Molecular structure in the solid state (X‐Ray diffraction) and in solution (1H and 13C NMR) of nifurtimox and two pyrazol‐1‐Yl analogs

The crystal and molecular structure of tetrahydro-3-methyl-4[(5-nitrofurfurylidene)amino]-2H-thiazine 1, 1-dioxide (Nifurtimox) 1, 1-[(5-nitrofurfurylidene)amino]pyrazole 2, and 1-[(5-nitrothenylidene)amino] pyrazole 3 have been solved by X-Ray crystallography. Compound 1 presents the E-sE conformation along the N = C-C moiety while 2 and 3 presents an E-sZ one. In spite of their molecular similarity (sulfur instead of oxygen in the ring), compounds 2 and 3 pack in quite different ways. In solution (1H and 13C NMR) the only difference with the solid structures concerns the ∼ 180° rotation of the furane ring in compound 1 which thus becomes similar to the other two compounds (sZ). A detailed analysis of the seven proton system of the 1,4-thiazine 1,1-dioxide ring established that in solution too, the ring has a chair conformation with the C-methyl group in an equatorial position.