Chapter 15, Problem 1LGP

The structure of thyroxine, a thyroid hormone that helps to regulate metabolic rate, was determined in part by comparison with a synthetic compound believed to have the same structure as natural thyroxine. The final step in the laboratory synthesis of thyroxine by Harington and Barger, shown below, involves an electrophilic aromatic substitution. Draw a detailed mechanism for this step and explain why the iodine substitutions occur ortho to the phenolic hydroxyl and not ortho to the oxygen of the aryl ether. [One reason iodine is required in our diet (e.g., in iodized salt) is for the biosynthesis of thyroxine.]