Some 2,5- and 5,6-dihalonicotinic acids and their precursors. IV

Abstract

The preparation of 2,5-dichloro-, 2-chloro-5-iodo-, 5,6dichloro-, and 6-chloro-5-iodonicotinic acid by oxidation of the appropriate dihalopicoline is described. The syntheses of the dihalopicolines are also presented. The generation of 5-chloro-6-iodonicotinic acid by iodide displacement of 5,6-dichloronicotinic acid is described. Experimental and spectral data for all new compounds are reported.In recent years haloand dihalonicotinic acids and their derivatives have received attention as potential hypolipidemic agents (1-4). We have previously reported the synthesis of a variety of dihalonicotinic acids of potential medicinal interest (6-8). In this communication we report the synthesis of dihalonicotinic acids IV, V, IX, and X by permanganate oxidation of the corresponding dihalopicolines II, III, Vil, and VIII, respectively. Acid XI was generated by prolonged reflux of acid IX with sodium iodide in methyl ethyl ketone.2,5-Dichloro-3-picoline (II) and 2-chloro-5-lodo-3-picoline (III) were obtained via dlazotlzatlon of 5-amino-2-chloro-3picoline (I) (7). 5,6-Dichloro-3-picoline (VII) and 6-chloro-5iodo-3-picoline (VIII) were produced in analogous fashion from 5-amlno-6-chloro-3-picollne (VI) (9).

Some 2,5- and 5,6-dihalonicotinic acids and their precursors. 5

“…Compounds possessing hypolipidemic activity are the subject of extensive pharmaceutical research. Halo and dihalonicotinic acids and their derivatives have received attention as potential hypolipidemic agents (1-4), and in this communication we wish to report the preparation and characterization of four new dihalonicotinic acids as an extension of our previous work (5)(6)(7)(8).…”

Some methyl 2,5- and 5,6-dihalonicotinates

“…We have previously reported the synthesis of a series of 2,5and 5,6-dihalonicotinic acids of potential medicinal interest (1)(2)(3)(4)(5). As an extension of that work, we now wish to report the preparation and characterization of the methyl esters (I-VIII) of eight of the aforementioned acids.…”