Nitrosation of phenacetin. Formation of N-nitroso-2-nitro-4-ethoxyacetanilide as an unstable product of the nitrosation in dilute aqueous-acidic solution.
Reaction of phenacetin with N2O4 in glacial acetic acid at 10(0) C gives N-nitroso-2-nitro-4-ethoxyacetanilide. This N-nitrosoacylarylamine is stable at low temperatures (--30 degress C) but unstable at ambient temperature. No intact N-nitroso-2-nitro-4-ethoxyacetanilide can be detected when phenacetin is nitrosated under conditions simulating those in the stomach (37 degrees C, pH 1). Instead, 2-nitro-4-ethoxybenzenediazonium chloride is the main reaction product found. Under the conditions applied, the N-nitrosoacylarylamine rapidly rearranges by 1,3-migration of the acetyl group. The resulting diazoester dissociates into the corresponding diazonium salt. Trapping of the diazonium ion with 1-naphthol as an azo dye provides a useful means to identify the parent N-nitroso compound and to measure colorimetrically its rate of formation. The yields obtained in dilute aqueous nitrosation mixtures are lower than expected; the reasons for this finding are discussed. Preliminary results of animal experiments show that the N-nitroso compound is a directly acting carcinogen.
D000083:Acetanilides / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D002273:Carcinogens / Q000138:chemical synthesis*; D002855:Chromatography, Thin Layer; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry; D008722:Methods; D009589:Nitrogen Oxides; D009603:Nitroso Compounds / Q000138:chemical synthesis*; D009608:Nitrous Acid; D010615:Phenacetin; D013696:Temperature
D000083:Acetanilides; D002273:Carcinogens; D009589:Nitrogen Oxides; D009603:Nitroso Compounds; D010615:Phenacetin; D009608:Nitrous Acid