Planarity of heteroaryl­dithio­carbazic acid derivatives showing tuberculostatic activity. IV. Diesters of benzoyl­carbonohydrazonodithioic acid

Dimethyl (3,4-dichloro­benzo­yl)carbonohydrazonodithio­ate, C₁₀H₁₀Cl₂N₂OS₂, (D1), dibenzyl (3,4-dichloro­benzo­yl)car­bono­hydrazonodithio­ate, C₂₂H₁₈Cl₂N₂OS₂, (D2), dimethyl (3,4-dichloro­benzo­yl)-1-methyl­carbonohydrazonodithio­ate, C₁₁H₁₂Cl₂N₂OS₂, (D3), 3,4-dichloro-N'-(1,3-dithio­lan-2-yl­idene)-N-methyl­benzohydrazide, C₁₁H₁₀Cl₂N₂OS₂, (D4), were synthesized as potential tuberculostatics. Compound (D1) (with two molecules in the asymmetric unit) was the only one showing tuberculostatic activity of the same range as the common drugs isoniazid and pyrazinamide. The mol­ecular structures of the studied compounds depend on the substitution at the N atom adjacent to the carbonyl group. In the case of the unsubstituted derivatives (D1) and (D2), their central frames are generally planar with a twist of the 3,4-dichloro­phenyl ring by 30-40°. Until now, coplanarity of the aromatic ring with the (methyl­ene)carbonohydrazone fragment has been considered a prerequisite for tuberculostatic activity. The N-methyl­ated derivatives (D3) and (D4) show an additional twist along the N-C(=O) bond by 20-30° due to the spatial repulsion introduced by the methyl substituent.

Planarity of benzoyl­hydrazine-dithio­carbazoate tuberculostatics. I. N'-Methyl-substituted 3,4-dichloro­benzoyl monoesters

Methyl 2-(3,4-dichloro­benzoyl)-1-methyl­hydrazine­carbo­di­thio­­ate, C₁₀H₁₀Cl₂N₂OS₂, (F1), butyl 2-(3,4-dichloro­ben­zoyl)-1-methyl­hydrazine­carbodithio­ate, C₁₃H₁₆Cl₂N₂OS₂, (F2), and 3,4-dichloro-N-(2-sulfanylidene-1,3-thia­zinan-3-yl)benz­amide, C₁₁H₁₀Cl₂N₂OS₂, (F3), were studied by X-ray diffraction to test our hypothesis that planarity of aryl­­oylhydrazinedithio­carbazic acid esters is a prerequisite for tuberculostatic activity. All compounds examined in this study are inactive and nonplanar due to twists along two specific bonds in the central frame of the mol­ecules. The significant twist at the N-N bond, with an C-N-N-C(S) torsion angle of about 85°, results from repulsion caused by a methyl substituent at the N' atom of the hydrazide group. The other twist is that within the benzoyl group at the C(O)-Ph bond, i.e. the N-C(=O)-C(phenyl)-C torsion angle: the values found in the studied structures (25-30°) are in agreement with those observed in other compounds containing a similar fragment. As some nonplanar benzoyl derivatives are active, it seems that planarity of the hydrazine­dithio­ate fragment is more important for tuberculostatic activity than planarity of the aryloyl group.