Synthesis, crystal structures and tautomerism in novel oximes based on hydroxyalkylpyrazolones

Abstract

Two novel hydroxyethyl pyrazolones were obtained by condensation of 2-hydroxyethylhydrazine with ethyl acetoacetate or ethyl benzoylacetate, later nitrosation of the C4 carbon atom in the heterocyclic moiety, afforded two novel oxime-derivatives. The ¹H and ¹³C NMR data show that 1-(2-hydroxyethyl)-3-methyl-5-pyrazolone (1) is largely present together with a very small amount of the 5-one tautomer in DMSO-d₆; in contrast, 1-(2-hydroxyethyl)-3-phenyl-5-pyrazolone (2) is found as a single tautomer in CDCl₃. Two diastereomers occur in DMSO-d₆ in 1-(2-hydroxyethyl)-3-methyl-4-hydroxyimino-5-pyrazolone (3) while in 1-(2-hydroxyethyl)-3-phenyl-4-hydroxyimino-5-pyrazolone (4), a single species is present in CDCl₃. Despite the polarity differences in the solvents used, remarkably the oxime tautomers proved to be more stable in both cases and DMSO-d₆ only allows the equilibrium between E/Z diastereomers. Single crystal X-ray diffraction data of 1, 3 and 4 are presented, they show that 1 occurs as a keto-enamine tautomer, in clear contrast with the situation in solution; in the case of 3 and 4, the tautomeric equilibrium remains shifted to the oximes in the solid phase as the Z-diastereomer, exclusively. This finding is the opposite of what was described in a previous report for 1-alkyl-3-methyl-4-hydroximino-5-pyrazolone, where the E-diastereomer was present. Besides, the data show that the oxime motif is not affected by the substitution changes described in C3. IR data in the solid phase supports the crystal structures and suggest that 2 occurs as a similar tautomer as 1.