Ali Soulozi Seye Hami Reza Shojaei Ali Ramazani Katarzyna ?lepokura Taeusz Lisa (Department of Chemistry, Urmia Branh, Islami Aza University, P. O. Box 969, Urmia, Iran) (Department of Physis, Urmia Branh, Islami Aza University, P. O. Box 969, Urmia, Iran) (Department of Chemistry, Zanjan Branh, Islami Aza University, P. O. Box 49195-467, Zanjan, Iran) (Faulty of Chemistry, University of Wro?aw, 14 Joliot-Curie St., 50-383 Wro?aw, Polan)

1 INTRODUCTION

The thiazoles and their derivatives have attracted the attention of chemists for many years[1-2]. Thiazole derivatives occur widely in a range of natural products. For example, the thiazolium ring present in vitamin B1serves as an electron sink, and its coenzyme form is important for the decarboxylation of αketo acids[3]. Thiazoles and their derivatives are known to exhibit pharmacological activity. Among them, antimicrobial, antihistaminic, antiparasitic,antihelminthic, antipyretic, and antiviral preparations were found[4-9]. Aryl-substituted thiazoles are important organic functional materials such as fluorescent dyes and liquid crystals. Thiazole orange is used as fluorescent intercalator for determining DNA binding affinity and sequence selectivity of small molecules[10]. Due to their broad utility in the pharmaceutical industry[11-17], the development of novel methods for the synthesis of 2-aminothiazoles would provide additional lead molecules for drug discovery. Herein we report the synthesis and crystal structure of new derivative of 2-aminothiazole,methyl 2-(diphenylamino)-4-phenyl-1,3-thiazole-5-carboxylate.

2 EXPERIMENTAL

2.1 Reagents and physical measurements

Starting materials and solvents were obtained from Merck (Germany) and Fluka (Switzerland) and were used without further purification. TLC and NMR indicated no side product. Melting points were measured on an Electrothermal 9100 apparatus and were uncorrected. IR spectra were measured on a Shimadzu IR-460 spectrometer.1H and13C NMR spectra were measured (CDCl3solution) with a Bruker DRX-300 AVANCE spectrometer at 300.13 and 75.467 MHz, respectively. Elemental analyses were performed using a Heraeus CHN-O-Rapid analyzer. Flash chromatography columns were prepared from Merck silica gel powder.

2.2 Preparation of the title compound

To a stirred solution of benzoyl isothiocyanate (1,0.163 g, 1 mmol) and diphenylamine (2, 1 mmol) in dry CH2Cl2(5 mL) was added dropwise a mixture of dimethyl acetylenedicarboxylate (1 mmol) in dry CH2Cl2(3 mL) at room temperature over 2 min.after 0.5 h and silica gel powder (2 g), and the solvent was evaporated. The dry materials were heated for 1 h at 90 ℃ and then placed over a column of silica gel (10 g). The column chromatography was washed using ethyl acetate/light petroleum ether (2:10) as an eluent. The solvent was removed under reduced pressure and the products were obtained. Yellow crystal, yield 84%, m. p.: 212.1–212.6 ℃ Elemental Anal. Calcd. (%) for C23H18N2O2S (386.47): C, 71.48; H, 4.69; N, 7.25.Found (%): C, 71.06; H, 4.71; N, 7.21. IR (KBr): v 3064, 2951, 1704, 1338, 1246 cm-1.1H NMR(CDCl3, 300 MHz): δ 3.71 (s, 3H, CH3); 7.30–7.32(m, 2H, arom CH); 7.36–7.49 (m, 11H, arom CH);7.77–7.81(m, 2H, arom).13C NMR (CDCl3, 62.5 MHz): δ 51.70 (CH3); 126.15, 126.86, 127.57,128.80, 129.74 (15CH, arom); 126.78, 129.04,129.93, 133.72, 144.14 (5C); 170.05 (C=O).

Single crystals of the title compound were prepared by using the branch tube method in nhexane/ethyl acetate (10:1) solvent at 45 ℃ during a week. The yellow crystals were filtered off, washed with cold n-hexane and dried at r. t.

2.3 Computational details

The structure was optimized using DFT, along with the B3LYP functional and the 6-31G basis set.At this stage, we would like to recall that, compared with experiment or benchmark theoretical results,the B3LYP predictions for bond lengths and bond angles are generally superior to the MP2 ones[18].Indeed, the B3LYP approach is known to provide structural as well as harmonic vibrational frequencies of quality comparable to the CCSD(T) level[19]above the described calculations which have been performed using the Gaussian 03 package of programs[20].

2.4 Crystal structure determination

The crystallographic measurement for 4 was performed on a κ-geometry Xcalibur PX four-circle diffractometer with a graphite-monochromatized Mo-Kα radiation (ω and φ scans). Data were corrected for Lorentz and polarization effects. Data collection,cell refinement, and data reduction and analysis were carried out with the Xcalibur PX soft-ware,CRYSALIS CCD and CRYSALIS RED, resp.[21]. Empirical absorption correction was applied to the data with the use of CRYSALIS RED. The structure was solved by direct methods with the SHELXS-97 program[22], and refined using SHELXL-97[22]with anisotropic thermal parameters for non-hydrogen atoms.The H atoms were found in difference Fourier maps.In the final refinement cycles, they were treated as riding atoms in geome-trically optimized positions,with C–H = 0.95–0.98 ? and Uiso(H) = 1.2Ueq(CH)or 1.5Ueq(CH3).

The figures presenting the molecular structure of 4 were made using the DIAMOND program[23]. A summary of the conditions for data collection and structure refinement parameters is given in Table 1.

3 RESULTS AND DISCUSSION

As shown in Scheme 1, the benzoyl isothiocyanate (1), diphenylamine (2) and dimethyl acetylenedicarboxylate (3) underwent a smooth 1:1:1 addition reaction in the presence of SiO2at 90 ℃ to afford the methyl 2-(diphenylamino)-4-phenyl-1,3-thiazole-5-carboxylate (4) in fairly good yield (Scheme 1).The structure of the product was deduced from its IR,1H NMR,13C NMR, and elemental analysis.

The structure of compound 4 was finally confirmed by a single-crystal X-ray structure determi-nation. The overall molecular structure of methyl 2-(diphenylamino)-4-phenyl-1,3-thiazole-5 carboxylate in the solid state (Fig. 1, Table 1) is similar to that of the diisopropylamino analogue reported by us recently[24]. The COOMe group is planar and is almost coplanar with the plane of the thiazole ring,and the molecule has the C=O,S anti-periplanar conformation (see C(5)–O(1)–C(4)–C(3) and S(1)–C(3)–C(4)–O(2) torsion angles in Table 2). Due to the conjugation of exocyclic N(2) atom lone pair with the thiazole system, giving rise to the partial double-bond character of the C(1)–N(2) bond(1.372(2) ? vs. 1.431(2) and 1.445(1) ? for C(12)–N(2) and C(18)–N(2), resp.) and the formal sp2hybridization of N(2), atoms N(2), C(12) and C(18)form planar moiety, which is coplanar with the thiazole ring. Similar to diisopropylamino analogue,atom N(2) in 4 deviates only slightly (at 0.009 ?)from the plane defined by C(1), C(12) and C(18),which is coplanar with the thiazole ring plane(intersection angle of 3.9(1)°). In contrast, the C(6)–C(11) phenyl ring is inclined to a much larger extent(at 40.4(1)°) to the thiazole ring, which is again the common feature of 4 and its diisopropylamino analogue (see also N(1)–C(2)–C(6)–C(11) torsion angle in Table 2). The two N(2)-bonded phenyl rings(C(12)–C(17) and C(18)–C(2)) are almost perpendicular to each other (inter-plane angle of 89.6(1)°),and orientation of one of them relative to the thiazole ring is accompanied by the intramo-lecular C–H··N contact, as show in Fig. 1.

Table 1. Crystallographic Data of Compound 4

Scheme 1. Chemical synthesis of the title compound, C23H18N2O2S

Fig. 1. X-ray structure of 4 showing the atom-numbering scheme and symmetry-independent C–H··N contact (dashed line). Displacement ellipsoids are drawn at the 50% probability level

Data given in Table 2 as well as the calculated structure shown in Fig. 2 reveal some similarity between the experimental and theoretical molecular structures of compound 4. The calculated molecule is also the C=O,S anti-periplanar conformer (C(5)–O(1)–C(4)–C(3) and S(1)–C(3)–C(4)–O(2) torsion angles of –179.73° and –177.67°, resp.), with sp2-hybridized N(2) atom of planar environment, and the two N(2)-bonded phenyl rings (C(12)–C(17) and C(18)–C(23)) oriented almost perpendicularly to each other (inclined at about 84°). However, the C(6)–C(11) phenyl ring is twisted at as little as –12°relative to the thiazole ring, which is the main difference between the calculated and solid-state structure of 4. In addition, S(1)–C(1) and S(1)–C(3) bond distances are almost 0.1 ? longer in the calculated structure.

In the crystal lattice, two adjacent molecules of 4,related by the action of an inversion centre, are joined to each other by the set of intermolecular contacts of C–H··O and C–H··π type (Table 3) to form centrosymmetric molecular dimers, as shown in Fig. 3. The thiazole rings in the molecules forming the dimer, i.e. at (x, y, z) and (–x+2, –y+1,–z+1), are parallel, with the centroids separation of 3.812(2) ? and the interplanar spacing of 3.6402(3)?, giving a centroid offset of 1.130 ?, which suggests that a π··π stacking interaction within the dimer could not be excluded. A direct c-axis translation generates the infinite ribbons of dimers via C–H··S interactions linking every dimer with one another (Fig. 4, Table 3).

Table 2. Selected Geometric Parameters (X-ray and Theoretical; ?, °) for 4

Table 3. Geometry of Proposed C–H··S/N/O/π Close Contacts for 4

Fig. 2. Theoretical geometric structure of 4

Fig. 3. Molecular dimmer formed by two molecules of 4 related by a centre of inversion, linked by the set of intermolecular interactions of C–H··O (blue thick dashed lines), C–H··π and π··π (blue thin dashed lines) types. Orange dashed lines – intramolecular C–H··N contacts. H atoms not involved in hydrogen bonding have been omitted for clarity. Symmetry codes are given in Table 3

Fig. 4. Arrangement of molecular dimmers of 4 within the ribbons along the c axis. Blue thick dashed lines represent intermolecular C–H··S contacts, orange dashed lines – intramolecular C–H··N bonds. H atoms not involved in hydrogen bonding have been omitted for clarity. Symmetry codes are given in Table 3

Acknowledgment

This work was supported by the Islamic Azad University, Urmia Branch Research Council.

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