A. N. Grozav

Synthesis and Biological Activity of 4-Chloro-1H-Imidazole-5-Carbaldehyde Thiosemicarbazones

A series of thiosemicarbazones, the structures of which were established by IR and PMR spectroscopy and mass spectrometry, were synthesized by condensation of 4-chloro-1H-imidazole-5-carbaldehydes with thiosemicarbazide. Some of the synthesized compounds were found to exhibit high inhibitory activity with respect to M. tuberculosis strains that was 1.5 times more effective than the reference drug isoniazid. Astudy of the antimicrobial activity of the synthesized thiosemicarbazones showed that their fungistatic properties were more pronounced than their bacteriostatic properties.

Polyfunctional imidazoles: VII. 1-aryl-4-chloro-5-[hydroxy(halo)methyl]-1H-imidazoles and their derivatives

The reduction of 1-aryl-4-chloro-1H-imidazole-5-carbaldehydes with sodium tetrahydridoborate gave 1-aryl-4-chloro-1H-imidazol-5-ylmethanols which were converted into 5-chloromethyl and 5-fluoromethyl derivatives. 1-Aryl-4-chloro-5-chloromethyl-1H-imidazoles reacted with sodium azide, secondary amines, thiols, and triphenylphosphine to produce the corresponding products of chlorine replacement in the 5-chloromethyl group.

Polyfunctional imidazoles: XIV. 4-sulfonyl-5-formyl-1H-imidazoles

Oxidative chlorination of 1-aryl-4-benzylsulfanyl-1H-imidazole-5-carbaldehydes gave 1-aryl-5-formyl-1H-imidazole-4-sulfonyl chlorides which reacted with secondary amines and phenols to produce the corresponding N,N-disubstituted 5-formylimidazole-4-sulfonamides and aryl sulfonates. The reaction of 1-aryl-5-formyl-1H-imidazole-4-sulfonyl chlorides with sodium azide, followed by reduction of the resulting sulfonyl azides, led to the formation of N-unsubstituted 5-formylimidazole-4-sulfonamides, and the reaction with alcohols, to 5-formylimidazole-4-sulfonic acids.

Convenient synthesis of 3-chloroimidazo[1,5-a]quinoxalines

Abstract5-Aminomethyl-1-(2-haloaryl)-4-chloroimidazoles prepared from 1-(2-haloaryl)-5-formyl-4-chloroimidazoles via simple transformations undergo intramolecular cyclization to 3-chloroimidazo[1,5-a]quinoxalines on heating in DMF in the presence of potassium carbonate.

Polyfunctional imidazoles: XIII.1 Addition and cyclization reactions of 1-aryl-4-chloro-5-(2-nitroethenyl)-1H-imidazoles with sulfur and nitrogen nucleophiles

Abstract1-Aryl-4-chloro-5-(2-nitroethenyl)-1H-imidazoles reacted with thiols and aromatic amines via Michael addition to give 5-[(1-arylsulfanyl)-2-nitroethyl)]-4-chloro-1H-imidazoles and N-[1-(1-aryl-4-chloro-1H-imidazol-5-yl)-2-nitroethyl]anilines, respectively. [2 + 3]-Cycloaddition of the title compounds to sodium azide afforded 4-(4-chloro-1H-imidazol-5-yl)-1H-1,2,3-triazoles.

Polyfunctional imidazoles: XII.1 Synthesis of 1-[(4-chloro-1H-imidazol-5-yl)methyl]-substituted 1,2,3-triazoles and dihydropyrrolo[3,4-d]triazoles from 5-(azidomethyl)-4-chloro-1H-imidazoles

Abstract1-Aryl-5-(azidomethyl)-4-chloro-1H-imidazoles reacted with terminal acetylenes in the presence of copper catalyst to give 1-[(1-aryl-4-chloro-1H-imidazol-5-yl)methyl]-1H-1,2,3-triazoles, and their reactions with N-arylmaleimides on heating in benzene afforded 5-aryl-1-[(1-aryl-4-chloro-1H-imidazol-5-yl)methyl]-3a,6a-dihydropyrrolo[3,4-d][1,2,3]triazole-4,6(1H,5H)-diones.

Polyfunctional imidazoles: X. Synthesis of 4-chloro-5-(2-nitroalkenyl)-1H-imidazoles and their reaction with 5-methyl-2,4-dihydro-3H-pyrazol-3-one

Condensation of 1-aryl-4-chloro-1H-imidazole-5-carbaldehydes with nitroalkanes in the presence of anhydrous ammonium acetate gave 4-chloro-5-(2-nitroalkenyl)-1H-imidazoles which reacted with 5-methyl-2,4-dihydro-3H-pyrazol-3-one according to the Michael addition scheme with formation of 4-[1-(4-chloro-1H-imidazol-5-yl)-2-nitroalkyl]-5-methyl-1H-pyrazol-3-ols.

Polyfunctional imidazoles: VIII. 1-Aryl-4-chloro-5-[R-sulfanyl(sulfonyl)methyl]-1H-imidazoles

Alkylation of (1-aryl-4-chloro-1H-imidazol-5-yl)methanethiols with alkyl halides, propargyl bromide, or chloroacetic acid gave 1-aryl-5-(R-sulfanylmethyl)-4-chloro-1H-imidazoles. 1-Aryl-4-chloro-5-(methylsulfanylmethyl)-1H-imidazoles and [(1-aryl-4-chloro-1H-imidazol-5-yl)methylsulfanyl]acetic acids were oxidized to the corresponding sulfones with potassium permanganate.

Polyfunctional imidazoles: VI. Synthesis of 2-amino-1-aryl-4-chloro-1H-imidazole-5-carboxylic acids derivatives

Aryl-2,4-dichloro-5-formylimidazoles by a successive treatment with hydroxylamine and thionyl chloride were converted into 1-aryl-2,4-dichloroimidazole-5-carbonitriles which by the action of sodium azide and tin(II) chloride were transformed into 2-amino-1-aryl-4-chloroimidazole-5-carbonitriles. The consecutive reactions of 2-azido-1-aryl-4-chloro-5-formylimidazoles with N-bromosuccinimide, methanol, or amides led to the formation of methyl esters and amides of 2-azido-1-aryl-4-chloroimidazole-5-carboxylic acids. The reduction of the latter with tin(II) chloride resulted in the corresponding derivatives of 2-amino-1-aryl-4-chloroimidazole-5-carboxylic acids, and the reduction of 2-azido-1-aryl-4-chloroimidazole-5-carboxylic acids was accompanied with decarboxylation and yielded 2-amino-1-aryl-4-chloroimidazoles.

Polyfunctional imidazoles: IV. Synthesis of 2-aryl-4-chloro-1-methyl(aryl)-1H-imidazole-5-carbaldehydes

Abstract2-Aroyl-2-[methyl(aryl)amino]acetamides reacted with the Vilsmeier-Haak reagent to give 2-aryl-4-chloro-1-methyl(aryl)-1H-imidazole-5-carbaldehydes.