3-Aminoquinoline

Potassium thiocyanate (100 g., 1.03 moles) is added to a solution of 115 g. (0.99 mole) of crude / -chloroethylamine hydrochloride (p. 76) in 200 ml. of water. The resulting solution is refluxed for 9 hours, after which it is cooled and 100 ml. of 40% aqueous sodium hydroxide solution is added. The mixture is extracted with five 300-ml. portions of ether. The combined ethereal solutions are dried over sodium sulfate, and the solvent is removed by distillation, leaving 72 g. (70%) of 2-aminothiazoline, m.p. 76-78°. One recrystallization from benzene gives a product melting at 80-82°. 

A mixture of 128 g. (0.81 mole) of p-chloronitrobenzene and a solution of 480 g. (2.0 moles) of sodium sulfide nonahydrate in 2 1. of water is heated to reflux for 8 hours. The cooled mixture is extracted with ether to remove a small amount of oil, the remaining aqueous solution is saturated with sodium chloride, and 240 g. (4.0 moles) of glacial acetic acid is added. The precipitated oil is removed by 

Zinc dust (20 g., 0.31 gram atom) is added slowly over a period of 30 minutes to a solution of 3.1 g. (0.01 mole) pf di-(o-nitrophenyl) disulfide [Org. Syntheses Coll. Vol. 1, 220 (1941)] in 350 ml. of warm glacial acetic acid. The mixture is boiled until colorless. A smaller amount of zinc can be used with a longer reaction time. The mixture is diluted with 2 volumes of water, cooled, and filtered to give 2.8 g. (90%) of the zinc salt of o-aminothiophenol. 

Seventy-five milliliters of concentrated hydrochloric acid is added to 8.5 g. of the zinc salt. The warm solution thus formed is filtered through asbestos and cooled in ice, whereupon the hydrochloride is precipitated. The solid hydrochloride is removed by filtration and recrystallized from concentrated hydrochloric acid and then from water to give an 80% yield (based on zinc salt) of product melting at 217° (cor.). 

---

Yan and associates developed a method for the analysis of iron based on its formation of a fluorescent metal-ligand complex with the ligand 5-(4-methylphenylazo)-8-aminoquinoline. In the presence of the surfactant cetyltrimethyl ammonium bromide the analysis is carried out... 

Trachelantamine, according to Syrneva, has a weak atropine-like action and also produces local anaesthesia. Its hydrolytic product, trache-lantamidine, which is structurally identical with tsoretronecanol, yields a p-aminobenzoyl derivative of -which the crystalline hydrochloride, m.p. 230-2°, is said to be as potent a local anaesthetic as cocaine hydrochloride. The chloro- -heliotridane (p. 606) formed by the aetion of thionyl ehloride on trachelantamidine reacts with 6-methoxy-8-aminoquinoline to form 6-methoxy-8-(pseMdoheliotridylamino)-quinoline,... 

An interesting case of the benzannulated B, N complex is species 58 (X = C1) (00AGE948), prepared from [(OC)Os(PPh3)2Cl(BCl2)] and 8-aminoquinoline. It reacts with tetra- -butyl ammonium iodide and forms 58 (X = I). 

Reaction of 8-aminoquinoline 567 with 3,4-dichlorodithiazolium chloride gave the quinolyl iminodithiazole 568 whose thermal rearrangement gave 569 via a molecular rearrangement process (96MI2775) (Scheme 95). 

The carbamates, derived from the reaction of 8-aminoquinoline with phenyl or ethyl chloroformate, upon reduction with NaBH4 gave the... 

Primaquine, an 8-aminoquinoline, eradicates the dormant stages (hypnozoites) of P. vivax and P. ovale from the liver. Its mode of action remains obscure. 

Ni(8-aminoquinoline),Cl2, 5, 84 NiC27M26Cl202P 2 NiCl2 (OPPh2CH2)2CH2, 5, 161 NiC27H27N4... 

Bromo-l-phthalimidopentane 3 was obtained in 72-82 g yield by refluxing 92 g of 1,4-dibromopentane 1, 55.5 g of potassium phthalimide 2, and 200 mL dry acetone on a steam bath for 30 h. Compound 3 (30 g) and 42 g 6-methoxy-8-aminoquinoline 4 refluxed at 130-135 °C for 6 h, extracted with benzene to separate insoluble 6-methoxy-8-aminoquinoline hydrobromide, the residue from evaporation of the benzene was refluxed with stirring with 100 mL of an alcoholic solution of 6 g hydrazine hydrate for 4 h, the solution was concentrated, made acidic to Congo red with 8 N hydrochloric acid, filtered, and washed with boiling water. The combined filtrate and washings was concentrated, made alkaline, extracted with benzene, and distilled in vacuo to give 20.5 g primaquine 6, which was treated with 19 mL 85% phosphoric acid in absolute ethanol, formed 42.5% primaquine diphosphate. 

Zinc Complexation withp-tosyl-8-aminoquinoline and adsorption on cation exchange resin Spectrofluorimetry 0.1 nM absolute [609]... 

The inhibition of both enzymes by primaquine and related compounds (8-aminoquinoline derivatives) possesses remarkable clinical implications to be discussed later (cf. Section 2.8.3). 

A membrane-permeant form of Quin-2 (systematic name 2-[(2-amino-5-methylphenoxy)methyl]-6-methoxy - 8 - aminoquinoline - A,A,A, A - tetraacetate) which upon binding of calcium ion results in fluorescence. See Fura-2... 

Primaquine Primaquine, 8-[(4-amino-l-methylbutyryl)amino]-6-methoxyquinoline (37.1.2.4), is made from 6-methoxy-8-nitroquinoline (37.1.2.1), which is synthesized in a Skraup reaction from 4-methoxy-2-nitroaniline and glycerol in the presence of sulfuric acid. The nitro group in this compound is reduced to make 6-methoxy-8-aminoquinoline (37.1.2.2). Alkylating the amino group with 4-bromo-l-phthalimidopentane gives 8-[(4-phthalimido-l-methylbutyryl)amino]-6-methoxyquinoline (37.1.2.3), the hydrazi-nolysis of which removes the phthalimide protection, giving primaqnine [28,29]. 

Primaquine is the most effective and most toxic drug from the whole series of known 8-aminoquinolines. It is generally used for treating exoerythrocyte forms of malaria caused by P. vivax and P. ovale. It also acts on the sexual forms of the plasmodia, which die in the human body upon using this drug. 

VI.a.2.1. AminoquinoUnes. The aminoquinolines currently used as antimalarials include the 4-amino-quinolines chloroquine and mefloquine and the 8-aminoquinoline primaquine. 

Non-falciparum malaria (like P. vivax) can still be treated with chloroquine although chloroquine resistant P. vivax has been reported from Irian Jaya and Papua New Guinea. In those areas treatment with mefloquine is recommended. To treat the liverstages an additional 2-3 weeks treatment with primaquine is given. It appears that tafenoquine (dosed once a week), a new 8-aminoquinoline, would be a better replacement for primaquine in preventing relapses in P. vivax malaria. 

Primaquine is the least toxic and most effective of the 8-aminoquinoline antimalarial compounds. The mechanism by which 8-aminoquinolines exert their antimalarial effects is thought to be through a quinoline-quinone metabolite that inhibits the coenzyme Q-mediated respiratory chain of the exoerythrocytic parasite. 

---