Some Derivatives of 7-Methoxy- and 10-Methoxybenzo (f) quinoline

Abstract

In an earlier paper2 the preparation of a number of 1-substituted arninobenzo(f)quinolines was described. As a continuation of this work the synthesis of two series of methoxybenzo(f)quinolines with a basic substituent in the 1-position has been undertaken. It was hoped that the presence of the methoxyl would enhance the antimalarial activity of this type of compound. Pharmacological testing of a number of these derivatives is in progress.The particular isomers chosen for study were 7rnethoxybenzo(f)quinoline (A) and 10-methoxybenzo(f)quinoline (B)" )The starting materials required were 5-methoxy-2-naphthylamine and 8-methoxy-2-naphthylamine. Synthesis of neither of these compounds has been reported in the literature. The aminonaphthols, from which the methyl ethers were prepared, were obtained by the alkali fusion of the appropriate naphthylaminesulfonic acid. To insure efficient conversion of the naphthols to their methyl ethers with dimethyl sulfate, it was necessary to protect the amino groups by acetylation, the acetyl groups being removed by subsequent hydrolysis.In this investigation the intermediate, 2-acetamido-5-naphtho1, was isolated as a stable crystalline hydrate with a melting point higher than that reported by earlier Since 8methoxy-2-naphthylamine was an unstable oil, it was isolated as the hydrochloride.The conversion of the methoxyamines into the desired methoxybenzo(f)quinolines was accomplished by previously described methods.2In order to introduce a basic substituent into the 1-position it was necessary to replace the hydroxyl with the more reactive chloro group which, normally, is easily displaced by an amino group. The 7-methoxy isomer reacted smoothly with phosphorus oxychloride to give the desired chloro compound, but all of our attempts to replace the hydroxyl in the 10-methoxy isomer were unsuccessful. It is believed that the group in the 10-or peri-position exerts a blocking effect upon the 1position of the nucleus. Furthermore, XX dif-1) Puke, Davis and Company Fellow. fered noticeably from XVII and X I , * in other properties, namely, melting point, color and solubility in alkali. I CHsO (1x1 (XVII) (XXI) rn. p. 1 8 3 O , yellow, m. p. 309', white, m. p. 288', white, insol. in OHsol. in OH-sol. in OH-Two amines, morpholine and piperidine, were condensed with l-chloro-7-methoxybenzo(f)quinoline yielding the corresponding 1-substituted aminobenzo(f)quinolines.Experimental 2-Naphthylan1ine-5-sulfotk acid (I) and 2-naphthylamine-8-sulfonic acid (11) were prepared by the sulfonation of 2-naphthylamine according to the procedure of Green and Vakil.6 2-Amino-&naphthol (III).-A mixture of 83 g. of I1 and 250 g. of potassium hydroxide was heated in an iron autoclave, equipped with a stirrer, for two and one-half hours a t 260'. The fusion melt was cooled and treated with two liters of water. Some insoluble tarry material was removed by filtration and the solution was acidified with concentrated hydrochloric acid. The mixture was filtered again to remove the acid-insoluble portion and the filt...

The biochemistry of aromatic amines. 9. Mercapturic acids as metabolites of aniline and 2-naphthylamine

“…2-Acetamido-6-naphthol was prepared by the method of Booth, Boyland & Manson (1955) and 2-acetamido-5naphthol by the acetylation of 2-amino-5-naphthol (Light and Co. Ltd., Colnbrook, Bucks.) (Mueller & Hamilton, 1944).…”

Application of the Sharpless Asymmetric Dihydroxylation Methodology to the Enantioselective Preparation of 2,3-Dihydroxytetrahydro-2-naphthoic Esters

“…The majority of the literature methods 8 for the synthesis of 1 are not synthetically useful, as a key intermediate is 2-aminonaphthyl-8-sulfonic acid, which can only be prepared in low yield. 8e, A more efficient synthesis was achieved starting from 1,7-dimethoxynaphthalene, and the details are presented in the Supporting Information.…”

Compounds of Pharmaceutical Interest From 4-Methoxy-1-Naphthylamine

“…Benzo(h)quinolines. A successful method of preparing benzo(h)quinolines from the naphthylamines was developed employing Mueller and Hamilton's modification (2) of the Conrad-Limpach reaction. Condensation of the amines with sodium ethyl ethoxalylacetate gave compounds which were readily cyclized by heating in mineral oil.…”