Synthesis, crystal structure, and Hirschfeld surface analysis of novel ethyl 5-bromo-2-(4-methoxyphenyl) oxazole-4-carboxylate.

A new oxazole derivative, ethyl 5-bromo-2-(4-methoxyphenyl) oxazole-4-carboxylate, was synthesized and characterized by IR spectroscopy, 13 C NMR, mass spectroscopy, and single-crystal X-ray diffraction analysis. The asymmetric unit of the title compound has two independent molecules (A and B) arranged in an inverted planar orientation, stabilized by intramolecular C-H · · · O and C-H · · · N hydrogen bonds and intermolecular C-H · · · O hydrogen bonds. The crystallographic parameter for the structure C 13 H 12 BrNO 4 is M =326.15 g/mol, monoclinic, sp. gr. P2 1 /n (no. 14), a = 14.828(2) Å, b = 7.1335(9) Å, c = 25.119(2) Å, β = 100.066(11)°, V = 2616.1(6) Å 3 , Z = 8. Hirschfeld surface analysis and two-dimensional fingerprint plots provided insights into the short intermolecular interactions, and it was found that H · · · H (34.4%) interactions contributed the most to the intermolecular interactions. In contrast, the contribution of C · · · C (2.5%) was the least among all interactions.


Materials and methods
Reagent-grade chemicals and solvents were purchased from CDH, Merck, Sigma, Alfa Aesar, or Rankem.The reaction completion was monitored on normal-phase precoated silica using aluminium back-TLC plates (Merck KGaA, Darmstadt, Germany).The melting point was determined using an OPTIMELT automated system and uncorrected.
The two-step synthetic protocol is outlined in Scheme 1

Procedure for synthesis of ethyl 2-(4-methoxyphenyl) oxazole-4-carboxylate (I)
To a solution of 4-methoxy benzamide (250 mg, 1.65 mmol) and in toluene/dioxane (1:1) (20 ml) at 23 o C, ethyl bromopyruvate (0.625 ml, 4.98 mmol) was added, and the reaction mixture was heated to reflux while stirring for 24 h.After confirming the completion of the reaction using TLC, the mixture was cooled to room temperature and concentrated under a vacuum.The residue was extracted using ethyl acetate and washed with brine.The organic layer was then dried over sodium sulfate.The crude product was purified by silica gel column chromatography using Petroleum ether: ethyl acetate (97:3) to yield compound I, ethyl 2-(4-methoxyphenyl) oxazole-4-carboxylate [31].Yield: 50%, m.p 100-102 o C.

Characterization
The FTIR spectra of the title compound were recorded on an IR prestige 21, SHI-MADZU spectrophotometer (Shimadzu Corporation, Japan) in the range of 400-4000 cm -1 using KBr pellets.  ) corresponds to the triplet due to the CH 2 group of the ester, 3.85 (s, 3H) corresponds to the singlet of the CH 3 group of the methoxy group on the aromatic ring, 4.42 (q, J = 7.1 Hz, 2H) corresponds to the resonance offered by the CH 3 group of the ester; the four aromatic protons showed resonance at 6.95 (d, J = 8.8 Hz, 2H), 7.97 (d, J = 9.3 Hz, 2H).The 13 C NMR spectral properties corresponded to the structure of the molecule, wherein the δ values of the aliphatic and aromatic carbons were in their expected ranges.

X-ray crystallographic data collection and structure refinement
X-ray quality single crystals of ethyl 5-bromo-2-(4-methoxyphenyl) oxazole-4carboxylate (II) were obtained by dissolving the sample in a hot petroleum ether and ethyl acetate (95:5) solution, followed by slow cooling at room temperature.Crystals of suitable dimensions were mounted on a Rigaku Oxford Diffraction X-Calibur CCD system, controlled with user-inspired Crysalis Pro for crystallographic data acquisition with a layer of light mineral oil, and measurements were made using an Enraf Nonius Kappa CCD diffractometer with Mo Kα radiation (0.71073 Å).Using Olex-2 [32], the structure was solved using the Olex2.solve[33] structure solution program using charge flipping and refined with the SHELEXL [34] refinement package using least-squares minimization.ORTEP-3 for Windows [35] and Mercury [36] were used to display the stereo diagram and packing display.
The crystal crystallised in the monoclinic P21/n space group, with eight molecules in the unit cell, and the asymmetric unit comprised two independent molecules (A and B) stacked in an inverted orientation (Fig. 1).The phenyl rings of molecules A (C2-C7) and B (C15-C20) have a dihedral angle of 15.5(3)°, whereas the oxazole rings of molecules A and B have a dihedral angle of 5.4(3)°, indicating that both molecules (A and B) appear to be nearly coplanar with each other, and the oxazole and phenyl rings within the molecule have dihedral angles of 14.The packing in the crystal assumes a layer-like arrangement when viewed along the b-axis, as seen in Fig. 2, and the molecules adopt an extended conformation evident from the torsion angles of C11-03-C12-C13=177.2(7)°andC24-07-C25-C26=169.5(8)°respectively for molecules A and B. Further, the crystal packing along the layers is stabilised by intermolecular C-H• • •O hydrogen bonding and intermolecular O-C interaction with a bond distance of 3.22 Å between the molecules also between the layers, intermolecular C-H• • •N and C-H• • •O hydrogen bonding contribute to the stacking arrangement.In addition, the bromine atoms in molecules A and B interact with nitrogen, hydrogen, and oxygen atoms to stabilise the layered packing.Table 2 provides the crystallographic data and structure refinement statistics, and Tables 3 and 4 provide the bond length and bond angle information.

Refinement
All non-hydrogen atoms were refined using anisotropic thermal parameters.All the H atoms were placed in the calculated positions with C-H= 0.93 Å to 0.97 Å and allowed to refine the structure in riding motion approximations, in which Uiso was tied to the carrier atom, with fixed isotropic displacement parameters: Uiso (H)=1.5Ueq(C)for methyl groups and Uiso (H)=1.2eq(C) for C aromatic.

Hirschfeld Surface Analysis
Hirschfeld surface analysis [37] and two-dimensional fingerprint plots [38] were generated using Crystal Explorer 17.5 [39], which indicated significant interactions based on the d i and d e plots.Here, d i (along the X-axis) and d e (along the Y-axis) represent the closest internal and external distances on the Hirschfeld surface.The Hirschfeld surfaces of the title compound (II) were mapped over the d norm (a), shape index(b), and curvedness index(c).The shape index plot shows π-π stacking interactions, whereas the curvedness plots show surface patch characteristics of planar stacking (Fig. 3).In the two-dimensional fingerprint plot, the frequency of occurrence of the (d i d e ) pair is shown in blue, and the grey colour corresponds to the outline of the full fingerprint [42].The fingerprint plots of compound II (Fig. 4) revealed that

Conclusion
Ethyl 5-bromo-2-(4-methoxyphenyl) oxazole-4-carboxylate was synthesized using the method depicted in Scheme I and crystallized using Petroleum ether and ethyl acetate (95:5) solution.Further molecules were characterized by TLC, melting point, IR, NMR, and mass spectroscopy.The asymmetric unit with two molecules was stabilized by C-H. . .O and C-H. . .N intramolecular hydrogen bonding and C-H. . .O intermolecular hydrogen bonding along with π-π stacking interactions offered by the sp 2 hybridized carbons.Furthermore, the Hirschfeld surface analysis revealed that, in the lattice, H•••H (34.4%) was the most prevalent interaction, while C•••C interactions contributed the least to the intermolecular interaction profile, with a contribution of 2.5% in the entire lattice.

Acknowledgements
The authors are thankful to the funding agency DST-SERB, Govt. of India, for providing financial assistance through their project (EMR/2016/005711) dated August 7, 2017, and to Birla Institute of Technology, Mesra, Ranchi, India, for providing the

Scheme 1 .
Scheme 1.Reagents and conditions for the synthesis of Scheme 1.

Figure 1 .
Figure 1.ORTEP diagram of compound II with ellipsoids at the 50% probability level.

Figure 2 .
Figure 2. (a).Crystal packing of compound II along the b-axis (b).Close view of inter-& intra-molecular interactions made by the asymmetric unit atoms, only those H atoms are shown which are involved in bond formation.(as viewed in the Mercury program)

Figure 3 .
Figure 3. Hirschfeld surfaces of compound (II) mapped over dnorm(a), shape index(b), and curvedness index(c) Intermolecular interactions are shown by red-coloured areas [40, 41].Short interatomic interactions, like hydrogen bonds, are indicated by dark red colour on the d norm surface, while light red indicates other intermolecular interactions.In the two-dimensional fingerprint plot, the frequency of occurrence of the (d i d e ) pair is shown in blue, and the grey colour corresponds to the outline of the full fingerprint[42].The fingerprint plots of compound II (Fig.4) revealed that H•••H (34.4%) was the most prevalent interaction among all other interactions in the compound of interest.Further, the contributions follow the following order in the entire lattice, O•••H (20.1%) > C•••H (12.3%) > Br•••H (10.3%) > N•••H (3.7%) > C•••C (2.5 %).The C•••C interactions correspond to the small π-π stacking interactions observed between the sp 2 hybridized (C4-C22 and C3-C24) carbons of molecules A and B.
1H NMR and13C NMR spectra of the title compound were

Table 2 .
Crystallographic data X-ray data collection and structure refinement statistics for the structure C 13 H 12BrNO 4

Table 3 .
Selected bond lengths d (Å) of compound II