121816-79-3Relevant academic research and scientific papers
Synthesis and hypoxia-selective cytotoxicity of a 2-nitroimidazole mustard
Lee,Palmer,Wilson,Denny
, p. 1741 - 1744 (2007/10/03)
A four-step synthesis of 5-[N,N-bis(2-chloroethyl)amino]-1-methyl-2- nitroimidazole from 1-methyl2-nitroimidazole is described. This compound showed similar hypoxia-selective cytotoxicity to the dinitrobenzamide mustard SN 23862 in UV4 cells (ca. 40-fold), and superior selectivity (>7-fold) in repaircompetent AA8 cells.
Preparation and reactions of bromo-2-nitro- and bromo-2-aminoimidazoles
Farah, Salim F.,McClelland, Robert A.
, p. 427 - 432 (2007/10/02)
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--4-bromo-1-methylimidazole 9 as sole product, and the 5-bromo 6 giving two products identified as the monosubstituted 2--5-bromo-1-methylimidazole 13 and the disubstituted 2,5-bis-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--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-dihydroxyimidazolium ions 18.
Synthesis and Reactions of Brominated 2-Nitroimidazoles
Palmer, Brian D.,Denny, William A.
, p. 95 - 99 (2007/10/02)
Various approaches to the synthesis of the hitherto-unknown 4(5)-bromo-2-nitroimidazole (5) are reported.Direct bromination of 2-nitroimidazole with N-bromosuccinimide gave the unreported 4,5-dibromo-2-nitroimidazole (10) in quantitative yield, but this could be selectively debrominated to give compound (5).While 1-methyl-2-nitroimidazole readily gave 4-bromo-1-methyl-2-nitroimidazole (15) on bromination, this could not be demethylated to give (5), and bromination of various other N-protected 2-nitroimidazoles was also unsuccessful.Lithiation of 4-bromo-1-tritylimidazole (21) followed by quenching with propyl nitrate gave (after detritylation and methylation) a mixture of a dimer (28) and compound (15), indicating that the desired product (5) is produced in this reaction although it can only be isolated in derivatized form.The proposed route for formation of the dimer suggests a general reaction between 1-alkyl-4-bromo-2-nitroimidazoles and strong C- and N-nucleophiles, resulting in substitution at the 5-position.
