Steric group enforced aromatic cyclic trimer conformer in tripodal molecules

Abstract

A family of tripodal molecules (1–6) with/without steric ethyl groups at the central benzene scaffold and with furan/thiophene/pyridyl group at the 2-position of the benzimidazolyl unit was synthesised. Compounds 1–6 were characterized by elemental analysis and NMR spectroscopy. Compounds 1, 3, and 5 were further characterized by single crystal X-ray diffraction analysis. The molecular structures of 1 and 4 were optimized using density functional theory (DFT) calculations. X-ray and ¹H NMR studies reveal that the introduction of three ethyl groups into a central benzene scaffold of furan/thiophene/pyridyl substituted benzimidazolyl based tripodal molecules enhances the edge-to-face C–H⋯π interactions, thereby favouring the aromatic cyclic trimer motif, in solution and the solid state. The unsubstituted central benzene scaffold allows the furan/thiophene substituted benzimidazolyl units in the tripodal molecules to move freely thereby weakening the edge-to-face C–H⋯π interactions between the aromatic cyclic trimer motif. Molecular modelling calculations indicate that the energy minimized structures of the tripodal molecules adopt a symmetric cyclic aromatic motif conformation.

---

Introduction

Non-covalent aromatic motifs between heterocyclic units/phenylene units via the face-to-face π⋯π, and the edge-to-face C–H⋯π interactions make important contributions to biomolecular structures and functions.^1–3 Among several man-made molecules with aromatic motifs including dimers, trimers (ladder and cyclic clusters), tetramers, pentamers and higher order clusters, discrete molecules with aromatic cyclic trimer motif structures (Fig. 1), in solution or even in the solid state are very limited.^4–6 Due to the presence of aromatic cyclic trimer motif in half of all proteins and such motif is thought of as the basic building unit of higher order clusters, efforts are being directed toward the synthesis of molecule with aromatic cyclic trimer motif.^4–6

Fig. 1 Aromatic cyclic trimer.

Recently, two tripodal molecules (1,3,5-tri(2-(furan-2-yl)benzimidazol-1-ylmethyl)-2,4,6-trimethylbenzene (I), and 1,3,5-tri(2-(thiophen-2-yl)benzimidazol-1-ylmethyl)-2,4,6-tri methyl benzene (II) (Fig. 2)), possessing the benzene cyclic trimer motif, which is stabilized by the edge-to-face C–H⋯π interactions, both in solution and solid state were reported by us.⁶ The studies on I, and II indicate that the heterocyclic moiety at the 2-position of the benzimidazolyl (bim) enforces the three benzimidazolyl units to form the benzene cyclic trimer.⁶ In order to explore further and make library of discrete aromatic cyclic trimer, molecules I and II were sterically modified both at the central benzene scaffold and at the 2-position of the benzimidazolyl unit.

Fig. 2 Chemdraw structures of tripodal molecules.

Herein, six new tripodal molecules 1,3,5-tri(2-(furan-2-yl)benzimidazol-1-ylmethyl)-2,4,6-triethylbenzene (1), 1,3,5-tri(2-(furan-2-yl)benzimidazol-1-ylmethyl)-benzene (2), 1,3,5-tri(2-(thiophen-2-yl)benzimidazol-1-ylmethyl)-2,4,6-triethyl-benzene (3), 1,3,5-tri(2-(thiophen-2-yl)benzimidazol-1-ylmethyl)-benzene (4), 1,3,5-tri(2-(pyridyl-2-yl)benzimidazol-1-ylmethyl)-2,4,6-triethylbenzene (5), and 1,3,5-tri(2-(phenyl)benzimidazol-1-ylmethyl)-2,4,6-triethylbenzene (6) are reported (Fig. 2). Molecules 1–6 were characterized by elemental analysis, nuclear magnetic resonance (NMR) spectroscopy. The molecular structures of 1, 3 and 5 were further confirmed using single-crystal X-ray diffraction (XRD) analysis. The molecular structures of 1 and 4 were optimized using density functional theory (DFT) calculations.

Results and discussion

Preparations

Molecules 1–6 were prepared by the treatment of substituted benzimidazole (2-(furan-2-yl)-1H-benzimidazole (H-fbim) for 1-2; 2-(thiophen-2-yl)-1H-benzimidazole (H-tbim) for 3-4; 2-(pyridyl-2-yl)-1H-benzimidazole (H-pbim) for 5; 2-(phenyl)benzimidazole (H-phbim) for 6) and 1,3,5-tri(bromomethyl)-2,4,6-triethylbenzene or 1,3,5-tri(bromomethyl)-benzene and KOH in DMF (Scheme 1).^6–9 All molecules are air and moisture stable and soluble in organic solvents.

Scheme 1 Synthesis of 1–6 (X = O/S, Y = N/CH and R = CH₂CH₃/H).

Single crystal X-ray diffraction studies

The results of single-crystal X-ray studies showed that 1, 3 and 5 adopt a syn-conformation i.e., ababab-type with three benzimidazolyl (bim) units on one side of the central benzene scaffold and three furan/thiophene/pyridyl and three methyl groups on the other side (Fig. 3, 4 and S1 in ESI†). Three benzene of bim rings are arranged in an almost the edge-to-face arrangement with the benzene edge directed over the centre of mass (COM) benzene ring of an adjacent benzene unit of bim. Three benzene of the bim contact each other through the C–H⋯π interactions (Table 1).¹ The distances between the COM of the benzene ring of bim units and the dihedral angles between the bim units are within the range for the symmetrical benzene cyclic trimer motif.¹

Fig. 3 Molecular structure of 3 (top-left, H atoms are removed). Cyclic aromatic trimer motif in 3 (top-right, a/b/c = COM of benzene, H atoms and other units are omitted). Two different views of 3 (bottom). The carbon atoms of each tbim are colored differently. C = gray, green, turquoise, pink; N = blue; S = yellow; H = white.

Fig. 4 Molecular structure of 5 (left: H atoms are removed). Cyclic aromatic trimer motif in 5 (right: H atoms and other units are omitted). C = gray, N = blue.

Table 1 Two geometrical parameters (r, Å = distance between the COM of benzene of benzimidazolyl residues; τ° = dihedral angle between the benzimidazolyl units) in the X-ray structures 1, 3, and 5. 1a is optimized structure of 1

	1	1a	3	5
rab	5.13	5.74	5.09	5.30
rbc	5.19	5.77	5.40	5.07
rac	5.06	5.76	5.43	4.97
τab	64	60	65	56
τbc	54	59	59	62
τca	61	60	55	62

---

The major difference between 1 and 3 is in the orientation of five-member aromatic ring (furan/thiophene). The bim and furan unit in 1 are almost planar. The oxygen atom of furan ring is directed toward the methylene unit (furan-CH₂-central benzene), and contacts with the CH₂ through the hydrogen bonding interaction. The sulfur atoms are directed away from each other and the centre of the molecule in 3 similar to the thiophene arrangement found in II.⁶ Each molecule in 1 interacts with three neighbouring molecules using three fbim units. The intermolecular offset face-to-face π⋯π interactions were found between the anti-cofacially arranged fbim units in 1 (Fig. S1 in ESI†).

¹H NMR studies

The ¹H NMR spectrum of 1 in d₆-DMSO (Fig. 5) displayed well-separated, and a single set of signals for furan protons (H^3′–H^5′) and H⁴ and H⁵ protons of benzimidazolyl (bim). The H⁶ and H⁷ protons of benzene of bim are merged together in 1. A single sharp peak at δ 5.65 ppm corresponds to the methylene (–CH₂–) protons. Among the furan protons, the H^3′ and H^4′ were slightly shifted downfield in 1 compared to the free fbim. No significant shift was observed for the H^5′ proton. The H⁴ and H⁵ protons of bim were slightly upfield shifted, whereas the H⁶ and H⁷ were remarkably upfield shifted in 1 compared to the free fbim. A single set of chemical resonances for all protons of 1, revealing the presence of a single conformer, preferably syn-conformer or the presence of syn-conformers (c and d in Fig. 6), that undergo a rapid equilibrium in solution on the NMR time scale.^6,10

Fig. 5 Partial ¹H NMR spectra of H-fbim, 2 and 1 in d₆-DMSO.

Fig. 6 Various possible conformers (a–d) for tripodal ligands due to different orientation of benzimidazolyl units. Ball represents substituted group on benzimidazolyl unit.⁶

From the X-ray structure of 1, upfield signals for the H⁶ and H⁷ due to the edge-to-face C–H⋯π interactions between three benzene units of bim would be expected. A similar ¹H NMR pattern for H⁶ and H⁷ was also observed in the case of methyl substituted tripodal molecule I.⁶ The result supports that the major conformer in solution retain the same structure as that found in the solid state. Other possibility is the presence of a mixture of syn-conformers (c and d in Fig. 6), which undergo a rapid equilibrium on the NMR time scale.⁶ It is important to compare the chemical resonances of H⁶ and H⁷ in the ethyl substituted 1 and the methyl substituted I, because other units are similar in both the molecules. The upfield shift value for H⁶ is a little higher in 1 than I, which suggested that the steric group on the central benzene of the tripodal molecules influences the orientation of cyclic aromatic trimer.

Molecule 3 in d₆-DMSO displays a similar ¹H NMR pattern like those of 1 with slight difference of chemical resonance for the H⁶ and H⁷ protons (Fig. 7 and S2 in ESI†). Both H⁶ and H⁷ signals are started to broaden, while these are as triplet and doublet in the free H-tbim and the methyl substituted tripodal molecule II. However, the H⁶ proton signal was more upfield shifted similar to 1. The result indicates that molecule 3 also adopts the cyclic aromatic trimer structure like those of I, II, and 1. The broadness of H⁶ and H⁷ resonance may be due to either the tbim unit oscillates back and forth slowly or the presence of mixture of syn-conformers, which undergo a slow equilibrium on the NMR time scale. Other protons of the tbim unit in 3 appeared as sharp signals.

Fig. 7 Partial variable temperature ¹H NMR spectra of 3 in d₆-DMSO.

In order to ascertain this, a variable temperature ¹H NMR experiment was performed for 1 and 3. A single set of well-resolved chemical resonances was observed for both 1 and 3 in d₆-DMSO at 50/100 °C. In particular, the H⁶ and H⁷ appeared as triplet and doublet with slight downfield shift at high temperature (Fig. 7 and S3†). At low temperature (−55 °C), the H⁶ and H⁷ protons of 1 were shifted upfield significantly in relative to room-temperature chemical resonances in CDCl₃ (Fig. S4†). No additional peaks were observed at −55 °C for compound 1. Compound 3 showed a single set of peaks for all the protons except H⁶ and H⁷ protons (Fig. S5†). Three sets of broad peaks were observed for H⁶ and H⁷ protons of 3. The results indicate that three types of syn-conformers exist in solution, which undergo rapid equilibrium at high temperature (50/100 °C), and slow equilibrium at low temperature (−55 °C). Further, the above results reveal that compounds 1 and 3 adopt syn-conformation in d₆-DMSO and CDCl₃.

The ¹H NMR spectra of 5 and 6 in d₆-DMSO (Fig. 8 and 9) indicate that these molecules adopt the cyclic aromatic trimer conformer in solution similar to 1 and 3. In addition, the methylene protons (–CH₂–) in 5 appeared in the aromatic region as a sharp singlet (δ 6.30 ppm) i.e. downfield shifted compare to the free H-pbim. Molecules I, II, 1–4 and 6 displayed chemical resonance for the methylene around δ ∼ 5.88–5.45 ppm. It suggests that the methylene protons might be involved in the hydrogen bonding interactions with the pyridyl nitrogen donor, thus shifting the methylene resonance to downfield. The known 1,3,5-tri(2-(pyridyl-2-yl)benzimidazol-1-ylmethyl)-2,4,6-trimethylbenzene (III)⁹ was synthesized using the similar route and studied to compare with 5. The ¹H NMR data of III (Fig. 8 middle) clearly indicates that the cyclic aromatic trimer motif present in the solution. This result also supports that the ethyl groups at the central benzene scaffold favour the formation of cyclic aromatic trimer motif.

Fig. 8 Partial ¹H NMR spectra of H-pbim, III and 5 in d₆-DMSO.

Fig. 9 Partial ¹H NMR spectra of H-phbim and 6 in d₆-DMSO.

The ¹H NMR spectrum of 2 (middle in the Fig. 5) possessing the unsubstituted benzene centre scaffold in d₆-DMSO displayed well-separated, and a single set of signals. The proton pattern of 2 is different from the tripodal molecules with substituted benzene centre scaffold I-II, 1, 3 and 5. The benzimidazolyl protons H⁴ and H⁵ are slightly downfield shifted, whereas the H⁷ and H⁶ are slightly upfield shifted in 2 compared to the free H-fbim. The protons H⁴ and H⁵ are little downfield shifted compare to 1, while H⁷ and H⁶ are highly downfield shifted. The single set of signals for all protons with a slight upfield shift for the H⁷ and H⁶ protons in 2 in comparison to free fbim may be due to the adoptation of 2 as a syn-conformer possessing the cyclic benzene trimer motif with the very weak edge-to-face C–H⋯π interactions between three benzene units. The furan protons (H³, H⁴, and H⁵) appeared in the upfield region in 2 compared to the free H-fbim. These protons H^3′, H^4′, and H^5′ were highly upfield shifted compared to 1. This may be due to either presence of the predominant syn-conformer with the cyclic benzene trimer above to the central benzene scaffold and cyclic thiophene trimer below to the benzene unit in solution or the mixture of two conformers, which undergo rapid equilibrium in the NMR time scale by tilting the furan benzimidazolyl units as shown in Fig. 10. Molecule 4 showed the similar ¹H NMR spectral pattern like that of 2 (Fig. S2 in ESI†).

Fig. 10 Two syn-conformers of 2 with the strong edge-to-face C–H⋯π cyclic benzene trimer (left) and without C–H⋯π cyclic benzene trimer interactions.

Computational studies of 1 and 4

A DFT experiment was performed for 1 and 4 to know the global minima of the energy structures. The tripodal molecule possessing ethyl substituent groups on the central benzene scaffold (1) adopt the highly symmetrical, cyclic aromatic trimer conformation with cone-shaped tripodal structure (Fig. S6†).

The optimized structure of unsubstituted central benzene scaffold based molecule 4 adopts a propeller like geometry with close to cylindrical shaped structure in which three benzimidazolyl residues are arranged in the edge-to-face arrangement with the benzene edge of benzimidazolyl located over the COM benzene ring of the adjacent benzimidazolyl units (Fig. 11). The average distance between the COM of three aromatic residues is ∼6.18 Å, suggesting that a weak edge-to-face C–H⋯π interaction is present in the cyclic benzene trimer motif.⁶ However, the cooperative C–H⋯π interactions in the trimer provide stabilization to the syn-conformer. Similarly, all three thiophene units are arranged in a cyclic manner with the COM distance of ∼10.35 Å.

Fig. 11 DFT energy minimized structure of 4 (left: H atoms are removed) The carbon atoms of each tbim are colored differently. (Distance_COM⋯COM Å: r_ab = 6.13, r_bc = 6.21, and r_bc = 5.91) C = black, green, turquoise, pink; N = blue; S = yellow; H = white.

Conclusions

A family of tripodal molecules possessing the cyclic aromatic trimer motif was synthesized using substituted benzimidazole and alkyl-substituted benzene scaffold. In addition, two tripodal molecules without alkyl substitution on the central core were also synthesized and studied. The results clearly confirm that the steric groups furan, thiophene, and pyridine at the 2-position of the benzimidazolyl and alkyl (methyl/ethyl) at the center of benzene scaffold play a role in arranging three benzimidazolyl units. The edge-to-face C–H⋯π interactions between the three benzene units stabilize the cyclic benzene trimer motif both in solution and the solid state. On going from methyl substituted to ethyl substituted at the benzene scaffold, the C–H⋯π interaction among the cyclic benzene trimer is strengthened. On the other hand, the molecule possessing furan/thiophene at the 2-position of benzimidazolyl with unsubstituted benzene scaffold favours syn-conformer structure with very weak/no C–H⋯π interactions between the trimer unit. The work demonstrates that discrete molecules with aromatic cyclic trimer motif arrangement both in solid and solution state can be designed and prepared. This work is part of our research aimed at designing the tripodal molecules with the aromatic cyclic trimer motif.

Experimental

General experimental methods

o-Phenylenediamine, 2-thiophenecarboxaldehyde, furan-2-carboxaldehyde, 1,3,5-tris(bromomethyl)-benzene, 1,3,5-tris(bromomethyl)-2,4,6-triethylbenzene (tbteb), mesitylene, 2-pyridyl-2-benzimidazole and dimethylformamide (DMF) were purchased from commercial sources and used as received. 2-Thiophene-2-benzimidazole 2-furan-2-benzimidazole and phenyl-2-benzimidazole were prepared following a similar procedure to that reported earlier (ESI S1–S3†). ¹H spectra were recorded on an JEOL ECX 400 NMR and Bruker AVANCEIII 400 and 500 MHz spectrometers operating at 400 MHz. The chemical shifts are reported in parts per million (ppm) relative to residual solvent signal. Melting points for compounds were recorded in BUCHI laboratory equipment-Melting point M-560.

Computational details

The geometry optimizations of 1 and 4 were carried out in the DMSO solvent medium using B3LYP method with 6-311+G (d,p)¹¹ basis set using Gaussian 09 program package.¹² The initial geometry for 1 was obtained from the X-ray crystal structure coordinates.

X-ray crystallography

Intensity data of suitably sized crystals 1 and 3 were collected on a Rigaku Saturn 724+CCD diffractometer for unit cell determination and three dimensional intensity data collection. 800 frames in total were collected at 120 and 150 K, respectively, with the exposure time of 18 s per frame. Data integration, indexing and absorption correction using Crystal clear followed by structure solution using the programs in WinGX module.^13a Intensity data of crystal of 5 were collected on Oxford CCD X-ray diffractometer (Xcalibur, Eos, Gemini) equipped with Cu Kα radiation (λ = 1.54184 Å) source. Data reduction was performed using CrysAlisPro 1.171.37.35h (release 09-02-2015 CrysAlis171 NET). The structures were solved by direct methods using SIR 92,^13b which revealed the atomic positions, and refined using the SHELXL-2014/7 program (within the WinGX program package).^13a,d Non-hydrogen atoms were refined anisotropically. The solvent molecules could not be modelled and hence their contributions to intensities were excluded using SQUEEZE option in PLATON for 1, 3, and 5. The disordered one furan unit in 1 has been successfully modelled using the PART 1 (O3, C22, C45–C47) and PART 2 (O3A, C22A, C45A–C47A) instructions. After refining as a free variable, the site-of-occupancy is almost 0.63 and 0.37, respectively. The nonhydrogen atoms of the furan unit have been constrained or restrained with appropriate instructions such as AFIX43 (O3, C22, C45–C47 in PART 1, and O3A, C22A, C45A–C47A in PART 2), DELU, and SIMU. The detailed crystallographic data's of 1, 3 and 5 are given in ESI (Table S1†).

Synthesis and characterization details

1: a mixture of 2-furan-2-benzimidazole (313.9 mg, 1.70 mmol) and KOH (190.8 mg, 3.40 mmol) was stirred in DMF (10 mL) at room temperature for 1 h. 1,3,5-Tri(bromomethyl)-2,4,6-triethylbenzene (250.5 mg, 0.56 mmol) was added to the reaction mixture and continuously allowed to stir for 72 h. The reaction was quenched by adding water (200 mL). The powder was collected by filtration. Yellow colour crystals 1 were obtained from 1 : 1 chloroform/methanol at room temperature after few days. Yield: 94% (400.6 mg, 0.53 mmol, for C₄₈H₄₂N₆O₃). Mp: 251–253 °C (dec.). ¹H NMR (400 MHz, DMSO-d₆): δ 7.99 (s, 3H, H^5′), 7.60 (d, 3H, J_HH = 7.64 Hz, H⁴), 7.33 (d, 3H, J_HH = 4.04 Hz, H^3′), 7.11 (t, 3H, J_HH = 7.64 Hz, H⁵), 6.90–6.77 (m, 3H, H^4′), 6.33–6.28 (m, 6H, H⁶⁻⁷), 5.80 (s, 6H, –CH₂–), 2.66 (d, 6H, J_HH = 7.64 Hz, –CH₂–), and 0.76 (s, 9H, –CH₃–). HRMS (m/z): [M + H]⁺ calc for C₄₈H₄₂N₆O₃, 751.3397; found: 751.3543.

2: a mixture of 2-furan-2-benzimidazole (387.6 mg, 2.104 mmol) and KOH (235.8 mg, 4.20 mmol) was stirred in DMF (10 mL) at room temperature for 1 h. 1,3,5-Tris(bromomethyl)benzene (250.8 mg, 0.702 mmol) was added to the reaction mixture and continuously allowed to stir for 72 h. The reaction was quenched by adding water (200 mL). The pale brown powder was collected by filtration. Yield: 69% (325 mg, 0.487 mmol). ¹H NMR (400 MHz, DMSO-d₆): δ 7.64 (d, 3H, J_HH = 8.4 Hz, H⁴), 7.56 (s, 3H, H^5′), 7.36 (d, 3H, J_HH = 8.4 Hz, H⁷)), 7.24 (t, 3H, J_HH = 7.63 Hz, H⁵), 7.15 (t, 3H, J_HH = 7.63 Hz, H⁶), 6.93 (d, 3H, J_HH = 3.05 Hz, H^3′), 6.90 (s, 3H, arene), 6.57–6.56 (m, H^4′), and 5.56 (s, 6H, –CH₂–).

3: a mixture of 2-thiophene-2-benzimidazole (360.5 mg, 1.8 mmol) and KOH (210 mg, 3.742 mmol) was stirred in DMF (10 mL) at room temperature for 1 h. 1,3,5-Tri(bromomethyl)-2,4,6-triethylbenzene (265.8 mg, 0.602 mmol) was added to the reaction mixture and continuously allowed to stir for 72 h. The reaction was quenched by adding water (200 mL). The white powder was collected by filtration and dissolved in hot methanol. Colourless crystals were obtained at room temperature after few days. Yield: 81.19% (391 mg, 0.489 mmol). ¹H NMR (400 MHz, DMSO-d₆): δ 7.88–7.85 (m, 6H, H^4′,5′), 7.60 (d, 3H, J_HH = 7.96 Hz, H⁴), 7.29 (t, 3H, J_HH = 4.26 Hz, H^3′), 7.12 (t, 3H, J_HH = 7.64 Hz, H⁵), 6.36 (s, 3H, H⁶), 6.20 (d, 3H, J_HH = 7.92 Hz, H⁷), 5.69 (s, 6H), 2.5 (6H, –CH₂–) and 0.65 (s, 9H, H⁹). HRMS (m/z): [M + H]⁺ calc for C₄₈H₄₃N₆S₃, 799.2633; found: 799.2688.

4: a mixture of 2-thiophene-2-benzimidazole (445.2 mg, 2.22 mmol) and KOH (250 mg, 4.44 mmol) was stirred in DMF (10 mL) at room temperature for 1 h. 1,3,5-Tris(bromomethyl)benzene (264.6 mg, 0.741 mmol) was added to the reaction mixture and continuously allowed to stir for 72 h. The reaction was quenched by adding water (200 mL). The pale yellow powder was collected by filtration. Yield: 62% (328 mg, 0.458 mmol). ¹H NMR (400 MHz, DMSO-d₆): δ 7.68–7.64 (m, 6H, H^5′ & H⁴), 7.33 (d, 3H, J_HH = 7.92 Hz, H⁷), 7.23 (t, 3H, J_HH = 7.32 Hz, H⁵), 7.18–7.15 (m, 6H, H^4′ & H⁶), 6.94–6.91 (m, 3H, H^3′), 6.75 (s, 3H, arene), and 5.54 (s, 6H, –CH₂–).

5: a mixture of 2-pyridyl-2-benzimidazole (351.9 mg, 1.80 mmol) and KOH (201.7 mg, 3.59 mmol) was stirred in DMF (10 mL) at room temperature for 1 h. 1,3,5-tri(bromomethyl)-2,4,6-triethylbenzene (264.5 mg, 0.59 mmol) was added to the reaction mixture and continuously allowed to stir for 72 h. Colourless needle type crystals of 5 were obtained by crystallization from hot chloroform/methanol (1 : 1) after few days at room temperature. Yield: 87% (409.1 mg, 0.52 mmol). ¹H NMR (400 MHz, DMSO-d₆): δ 8.76 (d, 3H, J_HH = 5.36 Hz, H^6′), 8.28 (d, 3H, J_HH = 7.64 Hz, H³), 8.03 (d, 3H, J_HH = 7.64 Hz, 1.52 Hz, H^5′), 7.68 (d, 3H, H⁴), 7.55–7.52 (m, 3H, H^4′), 7.14 (t, 3H, J_HH = 7.64 Hz, H⁵), 6.45 (6H, J_HH = 8.36 Hz, H⁶⁻⁷), 6.26 (s, 6H, –CH₂–), 2.86–2.82 (m, 6H, –CH₂–) and 0.68 (s, 9H, –CH₃–). HRMS (m/z): Calc. 784.3876. Found: 784.3854.

6: a mixture of phenyl-2-benzimidazole (500 mg, 2.57 mmol) and KOH (290.1 mg, 5.17 mmol) was stirred in DMF (10 mL) at room temperature for 1 h. 1,3,5-Tri(bromomethyl)-2,4,6-triethylbenzene (378.3 mg, 0.86 mmol) was added to the reaction mixture and continuously allowed to stir for 72 h. The reaction was quenched by adding water (250 mL). Colourless powder 6 was collected by filtration. Yield: 91% (608.5 mg, 0.78 mmol). ¹H NMR (400 MHz, DMSO-d₆): δ 7.80 (s, broad, 6H, phenyl), 7.64 (d, 3H, J_HH = 8 Hz, H⁴), 7.56 (s, broad, 9H, phenyl), 7.14 (t, 3H, J_HH = 8 Hz, H⁵), 6.46 (t, J_HH = 7.6 Hz, 3H, H⁶), 6.34 (d, J_HH = 8.4 Hz, 3H, H⁷), 5.45 (s, 6H, –CH₂–), 2.44 (d, J_HH = 6.8 Hz, 6H, –CH₂–) and 0.43 (t, J_HH = 6.8 Hz, 9H, –CH₃–). HRMS (m/z): [M + H]⁺ calc for C₅₄H₄₉N₆ Calc. 781.4013. Found: 781.4032.

Acknowledgements

We are grateful to Prof. Dr R. V. Krishnakumar, Department of Physics, Thiagarajar College, Madurai-India for his help in solving the structures. We thank Prof. R. Murugavel for the use of his Single Crystal X-ray Diffraction Facility established through a DAE-SRC Outstanding Investigator Award.

References

1. E. Lanzarotti, R. R. Biekofsky, D. A. Estrin, M. A. Marti and A. G. Turjanski, J. Chem. Inf. Model., 2011, 51, 1623 and references therein.
2. C. A. Hunter, J. Singh and J. M. Thornton, J. Mol. Biol., 1991, 218, 837; N. Kannan and S. Vishveshwara, Protein Eng., 2000, 13, 753; H. Krause, B. Ernstberger and H. J. Neusser, Chem. Phys. Lett., 1991, 184, 411; A. de Meijere and F. Huisken, J. Chem. Phys., 1990, 92, 5826; T. Iimori, Y. Aoki and Y. Ohshima, J. Chem. Phys., 2002, 117, 3675; O. Engkvist, P. Hobza, H. L. Selzle and E. W. Schlag, J. Chem. Phys., 1999, 110, 5758; C. Gonzalez and E. C. Lim, J. Phys. Chem. A, 2001, 105, 1904; T. P. Sauer and C. D. Sherrill, J. Phys. Chem. A, 2005, 109, 10475.
3. S. Janich, R. Frohlich, A. Wakamiya, S. Yamaguchi and E. U. Wurthwein, Chem.–Eur. J., 2009, 15, 10457.
4. T. Morimoto, H. Uno and H. Furuta, Angew. Chem., Int. Ed. Engl., 2007, 46, 3672; H. Uno, Y. Fumoto, K. Inoue and N. Ono, Tetrahedron, 2003, 59, 601; M. Sathiyendiran, J. Y. Wu, M. Velayudam, G. H. Lee, S. M. Peng and K. L. Lu, Chem. Commun., 2009, 3795.
5. S. Kato, T. Nakagaki, T. Shimasaki and T. Shinmyozu, CrystEngComm, 2008, 10, 483; S. Kumar and A. Das, J. Chem. Phys., 2012, 136, 174302.
6. P. Elumalai, P. Rajakannu, F. Hussain and M. Sathiyendiran, RSC Adv., 2013, 3, 2171.
7. C. Y. Su, Y. P. Cai, C. L. Chen, F. Lissner, B. S. Kang and W. Kaim, Angew. Chem., Int. Ed., 2002, 41, 3371; D. Y. Lee, N. Singh, M. J. Kim and D. O. Jang, Org. Lett., 2011, 13, 3024; B. Shankar, F. Hussain and M. Sathiyendiran, J. Organomet. Chem., 2012, 719, 26; B. Shankar, P. Elumalai, R. Shanmugam and M. Sathiyendiran, J. Organomet. Chem., 2014, 749, 224; P. Rajakannu, P. Elumalai, B. Shankar, F. Hussain and M. Sathiyendiran, Dalton Trans., 2013, 42, 11359; P. Rajakannu, P. Elumalai, F. Hussain and M. Sathiyendiran, J. Organomet. Chem., 2013, 725, 1.
8. X. Han, H. Ma and Y. Wang, Russ. J. Org. Chem., 2008, 44, 863.
9. J. Hua, H. Yao, Y. Bai, D. Zhao, S. Chena and J. Zhaoa, Polyhedron, 2014, 78, 1.
10. C. L. Chen, J. Y. Zhang and C. Y. Su, Eur. J. Inorg. Chem., 2007, 2997; M. Arunachalam, E. Suresh and P. Ghosh, Tetrahedron Lett., 2007, 48, 2909; M. Arunachalam and P. Ghosh, Chem. Commun., 2009, 3184; X. F. Wang, Y. Li, Z. Su, T. A. Okamura, G. Wu, W. Y. Sun and N. Ueyama, Z. Anorg. Allg. Chem., 2007, 633, 2695; G. C. Xu, Y. J. Ding, T. A. Okamura, Y. Q. Huang, G. X. Liu, W. Y. Sun and N. Ueyama, CrystEngComm, 2008, 10, 1052; W. Y. Sun, J. Fan, J. Hu, K. B. Yu and W. X. Tang, J. Chem. Crystallogr., 2000, 30, 115.
11. A. D. Becke, Phys. Rev. A: At., Mol., Opt. Phys., 1988, 38, 3098; A. D. Becke, J. Chem. Phys., 1993, 98, 5648; C. Lee, W. Yang and R. G. Parr, Phys. Rev. B: Condens. Matter Mater. Phys., 1988, 37, 785; R. Ditchfield, W. J. Hehre and J. Pople, J. Chem. Phys., 1971, 54, 724; Y. Zhao and D. G. Truhlar, Theor. Chem. Acc., 2008, 120, 215.
12. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery Jr, J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski and D. J. Fox, Gaussian 09, Revision A.02, Gaussian, Inc., Wallingford, CT, 2009.
13. (a) L. J. Farrugia, WinGX, Version 1.80.05, J. Appl. Crystallogr. 1999, 32, 837; (b) A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, M. C. Burla, G. Polidori and M. Camalli, J. Appl. Crystallogr., 1994, 27, 435; (c) G. M. Sheldrick, SHELXL-97, Program for crystal structure refinement, University of Göttingen, Göttingen, Germany, 1997; (d) G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr., 2008, 64, 112.

---

Footnote

† Electronic supplementary information (ESI) available: X-ray crystallographic file in CIF format for 1, 3 and 5. Molecular structure of 1, optimized geometry, NMR spectra, and tables of XRD data. CCDC 1419799, 1051126 and 1051212. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ra05151g

---