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Glycerol containing triacetylborate mediated syntheses of novel 2-heterostyryl benzimidazole derivatives: a green approach.

1. Introduction

Using solvents in chemical synthesis represents a greater challenge in terms of green chemistry and among them solvents like water, PEG-600, and ionic liquids have proved to be potential green solvents for organic synthesis. In the past [1], glycerol as solvent has not been used extensively for organic synthesis and in recent years, various developments have been made to prove that glycerol can be used as an alternate solvent and can feasibly be considered as an efficient green solvent [2, 3]. Cinnamic acids and its derivatives (i-iv) (Figure 1) such as ethyl cinnamate, sodium cinnamate, and benzylcinnamate have century old history as potential antituberculosis agents [4-7]. Benzimidazole scaffold being an important pharmacophore and privileged structure in medicinal chemistry [8, 9], a new series of 5-(bromo/nitro)-2-styryl-benzimidazoles were synthesized earlier using cinnamic acids in ethylene glycol under reflux conditions and showed good antimicrobial and antitubercular activities (vii) [10, 11]. 2-Styryl-benzimidazoles and its analogues (v) were also reported as MAO-B inhibitors [12], in which the styryl compounds were synthesized using 2-methylbenzimidazole condensed with aromatic aldehydes refluxing at 180[degrees]C for 24 h (Figure 1).

Recently, some new styryl benzimidazoles were reported as probes for imaging neurofibrillary tangles in Alzheimer's disease [13], in which new iodo derivatives of styrylbenzimidazoles were prepared by the condensation of substituted o-phenylenediamines with cinnamaldehydes refluxing in DMF [13]. Other methods for the preparation of 2-styrylbenzimidazoles involves the use of PPA at 200[degrees]C gave a low 30% yield [10] and the conventional Phillips method, in which o-phenylenediamine condensed with cinnamic acids refluxing in 4N HCl, for the synthesis of 2-styrylbenzimidazoles, resulted in the recovery of starting material [10].

The widespread interest in benzimidazole containing skeletons having a wide spectrum of activity has promoted extensive studies for their synthesis. While there are many strategies available for benzimidazole synthesis, there are a few methods available for the preparation of 2-styryl type of benzimidazoles. The earlier methods involve nongreen [14-17] routes like using PPA or high temperatures, long reaction times, various work-up methods, and low yields made to look for other methods for the synthesis of 2-styryl type of benzimidazoles. Though the above methods were effective in completion of the reaction, but they suffer from eco-friendly practise. Therefore, the discovery of practicable greener routes utilizing easily available starting materials like glycerol and triacetylborate which were considered as environmentally friendly for the synthesis of 2-hetero/styrylbenzimidazoles continues to attract the attention of researchers.

In continuation of our earlier work on the synthesis of 2-styrylbenzimidazoles, now we wish to extend our approach by using other heterocyclic aldehydes like furfuraldehyde, piperonaldehyde and thiophene-2-aldehyde, and so forth, in addition to benzaldehyde derivatives, in a very green way by using glycerol and triacetylborate as green and as a recyclable reaction medium.

2. Materials and Methods

All the reagents used in this work were obtained from commercial suppliers. Solvents were freshly distilled before being used. Melting points were determined using a Buchi Melting Point B-545 apparatus and are uncorrected. TLC analyses were done on glass plates coated with silica gel GF-254 and spotting was done using Iodine/UV lamp. IR spectra were recorded on a Perkin-Elmer model 446 instrument in KBr phase. [sup.1]H NMR were recorded in CD[Cl.sub.3]/DMSO using 400 MHz Varian Gemini spectrometer and mass spectra were recorded on LC-MS spectrometer, model HP5989A.[sup.13]C NMR was recorded in DMSO using 100 MHz spectrometer.

2.1. General Procedure for the Synthesis of 2-Styrylbenzimidazole Derivatives from O-PDA and Cinnamic Acids. An intimate mixture of o-penylenediamine 1 (1.08 g, 10 mM) was dissolved in a 100 mL round bottom flask. To this, triacetylborate (0.2 g, 10 mol%) was added, followed by the addition of cinnamic acids 2 (10 mM) and allowed it to boil at 160-180[degrees]C in oil-bath for 3h using Dean-Stark apparatus. The completion of the reaction was monitored by checking TLC. At the end of this period, the reaction mixture was poured into ice cold water. The pH of the solution was adjusted to 8.0-10.0. The formed product was filtered, dried and recrystallized by using a suitable solvent.

2.2. General Procedure for the Synthesis of 2-Styrylbenzimidazole Derivatives from 2-Methylbenzimidazoles and Aromatic Aldehydes. An intimate mixture of 2methylbenzimidazole 4(a-b) (1.32 g, 10 mM) was dissolved in 10 mL of glycerol in a 100 mL round bottom flask. To this, triacetylborate (0.2 g, 10mol%) was added, followed by the addition of corresponding aromatic aldehydes 5(a-i) (10 mM) and allowed it to boil at 160-180[degrees]C in oil-bath for 3h using Dean-Stark apparatus. The completion of the reaction was monitored by checking TLC. At the end of this period, the reaction mixture was poured into ice cold water and the pH of the solution was adjusted to 8.0-10.0. Filter the compound and recrystallize it by using a suitable solvent.

2.2.1. (E)-2-(2-(Benzo[d][1,3]dioxol-5-yl)vinyl)-1H-benzimidazole (3f). Wheatish light brown crystals, Yield (2.2 g, 85%), m.p 200-204[degrees]C, IR (KBr, [v.sub.max] in [cm.sup.-1]): 3435 (-NH), 2922 (=C-H), 1683 (C=N), 1620 (C=C), [sup.1]H NMR (DMSO-[d.sub.6], 400 MHz) [delta] ppm: 2.5 (s, 2H, -C[H.sub.2]), 72-74 (d, 1H, -C=CH, [J.sub.H-H] = 16.4 Hz), 75-73 (m, 4 aryl, 3 phenyl protons), 7.8-8.0 (d, 1H, -CH=C, [J.sub.H-H] = 16.4 Hz), 10.0 (s, 1H, -NH of benzimidazole), [sup.13]C NMR (DMSO-[d.sub.6], 100 MHz) [delta] ppm: 102.29, 108.54, 109, 122, 124, 128, 130, 132, 134, 138, 148, 152 (1 dioxymethylene carbon, 6 aryl carbons, 6 phenylic carbons, 2 vinylic carbons and 1 imidazole quaternary carbon), MS (m/z): 265.10 ([M.sup.+*]), Anal. Calcd. for [C.sub.16][H.sub.12][N.sub.2][O.sub.2]: C, 72.72; H, 4.58; N, 10.60; 0, 12.11% Found: C, 72.84; H, 4.70; N, 10.68; O, 12.25%.

2.2.2. (E)-2-(2-(Furan-2-yl)vinyl)-1H-benzimidazole (3g). Brown crystals, Yield (1.97 g, 94%), m.p 218-220[degrees]C, IR (KBr, [v.sub.max] in [cm.sup.-1]): 3405 (-NH), 3101 (=C-H), 1894 (C=N), 1633 (C=C), [sup.1]H NMR (DMSO-[d.sub.6], 400 MHz) [delta] ppm: 6.91-6.95 (d, 1H, -C=CH (vinylic proton), [J.sub.H-H] = 16.4 Hz), 7.16-7.18 (t, 1H, furan proton), 7.23-7.28 (q, 2H, phenylic protons), 7.44-7.45 (d, 1H, furan proton), 7.57-7.61 (q, 2H, phenylic protons), 7.67-7.68 (d, 1H, furan proton), 7.92-7.96 (d, 1H, -CH=C-(vinylic proton), [J.sub.H-H] = 16.4 Hz), 10.0 (s, 1H, -NH of benzimidazole), [sup.13]C NMR (DMSO-[d.sub.6], 100 MHz) [delta] ppm: 114.47, 114.50, 122.87, 127.96, 128.51, 129.15, 129.48, 137.39, 140.33, 149.87 (6 aryl carbons, 4 furyl carbons, 2 vinylic carbons and 1 imidazole quaternary carbon), MS (m/z): 211.10 ([M.sup.+*]), Anal. Calcd. for [C.sub.13][H.sub.10][N.sub.2]O: C, 74.27; H, 4.79; N, 13.33; O, 7.61% Found: C, 74.34; H, 4.84; N, 13.60; O, 7.73%.

2.2.3. (E)-2-(2-(Thiophen-2-yl)vinyl)-1H-benzimidazole (3h). Light green crystals, Yield (1.97 g, 92%), m.p 198-200[degrees]C, IR (KBr, [v.sub.max] in [cm.sup.-1]): 3405 (-NH), 3101 (=C-H), 1894 (C=N), 1633 (C=C), [sup.1]H NMR (DMSO-[d.sub.6], 400 MHz) [delta] ppm: 6.91-6.95 (d, 1H, -C=CH (vinylic proton), [J.sub.H-H] = 16.4 Hz), 7.16-7.18 (t, 1H, thiophenyl proton), 7.23-7.28 (q, 2H, phenylic protons), 7.44-7.45 (d, 1H, thiophenyl proton), 7.57-7.61 (q, 2H, phenylic protons), 7.67-7.68 (d, 1H, thiophenyl proton), 7.92-7.96 (d, 1H, -CH=C-(vinylic proton), [J.sub.H-H] = 16.4 Hz), 10.0 (s, 1H, -NH of benzimidazole), [sup.13]C NMR (DMSO-[d.sub.6], 100 MHz) [delta] ppm: 114.47, 114.50, 122.87, 127.96, 128.51, 129.15, 129.48, 137.39, 140.33, 149.87 (6 aryl carbons, 4 thiophenyl carbons, 2 vinylic carbons and 1 imidazole quaternary carbon), MS (m/z): 227.07 ([M.sup.+*]), Anal. Calcd. for C13H10N2S: C, 69.00; H, 4.45; N, 12.38; S, 14.17% Found: C, 69.24; H, 4.52; N, 12.40; S, 14.27%.

2.2.4. (E)-Phenyl(2-styryl-1H-benzimidazol-6-yl)methanone (3i). Light orange crystals, Yield (2.9 g, 90%), m.p 202-204[degrees]C, IR (KBr, [v.sub.max] in [cm.sup.-1]): 3401 (-NH), 2956 (=C-H), 1891 (C=N), 1610 (C=C), 1644 (C=O), [sup.1]H NMR (DMSO-[d.sub.6], 400 MHz) [delta] ppm: 7.33-7.37 (d, 1H, -C=CH, vinylic proton, [J.sub.H-H] = 16.4 Hz), 7.48-7.67 (m, 8 aryl, 5 phenyl), 10.2 (s, 1H, -NH of benzimidazole), [sup.13]C NMR (DMSO-[d.sub.6], 100 MHz) d ppm: 102, 106, 108, 110, 112, 120, 121, 122, 128, 129, 130, 132, 142, 148, 152, 190 (12 aryl carbons, 6 phenyl carbons, 2 vinylic carbons, 1 imidazole quaternarycarbon and 1 carbonyl carbon), MS (m/z): 325.2 ([M.sup.+*]), Anal. Calcd. for [C.sub.22][H.sub.16][N.sub.2]O: C, 81.46; H, 4.97; N, 8.64; O, 4.93% Found: C, 81.54; H, 4.99; N, 8.76; O, 4.97%.

2.2.5. (E)-(2-(4-Fluorostyryl)-1H-benzimidazol-6-yl)(phenyl) methanone (3j). Black crystals, Yield (1.97 g, 90%), m.p 178-180[degrees]C, IR (KBr, [v.sub.max] in [cm.sup.-1]): 3432 (-NH), 3178 (=C-H), 1909 (C=N), 1628 (C=C), 1700 (C=O), [sup.1]H NMR (DMSO-[d.sub.6], 400 MHz) [delta] ppm: 7.09-7.13 (d, 1H, -C=CH- vinulic proton, [J.sub.H-H] = 16.4 Hz), 7.3-79 (m, 8 aryl, 4 phenyl), 8.09-8.13 (d, 1H, -CH=C-, vinylic proton, [J.sub.H-H] = 16.4 Hz), 10.2 (s, 1H, -NH of benzimidazole), [sup.13]C NMR (DMSO-[d.sub.6], 100 MHz) d ppm: 102.29, 106.24, 108.53, 110, 112, 120, 121, 122, 128.51, 129, 130, 132, 142, 148, 152, 190.91 (12 aryl carbons, 6 phenyl carbons, 2 vinylic carbons, 1 imidazole quaternary carbon and 1 carbonyl carbon), MS (m/z): 343.2 ([M.sup.+*]), Anal. Calcd. for [C.sub.22][H.sub.15]F[N.sub.2]O: C, 77.18; H, 4.42; F, 5.55; N, 8.18; O, 4.67% Found: C, 77.32; H, 4.69; F, 5.69; N, 8.27; O, 4.73%.

2.2.6. (E)-(2-(4-Chlorostyryl)-1H-benzimidazol-6-yl)(phenyl) methanone ield (3.2 g, 90%), m.p 130-132[degrees]C, IR (KBr, [v.sub.max] in [cm.sup.-1]): 3426 (-NH), 2898 (=C-H), 1909 (C=N), 1601 (C=C), 1680 (C=O), [sup.1]H NMR (DMSO-[d.sub.6], 400 MHz) [delta] ppm: 7.09-7.13 (d, 1H, -C=CH- vinulic proton, [J.sub.H-H] = 16.4 Hz), 73-79 (m, 8 aryl, 4 phenyl), 8.09-8.13 (d, IH, -CH=C-, vinylic proton, [J.sub.H-H] = 16.4 Hz), 10.2 (s, 1H, -NH of benzimidazole), [sup.13]C NMR (DMSO-[d.sub.6], 100 MHz) [delta] ppm: 102.29, 106.24, 108.53, 110, 112, 120, 121, 122, 128.51, 129, 130, 132, 142, 148, 152, 190.91 (12 aryl carbons, 6 phenyl carbons, 2 vinylic carbons, 1 imidazole quaternary carbon and 1 carbonyl carbon), MS (m/z): 359.1 ([M.sup.+*]), Anal. Calcd. for [C.sub.22][H.sub.15]Cl[N.sub.2]O: C, 73.64; H, 4.21; Cl, 9.88; N, 7.81; O, 4.46% Found: C, 73.52; H, 4.39; Cl, 9.96; N, 7.87; O, 4.53%.

2.2.7. (E)-(2-(4-Nitrostyryl)-1H-benzimidazol-6-yl)(phenyl) methanone (3l). Light yellow crystals, Yield (3.2 g, 90%), m.p 210-212[degrees]C, IR (KBr, [v.sub.max] in [cm.sup.-1]): 3410 (-NH), 2960 (=C-H), 1680 (C=N), 1620 (C=C), 1670 (C=O), [sup.1]H NMR (DMSO-[d.sub.6], 400 MHz) [delta] ppm: 70-8.3 (m, 8 aryl, 4 phenyl and 2 vinylic protons, [J.sub.H-H] = 16.4 Hz), 10.2 (s, 1H, -NH of benzimidazole), [sup.13]C NMR (DMSO-[d.sub.6], 100 MHz) [delta] ppm: 102, 106, 108, 110, 112, 120, 121, 122, 128, 129, 130, 132, 142, 148, 152, 190 (12 aryl carbons, 6 phenyl carbons, 2 vinylic carbons, 1 imidazole quaternary carbon and 1 carbonyl carbon), MS (m/z): 370.2 ([M.sup.+*]), Anal. Calcd. for [C.sub.22][H.sub.15][N.sub.3][O.sub.3]: C, 71.54; H, 4.09; N, II. 38; O, 12.99% Found: C, 71.62; H, 4.29; N, 11.47; O, 13.05%.

2.2.8. (E)-(2-(4-Methylstyryl)-1H-benzimidazol-6-yl)(phenyl) methanone (3m). Black crystals, Yield (3.2 g, 90%), m.p 198-200[degrees]C, IR (KBr, [v.sub.max] in [cm.sup.-1]): 3420 (-NH), 3214 (=C-H), 1642 (C=N), 1603 (C=C), 1616 (C=O), [sup.1]H NMR (DMSO-[d.sub.6], 400 MHz) [delta] ppm: 2.4 (s, 3H, -C[H.sub.3]), 7.0-8.2 (m, 8 aryl, 4 phenyl and 2 vinylic protons, [J.sub.H-H] = 16.4 Hz), 10.0 (s, 1H, -NH of benzimidazole), [sup.13]C NMR (DMSO-[d.sub.6],100 MHz) [delta] ppm: 21, 102, 106, 108, 110, 112, 120, 121, 122, 128, 129, 130, 132, 142, 148, 152,190 (12 aryl carbons, 6 phenyl carbons, 2 vinylic carbons, 1 imidazole quaternary carbon and 1 carbonyl carbon), MS (m/z): 370.2 ([M.sup.+*]), Anal. Calcd. for [C.sub.22][H.sub.15][N.sub.3][O.sub.3]: C, 71.54; H, 4.09; N, 11.38; O, 12.99% Found: C, 71.62; H, 4.29; N, 11.47; O, 13.05%.

2.2.9. (E)-(2-(2-(Benzo[d][1,3]dioxol-5-yl)vinyl)-1H-benzimidazol-6-yl)(phenyl)methanone (3n). Dark brown crystals, Yield (3.2 g, 90%), m.p > 240[degrees]C, IR (KBr, [v.sub.max] in [cm.sup.-1]): 3422 (-NH), 2917 (=C-H), 1644 (C=N), 1575 (C=C), 1609 (C=O), [sup.1]H NMR (DMSO-[d.sub.6], 400 MHz) d ppm: 2.5 (s, 2H, -C[H.sub.2]), 6.2-6.26 (d, 1H,-C=CH-, vinylic proton, [J.sub.H-H] = 16.4 Hz), 70 8.0 (m, 8 aryl, 4 phenyl and 1 vinylic protons, [J.sub.H-H] = 16.4 Hz), 9.8 (s, 1H, -NH of benzimidazole), [sup.13]C NMR (DMSO-[d.sub.6], 100 MHz) d ppm: 114.30, 115.04, 116.96, 125.42, 128.45, 128.68, 129.12, 129.30, 129.48, 129.59, 131.08, 132.22, 132.33, 133.76, 134.37, 137.58, 137.64, 137.74, 195.17 (1 dioxymethylene carbon, 12 aryl carbons, 6 phenylic carbons, 2 vinylic carbons, 1 imidazole quaternary carbon, 1 carbonyl carbon), MS (m/z): 370.2 ([M.sup.+*]), Anal. Calcd. for [C.sub.22][H.sub.15][N.sub.3][O.sub.3]: C, 71.54; H, 4.09; N, 11.38; O, 12.99% Found: C, 71.62; H, 4.29; N, 11.47; O, 13.05%.

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2.2.10. (E)-(2-(2-(Furan-2-yl)vinyl)-1H-benzimidazol-6-yl) (phenyl)methanone (3o). Black crystals, Yield (3.2 g, 90%), m.p 100-102[degrees]C, IR (KBr, [v.sub.max] in [cm.sup.-1]): 3423 (-NH), 2921 (=C-H), 1642 (C=N), 1597 (C=C), 1617 (C=O), [sup.1]H NMR (DMSO-[d.sub.6], 400 MHz) [delta] ppm: 6.6-8.1 (m, 8 aryl, 3 furanyl and 2 vinylic protons, [J.sub.H-H] = 16.4 Hz), 10.2 (s, 1H, -NH of benzimidazole), [sup.13]C NMR (DMSO-[d.sub.6], 100 MHz) [delta] ppm: 111, 112, 118, 125.12, 128.45, 128.68, 128.91, 129.47, 130.43, 131.85, 132.27, 137.75, 139.96, 152.32, 195.27 (12 aryl carbons, 4 furanyl carbons, 2 vinylic carbons, 1 imidazole quaternary carbon and 1 carbonyl carbon), MS (m/z): 370.2 ([M.sup.+*]), Anal. Calcd. for [C.sub.22][H.sub.15][N.sub.3][O.sub.3]: C, 71.54; H, 4.09; N, 11.38; 0,12.99% Found: C, 71.62; H, 4.29; N, 11.47; 0,13.05%.

2.2.11. (E)-Phenyl(2-(2-(thiophen-2-yl)vinyl)-1H-benzimidazol-6-yl)methanone (3p). Light green crystals, Yield (3.2 g, 90%), m.p 108-110[degrees]C, IR (KBr, [v.sub.max] in [cm.sup.-1]): 3427 (-NH), 3060 (=C-H), 1633 (C=N), 1597 (C=C), 1614 (C=O), 1H NMR (DMSO-[d.sub.6], 400 MHz) [delta] ppm: 6.6-8.1 (m, 8 aryl, 3 thiophenyl and 2 vinylic protons, [J.sub.H-H] = 16.4 Hz), 10.2 (s, 1H, -NH of benzimidazole), [sup.13]C NMR (DMSO-[d.sub.6], 100 MHz) 5 ppm: 111, 112, 118, 125.12, 128.45, 128.68, 128.91, 129.47, 130.43, 131.85, 132.27, 137.75, 139.96, 152.32, 195.27 (12 aryl carbons, 4 thiophenyl carbons, 2 vinylic carbons, 1 imidazole quaternary carbon and 1 carbonyl carbon), MS (m/z): 370.2 ([M.sup.+*]), Anal. Calcd. for [C.sub.22][H.sub.15][N.sub.3][O.sub.3]: C, 71.54; H, 4.09; N, 11.38; 0, 12.99% Found: C, 71.62; H, 4.29; N, 11.47; O, 13.05%.

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3. Results and Discussion

In continuation of our earlier strategies for the establishment of 2-styryl-benzimidazoles using green solvents like ethylene glycol [10], now we have developed a highly efficient and simple green methodology for the synthesis of 2-styrylbenzimidazole derivatives 3(a-p), by direct condensation of equivalent amounts of substituted o-phenylenediamines 1(ab) with various cinnamic acids 2(a-h) using 10-20 mol % of triacetylborate and glycerol (10 mL) as reaction medium at 160-180[degrees]C for 3-5 h Scheme 1).

In an alternative approach, 2-methylbenzimidazoles 4(ab) were condensed with a variety of aromatic aldehydes 5(a-h) using glycerol (10 mL) as solvent and triacetylborate (10-20 mol %) at 150-180[degrees]C for 5-6 h resulted 2-styrylbenzimidazole derivatives 3(a-p) (Scheme 2). The most important advantages of our method are as follows: (a) it is totally green procedure that involves homogeneous catalysis; (b) only 10-20 mol % of triacetylborate is sufficient to complete the reaction; (c) the very simple workup does not involve the use of any acids; (d) the products, which in general possess stable high melting points, solidify readily and hence can be very easily collected and recrystallized from suitable solvent without need for further purification; (e) used triacetylborate is cheap and readily available; (f) the yields of all the products are good and the reaction procedure is highly a general one with 100% conversion in all the cases (no starting materials were apparent by TLC).

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In order to ascertain the necessity of triacetylborate, glycerol, or both, the correct solvent and the required temperature, the reaction of 4-chlorobenzaldehyde (5c) with 2-methylbenzimidazole (4a) was carried out separately in glycerol alone (entry 2), without glycerol and triacetylborate, that is, solvent free manner (entry 1), only triacetylborate (2-20 mol %) (entries 3, 4, and 5), or both triacetylborate and glycerol (10 mL) (entries 6 to 9) or in other solvents (entries 10,11) at various temperatures (Table 1). Itwasfound that only 10 mol% of triacetylborate and glycerol as reaction medium at 170[degrees]C Table 1, entry 8 (#)) provided the best conditions for the synthesis of 2-styryl type benzimidazoles in good yields. The method is further suitable for heteroaromatic aldehydes like furfural, thiophene-2-carboxaldehyde, and piperonaldehyde.

Triacetylborate is prepared according to the reported procedure [18], which is soluble in glycerol, maintaining the optimum acidity of the reaction medium and at the same time it is not necessary to use acids like [H.sub.2]S[O.sub.4] or HCl and oxalic acid to prepare salts or to recover the product during the work-up process. Both triacetylborate and glycerol, being highly soluble in water, can be recycled after the reaction. The water solution obtained as the filtrate can be lyophilized to reclaim the boric acid (tested by the usual way of obtaining the green flame of ethyl borate with ethanol without adding Conc. [H.sub.2]S[O.sub.4]) which, when dried, could be further reused for the preparation of triacetylborate.

The reaction proceeds by the formation of a solketal/glycerol aldehyde acetal [19, 20] type of intermediate (ix) formed by the condensation of glycerol (viii) and aromatic aldehyde (5) in presence of triacetylborate (vii), which act as a Lewis acid, is further reacted with 2-methylbenzimidazole 4(a-b), and forms 2-styryl-benzimidazole 3(a-p) by losing water molecules. At the end glycerol as a by-product can be collected as filtrate and purified for further usage (Scheme 3).

This reaction mechanism can be explained in another approach, in which triacetylborate (vii) and glycerol (viii) react together to form an intermediate by losing two acetate molecules and combine with cinnamic acid (4), where the boron loses its third acetate molecule and accepts electrons from the oxygen atom of cinnamic acid and forms intermediate (x), which is further reacts with o-pheneylenediamine (1) and undergoes intramolecular cyclisation to form the final product (3) (Scheme 4).

The above reactions using triacetylborate as the reagent was found to be general and has been extended to all other derivatives, yielding 3(a-p). All the reactions done can be summarized in Table 2.

4. Conclusions

We have highlighted the potential of triacetylborate and glycerol for the first time as a cheap, mild, highly efficient, nontoxic, and recyclable reaction medium for the high yielding synthesis of 2-hetero/styryl-benzimidazoles at 160-180[degrees]C with wide variations both in the aldehydes and cinnamic acids and also in the 2-methylbenzimidazoles. Thus, this green approach opens an important alternative to the use of volatile organic solvents and, therefore, should be highly beneficial to both academics and industry.

http://dx.doi.org/10.1155/2014/260726

Conflict of Interests

The authors declare that there is no conflict of interests regarding publication of this paper.

Acknowledgments

The authors are thankful to the authorities of Jawaharlal Nehru Technological University, Hyderabad, for providing laboratory facilities. The authors are also grateful to the CSIR-CDRI, Lucknow, for providing financial support in the form of OSDD project. The authors are also thankful to CFRD, Osmania University, Hyderabad, for providing spectral analysis.

References

[1] Y. Gu and F. Jerome, "Glycerol as a sustainable solvent for green chemistry," Green Chemistry, vol. 12, no. 7, pp. 1127-1138, 2010.

[2] Y. Gu, J. Barrault, and F. Jerome, "Glycerol as an efficient promoting medium for organic reactions," Advanced Synthesis & Catalysis, vol. 350, no. 3, pp. 2007-2012, 2008.

[3] A. Wolfson, C. Dlugy, and Y. Shotland, "Glycerol as a green solvent for high product yields and selectivities," Environmental Chemistry Letters, vol. 5, no. 2, pp. 67-71, 2007

[4] J. P. Warbasse, "Spontaneous torsion of the pedicle of ovarian tumors; with the report of a case of rotated ovarian cyst with extensive intra-mural hemorrhage," Annals of Surgery, vol. 19, pp. 440-452, 1894.

[5] M. J. Jacobson, "Ethylcinnamate in experimental tuberculosis," Bulletins et Memoires de la Societe Medicale des Hopitaux de Paris, vol. 35, pp. 322-325, 1919.

[6] H. J. Corper, H. Gauss, and W. A. Gekler, "Studies on the inhibitory action of sodium," Colorado American Review of Tuberculosis, vol. 4, pp. 464-473, 1920.

[7] H. Gainsborough, "A note on the use of benzyl cinnamic ester in tuberculosis. The method of jacobson," The Lancet, vol. 211, no. 5462, pp. 908-909, 1928.

[8] A. Khalafi-Nezhad, M. N. Soltani Rad, H. Mohabatkar, Z. Asrari, and B. Hemmateenejad, "Design, synthesis, antibacterial and QSAR studies of benzimidazole and imidazole chloroaryloxyalkyl derivatives," Bioorganic & Medicinal Chemistry, vol. 13, no. 6, pp. 1931-1938, 2005.

[9] B. E. Evans, K. E. Rittle, M. G. Bock et al., "Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists," Journal of Medicinal Chemistry, vol. 31, no. 12, pp. 2235-2246, 1988.

[10] P. K. Dubey, R. Kumar, J. S. Grossert, and D. L. Hooper, "A facile and convenient method for the preparation of 2-styrylbenzimidazoles," Indian Journal of Chemistry B, vol. 38, no. 10, pp. 1211-1213, 1999.

[11] R. V. Shingalapur, K. M. Hosamani, and R. S. Keri, "Synthesis and evaluation of in vitro anti-microbial and anti-tubercular activity of 2-styryl benzimidazoles," European Journal of Medicinal Chemistry, vol. 44, no. 10, pp. 4244-4248, 2009.

[12] J. P. Petzer, S. Steyn, K. P. Castagnoli et al., "Inhibition of monoamine oxidase B by selective adenosine A2A receptor antagonists," Bioorganic & Medicinal Chemistry, vol. 11, no. 7, pp. 1299-1310, 2003.

[13] K. Matsumura, M. Ono, M. Yoshimura et al., "Synthesis and biological evaluation of novel styryl benzimidazole derivatives as probes for imaging of neurofibrillary tangles in Alzheimer's disease," Bioorganic & Medicinal Chemistry, vol. 21, no. 11, pp. 3356-3362, 2013.

[14] M. M. Heravi, S. Sadjadi, H. A. Oskooie, R. H. Shoar, and F. F. Bamoharram, "Heteropolyacids as heterogeneous and recyclable catalysts for the synthesis of benzimidazoles," Catalysis Communications, vol. 9, no. 4, pp. 504-507, 2008.

[15] K. Bahrami, M. M. Khodaei, and I. Kavianinia, "A simple and efficient one-pot synthesis of 2-substituted benzimidazoles," Synthesis, no. 4, pp. 547-550, 2007

[16] X. Han, H. Ma, and Y. Wang, "p-TsOH catalyzed synthesis of 2-arylsubstituted benzimidazoles," Arkivoc, vol. 2007, no. 13, pp. 150-154, 2007.

[17] B. Das, H. Holla, and Y. Srinivas, "Efficient (bromodimethyl)sulfonium bromide mediated synthesis of benzimidazoles," Tetrahedron Letters, vol. 48, no. 1, pp. 61-64, 2007.

[18] C. I. Chiriac, F. Tanasa, and M. Onciu, "A novel approach in cinnamic acid synthesis: direct synthesis of cinnamic acids from aromatic aldehydes and aliphatic carboxylic acids in the presence of boron tribromide," Molecules, vol. 10, no. 2, pp. 481487, 2005.

[19] N. Suriyaprapadiloka and B. Kitiyanan, "Synthesis of solketal from glycerol and its reaction with benzyl alcohol," Energy Procedia, vol. 9, pp. 63-69, 2011.

[20] C. Crotti, E. Farnetti, and N. Guidolin, "Alternative intermediates for glycerol valorization: iridium-catalyzed formation of acetals and ketals," Green Chemistry, vol. 12, no. 12, pp. 2225-2231, 2010.

Ashok Kumar Taduri, P. N. Kishore Babu, and B. Rama Devi

Department of Chemistry, College of Engineering, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad Andhra Pradesh 500 085, India

Correspondence should be addressed to Ashok Kumar Taduri; ashok.jntu@gmail.com

Received 9 November 2013; Revised 20 February 2014; Accepted 24 March 2014; Published 27 April 2014

Academic Editor: Robert Salomon

TABLE 1: Synthesis of 2-(2-(4-chloro-phenyl)-vinyl)-1-H-benzimidazoles.

Entry    Triacetylborate    glycerol *     Solvents used    Time (h)
             (mol-%)       used (+) not
                             used (-)

1.             --               -               --             05
2.             --               +            Glycerol          05
3.              2               -               --             05
4.              5               -               --             05
5.             10               -               --             05
6.              2               +            Glycerol          05
7               5               +            Glycerol          05
8. (#)       10 (#)           + (#)        Glycerol (#)      05 (#)
9.             20               +            Glycerol          05
10.            20               -         Ethylene glycol      06
11.            20               -             PEG-600          06

Entry    Yield (%)

1.          50
2.          50
3.          60
4.          68
5.          70
6.          60
7           78
8. (#)    90 (#)
9.          84
10.         60
11.          0

Reactions were carried out in oil bath using Dean-Stark apparatus
at 160[degrees]C (entries 2, 6, 7, 8, and 9), 120[degrees]C
(entry 11), 190[degrees]C (entry 10), or under solvent free
conditions at 180[degrees]C (entries 1, 3, 4, and 5).

* 10 mL glycerol was used in all the above reactions.
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Title Annotation:Research Article
Author:Taduri, Ashok Kumar; Babu, P.N. Kishore; Devi, B. Rama
Publication:Organic Chemistry International
Article Type:Report
Date:Jan 1, 2014
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