A Convenient Synthesis of 4(5)-Alkylacyl-1H-imidazoles from 4(5)-Imidazolecarboxaldehyde

 

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Abstract

A convenient synthesis of 4(5)-acyl-1H-imidazoles from 4(5)-imidazolecarboxaldehyde without N-protecting group is described. 4(5)-Cyanoimidazole could be synthesized from commercially available 4(5)-imidazolecarboxaldehyde in one-pot. Treatment of 4(5)-cyanoimidazole with various alkylmagnesium bromides followed by addition of aqueous sulfuric acid afforded 4(5)-acyl-1H-imidazoles in good yield.

References

• 1 Thompson SK. Murthy KHM. Zhao B. Winborne E. Green DW. Fisher SM. DesJarlais RL. Tomaszek TA. Meek TD. Gleason JG. Abdel-Meguid SS. J. Med. Chem.  1994,  37:  3100 
  CrossrefGoogle Scholar
• 2 Smith HJ. Nicholls PJ. Simons C. Lain RL. Exp. Opin. Ther. Patents  2001,  11:  789 
  CrossrefGoogle Scholar
• 3 Cordi AA. Persigand T. Lecouve J.-P. Synth. Commun.  1996,  26:  1585 
  Google Scholar
• 4a Cossement E, Geerts J.-P, Gobert J, and Michel P. inventors; US Patent  4814343.  ; Chem. Abstr. 1988, 109, 231016
  Crossref
• 4b Kelly JL. Miller CA. McLean EW. J. Med. Chem.  1977,  20:  721 
  CrossrefGoogle Scholar
• 5 Grimmett MR. In Advances in Heterocyclic Chemisry   Vol. 12:  Katritzky AR. Boulton AJ. Academic Press; New York: 1970.  p.179 
  Google Scholar
• 6a Iddon B. Heterocycles  1985,  23:  417 
  CrossrefGoogle Scholar
• 6b Kirk KL. J. Heterocycl. Chem.  1985,  22:  57 
  CrossrefGoogle Scholar
• 6c Iddon B. Khan N. Tetrahedron Lett.  1986,  27:  1635 
  CrossrefGoogle Scholar
• 6d Carpenter AJ. Chadwick DJ. Tetrahedron  1986,  42:  2351 
  CrossrefGoogle Scholar
• 7 Reiter LA. J. Org. Chem.  1987,  52:  2714 
  CrossrefGoogle Scholar
• 8 Gelens E. Koot WJ. Menge WMPB. Ottenheijm HCJ. Timmerman H. Bioorg. Med. Chem. Lett.  2000,  10:  1935 
  CrossrefGoogle Scholar
• 9 Matthews DP. Whitten JP. McCarthy JR. J. Org. Chem.  1986,  51:  3228 
  Google Scholar
• 10 Leone-Bay A. Glaser L. Synth. Commun.  1987,  17:  1409 
  Google Scholar
• 11 Pierce ME. Carini DJ. Huhn GF. Wells GJ. Arnett JF. J. Org. Chem.  1993,  58:  4642 
  Google Scholar
• 12 Alvernhe G. Laurent A. Tetrahedron Lett.  1973,  13:  1057 
  Google Scholar
• 14 Iwasaki S. Helv. Chim. Acta  1976,  59:  2738 
  CrossrefGoogle Scholar

During the dropwise addition of isopropylmagnesium bromide in THF to a solution of 4(5)-cyanoimdazole(2) in THF, the reaction mixture solidified to a cake and could not be stirred. This procedure is unsuitable for large-scale synthesis.