H₂O₂/Fe(NO₃)₃-Promoted Synthesis of 2-Arylbenzimidazoles and 2-Arylbenzothiazoles

Abstract

A new, convenient synthesis of 2-substituted benzimidazoles and benzothiazoles is described. Short reaction time, easy and quick isolation of the products, environmentally friendly procedure, excellent chemoselectivity and excellent yields are main advantages of this procedure.

Key words

2-arylbenzimidazole - 2-arylbenzothiazole - hydrogen peroxide - chemoselectivity - aryl aldehydes - solvent-free

References and Notes

• 1 Navarrete-Vázquez G. Yepez-Mulia L. Hernández-Campos A. Tapia A. Hernández-Luis F. Cedillo R. González J. Martínez-Fernández M. Martínez-Grueiro M. Castillo R. Bioorg. Med. Chem.  2003,  11:  4615 
• 2a Özden S. Atabey D. Yýldýz S. Göker H. Bioorg. Med. Chem.  2005,  13:  1587 
• 2b Palmer PJ. Trigg RB. Warrington JV. J. Med. Chem.  1971,  14:  248 
• 3a Andrzejewska M. Yépez-Mulia L. Cedillo-Rivera R. Tapia A. Vilpo L. Vilpo J. Kazimierczuk Z. Eur. J. Med. Chem.  2002,  37:  973 
• 3b Hall IH. Peaty NJ. Henry JR. Easmon J. Heinisch G. Purstinger G. Arch. Pharm. (Weinheim, Ger.)  1999,  332:  115 
• 4 Bénéteau V. Besson T. Guillard J. Léonce S. Pfeiffer B. Eur. J. Med. Chem.  1999,  34:  1053 
• 5 Kücükbay H., Durmaz R., Orhan E., Günal S.; Farmaco; 2003, 58: 431
• 6a Benazzouz A. Boraud T. Dubédat P. Boireau A. Stutzmann J.-M. Gross C. Eur. J. Pharmacol.  1995,  284:  299 
• 6b Jimonet P. Audiau F. Barreau M. Blanchard J.-C. Boireau A. Bour Y. Coléno M.-A. Doble A. Doerflinger G. Huu CD. Donat M.-H. Duchesne JM. Ganil P. Guérémy C. Honoré E. Just B. Kerphirique R. Gontier S. Hubert P. Laduron PM. Blevec JL. Meunier M. Miquet J.-M. Nemecek C. Pasquet M. Piot O. Pratt J. Rataud J. Reibaud M. Stutzmann J.-M. Mignani S. J. Med. Chem.  1999,  42:  2828 
• 7a Hamdouchi C. de Blas J. del Prado M. Gruber J. Heinz BA. Vance L. J. Med. Chem.  1999,  42:  50 
• 7b Girardet J.-L. Townsend LB. J. Org. Chem.  1999,  64:  4169 
• 7c Yeh C.-M. Tung C.-L. Sun C.-M. J. Comb. Chem.  2000,  2:  341 
• 7d Chen JJ. Wei Y. Drach JC. Townsend LB. J. Med. Chem.  2000,  43:  2449 
• 7e Tumelty D. Cao K. Holmes CP. Org. Lett.  2001,  3:  83 
• 7f Mann J. Baron A. Opoku-Boahen Y. Johansson E. Parkinson G. Kelland LR. Neidle S. J. Med. Chem.  2001,  44:  138 
• 7g Raju B. Nguyen N. Holland GW. J. Comb. Chem.  2002,  4:  320 
• 7h Akamatsu H. Fukase K. Kusumoto S. J. Comb. Chem.  2002,  4:  475 
• 7i Hoesl CE. Nefzi A. Houghten RA. J. Comb. Chem.  2003,  5:  155 
• 7j Vourloumis D. Takahashi M. Simonsen KB. Ayida BK. Barluenga S. Winters GC. Hermann T. Tetrahedron Lett.  2003,  44:  2807 
• 8a Chua M.-S. Shi D.-F. Wrigley S. Bradshaw TD. Hutchinson I. Shaw PN. Barrett DA. Stanley LA. Stevens MFG. J. Med. Chem.  1999,  42:  381 
• 8b Kashiyama E. Hutchinson I. Chua M.-S. Stinson SF. Phillips LR. Kaur G. Sausville EA. Bradshaw TD. Westwell AD. Stevens MFG. J. Med. Chem.  1999,  42:  4172 
• 8c Hutchinson I. Chua M.-S. Browne HL. Trapani V. Bradshaw TD. Westwell AD. Stevens MFG. J. Med. Chem.  2001,  44:  1446 
• 8d Leng W. Zhou Y. Xu Q. Liu J. Macromolecules  2001,  34:  4774 
• 8e Hutchinson I. Jennings SA. Vishnuvajjala BR. Westwell AD. Stevens MFG. J. Med. Chem.  2002,  45:  744 
• 9 Kochi M. Green Reaction Media for Organic Synthesis   Blackwell; Oxford: 2005. 
• 10 Seddon KR. Nature (London)  2003,  2:  363 
• 11 Catalytic Oxidations with Hydrogen Peroxide as Oxidant   Strukul G. Kluwer Academic; Dordrecht: 1992. 
• 12 Noyori R. Aoki M. Sato K. Chem. Commun.  2003,  1977 
• 13a Bahrami K. Tetrahedron Lett.  2006,  47:  2009 
• 13b Khodaei MM. Bahrami K. Khedri M. Can. J. Chem.  2007,  58:  7 
• 13c Khodaei MM. Bahrami K. Karimi A. Synthesis  2008,  1682 
• 13d Bahrami K. Khodaei MM. Kamali S. Chin. J. Chem.  2008,  26:  1119 
• 14 Bahrami K. Khodaei MM. Kavianinia I. Synthesis  2007,  547 
• 15 Eynde JJV. Delfosse F. Lor P. Haverbeke YV. Tetrahedron  1995,  51:  5813 
• 16 Das B. Holla H. Srinivas Y. Tetrahedron Lett.  2007,  48:  61 
• 17 Wang Y. Sarris K. Sauer DR. Djuric SW. Tetrahedron Lett.  2006,  47:  4823 
• 18 Ben-Alloum A. Bougrin K. Soufiaoui M. Tetrahedron Lett.  2003,  44:  5935 
• 19 Gogoi P. Konwar D. Tetrahedron Lett.  2006,  47:  79 
• 20 Ben-Alloum A. Bakkas S. Souflaoui M. Tetrahedron Lett.  1998,  39:  4481 
• 21 Bougrin K. Loupy A. Souflaoui M. Tetrahedron  1998,  54:  8055 
• 22 Hein DW. Alheim RJ. Leavitt JJ. J. Am. Chem. Soc.  1957,  79:  427 
• 23 Ben-Alloum A. Bakkas S. Souflaoui M. Tetrahedron Lett.  1997,  38:  6395 
• 25 Charlton PT. Mlalipliant GK. Oxley P. Peak DA.
  J. Chem. Soc.  1951,  485 
• 26 George B. Papadopoulos EP. J. Org. Chem.  1977,  42:  441 

24

Ferric nitrate, hydrogen peroxide (30%) as well as all the aromatic aldehydes, 1,2-phenylenediamine derivatives and 2-aminothiophenol employed as substrates are commer-cially available and were used without further purification. The concentration of the commercial 30% H₂O₂ solution was checked iodometrically prior to use.
General procedure for the Synthesis of Benzimidazoles and Benzothiazoles: A mixture of 1,2-phenylenediamine (1 mmol), aryl aldehyde (1 mmol), H₂O₂ (30%, 4 mmol, 0.4 mL) and Fe(NO₃)₃˙9 H₂O (0.1 mmol, 0.04 g) was heated at 50 ˚C for the appropriate time as mentioned in Table 2. After completion of the reaction, the reaction mixture was dissolved in EtOH (10 mL) and then poured into ice-water (30 mL). The pure solid product was filtered, washed with ice-water and subsequently dried. An identical procedure was employed using 2-aminothiophenol (1 mmol), aryl aldehyde (1 mmol) in the presence of 30% H₂O₂ (4 mmol) and Fe(NO₃)₃.9 H₂O (0.1 mmol) for the synthesis of benzothiazoles (Table 4).
Spectroscopic and Physical Data for Selected Compounds:
2-Phenyl-1 H -benzimidazole: mp 290-291 ˚C (lit. [¹8] 292 ˚C). ^¹H NMR (200 MHz, DMSO-d ₆): δ = 7.19-7.23 (m, 2 H), 7.51-7.61 (m, 5 H), 8.16-8.21 (m, 2 H), 12.91 (br, 1 H, NH). ^¹³C NMR (50 MHz, DMSO-d ₆): δ = 120.1, 123.0, 127.0, 127.3, 129.8, 130.8, 131.0, 152.1.
2-(2-Chlorophenyl)-1 H -benzimidazole: mp 232-234 ˚C (lit. [¹8] 234 ˚C). ^¹H NMR (200 MHz, DMSO-d ₆): δ = 7.26-7.32 (m, 2 H), 7.56-7.73 (m, 5 H), 7.93-7.96 (m, 1 H), 12.78 (br, 1 H, NH). ^¹³C NMR (50 MHz, DMSO-d ₆): δ = 112.1, 119.4, 122.1, 123.1, 127.8, 130.3, 130.7, 131.6, 132.4, 149.4.
2-(4-Hydroxyphenyl)-1 H -benzimidazole: mp 276-278 ˚C (lit. [²5] 279 ˚C). ^¹H NMR (200 MHz, DMSO-d ₆): δ = 5.04 (br, 1 H, OH), 6.91 (d, J = 8.7 Hz, 2 H), 7.12-7.21 (m, 2 H), 7.48-7.57 (m, 2 H), 7.97 (d, J = 8.7 Hz, 2 H), 10.02 (br, 1 H, NH). ^¹³C NMR (50 MHz, DMSO-d ₆): δ = 120.1, 121.4, 125.9, 127.6, 133.9, 144.2, 157.2, 165.
2-(3-Bromophenyl)benzothiazole: mp 91-93 ˚C. ^¹H NMR (200 MHz, DMSO-d ₆): δ = 7.34-7.66 (m, 4 H), 7.91-8.12 (m, 3 H), 8.29-8.31 (m, 1 H). ^¹³C NMR (50 MHz, DMSO-d ₆): δ = 122.1, 123.5, 123.8, 126, 126.6, 126.9, 130.6, 130.9, 134.2, 135.4, 135.8, 154.3, 166.5. Anal. Calcd for C₁₃H₈NSBr: C, 53.81; H, 2.70; N, 4.83; S, 11.05. Found: C, 54.00; H, 2.70; N, 5.20; S, 11.10.
2-(4-Formylphenyl)benzothiazole: mp 135-136 ˚C. ^¹H NMR (200 MHz, DMSO-d ₆): δ = 7.39-7.56 (m, 2 H), 7.90-8.26 (m, 6 H), 10.06 (s, 1 H).^¹³C NMR (50 MHz, DMSO-d ₆): δ = 122.2, 124.1, 126.0, 126.3, 127.1, 128.4, 130.7, 135.8, 138.0, 139.1, 154.5, 191.9. Anal. Calcd for C₁₄H₉NSO: C, 70.27; H, 3.79; N, 5.85; S, 13.41. Found: C, 70.00; H, 3.70; N, 6.10; S, 13.20.
2-(4-Methylphenyl)benzothiazole: mp 85-86 ˚C (lit. [²6] 85-86 ˚C). ^¹H NMR (200 MHz, DMSO-d ₆): δ = 2.41 (s, 3 H), 7.24-7.48 (m, 4 H), 7.86-8.04 (m, 4 H). ^¹³C NMR (50 MHz, DMSO-d ₆): δ = 22.0, 122.0, 123.5, 125.5, 126.7, 127.9, 130.2, 131.3, 135.4, 141.9, 154.6, 168.7.