Cyclization of trifluoro-<Emphasis Type="Italic">N</Emphasis>-(prop-2-yn-1-yl)methanesulfonamides to <Emphasis Type="Italic">N</Emphasis>-(hydroxymethyl)-1,2,3-triazoles

Three-component heterocyclizations of trifluoro-N-(prop-2-yn-1-yl)methanesulfonamide, trifluoro-N-pheny-N-(prop-2-yn-1-yl)methanesulfonamide, and trifluoro-N,N-di(prop-2-yn-1-yl)methanesulfonamide with formaldehyde and sodium azide afforded N-{[2-(hydroxymethyl)-2H-1,2,3-triazol-4-yl]methyl}-, N-{[2-(hydroxymethyl)-2H-1,2,3-triazol-4-yl]methyl}-N-phenyl-, and N,N-bis{[2-(hydroxymethyl)-2H-1,2,3-triazol-4-yl]methyl}trifluoromethanesulfonamides as the major products together with minor 1-(hydroxymethyl)-1H-1,2,3-triazole isomers.     

Reactions of <Emphasis Type="Italic">N</Emphasis>-acetyl- and <Emphasis Type="Italic">N</Emphasis>-ethoxycarbonyl-2-(1-cycloalken-1-yl)anilines with <Emphasis Type="Italic">meta</Emphasis>-cloroperbenzoic acid

Reaction of N-ethoxycarbonyl-2-(1-cycloalken-1-yl)anilines with meta-cloroperbenzoic acid leads to the corresponding 2-[1-o-(3-chlorobenzoyl)-2-hydroxycyclopent-1-yl]anilines. 5-(2-Acetylaminophenyl)-5-oxopentanic or 6-oxohexanic acids are formed as main products in the reaction of N-acetyl-2-(1-cycloalken-1-yl)anilines with m-chloroperbenzoic acid in CH₂Cl₂. N-Acetyl-2-(1-cyclopenten-1-yl)-3,6-dimethylaniline is an exception in this series since its reaction stops at the stage of epoxide formation.     

Synthesis of <Emphasis Type="Italic">N</Emphasis>-(4-oxo-3,4-dihydroquinazolin-3-yl)succinimide and <Emphasis Type="Italic">N</Emphasis>-(4-oxoquinazolin-3-yl)succinamic acid derivatives based thereon

The reaction of anthranilic acid hydrazide with diethyl oxalate under microwave irradiation was accompanied by decarboxylation with formation of 3-amino-3,4-dihydroquinazolin-4-one, and acylation of the latter with succinic anhydride gave N-(4-oxo-3,4-dihydroquinazolin-3-yl)siccinimide which was converted into various N-(4-oxo-3,4-dihydroquinazolin-3-yl)succinamic acid derivatives.     

Molecular properties of the copolymers of <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-diallyl-<Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-dimethylammonium chloride and maleic acid

The hydrodynamic and conformational properties of molecules of poly(N,N-diallyl-N,N-dimethylammonium chloride) and N,N-diallyl-N,N-dimethylammonium chloride-maleic acid copolymers of different compositions in solutions with various ionic-strength and pH values, as well as of the polyelectrolyte complex based on the copolymer with dodecyl sulfate anions in chloroform, are studied. For poly(N,N-diallyl-N,N-dimethylammonium chloride) molecules in a 1 M NaCl solution, the Kuhn segment length and the hydrodynamic diameter of the chain are estimated as A = 3.9 nm and d = 0.48 nm, respectively. In acidic solutions with pH 3.5, the copolymers demonstrate behavior typical for polyelectrolytes. In an alkaline solution with pH 13, when 1 M NaCl is added to the solution of the copolymer containing 29 mol % maleic acid units, there is an antipolyelectrolyte effect that manifests itself as an increase in the intrinsic viscosity of the copolymer and in the hydrodynamic radius of its molecules. It is found that an increase in the fraction of maleic acid units in the copolymer from 12 to 42 mol % brings about a reduction in the equilibrium rigidity of its macromolecules from 4.1 to 2.2 nm. The equilibrium rigidity of polyelectrolyte-complex molecules is higher than that of initial copolymer molecules owing to steric interactions arising between the aliphatic chains of dodecyl sulfate anions. In an electric field, the molecules of the complex are oriented owing to the induced dipole moment resulting from the displacement of dodecyl sulfate anions along the chain contour.     

Synthesis of new amides of the <Emphasis Type="Italic">N</Emphasis>-methylpiperazine series

New carboxylic acid amides containing an N-methylpiperazine fragment were synthesized by reactions of 1-methylpiperazine or 3- and 4-(4-methylpiperazin-1-ylmethyl)aniline with 4-chlorobenzoyl chloride and of 4-methyl-3-nitroaniline with 4-(4-methylpiperazin-1-ylmethyl)benzoyl chloride or benzotriazol-1-yl 4-(4-methylpiperazin-1-ylmethyl)benzoate. 4-Chloro-N-[4-(4-methylpiperazin-1-ylmethyl)phenyl]benzamide reacted with imidazole, quinolin-5-amine, and 2-methylquinolin-5-amine to give substituted 4-amino-N-[4-(4-methylpiperazin-1-ylmethyl)phenyl]benzamides. 4-Methyl-3-nitrophenyl-4-methylpiperazin-1-yl-substituted benzamides were reduced with hydrazine hydrate over Raney nickel to obtain N-(3-amino-4-methylphenyl)-4-(4-methylpiperazin-1-ylmethyl)benzamide as key intermediate in the synthesis of antileukemic agent imatinib and its isomer with alternative position of the amide group, 4-[(3-amino-4-methylphenylamino)methyl]phenyl-(4-methylpiperazin-1-yl)methanone.     

Regioselective synthesis of polyfluoroalkyl-substituted 7-(1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-1-yl)-6,7-dihydro-1<Emphasis Type="Italic">H</Emphasis>-indazol-4(5<Emphasis Type="Italic">H</Emphasis>)-ones

3-Polyfluoroalkyl-6,6-dimethyl-7-(1H-1,2,3-triazol-1-yl)-6,7-dihydro-1H-indazol-4(5H)-ones were synthesized with high regioselectivity by 1,3-dipolar cycloaddition of terminal alkynes (phenylacetylene, hex- 1-yne, hept-1-yne, and but-3-yn-1-ol) to 7-azido-6,6-dimethyl-3-polyfluoroalkyl-6,7-dihydro-1H-indazol-4(5H)-ones which were prepared by bromination of 6,6-dimethyl-3-polyfluoroalkyl-6,7-dihydro-1H-indazol- 4(5H)-ones with N-bromosuccinimide in anhydrous carbon tetrachloride, followed by treatment of the corresponding 7-bromo derivatives with sodium azide.     

Electroluminescence and photovoltaic properties of bis{<Emphasis Type="Italic">N</Emphasis>-[2-(benzothiazol-2-yl)phenyl]-<Emphasis Type="Italic">N</Emphasis>-(4-methylphenylsulfonyl)amido}zinc

A dual function (electroluminescence and photosensitivity) of devices based on bis{N-[2-(benzothiazol-2-yl)phenyl]-N-(4-methylphenylsulfonyl)amido}zinc was studied. It was shown that both luminescent and photovoltaic properties are strongly dependent on exсiplex formation.     

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.     

Intra- and intermolecular hydrogen bonding in solutions of <Emphasis Type="Italic">N</Emphasis>-(2-hydroxy-3,8-diiodocyclooctyl)trifluoroacetamide and <Emphasis Type="Italic">N</Emphasis>-(4-iodo-2,2,5,5-tetramethyltetrahydrofuran-3-yl)trifluoroacetamide

The methods of IR spectroscopy and quantum chemistry (B3LYP/DGDZVP) were applied to investigation of the types of self-associates formed in solutions of N-(2-hydroxy-3,8-diiodocyclooctyl)trifluoroacetamide and N-(4-iodo-2,2,5,5-tetramethyltetrahydrofuran-3-yl)trifluoroacetamide in CCl₄ by means of hydrogen bonding. The ОН group of N-(2-hydroxy-3,8-diiodocyclooctyl)trifluoroacetamide participates in the formation of intramolecular hydrogen bond ОH···О=С, while chain dimers are formed due to interactions between the NH and С=О groups of the neighboring molecules. Due to the formation of the intramolecular bond, the dimers of N-(2-hydroxy-3,8-diiodocyclooctyl)trifluoroacetamide are energetically less stable than the chain dimer of N-(4-iodo-2,2,5,5-tetramethyltetrahydrofuran-3-yl)trifluoroacetamide.     

Crystallographic study and molecular modeling on the oxidation product of <Emphasis Type="Italic">N</Emphasis>-[(8<Emphasis Type="Italic">R</Emphasis>)-2-methoxy-5,6,7,8,9,10-hexahydro-6,9-methanocyclohepta[<Emphasis Type="Italic">b</Emphasis>]indol-8-yl]acetamide

Crystallization of N-[(8R)-2-methoxy-5,6,7,8,9,10-hexahydro-6,9-methanocyclohepta[b]indol-8-yl]acetamide was accompanied by oxidation at the C^5a–C^10a bond with formation of N-[(5S)-10-methoxy-2,8-dioxo-1,2,3,4,5,6,7,8-octahydro-3,6-methano-1-benzazecin-5-yl]acetamide whose structure was determined by X-ray analysis. Docking of this compound into melatonin-binding pocket of MT_1A receptor was simulated by computer-assisted molecular modeling.     

Atropisomeric <Emphasis Type="Italic">N</Emphasis>-acyl-<Emphasis Type="Italic">N</Emphasis>-(cyclopentenylphenyl)glycines in the synthesis of oxazolo[3,4-<Emphasis Type="Italic">a</Emphasis>]benzoxazocinones

Intramolecular [3+2]-cycloaddition was studied of munchnones generated at heating syn- and anti-atropisomers of N-acyl-N-[6-methyl-2-(cyclopent-2-en-1-yl)phenyl]glycines with acetic anhydride. By spectral and X-ray diffraction analysis syn-isomers of acids and tetrahydro-1,4,7-methanetriyl[1,3]oxazolo[3,4-a][1]- bensazocin-3(3aH)-ones were identified.     

Molecular structure of <Emphasis Type="Italic">N</Emphasis>-(<Emphasis Type="Italic">o</Emphasis>-and <Emphasis Type="Italic">p</Emphasis>-hydroxybenzyl)cytisine

The molecular structures of N-(o-and p-hydroxybenzyl)cytisine were investigated by NMR spectroscopy, x-ray structure analysis, and molecular modeling. It was found that NMR resonances of the OH and aromatic protons in N-(o-hydroxybenzyl)cytisine were doubled because of the presence of two conformers in solution. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 165–168, March–April, 2008.     

Reduction of <Emphasis Type="Italic">N</Emphasis>-(polychloroethylidene)- and <Emphasis Type="Italic">N</Emphasis>-(1-hydroxypolychloroethyl) arenesulfonamides with adamantane in the presence of superacids

N-(2,2,2-Trichloroethylidene)-, N-(2,2-dichloro-2-phenylethylidene)-, and N-(1-hydroxy-2-polychloroethyl) arenesulfonamides reacted with adamantane in carbon tetrachloride in the presence of oleum or concd. H₂SO₄-P₄O₁₀ mixture to give the corresponding N-(2-polychloroethyl)arenesulfonamides as a result of reduc-tion of the azomethine and OH group, respectively.     

<Emphasis Type="Italic">N</Emphasis>-(4-(quinazolin-2-yl)phenyl)benzamide derivatives with potent anti-angiogenesis activities: synthesis and evaluation

Expanding our studies on the anti-angiogenesis activities of 2,4-disubstituted quinazoline derivatives [8], a series of novel N-(2-(quinazolin-2-yl)phenyl)benzamide (SZ) derivatives were designed and synthesized. Cytotoxicity assays indicated that most of these compounds displayed similar cytotoxicity against tumor cells in comparison with our previously reported, but showed a higher cytotoxicity against HUVECs. The SZ derivatives showed a remarkable inhibitive effect against the migration and adhesion of HUVECs, in addition to demonstrating significant in vivo anti-angiogenesis activities in the chick embryo chorioallantoic membrane (CAM) assay. The results proved that the introduction of an aryl group with a basic amide side chain on the 4′ position linked to the amide of the C-2 substituted quinazoline scaffold is an effective approach to improve the anti-angiogenic activity of quinazoline derivatives.     

Synthesis and structure of <Emphasis Type="Italic">N</Emphasis>-(diaminomethylidene)- and <Emphasis Type="Italic">N</Emphasis>-[bis(cyclohexylamino)methylidene]trifluoromethanesulfonamides

N-Trifluoromethylsulfonyl-substituted guanidines CF₃SO₂N=C(NHR)₂ (R = H, cyclohexyl) were synthesized in nearly quantitative yield by reactions of N-sulfinyltrifluoromethanesulfonamide CF₃SO₂N=S=O with urea and of trifluoromethanesulfonamide with N,N′-dicyclohexylcarbodiimide. N-[Bis(cyclohexylamino)-methylidene]trifluoromethanesulfonamide was subjected to protonation with trifluoromethanesulfonic acid and bis(trifluoromethanesulfonyl)imide, and the structure of the resulting salts and initial N-trifluoromethylsulfonylguanidines was studied by NMR and IR spectroscopy and DFT quantum-chemical calculations.     

Photochromism of an <Emphasis Type="Italic">N</Emphasis>-aminofulgimide-derived Schiff base

A Schiff base was synthesized from 5-methoxysalicylaldehyde and N-aminofulgimide, viz., 1-amino-3-[1-(2,5-dimethylthiophen-3-yl)ethylidene]-4-isopropylidenepyrrolidine-2,5-dione. The compound synthesized undergoes photochromic transformations typical of those of N-aminofulgimide studied earlier. A bathochromic shift of the absorption bands of the open and cyclic forms of the obtained Schiff base compared to the starting N-aminofulgimide was observed.     

Halocyclization of 2-(2-{4-[allylamino(thioxo)methyl]piperazin-1-yl}ethyl)-1<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">de</Emphasis>]isoquinoline-1,3(2<Emphasis Type="Italic">H</Emphasis>)-dione

Cyclization of 2-(2-{4-[allylamino(thioxo)methyl]piperazin-1-yl}ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione by the action of iodine, bromine, or sulfuryl chloride gave 2-(2-{4-[4,5-dihydro-5-(halomethyl)-thiazol-2-yl]piperazin-1-yl}ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione hydrohalides which were converted into 2-{2-[4-(5-methylthiazol-2-yl)piperazin-1-yl]ethyl}-1H-benzo[de]isoquinoline-1,3(2H)-dione.     

Functionalization of highly electrophilic <Emphasis Type="Italic">N</Emphasis>-(2,2,2-trichloroethylidene)- and <Emphasis Type="Italic">N</Emphasis>-(2,2-dichloro-2-phenylethylidene) arenesulfonamides with dithiooxamide

Depending on the reactant ratio, dithiooxamide (ethanedithioamide) reacted as N-nucleophile or N,N′-binucleophile with highly electrophilic aldimines, N-(2,2,2-trichloroethylidene)- and N-(2,2-dichloro-2-phenylethylidene)arenesulfonamides, to give the corresponding mono- or bis-adducts, N-[2-polychloro-1-(arylsulfonylamino) ethyl]ethanedithioamides or N,N′-bis[2-polychloro-1-(arylsulfonylamino)ethyl]ethanedithioamides, in good yield.     

Synthesis and properties of <Emphasis Type="Italic">N</Emphasis>-nitro-<Emphasis Type="Italic">O</Emphasis>-(4-nitrophenyl)hydroxylamine

Salts of N-nitro-O-(4-nitrophenyl)hydroxylamine were synthesized by a new method of oxidative nitration, involving the reaction of O-(4-nitrophenyl)hydroxylamine with KNO₂ or NaNO₂ in the presence of PhI(OAc)₂ or PhIO as oxidants. When using Na¹⁵NO₂, the samples containing the nitro group labeled with the ¹⁵N isotope were obtained. Acidification of the appropriate salt gave N-nitro-O-(4-nitrophenyl)hydroxylamine. It is the first N-nitrohydroxylamine isolated in the H-form. Its thermal stability was investigated and the probable mechanism of decomposition was suggested. From a comparison of the ¹⁴N and ¹⁵N NMR spectra of N-nitro-O-(4-nitrophenyl)hydroxylamine with those of its O- and N-methylated derivatives, its equilibrium with the aci-form (N=NOOH) was inferred.     

Synthesis of 1-{4a,6-dimethyl-4a,9a-dihydropyrano-[3,4-<Emphasis Type="Italic">b</Emphasis>]indol-9(1<Emphasis Type="Italic">H</Emphasis>)-yl}ethanone

Heating of the bromination product of 4-methyl-3,6-dihydro-2H-pyran with 4-toluidine or 2-bromo-4-methylamiline in triethylamine gave 4-methyl-N-(4-methylphenyl)- and N-(2-bromo-4-methylphenyl)-4-methyl-3,6-dihydro-2H-pyran-3-amines which were converted into the corresponding amides by reaction with bromo- or chloroacetyl chloride. 1-{4a,6-Dimethyl-4a,9a-dihydropyrano[3,4-b]indol-9(1H)-yl} ethanone was synthesized in good yield by heating N-(2-bromo-4-methylphenyl)-N-(4-methyl-3,6-dihydro-2Hpyran-3-yl)acetamide in boiling toluene in the presence of palladium(II) acetate, triphenylphosphine, copper(II) acetate, triethylamine, and potassium carbonate.