Crystal structure and Hirshfeld surface analysis of N-(5-iodo-4-phenylthiazol-2-yl)acetamide

The title compound crystallizes with two independent molecules in the asymmetric unit. In the crystal, molecules are linked by N—H⋯O hydrogen bonds, C—H⋯π, I⋯S and I⋯I interactions into a three-dimensional network.


Chemical context
The 1,3-thiazole ring is a structural motif frequently found in the pharmaceutical field in antibacterial (Alam et al., 2014), antifungal (Yu et al., 2007) and antiviral (Liu et al., 2011) agents among others. In the chemotherapy of protozoal diseases, 5-bromo-2-aminothiazole derivatives have been investigated as privileged structures in biological tests against intestinal parasites such as Giardia (Mocelo-Castell et al., 2015). Halo-1,3-thiazole derivatives have proven to be suitable substrates in oxidative addition reactions in the presence of palladium (Wang et al., 2015;Hä mmerle et al., 2010). The presence of halogens in the core of thiazole derivatives opens the door to using them as suitable substrates for coupling reactions and to expand the therapeutic potential of a compound by improving the pharmaceutical properties. Transition-metal-catalysed reactions constitute one of the most important and attractive research areas in academia, as well as in the pharmaceutical and fine chemical industries (Zhao et al., 2017;Jana et al., 2011). Cross-coupling reactions usually require, in addition to a transition metal, that the electrophilic coupling partner possesses leaving groups such as Br À or I À among others. The development of suitable halo-1,3thiazole substrates for cross-coupling reactions allows us to report the crystal structure and the Hirshfeld surface analysis of N-(5-iodo-4-phenylthiazol-2-yl)acetamide.

Structural commentary
The title 2-acetoamidothiazole derivative crystallizes in the monoclinic space group P2 1 /c with two crystallographically ISSN 2056-9890 independent molecules in the asymmetric unit (Fig. 1). The principal difference between these molecules is the dihedral angle between the phenyl and thiazole rings. In molecule A, the thiazole ring (S1/N2/C3-C5) makes a dihedral angle of 38.94 (16) with the adjacent phenyl ring (C6-C11) while for molecule B the dihedral angle between the S2/N4/C14-C16 and C17-C22 rings is 32.12 (15) . Unlike the related compound 2-acetamido-4-p-tolyl-1,3-thiazole (Lynch et al., 2004) in which the molecule is essentially flat, the presence of the iodine atom at C5 or C16 of the title compound induces rotation of the phenyl group attached to the thiazole ring, as also observed in some bromine-substituted phenylthiazole compounds (see the Database survey).

Hirshfeld surface analysis and two-dimensional fingerprints plots
A Hirshfeld surface analysis was carried out using Crystal Explorer17.5 (Turner et al., 2017) in order to acquire a better understanding of the nature of the intermolecular interactions in the title compound. The Hirshfeld surface was generated using a standard (high) surface resolution with the three-  Table 1 Hydrogen-bond geometry (Å , ).

Figure 2
Part of the crystal structure of the title compound, showing the formation of hydrogen bonds and IÁ Á ÁI contacts (red dashed lines) in the ac plane.

Figure 1
Molecular structure of the two crystallographically independent molecules in the asymmetric unit of the title compound, with the atom labelling. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as spheres of arbitrary radius.

Figure 3
Packing viewed along the a-axis direction showing C-HÁ Á Á and IÁ Á ÁS interactions as red dashed lines.

Synthesis and crystallization
A mixture of N-(4-phenylthiazol-2-yl) acetamide (0.5 mmol, 109 mg, 1 eq) and iodine (1 mmol, 127 mg, 2 eq) was placed in an open vessel containing a Teflon-coated stir bar. The mixture was dissolved in 3 mL of ethanol and the vessel was placed in the microwave cavity (CEM, Discover) and subjected to MW irradiation (150 W) for 60 min, at 363 K and a pressure of 2 psi. The reaction mixture was then cooled at room temperature and 5 mL of NH 4 OH were added. The obtained mixture was dissolved in ethyl acetate (50 mL) and washed with brine (3Â). The organic layer was separated, dehydrated with Na 2 SO 4 , and evaporated in vacuo until dryness. The product was purified by flash column chromatography (silica gel, 2-25 mm) with a mixture of petrol-dichloromethaneacetone (5:3:2). The title compound was obtained as paleyellow needles in 30% yield (52.2 mg, 0.15 mmol). A diluted solution of the compound was prepared in hexane and kept on a dry and dark place at room temperature. Crystals were obtained after one week of slow evaporation.  The three-dimensional Hirshfeld surface of the title compound mapped over d norm , showing the N-HÁ Á ÁO hydrogen bonds.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. Hydrogen atoms bonded to C atoms were positioned geometrically and refined using a riding model: C-H = 0.95-1.00 Å with U iso (H) = 1.2U eq (C) or 1.5U eq (C-methyl).

N-(5-Iodo-4-phenylthiazol-2-yl)acetamide
Crystal data Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.