Synthesis of 2-thioxoimidazolines via reaction of 1-unsubstituted 3-aminoquinoline-2,4-diones with isothiocyanates

3-Alkyl/aryl-3-amino-1H,3H-quinoline-2,4-diones react with alkyl/aryl isothiocyanates to give 3a-alkyl/aryl-1,2,3,3a-tetrahydro-9b-hydroxy-2-thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-ones in high yields. These compounds rearrange in boiling acetic acid or concd hydrochloric acid to give novel 4-(2-aminophenyl)-1H-imidazole-2(3H)-thiones, 1,3-bis(2-(2,3-dihydro-2-thioxo-1H-imidazol-5-yl)phenyl)ureas and minor N-(2-(2,3-dihydro-2-thioxo-1H-imidazol-4-yl)phenyl)acetamides. In the presence of ethanol, the starting compounds rearrange in boiling acetic acid to give ethyl 2-(2,3-dihydro-2-thioxo-1H-imidazol-4-yl)phenylcarbamates. All compounds were characterized by their ¹H, ¹³C, IR and MS spectra and some of them also by ¹⁵N NMR data. The structures of two compounds were supported by single-crystal X-ray diffraction.     

S<Stack><Subscript>N</Subscript><Superscript>H</Superscript></Stack> Reaction of lithiated nitronyl nitroxide with quinoline <Emphasis Type="Italic">N</Emphasis>-oxide

The S_N^H reaction of lithiated 4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl 3-oxide with quinoline N-oxide affords 4,4,5,5-tetramethyl-2-(1-oxidoquinolin-2-yl)-4,5-dihydro-1H-imidazole-1-oxyl 3-oxide.     

Synthesis of 3-alkoxycarbonylaminomethylcarbonylamino-4-benzoyl-1,2-dihydropyridines and their cyclization to 5-phenyl-1,3,8,9-tetrahydro-2H-pyrido[3,4-e]-1,4-diazepin-2-ones

The regiospecific reaction of 3-benzyloxycarbonylaminomethylcarbonylamino-4-benzoylpyridine (6a) , or 3-t-butoxycarbonylaminomethylcarbonylamino-4-benzoylpyridine (6b) , with either acetyl chloride or ethyl chloroformate, and either n-butylmagnesium chloride or phenylmagnesium bromide afforded the respective 1-acetyl (or ethoxycarbonyl)-2-n-butyl (or phenyl)-3-benzyloxy (or t-butoxy) carbonylaminomethylcarbonylami-no-4-benzoyl-1,2-dihydropyridines 7 in 60-75% yield. Reaction of 1-acetyl (or ethoxycarbonyl)-2-n-butyl (or phenyl)-3-t-butoxycarbonylaminomethylcarbonyl-4-benzoyl-1,2-dihydropyridines 7b, 7f, 7d, 7h with trifluoroacetic acid gave the corresponding 5-phenyl-8-acetyl (or ethoxycarbonyl)-9-n-butyl (or phenyl)-1,3,8,9-tetrahydro-2H-pyrido[3,4-e]-1,4-diazepin-2-ones 8a, 8b, 8c, 8d respectively in 45–63% yield. N¹-Methylation of 5-phenyl-8-acetyl-9-n-butyl (or phenyl)-1,3,8,9-tetrahydro-2H-pyrido[3,4-e]-1,4-diazepin-2-ones 8a, 8b using sodium hydride and iodomethane yielded the corresponding N¹-methyl derivatives 9a (48%) and 9b (54%). Oxidation of 5,9-diphenyl-8-ethoxycarbonyl-1,3,8,9-tetrahydro-2H-pyrido[3,4-e]-1,4-diazepin-2-one (8d) using p-chloranil afforded 1,3-dihydro-5,9-diphenyl-2H-pyrido[3,4-e]-1,4-diazepin-2-one (10) . 5-Phenyl-8-acetyl-9-n-butyl-1,3,8,9-tetrahydro-2H-pyrido[3,4-e]-1,4-diazepin-2-one (8a) and the corresponding 8-ethoxycarbonyl analog 8c exhibited weak anticonvulsant activity indicating that 8a and 8c may be acting at the same site as the 7-halo-1,4-benzodiazepin-2-one class of compounds.     

Seven-membered metallocycle in the CuII complex with deprotonated 2-(2-hydroxy-3-nitrophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl 3-oxide

The reaction of CuCl₂ with deprotonated 2-(2-hydroxy-3-nitrophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl 3-oxide afforded a bis-chelate complex containing seven-membered metallocycles.     

Studies on isocyanides and related compounds. Investigation on the reaction between (Z)-alkyl 3-dimethylamino-2-isocyanoacrylates and acyl chlorides

The reaction between (Z)-methyl 3-dimethylamino-2-isocyanoacrylate ( 1a ) and acyl chlorides 2a,b did not afford methyl 2-acyl-1-methyl-1H-imidazole-4-carboxylates 3a,b , as previously reported, but 2-acyl-4-dimeth-ylaminomethyleneoxazol-5(4H)-ones 4a,b.     

XPS spectra of free nitroxyl radicals and their electronic structure

The N(1s) and O(1s) XPS spectra of stable nitroxyl radicals and molecules with a related heterocycle structure: 4,4,5,5-tetramethyl-2-phenyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl, 4,4,5,5-tetramethyl-2-(3-nitrophenyl)-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl, 4,4,5,5-tetramethyl-2-(2-hydroxyphenyl)-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl, 4,4,5,5-tetramethyl-2-(2-hydroxy-3-nitrophenyl)-4,5-dihydro-1Himidazole-3-oxide-1-oxyl, and 4,4,5,5-tetramethyl-2-phenyl-4,5-dihydro-1H-imidazole-3-oxide were studied. The possibility to apply X-ray electron spectra for investigation of the charge electron and spin density distribution on free radical atoms and at their coordination by a metal is considered.     

Syntheses and structures of azol-1-yl derivatives of nitronyl and imino nitroxides

2-(Pyrazol-1-yl)-, 2-(imidazol-1-yl)-, 2-([1,2,4]triazol-1-yl)-, and 2-(benzotriazol-1-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl were prepared by reactions of 2-bromo-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (NIT-Br) with the corresponding sodium azolides. In prepared 2-(azol-1-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyls, the NIT-N_Het bond is readily hydrolyzed. Reduction of imidazole-3-oxide-1-oxyls leads to corresponding 2-(azol-1-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyls, which are much more stable against hydrolysis. The structures of spin-labeled imidazoles, [1,2,4]triazoles and benzotriazoles are confirmed by X-ray analysis, showing that the paramagnetic molecules form packings with motifs from centrosymmetric dimers to topologically linear chains.     

Synthesis of novel derivatives of 2-(azolylimino)thiazoline

Successive alkylation of 5-(3-phenylthioureido)-3H-imidazole-4-carboxamides with alkyl halides and chloroacetone gave (N-oxopropylimidazolyl)isothioureas, which were easily converted into derivatives of purine and imidazopyrazinone. In the case of ethyl 5-(3-phenylthioureido)-3H-imidazole-4-carboxylate, primary alkylation occurs at the N atom of the imidazole ring. Reactions of 5-(3-phenylthioureido)-3H-imidazole-4-carboxamides with haloketones afforded a number of 4-hydroxy-2-imidazolyliminothiazolidines and 2-imidazolylimino-Δ⁴-thiazolines.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2196–2204, October, 2004.     

Enantioseparation of Some New 1-(2-Naphthyl)-1-ethanol Ester Derivatives by HPLC on Chiralcel OD

The direct enantiomeric resolution of racemic 2-(1H-imidazole-1-yl)-1-naphthalene-2-yl)ethanol esters, 1-(naphthalene-2-yl)ethanol esters, and 1-(1-hydroxynaphthalene-2-yl)-2-(1H-imidazole-1-yl)ethanol on silica-based cellulose tris(3,5-dimethylphenylcarbamate) (Chiralcel OD) column is described. The separations were performed using mobile phases which consist of alcohol (methanol, ethanol or 2-propanol)/n-hexane in various proportions. The effect of structural features of the solutes along with the nature and concentration of alcohol in the mobile phase on the discrimination between the enantiomers was examined for different mobile phase compositions. The results suggest that not only the structure and concentration of alcohol in the mobile phase, but also the subtle structural differences in racemates can have a pronounced effect on enantiomeric separation and retention. Baseline separations were obtained for 2-(1H-imidazole-1-yl)-1-naphthalene-2-yl)ethanol esters carrying imidazole ring in addition to ester functional group in their structures. The α values of the resolved enantiomers of 2-(1H-imidazole-1-yl)-1-naphthalene-2-yl)ethanol esters were in the range of 1.49–1.62 while the R _s values varied from 4.20 to 6.75 when methanol/n-hexane (70:30 v/v) was used as mobile phase.

     

Reaction of 4,5-Dihydro-1H-pyrazole-3,5,5-tricarboxylic Acids Esters with Halogens

Esters of 4-R-4,5-dihydro-1H-pyrazole-3,5,5-tricarboxylic acids with chlorine yield esters of 4-R-5-chloro-4,5-dihydro-3H-pyrazole-3,3,5-tricarboxylic acids that at thermolysis provide the esters of the corresponding 2-chlorocyclopropanetricarboxylic acid. The same esters react with bromine in dichloromethane at room temperature to give a mixture of esters of the corresponding 1H-pyrazole-3,5-dicarboxylic acids and 5-bromo-4,5-dihydro-3,3,5-tricarboxylic acids. From 5,5-diethyl 3-methyl 4,5-dihydro-1Hpyrazole-3,5,5-tricarboxylate and N-iodosuccinimide or a system iodine-silver trifluoroacetate we obtained 1,1-diethyl 2-methyl 2-iodocyclopropane-1,1,2-tricarboxylate.     

Identification of some isomeric 3,5-unsymmetrically substituted 1-aroyl-pyrazole derivatives by NMR spectroscopy

The ¹H and ¹³C nmr chemical shifts are used for the structural assignment of isomeric 1-aroyl-4,5-dihydro-5-hydroxy-4,4-dimethyl-1H-pyrazoles 1 unsymmetrically substituted with phenyl or methyl in the 3,5-positions of the pyrazole ring. The ¹H nmr spectra of 1-aroyl- or 1-acetyl-4-methyl-1H-pyrazoles 2 are useful in structure elucidation of unsymmetrically 3- or 5-methyl substituted derivatives.     

Synthesis of 3-pyrrol-3′-yloxindoles with a carbamate function

By the reaction of methyl {4(3)-[2-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)acetyl]phenyl} carbamates with ethyl 3-aminocrotonate at boiling in the mixture toluene-anhydrous ethanol, 2: 1, ethyl 5-{3(4)-[(methoxycarbonyl)amino]phenyl}-2-methyl-4-(2-oxo-2,3-dihydro-1H-indol-3-yl)-1H-pyrrole-3-carboxylates were obtained. The condensation of methyl {3(4)-[2-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)acetyl] phenyl}carbamates with ethyl acetoacetate in the presence of ammonium acetate and 20 mol% of 1-methyl-3-butylimidazolium chloride or 1-methyl-3-octylimidazolium tetrafluoroborate at boiling in anhydrous ethanol led to the formation of the corresponding 3-pyrrol-3′-yloxindoles with a carbamate function.     

Two 3-D metal-organic frameworks constructed by 2-methyl or 2-ethyl imidazole dicarboxylates

Two polymeric frameworks, [Zn₅(MIDC)₂(HMIDC)₂(phen)₅] _n (1) (H₃MIDC?=?2-methyl-1H-imidazole-4,5-dicarboxylic acid, phen?=?1,10-phenanthroline) and {[Ca₂(HEIDC)₂(H₂O)]?·?H₂O} _n (2) (H₃EIDC?=?2-ethyl-1H-imidazole-4,5-dicarboxylic acid), have been solvothermally synthesized and structurally characterized by single-crystal X-ray diffraction. Compound 1 exhibits a 3-D structure constructed from 2-D layer motifs joined by µ ₂-HMIDC^2? or µ ₃-MIDC^3? ligands. Compound 2 also presents a 3-D framework, generated from 1-D chains linked by HEIDC^2? ligands by two different µ₅-modes. The thermal and solid-state photoluminescence properties of both the complexes have been determined.     

Polyfunctional imidazoles: IV. Synthesis of 2-aryl-4-chloro-1-methyl(aryl)-1<Emphasis Type="Italic">H</Emphasis>-imidazole-5-carbaldehydes

2-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.     

Synthesis of 5-aryl-3-carbazoyl-1,3,4-oxadiazol-2(3H)-one. Derivatives and their ring transformation into 5-benzamido-1,2,4-triazolidine-3,5-dione derivatives

Some 5-aryl-3-carbazoyl-1,3,4-oxadiazol-2(3H)-one derivatives 6 and 9 have been synthesized in two ways. The expected thermal ring transformation into 2,5-disubstituted 1,3,4-oxadiazoles did not occur but, by acid hydrolysis of 5-aryl-3-[3-benzylidene-2-methyl(or phenyl)carbazoyl]-1,3,4-oxadiazol-2(3H)-ones 6 , a new ring transformation took place and the corresponding 4-benzamido-1-methyl(or phenyl)-1,2,4-triazolidine-3,5-dione derivatives 11 were formed. The 4-amino-1-phenyl-1,2,4-triazolidine-3,5-dione ( 19 ) has been prepared and its structure was confirmed by some reactions.     

2-Imidazoline Nitroxide Derivatives of Cymantrene

The 2-imidazoline nitroxide derivatives of cymantrene—2-(η⁵-cyclopentadienyl)tricarbonylmanganese(I)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (NNMn) and 2-(η⁵-cyclopentadienyl)tricarbonylmanganese(I)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl (INMn) were synthesized. It was shown that NNMn and INMn exhibit a sufficiently high kinetic stability both in solids and in solutions under normal conditions. Their structural characteristics, magnetic properties and electrochemical behavior are close to Re(I) analogs. This opens the prospect of using paramagnetic cymantrenes as prototypes in the design of Re(I) half-sandwiched derivatives for theranostics, where therapy is combined with diagnostics by magnetic resonance imaging due to the contrast properties of nitroxide radicals.     

Interaction of 1,5-disubstituted 3-methyl-2-oxo-2,3-dihydro- 1<Emphasis Type="Italic">H</Emphasis>-imidazole-4-carbonitriles with hydrogen sulfide

The reaction of 1-alklyl(aryl)-5-alkyl(aryl)amino-3-methyl-2-oxo-2,3-dihydro-1H-imidazole-4-carbo-nitriles with hydrogen sulfide was investigated. Unexpectedly, this led, after treatment of the reaction products with triethyl orthoformate, to 1,2,4-dithiazol-5-ylidene-5-thioxoimidazolidin-2-one derivatives.     

1,3-Dipolar cycloaddition of cyclic α-methoxynitrones, derivatives of 2H-imidazole 1-oxide and 4H-imidazole 3-oxide

The reactions of cyclic aldo- and -methoxynitrones of the 2H-imidazole-1-oxide and 4H-imidazole 3-oxide series with isocyanates, phenyl isothiocyanate, N-phenylmaleimide, and dimethyl acetylenedicarboxylate were studied. The reactions give the corresponding 1,3-dipolar cycloaddition products. 2,2-Dimethyl-4-phenyl-2H-imidazole 1-oxide does not enter into a similar reaction with isocyanates or phenyl isothiocyanate.     

Synthesis of 5,6-dihydroxy-2-phenyl-4-pyrimidinecarboxylic acid,methyl ester,a corrected structure

Pyrolysis of the adduct of benzamide oxime and dimethyl acetylenedicarboxylate leads to 5,6-dihydroxy-2-phenyl-4-pyrimidinecarboxylic acid methyl ester ( 4a ) rather than 4,5-dihydro-α,4-dioxo-2-phenyl-1H-imidazole-5-acetic acid, methyl ester ( 1 ).     

Synthesis of some isomeric 4-ethoxycarbonyl-3-and 5-(1- and 2-hydroxyalkyl)-1,3- and 1,5-dimethylpyrazoles from 3-(2H)furanones and 2,3-dihydro-4-pyrones

The title compounds were prepared by reaction of 3-(2H)furanones and 2,3-dihydro-4-pyrones with methylhydrazine or alternatively by methylation of the corresponding N-unsubstituted pyrazoles. ¹³C and ¹H nmr were used to assign the isomeric 3-methyl or 5-methyl structures.