Cinnolinones synthesis

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. 

This approach was described in CHEC-I as of importance only for the synthesis of cinnolines <84CHEC-i(3B)i>. Most of the examples given involve the insertion of nitrogen as the sixth atom by diazotization of o-aminophenyl derivatives, in which the ortho substituent is generally an alkene, alkyne, or enolisable ketone. Another example is the synthesis of 3-substituted-4(l//)-cinnolinones via diazotisation of o-aminophenylalkynes (Scheme 90) the precursor is readily made by palladium and copper iodide catalysis <89H(29)1255>. 

Most such cinnolinones have been made by primary synthesis (see Chapter 1), a few by hydrolysis of halogenocinnolines (see Section 3.2), and others using procedures illustrated in the examples below it is noteworthy that several useful preparative routes, such as hydrolysis of alkylthiocinnolines or other types of thiocinnoline, appear to be unrepresented in the 1972-2004 literature. 

Note The formation of these ethers by primary synthesis Chapter 1), by alcoholysis or phenolysis of halogenocinnolines (Section 3.2), and by alkylation of tautomeric cinnolinones (Section 4.1.2.1) has been covered already. Other routes appear to be unrepresented. 

Note-. These acylcinnolines have been made by primary synthesis (see Chapter 1), Reissert-type addition to cinnoline (Section 2.1.3), oxidation of alkylcin-nolines (Section 2.2.2), displacement of halogeno substituents (Section 3.2), hydrolysis of dihalogenomethylcinnolines (Section 3.2), N-acylation of tautomeric cinnolinones (Section 4.1.2.2), oxidation of extranuclear hydro-xycinnolines (Section 4.2), or as illustrated here. 

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