1-Bromo-3,3,3-trifluoro-1-nitropropene: Synthesis and reaction with phenyl azide

An improved procedure was developed for the synthesis of 3,3,3-trifluoro-1-nitropropene, and a new representative of gem-bromonitroalkenes, 1-bromo-3,3,3-trifluoro-1-nitropropene, was synthesized therefrom. Its reaction with phenyl azide gave a mixture of two regioisomeric 1,2,3-triazoles, from which pure 5-nitro-1-phenyl-4-(trifluoromethyl)-1H-1,2,3-triazole was isolated.     

Synthesis of tertiary amines containing <Emphasis Type="Italic">gem</Emphasis>-dichlorocyclopropane and cycloacetal fragments

Reactions of secondary amines containing gem-dichlorocyclopropane and cycloacetal fragments with allyl chloride, trans-1,3-dichloropropene, benzyl chloride, and chloromethyl-gem-dichlorocyclopropane were studied. The corresponding tertiary amines were obtained in 20–85% yield. Microwave radiation stimulates N-alkylation of the secondary amine containing the heterocyclic moiety. The structures of the tertiary amines prepared were studied. The configuration of the double bond in the trans-1,3-dichloropropene derivative is retained.     

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%).     

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.     

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.     

Bis(<Emphasis Type="Italic">gem</Emphasis>-dihalocyclopropanes): synthesis and heterocyclization upon treatment with nitronium triflate

A reaction of octa-1,7and deca-1,9-dienes with an excess of bromofluorocarbene proceeds predominantly with the formation of a monoadduct, whereas the bis-adduct can be prepared by repeated cyclopropanation. The [1+2] cycloaddition of dichlorocarbene to the monoadduct of bromofluorocarbene with deca-1,9-diene gave a new bis(cyclopropane) containing gem-dichloro- and gem-bromofluorocyclopropane fragments in one molecule. The bis-adducts obtained were subjected to the heterocyclization with nitronium triflate: in the case of bis(gem-bromofluorocyclopropane) the reaction proceeded with retention of one dihalocyclopropane fragment and gave mononuclear pyrimidine N-oxide.     

Microwave promoted synthesis and anticological screening of <Emphasis Type="Italic">β</Emphasis>-aminobisphosphonates-based benzothiazole motif against human breast and colon cancer diseases

New antineoplastic series of substituted benzothiazolo-β-aminobisphosphonic acids have been developed on the basis of the prospecting potency of the benzothiazole motifs and the aminomethylenebisphosphonate moiety as well as on the prediction of the biological activity utilizing computer program PASS, version 2014-1. Target compounds were obtained in excellent yields (70–90%) via Phospha–Michael-type addition reaction of tetraethyl methylene-1,1-bisphosphonate reagent to a group of Schiff bases incorporating benzothiazole moiety. The reactions proceeded under microwave irradiation, utilizing the advantages of the environment, friendly protocol such as high efficiency, short reaction time, and excellent yields. In consistency with the prospected results, the new NBP acids revealed positive properties against human breast and colon tumor cell lines. Remarkable potency for six lead compounds (out of 12) was observed against breast (MCF7, MDAMB/435, MDAMB/231/ATCC, HS-578T with GI₅₀: 2.05–6.47 μM) and colon (COLO-205, HCT-116, HCC-2998, and SW-620 with GI₅₀: 3.03–7.92 μM) carcinoma cell lines when compared with the positive control Adriamycin (breast, GI₅₀: 3.27–6.64 μM; colon, GI₅₀: 4.09–8.75 μM). Notably, there is a consistency between the prediction and the determined biological results.     

β-Acetyl-β-nitrostyrenes: Structure and use for synthesis of heteryl-containing structures

¹H, IR, and electronic absorption spectroscopy and X-ray diffraction analysis were used to establish that 1-acetyl-1-nitro-2-phenyl-and 2-(p-methoxyphenyl)ethenes have Z configuration, and their 2-(p-N,Ndimethylaminophenyl)-substituted analog exists in chloroform-d ³ as a mixture of Z and E isomers. The reactions of gem-acetylnitroethenes with N-methylpyrrole were shown to involve alkylation at the C²-reaction center of the heterocycle. The reactions of these nitroalkenes with hydrazine form pyrazoles and azines, with acetylhydrazine, the corresponding hydrazones (via transalkenylation), and with sodium azide, acetylsubstituted 1,2,3-triazoles.     

Reaction of <Emphasis Type="Italic">N</Emphasis>-phenyltriflamide with 1,2-dibromoethane and propargyl bromide. Unexpected cleavage of С–С and С–N bonds

Reaction of N-phenyltriflamide with 1,2-dibromoethane under basic conditions in DMSO unexpectedly results in N-methyl-N-phenyltriflamide and 1,3-diphenylurea. The presumed reaction mechanism includes the formation of unstable intermediate disubstitution product TfN(Ph)CH₂CH2N(Ph)Tf that suffers the the С–С bond cleavage resulting in TfN(Me)Ph and N,N′-methanediylbis(N-phenyltriflamide). The latter reacts with K₂CO₃ releasing two molecules of potassium triflinate and after hydrolysis of diphenylcarbodiimide PhN=C=NPh gives 1,3-diphenylurea. With propargyl bromide, N-phenyltriflamide affords N-propargyl-Nphenyltriflamide in high yield. The bromination of the latter results in a mixture of Z,E-isomers of N-(2,3-dibromoprop-2-en-1-yl)-N-phenyltriflamide which undergo dehydrobromination giving first N-(3-bromopropanedienyl)-N-phenyltriflamide and then the products of the C–N bond cleavage: N-phenyltriflamide and 3,3-dimethoxyprop-1-yne.     

Synthesis of isoxazole derivatives of 4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazole

Cyclocondensation of pent-1-en-4-yn-3-one with phenylhydrazine and p-tolylhydrazine occurs at the positions 1, 3. Proceeding from the 1-aryl-3-ethynyl-4,5-dihydro-1H-pyrazoles formed in the reaction in yields up to 95% we prepared potentially biologically active isoxazole derivatives of pyrazoline. The structure of 5-[1-(4-methylphenyl)-4,5-dihydro-1H-pyrazol-3-yl]-3-phenyl-1,2-oxazole was studied by X-ray diffraction analysis.     

Fusion of 2-(furan-2-yl)thiazole to 1-methyl-1<Emphasis Type="Italic">H</Emphasis>-benzimidazole

Methylation of 5(6)-nitro-1H-benzimidazole with methyl iodide in the presence of potassium hydroxide and N-methylpyrrolidin-2-one gave a mixture of isomeric 1-methyl-5-nitro- and 1-methyl-6-nitro-1H-benzimidazoles which were reduced with tin in concentrated aqueous HCl on heating. The resulting amines reacted with furan-2-carbonyl chloride in N-methylpyrrolidin-2-one to give furan-2-carboxamides which were treated with excess P₂S₅ in pyridine. Oxidation of isomeric furan-2-carbothioamides with K₃[Fe(CN)₆] in alkaline medium afforded a mixture of intramolecular cyclization products, 2-(furan-2-yl)-6-methyl-6H-imidazo[4,5-g][1,3]benzothiazole and 2-(furan-2-yl)-8-methyl-8H-imidazo[4,5-g][1,3]benzothiazole which were separated by column chromatography and identified.     

Reaction of 2-methylquinoline with 3-phenylprop-2-ynenitrile in the KOH—H<Subscript>2</Subscript>O system

The reaction of 2-methylquinoline with 3-phenylprop-2-ynenitrile in the presence of water (0—25 °C, 20 mol.% KOH, 5 equiv. H₂O) is accompanied by the loss of aromaticity of the quinoline nucleus and results in double functionalization of the molecule at the nitrogen atom and the methyl group. Two 2-cyano-1-phenylethenyl groups were introduced into the molecule to form (2E,4E)-4-{1-[(Z)-2-cyano-1-phenylethenyl]quinolin-2(1H)-ylidene}-3-phenylbut-2-enenitrile in 59—67% yield. This reaction is stereoselective: the N-2-cyano-1-phenylethenyl-substituent has the Z-configuration, while the 1,3-diene moiety at the methyl group has the E,E-configuration. (2E)-3-Phenyl-4-(quinolin-2-yl)but-2-enenitrile that formed as a by-product (0—24% yields) is formally the addition product of the methyl group of the quinoline substrate at the acetylenic bond.     

New catalysts of dry reforming of methane into synthesis gas

New catalysts have been developed for the production of synthesis gas via a resource-saving and environmentally friendly process—dry reforming of methane. The catalysts are fabricated from NdCaCo_1–xNi _x On precursors (x = 0, 0.2, 0.4, 0.6, 0.8, 1) synthesized by a ceramic method. According to X-ray powder diffraction, when reacting with an equimolar CH₄/CO₂ mixture at 800–900°С, the precursors are converted into a mixture of neodymium and calcium oxides and cobalt and nickel metals. The catalyst based on NdCaNiO _n at 850°С has ensured high conversions of methane (91%) and CO₂ (86%) at СО and hydrogen yields of 88 and 78%, respectively. At 940°С, the yield of CO is close to the quantitative one (97%).     

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.     

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.     

Thebaine Adducts with Maleimides. Synthesis and Transformations

Diels-Alder reaction of thebaine with maleimides is structurally specific and yields [7,8,3′,4′ ]-succinimido-endo-ethenotetrahydrothebaines containing N′-alkyl, cycloalkyl, aralkyl or aryl substituents. N′-[1(S)-hydroxymethyl-2-methylpropyl]-succinimido-6,14-endo-ethenotetrahydrothebaine formed in reaction of S-valinol with (7α,8α)-anhydrido-6,14-endo-ethenotetrahydrothebaine. The reduction of the adducts by LiAlH₄ afforded N′-substituted 7,8-pyrrolidino-endo-ethenotetrahydrothebaines. The reduction of fused succinimides by NaBH₄ resulted in the corresponding 2′α-hydroxylactam derivatives. O-Demethylation of the tetrahydrothebaine pyrrolidine derivatives effected by BBr₃ afforded compounds of the tetrahydrooripavine series. The O-demethylation of tetrahydrothebaine succinimide derivatives gave rise to the corresponding 6-demethyl-endo-ethenotetrahydrooripavines. Alkylation conditions were found for N′-(4-hydroxyphenethyl)-substituted tetrahydrothebaine succinimide derivatives.     

Quinoxaline-2,3-dithiol in reactions with propargyl bromide and 1,3-dibromopropyne

Propargyl bromide with quinoxaline-2,3-dithiol in DMSO in the presence of K₂CO₃ affords 2,3-bis-(2-propynylsulfanyl)quinoxaline in good yield whereas in absolute methanol in the presence of sodium methoxide at 20°C a 1:2 mixture of 2,3-bis(2-propynylsulfanyl)quinoxaline and 3-(2-propynylsulfanyl)-2(1H)-quinoxalinethione is formed. Individual 3-(2-propynylsulfanyl)-2(1H)-quinoxalinethione was obtained by crystallization of this mixture from ether. The reaction of 1,3-dibromopropyne with quinoxaline-2,3-dithiol in ethanol in the presence of NaOH at heating results in 2-bromomethylidene-1,4-(3H)-dithiino[2,3-b]quinoxaline in 77% yield. Performing this reaction in methanol in the presence of sodium methoxide during long heating (16 h) led to 2,3-bis[(3-bromo-2-propynyl)sulfanyl]quinoxaline in 72% yield.     

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.     

Phase Equilibrium States in the <Emphasis Type="Italic">n</Emphasis>-Dodecane–<Emphasis Type="Italic">n</Emphasis>-Hexadecane–Cyclododecane System

A three-component system comprising cyclododecane and n-alkanes is studied by means of differential thermal analysis on a differential scanning microcalorimeter. It is concluded that the investigated system is of the eutectic type and the n-dodecane–n-hexadecane–cyclododecane eutectic mixture system is 73.0 wt % n-С₁₂Н₂₆, 9.0 wt % n-С₁₆Н₃₄, and 18.0 wt % С₁₂Н₂₄. Its melting point is found to be ?17.7°C.     

Unexpected reactions of dichloro(ethyl)silane with DMSO in organic solvents

The effect of the solvent nature on the composition of the products formed upon the reaction between EtSi(H)Cl₂ and DMSO (molar ratio 1: 1, 0 °C) was revealed. This reaction in non-polar and low polar solvents (toluene, chloroform) gives oligoethyl(hydro)cyclo-siloxanes ((EtSi(H)O) _n , n = 3—8) as the major products in the yields up to 77%. In MeCN, oligoethyl(hydro)cyclosiloxanes are formed along with cyclic monochlorinated siloxanes ((EtSi(H)O) _n (EtSi(Cl)O), n = 2—7) in a ratio of ~7: 3 (68: 29 wt.%). In excess diethyl ether, the overall yield of oligoethyl(hydro)cyclosiloxanes does not exceed 25% and the major products are linear α,ω-diethoxyoligoethyl(hydro)siloxanes (EtO(EtSi(H)O) _n Et, n = 2—7) formed in 70—75% yields. A plausible reaction mechanism leading to the final products was suggested. Apparently, the reaction proceeds via ethyl(hydro)-and chloro(ethyl)silanones as intermediates.