Determination of organic pharmaceuticals with N-bromosuccinimide. Part III. Some pyrazolone derivatives by direct titration

Abstract

Seven members of the pyrazolone group have been studied, namely, 3-methyl-1-phenyl-3-pyrazolin-5-one (MPP), phenazone (2,3-dimethyl-1-phenyl-3-pyrazolin-5-one), 4-aminophenazone (4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one), aminophenazone (amidopyrine; 2,3-dimethyl-4-dimethylamino-1-phenyl-3-pyrazolin-5-one), dipyrone [sodium (2,3-dimethyl-5-oxo-1-pheyl-3-pyrazolin-4-yl)methylaminomethanesulphonate], morazone [2,3-dimethyl-4-(3-methyl-2-phenylmorpholinomethyl)-1-phenyl-3-pyrazolin-5-one] and propyphenazone (4-isopropyl-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one). The direct titration of the pyrazolone group with standard N-bromosuccinimide was only successful for MPP and phenazone in glacial acetic acid using methyl orange as the indicator. The concentration of the acetic acid must be not less than 9 N at the end of the titration. MPP can also be titrated successfully in 1 N hydrochloric acid, the end-point being detected either by methyl orange or potentiometrically. The molar ratio of the reaction was found to be always 1 : 1 (phenazone : N-bromosuccinimide) and 1 : 2 (MPP : N-bromosuccinimide).

A reaction mechanism is suggested involving the formation of a 4-bromo derivative during the titration of either MPP or phenazone with N-bromosuccinimide. A second molecule of N-bromosuccinimide is consumed in brominating the secondary amino group in the case of MPP.