Abstract

Ab initio calculations at HF/6-31G* and MP2/6-31G* levels have been carried out on the prototropic and annular tautomerism of pyrazolo [3,4-d] pyridazine (PP) in the gas phase. To account for the solvent effect the SCRF method (I = 4) has been applied. PP(9) is the most stable species in the gas phase, being PP(8) at ca. 4 kcal/ mol over the former. The proton migration to the pyridazine ring is unlikely to occur in the gas phase since PP(1) and PP(2) lie at ca 10 kcal/mol. The relative energies of the four tautomers vary dramatically in aqueous solution and depends strongly according to the SCRF methods, i.e., whether the solute charge distribution is truncated at I=1 or I=4. In both cases the four tautomeric forms could be in equilibrium and hence the annular tautomerism is more likely to occur in solution.