Journal of the Korean Chemical Society (대한화학회지)

Korean Chemical Society (대한화학회)
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Chemoselective Synthesis of 2-Aryl-1-arylmethyl-1H-benzo[d]imidazoles Using Indion 190 Resin as a Heterogeneous Recyclable Catalyst

회수 가능한 indion 190 resin 촉매를 이용한 2-aryl-1-arylmethyl-1Hbenzo[d]imidazoles계 화합물의 선택적인 합성

  • Reddy, L. Srinivasula (Department of Chemistry, S.V.University) ;
  • Reddy, N. C. Gangi (Department of Chemistry, Yogi Vemana University) ;
  • Reddy, T. Ram (Department of Chemistry, S.V.University) ;
  • Lingappa, Y. (Department of Chemistry, Yogi Vemana University) ;
  • Mohan, Reddy Bodireddy (Department of General Engineering, Basic Sciences and Humanities, Sree Vidyanikethan Engineering College)
  • Received : 2010.07.19
  • Accepted : 2010.09.07
  • Published : 2011.04.20
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Abstract

Keywords

INTRODUCTION

1,2-Disubstituted benzimidazoles show significant activity against several viruses such as HIV, herpes (HSV-1), RNA, influenza, and human cytomegalovirus (HCMV).1-5 In addition, benzimidazoles are also used in various fields of chemistry as topoisomerase inhibitors, selective neuropeptide YY1 receptor antagonists, angiotensin II inhibitors, 5-HT3 antagonists in isolated guinea pig ileum, potential antitumor agents, antimicrobial agents, smooth muscle cell proliferation inhibitors, factor Xa inhibitors and in the treatment of interstitial cystitis.6-11 In light of the affinity, they display towards a variety of enzymes and protein receptors, medicinal chemists would certainly classify them as ‘privileged sub-structures’ for drug design.12,13 In view of remarkable biological activities of the substituted benzimidazoles, their preparation has gained significant interest in recent years. A number of improved methods have been developed for the synthesis of benzimidazoles involves a reaction between an o-phenylendiamine and a carboxylic acid or its derivative (nitrile, amidate and orthoester) under harsh dehydrating condition.14-17 The most popular strategies for the synthesis of 1,2-disubstitted benimidazoles include N-alkylation of 2-substituted benimidazole in the presence of strong base,18,19 N-alkylation of o-nitroanilides followed by a reductive cyclization,20,21 cyclocondensation of N-substituted o-aminoanilides,22 and the condensation of N-substituted phenylenediamine with sodium salt of α-hydroxy benzylsulphonic acid.23 In addtion, 1,2-disbstituted benzimidazoles are also be accessed by direct one-step condensation of o-phenylenediamines with aldehydes by involving the influence of different acid catalysts under various reaction conditions24-33 or by using polymer-supported hypervalent iodine (PDIAS) as a reagent.34 But one of the major margins of these methodologies is that they show poor selectivity in terms of N-substitution, which results in the formation of two compounds i.e, the formation of a 2-substituted benzimidazole along with 1,2-disubstituted benzimidazole as a mixture.24-26,28,33-40

Herein, we report the synthesis of 1,2-disubtituted benzimidazoles (3) by the reaction of an o-phenylenediamine (1) and various aromatic aldehydes (2) in the presence of Indion 190 resin (Scheme 1).

The plausible mechanism of conversion is shown in Scheme 2. The activation of the aldehydic carbonyl oxygen by the acidic proton of Indion 190 resin and followed by condensation with o-phenylenediamine gives dibenzylidene-o-phenylenediamine (4), which is on further cyclization followed by hydride shift provides 1,2-disubtituted benzimidazoles.

Scheme 1.Preparation of 2-aryl-1-arylmethyl-1H-benzo[d]imidazoles (3).

Scheme 2.The formation of 2-aryl-1-arylmethyl-1H-benzo[d] imidazoles (3) from o-phenylenediamine (1) and aromatic aldehyde (2) through dibenzylidene-o-phenylenediamine (4).

 

RESULTS AND DISCUSSIONS

At the beginning, to evaluate the catalytic efficiency of Indion 190, the reaction of o-phenelenediamine (1) and benzaldehyde (2a) was carried out by employing 0.100 g of the catalyst in methanol at room tempetarure for 24 h. However, the resulting yield was not good (entry a, Table 1). Later optimization of the reaction conditions was studied next to increase the yield of the product. Towards this direction, reactions were performed in various solvents by loading different amounts of catalyst. The results were listed in Table 1. The conversion was significantly increased to 96% within shoter time by adding 0.100 g of the catalyst in acetonitrile (entry f, Table 1). Other solvents such as DMF, acetone, DCM, ethanol and methanol are provided unfavorable results for this reaction.

The efficiency of this method was proved by reacting various aromatic aldehydes (2) with o-phenylenediamine (1) using 0.100 g of Indion 190 resin in acetonitrile (Scheme 1, Table 2). However, an aldehyde with a strong electron withdrawing group afforded the product with high yield in less time compared to an aldehyde with a strong electron releasing group. As for an example the reaction of p-nitrobenzaldehyde (2e) reacted with o-phenylenediamine (1) takes 3.5 h to form its corresponding product (3e) with an yield of 93% (entry e, Table 2), while, p-methoxybenzaldehyde (2c) has taken 5.0 h to provide its corresponding product (3c) with an yield of 82% (entry c, Table 2).

Table 1.Effect of the solvent on time and isolated yield of the reaction of o-phenylenediamine (1) and benzaldehyde (2a) in presence of a catalytic amounts of Indion 190.

The catalyst, Indion 190 resin is a commercially available acidic reagent. It can be easily handled and removed by filtration from the reaction mixture. Thus the process is environmentally benign. The catalyst was recovered, activated and reused for consecutive times without loss of selectivity.

In conclusion, we have developed a novel and highly efficient method for the synthesis of 2-aryl-1-arylmethyl-1H-benzo[d]imidazoles (3) in high yields from an o-phenylenediamine (1) and a wide variety of aromatic aldehydes (2) in the presence of Indion 190 resin as a heterogeneous catalyst. The mildness of the conversion, simple experimental procedure, clear reaction profiles, high yields and chemoselectivity, short reaction times and reusability of the catalyst are the noteworthy advantages of the protocol. We feel the procedure can be utilized for large-scale eco-friendly preparation of 2-aryl-1-arylmethyl-1H-benzo[d]imidazoles (3).

General Experimental Procedure

In a 50 mL, round-bottom flask, o-phenylenediamine (1) (1 mmol) and an aromatic aldehyde (2a) (2 mmol) were stirred in the presence of Indion 190 in an acetonitrile (10 ml) at 50-60 ℃ emperature. The reaction progress was monitored by TLC. After completion of the reaction (as shown in Table 2), the reaction mixture and catalyst were separated by filtration. The filtrate was concentrated under reduced pressure to furnish the crude product, which was further purified by column chromatography [Silica gel, EtOAc/hexane (1:6)] to obtain the pure 2-aryl-1-arylmethyl-1H-benzo[d]imidazoles. The catalyst was washed with water, activated and reused for fresh reactions. All the compounds gave satisfactory spectroscopic data in accordance with their proposed structures. Compounds 3a-d, 3f and 3j are synthesized and reported in literature.32 The spectral data of unknown compounds 3e, 3g-i and 3k were given below.

Table 2.aPhysical Properties of Indion 190 resin: Macroporous Strong Acidic Cationic resin, styrene DVB matrix, SO3- functional group, particle size range 0.42-1.2, Max. Operating temp. 150 ℃, total exchange capacity 4.7 meq/g. and the structures of the products were determined from their spectroscopic (1H NMR and MS) and elemental analysis data.

Compound 3e

mp: 131-133 ℃; 1H NMR (400 MHz, CDCl3): δ 5.58 (s, 2H), 7.52-7.20 (m, 4H), 7.78 (dd, J = 8.0 and 2.0 Hz, 1H), 7.83 (d, J = 9.2 Hz, 1H), 7.93 (d, J = 8.4 Hz, 2H), 8.24(d, J = 8.8 Hz, 2H), 8.38-8.31 (m, 2H); ESI-MS (m/z): 375 (M++1); Anal. Calcd for C20H14N4O4: C, 64.17; H, 3.77; N, 14.97. Found: C, 64.12; H, 3.74; N, 14.93.

Compound 3g

mp: 93-95 ℃; 1H NMR (400 MHz, CDCl3): δ 5.72 (s, 2H), 6.87 (d, J = 6.2 Hz, 1H), 6.90 (dd, J = 8.0 and 2.0 Hz, 1H), 7.16 (d, J = 8.0 Hz, 1H), 7.31-7.24 (m, 3H), 7.39 (d, J = 8.8 Hz, 1H), 7.48 (dd, J = 8.0 and 2 Hz, 1H), 7.53 (dd, J = 8.0 and 2.0 Hz, 1H), 7.84 (d, J = 9.2 Hz, 1H); ESI-MS (m/z): 297 (M++1); Anal. Calcd for C16H12N2S2: C, 64.83; H, 4.08; N, 9.45. Found: C, 64.75; H, 4.04; N, 9.42.

Compound 3h

mp: 122-126 ℃; 1H NMR (400 MHz, CDCl3): δ 1.25 (s, 18H), 5.45 (s, 2H), 7.06 (d, J = 8.0 Hz, 2H), 7.22 (dd, J = 8.2 and 2.8 Hz, 2H), 7.35-7.29 (m, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.66 (d, J = 8.2 Hz, 2H), 7.86 (d, J = 8.4 Hz, 2H); ESI-MS (m/z): 397 (M++1); Anal. Calcd for C28H32N2: C, 84.80; H, 8.13; N, 7.06. Found: C, 84.76; H, 8.10; N, 7.04.

Compound 3i

mp: 230 ℃; 1H NMR (400 MHz, CDCl3): δ 5.56 (s, 2H), 6.91 (dd, J = 7.8 and 2.1 Hz, 1H), 6.99 (dd, J = 7.6 and 2.3 Hz, 1H), 7.64-7.35 (m, 15H), 7.7 (d, J = 8.2 Hz, 2H), 7.82 (d, J = 8.0 Hz, 2H), 7.90 (d, J = 8.4 Hz, 2H); ESI-MS (m/z): 437 (M++1); Anal. Calcd for: C32H24N2: C, 88.04; H, 5.54; N, 6.42. Found: C, 88.00; H, 5.50; N, 6.38.

Compound 3k

mp: 119-123 ℃; 1H NMR (400 MHz, CDCl3): δ 2.22 (s, 6H), 2.38 (s, 3H), 2.58 (s, 3H), 5.17 (s, 2H), 6.53 (d, J = 8.2 Hz, 1H), 6.83 (dd, J = 8.0 and 2.6 Hz, 1H), 7.00-6.95 (m, 2H), 7.31-7.15 (m, 4H), 7.86 (d, J = 8.0 Hz, 2H); ESIMS (m/z): 341 (M++1); Anal. Calcd for C24H24N2: C, 84.67; H, 7.11; N, 8.23; Found: C, 84.65; H, 7.07; N, 8.21.

References

  1. Tebbe, M. J.; Spitzer, W. A.; Victor, F.; Miller, S. C.; Lee, C. C.; Sattelberg, T. R.; Mckinney, E., Tang, C. J. J. Med. Chem. 1997, 40, 3937. https://doi.org/10.1021/jm970423k
  2. Porcari, A. R.; Devivar, R. V.; Kucera, L. S.; Drach, J. C.; Townsend, L.B. J. Med. Chem. 1998, 41, 1252. https://doi.org/10.1021/jm970559i
  3. Roth, M.; Morningstar, M. L.; Boyer, P. L.; Hughes, S. H.; Bukheit, R. W.; Michejda, C. J. J. Med. Chem. 1997, 40, 4199. https://doi.org/10.1021/jm970096g
  4. Migawa, M. T.; Giradet, J. L.; Walker, J. A.; Koszalka, G. W.; Chamberlain, S. D.; Drach, J. C.; Townsend, L. B. J. Med. Chem. 1998, 41, 1242. https://doi.org/10.1021/jm970545c
  5. Tamm, I. Science. 1957, 126, 1235.
  6. Kim, J. S.; Gatto, B.; Yu, C.; Liu, A.; Liu, L. F.; Lavioe, E. J. Med. Chem. 1996, 39, 992. https://doi.org/10.1021/jm950412w
  7. Zarrinmayeh, H.; Zimmerman, D. M.; Cantrell, B. E.; Schober, D. A.; Bruns, R. F. Bioorg. Med. Chem. Lett. 1999, 9, 647. https://doi.org/10.1016/S0960-894X(99)00082-7
  8. Kohara, Y.; Kubo, K.; Imamiya, E.; Wada, T.; Inada, Y.; Naka, T. J. Med. Chem. 1996, 39, 5228. https://doi.org/10.1021/jm960547h
  9. Lopez, M. L. R.; Benhamu, B.; Morcillio, M. J.; Tejada, I. D.; Orensanz, L.; Alfaro, L.; Martin, M. I. J. Med. Chem. 1999, 33, 814.
  10. Forseca, T.; Gigante, B.; Gilchrist, T. L. Tetrahedron. 2001, 57, 1793. https://doi.org/10.1016/S0040-4020(00)01158-3
  11. Zhao, J.; Arnaiz, B.; Griedel; B.; Sakata, J.; Dallas; M.; Whitlow, L.; Trinh, D.; Post, J.; Liang, A.; Morrissey, M.; Shaw, K. Bioorg. Med. Chem. Lett. 2000, 10, 963. https://doi.org/10.1016/S0960-894X(00)00139-6
  12. Evans, B. E.; Rittle, K. E.; Bock, M. G.; Dipardo, R. M.; Freidinger, R. M.; Whitter, W. L.; Lundell, G. F.; Vender, D. F.; Anderson, P. S.; Chang, R. S.; Chang, R.S.L.; Lotti, V. J; Gerino, D. J.; Chen, T. B.; Kling, P. J.; Kunkel, K. A.; Springer, J. P.; Hirsh field, J. J. Med. Chem. 1988, 31, 2235. https://doi.org/10.1021/jm00120a002
  13. Mason, J. S.; Morize, I.; Menard, P. R.; Cheney, D. L.; Hume, C.; Labaudiniere, R. F. J. Med. Chem. 1999, 42, 3251. https://doi.org/10.1021/jm9806998
  14. Preston, P. N. Chemistry of Heterocyclic Compounds; Vol. 40, Weissberger, A., Taylor, E. C., Eds.; Wiley & Sons: 1981.
  15. Sun, Y. C.; Chi, C. M. Synlett. 2000, 591.
  16. Huang, W.; Scarborough, R. M. Tetrahedron Lett. 1999, 40, 2665. https://doi.org/10.1016/S0040-4039(99)00293-2
  17. Dudd, L. M.; Venardou, E.; Garcia-Verdugo, E.; Licence, P.; Blake, A. J.; Wilson, C.; Poliako, M. Green Chem. 2003, 5, 187. https://doi.org/10.1039/b212394k
  18. Porcari, A. R.; Devivar, R. V.; Kucera, L. S.; Drach, J. C.; Townsend, L. B. Design. J. Med. Chem. 1998, 41, 1252. https://doi.org/10.1021/jm970559i
  19. Ries, U. J.; Mihm, G.; Narr, B.; Hasselbach, K. M.; Wittneben, H.; Entzeroth, M.; van Meel, J. C. A.; Wienen, W.; Hauel, N. H. J. Med. Chem. 1993, 36, 4040. https://doi.org/10.1021/jm00077a007
  20. Roth, T.; Morningstar, M. L.; Boyer, P. L.; Hughes, S. H.; Buckheit Jr., R. W.; Michejda, C. J. J. Med. Chem. 1997, 40, 4199. https://doi.org/10.1021/jm970096g
  21. Morningstar, M. L.; Roth, T.; Farnsworth, D. W.; Smith, M. K.; Watson, K.; Buckheit Jr., R.W.; Das, K.; Zhang, W.; Arnold, E.; Julias, J. G.; Hughes, S. H.; Michejda, C. J. J. Med. Chem. 2007, 50, 4003. https://doi.org/10.1021/jm060103d
  22. Takeuchi, K.; Bastian, J. A.; Gifford-Moore, D. S.; Harper, R. W.; Miller, S. C.; Mullaney, J. T.; Sall, D. J.; Smith, G. F.; Zhang, M.; Fisher, M. J. Bioorg. Med. Chem. Lett. 2000, 10, 2347. https://doi.org/10.1016/S0960-894X(00)00454-6
  23. Gker, H.; Ozden, S.; Ylldlz, S.; Boykin, D. W. Eur. J. Med. Chem. 2005, 40, 1062. https://doi.org/10.1016/j.ejmech.2005.05.002
  24. Smith, J. G.; Ho, I. Tetrahedron Lett. 1971, 12, 3541. https://doi.org/10.1016/S0040-4039(01)97226-0
  25. Nagata, K.; Itoh, T.; Ishikawa, H.; Ohsawa, A. Heterocycles. 2003, 61, 93. https://doi.org/10.3987/COM-03-S47
  26. Itoh, T.; Nagata, K.; Ishikawa, H.; Ohsawa, A. Heterocycles. 2004, 63, 2769. https://doi.org/10.3987/COM-04-10215
  27. Perumal, S.; Mariappan, S.; Selvaraj, S. Arkivoc. 2004, 8,46.
  28. Chakrabarty, M.; Karmakar, S.; Mukherji, A.; Arima, S.; Harigaya, Y. Heterocycles. 2006, 68, 967. https://doi.org/10.3987/COM-06-10692
  29. Sun, P.; Hu, Z. J. Heterocycl. Chem. 2006, 43, 773. https://doi.org/10.1002/jhet.5570430338
  30. Salehi, P.; Dabiri, M.; Zolfigol, M. A.; Otokesh, S.; Baghbanzadeh, M. Tetrahedron Lett. 2006, 47, 2557. https://doi.org/10.1016/j.tetlet.2006.02.049
  31. Varala, R.; Nasreen, A.; Enugala, R.; Adapa, S. R. Tetrahedron Lett. 2007, 48, 69. https://doi.org/10.1016/j.tetlet.2006.11.010
  32. Saikat, D. S.; Dilip, K. Synth. Commun. 2009, 39, 980. https://doi.org/10.1080/00397910802448440
  33. Jacob, R. G.; Dutra, L. G.; Radatz, C. S.; Mendes, S. R.; Perin, G; Lenardao, E. J. Tetrahedron Lett. 2009, 50, 1495. https://doi.org/10.1016/j.tetlet.2009.01.076
  34. Kumar, A.; Maurya, R. A.; Ahmad, P. J. Comb. Chem. 2009, 11, 198. https://doi.org/10.1021/cc8001876
  35. Kokare, Nagnnath D.; Sangshetti, Jaiprakash N.; Shinde, Devanand B. Synthesis. 2007, 18, 2829.
  36. Yadav, J. S.; Reddy, B. V. Subba; Premalatha, K.; Shankar, K. Shiva. Canadian Journal of Chemistry. 2008, 86, 124. https://doi.org/10.1139/v07-140
  37. Ma, Huiqiang; Wang, Yulu; Li, Jianping; Wang, Jinye. Heterocycles.2007, 71, 135. https://doi.org/10.3987/COM-06-10920
  38. Ravi, Varala; Ramu, Enugala; Vijay, Kotra; Rao, Adapa Srinivas. Chemical and Pharmaceutical Bulletin 2007, 55, 1254. https://doi.org/10.1248/cpb.55.1254
  39. Niknam, Khodabakhsh; Zolfigol, Mohammad Ali; Safikhani, Negar. Synth. Commun. 2008, 38, 2919. https://doi.org/10.1080/00397910801993743
  40. Beheshtiha, Yahya S.; Heravi, Majid M.; Saeedi, Mina; Karimi, Narges; Zakeri, Masumeh; Tavakoli-Hossieni, Niloofar. Synth. Commun. 2010, 40, 1216. https://doi.org/10.1080/00397910903062280

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