Cinnolinones reactions

When reviewed in CHEC-I some examples of cyclization y to the heteroatom had been described for the synthesis of pyridazines, but the method was of most importance in the synthesis of cinnolines. Examples of pyridazine syntheses included cyclization of ketazines with EDA, and intramolecular Wittig reactions of phosphoranes derived from phosphacumuleneneylides and the hydrazones produced from 1,3-dicarbonyl compounds and aryldiazonium salts. Synthetically useful approaches to cinnolines given include the intramolecular Friedel-Crafts acylation of the diacid chlorides derived from the condensation products of aryldiazonium salts and diethyl malonate to give 4(l//)-cinnolinones, and thermal cyclization of iminium hydrazones obtained from enamine esters and aryldiazonium salts. 

Ethoxycarbonylmethyl)cyclohexane (100) gave 4,4a,5,6,7,8-hexahydro-3 (27/)-cmnolinone (101) (H2NNH2 H2O, EtOH, reflux, 1 h 72%) and thence 5,6,7,8-tetrahydro-3(2f/)-cinnolinone (102) (CuCl2, MeCN, reflux, 1 h 87%) minor variations in the foregoing reaction produced lower yields. ... 

The conversion of tautomeric cinnolinones into halogenocinnolines has been covered in Section 3.1. Other reactions are discussed in the subsections that follow. 

Several other important reactions of tautomeric cinnolinones are represented in the more recent literature, as illustrated in the following classified examples. 

Methylsulfinyl-4(l/i)-cumoIinone (12) gave 3-acetoxymethylthio-4(l//)-cinnolinone (11) (neat AC2O, reflux, 4h 65% by a Pummerer-type reaction and additional acetylation) or 4-chloro-3-chloromethylthiocinnoline (13) (neat SOCI2, reflux, 6h 92% note additional chlorolysis). ... 

The oxidative alkylamination of 2-methyl-3(2/7)-cinnolinone 29 by action of secOTidary alkylamines in the presence of KMn04 in THF under ambient conditions proceeds rather smoothly, leading to the formation of the expected 4-alkylamino-2-methyl-3(2//)-cinnolinones 30 (Scheme 24) [78], Interestingly, the analogous reaction with primary alkylamines is accompanied by a partial or complete... 

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