Cinnoline 4-amino

Cinnoline, 4-alkylamino-3-phenyl-tautomerism, 3, 5 Cinnoline, 4-amino-biological aaivity, 3, 56 nitration, 3, 21 tautomerism, 3, 5 Cinnoline, dihydro-... 

Cinnoline, 4-alkylamino-3-phenyl-tautomerism, 3, 5 Cinnoline, 4-amino-biological aaivity, 3, 56 nitration, 3, 21 tautomerism, 3, 5 Cinnoline, dihydro-N-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... 

Chemical reactivity, as method to study tautomerism, 321 Chromone, 2-hydroxy-, 346 Chromonediols, 363 Cinchonie acids, 2-thienyl-, 99 Cinnoline 4-amino-, 415... 

This type of cyclization is important only for the formation of cinnolines. In all cases, the starting compounds have an ortho amino group, which upon diazotization undergoes ring closure with the other functionality, most frequently with a multiple bond. 

In a similar manner to the formation of pyridazines from AT-aminopyrroles, cinnolines or phthalazines are obtainable from the corresponding 1-aminooxindoles or 2-amino-phthalimides. If the relatively inaccessible 1-aminooxindoles are treated with lead tetraacetate, mercuric acetate, r-butyl hypochlorite (69JCS(C)772) or other agents, cinnolones are formed as shown in Scheme 105. The reaction was postulated to proceed via an intermediate... 

Amino-pyrazines and -pyridazines have been shown to exist predominantly in the amino form by infrared spectroscopic studies (cf. Table VI). Ultraviolet spectral data have been interpreted to indicate that 4-aminocinnoline exists predominantly in the imino form 256, but this conclusion, which was based on comparison of its spectrum with those of cinnolin-4-one and 4-ethoxycinnoline, is probably incorrect. Ultraviolet spectroscopic data strongly support the predominance of amino structures for 2-aminopyrazine (257) and 2-aminoquin-oxaline how ever, the former compound was at first erroneously concluded to exist in the imino form from ultraviolet spectral evidence. Isolation of two isomers of 2-amino-8-dimethylamino-3-methylphenazine, assigned the amino and imino structures 258 and 259, respectively, has been claimed, but it is very unlikely that these assignments are correct. 

Atkinson and Taylor summarized the evidence in support of the earlier assumption, arising from the evidence discussed above, that quatemization occurs on N-1 and also showed that 4-amino-, 4-amino-6-nitro-, and 4-amino-7-chloro-cinnoline gave two salts with methyl iodide, while 4-amino-8-nitrocinnoline gave only one salt and the... 

The activation in cinnolines is sufficient to enable nucleophilic substitution of poor leaving groups such as amino and phenoxy... 

It should be emphasized, however, that classical syntheses of cinnolines by conventional methods are reported to give higher yields. For example, Jacobs and Winstein (1946) obtained 4-methylcinnoline in 90% yield by diazotization of 2-(2 -amino-phenyl)propene in 10% aqueous H2S04, storing the solution diluted ten-fold for three days, rendering alkaline with NaOH, and extracting with benzene. 

The reaction of a-oxophenylhydrazones with 2-amino-1,1,3-tricyanopropene and diethyl 1-cyano-2-aminopropene-l,3-dicarboxylate has been shown to afford polyfunctionally substituted pyridazines and cinnolines <96JCR(S)434>. A study of haloazodienes has led to a new, general... 

Alkylation of ll-mercaptopyrido[l,2-h]cinnolin-6-ium hydroxide inner salts (e.g., 41) with ethyl bromoacetate gave ll-(ethoxycarbonylmethyl(thio derivatives 64 (R = H), which could be hydrolyzed to the ll-(carboxy-methyl)thio derivative or back to the starting compound 41 (74JHC125). Hydrolysis of the ll-bis(methoxycarbonyl)methylene 66 (R = H), and 2-cyano derivatives of 17 (R = H) in boiling HCl afforded 11-methyl and 2-carboxylic acid derivatives, respectively (74JHC125). The 2-nitro derivative of 17 (R = H) was reduced to the 2-amino derivative over Pd/C with NaBH4 in aqueous methanol, and the 2-amino group was acylated with acetic anhydride at 100°C. 

Cyclization of 1 -amino-8-(2-hydroxyalkyl)-4-oxoquinoline-3-carboxyl-ates (130) on the action of diethyl azodicarboxylate in the presence of triphenylphosphine afforded 7-oxopyrido[3,2,l-jy]cinnoline-8-carboxylates (131) (92EUP470578). 

Cyclization of l-[M2,2-bis(fer/)-butyloxycarbonyl)ethyl -A -methyl-amino]-5,6,7,8-tetrafluoro-4-oxoquinoline-3-carboxylates (142, R = F) in the presence of CS2CO3 gave 7-oxopyrido[3,2,l-//]cinnoline-3,3,8-tricarbox-ylates (143) (92EUP470578,92MIP1 95JOC3928 96JCS(CC)61). The cyclization was accompanied by some N—N bond cleavage (5-20%). 

In spite of the fact, that it is accomplished by the attack of a nitrogen atom on a triple bond, the copper catalysed ring closure of (o-ethynylphenyl)-triazenes follows a different mechanistic pathway. In the presence of copper(I) chloride in dichloroethane the starting triazenes are converted into 7V-amino-isoindazoles, while their thermal transformation gives predominantly cinnolines (3.51.),65... 

Several other sequences based on the alkylation of cinnoline derivatives have been reported to furnish betaines (233). Treatment of 4-methoxy- and 4-phenoxycinnolines with methyl iodide gives 2-methylcinnolinium iodides (237 R = Me or Ph) which are converted to 2-methylcinnolinium-4-olate (243) by hot hydrobromic acid. In a closely related approach 4-amino-or 4-methylaminocinnolines have been methylated and the 2-methyl-4-aminocinnolinium salts (238 R = H or Me) subsequently hydrolyzed to the betaine (243) by hot aqueous alkali. ... 

Oxidation of 3-amino-2-(2,5-dihydroxybenzyl)quinazolin-(3i/)-one (494) with acidic ferric chloride or aqueous sodium hydroxide gave a quinone that spontaneously cyclized to the quinazolino[3,2-fc]cinnoline-2,7(13//)-dione (495) [66JCS(C)2190]. 

Only pyrazine and its benzo derivatives are easily converted into di-A-oxides, although di-A-oxides have been reported, for example, in the pyridazine, pyrimidine and cinnoline series. Oxidation of 3-amino-1,2,4-triazine 2-oxide with H202 in polyphosphoric acid at 24°C affords 3-amino-1,2,4-triazine 2,4-dioxide (78). However, 3-amino-1,2,4-triazine with peracetic or... 

A new, efficient and general synthesis of 4-amino-3-arylcinnolines has been described recently, starting from arylhydrazines and aryl trifluoromethyl ketones, and the following is a typical example. Addition of a THF solution of the hydrazone formed from phenylhydrazine and 2-trifluoroacetylthiophene to 5 equivalents of KHMDS in THF at -78°C, then slow warming of the mixture to room temperature and stirring at room temperature for several hours, gave 4-amino-3-(2-thienyl)cinnoline in 68% yield after work-up (quench with ether, then a wash with brine). 

Condensation of 5-(arylethynyl)-3-(diethylamino)naphthoquinones 64 with hydrazine afforded 3-benzyl-9-(diethyl-amino)bcnzo[zA ]cinnolin-7-oncs 66. Replacement of the arylethynyl substituent in the starting naphthaquinone by a 3-hydroxyalk-l-ynyl group leads to a change in the direction of cyclization, resulting in substituted naphtha[l,8-zv/ -l,2-diazepin-8-ones 65, as condensation products <2001RCB1668> (Scheme 13). 

The oxidation of 5-aminophenanthridone with lead tetraacetate in methylene chloride leads to benzocoumarin and phenanthridone rather than benzo[c]cinnoline (cf. the oxidation of l-amino-3,4,5,6-tetraphenylpyridone349). 

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