Amines quinolines, 4-hydroxy

Supplement 1953 3242-3457 Hydroxy-carboxylic acids, 190 In i doxylic acid, 226. Carbonyl-carboxylic acids, 284. i Sulphonic acids, 386 Quinoline sul-phonic acid, 390. Amines, 419 2-Aminopyridine, 428. Amino-carboxylic acids, 541 Tryp- tophane, 545. Hydrazines, 563. Azo. compounds, 572. Diazo compounds, 590. ... 

Reductive amination of dihydropyran (which may be regarded as the dehydration product of the cyclic acetal of 5-hydroxy-pentanal) in the presence of isopropylamine and a trace of acid affords the aminoalcohol, 96. Treatment of this compound with thionyl chloride affords the haloamine, 97. Alkylation of the quinoline, 92, with this halide yields pentaquine (98). ... 

Silylation-aminations of a variety of other hydroxy-N-heterocycles, for example 4(lH)-pyridinone, 2(lH)-pyrimidone, uracil, 2(lH)-quinoline, and 9(10H)-acridone are described in the full paper, which was published in English [27]. 

The oxidising agent usually employed is the nitro-compound corresponding to the amine, e.g., nitrobenzene when aniline is the base for p-toluidine, p-nitrotoluene serves, and so on. Arsenic acid, however, can be generally employed, and gives better results. The reaction is capable of very wide application nitro-, halogen-, hydroxy-, carboxy-quinolines can all be obtained from the corresponding amines the amino-naphthalenes also react. Diamines yield the so-called phen-anthrolines. (B., 16, 2519 23, 1016.)... 

The reduction of 2, either catalytically or with zinc in acetic acid, leads to 3-amino-4-hydroxy-2-quinolone 20 [72TH000], These amino compounds are rather unstable they dimerize with loss of ammonia to "bis-amines", which in turn are readily oxidized to dyes similar to those obtained from ninhydrin and primary amines [68M1205] [68M1543], The amino derivatives 20 are therefore conveniently converted into 0,N-diacetyl derivatives, the N-acetyl derivative 21, or its dehydrated form, the oxazolo derivative 22 [95MI000], The variety of biological activity of oxazolo-quinolines of type 22 has been detected only in recent years [94JHC1647],... 

Thermal cyclization was also the route employed to prepare 9-hydroxy-7-methyl-l/f-pyrazolo[3,4-/]quinoline (74) from the 6-aminoindazole/ethyl acetoacetate condensation adduct shown in Equation (41) <92JMC4595>. The hydroxyl substituent of compound (74) was then converted (POCl3, DMF) to a chloro, which in turn was displaced by treatment with aryl amines to give tricyclics with potent in vivo immunostimulatory activity like that noted for regioisomeric l//-imidazo[4,5-/]quinolines but unlike the inactive pyrazolo[4,3-/]quinolines. Although it was noted with some interest that none of the linear tricyclic isomer had been isolated, this finding actually parallels that reported earlier for the similar condensation of 1- and (V(6)-alkyl and unsubstituted 6-amino-indazoles with diethyl ethoxymethylenemalonate <83JHC1351>. 

EtOH), were first isolated in 1872 and 1877, respectively (14). Quin-amine was observed to give indole color reactions (7, 15), and 2,3-dimethylindole was a result of zinc dust distillation of the alkaloid (15). With chromic acid (9), the quinuclidine carboxylic acid (III) was obtained, and with nitric acid 3,6,8-trinitro-4-hydroxyquinoline was isolated (15, 16). This quinoline is a consequence of fission of the indole and recyclization, with nitration preceding and following these steps [cf. ozonolysis of yohimbine to furnish a 2,3-disubstituted 4-hydroxy-quinoline (17)]. 

Ifenprodil (= l-Methyl-2-hydroxy-2-(4-hydroxyphenyl) ethyl-1 -(4-benzyl-piperidine)] -(aryl piperidine) [at(/o-3-(Indol-2-yl)-8-methyl-8-azabicyclo-[3.2.1] octane] (indolotropane) [Kynurenic acid (= 4-Hydroxy-2-quinolinecarboxylic acid)] (quinoline carboxylic acid) [Memantine (= 1-Amino-3,5 dimethyladamantane)] (amino adamantane, amino cyclic aliphatic) [Methadone (= 6-Dimethylamino-4,4-diphenyl-3-heptanone)] (aryl tertiary amine) [em/o-3-(l -Methylindol-2-yl)-8-methyl-8-azabicyclo-[3.2.1] octane(indolotropane) exo- 3-( 1 -Methylindol-2-yl)-8-methyl-8-... 

For the preparation of 4-(1.2.3.4-tetrahydroquinolino)-phenol 17 three different procedures were worked out [Eqs. (6)-(8)]. 17 was prepared by reacting N-p-methoxyphenyl-anthranilic acid with acetic anhydride and subsequent saponification to l-p-methoxyphenyl-4-hydroxy-2-quinolone, reaction withPOCl3 to form l-p-methoxyphenyl-4-chloro-2-quinolone, hydrogenation to l-(p-methoxy-phenyl)-3.4-dihydro-2-quinolone, splitting the ether with HBr to l-(p-hydroxy-phenyl)3.4-dihydro-2-quinolone, and reduction with LiAlH4 [Eq. (6)J. Another synthetic possibility was the reaction of p-anilinophenol with (3-propiolactone and subsequent cyclization to l-(p-acetoxyphenyl)2.3-dihydro-4-quinolone 18. The next step, the Wolff-Kishner reduction, led directly to the desired product [Eq. (7)]. The third way, the direct amination of p-iodoanisole with 1.2.3.4-tetrahydro-quinoline and the subsequent splitting of 4-(1.2.3.4-tetrahydro-quinolino)-anisol with HBr was the best one [Eq. (8)]. Saponification of l-(p-acetoxyphenyl>2.3-... 

Hydroxy-2-(trifluoromethyl)pyridine derivatives 80 (Scheme 31) were linked [53] to the acetamide moiety in the usual way. Pyridyloxy-acetamides 81 smoothly rearranged into the respective 4-aminopyridines 82 when heated with potassium carbonate in DMF at 150 °C. Acid hydrolysis provided amines 83. In a similar way, hydroxy-quinolines and hydroxy-acridines were transformed into the respective amines [50,54]. 

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