Crystal structures of ethyl {2-[4-(4-isopropylphenyl)thiazol-2-yl]phenyl}carbamate and ethyl {2-[4-(3-nitrophenyl)thiazol-2-yl]phenyl}carbamate

Two new thiazole derivatives – the structural analogs of the alkaloid Thiosporine B – were studied by X-ray diffraction.


Chemical context
Marine actinomycetes are prolific producers of biologically active natural products. This unique habitat has led to the abundant chemical diversity of metabolites that provides a foundation for the discovery of promising drug lead compounds. Among all known marine microbial secondary metabolites, over half were produced by actinomycetes Lam et al., 2006;Fu et al., 2011). From this resource, more than 400 new active secondary metabolites have been isolated (Bé rdy, 2005;Bull & Stach, 2007;Molinski et al., 2009). Some of them represented by abyssomycin C (Bister et al., 2004), diazepinomicin (Charan et al., 2004), salinosporamide A (Feling et al., 2003) and the marinomycins (Kwon et al., 2006) are potent antibiotics and possess novel structures. A comparatively large class of natural compounds possessing biological activity contains imidazole, thiazole, or oxazole moieties. Studies of biological activity (Zabriskie et al., 1990;Carroll et al., 1996;Taori et al., 2008) as well as a total synthesis of thiazoles containing alkaloids isolated from marine microorganisms are very important directions. In many cases, the substances mentioned above have promising antitumor (Luesch et al., 2001) and antibacterial (Shimanaka et al., 1994;Yun et al., 1994) activities.
In this paper we report a synthetic approach to the preparation of new thiazole derivatives (I) and (II) containing aryl fragments -the structural analogs of alkaloid Thiosporine B (Fu & MacMillan, 2015) -and their investigation by single crystal X-ray diffraction. , allowing for the different substituents on the benzene rings. Both molecules adopt a near-planar V-shaped conformation, which is consolidated by intramolecular N7-H7Á Á ÁN3 and C8-H8Á Á ÁO1 hydrogen bonds (Tables 1 and 2, Figs. 1 and 2) as well as an intermolecularinteractions (see Section 3 below). There exists a small twist of 10.27 (15) between the central thiazole and 4-benzene rings in (I) only. Surprisingly, the ethyl (phenyl)carbamate substituents (with the exception of some hydrogen atoms of the ethyl fragment) are perfectly coplanar with the thiazole ring in both molecules.

Supramolecular features
Although the similarity of the molecular geometries and types of intramolecular interactions might lead to similar packing motifs, this is not found in the case of (I) and (II). The intermolecular interactions, namely,interactions and C-HÁ Á ÁO hydrogen bonding, combined in a different way, give rise to various packing networks.
In (I), the crystal packing consists of stacks along the a axis ( Fig. 3), in which the molecules are linked to each other by (S1)Á Á Á(C7) [1 + x, y, z] interactions at distances of 3.463 (3) Å (Fig. 4). No other directional intermolecular interactions are observed in (I).
The situation in the case of (II) is quite different. The molecules of (II) form chains via C5-H5Á Á ÁO1(Àx + 3 2 , y À 1, z À 1 2 ) hydrogen bonds ( The molecular structure of (I). Displacement ellipsoids are shown at the 50% probability level. Dashed lines indicate the intramolecular hydrogen bonds. H atoms are presented as small spheres of arbitrary radius.

Figure 2
The molecular structure of (II). Displacement ellipsoids are shown at the 50% probability level. Dashed lines indicate the intramolecular hydrogen bonds. H atoms are presented as small spheres of arbitrary radius. Table 1 Hydrogen-bond geometry (Å , ) for (I).  Table 2 Hydrogen-bond geometry (Å , ) for (II). out that the molecules within the chains are coplanar, forming a ribbon-like motif. Further, the ribbons are packed in layers parallel to (100) viastacking interactions (Fig. 6). The distance between the ribbons in the layers is 3.216 (3) Å . Importantly, the ribbons of adjacent layers are not parallel to each other, but disposed at an interplane angle of 39.91 (2) (Fig. 6). Thus, the crystal of (II) comprises alternating layers, in which molecules are arranged in a different manner.

Synthesis and crystallization
A solution of ethyl (2-carbamothioylphenyl)carbamate (2.24 g, 10 mmol) and the appropriately substituted phenacyl bromide (10 mmol) in 95% EtOH (50 ml) was heated for 12 h under reflux. After cooling to room temperature, the solution was basified with saturated NaHCO 3 solution to yield the expected product (I) or (II) (Fig. 7). The reaction mixture was filtered and the isolated solid was washed with water and dried A fragment of the stack in (I). Dashed lines indicate the intermolecular SÁ Á ÁC interactions within the stack.

Figure 6
Crystal structure of (II) demonstrating the mutual arrangement of the hydrogen-bonded chains. Dashed lines indicate the intramolecular N-HÁ Á ÁN and C-HÁ Á ÁO and intermolecular C-HÁ Á ÁO hydrogen bonds.

Figure 3
The crystal structure of (I). Dashed lines indicate the intramolecular N-HÁ Á ÁN and C-HÁ Á ÁO hydrogen bonds.
in vacuo. The compounds were isolated as pale-yellow crystalline solids in 51% and 74% yield for the i-propyl (I) and nitro (II) derivatives, respectively. Single crystals of the products were obtained by slow crystallization from N,N-dimethylformamide solution.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3 Synthesis of the title thiazoles (I) and (II).  National Research Center 'Kurchatov Institute' (Moscow, Russian Federation) using a MAR CCD detector. For each compound, a total of 360 images were collected using an oscillation range of 1.0 (' scan mode) and corrected for absorption using the SCALA program (Evans, 2006). The data were indexed, integrated and scaled using the utility iMOSFLM in the program CCP4 (Battye et al., 2011). The hydrogen atoms of the amino groups were localized in difference-Fourier maps and refined in isotropic approximation with the constraint U iso (H) = 1.2U eq (N). The other hydrogen atoms were placed in calculated positions with C-H = 0.95-1.00 Å and refined using a riding model with U iso (H) = 1.5U eq (C) for the methyl group and 1.2U eq (C) for the other groups. For both compounds, data collection: Automar (MarXperts, 2015); cell refinement: iMosflm (Battye et al., 2011); data reduction: iMosflm (Battye et al., 2011); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

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.