Cinnoline hydroxy

Little is known quantitatively about substituent effects in the nitration of derivatives of azanaphthalenes. In preparative experiments 4-hydroxy-quinoline, -cinnoline, and -quinazoline give the 6- and 8-nitro compounds, but with nitric acid alone 4-hydroxyquinoline and 2,4-di-hydroxyquinoline react at With nitric acid, 4-hydroxycinnoline... 

Partial rate factors for the nitration of 4-hydroxyquinoline and its derivatives are given in table 10.6. Comparison with the values for quinolinium (table 10.4) show that the introduction of a 4-hydroxy or a 4-methoxy group into the latter activates the 6-position by factors of 3-3 X 10 and 1-6 X 10 , respectively, and the 8-position by factors of 29-5 and 23, respectively. What has been said above makes the significance of partial rate factors which may be calculated for 4-hydroxy-cinnoline uncertain. 

When large groups, such as phenyl, bromo, ethoxycarbonyl or nitro are attached at position 3, the principal products are l-alkylcinnolin-4(l/f)-ones. Cyanoethylation and acetylation of cinnolin-4(l/f)-one takes place exclusively at N-1. Phthalazin-l(2/f)-ones give 2-substituted derivatives on alkylation and acylation. Alkylation of 4-hydroxyphthala2in-l(2/f)-one with an equimolar amount of primary halide in the presence of a base leads to 2-alkyl-4-hydroxyphthalazin-l(2/f)-one and further alkylation results in the formation of 4-alkoxy-2-alkylphthalazinone. Methylation of 4-hydroxy-2-methyl-phthalazinone with dimethyl sulfate in aqueous alkali gives a mixture of 4-methoxy-2-methylphthalazin-l(2/f)-one and 2,3-dimethylphthalazine-l,4(2//,3//)-dione, whereas methylation of 4-methoxyphthalazin-l(2/f)-one under similar conditions affords only 4-methoxy-2-methylphthalazinone. 

V-aminoindoles from, 4, 361 Cinnoline, 3,4-diphenyl-synthesis, 3, 42 Cinnoline, 3-hydroxy-synthesis, 2, 92 tautomerism, 3, 4 Cinnoline, 4-hydroxy-tautomerism, 3, 4 Cinnoline, 4-methyl-nitration, 3, 21... 

Cinnolin-4(lH)-one, 8-hydroxy-iodination, 3, 21 Cinnolin-4-ones synthesis, 3, 56 Circular dichroism indolizidines, 4, 450 pyridines and benzo derivatives, 2, 126... 

Both pK and ultraviolet spectral data indicate that 3- and 4-mono-hydroxy-pyridazines and -cinnolines exit predominantly in the oxo... 

There is a discrepancy in the literature concerning 4-hydroxy-cinnoline. Whereas two measurements of pKa values indicate that the cinnolinone structure predominates by a large factor in aqueous solution (see Table III), comparison of the ultraviolet spectra of 4-hy-... 

Ratio of the Oxo Form to the Hydroxy Form (pKr) for 3- AND 4-Monohydroxy-pyridazines and -cinnolines... 

Recent work has justified the suspicions that the methylated cinnolones had been allocated the incorrect structures. D. E. Ames and H. Z. Kucharska [J. Chem. Soc. 4924 (1963)] have shown that the compound previously believed to be l-methyl-4-cinnolone is the dipolar anhydro-base of 4-hydroxy-2-methyl-cinnolinium hydroxide. It is likely, therefore, that those cinnoline salts whose structures had been based upon the presumed l-methyl-4-cinnolones are, in fact, 2-salts of structure 56. (Cf. p. 28.)... 

Aryloxy, hydroxy arylsulfonyloxy, and phosphoryloxy. The 4-toluenesulfonyloxy and 4-nitrophenyloxy groups approximate the chloro group in replaceability in benzene derivatives. The former appears to be less reactive than chloro toward hydroxide on quinoline and -phenoxy on pyrimidine is relatively unreactive toward sulfanilamide anion or ammonia. On cinnoline, quinazoline, or quinoline, a 4-phenoxy group is less reactive than a chloro group. 

The values of perhydropyrido[l,2-f)]pyridazine and its 2-oxo derivative were found to be 2.80 0.04 and 7.32 0.03, respectively (72KGS220), whereas that of anhydro 4-hydroxy-2-methyl-5,6,7,8-tetrahydropyrido(l,2-6]pyridazinium hydroxide (16) was determined by spectrophotometry to be 2.77 (71CPB159). UV spectroscopic measurements in sulfuric acid gave a pKa value of -0.25 for pyrido[l,2-6]cinnoline derivative (17, R = H) (74JHC125). 

The 5-methyl derivative 43 was obtained from pyrido[l,2-h]cinnolin-6-ium hydroxide inner salt 17 (R = H) with dimethyl sulfate (74JHC125). Protonation of 17 (R = H) occurred on the 5-nitrogen and not the oxygen, but its 1,2,3,4,7,8,9-octahydro derivative 45 was protonated on the oxygen to produce the 11-hydroxy salt. 

The 1-hydroxymethyl group of l-hydroxymethyl-7-oxo-l//,7//-pyrido [3,2,l-y]cinnoline-8-carboxylate (81) was O-alkylated by treatment with diethylaminosulfur trichloride and an alcohol in THE. The 4-hydroxy group of 4-hydroxy-7-oxo-l//,7//-pyrido[3,2,l-t7]cinnoline-8-carboxylate... 

Thus, while the 3-hydroxyisoquinoline-3-isoquinolinone equilibrium (80 81) and that of the cinnoline derivatives (82 83) favour the keto forms (81, 83), the proportion of hydroxy tautomers is considerably greater than in the corresponding unfused systems. The benzo-fusion in 2- and 4-quinolinone and in 1-isoquinolinone has the effect of reducing the aromaticity of the heterocyclic ring, and consequently of lowering the proportion of the hydroxy tautomers. 

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