Nuclear Magnetic Resonance for the Structural Study of Bioactive Semicarbazones

Abstract

NMR studies of bioactive semicarbazones are described.

Introduction

Within our work on the development of bioactive compounds, we have employed the semicarba-zone moiety as a joining function between different pharmacophores.

Knowing the geometric isomer at the iminic union of the semicarbazone group, as well as the N-oxide positional isomer that was obtained in the synthetic procedure, were very important for deter-mining the structure of the biologically active compound. The lack of crystals to determine unequivo-cally the exact structure of the product obtained led us to use NMR spectroscopy for this purpose.

Experimental

All the experiments were carried out on a DPX-Bruker 400 (400 y 100 MHz) instrument. We car-ried out NOE difference (1D y 2D) experiments at different mixing times in order to determine the geometric isomer of the iminic junction.

We also carried out ¹H-NMR and ¹³C-NMR experiments at variable temperatures and EXSY ex-periments in order to determine the N-oxide position.

Results and Discussion

All the semicarbazones studied were in the E isomeric form. The N-oxide moiety in the derivatives of the heterocycle 1,2,5-oxadiazoles was found fixed at the 2 position. The derivatives of the heterocy-cle benzo[1,2-c]1,2,5-oxadiazoles were presented as a mixture of the different positional isomers of the N-oxide function, at room temperature.