REACTION OF HETEROARYL THIOLS WITH CONJUGATED AZOALKENES - REGIOSELECTIVE PREPARATION OF 4-(HETEROARYLTHIO)-1H-PYRAZOL-5(2H)-ONES - X-RAY CRYSTAL-STRUCTURES OF METHYL 2-((PYRIMID-2-YL)THIO)ACETOACETATE (AMINOCARBONYL)HYDRAZONE AND METHYL-4-((PYRIMID-2-YL)THIO)-1H-PYRAZOL-5(2H)-ONE

Heteroaryl thiols easily react with conjugated azoalkenes to give alph a-(heteroarylthio)hydrazones, by 1,4-addition to the azo-ene system. T he treatment of the latter compounds with sodium methoxide and then wi th trifluoroacetic acid affords regioisomeric 4-(heteroarylthio)-1H-py razol-5(2H)-ones. In general, these reactions can be successfully exec uted in two as well as one pot procedures. X-ray diffraction studies o f methyl 2-((pyrimid-2-yl)thio)acetoacetate (aminocarbonyl)hydrazone u nequivocally show that the preliminary 1,4-addition occurs by nucleoph ilic attack of the thiol function of heteroaryl thiols to the azo-ene system of conjugated azoalkenes. X-ray structure determination of meth yl-4-((pyrimid-2-yl)thio)-1H-pyrazol-5(2H)-one was carried out in orde r to determine the behavior of alpha-(heteroarylthio) hydrazones in th e ring closure and the nature of the heterocycle. In particular, this investigation afforded information about the hydrogen bondings and the stereochemistry of this molecule and clarified some spectroscopic evi dence. A detailed H-1 and C-13 NMR study of these compounds in DMSO-d( 6) showed separate signals for the ''NH'' and ''OH'' tautomers, as wel l as a solvent effect on the enol-keto equilibrium. The conversion of the initial keto form to the related enol form was often complete. The equilibration was found to be extraordinarily slow, requiring in some cases 720 h at room temperature and corresponding to Delta G approxim ate to 25-30 kcal mol(-1). These findings suggest that the regioisomer ic structure assignments reported in the literature for some 5- and 3- hydroxypyrazoles in solution should be reconsidered. In order to avoid misunderstandings about the correct nomenclature of heterocycle deriv atives, we believe that such assignments should be supported, when pos sible, by the appropriate X-ray crystal structure determinations.