Synthesis, potent anti-TB activity against M. tuberculosis ATTC 27294, crystal structures and complex formation of selected 2-arylidenehydrazinylbenzothiazole derivatives

Abstract The synthesis, anti-TB activity, crystal structures and ligand ability of a number of 2-arylidene - benzylidenehydrazinylbenzothiazole derivatives, 1 , have been investigated. The compounds 1 were obtained from 2-hydrazinobenzothiazole and substituted benzaldehydes in refluxing methanol in yields, after recrystallisation, of 55–75%. The crystal structure determination of compounds, 1e ( aryl = 4-MeOC 6 H 4 ) , 1h (aryl = pyridin-2-yl), 1f (aryl = 2-HO-5-MeC 6 H 3 ) revealed amino forms, whereas an imino form was found for 1f (aryl = 2-HO-4-MeOC 6 H 3 ). Despite the different tautomeric forms of 1e and 1h , the two compounds have similar cell dimensions and furthermore their intermolecular interactions combine to form similar sub-structures. Pairs of N H⋯N hydrogen bonds and π···dπ stacking interactions produce dimers in all compound. The compounds with the best anti-mycobacterial activity were found to be 1c (aryl = 2-O 2 NC 6 H 4 ), 1d , (aryl = 2-HOC 6 H 4 ), 1e and 1h , all having superior activities to that of the standard drug, ethambutol. Moreover two of these compounds have the capacity to act as tridentate ligands, namely 1d [a potential ONN chelator] and 1h [a potential NNN chelator]. Compound 1d (HL) acts as a tridentate O,N,N -donor to Cu (II) in forming the dimeric octahedral complex {[(L) (H 2 O)Cu][ O 3 SCF 3 ] } 2 , 3 , from Cu (II) ( O 3 SCF 3 ) 2 in moist MeOH. The monomeric square-pyramidal [(L) (H 2 O)Cu][ O 3 SCF 3 ], with an axial OS(O 2 )CF 3 ligand and equatorial H 2 O ligand, dimerizes through extensive π···π interactions involving two complete planar L-Cu fragments. The dimers are linked into a three dimensional array by O H⋯O and N H⋯O hydrogen bonds and by further π···π interactions. Complex 3 , while still very active, has only about 40% of the activity of its ligand against M. tuberculosis ATTC 27294.