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.     

Alkylation of 2-(methylsulfanyl)-6-polyfluoroalkylpyrimidin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones with haloalkanes

The alkylation of ambident anions of 2-(methylsulfanyl)-6-(polyfluoroalkyl)pyrimidin-4(3H)-ones with 4-bromobutyl acetate leads to concurrent formation of O- and N-(4-acetoxybutyl) derivatives. Polar aprotic solvents favor formation of the O-isomer, and weakly polar dioxane favors N-alkylation. The reaction of 2-(methylsulfanyl)-6-(trifluoromethyl)pyrimidin-4(3H)-one with an equimolar amount of 1,2-dibromoethane in polar acetonitrile gives a mixture of N,N-, O,O-, and N,O-bridged bis-pyrimidines, as well as N- and O-[2-(methylsulfanyl)ethyl] derivatives, whereas in the presence of 10 equiv of 1,2-dibromoethane the N,O-isomer is formed as the only product. The reaction in weakly polar tetrahydrofuran yields N,N- and N,O-bispyrimidines.     

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.     

3-(1-Methyl-1-nitroethyl-1-<Emphasis Type="Italic">ONN</Emphasis>-azoxy)-4-aminofuroxan. Synthesis and transformations of the amino group

A four-step procedure to convert 4-(1-methyl-1-nitroethyl-1-ONN-azoxy)-3-cyanofuroxan into 3-(1-methyl-1-nitroethyl-1-ONN-azoxy)-4-aminofuroxan was developed. The pathways of transformation of the amino group of the synthesized compound into N-nitramino-, N-alkyl-N-nitramino-, N,N’-methylenediamino-, N,N’-methylene-N,N’-dinitramino-, and azo groups were studied.     

Synthesis of <Emphasis Type="Italic">ortho</Emphasis>-carboranyl derivatives of (<Emphasis Type="Italic">S</Emphasis>)-asparagine and (<Emphasis Type="Italic">S</Emphasis>)-glutamine

(S)-Asparagine and (S)-glutamine ortho-carboranyl derivatives with free amino and carboxy groups in the α-position were synthesized. By an example of N ^γ-(1,2-dicarba-closo-dodecarboran-3-yl)-(S)-glutamine it was demonstrated that the developed synthetic approach carboranyl derivatives of amino acids allowed the preparation of optically pure isomers.     

Thermooxidative decomposition of heterocyclic <Emphasis Type="Italic">N</Emphasis>-oxides

Thermooxidative decomposition of pyridine N-oxide, 4-(4-dimethylaminostyryl)pyridine N-oxide, 4-(4-methoxystyryl)pyridine N-oxide, quinoline N-oxide, 2-methylquinoline N-oxide, 4-chloroquinoline N-oxide, 2-styrylquinoline N-oxide, and 2-(4-dimethylaminostyryl)quinoline N-oxide was studied. The kinetic parameters of the thermooxidative processes were calculated according to three independent procedures. The relation between the nature of heterocyclic N-oxide and its stability to thermal oxidation was analyzed.     

4-aryl-2-hydroxy-4-oxobut-2-enoic acids <Emphasis Type="Italic">N</Emphasis>-(2-pyridyl)amides in reactions with diazo compounds

Reactions of 4-aryl-2-hydroxy-4-oxobut-2-enoic acids N-(2-pyridyl)amides with diazomethane, diazoethane, diaryldiazomethanes, and diazofluorene lead to the formation of 2-alkoxy-4-aryl-4-oxobut-2-enoic acids N-(2-pyridyl)amides, 3-aroyl-5-methylpyrazole-4-carboxylic acids N-(2-pyridyl)amides, and 3-alkoxy-3-(2-aryl-2-oxoethyl)-2,3-dihydro-2-oxoimidazo[1,2-a]pyridines. The composition and structure of compounds obtained depend on the nucleophilic nature of the diazo compound and on the character of substituents in the aryl and pyridine parts of the substrate.     

Reactions of <Emphasis Type="Italic">N</Emphasis>-(Polychloroethylidene)arene-and - trifluoromethanesulfonamides with indoles

N-(Polychloroethylidene)arene-and -trifluoromethanesulfonamides reacted with indole and N-substituted indoles to give the corresponding N-[2,2-dichloro(or 2,2,2-trichloro)-1-(1H-indol-3-yl)ethyl]-substituted sulfonamides. Unlike N-(2,2,2-trichloroethylidene)trifluoromethanesulfonamide, less electrophilic N-(poly-chloroethylidene)arenesulfonamides failed to react with 1-(4-nitrophenyl)-1H-indole. Previously unknown N,N’-bis(2,2-dichloroethylidene)biphenyl-4,4’-disulfonamide reacted with 1-benzyl-1H-indole at both azomethine fragments. Likewise, reactions of 1,6-bis(1H-indol-1-yl)hexane and 1,4-bis(1H-indol-1-ylmethyl)-benzene with N-sulfonyl trichloroacetaldehyde imines involved both indole rings in the former.     

Design,synthesis and anti-mycobacterial evaluation of some new <Emphasis Type="Italic">N</Emphasis>-phenylpyrazine-2-carboxamides

N-Phenylpyrazine-2-carboxamides (anilides of pyrazinoic acids with simple substituents in various positions) were previously shown to possess significant biological activities in vitro, markedly anti-mycobacterial and photosynthesis-inhibiting activity. Based on structure-activity relationships (SAR) extracted from previously published series, 25 new anilides of non-substituted pyrazinoic acid (POA), 5-CH₃-POA, 6-Cl-POA, 5-tert-butyl-POA and 5-tert-butyl-6-Cl-POA were designed and synthesised. The phenyl part was substituted with simple hydrophobic substituents chosen from methyl and halogens. 5-tert-Butyl-N-(5-fluoro-2-methylphenyl)pyrazine-2-carboxamide (9), N-(3-chloro-4-methylphenyl)-5-methylpyrazine-2-carboxamide (12), 6-chloro-N-(3-chloro-4-methylphenyl)pyrazine-2-carboxamide (13) and 6-chloro-N-(5-iodo-2-methylphenyl)pyrazine-2-carboxamide (18) possessed whole cell anti-mycobacterial activity in vitro against Mycobacterium tuberculosis H37Rv with minimum inhibitory concentration (MIC) of around 10 μM. Importantly, no cytotoxicity in the HepG2 model was detected in vitro at the concentrations tested and the estimated IC50 values were in hundreds of μM, indicating promising selectivity. N-(3-Chloro-4-methylphenyl)pyrazine-2-carboxamide (11) and N-(4-chloro-2-iodophenyl)pyrazine-2-carboxamide (21) exerted significant activity against Mycobacterium kansasii with MIC 12.6 μM and 8.7 μM, respectively. No activity was detected against Mycobacterium avium. SAR were in accordance with those observed for the derivatives previously published.     

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.     

Synthesis and biological activity of arylaliphatic <Emphasis Type="Italic">N</Emphasis>-(2-aminoethyl)-<Emphasis Type="Italic">N</Emphasis>-(2-hydroxy-2-phenylethyl)carboxamides

N-(2-Aminoethyl)-N-(2-hydroxy-2-phenylethyl)carboxamides were synthesized from styrene oxide by ring opening with N,N-disubstituted ethylenediamines followed by N-acylation. Synthesized compounds have pronounced antiarrhythmic activity and low toxicity.     

Reactions of arylsulfinyl chlorides and <Emphasis Type="Italic">N</Emphasis>-(arylsulfonyl)arylsulfinimidoyl chlorides with <Emphasis Type="Italic">p</Emphasis>-aminophenols

In reactions of arylsulfinyl chlorides and N-(arylsulfonyl)arylsulfinimidoyl chlorides with p-aminophenols formed N-arylthio-1,4-benzoquinone imines, evidently through a stage of N-arylsulfinyl-4-aminophenols and N-(N-arylsulfonyl)arylsulfinylimidoyl-4-aminophenols that under the reaction conditions eliminate respectively H₂O and ArSO₂NH₂.     

Synthesis of Dicarboxylic Acid Amides and Diamides on the Basis of [4-(4-Methoxyphenyl)tetrahydro-2<Emphasis Type="Italic">H</Emphasis>-pyran-4-yl]methanamine

The condensation of various nonaromatic amines with ethyl N-{[4-(4-methoxyphenyl)tetrahydro-2H-pyran-4-yl]methyl}oxamate prepared from [4-(4-methoxyphenyl)tetrahydro-2H-pyran-4-yl]methanamine and diethyl oxalate afforded the corresponding N,N'-disubstituted oxamides. N-Aryloxamides were synthesized by the reaction of [4-(4-methoxyphenyl)tetrahydro-2H-pyran-4-yl]methanamine with ethyl N-aryloxamates. The condensation of N-{[4-(4-methoxyphenyl)tetrahydro-2H-pyran-4-yl]methyl}succinamic acid with primary amines gave N,N'-disubstituted siccinamides.     

Synthesis and structure of silicon-containing <Emphasis Type="Italic">N</Emphasis>-methyland <Emphasis Type="Italic">N</Emphasis>-benzoylamides of diisopropylphosphoric acid

Diisopropyl N-benzoyl-N-(trimethylsilyl)phosphoramidate reacts with ClCH₂SiMe₂Cl under mild conditions to form diisopropyl N-benzoyl-N-[(chlorodimethylsilyl)methyl]phosphoramidate (III). Diisopropyl N-methyl-N-(trimethylsilyl)phosphoramidate with ClCH₂SiMe₂Cl affords an N-transsilylation product which does not rearrange into diisopropyl N-[(chlorodimethylsilyl)methyl]-N-methylphosphoramidate (XV) even under severe conditions (4 h, 130°C). Compound XV was prepared by the reaction of diisopropyl phosphorochloridate with N-[(methoxydimethylsilyl)methyl]-N-methylamine followed by treatment of diisopropyl N-[(methoxydimethylsilyl)methyl]-N-methylphosphoramidate with boron trichloride. Analysis of experimental and calculated ²⁹Si chemical shifts points to a five-coordinate silicon atom in compound III and a fourcoordinate silicon atom in compound XV. According to B3LYP calculations with due regard to solvent effects, compound III is an isomer with a C=O→Si bond. By variation of substituents at silicon, phosphorus, and carbonyl carbon atoms, chelate structures with either C=O→Si or P=O→Si dative bonds can be obtained.     

Free-Radical Co-Oligomerization of <Emphasis Type="Italic">N</Emphasis>-Vinylpyrroles with <Emphasis Type="Italic">N</Emphasis>-Vinylpyrrolidone: A Route to New Bioactive Oligomers

Co-oligomerization of N-vinylpyrroles (N-vinyl-2,3-dimethylpyrrole, N-vinyl-2-phenylpyrrole, N-vinyl-2,3-diphenylpyrrole, N-vinyl-2-(2-thienyl)pyrrole, and N-vinyl-2-[1-(4,5,6,7-tetrahydroindolyl) ethyl]-4,5,6,7-tetrahydroidole) with N-vinylpyrrolidone in the presence of a radical initiator (AIBN) gives co-oligomers with molecular masses of 1600–5200 in up to 87% yield. The products are readily soluble in organic solvents (benzene, 1,4_dioxane, and chloroform), and in the case of high N-vinylpyrrolidone content, also in ethanol and in water. The co-oligomers are non-toxic or have low toxicity (the lethal dose LD₅₀ = 1300–2000) and possess biological activity.     

Reaction of transsilylation of <Emphasis Type="Italic">N</Emphasis>-methyl-<Emphasis Type="Italic">N</Emphasis>-trimethylsilylacetamide with silanes ClCH<Subscript>2</Subscript>SiR<Superscript>1</Superscript>R<Superscript>2</Superscript>Cl

The reaction of N-methyl-N-trimethylsilylacetamide with silanes ClCH₂SiR¹R²Cl (R¹, R² = H, Me; H, Ph; Ph₂) leads to the formation of (O→Si) chelate compounds with pentacoordinate silicon: N-[chloro(methyl)-silyl]methyl-, N-[chloro(phenyl)silyl]methyl-, and N-[chloro(diphenyl)silyl]methyl-N-methylacetamides. From the data of multinuclear NMR spectroscopy, the intermediates of the reaction of N-methyl-N-trimethylsilylacetamide with ClCH₂SiPhHCl and ClCH₂SiPh²Cl are stable in CDCl₃ solution at room temperature during several days and slowly rearrange to the final (O–Si) chelate compounds.     

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.     

Rearrangements of <Emphasis Type="Italic">N</Emphasis>-ethoxycarbonylmethyl-1,2,3,4-tetrahydroquinolinium halogenalkylates effected by sodium hydride. Synthesis of 2,3,4,5-tetrahydro-1<Emphasis Type="Italic">H</Emphasis>-3-benzazepines

Quaternary salts obtained from N-alkyl-1,2,3,4-tetrahydroisoquinolines and ethyl haloacetates or diethyl bromomalonate under the action of sodium hydride in boiling 1,4-dioxane were converted into N-alkyl-N-ethoxycarbonyl-2,3,4,5-tetrahydro-1H-3-benzazepines in 49–60% yield. From the reaction mixture by column chromatography products of β-elimination by Hofmann reaction, 2-(N-methyl-N-ethoxycarbonylmethyl)-aminomethylstyrenes were also isolated (yield 0.6–16%).     

Oligomerization of <Emphasis Type="Italic">N</Emphasis>-vinylpyrroles under the action of iodine

The oligomerization of N-vinylpyrroles (N-vinyl-4,5,6,7-tetrahydroindole, N-vinyl-2-[1-(1-4,5,6,7-tetrahydroindole)ethyl]-4,5,6,7-tetrahydroindole, N-vinyl-2-phenylpyrrole, N-vinyl-3-heptyl-2-phenylpyrrole, N-vinyl-2,3-diphenylpyrrole, and N-vinyl-2-(2-naphthyl)pyrrole) under the action of iodine vapor leads to the formation of iodine-containing oligomers with an iodine content of 17–52% and a yield of up to 99%. The oligomers are paramagnetic and possess conductivity; they are readily soluble in organic solvents (benzene, dioxane, and chloroform) and are stable up to 110–260°C.