6-Chloro-8-Ethylquinoline and Some Derivatives.

Abstract

A SEARCH of the literature revealed no information concerning 6-chloro-8-ethylquinoline and hence the preparation of it and some of its derivatives was undertaken. A comparison of the properties of such compounds with those of 6-chloro-8-methylquinoline and its derivatives as reported by Irving, Greene, Peterson, and Capps (3) as well as with those of 6-bromo-8-ethylquinoline as reported by Beasley, Brown and Capps (2) appeared to be of interest. 6-Chloro-8-ethylquinoline was prepared from 2-amino5-chloroethylbenzene by the modified Skraup method as reported by Altau and others ( I ) . The 2-amino-5-chloroethylbenzene was obtained from the chlorination of 2acetamidoethylbenzene, which in turn had been synthesized from ethylbenzene (1). A solution of 6-chloro-8-ethylquinoline in sulfuric acid (sp. gr. 1.84) was added to a solution of fuming nitric acid (sp. gr. 1.5) in sulfuric acid (sp. gr. 1.84) a t 0-5 prior to increasing the internal temperature to 60 and maintaining it for 30 minutes. The structure of the 6chloro-8-ethyl-5-nitroquinoline, thus obtained, was established by comparing its properties with those of an authentic sample as synthesized by a Skraup ring-closure upon 2-acetamido-4-nitro-5-chloroethylbenzene ( 1 ) . 6-Chloro-8-ethyl-1-methylquinolinium ethyl sulfate resulted when 6-chloro-8-ethylquinoline was heated with dimethyl sulfate a t 135-140. 6-Chloro-8-ethyl-1-methyl2-quinolone was obtained by the oxidation of the methylquinolinium salt with alkaline ferricyanide solution a t 60°-650. A mixture of phosphorus oxychloride and phosphorus pentachloride reacted with the quinolone, when heated in an oil bath a t 125-130, yielding 2,6-dichloro8-ethylquinoline, which was then hydrolyzed by heating with sulfuric acid (52.5 ml.; sp. gr. 1.84)-water (36 ml.) solution. 6-Chloro-8-ethyl-2-hydroxyquinoline was nitrated with a mixture of sulfuric acid (sp. gr. 1.84) and nitric acid (sp. gr. 1.42) under relatively mild conditions yielding 6-chloro8-ethyl-2-hydroxy-5-nitroquinoline. An authentic sample of 6-chloro-8-ethyl-2-hydroxy-5-nitroquinoline was prepared for comparison purposes from 6-chloro-8-ethyl-5-nitroquinoline via 6-chloro-8-ethyl-l-methyl-5-nitro-2-quinolone and 2,6-dichloro-8-ethyl-5-nitroquinoline. The 6-chloro-8ethyl-l-methyl-5-nitro-2-quinolone was prepared according to modifications of conditions reported by Beasley, Brown, and Capps (2) for reacting 6-brome-8-ethyl-5-nitroquinoline with dimethyl sulfate and then oxidizing with alkaline hydrogen peroxide. Reaction of the 6-chloro-8-ethyl-lmethyl-5-nitro-2-quinolone with a mixture of phosphorus oxychloride and phosphorus pentachloride, while being heated in an oil bath a t 125-130°, gave some 2,6-dichloro8-ethyl-5-nitroquinoline, which was hydrolyzed upon heating with sulfuric acid (50 ml.; sp. gr. 1.84)-water (25 ml.) solution to 6-chloro-8-ethyl-2-hydroxy-5-nitroquinoline. A dinitro derivative of 6-chloro-8-ethyl-2-hydroxyquinoline formed, along with an unseparated mixture, upon nitration under more stringent conditions, while using a mixture of fuming nitric acid (sp. gr. 1.5) and sulfuric acid (sp. gr. 1.84). No attempt was made establish the structure of this dinitro derivative: The 2,6-dichloro-8-ethyl-5-nitroquinoline, as obtained from 6-chloro-8-ethyl-5-nitroquinoline, also served as a reference compound for indicating the position taken by the nitro group during the nitration of 2,6-dichloro-8-ethylquinoline with a mixture of sulfuric and fuming nitric acid. 6-Chloro-8-ethyl-5-nitroquinoline and 2,6-dichloro-8ethyl-5-nitroquinoline were each reduced independently with hydrogen a t 40 p.s.i. pressure, in the presence of Raney nickel catalyst, to the corresponding amine. 6-Chloro-8-ethyl-5-nitroquinoline was reduced also with a mixture of stannous chloride and hydrochloric acid to 5-amino-6-chloro-8-ethylquinoline. Heating 5-amino-6-chloro-8-ethylquinoline and 5-amino2,6-dichloro-8-ethylquinoline under refluxing conditions with a solution of acetic anhydride and glacial acetic acid gave the corresponding acetamido derivatives. The benzoylation of 5-amino-6-chloro-8-ethylquinoline and 5-amino-2,6-dichloro-8-ethylquinoline under SchottenBaumann conditions ( 4 ) yielded the corresponding benzamido derivatives.