The reaction of nitrohalogenoimidazoles with amino alcohols has been insufficiently investigated, while the chemical characteristics of the two described compounds have not been investigated [2]. In the search for biologically active compounds we studied the reaction of l-alkyl(1,2-dialkyl)-4-nitro-5-chloro(bromo)imidazoles (I-VII) and 1-alkyl(l,2-dialkyl)-4chloro-5-niti'oimidazoles (VIII, IX) with lower amino alcohols (2-aminoethanol and 3-aminopropanol) in greater detail. The reaction takes place readily in isobutanol or in an excess of the amino alcohol itself at 70-100"C and leads to the corresponding substituted 4-nitro-5-aminoimidazoles (X-XXI) and 4-amino-5-nitroimidazoles (XXII-XXIV) with satisfactory and high yields (65-95%).On heating in n-butanol (110-117~ as described in [2], appreciable resinification of the reaction mixture is observed, and the yields of the targeted compounds are reduced to 55-60%.Theoretically the nucleophilic substitution of 4-nitro-5-halogenoimidazoles (I-VII) and 4 halogeno-5-nitroimidazoles (VIII, IX) with such bifunctional compounds as o~-and t-amino alcohols can take place in two directions. The reaction involving the amino group leads to the formation of derivatives of nitroaminoimidazoles (X-XXI) and (XXII-XXIV), while the reaction through the hydroxyl group leads to derivatives of 4-nitro-5-hydroxyimidazoles (structure A) and their 4-hydroxy-5-nitro isomers.The ethers of 4-nitro-5-hydroxyimidazoles are formed during the reaction of 4-nitro-5-halogenoimidazoles with hydroxyl-containing compounds in the presence of alkaline agents [1-4], although with aminophenols under similar conditions 4-nitro-5-hydroxyphenylaminoimidazoles are obtained [1, 5]. Under our selected experimental conditions it was not possible to identify ethers with structure A. The selectivity of the reaction of nitrohalogenoimidazoles with amino alcohols is probably explained by the higher nucleophilicity of the amino group in the molecule of the amino alcohol, as also in the case of aminophenols [1]. Such a reaction of nitrohalogenoimidazoles with amino alcohols is not exceptional. It was shown in a number of papers that aromatic and heterocyclic compounds containing a mobile halogen atom enter into nucleophilic substitution with amino alcohols through the amino group. Thus, 2-hydroxyethylaminonitrobenzene [6, 7] and 8-(2-hydroxyethylamino)adenine [8] respectively were obtained in the reaction of 2-nitrochlorobenzene and 8-bromoadenine with 2aminoethanol.*For Communication 96, see [1].

Three groups of biologically active amino acids containing the imidazole nucleus within their structure are known. These are the irreplaceable amino acid histidine [2], the biosynthetic precursor of the purine nucleotides 4(5)-amino-5(4)-imidazolecarboxamide and its antagonists [3][4][5][6][7], and 1-carboxyalkylimidazoles [8][9][10][11] in which a nitrogen atom is common to both amino acid and imidazole.N-Substituted amino acids in which one hydrogen atom of the amino group is replaced by imidazole residue have not been described in the literature. With the aim of obtaining this type of compound we have studied the reaction of 5-chloro-1-methyl-4-nitro-(I), 5-bromo-1,2-dimethyl-4-nitro-(I1), and 4-chloro-1-methyl-5-nitroimidazoles (III) with a series of aliphatic and aromatic amino acids (glycine, valine, 13-alanine, y-aminobutyric, paminophenylacetic, and m-and o-aminobenzoic acids).The reaction of nitrohaloimidazoles I and II with amino-acids proceeds readily on heating the components in water or in n-butanol in the presence of potassium hydroxide and leads to formation of the corresponding Nimidazolyl-substituted amino acids IV -IX (in 65-80% yield).The reaction of 5-halo-4-nitroimidazoles I and II with anthranilic acid proceeds with significantly more difficulty. It occurs only under the conditions of the Ullman reaction, i.e. on extended boiling in amyl alcohol in the presence of sodium bicarbonate and cuprous chloride catalyst. The more reactive 4-chloro-l-methyl-5-nitroimidazole III reacts with anthranilic acid without a catalyst. Yields of the N-imidazolyl-substituted anthranilic acids X -XII were 61-72%.The esters of certain N-imidazolylamino acids (especially anthranilic) XIII -XVI are of particular interest. Acid X is readily esterified in methanol in the presence of hydrogen chloride with formation of methyl ester XIII (in 90% yield). Acid XI, which is similar in structure, under the same conditions forms methyl ester XIV in 20% yield. Ester XIV was obtained in high yield (86%) by the reaction of acid XI with dimethyl sulfate in DMF in the presence of potassium carbonate.N-(1-Methyl-5-nitro-4-imidazolyl)anthranilic acid XII as its potassium salt was esterified With dimethyl sulfate and alkyl halides (CH3I, C2H5I) in DMF. The methyl XV and ethyl XVI esters were obtained in this way in 61-65% yield. Samples of ester XV obtained by the different methods proved to be identical. *For Part 97 see [1].

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/~

No abstract

No abstract