Quinolines 4- hydroxy- from

C-9, and C-10, always with a phenolic hydroxy group at the 8a position. Moreover, they differ from one another by the oxidation state of the benzylic C-13 as well as by substitution and degree of saturation of the isoquinoline fragment. These alkaloids, classified as benzylisoquinoline alkaloids (2,70-74), have recently been called by Shamma et al. (75-77) pseudobenzyliso-quinolines originating from protoberberine alkaloids. In Table V a list of 8,8a-secoberbine alkaloids, sources, and spectral data are presented. 

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>. 

A method was developed for the synthesis of quinoline derivatives from isatoic anhydrides and lactones. The amino ketones formed at the first stage were then converted into the desired products by cyclocondensation after isolation or by direct heating of the reaction mass. Thus, the reaction of the anhydride 2 with the butyrolactones 94 in the presence of lithium diisopropylamide gave the amino ketones (95) (yield 99%), which when boiled in toluene gave 4-hydroxy-3-R-l-methyl-2-quinolones 96 (yield 98% with R = H or 70% with R = Me). It was established that the latter exist in two isomeric forms 96a,b [57],... 

Quinoline, amino-2-hydroxy-4-methyl-azo pigments from, 1, 334 Quinoline, 8-amino-6-methoxy-as antimalarial, 2, 517 Quinoline, 4-amino-2-methyl-protonation, 2, 341 Quinoline, anilino-3-substituted... 

Quinolin-2-one, 3-cyano-4-hydroxy-synthesis, 2, 428 Quinolin-2-one, 3,4-dialkyl-Knorr synthesis, 2, 425 Quinolin-2-one, dihydro-Camps synthesis, 2, 418 synthesis, 2, 402 from benzazepinones, 2, 506 from indanone oxime, 2, 487 from indanones, 2, 488 by intramolecular Friedel-Crafts reactions, 2, 421... 

Attempts have been made to deduce the structure of the predominant form of a potentially tautomeric compound from the shifts which occur in the ultraviolet spectrum of the compound in question on passing from neutral to basic or acidic solutions. The fact that no bathochromic shifts were observed for 2- and 4-hydroxy quinoline and 1-hydroxyisoquinoline under these conditions was taken as evidence that they existed in the oxo form [similar work on substituted quinol-4-ones led to no definite conclusions ]. A knowledge of the dissociation constants is essential to studies of this type, and the conclusions can, in any case, be only very tentative. A further dif-... 

On boiling the methiodide with 70% sulfuric acid an N-methyl-oxo derivative was obtained, and this in turn gave 3-amino-2-phenyl-quinoline, methylamine, and ammonia on fusion with soda lime. The bulk of the evidence therefore favors quaternization at N-2 (cf, 154), in which case the acid-hydrolysis product is 155. Quaternization at N-2 would be expected because of the steric influence of the 10-phenyl group and the influence of the 4-amino group (cf. 4-hydroxy-pyridazine ) in the pyridazine-type ring, although the partial double-bond character of that ring is probably different from that in pyridazine itself. 

A mixture of 48 parts by weight of diethyl[(3,4-methylenedioxyanilino)methylene] malonate and 500 parts by weight of diphenyl ether is refluxed for 1 hour. The mixture is allowed to cool to about 25°C with stirring and 500 parts by weight of petroleum ether are added. Filtration gives 3-carbethoxy-6,7-methylenedioxy-4-hydroxy-quinoline as a brown solid, MP 276° to 281°C. Several recrystallizations from dimethylformamide gives almost colorless analytical material, MP 285° to 286°C, (decomposes). 

A mixture of 26 parts of 3-carbethoxy-6,7-methylenedioxy-4-hydroxy-quinoline, 16 parts of sodium hydroxide and 50 parts of dimethylformamide is heated at 70° to 75°C for 2 hours, then 31 parts of ethyl iodide is added over 1 hour with continued heating and stirring. After an additional 3 to 4 hours of heating (at 70° to 75°C) and stirring, the mixture is diluted with 500 parts of water, refluxed for 3 to 4 hours, acidified with concentrated hydrochloric acid and filtered to yield 18 to 22 parts of 1-ethyl-1,4-dihydro-6,7-methylene-dioxy-4-oxo-3-quinoline-carboxylic acid, MP 309° to 314°C (decomposes). The analytical sample from dimethylformamide melts at 314° to 316°C (decomposes). 

Heteroatom rings, such as that found in quinoline derivatives, can be generated from amino-ketones with [hydroxy(tosyloxy)iodo]benzene and perchloric acid. Cyclic imines are converted to pyridine derivatives with NCS and then excess sodium methoxide. ... 

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