A simple and efficient synthesis of N-[3-chloro-4-(4-chlorophenoxy)-phenyl]-2-hydroxy-3,5-diiodobenzamide, rafoxanide

A method for the synthesis of rafoxanide 6, a halogenated salicylanilide used as an efficient anthelmintic in sheep and cattle, is presented. Rafoxanide 6 was synthesized in only three steps from readily available 4-chlorophenol with 74% overall yield. The synthesis has two key stages: the first was salicylic acid iodination, adding iodine in the presence of hydrogen peroxide, which allowed obtaining a 95% yield. The second key stage was the reaction of 3,5-diiodosalicylic acid 5 with aminoether 4, where salicylic acid chloride was formed in situ with PCl3 achieving 82% yield. Chemical characterization of both intermediates and final product was achieved through physical and spectroscopic (IR, NMR and MS) techniques.

Automated summary

This paper presents a method for synthesizing rafoxanide 6, a halogenated salicylanilide used as an efficient anthelmintic in sheep and cattle. The synthesis involves three steps starting from readily available 4-chlorophenol, with an overall yield of 74%. The key stages of the synthesis are salicylic acid iodination achieving a yield of 95% and the reaction of 3,5-diiodosalicylic acid 5 with aminoether 4, resulting in a yield of 82%. The intermediates and final product were characterized using physical and spectroscopic techniques.