Quinolines. III. The Synthesis of 5- and 7-Chloro- and Bromo-3-methyl-4-dialkylaminoalkylaminoquinolines

Abstract

Vol. 68 mixed melting point with fluorenone-hydrazone prepared by the interaction of fluorenone and hydrazine was unchanged; hydrochloride, deep yellow crystals melting at 268= (dec.).Reaction of 9-Chlorofluorene with Piperidine.-Colorless needles were deposited from a solution of 0.5 g. of 9chlorofluorene in 5 cc. of piperidine kept at room temperature for a few hours. The product, 9-(N-piperidino)fluorene, was recrystallized from ethyl alcohol and melted at 99°.

Structural Specificity of Chloroquine−Hematin Binding Related to Inhibition of Hematin Polymerization and Parasite Growth

“…Chemistry. CQ analogues 4 (7-chloro-4-(4-(ethylamino)-1methylbutyl)aminoquinoline dioxalate), 50 5 (7-chloro-4-(5-(diethylamino)-1-methylamyl)aminoquinoline), 51 6 (7-chloro-4-(5ethyl-1-methylheptyl)aminoquinoline hydrochloride), 8 (7bromo-4-(4-(diethylamino)-1-methylbutyl)aminoquinoline), 14 11 52,53 and 13 (7-chloro-3-methyl-4-(4-(diethylamino)-1-methylbutyl)aminoquinoline) 54 were obtained from the Division of Experimental Therapeutics inventory at the Walter Reed Army Institute of Research. CQ analogue 3 (7chloro-4-(4-(diethylamino)-1-methylethyl)aminoquinoline) 55 was obtained from the Hoffmann-La Roche inventory.…”

Quinoline formation via a modified Combes reaction: examination of kinetics, substituent effects, and mechanistic pathways

“…Quinolines, which are important precursors to pharmaceuticals and agrochemicals, [1][2][3][4] have been studied extensively from a synthetic point of view. [5][6][7][8][9][10][11][12][13][14] The Combes quinoline synthesis depicted in Scheme 1 uses a b-diketone substrate, setting it apart from other quinoline preparations. [15] The reaction, which involves nucleophilic addition to the carbonyl, imine, and enamine intermediates and electrophilic aromatic annulation has been qualitatively investigated in terms of substituent effects on product regiochemistry and aniline reactivity, but a systematic kinetics investigation of this condensation is lacking.…”

“…The problems attendant with early quinoline formation methods which used concentrated sulfuric acid as a dehydrating reagent at high temperatures [12][13][14]17] can be ameliorated by substituting mixtures of polyphosphoric acid (PPA) and selected alcohols. [28,29] The resulting polyphosphoric ester (PPE) catalysts are milder and more effective as dehydrating/cyclizing reagents than concentrated H 2 SO 4 or neat PPA.…”

Organic chemistry

“…Autoxidation of cholesterol (and other A5-steroids) in aqueous colloidal solution gives the epimeric 3( p) : 7-dihydroxycholestenes (and analogous compounds) ; the 7" p "-compound had previously been prepared,g1 and it now appears that the 7" a "-compound, resulting from 7-ketocholesterol by reduction with aluminium i s o p r o p ~x i d e , ~~ is a mixture of epimerides containing up to 20% of the 7ccp"-compound;93 the same may be expected t o be true of one of the epimeric 3(a) : 7-dihydro~ycholestenes.~ Although one of the epimeric 3(p) : 7-dibenzoyloxycholestenes should be subject to steric hindrance at C,, both by treatment with cold sodium methoxida give 7-monobenzoates.93* 95 Differences in reactivity are disclosed in elimination reactions, wherein the 7"a "-compounds readily give cholest-7-ene derivatives, whilst the 7" p "-compounds are resistant. [93][94][95][96] There is thus no direct evidence upon which an assignment of configuration at C, in the sterol series can be based; 97 a correlation with the known orientation of the 7-hydroxyl group in the bile acids (XLVII), (L), and (LII) is much to be desired. Indirect evidence based on optical rotatory powers permits, however, a provisional allocation.…”