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

Abstract

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. TheN-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.