Stability of Isoniazid and Its Related Compounds. VI. : Oxydative Degradation of Isoniazid

Abstract

Oxidative degradation of isoniazid (INAH) with Mn²⁺ was examined and the result from the analysis of reaction products shows that the main products are isonicotinic acid and isonicotinamide, and a small amount of by-products are 1, 2-diisonicotinoylhydrazine and isonicotinaldehydeisonicotinoylhydrazone. It was found that INAH makes chelates with Mn²⁺ in the ratio of 1 : 1 and 1 : 2, these chelates are oxidized to Mn³⁺ compounds by oxygen and then degraded, and that apparent degradation velocity of INAH is determined by the concentration and degradation rate of each of the chelates. The activation energy of the degradation reaction of chelate compounds, INAH-Mn⁺ and INAH-Mn-INAH, was 11.7 and 10.0 kcal/mole, respectively. The degradation of INAH with Mu²⁺ is accomplished by a three-step process ; first Mn²⁺ forms a chelate with INAH, then Mn²⁺ of the chelate is oxidized to Mn³⁺ by oxygen, and then the high electron affinity of Mn³⁺ cleaves the C=N and N-N bonds.