O-aminophenylpropiolic acid

This method is suitable only for the preparation of 4-substituted and/or 3,4-disubstituted derivatives, the substituents being only alkyl, aryl or heteroaryl groups. The presence of electron-withdrawing groups in the unsaturated side chain prevents the cyclization step. This is understandable if the influence of such groups on the stability of the intermediate carbonium ion is considered. Of more limited application is the analogous cyclization of diazotized o-aminophenylpropiolic acids, the reaction being referred to as the Richter synthesis (Scheme 70). A related synthesis (also referred to as the Neber-Bossel synthesis)... 

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). ... 

The o-aminophenylpropiolic acid 4 (20 g) in water (60 mL) and aqueous ammonia (9 mL, d = 0.88) was added with shaking during 15 minutes to a mixture prepared from ferrous sulfate (220 g), water (440 mL), and aqueous ammonia (110 mL, d = 0.88). After 45 minutes, with occasional shaking but no external cooling, the suspension was filtered. The residue was washed with water, and the combined filtrates were treated with ammonium acetate (60 g) and made weakly acidic with acetic acid. The solution was then cooled to 0°C by addition of crushed ice, and then made acidic to Congo-red with concentrated hydrochloric acid (70-80 mL). Additional hydrochloric acid (20 mL, 2 N) was immediately added, and the turbid solution which resulted was diazotized with 20% aqueous sodium nitrite, after which the mixture was kept at 70°C. The cinnoline acid 6 was separated over 45 minutes as a dark brown, granular solid (12.5 g), m.p. 260-265°C. ... 

---

See also in sourсe #XX -- [ , ]

---