Efficient One-Pot Synthesis of 2-Substituted Benzimidazoles from Triacyloxyborane Intermediates

Abstract

An efficient one-pot synthesis of 2-substituted benzim­idazoles via triacyloxyborane intermediates is reported. The mild protocol is efficient and tolerant of acid-labile functional groups.

Key words

benzimidazoles - borane-THF - carboxylic acids - tri­acyloxyboranes - diacyloxyboric acids - benzoxazoles

References and Notes

• 1a Fellenius E. Berglindh T. Sachs G. Olbe L. Elander B. Sjostrand SE. Wallmark B. Nature (London)  1981,  290:  159 
• 1b Yamada M. Yura T. Morimoto M. Harada T. Yamada K. Honma Y. Kinoshita M. Sugiura M.
  J. Med. Chem.  1996,  39:  596 
• 2a Eriksson BI. Smith H. Yasothan U. Kirkpatrick P. Nat. Rev. Drug Discovery  2008,  7:  557 
• 2b Hauel NH. Nar H. Priepke H. Ries U. Stassen J. Wienen W.
  J. Med. Chem.  2002,  45:  1757 
• 2c Ueno H. Katoh S. Yokota K. Hoshi J.-i. Hayashi M. Uchida I. Aisaka K. Hase Y. Cho H. Bioorg. Med. Chem. Lett.  2004,  14:  4281 
• 3 Mizuno CS. Chittiboyina AG. Shah FH. Patny A. Kurtz TW. Pershadsingh HA. Speth RC. Karamyan VT. Carvalho PB. Avery MA. J. Med. Chem.  2010,  53:  1076 
• 4a Spasov AA. Yozhitsa IN. Bugaeva LI. Anisimova VA. Pharm. Chem. J.  1999,  33:  232 
• 4b Beaulieu PL. Bousquet Y. Gauthier J. Gillard J. Marquis M. McKercher G. Pellerin C. Valois S. Kukolj G. J. Med. Chem.  2004,  47:  6884 
• 4c Roth T. Morningstar ML. Boyer PL. Hughes SH. Buckheit RW. Michejda CJ. J. Med. Chem.  1997,  40:  4199 
• 5a Mann J. Baron A. Opoku-Boahen Y. Johansson E. Parkinson G. Kelland LR. Neidle S. J. Med. Chem.  2001,  44:  138 
• 5b Soderlind K.-J. Gorodetsky B. Singh AK. Bachur NR. Miller GG. Lown JW. Anti-Cancer Drug Des.  1999,  14:  19 
• 5c Kim JS. Gatto B. Yu C. Liu A. Liu LF. LaVoie EJ. J. Med. Chem.  1996,  39:  992 
• 5d Chen AY. Yu C. Gatto B. Liu LF. Proc. Natl. Acad. Sci. U.S.A.  1993,  90:  8131 
• 6 Janssens F. Torremans J. Janssen M. Stokbroekx RA. Luyckx M. Janssen PAJ. J. Med. Chem.  1985,  28:  1925 
• 7 Schwartz G. Fehse K. Pfeiffer M. Walzer K. Leo K. Appl. Phys. Lett.  2006,  89:  83509 
• 8a Asensio JA. Gomez-Romero P. Fuel Cells  2005,  5 
• 8b Weber J. Antonietti M. Thomas A. Macromolecules  2007,  40:  1299 
• For comprehensive reviews on the chemistry of benz-imidazoles, see:
• 9a Wright JB. Chem. Rev.  1951,  48:  397 
• 9b Preston PN. Chem. Rev.  1974,  74:  279 
• 9c Grimmett MR. Imidazoles and their Benzo Derivatives, In Comprehensive Heterocyclic Chemistry   Vol. 5:  Katritzky AR. Rees CW. Pergamon Press; Oxford: 1984.  p.457-487  
• 9d Preston PN. Benzimidazoles and Congeneric Tricyclic Compounds, In The Chemistry of Heterocyclic Compounds   Part 1, Vol. 40:  Weissberger A. Taylor EC. Wiley; New York: 1981.  p.6-60  
• 10a Sluiter J. Christoffers J. Synlett  2009,  63 
• 10b Czarny A. Wilson WD. Boykin DW. J. Heterocycl. Chem.  1996,  33:  1393 
• 10c Tidwell RR. Geratz JD. Dann O. Volz G. Zeh D. Loewe H. J. Med. Chem.  1978,  21:  613 
• 10d Fairley TA. Tidwell RR. Donkor I. Naiman NA. Ohemeng KA. Lombardy RJ. Bentley JA. Cory M. J. Med. Chem.  1993,  36:  1746 
• 10e Treu M. Karner T. Kousek R. Berger H. Mayer M. McConnell DB. Stadler A. J. Comb. Chem.  2008,  10:  863 
• 11a Murai K. Takaichi N. Takahara Y. Fukushima S. Fujioka H. Synthesis  2010,  520 
• 11b Beaulieu PL. Haché B. von Moos E. Synthesis  2003,  1683 ; and references cited therein
• 11c Eynde JJV. Delfosse F. Lor P. Van Haverbeke Y. Tetrahedron  1995,  51:  5813 
• 11d Du L. Wang Y. Synthesis  2007,  675 
• 12 Yamamoto Y. Mizuno H. Tsuritani T. Mase T. J. Org. Chem.  2009,  74:  1394 
• 13a Evindar G. Batey RA. Org. Lett.  2003,  5:  133 
• 13b Yang D. Fu H. Hu L. Jiang Y. Zhao Y. J. Org. Chem.  2008,  73:  7841 
• 13c Zou B. Yuan Q. Ma D. Angew. Chem. Int. Ed.  2007,  46:  2598 
• 13d Murru S. Patel BK. Le Bras J. Muzart J. J. Org. Chem.  2009,  74:  2217 
• 13e Brian CT. Steer JT. J. Org. Chem.  2003,  68:  6814 
• 13f She J. Jiang Z. Wang Y. Synlett  2009,  2023 
• 13g Zheng N. Anderson KW. Huang X. Nguyen HN. Buchwald SL. Angew. Chem. Int. Ed.  2007,  46:  7509 
• 13h Brasche G. Buchwald SL. Angew. Chem. Int. Ed.  2008,  47:  1932 
• 13i Brian CT. Brunton SA. Tetrahedron Lett.  2002,  43:  1893 
• 14a Pelter A. Levitt TE. Nelson P. Tetrahedron  1970,  26:  1545 
• 14b Collum DB. Chen S. Ganem B. J. Org. Chem.  1978,  43:  4393 
• 14c Ishihara K. Ohara S. Yamamoto H.
  J. Org. Chem.  1996,  61:  4196 
• 14d Huang Z. Reilly JE. Buckle RN. Synlett  2007,  1026 
• 15a Ramsden CA. Rose HL. J. Chem. Soc., Perkin Trans. 1  1997,  2319 
• 15b Nasal A. Kaliszan R. Kuzmierkiewicz W. QSAR  1987,  6:  22 
• 15c Blacker AJ. Farah MM. Hall MI. Marsden MP. Saidi O. Williams JM. Org. Lett.  2009,  11:  2039 
• 15d Moorthy JA. Neogi I. Tetrahedron Lett.  2011,  52:  3868 
• 15e Trivedi R. De S K. Gibbs RA. J. Mol. Catal. A: Chem.  2006,  245:  8 
• 16a Roeder CJ. Day AR. J. Org. Chem.  1941,  6:  25 
• 16b Morgan KJ. Turner AM. Tetrahedron  1969,  25:  915 
• 16c Maras N. Kocevar M. Helv. Chim. Acta  2011,  94:  1860 

17

General Procedure for the Formation of Benzimidazoles
To a carboxylic acid (2 mmol) in toluene (10 mL) in an ice-water bath was added dropwise a solution of borane-THF (1 M, 0.70 mmol) in THF. The mixture was stirred at r.t. for 30 min. Benzene-1,2-diamine (0.66 mmol) was added, and the mixture was heated at reflux with stirring for 12 h. After cooling, the mixture was concentrated in vacuo, and the residue was purified by flash chromatography. The physical data of the products in Table  [¹] , entries 1-11, 15, and 16 are consistent with those of reported literatures,^{¹0e,¹¹c,d,¹5} or those of authentic samples. The new compound characterizations are provided below.
tert -Butyl 2-(5-Methyl-1 H -benzo[ d ]imidazol-2-yl)-ethylcarbamate (Table 1, Entry 12)
^¹H NMR (300 MHz, CDCl₃): δ = 7.43 (d, J = 8.1 Hz, 1 H), 7.32 (s, 1 H), 7.04 (d, J = 8.1 Hz, 1 H), 5.40 (br, 1 H), 3.68-3.61 (m, 2 H), 3.12-3.18 (m, 2 H), 2.45 (s, 3 H), 1.40 (s, 9 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 156.7, 152.2, 132.0, 123.7, 114.3, 114.0, 79.9, 38.4, 30.2, 28.4, 21.6. ESI-HRMS: m/z calcd for C₁₅H₂₁N₃O₂ + H⁺: 276.1712; found 2761723. tert -Butyl 4-[(5-Chloro-1 H -benzo[ d ]imidazol-2-yl)-methyl]piperidine-1-carboxylate (Table 1, Entry 13) ^¹H NMR (500 MHz, CD₃OD): δ = 7.53 (d, J = 1.9 Hz, 1 H), 7.47 (d, J = 8.7 Hz, 1 H), 7.20 (dd, J = 1.5, 8.6 Hz, 1 H), 4.15 (d, J = 13.2 Hz, 2 H), 2.83 (d, J = 7.3 Hz, 2 H), 2.76 (br, 2 H), 2.10-2.02 (m, 1 H), 1.66 (d, J = 12.2 Hz, 2 H), 1.44 (s, 9 H), 1.36-1.28 (m, 2 H). ^¹³C NMR (125 MHz, CD₃OD): δ = 156.6, 156.5, 140.4, 137.8, 129.0, 123.8, 116.3, 115.4, 81.0, 44.6, 37.0, 36.4, 33.0, 28.7. ESI-HRMS: m/z calcd for C₁₈H₂₄ClN₃O₂ + H⁺: 350.1635; found: 350.1642.
5-Bromo-2-(thiophen-2-ylmethyl)-1 H -benzo[ d ]-imidazole (Table 1, Entry 14)
^¹H NMR (500 MHz, CD₃OD): δ = 7.72 (d, J = 1.5 Hz, 1 H), 7.47 (d, J = 8.5 Hz, 1 H), 7.41 (dd, J = 1.5, 8.5 Hz, 1 H), 7.32 (dd, J = 1.5, 5.5 Hz, 1 H), 7.04-7.03 (m, 1 H), 6.99 (dd, J = 3.5, 5.0 Hz, 1 H), 4.52 (s, 2 H). ^¹³C NMR (125 MHz, CD₃OD): δ = 155.8, 141.1, 139.4, 138.4, 128.1, 127.6, 126.6, 126.1, 118.7, 117.0, 116.3, 30.3. ESI-HRMS: m/z calcd for C₁₂H₉BrN₂S + H⁺: 292.9748; found: 292.9768.