Synthesis of new 3<Emphasis Type="Italic">H</Emphasis>-pyrrole derivatives from 3-aryl-2-oxa-7-azaspiro[4.4]nona-3,6,8-trienes

8-Amino-3-aryl-1-imino-4-methyl-6-(morpholin-4-yl)-2-oxa-7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitriles reacted with acetic anhydride to give different products, depending on the solvent. The reaction in tetrahydrofuran gave the corresponding N-acyl derivatives at the imino group, whereas in pyridine 5-amino-2-morpholin-4-yl-3-(1-aryl-1-oxopropan-2-yl)-3H-pyrrole-3,4-dicarbonitriles were formed as a result of opening of the furan ring.     

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).     

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.     

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.     

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.     

Reductive alkylation of disulfides. Synthesis of 2-(alkylsulfanyl)-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-3-carbonitriles

Reaction of 2,2′-(disulfanediyl)bis(1H-pyrrole-3-carbonitriles) with alkyl halides in ethanol in the presence of sodium tetrahydridoborate afforded 2-(alkylsulfanyl)-1H-pyrrole-3-carbonitriles.     

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.     

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.     

<Emphasis Type="Italic">Z</Emphasis>-and <Emphasis Type="Italic">E</Emphasis>-conformers of <Emphasis Type="Italic">N</Emphasis>-chloroacetylcytisine

N-Chloroacetylcytisine was synthesized by acylation of (–)-cytisine. Stable Z- and E-conformers with respect to rotational isomerism around the N-12–CO bond were found in PMR spectra at room temperature. The point at which PMR resonances of the Z- and E-conformers coalesced upon heating was measured. The transition barrier between the conformers was estimated.     

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.     

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.     

Synthesis of amino acid conjugates of glycyrrhizic acid using <Emphasis Type="Italic">N</Emphasis>-hydroxyphthalimide and <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>'-dicyclohexylcarbodiimide

Synthesis of amino acid conjugates of glycyrrhizic acid with the use of N-hydroxyphthalimide, N,N'-dicyclohexylcarbodiimide, and tert-butyl esters of L-amino acids (valine, isoleucine, phenylalanine, and methionine) was performed followed by deprotection with trifluoroacetic acid. The target amino acid conjugates were isolated by column chromatography on silica gel in 40–45% yield. The structure of the prepared compounds was confirmed by IR and ¹³C NMR spectroscopy.     

<Emphasis Type="Italic">N</Emphasis>-halohexamethyldisilazanes

The review is devoted to N-halohexamethyldisilazanes, perspective but scantily studied halogenating agents. Methods of preparation, physiochemical characteristics, and synthetic potential are considered. Mechanisms of a number of reactions are presented.     

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.     

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.     

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.