2-Chloro-3-nitro-5-(trifluoromethyl)benzoic acid and -benzamide: structural characterization of two precursors for antitubercular benzothiazinones

Abstract

8-Nitro-1,3-benzothiazin-4-ones are a promising class of new antitubercular agents, two candidates of which, namely BTZ043 and PBTZ169 (INN: macozinone), have reached clinical trials. The crystal and molecular structures of two synthetic precursors, 2-chloro-3-nitro-5-(trifluoromethyl)benzoic acid, C8H3ClF3NO4 (1), and 2-chloro-3-nitro-5-(trifluoromethyl)benzamide, C8H4ClF3N2O3 (2), are reported. In 1 and 2, the respective carboxy, carboxamide and the nitro groups are significantly twisted out of the plane of the benzene ring. In 1, the nitro group is oriented almost perpendicular to the benzene ring plane. In the crystal, 1 and 2 form O—H...O and N—H...O hydrogen-bonded dimers, respectively, which in 2 extend into primary amide tapes along the [101] direction. The trifluoromethyl group in 2 exhibits rotational disorder with an occupancy ratio of 0.876 (3):0.124 (3).

Keywords

• benzothiazinones
• btz043
• pbtz169
• nitrobenzoic acids
• nitrobenzamides
• antituberculosis drugs
• hydrogen bonds
• crystal structure