Table of Contents
Organic Chemistry International
Volume 2014, Article ID 260726, 9 pages
http://dx.doi.org/10.1155/2014/260726
Research Article

Glycerol Containing Triacetylborate Mediated Syntheses of Novel 2-Heterostyryl Benzimidazole Derivatives: A Green Approach

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

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

Academic Editor: Robert Salomon

Copyright © 2014 Ashok Kumar Taduri et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A very simple, mild, efficient, and novel green methodology has been developed for the syntheses of some 2-hetero/styryl-benzimidazoles. Title compounds were synthesized by the condensation of -phenylenediamine with cinnamic acids at 150–180°C for 5-6 h using glycerol containing triacetylborate (10–20 mol%) as the reaction medium. In an alternative approach, condensation of 2-methylbenzimidazole derivatives with aromatic aldehydes was done using glycerol containing triacetylborate (10–20 mol%) as the reaction medium.

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 [47]. 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°C for 24 h (Figure 1).

260726.fig.001
Figure 1: Cinnamic acid and its derivatives showing various biological activities.

Recently, some new styryl benzimidazoles were reported as probes for imaging neurofibrillary tangles in Alzheimer’s disease [13], in which new iodo derivatives of styryl-benzimidazoles were prepared by the condensation of substituted -phenylenediamines with cinnamaldehydes refluxing in DMF [13]. Other methods for the preparation of 2-styrylbenzimidazoles involves the use of PPA at 200°C gave a low 30% yield [10] and the conventional Phillips method, in which -phenylenediamine condensed with cinnamic acids refluxing in 4 N 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 [1417] 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. 1H NMR were recorded in CDCl3/DMSO using 400 MHz Varian Gemini spectrometer and mass spectra were recorded on LC-MS spectrometer, model HP5989A. 13C NMR was recorded in DMSO using 100 MHz spectrometer.

2.1. General Procedure for the Synthesis of 2-Styryl-benzimidazole 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°C in oil-bath for 3 h 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-Styryl-benzimidazole Derivatives from 2-Methylbenzimidazoles and Aromatic Aldehydes

An intimate mixture of 2-methylbenzimidazole 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, 10 mol%) was added, followed by the addition of corresponding aromatic aldehydes 5(a-i) (10 mM) and allowed it to boil at 160–180°C in oil-bath for 3 h 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°C, IR (KBr, in cm−1): 3435 (–NH), 2922 (=C–H), 1683 (C=N), 1620 (C=C), 1H NMR (DMSO-, 400 MHz) ppm: 2.5 (s, 2H, –CH2), 7.2–7.4 (d, 1H, –C=CH, JH-H = 16.4 Hz), 7.5–7.3 (m, 4 aryl, 3 phenyl protons), 7.8–8.0 (d, 1H, –CH=C, JH-H = 16.4 Hz), 10.0 (s, 1H, –NH of benzimidazole), 13C NMR (DMSO-, 100 MHz) 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 (/): 265.10 (M+), Anal. Calcd. for C16H12N2O2: C, 72.72; H, 4.58; N, 10.60; O, 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°C, IR (KBr, in cm−1): 3405 (–NH), 3101 (=C–H), 1894 (C=N), 1633 (C=C), 1H NMR (DMSO-, 400 MHz) ppm: 6.91–6.95 (d, 1H, –C=CH (vinylic proton), JH-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), JH-H = 16.4 Hz), 10.0 (s, 1H, –NH of benzimidazole), 13C NMR (DMSO-, 100 MHz) 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 (/): 211.10 (M+), Anal. Calcd. for C13H10N2O: 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°C, IR (KBr, in cm−1): 3405 (–NH), 3101 (=C–H), 1894 (C=N), 1633 (C=C), 1H NMR (DMSO-, 400 MHz) ppm: 6.91–6.95 (d, 1H, –C=CH (vinylic proton), JH-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), JH-H = 16.4 Hz), 10.0 (s, 1H, –NH of benzimidazole), 13C NMR (DMSO-, 100 MHz) 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 (/): 227.07 (M+), 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°C, IR (KBr, in cm−1): 3401 (–NH), 2956 (=C–H), 1891 (C=N), 1610 (C=C), 1644 (C=O), 1H NMR (DMSO-, 400 MHz) ppm: 7.33–7.37 (d, 1H, –C=CH, vinylic proton, JH-H = 16.4 Hz), 7.48–7.67 (m, 8 aryl, 5 phenyl), 10.2 (s, 1H, –NH of benzimidazole), 13C NMR (DMSO-, 100 MHz) 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 (/): 325.2 (M+), Anal. Calcd. for C22H16N2O: 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°C, IR (KBr, in cm−1): 3432 (–NH), 3178 (=C–H), 1909 (C=N), 1628 (C=C), 1700 (C=O), 1H NMR (DMSO-, 400 MHz) ppm: 7.09–7.13 (d, 1H, –C=CH– vinulic proton, JH-H = 16.4 Hz), 7.3–7.9 (m, 8 aryl, 4 phenyl), 8.09–8.13 (d, 1H, –CH=C–, vinylic proton, JH-H = 16.4 Hz), 10.2 (s, 1H, –NH of benzimidazole), 13C NMR (DMSO-, 100 MHz) 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 (/): 343.2 (M+), Anal. Calcd. for C22H15FN2O: 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 (3k)

Brown crystals, Yield (3.2 g, 90%), m.p 130–132°C, IR (KBr, in cm−1): 3426 (–NH), 2898 (=C–H), 1909 (C=N), 1601 (C=C), 1680 (C=O), 1H NMR (DMSO-, 400 MHz) ppm: 7.09–7.13 (d, 1H, –C=CH– vinulic proton, JH-H = 16.4 Hz), 7.3–7.9 (m, 8 aryl, 4 phenyl), 8.09–8.13 (d, 1H, –CH=C–, vinylic proton, JH-H = 16.4 Hz), 10.2 (s, 1H, –NH of benzimidazole), 13C NMR (DMSO-, 100 MHz) 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 (/): 359.1 (M+), Anal. Calcd. for C22H15ClN2O: 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°C, IR (KBr, in cm−1): 3410 (–NH), 2960 (=C–H), 1680 (C=N), 1620 (C=C), 1670 (C=O), 1H NMR (DMSO-, 400 MHz) ppm: 7.0–8.3 (m, 8 aryl, 4 phenyl and 2 vinylic protons, JH-H = 16.4 Hz), 10.2 (s, 1H, –NH of benzimidazole), 13C NMR (DMSO-, 100 MHz) 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 (/): 370.2 (M+), Anal. Calcd. for C22H15N3O3: 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%.

2.2.8. (E)-(2-(4-Methylstyryl)-1H-benzimidazol-6-yl)(phenyl)methanone (3m)

Black crystals, Yield (3.2 g, 90%), m.p 198–200°C, IR (KBr, in cm−1): 3420 (–NH), 3214 (=C–H), 1642 (C=N), 1603 (C=C), 1616 (C=O), 1H NMR (DMSO-, 400 MHz) ppm: 2.4 (s, 3H, –CH3), 7.0–8.2 (m, 8 aryl, 4 phenyl and 2 vinylic protons, JH-H = 16.4 Hz), 10.0 (s, 1H, –NH of benzimidazole), 13C NMR (DMSO-, 100 MHz) 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 (/): 370.2 (M+), Anal. Calcd. for C22H15N3O3: 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°C, IR (KBr, in cm−1): 3422 (–NH), 2917 (=C–H), 1644 (C=N), 1575 (C=C), 1609 (C=O), 1H NMR (DMSO-, 400 MHz) ppm: 2.5 (s, 2H, –CH2), 6.2–6.26 (d, 1H, –C=CH–, vinylic proton, JH-H = 16.4 Hz), 7.0–8.0 (m, 8 aryl, 4 phenyl and 1 vinylic protons, JH-H = 16.4 Hz), 9.8 (s, 1H, –NH of benzimidazole), 13C NMR (DMSO-, 100 MHz) 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 (/): 370.2 (M+), Anal. Calcd. for C22H15N3O3: 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%.

2.2.10. (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°C, IR (KBr, in cm−1): 3423 (–NH), 2921 (=C–H), 1642 (C=N), 1597 (C=C), 1617 (C=O), 1H NMR (DMSO-, 400 MHz) ppm: 6.6–8.1 (m, 8 aryl, 3 furanyl and 2 vinylic protons, JH-H = 16.4 Hz), 10.2 (s, 1H, –NH of benzimidazole), 13C NMR (DMSO-, 100 MHz) 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 (/): 370.2 (M+), Anal. Calcd. for C22H15N3O3: 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%.

2.2.11. (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°C, IR (KBr, in cm−1): 3427 (–NH), 3060 (=C–H), 1633 (C=N), 1597 (C=C), 1614 (C=O), 1H NMR (DMSO-, 400 MHz) ppm: 6.6–8.1 (m, 8 aryl, 3 thiophenyl and 2 vinylic protons, JH-H = 16.4 Hz), 10.2 (s, 1H, –NH of benzimidazole), 13C NMR (DMSO-, 100 MHz) 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 (/): 370.2 (M+), Anal. Calcd. for C22H15N3O3: 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%.

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-styryl-benzimidazole derivatives 3(a–p), by direct condensation of equivalent amounts of substituted -phenylenediamines 1(a-b) with various cinnamic acids 2(a–h) using 10–20 mol % of triacetylborate and glycerol (10 mL) as reaction medium at 160–180°C for 3–5 h (Scheme 1).

260726.sch.001
Scheme 1: Synthesis of 2-styrylbenzimidazoles 3(a–p) from 1(a-b) and 2(a–h).

In an alternative approach, 2-methylbenzimidazoles 4(a-b) 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°C for 5-6 h resulted 2-styryl-benzimidazole 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).

260726.sch.002
Scheme 2: Synthesis of 2-styrylbenzimidazoles 3(a–p) from 4(a-b) and 5(a–h).

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). It was found that only 10 mol% of triacetylborate and glycerol as reaction medium at 170°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.

tab1
Table 1: Synthesis of 2-(2-(4-chloro-phenyl)-vinyl)-1-H-benzimidazoles.

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 H2SO4 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. H2SO4) 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).

260726.sch.003
Scheme 3: Plausible mechanism for the formation of 2-styrylbenzimidazoles (3) from (4) and arylaldehyde (5) using glycerol and triacetylborate.

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).

260726.sch.004
Scheme 4: The alternative proposed mechanism for the formation of (3) from (1) and (4) using glycerol and triacetylborate.

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.

tab2
Table 2: Synthesis of 2-hetero/styryl-benzimidazoles 3(a–p) from cinnamic acids 2(a–h) and benzaldehydes 5(a–h).

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°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.

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. View at Publisher · View at Google Scholar
  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. View at Publisher · View at Google Scholar
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar
  5. M. J. Jacobson, “Ethylcinnamate in experimental tuberculosis,” Bulletins et Mémoires de la Société Médicale des Hôpitaux de Paris, vol. 35, pp. 322–325, 1919. View at Google Scholar
  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. View at Google Scholar
  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. View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar · View at Scopus
  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. 481–487, 2005. View at Google Scholar · View at Scopus
  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. View at Publisher · View at Google Scholar
  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. View at Publisher · View at Google Scholar · View at Scopus