Reaction 5-(Arylmethylidene)pyrimidine-2,4,6(1<Emphasis Type="Italic">H</Emphasis>,3<Emphasis Type="Italic">H</Emphasis>,5<Emphasis Type="Italic">H</Emphasis>)-triones with L-Proline and Aldehydes

Boiling in toluene of 5-(arylmethylidene)pyrimidine-2,4,6(1H,3H,5H)-triones with L-proline and aldehyde led to the formation of previously unknown substituted 1′-arylhexahydro-1H-spiro[pyrimidine-5,2′-pyrrolysine]-2,4,6(1H,3Н,5Н)-triones.     

Regioselectivity in the reactions of <Emphasis Type="Italic">N</Emphasis>-(polychloroethylidene)-sulfonamides with 1<Emphasis Type="Italic">H</Emphasis>-pyrrole and 1-methyl-1<Emphasis Type="Italic">H</Emphasis>-pyrrole

N-(2,2,2-Trichloroethylidene)arenesulfonamides react with 1H-pyrrole and 1-methyl-1H-pyrrole to give the corresponding N-[2,2,2-trichloro-1-(1H-pyrrol-2-yl)ethyl]arenesulfonamides. The reaction of N-(2,2,2-trichloroethylidene)trifluoromethanesulfonamide with pyrrole leads to a mixture of 2-mono-and 2,5-disubstituted pyrroles, whereas in the reaction with 1-methyl-1H-pyrrole only the 2-substituted compound is formed. N-(2,2-Dichloro-2-phenylethylidene)-4-methylbenzenesulfonamide reacts with 1H-pyrrole to form N-[2,2-dichloro-2-phenyl-1-(1H-pyrrol-2-yl)ethyl]-4-methylbenzenesulfonamide, and its reaction with 1-methyl-1H-pyrrole gives a mixture of 2-and 3-monosubstituted derivatives. The results of quantum-chemical calculations of the initial reactants and products indicate that the process is orbital-controlled. A good agreement is observed between the experimental data and theoretical conclusions concerning the dependence of the reaction regioselectivity on the nature of substituents in the electrophile molecule.     

Recyclization of 1,3-dialkyl-6-nitro-1<Emphasis Type="Italic">H</Emphasis>-imidazo[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridine-2,5(3<Emphasis Type="Italic">H</Emphasis>,4<Emphasis Type="Italic">H</Emphasis>)-diones into imidazole derivatives

Treatment of 5-amino-1,3-dialkyl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones with sodium nitrite in aqueous HCl gave 1,3-dialkyl-1H-imidazo[4,5-b]pyridine-2,5(3H,4H)-diones which were nitrated with potassium nitrate in sulfuric acid to 6-nitro derivatives, and the latter underwent recyclization into 4-amino-1,3-dialkyl-5-(1H-pyrazol-5-yl)-2,3-dihydro-1H-imidazol-2-ones by the action of hydrazine hydrate.     

2<Emphasis Type="Italic">H</Emphasis>-Benzimidazole <Emphasis Type="Italic">N</Emphasis>-oxides: synthesis,chemical properties,and biological activity

The review presents and summarizes comprehensive data starting from 2006 on the synthesis of mono- and di-N-oxides of 2H-benzimidazoles and their chemical properties. Especial attention was paid to the chemical transformations of 2H-benzimidazole 1,3-dioxides upon heating to give 3H-2,1,4-benzoxadiazine 4-oxides and 2H-benzimidazole mono-N-oxides. The biological activity of compounds was covered.     

Cyclizations of monocyclic 5-nitropyridin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones

Reactions of 5-nitropyridin-2(1H)-one and its N-methyl derivative with hydrazine hydrate led to the formation of (1H-pyrazol-3-yl) acetohydrazide. Under analogous conditions, 1,3-dimethyl-5-nitropyridin2(1H)-one gave rise to 2-(1H-pyrazol-3-yl)propionohydrazide, while 6-methyl-5-nitropyridin-2(1H)-one was converted into (5-methyl-1H-pyrazol-3-yl)acetohydrazide. Hydrazinolysis of 4-methyl-5-nitropyridin-2(1H)-one resulted in the formation of 3-methyl-4-nitro-1H-pyrazole. The mechanism of recyclization of nitropyridine derivatives by the action of hydrazine hydrate was studied using 5-nitropyridin-2(1H)-one and 1-methyl-5-nitropyridin-2(1H)-one as examples.     

Binuclear copper(II) complexes with acyldihydrazones of <Emphasis Type="Italic">N</Emphasis>-benzenesulfonyl-<Emphasis Type="Italic">L</Emphasis>-aspartic acid

The structure and the EPR spectra of copper(II) coordination compounds with acyldihydrazones of N-benzenesulfonyl-L-aspartic acid and salicylaldehyde (2-hydroxyacetophenone) were described. The compounds were studied by chemical and thermal analyses, IR spectroscopy, and EPR. The molecular and crystal structures of copper(II) complexes with N-benzenesulfonyl-L-aspartic acid bis(salicylidene)hydrazone (H₄L¹) [Cu₂L¹ · 2Py] · 1.5 H₂O was determined by X-ray diffraction. The crystals are triclinic: a = 10.4714(4) Å, b = 12.9702(5) Å, c = 14.6187(9) Å, α = 104.763(2)°, β = 93.082(2)°, γ = 111.4240(10)°, space group P \(\bar 1\), Z = 2. The binuclear complexes containing copper cations whose coordination polyhedra are connected by an aliphatic spacer (Cu...Cu, 8.669 Å) are additionally linked by phenoxy bridges (Cu...Cu, 3.398 Å). The EPR spectra of these compounds in solutions exhibit an isotropic signal of seven HFS lines due to two equivalent copper ions with the spin Hamiltonian parameters g = 2.115?2.120, a _Cu = (35.5?38.0) × 10^?4 cm^?1, which is indicative of weak exchange interactions between the paramagnetic sites.     

Electrophilic cyclization of <Emphasis Type="Italic">N</Emphasis>-allyl(propargyl)-5-amino-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-4-carboxamides. Synthesis of 4-[(dihydro)oxazol-2-yl]-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-5-amines

N-Allyl-5-amino-1H-pyrazole-4-carboxamides in reactions with polyphosphoric acid, with N-halosuccinimides in chloroform, and with (chlorosulfanyl)benzenes in nitromethane in the presence of lithium perchlorate underwent cyclization involving the N-allylamide fragment to give 4-[5-methyl(halomethyl)-4,5-dihydrooxazol-2-yl]-1H-pyrazol-5-amines and 2-(5-amino-1H-pyrazol-4-yl)-5-[(arylsulfanyl)methyl]-4,5-dihydro-1,3-oxazolium perchlorates, respectively. Analogous reactions of N-propargyl-5-amino-1H-pyrazole-4-carboxamides with polyphosphoric acid afforded 4-(5-methyloxazol-2-yl)-1H-pyrazol-5-amines, and with (chlorosulfanyl) benzenes, 2-(5-amino-1H-pyrazol-4-yl)-5-[(arylsulfanyl)methylidene]-4,5-dihydro-1,3-oxazolium perchlorates.     

Synthesis and antibacterial activity of new <Emphasis Type="Italic">N</Emphasis>-substituted 7-amino-4-methyl-2<Emphasis Type="Italic">H</Emphasis>-chromen-2-ones

N-Substituted 7-amino-4-methyl-2H-chromen-2-ones containing one or two functionalized azole or azine moieties were synthesized. The structures of all synthesized compounds were confirmed by IR, ¹H NMR, and ¹³C NMR spectroscopy. Some of the synthesized compounds exhibited weak antibacterial activity against Rhizobium radiobacter, Escherichia coli, and Xanthomonas campestris.     

Synthesis of oxo derivatives of <Emphasis Type="Italic">N</Emphasis>-(<Emphasis Type="Italic">p</Emphasis>-tolysulfonyl)hexahydrocycloalka[<Emphasis Type="Italic">b</Emphasis>]indoles

Hydroxymercuration-demercuration of N-p-tolysulfonyl-4,4a,9,9a-tetrahydro-3H-carbazoles and N-p-tolyl(or methyl)sulfonyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles leads to the formation of the corresponding N-p-tolylsulfonyl-2,3,4,4a,9,9a-hexahydro-1H-carbazol-2-ols and N-p-tolyl(or methyl)sulfonyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indol-2-ols. The latter are oxidized to 2-oxo derivatives with potassium dichromate. The oxidation of 2-methoxy-8-methyl-N-p-tolylsulfonyl-2,3,4,4a,9,9a-hexahydro-1H-carbazol-1-ol under analogous conditions gives 2-methoxy-8-methyl-N-p-tolysulfonyl-2,3,4,4a,9,9a-hexahydro-1H-carbazol-1-one.     

Cyclocondensation of <Emphasis Type="Italic">N</Emphasis>-aryl-3-oxobutanethioamides with 1<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazol-5-amine

Reactions of N-aryl-3-oxobutanethioamides with 1H-1,2,4-triazole-5-amine give mixtures of 7-arylamino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidines, 5-methyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-7-thione, 7-methyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-5-thione, and 5-arylamino-7-methyl[1,2,4]triazolo[ 1,5-a]pyrimidines whose ratio depends on the substituent in the aryl group of initial N-aryl-3-oxobutanethioamide and solvent nature (the presence of a proton-donor solvent).     

Alkylation of 3-methyl-1<Emphasis Type="Italic">H</Emphasis>-acenaphtho[5,6-<Emphasis Type="Italic">de</Emphasis>]pyridazine

Alkylation of 3-methyl-1Н-acenaphtho[5,6]pyridazine with methyl and propyl iodides as well as with benzyl chloride in alkaline medium leads to the formation of the corresponding both N- and С-substituted pyridazine derivatives and also to the dimerization product of the initial compound. The ratio of obtained compounds depends on the used hydride, reaction temperature, and solvent.     

<Emphasis Type="Italic">S</Emphasis>-functional derivatives of 3,4-dihydro-2<Emphasis Type="Italic">H</Emphasis>-1,4-thiasilines

The first cyclic unsaturated S-functional derivatives of 4,4-diphenyl-3,4-dihydro-2H-1,4-thiasiline, S-oxide, S,S-dioxide, and S-sulfonimide, were prepared. Oxidation of the hydrolytically less stable 4,4-dimethyl-3,4-dihydro-2H-1,4-thiasiline leads to the corresponding sulfoxide and sulfone along with the ring opening products, siloxanes containing the sulfoxide or sulfonyl group.     

7,8,9-trimethyl-1-phenyl-3<Emphasis Type="Italic">H</Emphasis>-pyrrolo[2,1-<Emphasis Type="Italic">d</Emphasis>][1,2,5]triazepin-4(5<Emphasis Type="Italic">H</Emphasis>)-one. Synthesis and reactions

A strategy was developed for the synthesis of 7,8,9-trimethyl-1-phenyl-3H-pyrrolo[2,1-d][1,2,5]-triazepin-4(5H)-one, reactions of its functionalization at the С⁴ atom and aza rings fusion at the С⁴?N³ bond were explored. The formation mechanism of the pyrrolo-1,2,5-triazepinone scaffold was suggested.     

Synthesis and Study of Macroheterocyclic Compounds Based on 2,6-Dihydro-1<Emphasis Type="Italic">H</Emphasis>-cyclopenta[<Emphasis Type="Italic">cd</Emphasis>]phenalene-5,7-diimine

Previously unknown macroheterocyclic compounds containing cyclopenta[cd]phenalene and 1-phenyl-1,2,4-triazole, 1,3,4-thiadiazole, or pyridine fragments were synthesized by reaction of 2,6-dihydro-1H-cyclopenta[cd]phenalene-5,7-diimine with heteroaromatic diamines.     

Reactions of 3-Aroylpyrrolo[1,2-<Emphasis Type="Italic">a</Emphasis>]quinoxaline-1,2,4(5<Emphasis Type="Italic">H</Emphasis>)-triones with 2,3-Dihydrofuran and 3,4-Dihydro-2<Emphasis Type="Italic">H</Emphasis>-pyran

3-Aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones reacted with 2,3-dihydrofuran and 3,4-dihydro-2H-pyran to give mixtures of the corresponding hetero-Diels–Alder (furo- and pyrano[3″,2″: 5′,6′]pyrano- [4′,3′: 2,3]pyrrolo[1,2-a]quinoxalines) and Michael adducts (furyl- and pyranylpyrrolo[1,2-a]quinoxalines).     

Tautomerism of azacycles: III. Molecular and crystal structures of 3<Emphasis Type="Italic">H</Emphasis>-and 2-phenyl-1<Emphasis Type="Italic">H</Emphasis>,4<Emphasis Type="Italic">H</Emphasis>-4,5-dihydro-1,2,4-triazole-5-thiones

Compounds capable of tautomerism: sulfanyl-1,2,4-triazole, its C-phenyl derivative, and the crystal hydrate of the latter, were studied by single crystal X-ray diffraction. In the crystals they exist in the form of 3-R-1(H),4(H)-4,5-dihydro-1,2,4-triazole-5-thione with a considerable contribution of the bipolar structure. Published data on the tautomerism of sulfanyl-1,2,4-triazoles and their N-substituted analogs and on the correlation between the spectral characteristics and structures of sulfanyl-1,2,4-triazoles capable of tautomerism are discussed.     

Ultrasound-Assisted Synthesis of 5<Emphasis Type="Italic">H</Emphasis>-Chromeno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridine Derivatives

An environmentally friendly method has been developed for the preparation of 5H-chromeno[2,3-b]pyridine derivatives in an aqueous medium under ultrasound irradiation.     

Polyfunctional imidazoles: XIV. 4-sulfonyl-5-formyl-1<Emphasis Type="Italic">H</Emphasis>-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.     

Prototropic equilibrium in 1(11)<Emphasis Type="Italic">H</Emphasis>-2, 3, 4, 5-tetrahydro[1, 3]diazepino[1, 2-<Emphasis Type="Italic">a</Emphasis>]benzimidazole,synthesis and pharmacological properties of its <Emphasis Type="Italic">N</Emphasis>-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 and antimicrobial screening of novel 9-{2-[(1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-4-yl)methoxy]phenyl}-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1<Emphasis Type="Italic">H</Emphasis>-xanthene-1,8(2<Emphasis Type="Italic">H</Emphasis>)-dione derivatives

A series of novel 9-{2-[(1H-1,2,3-triazol-4-yl)methoxy]phenyl}-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione derivatives were synthesized by a click chemistry approach. The structures of all the newly synthesized compounds were characterized by IR, MASS, ¹H and ¹³C NMR spectral data. The final analogues showed good to excellent antibacterial and antifungal activities in an agar well diffusion assay. Compounds 6i and 6f were the most active against all the test bacterial and fungal strains.