Preparation and reactions of bromo-2-nitro- and bromo-2-aminoimidazoles

Abstract

Treatment of 1-methyl-2-nitroimidazole with bromine in water resulted in rapid dibromination to give 4,5-dibromo-1-methyl-2-nitroimidazole. In dioxane, the bromination was slower, and could be controlled to give 4-bromo-1-methyl-2-nitroimidazole 5 and 5-bromo-1-methyl-2-nitroimidazole 6 in a 4:1 ratio. In an attempt to displace the bromine, the monobromo compounds were treated with cysteamine hydrochloride. In each case the nitro group was displaced instead, the 4-bromo 5 resulting in 2-[(2-aminoethyl)thio]-4-bromo-1-methylimidazole 9 as sole product, and the 5-bromo 6 giving two products identified as the monosubstituted 2-[(2-aminoethyl)thio]-5-bromo-1-methylimidazole 13 and the disubstituted 2,5-bis[2-(aminoethyl)thio]-1-methylimidazole 12. The latter product forms by further reaction of the former and was the sole material observed at long reaction times. A fraction of 12 may also originate from an initial displacement of bromine giving 5-[(2-aminoethyl)thio]-1-methyl-2-nitroimidazole 14, although this cannot be observed due to a rapid further displacement of its nitro group. The bromonitroimidazoles 5 and 6 were reduced to 4-bromo-2-amino-1-methylimidazole 25 and 5-bromo-2-amino-1-methylimidazole 26 with Zn/HCl. On reflux in water, in the presence or absence of cysteamine hydrochloride, these undergo a protodebromination resulting in the same product, 2-amino-1-methylimidazole 17. In D2O the 4-bromo isomer was demonstrated to react specifically to give 2-amino-4-deuterio-1-methylimidazole 27. Attempted preparation of the bromoaminoimidazoles 25 and 26 by bromination of 2-amino-1-methylimidazole in water resulted in the clean formation of cis and trans 2-amino-4,5-dihydro-4,5-di-hydroxyimidazolium ions 18.