Crystal structure of (E)-4-{1-[2-(carbamothioyl)hydrazin-1-ylidene]ethyl}phenyl 4-methylbenzoate

The asymmetric unit of the title compound, C17H17N3O2S, consists of two independent molecules, A and B, with different conformations: in molecule A, the dihedral angles between the central benzene ring and the pendant tolyl and carbamothioylhydrazono groups are 71.12 (9) and 5.95 (8)°, respectively. The corresponding angles in molecule B are 50.56 (12) and 26.43 (11)°, respectively. Both molecules feature an intramolecular N—H⋯N hydrogen bond, which closes an S(5) ring. In the crystal, molecules are linked by N—H⋯O, N—H⋯S and C—H⋯O hydrogen bonds, generating a three-dimensional network.


S1. Comment
Thiosemicarbazone and its derivatives are a class of O, N, S-tridentate donor ligands capable of stabilizing both higher and lower oxidation states of transition metal ions. The biological activities of these ligands are linked to their chelating ability with transition metal ions through phenol O, azomethine N and thiolate S atoms (Seena et al., 2006). Thiosemicarbazones are significant intermediates in drugs synthesis, formation of metal complexes and heterocycles such as thiadiazolines preparation (Sau et al., 2003). Thiosemicarbazones are reported as compounds which present significant antifungal activity. Their metal complexes also exhibit antifungal properties (Reis et al., 2013).
Thiosemicarbnazones are inhibitors of DNA replication and also of many proteases. This inhibitory activity defends the level of interest given to them in the fight against microbial and parasitic diseases. Thiosemicarbazones have many biological activities such as antiviral, antibacterial, antitumor, African trypanosome (Fatondji et al., 2013).
The title compound, C 17 H 17 O 2 N 3 S 1 , crystallizes in triclinic P -1 space group. The asymmetric unit of title compound  (Table. 1 & Fig. 2). In the crystal packing N-H···S type of intermolecular interaction shows R 2 2 (8) dimer formation.

S2. Experimental
A 250-ml two neck RB flask was taken and fitted with condenser and an addition funnel. 0.5mol of 4-hydroxy acetophenone was taken and 200ml of chloroform was added to it with stirring. The reaction mixture was cooled at 5-10°c.
0.5mol of para-tolouyl chloride was added drop wise to the reaction mixture. Stirring was continued for another 15mins and 0.5mol of potassium carbonate was slowly added. Reaction was continued for 2 hours and monitored using TLC. The reaction mass was transferred into 1l beakers and washed twice with water (2x250ml). The chloroform layer was separated and washed with 10% NaOH solution (2x250ml). The chloroform layer was separated and dried with anhydrous sodium sulphate. The chloroform layer was filtered and concentrated under reduced pressure using rotary vacuum, cooled and hexane was added to it. Solid was precipitated, filtered and the product was air dried. Thiosemicarbazide (0.1mole) dissolved in 20 ml of 1N hydrochloric acid was added slowly in constant stirring to 4-Methyl- benzoic acid 4-acetyl-phenyl ester (0.1mole) dissolved in 50 ml of ethanol. After addition of thiosemicarbazide, novel 4-(1-(2-carbamothioylhydrazono)ethyl) phenyl 4-methylbenzoate (in solid form) was formed within 4 mins. The precipitate was filtered and washed with water, followed by Hexane wash and the product was air dried. After purification the compound was recrystallised from CHCl 3 solution to yield colourless blocks.

S3. Refinement
The hydrogen atoms were placed in calculated positions with C-H = 0.93Å to 0.96 Å & N-H = 0.85 Å to 0.86 Å and refined in the riding model with fixed isotropic displacement parameters:U iso (H) = 1.5U eq (C) for methyl group and U iso (H) = 1.2U eq (C) for other groups. The hydrogen atom H2Awas obtained from the difference fourier map.

Figure 1
The molecular structure of the title compound, showing displacement ellipsoids drawn at 30% probability level.

Figure 2
The crystal packing of the title compound viewed down b axis. H-atoms not involved in H-bonds have been excluded for clarity.