SPIRO MEISENHEIMER COMPLEXES FROM 7-(2-HYDROXYETHOXY)-4-NITROBENZOFURAZAN AND 7-(2-HYDROXYETHOXY)-4-NITROBENZOFUROXAN - KINETIC STUDY IN AQUEOUS-SOLUTION

Cyclization of 7-(2-hydroxyethoxy)-4-nitrobenzofurazan and 7-(2-hydroxyethoxy)-4-nitrobenzofurazan [antineoplastic drugs] occurs in aqueous solution containing base to give the spiro Meisenheimer-type complexes 5 and 8, which have a high thermodynamic stability. A similar reaction occurs in Me2SO where the structures of 5 and 8 could be fully characterized by 1H NMR spectroscopy. The kinetics of formation and decomposition of 5 and 8 were studied by the stopped-flow method between pH 1 and 12 in aqueous solution. Compound 5 is only 2.5-fold more stable than 8 (pKa5 = 6.86; pKa8 = 7.26), but it forms and decomposes much faster than its furoxanic analog. These differences in rates are attributed to the N-oxide group, which probably exerts a very unfavorable influence on the C.sbd.O bond-forming and bond-breaking processes associated with formation and decomposition of the furoxanic adduct 8. The ring opening of 5 and 8 is subject to general acid catalysis in aqueous solution with a Bronsted coefficient .alpha. of 0.44. The results are discussed by comparison with those obtained for benzenic analogs.