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.     

<Emphasis Type="Italic">N</Emphasis>-(2-chloro-1,2-difluorovinyl) derivatives of azoles

Reactions of N-(2,2-dichloro-1,1,2-trifluoroethyl)-substituted azoles with zinc, magnesium, butyllithium, and tris(diethylamino)phosphine were studied, and optimal conditions for the preparation of the corresponding N-(2-chloro-1,2-difluorovinyl) derivatives were found [tris(diethylamino)phosphine, chlorotrimethylsilane]. Some reactions of the obtained unsaturated fluorinated compounds with sulfur-centered nucleophiles were examined.     

Reactions of 1-nitrocyclohexene with <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-binucleophiles

A modification of 1-nitrocyclohexene synthesis is proposed; its reaction with phenylhydrazine and benzoic acid hydrazide is shown to afford monoadducts, and with hydrazine hydrate, bisaduct. With diphenylguanidine occurs heterocyclization to 1-phenyl-2-N-phenylamino-4,5,6,7-tetrahydrobenzimidazole, whose structure is confirmed by the X-ray diffraction data. The analysis performed for this compound of the electron density distribution function in the crystal made it possible to estimate the charge distribution, π-electrons delocalization nature, and the role of N-H…N, C-H…H-C and C-H…C interactions in the formation of the crystal packing.     

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.     

Reactions of <Emphasis Type="Italic">N</Emphasis>-(2,2,2-trichloroethylidene)- and <Emphasis Type="Italic">N</Emphasis>-(2,2-dichloro-2-phenylethylidene)arenesulfonamides with biuret

N-(2,2,2-Trichloroethylidene)- and N-(2,2-dichloro-2-phenylethylidene)arenesulfonamides react with an equimolar amount of biuret to give 1-(1-arylsulfonylamino-2,2,2-trichloroethyl)- or 1-(1-arylsulfonylamino-2,2-dichloro-2-phenylethyl)biurets. The reactions with 2 equiv of N-(polychloroethylidene)arenesulfonamides involve both amino groups in the biuret molecule, yielding the corresponding 1,5-bis(1-arylsulfonylamino-2,2,2-trichloroethyl)- and 1,5-bis(1-arylsulfonylamino-2,2-dichloro-2-phenylethyl)biurets.     

Synthesis of <Emphasis Type="Italic">N</Emphasis>-(2-aminoethyl)- and <Emphasis Type="Italic">N</Emphasis>-(3-aminopropyl)cytisine

2-(N-cytisinyl)acetamide or 3-(N-cytisinyl)propanamide were prepared by treatment of the methyl esters of N-cytisinylacetic or 3-(N-cytisinyl)propanoic acids with aqueous NH₄OH. N-(2-Aminoethyl)-or N-(3-aminopropyl)cytisine was synthesized by reduction of the amide with (i-Bu)₂AlH.     

Reactions of diphenyldithiophosphinic acid with <Emphasis Type="Italic">N</Emphasis>-alkyl-2-chloro-2-methylpropanimines

In contrast to O,O-dialkyldithiophosphoric acids, the reactions of more weak diphenyldithiophosphinic acid with N-alkyl-2-chloro-2-methylpropanimines at a 1 : 1 reagent ratio follow two pathways. The first route is nucleophilic substitution of the chlorine atom of the initially formed iminium salt with the diphenylthiophosphinylthio moiety and the second route is the reduction of the C–Cl bond of this iminium salt cation. The main reaction direction is nucleophilic substitution producing new iminium salts, namely, N-alkyl-2-(di phenyl thiophosphinylthio)-2-methylpropaniminium chlorides. These salts were used as the starting material to synthesize new organophosphorus compounds bearing aldehyde, imine, and acetal groups and 1,3-diazolidine cycle.     

Reactions of <Emphasis Type="Italic">N</Emphasis>-Allyl- and <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-Diallyltrifluoromethanesulfonamides with Carboxylic Acid Amides under Oxidizing Conditions

Reactions of acetamide and benzamide with N-allyltrifluoromethanesulfonamide in the presence of t-BuOCl–NaI afforded exclusively 2,5-bis(chloromethyl)-1,4-bis(trifluoromethanesulfonyl)piperazine. Analogous reaction with N,N-diallyltrifluoromethanesulfonamide gave mixed halogenation product at only one C=C double bond of the substrate.     

Conformations and properties of <Emphasis Type="Italic">O</Emphasis>-Alkyl-<Emphasis Type="Italic">S</Emphasis>-(2-<Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-dialkylamino)-ethylmethylthiophosphonates

Conformers of the biologically active compounds CH₃P(O)(OR)(SCH₂CH₂NR ₂ ^′ ), where (I) R = i-C₄H₉, R′ = C₂H₅ and (II) R = C₂H₅, R′ = i-C₃H₇, are calculated within the AM1 level of theory. The elongated and twisted forms with maximum and minimum distances between a nitrogen atom and those of a phosphorus tetrahedron, respectively, and bearing a syn and anti oriented alkoxy group relative to a phosphoryl oxygen, are studied. It is found that the differences between the energy, electronic, and geometric parameters of these forms are apparent in differences between their properties, e.g., the ability to participate in complexation and protonation, reactions that to some extent simulate the interaction between a substance and a biological object.     

Copolymer of <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-diallyl-<Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-dimethylammonium chloride with maleic acid as drug carrier

A copolymer of N,N-diallyl-N,N-dimethylammonium chloride with maleic acid of constant composition was prepared under the conditions of radical initiation. The possibility of the functionalization of the copolymer with drugs containing amino groups by polymer-analogous transformations was examined. Conditions were found for preparing conjugates of the copolymer with isoniazid. The structures and the quantitative compositions of the conjugates were determined by ¹³С NMR spectroscopy, and the possibility of preparing conjugates with controlled drug content was demonstrated.     

Thiocyanation of <Emphasis Type="Italic">N</Emphasis>-arylsulfonyl-, <Emphasis Type="Italic">N</Emphasis>-aroyl-, and <Emphasis Type="Italic">N</Emphasis>-[(<Emphasis Type="Italic">N</Emphasis>-arylsulfonyl)benzimidoyl]-1,4-benzoquinone imines

Reactions of thiocyanate ion with N-aroyl-, N-arylsulfonyl-, and N-(N-arylsulfonylbenzimidoyl)-1,4-benzoquinone imines follow the 1,4-addition pattern, and the adducts undergo intramolecular cyclization to give the corresponding N-substituted 5-amino-1,3-benzoxathiol-2-ones as final products.     

Synthesis of (<Emphasis Type="Italic">E</Emphasis>)-<Emphasis Type="Italic">N</Emphasis>-(3-alkoxy-4-acyloxyphenylmethylene)-<Emphasis Type="Italic">N</Emphasis>-(<Emphasis Type="Italic">e</Emphasis>-cyclohexyl)amines

Previously unknown E isomers of azomethines (Schiff bases) were synthesized from vanillal and vanillin esters by their reaction with cyclohexylamine.     

Reactions of <Emphasis Type="Italic">N</Emphasis>-aroxycarbonyltrichloroacetimidates with nucleophilic phosphorus derivatives

Aryl N-aroxycarbonyltrichloroacetimidates (Ar = Ph, 4-FC₆H₄) react with diphenylphosphinite according to the scheme of the aza-Perkow reaction to give the corresponding aryl N-(1-aroxy-2,2-dichloro-vinyl)-N-diphenylphosphinoylcarbamates. The structure of one of these compounds was confirmed by single crystal X-ray diffraction analysis. In the case of electron-accepting substituents (Ar = 4-O₂N₆H₄), the primary product undergoes mild -elimination to give nitrophenyl diphenylphosphinate and 1-nitrophenoxy-2,2-dichlorovinyl isocyanate. The reaction of trichloroacetimidates with triethyl phosphite yields a mixture of O- and N-phosphorylation products.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 11, 2004, pp. 1797–1803.Original Russian Text Copyright © 2004 by Rassukanaya, Onysko, Sinitsa, Bolbut, Chernega.This revised version was published online in April 2005 with a corrected cover date.     

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.     

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.     

Features of catalyzed hydration of 2-(dichloromethyl)-<Emphasis Type="Italic">N</Emphasis>-[(1<Emphasis Type="Italic">R</Emphasis>)-1-phenylethyl)]cyclopent-3-ene-1-carboxamides

The hydration of gem-dichloromethyl group in 2-(dichloromethyl)-N-[(1R)-1-phenylethyl)]cyclopent-3-ene-1-carboxamides in aqueous acetonitrile catalyzed by AgNO₃, FeCl₃·6H₂O, PdCl₂, and BaO was investigated. The optimum results were obtained at the use of BaO. It was demonstrated, that Pd-catalyzed reactions initiated intermolecular ether formation from the primary hydration products, bicyclic amides.     

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.     

Conformational isomerization of <Emphasis Type="Italic">N</Emphasis>-(naphthalen-1-yl)-<Emphasis Type="Italic">N</Emphasis>-(phenyl(quinolin-3-yl)methyl)amide derivatives

A series of N-(naphthalen-1-yl)-N-(phenyl(quinolin-3-yl)methyl)amide derivatives were designed and synthesized as anti-Mycobacterium tuberculosis drugs. NMR spectra showed that two conformational isomers of these compounds exist in solution, which is not due to cis-trans isomerization of amide bond. We proposed that the spatial interactions between three large aromatic groups caused the conformational isomerization, which was supported by molecular modeling and X-ray diffraction.