A new, efficient method for the synthesis of 2-aryl substituted benzimidazole by using silica supported periodic acid (H5IO6-SiO2) as a catalyst has been developed. The salient feature of the present method includes mild reaction condition, short reaction time, high yield and easy workup procedure. The synthesized benzimidazoles exhibited potent anticancer activity against MCF7 and HL60 cell lines. 1. Introduction The benzimidazole nucleus is commonly present in a large number of natural products as well as pharmacologically active compounds [1]. It shows a wide spectrum of biological and pharmacological properties such as antifungal [2], antimicrobial [3], anthelmintic [4, 5], antiviral [6, 7], topoisomerase inhibition [8] and anticancer activities [9]. Some of their derivatives are marketed as antifungal drug (Carbendazim) [10], anthelmintic drug (Mebendazole and Thiabendazole) [11], antipsychotic drug (Pimozide) [12] and antiulcer agent (Omeprazole) [13]. Owing to their interesting pharmacological properties, great attention has been paid to the synthesis of benzimidazoles. Two main synthetic methods were well known in the literature. The most common method is direct condensation of 1,2-phenylenediamine and carboxylic acids [14, 15] or their derivatives [16], that require strong acidic conditions and sometimes need high temperature or the use of microwave [17]. The other synthetic route involves a two-step procedure that includes the cyclo-dehydrogenation of aniline Schiff’s bases, which are often generated in situ from the condensation of 1,2-phenylenediamines and aldehydes [18], followed by oxidation with stoichiometric amount of oxidants, such as MnO2 [19], Oxone [20], NaHSO3 [21, 22], I2/KI/K2CO3/H2O [23] or catalytic use of CAN [24] and AIKIT-5 [25]. More recently, 2-alkyl substituted benzimidazoles are synthesized by using hexafluorophosphoric acid under microwave condition [26]. There is renewed interest in the silica supported catalyzed reactions [27]. These reactions have relatively shorter reaction time with high yield and cleaner chemistry. Moreover, the catalyst is easily separated from reaction mixture by simple filtration. There are very few reports involving solid supported catalyzed reaction for synthesis of benzimidazole derivatives. Jacob et al. [28] synthesized 1,2-disubstituted benzimidazoles by silica supported ZnCl2 catalyst that was found to be of poor yield. Patil et al. [29] developed a method for synthesis of 2-alkyl benzimidazoles using silica supported HBF4. Paul and Basu [30] described the synthesis of 1,2-disubstituted
References
[1]
G. Balboni, C. Trapella, Y. Sasaki et al., “Influence of the side chain next to C-terminal benzimidazole in opioid pseudopeptides containing the Dmt-Tic pharmacophore,” Journal of Medicinal Chemistry, vol. 52, no. 17, pp. 5556–5559, 2009.
[2]
W. A. Maxwell and G. Brody, “Antifungal activity of selected benzimidazole compounds,” Applied microbiology, vol. 21, no. 5, pp. 944–945, 1971.
[3]
D. Sharma, B. Narasimhan, P. Kumar, and A. Jalbout, “Synthesis and QSAR evaluation of 2-(substituted phenyl)-1H-benzimidazoles and [2-(substituted phenyl)-benzimidazol-1-yl]-pyridin-3-yl-methanones,” European Journal of Medicinal Chemistry, vol. 44, no. 3, pp. 1119–1127, 2009.
[4]
A. A. Farahat, E. Paliakov, A. Kumar et al., “Exploration of larger central ring linkers in furamidine analogues: synthesis and evaluation of their DNA binding, antiparasitic and fluorescence properties,” Bioorganic & Medicinal Chemistry, vol. 19, no. 7, pp. 2156–2167, 2011.
[5]
D. Valdez-Padilla, S. Rodríguez-Morales, A. Hernández-Campos et al., “Synthesis and antiprotozoal activity of novel 1-methylbenzimidazole derivatives,” Bioorganic & Medicinal Chemistry, vol. 17, no. 4, pp. 1724–1730, 2009.
[6]
Y. F. Li, G. F. Wang, P. L. He et al., “Synthesis and anti-hepatitis B virus activity of novel benzimidazole derivatives,” Journal of Medicinal Chemistry, vol. 49, no. 15, pp. 4790–4794, 2006.
[7]
H. Banie, A. Sinha, R. J. Thomas, J. C. Sircar, and M. L. Richards, “2-phenylimidazopyridines, a new series of golgi compounds with potent antiviral activity,” Journal of Medicinal Chemistry, vol. 50, no. 24, pp. 5984–5993, 2007.
[8]
P. S. Charifson, A. L. Grillot, T. H. Grossman et al., “Novel dual-targeting benzimidazole urea inhibitors of DNA gyrase and topoisomerase IV possessing potent antibacterial activity: intelligent design and evolution through the judicious use of structure-guided design and stucture-activity relationships,” Journal of Medicinal Chemistry, vol. 51, no. 17, pp. 5243–5263, 2008.
[9]
J. Chen, Z. Wang, C. M. Li et al., “Discovery of novel 2-aryl-4-benzoyl-imidazoles targeting the colchicines binding site in tubulin as potential anticancer agents,” Journal of Medicinal Chemistry, vol. 53, no. 20, pp. 7414–7427, 2010.
[10]
H. G？ker, C. Ku？, D. W. Boykin, S. Y？ld？z, and N. Altanlar, “Synthesis of some new 2-substituted-phenyl-1H-benzimidazole-5-carbonitriles and their potent activity against Candida species,” Bioorganic & Medicinal Chemistry, vol. 10, no. 8, pp. 2589–2596, 2002.
[11]
G. N. Vázquez, L. Yépez, A. H. Campos, et al., “Synthesis and antiparasitic activity of albendazole and mebendazole analogues,” Bioorganic & Medicinal Chemistry, vol. 11, no. 21, pp. 4615–4622, 2003.
[12]
K. J. Spivak and Z. Amit, “Effects of pimozide on appetitive behavior and locomotor activity: dissimilarity of effects when compared to extinction,” Physiology & Behavior, vol. 36, no. 3, pp. 457–463, 1986.
[13]
P. Lindberg, P. Nordberg, T. Alminger, et al., “The mechanism of action of the gastric acid secretion inhibitor omeprazole,” Journal of Medicinal Chemistry, vol. 29, no. 8, pp. 1327–1329, 1986.
[14]
S. B. Mohan, T. P. Behera, and B. V. V. Ravi Kumar, “Microwave irradiation versus conventional method: synthesis of benzimidazolyl chalcone derivatives,” International Journal of ChemTech Research, vol. 2, no. 3, pp. 1634–1637, 2010.
[15]
A. K. Tiwari and A. Mishra, “Synthesis and antiviral activity of N-substituted-2-subastituted benzimidazole derivatives,” Indian Journal of Chemistry B, vol. 45, pp. 489–493, 2006.
[16]
R. J. Perry and B. D. Wilson, “A novel palladium-catalyzed synthesis of 2-arylbenzimidazoles,” Journal of Organic Chemistry, vol. 58, no. 25, pp. 7016–7021, 1993.
[17]
K. Bourgrin, A. Loupy, and M. Soufiaoui, “Trois nouvelles voies de synthèse des dérivés 1, 3-azoliques sous micro-ondes,” Tetrahedron, vol. 54, no. 28, pp. 8055–8064, 1998.
[18]
V. R. Ruiz, A. Corma, and M. J. Sabater, “New route for the synthesis of benzimidazoles by a one-pot multistep process with mono and bifunctional solid catalysts,” Tetrahedron, vol. 66, no. 3, pp. 730–735, 2010.
[19]
I. Bhatnagar and M. V. George, “Oxidation with metal oxides-II: oxidation of chalcone phenylhydrazones, pyrazolines, o-aminobenzylidine anils and o-hydroxy benzylidine anils with manganese dioxide,” Tetrahedron, vol. 24, no. 3, pp. 1293–1298, 1968.
[20]
P. L. Beaulieu, B. Haché, and E. Von Moos, “A practical oxone-mediated, high-throughput, solution-phase synthesis of benzimidazoles from 1,2-phenylenediamines and aldehydes and its application to preparative scale synthesis,” Synthesis, no. 11, pp. 1683–1692, 2003.
[21]
M. A. Weidner-Wells, K. A. Ohemeng, V. N. Nguyen et al., “Amidino benzimidazole inhibitors of bacterial two-component systems,” Bioorganic and Medicinal Chemistry Letters, vol. 11, no. 12, pp. 1545–1548, 2001.
[22]
S. E. López, J. Restrepo, B. Pérez, S. Ortiz, and J. Salazar, “One pot microwave promoted synthesis of 2-aryl-1H-benzimidazoles using sodium hydrogen sulfite,” Bulletin of the Korean Chemical Society, vol. 30, no. 7, pp. 1628–1630, 2009.
[23]
P. Gogoi and D. Konwar, “An efficient and one-pot synthesis of imidazolines and benzimidazoles via anaerobic oxidation of carbon-nitrogen bonds in water,” Tetrahedron Letters, vol. 47, no. 1, pp. 79–82, 2006.
[24]
K. Bahrami, M. M. Khodaei, and F. Naali, “Mild and highly efficient method for the synthesis of 2-arylbenzimidazoles and 2-arylbenzothiazoles,” Journal of Organic Chemistry, vol. 73, no. 17, pp. 6835–6837, 2008.
[25]
M. A. Chari, D. Shobha, E. R. Kenawy, S. S. Al-Deyab, B. V. Subba Reddy, and A. Vinu, “Nanoporous aluminosilicate catalyst with 3D cage-type porous structure as an efficient catalyst for the synthesis of benzimidazole derivatives,” Tetrahedron Letters, vol. 51, no. 39, pp. 5195–5199, 2010.
[26]
C. Mukhopadhyay, S. Ghosh, S. Sengupta (Bandyopadhyay), and S. Deb, “Synthesis of 2-alkyl substituted benzimidazoles under microwave irradiation: anti-proliferative effect of some representative compounds on human histiocytic lymphoma cell U937,” RSC Advances, vol. 1, no. 6, pp. 1033–1037, 2011.
[27]
K. Wilson and J. H. Clark, “Solid acids and their use as environmentally friendly catalysts in organic synthesis,” Pure and Applied Chemistry, vol. 72, no. 7, pp. 1313–1319, 2000.
[28]
R. G. Jacob, L. G. Dutra, C. S. Radatz, S. R. Mendes, G. Perin, and E. J. Lenard？o, “Synthesis of 1,2-disubstitued benzimidazoles using SiO2/ZnCl2,” Tetrahedron Letters, vol. 50, no. 13, pp. 1495–1497, 2009.
[29]
A. V. Patil, B. P. Bandgar, and S. H. Lee, “Silica supported fluoroboric acid: an efficient and reusable heterogeneous catalyst for facile synthesis of 2-aliphatic benzothiazoles, benzoxazoles, benzimidazoles and imidazo[4,5-b]pyridines,” Bulletin of the Korean Chemical Society, vol. 31, no. 6, pp. 1719–1722, 2010.
[30]
S. Paul and B. Basu, “Highly selective synthesis of libraries of 1, 2-disubstituted benzimidazoles using silica gel soaked with ferric sulfate,” Tetrahedron Letters, vol. 53, no. 32, pp. 4130–4133, 2012.
[31]
D. Kumar, D. N. Kommi, R. Chebolu, S. K. Garg, R. Kumar, and A. K. Chakraborti, “Selectivity control during the solid supported protic acids catalysed synthesis of 1, 2-disubstituted benzimidazoles and mechanistic insight to rationalize selectivity,” RSC Advances, vol. 3, pp. 91–98, 2013.
[32]
S. Yamazaki, “Chromium(VI) oxide-catalyzed benzylic oxidation with periodic acid,” Organic Letters, vol. 1, no. 13, pp. 2129–2132, 1999.
[33]
L. Xu, J. Cheng, and M. L. Trudell, “Chromium(VI) oxide catalyzed oxidation of sulfides to sulfones with periodic acid,” Journal of Organic Chemistry, vol. 68, no. 13, pp. 5388–5391, 2003.
[34]
A. K. M. L. Rahman, M. Kumashiro, and T. Ishihara, “Direct synthesis of formic acid by partial oxidation of methane on H-ZSM-5 solid acid catalyst,” Catalysis Communications, vol. 12, no. 13, pp. 1198–1200, 2011.
[35]
V. U. Pawar, S. Ghosh, B. A. Chopade, and V. S. Shinde, “Design and synthesis of harzialactone analogues: promising anticancer agents,” Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 24, pp. 7243–7245, 2010.
[36]
M. Shen and T. G. Driver, “Iron(II) bromide-catalyzed synthesis of benzimidazoles from aryl azides,” Organic Letters, vol. 10, no. 15, pp. 3367–3370, 2008.
