T. A. Kuz’menko

1-amino-2-thiobenzimidazoleimines as novel ambidentate ligand systems

Azomethine derivatives of 1-amino-2-thiobenzimidazole (H2L) were synthesized and studied by IR and 1H NMR spectroscopy. Thiobenzimidazoline tautomeric form of these compounds was found to predominate in a solid state and DMSO solution. Novel mono-and binuclear metal chelates M(HL)2 and M2L2 (M = Ni(II), Cu(II), Co(II), Zn(II), Cd(II)) were synthesized on the basis of H2L derivatives and their composition and structures were established from IR, 1H NMR, EXAFS, and magnetochemical data. The composition of coordination sphere was shown to produce no effect on ferromagnetic exchange in binuclear Cu(II) complexes.

Prototropic equilibrium in 1(11)H-2, 3, 4, 5-tetrahydro[1, 3]diazepino[1, 2-a]benzimidazole, synthesis and pharmacological properties of its N-substituted derivatives

Based on the X-ray crystallography and 1H NMR spectroscopy data and quantum chemical studies, it was found that 1(11)H-2, 3, 4, 5-tetrahydro[1, 3]diazepino[1, 2-a]benzimidazole (1) exists almost exclusively in the 1H-prototropic form. To prepare the fixed 11H-diazepinobenzimidazole forms of 1, 1-R-2-(4-chlorobutylamino)benzimidazoles (R = Me, N=CHAr) were synthesized, which underwent thermal cyclization with the formation of a mixture of 11-Rsubstituted diazepine 1 and 1-R-2-(pyrrolidin-1-yl)benzimidazole. Alkylation of diazepine 1 in a neutral medium regioselectively gave 11-R-diazepinobenzimidazoles in high yield. Their 1-substituted isomers were obtained by carrying out this reaction in the system NaH—THF. The N(11)-derivatives of diazepinobenzimidazole 1 were found to inhibit dipeptidyl peptidase 4 (DPP-4), but less actively than a comparator drug sitagliptin. The compounds under study did not exhibit antiglycation action in vitro and virtually did not affect activity of α-glucosidase and glycogen phosphorylase. However, they are characterized by a strong antiaggregant effect, making these derivatives promising for further studies.

Synthesis of 1(11)H-2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole starting from benzimidazole-2-sulfonic acid. Intramolecular cyclization of 2-(δ-chlorobutylamino)benzimidazole

The intramolecular cyclization of 2-(δ-chlorobutylamino)benzimidazole (3c) follows the unusual pathway involving the predominant attack on the exocyclic amino group rather than on the much more nucleophilic endocyclic nitrogen atom. This reaction affords 2-pyrrolidinobenzimidazole and 1(11)H-2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole as the major product and the by-product, respectively. The cyclization can be directed exclusively toward the annulation of the diazepine ring only after the acetylation of the amino group of compound 3c. According to the quantum chemical calculations, the unusual regioselectivity of the cyclization of chloramine 3c is associated primarily with a substantially less steric strain and the higher entropy of pyrrolidine transition states compared to diazepine transition states.

1-Amino-2-hydrazinobenzimidazole and its reactions with some carbonyl compounds

Abstract1-Amino-2-hydrazinobenzimidazole was obtained for the first time by treating 1-aminobenzimidazole-2-sulfonic acid with hydrazine hydrate. This compound readily condensed with aromatic aldehydes involving both amino groups. The condensation with 2,4-pentanedione affords 1-amino-2-(3,5-dimethylpyrazol-1-yl)benzimidazole, and with α-ketoacids in glacial acetic acid yields mixtures of 10-acetylamino-3-R-1,2,4-triazino[4,3-a]benzimidazol-4(10H)-ones and 4-amino-2-R-1,2,4-triazino[2,3-a]benzimidazol-3(4H)-ones.

Regioselectivity of N-substitution in bis-alkylation of 1,2,4-triazolo[1,5-a]benzimidazole-2-thione

Cyclization of the corresponding N-substituted 1,2-diaminobenzimidazoles with carbon disulfide in refluxing DMF leads to 3-methyl- and 3-benzyl-1,2,4-triazolo[1,5-a]benzimidazole-2-thiones. Based on the results of their S-alkylation, quantum chemical calculations by the density functional theory method, and 1D and 2D NMR spectroscopic studies, it was concluded that the bis-alkylation of N-unsubstituted 1,2,4-triazolo[1,5-a]benzimidazole-2-thione in the presence of a base proceeds with the formation of N(4)-derivatives of 2-alkylthio-1,2,4-triazolo[1,5-a]benzimidazole, rather than N(3)-derivatives as was believed earlier.

Synthesis and Antimicrobial and Protistocidal Activity of 1-(2-Aryloxyethyl- and 2-Halobenzyl)-3-(2-Hydroxyethyl)-2-Imino-1,3-Dihydrobenzimidazolines

New 1-(2-aryloxyethyl- and 2-halobenzyl)-3-(2-hydroxyethyl)-2-imino-1,3-dihydrobenzimidazoline hydrochlorides were synthesized via reactions of 1-(2-aryloxyethyl- and 2-halobenzyl)-2-aminobenzimidazoles with ethylenechlorohydrin. These compounds were shown to possess both bactericidal activity against some pathogenic Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Escherichia coli) and pronounced protistocidal activity against the species Colpoda steinii.

Synthesis and Cyclization of 2-Amino- and 2-Methyl-Substituted 1,3-Diaminobenzimidazolium Salts

N-Amination of 1-amino(alkylamino, benzylidenamino)-substituted 2-amino- and 2-methylbenzimid-azoles with O-picrylhydroxylamine gave the respective 1,2,3-triamino- and 1,3-diamino-2-methylbenz-imidazolium salts, which cyclized upon treatment with acetic anhydride/K2CO3 into previously unreported derivatives of N-amino[1, 2, 4]triazolo[1,5-а]benzimidazoles and N-aminopyrazolo-[1,5-а]benzimidazoles. The presence of С-acetyl substituent in the formed pyrazolo[1,5-а]benz-imidazoles was interpreted by quantum-chemical calculations as resulting from acylation of the intermediate methylene base, not tricyclic system.

Fluorescent chemosensors based on N-aminoimidazole and N-aminobenzimidazole

Nowadays chemosensors are widely used in express determination of ions and neutral compounds in various samples [1, 2]. Ion-sensitive compounds have found application not only in analytical and environmental chemistry but also in biology. It is very important to design efficient and selective chemosensors for the determination and biovisualization of ions (cations and anions) involved in biological cell processes [3, 4]. We previously demonstrated the possibility of using anthracen-9-ylmethyl-substituted benzimidazol-2amines as efficient pH sensors [5, 6]. In continuation of these studies we have synthesized N-amino derivatives of imidazole and benzimidazole containing an anthracene fluorophore group linked to the NNH group. By reaction of benzimidazole-1,2-diamine (I) and 1-amino-4-phenyl-1H-imidazole-2-thiol (II) with anthracene-9-carbaldehyde in acetic acid we synthesized the corresponding Schiff bases which were reduced to diamines III and IV with sodium tetrahydridoborate. In the reaction with diamine I, only the N–NH2 amino group was involved in the condensation. The H NMR spectrum of III contained signals typical of protons in the NH2, NH, and CH2 groups. Amines III and IV showed anthracene-like fluorescence with an emission maximum at λ 414 (415) nm. Their chemosensor properties were studied in acetonitrile (c = 5 × 10 M) by comparing the fluorescence spectra before and after addition of cations (H, Zn, Cd, Ni, Cu, Pb, Hg) and anions (AcO, CN, NO3, F, Cl, see table). The results revealed different selectivities of III and IV toward ionic species. The fluorescence intensity of compound III considerably increased in the presence of H, Zn, and Cd ions and decreased on addition of Cu and Hg. Aminothiol IV turned out to be more sensitive in the determination of anions. It displayed selective increase in the fluorescence intensity in the presence of acetate ions. In all cases, addition of ions to solutions of III and IV did not induce appreciable change in the position of absorption and emission maxima.

1-Acylmethylbenzimidazole-2-sulfonic acids and their cyclization by N-nucleophiles

New preparation method was developed for derivatives of 1,4-dihydro-1,2,4-triazino[4,3-a]-, 2-aryl-1(9)H-, and 1-R-imidazo[1,2-a]benzimidazole underlain by newly synthesized 1-acylmethylbenzimidazole-2-sulfonic acids. The latter react with 2-aminoethanol affording along with the previously described compounds of the 1-(2-hydroxyethyl)imidazobenzimidazole series also compounds of formerly unknown polycyclic system, 2,3,11,12-tetrahydro-1,3-oxazolo[2,3-a]imidazo[1,2-a]benzimidazole.

2-aryl(hetaryl)-4H-[1,2,4]triazolo[1,5-a]benzimidazoles

Abstract2-(4-Methylphenyl)-4H-[1,2,4]triazolo[1,5-a]benzimidazole and its previously unknown 2-(2-furyl)- and 2-(2-thienyl)-substituted analogs were synthesized by cyclization of benzimidazole-1,2-diamine with the corresponding carboxylic acid chlorides. The IR, 1H, 13C, and 15N NMR, and mass spectra of the cyclization products in combination with the results of quantum-chemical calculations of NMR chemical shifts showed radical differences of [1,2,4]triazolo[1,5-a]benzimidazoles having no substituent on N4 from the recently reported low-melting products of oxidation of 2-amino-1-arylmethylideneaminobenzimidazoles with (diacetoxy-λ3-iodanyl)benzene, which, as we believe, were erroneously assigned analogous structure.