynylpyridine derivatives were examined in the iodination process to establish a route to pyridine‐containing macrocycles. The pentasubstituted 5‐iodopyridine derivative 21 could be prepared; however, attempts to achieve cyclotrimerization of this building block under different conditions were not successful. Reaction of 21 with copper chloride allowed isolation of a copper acetylide 22 , which aggregates to a triangular trimeric complex containing four copper(I) ions such as [ 23· Cu] + as monitored by ESI mass spectrometry.