untitled European Journal of Chemistry 2 (1) (2011) 58‐60 European Journal of Chemistry ISSN 2153‐2249 (Print) / ISSN 2153‐2257 (Online)  2011 EURJCHEM DOI:10.5155/eurjchem.2.1.58‐60.350 European Journal of Chemistry Journal homepage: www.eurjchem.com Synthesis, characterization and crystal structure of 2‐(4‐(methylthio)phenyl)‐1H‐benzo[d]imidazole Mohamed Ziaulla, Maralavadi Nagaraju Manjunatha, Kuderu Rajendraswamy Nagasundara and Noor Shahina Begum* Department of Chemistry, Bangalore University, Bangalore, IN‐560001, India *Corresponding author at: Department of Chemistry, Bangalore University, Bangalore, IN‐560001, India. Tel.: +91.80.22961344; fax: +91.80.22961331. E‐mail address: noorsb@rediffmail.com (N.S. Begum). ARTICLE INFORMATION ABSTRACT Received: 25 October 2010 Received in revised form: 04 December 2010 Accepted: 05 December 2010 Online: 31 March 2011 KEYWORDS An efficient synthesis of the title compound, 2‐(4‐(methylthio)phenyl)‐1H‐benzo[d]imidazole, was carried out by the condensation reaction of o‐phenylenediamine and p‐thiomethyl benzaldehyde in benzene. The structure was confirmed by spectroscopic data and elemental analyses. The molecular structure was determined from single crystal X‐ray diffraction data. The compound crystallizes in the orthorhombic space group Pbca with a = 8.544(2) Å, b = 9.700(3) Å, c = 29.684(8) Å, V = 2460.0(11) Å3, Z = 8. The crystal structure is stabilized by intermolecular C‐H…N, N‐H…N and ‐ interactions. 2‐(4‐(methylthio)phenyl)‐1H‐benzo[d]imidazole Benzimidazole Crystal structure Hydrogen bond ‐ Interactions Spectroscopy 1. Introduction Benzimidazoles and their derivatives exhibit a number of important pharmacological properties, such as antihistaminic [1], anti‐ulcerative [2], antiallergic [3], and antipyretic [4]. In addition, benzimidazole derivatives are effective against the human cytomegalovirus (HCMV) [5] and are also efficient selective neuropeptide Y Y1 receptor antagonists [6]. Most of the described methods for the synthesis of benzimidazoles make use of volatile organic solvents and involve solid‐phase synthesis via o‐nitroanilines [7‐10] or the condensation of o‐phenylenediamines with carboxylic acid derivatives [11], aldehydes [12‐17] and aryl halides [18]. We report herein the synthesis, structure and characterization of 2‐(4‐(methylthio)phenyl)‐1H‐benzo[d] imidazole. 2. Experimental 2.1. Materials and physical measurements All the chemicals were reagent grade; they were used as such without further purification. The solvents (methanol, ethanol, etc.) were purified according to the standard methods. The FT‐IR spectra in KBr pellet was recorded on a Nicolet impact 400D spectrometer in the range 4000‐400 cm‐1. The 1H NMR spectra in CDCl3 (using TMS as internal reference) was recorded on a Bruker 400 MHz spectrometer. The mass spectrum was recorded using Z‐spray electrospray ionization (ESI) source on Esquire 300 plus, Bruker Daltonics. The melting point was obtained using an electrothermal melting point apparatus. Elemental analysis is carried out using elementar‐ Vario EI III and Carlo Erba‐1108 instruments. 2.2. X‐ray analysis and refinement The X‐ray diffraction data for the compound 3 was collected on a Bruker Smart CCD Area Detector System, using MoK (λ=0.71073 Å) radiation for the crystal. Intensity data were collected up to a maximum of 26.37° in the –ф scan mode. The data were reduced using SAINTPLUS [19]. The structure was solved by direct methods using SHELXS97 [20] and difference Fourier synthesis using SHELXL97 [20]. The positions and anisotropic displacement parameters of all non‐ hydrogen atoms were included in the full‐matrix least‐square refinement using SHELXL97 [20] and the procedures were carried out for a few cycles until convergence was reached. A total of 17827 reflections were collected, resulting in 2520 [Rint = 0.0847] independent reflections of which the number of reflections satisfying I>2σ(I) criteria was 1382. These were treated as observed. The H atoms were placed at calculated positions in the riding model approximation (C‐H = 0.93 Å), with their temperature factors were set to 1.2 times those of the equivalent isotropic temperature factors of the parent atoms. All other non‐H atoms were refined anisotropically. The R factor for observed data finally converged to R = 0.0736 with wR2 = 0.1351 in the compound. The maximum and minimum values of residual electron density were 0.188 and ‐0.156 eÅ‐3. Molecular diagrams were generated using ORTEP [21]. The mean plane calculation was done using the program PARST [22]. Ziaulla et al. / European Journal of Chemistry 2 (1) (2011) 58‐60 59 Figure 1. Molecular structure of the title compound with the atomic‐numbering scheme. Displacement ellipsoids plotted at 50% probability level. Dotted line indicates intramolecular C4‐H4…N2 interaction. 2.3. Synthesis A mixture of o‐phenylenediamine (10 mmol) and p‐thio‐ methylbenzaldehyde (10 mmol) in benzene (100 mL) was refluxed for 2 h in a steam bath. On standing overnight yellow crystalline solid precipitated (Scheme 1). The yellow solid product formed was separated by filtration and washed with a mixture of water and n‐hexane. It was recrystallised from ethanol to get pale yellow crystals and then dried in vacuum over P2O5. The yellow product is produced in 90% (2.34 mg) yield. M.p.: 115 oC. FT‐IR (cm‐1): 1604 (C=N), 1471 (N‐H), 1331 (C‐N). 1H NMR (MeOH, 400 MHz, δ ppm): 7.989 (d, J=10.8 MHz, 2H), 7.575 (m, 2H), 7.378 (d, J=8.8 MHz, 4H), 7.224 (m, 2H), 4.82 (s, 1H), 2.533 (s, 3H). ESI‐MS (m/z): 240 (M++1). Anal. Calcd. for C14H12N2S.: C, 70.01; H, 5.04; N, 11.66; S, 13.32. Found: C, 69.71; H, 4.32; N, 12.41; S, 12.95.   Scheme 1 3. Results and discussion The various bands seen in the IR spectrum of compound 3 have been assigned to the bending modes of vibration of different groups present in the organic compound. The band at 3441 cm‐1 due to the stretching vibration of NH2 in o‐ phenylenediamine is not observed in the IR spectrum of compound 3. This implies the formation of compound 3 formation of compound 3 via a condensation reaction between o‐phenylenediamine and p‐methoxybenzaldehyde. A strong C=N stretching band in the IR spectrum of compound 3 seems to occur at around 1604 cm‐1. In the 1H NMR spectrum the singlet for the thiomethyl protons appeared at δ 2.53 ppm and the characteristic broad singlet for the proton of N1 appeared at δ 4.82 ppm. The signals for the aromatic protons were also noted in Section 2.3. Figure 1 shows the ORTEP diagram of the molecule with thermal ellipsoids drawn at 50% probability of the title compound. Table 1 gives the crystal data and the structure refinement. Selected bond lengths and bond angles are presented in Table 2. All non‐bonded interactions are tabulated in Table 3. The benzimidazole and thiomethyl phenyl groups are non‐planar with a dihedral angle of 26.73(2)° between them. The thiomethyl group is cis to benzimidazole ring. The molecular structure is primarily stabilized by a weak intramolecular C4‐H4…N2 hydrogen bond [C4‐H4 = 0.930 Å, H4…N2 = 2.702(3) Å, C4…N2 = 2.969(5) Å and the angle C4‐ H4…N2 = 97.41(3)°] leading to the formation of a pseudo‐five‐ membered hydrogen‐bonded pattern (S(5) according to Etter’s graph set analysis [23,24]). This pseudo‐five‐membered ring locks the molecular conformation and eliminates confor‐ mational flexibility. The bond lengths and angles for the benzimidazole moiety of the molecule are in good agreement, within experimental errors, with those observed in other benzimidazole derivatives [25‐31]. The N1‐C2 and N2‐C2 distances were found to be 1.356(4) Å and 1.325(4) Å, respectively. The cis orientation of the thiomethyl group and phenyl ring is characterized by the torsion angle C5‐C6‐S1‐C7 = 16.6(4)° in the molecule. Additionally, the crystal structure is stabilized by intermolecular [C‐H…N and N‐H…N] bonds. The C4‐H4…N1 and N1‐H1…N2 interactions together generates bifurcated hydrogen bonds from two donors, C4 and N2, to the same acceptor, N1. These bifurcated hydrogen bonds link the dimers into zig‐zag tapes along the crystallographic ‘a’ axis (Figure 2). Additionally, the supramolecular assembly is further stabilized by ‐ stacking interactions between the benzimidazole and thiomethyl phenyl rings (Figure 3). The C8…C14 (‐1+x, y, z) disposed at a distance of 3.742(5) Å. Figure 2. Packing diagram of 3 viewed along the ‘a’ axis. Dotted lines indicates C4‐H4…N1 and N1‐H1…N2 intermolecular interactions. Figure 3. View of the molecular packing in 3, showing π‐π stacking interactions between the benzimidazole and thiomethyl phenyl rings. 60 Ziaulla et al. / European Journal of Chemistry 2 (1) (2011) 58‐60 Table 1. Crystal data and structure refinement for compound 3. Empirical formula C14H12N2S Formula weight 240.32 Temperature 293(2) K Wavelength 0.71073 Å Crystal system, space group Orthorhombic, Pbca Unit cell dimensions a = 8.544(2)Å b = 9.700(3) Å c = 29.684(8) Å Volume 2460.0(11) Å3 Z 8 Calculated density 1.298 Mg/m3 Absorption coefficient 0.241 mm‐1 F(000) 1008 Crystal size 0.40 x 0.35 x 0.30 mm Theta range for data collection 1.37 to 26.37° Limiting indices ‐10 ≤ h ≤ 10 ‐12 ≤ k ≤ 11 ‐36 ≤ l ≤ 37 Reflections collected / unique 17827/2520 [R(int) = 0.1166] Completeness to theta 26.37 100.0 % Refinement method Full‐matrix least‐squares on F2 Data / restraints / parameters 2520 / 0 / 155 Goodness‐of‐fit on F2 0.962 Final R indices [I>2sigma(I)] R1 = 0.0736, wR2 = 0.1351 R indices (all data) R1 = 0.1496, wR2 = 0.1676 Largest diff. peak and hole 0.188 and ‐0.156 e. Å‐3 Measurement Bruker SMART CCD diffractometer Program system SAINTPLUS Structure determination Direct methods (SHELXL97, SHELXS97) Molecular graphics ORTEP‐3 (Farrugia, 1997) CCDC 763065 Table 2. Selected geometric parameters (Å, °) for 2‐(4‐(methylthio)phenyl)‐ 1H‐benzo[d]imidazole. Bond lengths C1‐N1 1.373(4) C6‐C8 1.393(5) C1‐C11 1.384(5) C6‐S1 1.764(4) C1‐C10 1.394(5) C7‐S1 1.771(5) C2‐N2 1.325(4) C8‐C9 1.370(5) C2‐N1 1.356(4) C10‐C14 1.390(5) C2‐C3 1.463(5) C10‐N2 1.397(4) C3‐C4 1.384(5) C11‐C12 1.379(5) C3‐C9 1.394(5) C12‐C13 1.389(5) C4‐C5 1.382(5) C13‐C14 1.370(5) C5‐C6 1.385(5) Bond Angles N1‐C1‐C11 132.0(3) C8‐C6‐S1 117.1(3) N1‐C1‐C10 105.6(3) C9‐C8‐C6 120.7(4) C11‐C1‐C10 122.4(3) C8‐C9‐C3 121.1(4) N2‐C2‐N1 112.4(3) C14‐C10‐C1 120.1(3) N2‐C2‐C3 124.5(3) C14‐C10‐N2 130.4(3) N1‐C2‐C3 123.1(3) C1‐C10‐N2 109.5(3) C4‐C3‐C9 118.0(3) C12‐C11‐C1 116.6(3) C4‐C3‐C2 120.7(3) C11‐C12‐C13 121.5(3) C9‐C3‐C2 121.3(3) C14‐C13‐C12 121.8(4) C5‐C4‐C3 121.3(3) C13‐C14‐C10 117.6(3) C4‐C5‐C6 120.4(4) C2‐N1‐C1 107.6(3) C5‐C6‐C8 118.6(3) C2‐N2‐C10 104.9(3) C5‐C6‐S1 124.3(3) C6‐S1‐C7 103.1(2) Table 3. Non‐bonded interactions and possible hydrogen bonds (Å, °) for compound 3 (D‐donor; A‐acceptor; H‐hydrogen). D—H···A D—H H···A D···A D—H···A C4‐H4…N2 0.930(4) 2.702(3) 2.969(5) 98 C4‐H4…N1 0.930(4) 2.948(3) 3.446(4) 115 N1‐H1…N2 0.860(3) 2.023(3) 2.856(4) 162 Acknowledgement The authors are thankful to the University Grants Commission, India for the financial assistance and Department of Science and Technology, India for data collection on the CCD facility. Our sincere thanks are due to the Raman Research Institute, Bangalore, for the elemental analysis and to the NMR Research Centre, Indian Institute of Science, Bangalore, for NMR spectra. Our thanks are also due to Prof. D. N. Sathyanarayana and Prof. T. N. Guru Row, Indian Institute of Science, Bangalore for their valuable suggestions. The authors also thank M. S. Ramaiah Institute of Technology, Bangalore, for their support and encouragement. Supplementary material CCDC‐763065 contains the supplementary crystallographic data for this paper. 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