Convenient Synthesis of Methyl 1-Methyl-2,4-dibromo-5-imidazolecarboxylate

Authors:
  • JOJohn F. O'COnnell
    John F. O'COnnell
  • JPJonathan Parquette
    Jonathan Parquette
  • WYWilliam E. Yelle
    William E. Yelle
  • WWWilhelm Wang
    Wilhelm Wang
  • HRHenry Rapoport
    Henry Rapoport
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Abstract
Three syntheses of methyl 1-methyl-2,4-dibromo-5-imidazolecarboxylate (8) are presented. One proceeds from sarcosine via ring closure, bromination, and desulfurization. The second uses N-methylimidazole, polybromination, and selective halogen-metal interchange. The third and most efficient and preparatively useful route begins with diaminomaleonitrile (13). Ring closure with triethyl orthoformate followed by methylation and hydrolysis affords 1-methyl-4,5-imidazoledicarboxylic acid (16). Regioselective decarboxylation followed by esterification yields methyl 1-methyl-5-imidazolecarboxylate (18). Subsequent dibromination gives the completely substituted imidazole 8. The primary purification in this sequence is fractional sublimation of 18 after the esterification step. An overall yield of 26% is achieved from diaminomaleonitrile (13) to methyl 1-methyl-2,4-dibromo-5-imidazolecarboxylate (8), which is a key intermediate for the synthesis of tricyclic imidazo cooked food mutagens.