Research in the imidazole series. 96. Reaction of 1-methyl-4-nitro-5-chlorimidazole with phenols, naphthols, and 8-hydroxyquinoline

Abstract

The reactions of 4-nitro-5-haloimidazoles with phenol and its derivatives have received very little attention [2, 3], and its reactions with naphthols and hydroxyquinolines have not been investigated at all.In connection with a search for biologically active substances, we investigated in more detail the reaction of 1-methyl-4-nitro-5-chlorimidazole (I) with phenol derivatives, and also with o~-and 3-naphthols and 8-hydroxyquinoline.In.contrast to the procedures described in [2, 3], which give low yields of the synthesized compounds (30-60%), we carried out the reaction of the nitrochlorimidazole I with hydroxy derivatives of benzene, naphthalene, and quinoline in an aqueous solution in the presence of an equimolar quantity of potassium hydroxide to bind the hydrogen chloride that is released. The optimal process temperature is 70-85~ At higher temperatures, considerable tarring of the reaction mass is observed.By the interaction of the imidazole I with 4-nitrophenol, ct-and B-naphthols, and 8-hydroxyquinoline, we obtained the corresponding 1-methyl-4-nitro-5-aryl(heteryl)oxyimidazoles (II-V).CI~,,.~N,/Me ROHI, R--O~eIN: e OzN~/~ KOH O2N~N/~

Reactions of halonitroimidazoles with nucleophiles (review)

“…In actual fact the reaction of 5-chloro-1-methyl-4-nitroimidazole 47 with 2-, 3-, and 4-aminophenols in an aqueous solution of potassium hydroxide takes place at the more nucleophilic center of the molecule-the NH 2 group, and 5-(hydroxyphenylamino)-1-methyl-4-nitroimidazoles 65 (structure B) are formed [21]. 5-Halo-4-nitro-and 4-halo-5-nitroimidazoles 13 and 17 react similarly with amino alcohols, leading to the formation of the corresponding 5-(hydroxyalkylamino)-4-nitro-and 4-(hydroxyalkylamino)-5-nitroimidazoles 66 and 67 [19,59].…”

“…5-Halo-4-nitroimidazoles 13 also react with phenols [16-18, 20, 21], naphthols [21], 2-hydroxy heterocycles [20], and 8-hydroxyquinoline [21], forming the ethers of 5-hydroxy-4-nitroimidazoles 16. O-Nucleophilic substitution in the reaction of 4-halo-5-nitroimidazoles 17 with sodium alcoholates [19,22], phenol [22], and 8-hydroxyquinoline [22] takes place in the same way as for 5-halo-4-nitroimidazoles, and the ethers of 4-hydroxy-5-nitroimidazoles 18 are obtained.…”

“…5-Halo-4-nitroimidazoles 13 react with ammonia [55], primary [16-18, 21, 56] and secondary [14,19,[56][57][58] amines, dialkylaminoalkylamines [16,17,20,56], amino alcohols [19,59], aminophenols [21], amino acids [60], and heterocyclic compounds containing a free NH group [20,57]. A large series of 5-amino-4-nitroimidazole derivatives 41-43 were synthesized as a result of these reactions.…”