Download PDF
Synlett 2010(6): 901-904  
DOI: 10.1055/s-0029-1219395
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Novel Synthesis of 2-Aminobenzimidazoles from Isoselenocyanates

Yuanyuan Xie*, Fan Zhang, Jianjun Li, Xiangjun Shi
Key Laboratory of Pharmaceutical Engineering of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P. R. of China
Fax: +86(571)88320752; e-Mail: pharmlab@zjut.edu.cn;
Further Information

Publication History

Received 10 December 2009
Publication Date:
17 February 2010 (online)

    Permissions and Reprints All articles of this category

Abstract

An efficient one-pot procedure for the synthesis of 2-aminobenzimidazoles from isoselenocyanates and various substituted diamines is described. Precipitation of elemental selenium from the reaction mixture greatly simplifies the purification procedure and also allows it to be re-used for preparation of isoseleno­cyanates. A possible mechanism for the formation of 2-aminobenzimidazoles is proposed.

Key words

2-aminobenzimidazoles - isoselenocyanates - cyclization - selenium recycling

    References and Notes

  • 1a Janssens F. Torremans J. Janssen M. Stokbroekx RA. Luyckx M. Janssen PA. J. Med. Chem.  1985,  28:  1925 
    Google Scholar
  • 1b Bovet D. Bovet-Nitti F. Médicaments du Système Nerveux Végétatif   5th ed.:  Karger; Basel: 1948.  p.741 
    Google Scholar
  • 1c The Extra Pharmacopeia   27th ed.:  Wade A. The Pharmaceutical Press; London: 1978.  p.1287 
    Google Scholar
  • 1d Martin EJ. Critchlow RE. J. Comb. Chem.  1999,  1:  32 
    Google Scholar
  • 2a Beaulieu C. Wang Z. Denis D. Greig G. Lamontagne S. O’Neill G. Slipetz D. Wang J. Bioorg. Med. Chem. Lett.  2004,  14:  3195 
    Google Scholar
  • 2b Kling A. Backfisch G. Delzer J. Geneste H. Graef C. Hornberger W. Lange UEW. Lauterbach A. Seitz W. Subkowski T. Bioorg. Med. Chem.  2003,  11:  1319 
    Google Scholar
  • 2c Snow RJ. Cardozo MG. Morwick TM. Busacca CA. Dong Y. Eckner RJ. Jacober S. Jakes S. Kapadia S. Lukas S. Panzenbeck M. Peet GW. Peterson JD. Prokopowicz AS. Sellati R. Tolbert RM. Tschantz MA. Moss N. J. Med. Chem.  2002,  45:  3394 
    Google Scholar
  • 3 Carpenter RD. DeBerdt PB. Lam KS. Kurth MJ.
    J. Comb. Chem.  2006,  8:  907 
    CrossrefGoogle Scholar
  • 4a Perkins JJ. Zartman AE. Meissner RS. Tetrahedron Lett.  1999,  40:  1103 
    Google Scholar
  • 4b Omar A.-MME. Ragab MS. Farghaly AM. Barghash AM. Pharmazie  1976,  31:  348 
    Google Scholar
  • 4c Wang X.-J. Zhang L. Xu Y. Krishnamurthy D. Senanayake CH. Tetrahedron Lett.  2004,  45:  7167 
    Google Scholar
  • 4d Omar A.-MME. Synthesis  1974,  41 
    Google Scholar
  • 4e Heinelt U. Schultheis D. Jager S. Lindenmaier M. Pollex A. Beckmann HSG. Tetrahedron  2004,  60:  9883 
    Google Scholar
  • 4f Omar A.-MME. Habib NS. Aboulwafa OM. Synthesis  1977,  864 
    Google Scholar
  • 5 Cee VJ. Downing NS. Tetrahedron Lett.  2006,  47:  3747 
    CrossrefGoogle Scholar
  • 6 Heimgartner H. Zhou Y. Atanassov PK. Sommen GL. Phosphorus, Sulfur Silicon Relat. Elem.  2008,  183:  840 
    CrossrefGoogle Scholar
  • 7 Fernández-Bolaños JG. López O. Ulgar V. Maya I. Fuentes J. Tetrahedron Lett.  2004,  45:  4081 
    CrossrefGoogle Scholar
  • 8 Koketsu M. Sakai T. Kiyokuni T. Garud DR. Ando H. Ishikara H. Heterocycles  2006,  68:  1607 
    CrossrefGoogle Scholar
  • 9 Dobson DC. James FC. Safarik I. Gunning HE. Strausz OP. J. Phys. Chem.  1975,  75:  771 
    Google Scholar
  • 10 Pittman RW. J. Chem. Soc.  1949,  1811 
    CrossrefGoogle Scholar
11

Typical Procedure for Compound 2e A mixture of 1-isoselenocyanato-4-methoxybenzene (1e; 0.212 g, 1 mmol) and phenylene-1,2-diamine (0.108 g, 1 mmol) were suspended in CHCl3 (20 mL). The reaction was carried out at r.t. After 10 min the reaction was ceased, and the reaction mixture was concentrated under vacuum. The residue was washed with a mixture of hexane and EtOAc (hexane-EtOAc = 20:1) to obtain 1-(2-aminophenyl)-3-(4-methoxyphenyl) selenourea (2e) as a yellow solid (0.313 g, 98% yield). ¹H NMR (400 MHz, DMSO-d 6): δ = 9.63 (s, 1 H), 9.34 (s, 1 H), 7.26-7.29 (m, 2 H), 6.96-7.02 (m, 2 H), 6.87-6.90 (m, 2 H), 6.74 (dd, 1 H, J = 1.2, 8.0 Hz), 6.56 (dt, 1 H, J = 1.6, 7.6 Hz), 4.89 (s, 2 H), 3.74 (s, 3 H). ¹³C NMR (100 MHz, DMSO-d 6): δ = 178.8, 157.0, 143.9, 132.5, 128.2, 127.4, 127.0, 124.4, 116.4, 115.9, 113.5, 55.2. HRMS (EI): m/z calcd for C14H15N3OSe: 320.0302; found: 320.0317.

12

Procedure for Controlled Experiment
1-(2-aminophenyl)-3-(4-methoxyphenyl) selenourea (2e,
1 mmol) was suspended in DMF (20 mL) with magnetic stirring. The reaction was carried out at 70 ˚C. A light-avoiding control and a nitrogen-atmosphere control reaction were set up at the same time. The reaction was monitored by TLC. 2-Aminophenylselenourea was totally converted into 3e after 4 h in normal and light-avoiding control. The reaction in nitrogen atmosphere was prolonged to 36 h, but only trace of 3e was found.

13

Typical Procedure for Compound 3e
A mixture of 1-isoselenocyanato-4-methoxybenzene (1e; 0.212 g, 1 mmol) and phenylene-1,2-diamine (0.108 g, 1 mmol) was suspended in DMF (20 mL). The reaction vessel was heat to 70 ˚C with magnetic stirring. Tracing by TLC, the reaction completed when selenourea 2e disappeared. The reaction mixture was then cooled to r.t. and filtered to separate solid selenium. The solid selenium was washed by EtOAc (10 mL). The combined filtrate was concentrated under vacuum, and the residue was purified by column chromatography on silica gel (hexane-EtOAc = 1:1). A white solid N-(4-methoxyphenyl)-1H-benzo[d]imidazol-2-amine (3e, 0.215 g, 90% yield), was then obtained. ¹H NMR (400 MHz, DMSO-d 6): δ = 10.79 (s, 1 H), 9.15 (s, 1 H), 7.65 (d, 2 H, J = 8.8 Hz), 7.26 (s, 2 H), 6.95-6.96 (m, 2 H), 6.91 (d, 2 H, J = 9.2 Hz), 3.73 (s, 3 H). ¹³C NMR (100 MHz, DMSO-d 6 + CDCl3): δ = 154.1, 151.7, 138.0, 133.9, 119.8, 119.5, 114.0, 112.2, 55.1. ESI-MS: m/z = 240 [M + H]+.