ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

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

Víctor Kesternich, Marcia Pérez-Fehrmann, Víctor Quezada, Mariña Castroagudín, Ronald Nelson, and Rolando Martínez

Departamento de Química, Facultad de Ciencias, Universidad Católica del Norte, Antofagasta, Chile

E-mail: vkestern@ucn.cl

Received: 19 December 2022  Accepted: 28 April 2023

Abstract:

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.

Keywords: Rafoxanide; Salicylanilide; Organoiodine

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-023-02846-9

Chemical Papers 77 (9) 5091–5095 (2023)