Richter cinnoline synthesis

The thermal cyclization of 2-alkynylbenzenediazonium salts represented by 2 to provide the 4-hydroxycinnoline derivatives 3 respectively is regarded as the von Richter cinnoline synthesis. " ... 

The mechanism of the von Richter cinnoline synthesis has been discussed in several... 

See the Borsche Cinnoline Synthesis and the von Richter Cinnoline Synthesis for other preparations of cinnolines. 

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

The von Richter cinnoline process was further extended to solid-phase synthesis. The route began from benzylaminomethyl polystyrene and the required diverse o-haloaryl resins represented by 21 were prepared from substituted o-haloanilines. A Pd-mediated cross-coupling reaction with 21 and the alkynes provided the alkynylaryl derivatives represented by alkyne 22. The von Richter cyclization reaction with hydrobromic or hydrochloric acid in acetone/HaO and cleavage from the resin occurred in the same step to furnish the cinnoline derivatives 23 in 47-95% yield and 60-90% purity (no yield reported for each entry). 

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

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 first synthesis of cinnoline was reported by von Richter in 1883. The diazonium chloride 5 which was obtained from o-aminophenylpropiolic acid (4), was heated in water at 70°C to provide the 4-hydroxycinnoline-3-carboxylic acid (6). When this acid 6 was heated above its melting point, carbon dioxide was liberated and 4-hydroxycinnoline (7) was obtained. Distillation of 4-hydroxycinnoline (7) with zinc dust furnished a small amount of oil, which was assumed to be cinnoline (8). The preparation of 4-hydroxycinnoline (7) was repeated by Busch and Klett, although in lower yield when compared to the original report. Busch and Rast later converted the 4-hydroxycinnoline (7) successfully to cinnoline (8) via the 4-chlorocinnoline (9). ... 

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. 

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) ... 

Some of us (94SC1733) have demonstrated that the classical Richter reaction (79MI1), the intramolecular cyclization of 2-alkynylaryldiazonium salts to give cinnolines, can be applied to the synthesis of not only 4-hydroxy- but also... 

Regitz reaction 263 Reissert reaction 409 Reissert synthesis (indole) 135 Remfiy-Hull synthesis (pyrimidine) 468 von Richter synthesis (cinnoline) 493 Ritter reaction 442... 

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