Cinnolines Widman-Stoermer synthesis

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

WIDMAN-STOERMER SYNTHESIS. The synthesis of cinnolines by cyclization of diazotized o-aminoarylethylenes at room temperature. 

In a cyclization reaction similar to the Widman- Stoermer synthesis of cinnolines (see Houben-Weyl, Vol. E9a, p 691), the diazotization of 2-(l-methylvinyl)pyridin-3-aminc in dilute hydrochloric acid gives 4-methylpyrido[3,2-c]pyridazine (3) in low yield.104... 

Cinnolines are prepared by an intramolecular cyclization of o-alkenyl or o-alkynyl aryldiazonium salts. For instance, (o-aminophenyl)alkynes 6 or alkyl(o-aminophenyl)ketones 8 (via the enol form) yield 4-hydroxycinnolines 7 (the v. Richter and Borsche syntheses, respectively), o-Aminostyrenes 10 afford 3,4-disubstituted cinnolines 11 (Widman-Stoermer synthesis) ... 

This reaction is related to the Widman-Stoermer Synthesis and von Richter Cinnoline... 

An important early method simulated the well-known Widman-Stoermer cinnoline synthesis. 3-Aminopyridine-2- or -4-alkenes such as (348) gave pyrido-[3,2-c]- or -[3,4-c]-pyridazines on diazotization and alkaline cyclization (66JCS(C)2053>. 

RICHTER - WIDMAN STOERMER Cinnoline Synthesis Synthesis of cinnolines from substituted anilines via diazonium salts. 

This approach is important for the synthesis of cinnolines. CHEC(1984) <1984CHEC(2)1> already covered several examples. The methodology used starts with an aniline ortho substituted with an alkene (Widman-Stoermer type), alkyne (Richter type), or enolisable ketone (Borsche type) which is diazotisized, delivering the sixth atom, allowing cyclization. CHEC-II(1996) <1996CHEC-II(6)1> gave more examples. 

The Borsche (or Borsche-Herbert) cinnoline synthesis constitutes the cyclization of an ort/zo-diazonium aryl ketone to form a 4-cinnolone, or 4-hydroxycinnoline. It is mechanistically related to the Widman-Stoermer and Richter cinnoline syntheses, which involve the cyclization of ortho-diazonium aryl olefins and ortho-diazomnm aryl alkynes, respectively. 

The Widman-Stoermer cinnoline synthesis refers to the conversion of an o-vinyl aniline 1 to the representative cinnoline 2 via an in situ generated diazonium intermiediate/ Cinnolines have shown utility as anticancer, fungicidal, bactericidal, antithrombotic, and antituberculosis agents as well as having been shown to embody anesthetizing and sedative activity. Widman and Stoermer s approach to cinnolines represents a classical approach to this ubiquitous core structure. 

The first of many steps for the Widman-Stoermer cinnoline synthesis is diazotization. Of critical importance is the formation of dinitrogen trioxide (6) or a nitrosonium equivalent. The formation of 6 is followed by the... 

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