Cinnolin-3-ones, synthesis

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... 

One of the widely used cinnoline syntheses is the transformation of diazotized o-aminoarylethylenes into this bicyclic system (Widman-Stoermer synthesis) (Scheme 69). 

The annelation of benzo rings on pyridazines was covered in CHEC-II(1996) <1996CHEC-II(6)1>. Maes and Matyus reported new examples in their synthesis of the dibenzo[// ]phthalazin-l(27r)-one and dibenzo[//]cinnolin-3(27/)-one skeleton. Palladium-catalyzed intramolecular arylation of 2-benzyl-5-(2-bromophenyl)-4-phenylpyridazin-3(2//)-one yielded 2-benzyldibenzo[/,4]phthalazin-l(2//)-one. The synthesis of this new tetracyclic pyridazinone from 2-benzyl-5-(2-aminophenyl) -phenylpyridazin-3(2//)-one via a Pschorr-type reaction was also investigated. Similarly, the con-stmction of 2-methyldibenzo[/, ]cinnolin-3(2//)-one from 2-methyl-5-(2-bromophenyl)-6-phenylpyridazin-3(27T)-one and 2-methyl-5-(2-aminophenyl)-6-phenyl-pyridazin-3(2//)-one was performed <2003T5919>. 

Although the [5+1] strategy is generally considered to be only useful for the synthesis of cinnolines, some examples appeared for the synthesis of pyridazine derivatives. Michael addition of 2-arylhydrazono-3-oxobutanoates 260 on acrylonitrile 261 yielded pyridazin-4(l//)-ones 262 (Scheme 65) <2001SC2569>. 

Cyclopent-2-en-l-one, 2-hydroxy-3-methyl-synthesis, 3, 693 Cyclopentenone, 4-methoxy-formation, 1, 423 Cyclopenthiazide as diuretic, 1, 174 Cyclopent[2,3-d]isoxazol-4-one structure, 6, 975 Cydophane conformation, 2, 115 photoelectron spectroscopy, 2, 140 [2,2]Cydophane conformation, 2, 115 Cyclophanes nomenclature, 1, 27 Cyclophosphamide as pharmaceutical, 1, 157 reviews, 1, 496 Cydopiloselloidin synthesis, 3, 743 Cydopolymerization heterocycle-forming, 1, 292-293 6 ff-Cy clopropa[5 a,6a]pyrazolo[ 1,5- a]pyrimidine pyrazoles from, S, 285 Cy dopropab enzopy ran synthesis, 3, 700 Cydopropachromenes synthesis, 3, 671 Cyclopropa[c]cinnolines synthesis, 7, 597 Cyclopropanation by carbenes... 

Another synthesis of pyrimido[5,4-c]cinnolin-4(3//)-ones (59) via 4-aminocinnolines (56) starts with arylhydrazono-cyanoacetic acid derivatives (58). Upon heating in the presence of A1C13 4-aminocinnolines (56) are formed. Cyclocondensation with formamide or triethyl ort/io-formate affords the pyrimido[5,4-c]cinnolin-4(3/7)-ones (59) (Scheme 10) <92JPS365>. 

Preparations of cinnolines by expansion of five-membered heterocycle rings include the oxidation of A-aminooxindoles 232 (Scheme 132) <1988JHC847>, the treatment of isatogens 233 with ammonia (Scheme 133), and the base-catalyzed conversion of 1-aminodioxindoles 234 into cinnolin-3-ones 235 (Scheme 134) <1960JA4634>. Additional examples of the synthesis of cinnolines by transformation of another ring are available in CHEC-III . 

Walther Borsche and Alfred Herbert first reported the spontaneous cyclization of an ort/io-diazonium acetophenone in 1941, as part of a larger study on the synthetic transformations of 2-bromo-5-nitroacetophenone carried out at the University of Frankfurt am Main. The authors did not draw especial attention to this observation, and it was not until four years later that Schofield and Simpson suggested that this reaction might offer a general route to 4-cinnolones. After 70 years, this general reaction yielding 4-cinnolones remains one of the most useful methods for the synthesis of cinnolines. 

Cinnolines are another relatively unfamiliar class of heterocycle. A synthesis employing tandem C—N bond formations has recently been reported by the Willis research group. Continuing their use of key 2-(2-haloalkenyl)aryl halide substrates, they demonstrated that when combined with diethyl hydrazine-1,2-dicarboxylate, these substrates could undergo tandem copper-catalyzed alkenylation and arylation processes to generate novel diethyl dihydrocinnoline-l,2-dicarboxylates such as 56 [108]. These intermediates could be isolated and then treated with aqueous sodium hydroxide to reveal cinnoline products, such as 57, in moderate to excellent yields as shown in Scheme 24.28. Alternatively, the aromatic products could be revealed by treatment with sodium hydroxide in situ in a one-pot process. 

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