Synthesis of 6-Methyl-4-(1-methyl-2-buten-1-yl)-2-(2-cyclohexen-1-yl)- and 6-Methyl-4-(1-methyl-2-buten-1-yl)-2-(1-cyclohexen-1-yl)anilines

Alkenylation of 6-methyl-2-(2-cyclohexen-1-yl)- and 2-(1-cyclohexen-1-yl)anilines with piperylene in the presence of AlCl₃ and transformation of the resulting cyclohexenylanilines into carbazole structures were studied.__________Translated from Zhurnal Prikladnoi Khimii, Vol. 78, No. 3, 2005, pp. 441–443.Original Russian Text Copyright © 2005 by Gataullin, Ishberdina, Sotnikov, Abdrakhmanov.     

Ultrasound- and microwave-assisted synthesis of (E)-1-aryl-3-[2-(piperidin-1-yl)quinolin-3-yl]prop-2-en-1-ones and (E)-1-aryl-3-[2-(pyrrolidin-1-yl)quinolin-3-yl]prop-2-en-1-ones,and their antimicrobial activity

Series of new (E)-1-aryl-3-[2-(piperidin-1-yl)quinolin-3-yl]prop-2-en-1-ones and (E)-1-aryl-3-[2-(pyrrolidin-1-yl)quinolin-3-yl]prop-2-en-1-ones have been efficiently prepared via the Claisen-Schmidt condensation of 2-(piperidin-1-yl)quinoline-3-carbaldehyde and 2-(pyrrolidin-1-yl)quinoline-3-carbaldehyde, respectively, with aryl methyl ketones under conditions of ultrasound and microwave irradiation. Structures of the products have been confirmed by IR, ¹H NMR, ¹³C NMR, and mass spectroscopy, as well as by elemental analysis. Evaluation of the in vitro antibacterial activity against bacterial (Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli) and fungal (Aspergillus niger and Candida metapsilosis) strains has revealed good antimicrobial activity of some of the tested compounds.     

Reaction of N-methylsulfonyl-and N-(p-tolylsulfonyl)-2-(cyclopent-1-en-1-yl)anilines with bromine in the presence of potassium thiocyanate and in methanol

The reactions of N-methylsulfonyl-and N-(p-tolylsulfonyl)-2-(cyclopent-1-en-1-yl)-6-methylaniline with molecular bromine in the presence of potassium thiocyanate gave N-methylsulfonyl-and N-(ptolylsulfonyl)-2-(5-isothiocyanatocyclopent-1-en-1-yl)-6-methylanilines. N-Methylsulfonyl-2-(cyclopent-1-en-1-yl)-6-methylaniline reacted with bromine in methanol in the presence of NaHCO₃ or with CuBr₂ in MeOH to afford N-methylsulfonyl-2-(5-methoxycyclopent-1-en-1-yl)-6-methylaniline. The reaction of N-methylsulfonyl-2-(5-isothiocyanatocyclopent-1-en-1-yl)-6-methylaniline with diethylamine led to the formation of N-methylsulfonyl-2-{5-[diethylamino(thioxo)methyl]aminocyclopent-1-en-1-yl}-6-methylaniline which was converted into 5-methyl-4-methylsulfonyl-2,3,3a,4-tetrahydrocyclopenta[b]indole by heating with potassium hydroxide.     

Kinetic resolution of 1-(benzofuran-2-yl)ethanols by lipase-catalyzed enantiomer selective reactions

Kinetic resolution of racemic 1-(benzofuran-2-yl)ethanols rac-1a–d was performed by lipase-catalyzed enantiomer selective acylation (E≫100) yielding (1R)-1-acetoxy-1-(benzofuran-2-yl)ethanes (R)-2a–d and (1S)-1-(benzofuran-2-yl)ethanols (S)-1a–d in highly enantiopure form. The degree of enantiomer selectivity for enzymatic alcoholysis/hydrolysis processes starting from racemic 1-acetoxy-1-(benzofuran-2-yl)ethane rac-2 was also tested under various conditions including supercritical CO₂ medium. Racemization-free lipase-catalyzed ethanolysis of the (1R)-1-acetoxy-1-(benzofuran-2-yl)ethanes (R)-2a–d yielded almost quantitatively the enantiopure (1R)-1-(benzofuran-2-yl)ethanols (R)-1a–d.     

Synthesis and reactions of N-acetyl- and N-(2-chloroacetyl)-N-[(2E)-1-methylbut-2-en-1-yl]-2-iodoanilines

The reaction of N-(1-methylbut-2-en-1-yl)-2-iodaniline with Ac₂O or ClCH₂C(O)Cl results in a mixture of syn- and anti-atropisomers of N-acetyl- and N-chloroacetyl-N-(1-methylbut-2-en-1-yl)-2-iodaniline in a ratio of 1:1. Ozonolysis of the latter followed by reduction with dimethyl sulfide in CH₂Cl₂ gives rise to the atropisomers mixture of 2-[N-(chloroacetyl)-N-(2-iodophenyl)]aminopropanal in a ratio of 1:3. When heated in boiling benzene, the mixture of atropoisomeric aldehydes reacts with triphenylphosphine to afford a mixture of 2-[(N-acetyl)-N-(2-iodophenyl)]aminopropanal atropisomers in 1:3 ratio.     

Heterocyclizations of 1-(Benzothiazol-2-yl)-4-phenylthiosemicarbazide

1-(Benzothiazol-2-yl)-4-phenylthiosemicarbazide reacted with methyl iodide in the presence of sodium acetate in boiling ethanol to give 2,2′-dithiobis[N-(5-methylsulfanyl-4-phenyl-4H-1,2,4-triazol-3-yl)-benzenamine]. The reaction of the title compound with dimethyl acetylenedicarboxylate in dioxane led to the formation of methyl 3-(benzothiazol-2-yl)-2-(2-methoxy-2-oxoethyl)-2,3-dihydro-1,3,4-thiadiazole-2-carboxylate.     

Rhodium(I) complexes with pyridazine, 4,6-dimethyl-pyrimidine, 4,6-bis(3,5-dimethylpyrazol-1-yl)pyrimidine, 3,6-bis(3,5-dimethylpyrazol-1-yl)pyridazine and 3-(3,5-dimethylpyrazol-1-yl)-6-chloropyridazine

The synthesis and properties of rhodium(I) complexes of formulae [“RhCl(diolefin)”₂(L)] (or [Rh(Cl(diolefin)(L)]), and [Rh(diolefin)(L)]_n(ClO₄)_n are reported. These complexes react with carbon monoxide to yield the related carbonyl derivatives. Ligands used were pyridazine, 4,6-dimethyl-pyrimidine, 4,6-bis(3,5-dimethylpyrazol-1-yl)pyrimidine, 3,6-bis(3,5-dimethylpyrazol-1-yl)pyridazine and 3-(3,5-dimethyl-pyrazol-1-yl)-6-chloropyridazine. Related iridium(I) and gold(I) compounds are also reported.     

Reaction of 1-vinylpyrrole-2-carbaldehydes with phosphorus pentachloride: a stereoselective synthesis of E-2-(2-dichloromethylpyrrol-1-yl)vinylphosphonyl dichlorides

1-Vinylpyrrole-2-carbaldehydes react with phosphorus pentachloride (benzene, 10-15 °C) to afford E-2-(2-dichloromethylpyrrol-1-yl)vinylphosphonium hexachlorophosphates in up to 85% yield, which after treatment with SO₂ (benzene, rt) are converted into E-2-(2-dichloromethylpyrrol-1-yl)vinylphosphonyl dichlorides in 50-75% yields.     

Degenerate rearrangement of 9-isopropenyl-9,10-dimethyl-phenanthren-9-yl and 9,10-dimethyl-9-(trans-1-methylprop-1-en-1-yl)phenanthren-9-yl cations

¹H NMR study has shown that long-lived 9-R-9,10-dimethylphenanthren-9-yl cations (R = isopropenyl, trans-1-methylprop-1-en-1-yl) generated in the system HSO₃F-SO₂ClF-CD₂Cl₂ at ?130°C undergo degenerate rearrangement via 1,2-vinyl shifts (ΔG’ = 37 and 39 kJ/mol, respectively, at ?88°C). Analysis of the geometric parameters of the initial structures and transition states calculated by the DFT method indicates that unfavorable steric factors are responsible for the sharp deceleration of 1,2-shifts of the isopropenyl and trans-1-methylprop-1-en-1-yl groups as compared to vinyl and cis-1-methylprop-1-en-1-yl groups, respectively.     

Synthesis and luminescent properties of neutral Eu(III) and Gd(III) complexes with 1-(1,5-dimethyl-1h-pyrazol-4-yl)-4,4,4-trifluoro-1,3-butanedione and 4,4,5,5,6,6,6-heptafluoro-1-(1-methyl-1H-pyrazol-4-yl)-1,3-hexanedione

Neutral [EuL₃Phen] complexes were synthesized by the reaction of EuCl₃ with heterocyclic diketones-1-(1,5-dimethyl-1H-pyrazol-4-yl)-4,4,4-trifluoro-1,3-butanedione and 4,4,5,5,6,6,6-heptafluoro-1-(1-methyl-1H-pyrazol-4-yl)-1,3-hexanedione—and 1,10-phenanthroline (Phen) in an aqueous alcohol solution in the presence of NaOH. The reaction of GdCl₃ with the same diketones under analogous conditions, but without adding 1,10-phenanthroline, yielded [GdL₃(H₂O)₂] complexes. The composition of the complexes was determined by elemental analysis, and their optical and luminescent properties were examined.     

Antibacterial Activity of a Promising Antibacterial Agent: 22-(4-(2-(4-Nitrophenyl-piperazin-1-yl)-acetyl)-piperazin-1-yl)-22-deoxypleuromutilin

A novel pleuromutilin derivative, 22-(4-(2-(4-nitrophenyl-piperazin-1-yl)-acetyl)-piperazin-1-yl)-22-deoxypleuromutilin (NPDM), was synthesized in our laboratory and proved excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). In this study, more methods were used to further study its preliminary pharmacological effect. The antibacterial efficacy and toxicity of NPDM were evaluated using tiamulin as the reference drug. The in vitro antibacterial activity study showed that NPDM is a potent bactericidal agent against MRSA that induced time-dependent growth inhibition and a concentration-dependent post-antibiotic effect (PAE). Toxicity determination showed that the cytotoxicity of NPDM was slightly higher than that of tiamulin, but the acute oral toxicity study proved that NPDM was a low-toxic compound. In an in vivo antibacterial effect study, NPDM exhibited a better therapeutic effect than tiamulin against MRSA in a mouse thigh infection model as well as a mouse systemic infection model with neutropenia. The 50% effective dose (ED₅₀) of NPDM in a Galleria mellonella infection model was 50.53 mg/kg. The pharmacokinetic properties of NPDM were also measured, which showed that NPDM was a rapid elimination drug in mice.     

Synthesis,Structure, and Anti-influenza Activity of 2-(Adamantan-1-yl)-5-aryl-1,3,4-oxadiazoles and 2-(Adamantan-1-yl)-5-aryltetrazoles

Two series of new adamantyl derivatives of polynitrogen heterocycles, 2-(adamantan-1-yl)-5-aryl- 1,3,4-oxadiazoles and 2-(adamantan-1-yl)-5-aryl-2H-tetrazoles, have been synthesized, and their structure has been determined by NMR spectroscopy, mass spectrometry, and X-ray analysis. Biological studies in vitro have revealed high inhibitory activity of some of the synthesized 2-(adamantan-1-yl)-5-aryl-2H-tetrazoles against H1N1 influenza A viruses in combination with a relatively low selectivity.     

Dienic sex pheromones : Stereoselective syntheses of (7E,9Z)-7,9-dodecadien-1-yl acetate, (E)-9,11-dodecadien-1-yl acetate,and of (9Z), 11E)-9,11- tetradecadien-1-yl acetate by palladium-catalyzed reactions

Pure (7E,9Z-7, 9-dodecadien-1-yl acetate (1), the sex pheromone of Lobesiabotrana, has been prepared in 21.6% overall yield by a reaction scheme involving; (i) the cross-coupling of (E) - 8 - (2 - tetrahydropyranyloxy) -1 - octenyldisiamylborane with 1 - bromo - 1 - butyne, in the presence of a Pd (O) catalyst and base; (ii) the acetylation of the crude product of this reaction; (iii) the (Z)-stereoselective reduction of the obtained conjugated (E)-enyn-1-yl acetate. (E)-9,11-Dodecadien-1-yl acetate (2), a sex pheromone component of Diparopsiscastanea, has been analogously obtained (in 54.3% overall yield) by cross-coupling of (E) - 10 - (2 - tetrahydropyranyloxy) - 1 - decenyl borane with vinyl bromide, in the presence of a Pd (O) catalyst and base, followed by acetylation of the crude product. Compound 2, which was 87.7% chemically pure, was purified by column chromatography over SiO₂-AgNO₃. Chemically pure (9Z, 11E) - 9,11 - tetradecadien - 1 - yl acetate (3), a sex pheromone component of Spodopteralittoralis, has been prepared (in 30.2% overall yield) by reaction of 10 - (2 - tetrahydropyranyloxy) - 1 - decynylamagnesium bromide with (E)-1-iodo-1-butene, in the presence of a Pd (O) catalyst, followed by acetylation of the crude product and by (Z)-stereoselective reduction of the obtained (E)-enyn-1-yl acetate.The stereoisomeric purity of 1, 2 and 3 has been evaluated by glc analysis on glass capillary columns or by reverse phase hplc analysis.     

Synthesis,spectral characterization and biological evaluation of novel 1-(2-(4,5-dimethyl-2-phenyl-1H-imidazol-1-yl)ethyl)piperazine derivatives

A simple, highly useful synthesis of 1-(2-(4,5-dimethyl-2-phenyl-1H-imidazol-1-yl)ethyl)piperazine derivatives is achieved by a four component cyclo condensation of diacetyl, aromatic aldehyde, 2-(piperazin-1-yl)ethanamine and ammonium acetate using SO₄²⁻/Y₂O₃ as a catalyst in ethanol. The synthesized compounds were characterized by IR, ¹H and ¹³C NMR and mass spectral studies. All the synthesized compounds were screened for their in vitro antimicrobial studies. Among the newly synthesized compounds 5d, 5e, 5h and 5m showed excellent antibacterial and antifungal activities when compared to the standard drugs.     

Ensembles of rings with a coumarin unit 1. Synthesis of 3-(2-R-thiazol-4-yl)-and 3-(4-R-thiazol-2-yl)coumarins

We have synthesized 3-(2-R-thiazol-4-yl)coumarins (R=H, CH₃, CH₂CN, Ar) by condensation of 3-(-bromoacetyl)coumarins with thioamides. We obtained 3-(4-R-thiazol-2-yl)coumarins (R=H, Ar) by several methods. By reaction of 2-cyanomethyl-4-phenylthiazole with 2-hydroxybenzaldehydes, we synthesized 2-imino-3-(4-phenylthiazol-2-yl)coumarins, which were converted to the corresponding coumarins by acid hydrolysis. For 3-(2-R-thiazol-4-yl)coumarins (R=CH₂CN), we carried out reactions with aromatic aldehydes. We propose alternative methods for synthesis of 2-[2-aryl(hetaryl)-1-cyanoethenyl]-4-(coumarin-3-yl)thiazoles.Ukrainian Pharmaceutical Academy, Kharkov 310002. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1345–1355, October, 1997.     

Reaction of Imidazoles and Triazoles with 1-(Benzotriazol-1-yl)-2-iodoethanone

Reactions of 2-methyl-1H-imidazole, 1H-benzimidazole, 4H-1,2,4-triazole, and 1H-benzotriazole with 1-(1H-benzotriazol-1-yl)-2-iodoethan-1-one in the absence of a base gave the corresponding N-mono- and N,N′-disubstituted derivatives. 4H-1,2,4-Triazole-3-thiol reacted with 1-(1H-benzotriazol-1-yl)-2-iodoethan-1- one to afford 1-([1,3]thiazolo[2,3-c][1,2,4]triazol-5-yl)-1H-benzotriazolium triiodide.     

Transamination of cyanothioacetamide with morpholine. Molecular and crystal structure of 3-(morpholin-1-yl)-3-thioxopropanenitrile and 3-(morpholin-1-yl)-3-thioxopropanethioamide

Transamination of cyanothioacetamide with equimolar amount of morpholine resulted in the formation of 3-(morpholin-1-yl)-3-thioxopropanenitrile, and with twofold excess of morpholine 3-(morpholin-1-yl)-3-thioxopropanethioamide was obtained. By the alkylation of the resulting products 2-[2-(morpholin-1-yl)-2-thioxoethylidene]thiazolidin-4-one, 3-amino-N-(4-acetylphenyl)-5-(morpholin-1-yl)-thiophene-2-carboxamide, 3-amino-3-methylthio-1-morpholinoprop-2-ene-1-thione, (2E,4E)-2-(morpholin-4-yl)thiocarbonyl)-5-phenylpenta-2,4-dienothioamide, and 3-{2??-[2??-(molrpholin-1-yl)-2-thioxoethyl]thiazol-4??-yl}-2H-chromen-2-one were synthesized. The 3-(morpholin-1-yl)-3-thioxopropanenitrile and 3-(morpholin-1-yl)-3-thioxopropanethioamide structures were studied by the X-ray diffraction.     

Luminescent zinc(II) and cadmium(II) complexes based on 2-(4,5-dimethyl-1H-imidazol-2-yl)pyridine and 2-(1-hydroxy-4,5-dimethyl-1H-imidazol-2-yl)pyridine

Complexes ZnL¹Cl₂, CdL¹Cl₂, ZnL ₂ ¹ Cl₂ ^·1.5H₂O, CdL ₂ ¹ Cl₂ ^·2H₂O, CdL ₂ ¹ Cl₂ ^·MeOH·H₂O [L¹ = 2-(4,5-dimethyl-1H-imidazol-2-yl)pyridine] and inner-complex compounds ZnL ₂ ² ·2H₂O, CdL ₂ ² [HL² = 2-(1-hydroxy-4,5-dimethyl-1H-imidazol-2-yl)pyridine] were synthesized. The complexes exhibit bright photoluminescence in the blue region of the spectrum, with the intensity exceeding this characteristic of the compounds L¹ and HL². Compound L¹ in aqueous solution is a potential chemosensor for the determination of zinc and cadmium.     

Synthesis and characterization of poly{2-[3-(1H-pyrrol-2-yl)phenyl]-1H-pyrrole} and its copolymer with EDOT

A pyrrole-functionalized monomer 2-[3-(1H-pyrrol-2-yl)phenyl]-1H-pyrrole (PyPhPy) was synthesized. The structure of monomer was investigated by Nuclear Magnetic Resonance (¹H NMR) and Fourier Transform Infrared (FTIR) spectroscopy. The chemical polymerization of PyPhPy (CPyPhPy) was realized using FeCl₃ as the oxidant. The electrochemical oxidative polymerization of polymer P(PyPhPy) and its copolymer with 3,4-ethylenedioxythiophene poly(2-[3-(1H-pyrrol-2-yl)phenyl]-1H-pyrrole-co-3,4-ethylenedioxythiophene) [P(PyPhPy-co-EDOT)] were achieved via potentiodynamic method by using NaClO₄/LiClO₄ as the supporting electrolyte in CH₃CN. Characterizations of the resulting polymers were performed by cyclic voltammetry (CV), FTIR, scanning electron microscopy (SEM), UV-Visible spectrophotometry (UV-Vis) and thermogravimetry analyses (TGA). Electrical conductivity of CPyPhPy, P(PyPhPy), and P(PyPhPyco-EDOT) were measured by four-probe technique.     

Structure of zinc complexes with 3-(pyridin-2-yl)-5-(arylideneiminophenyl)-1H-1,2,4-triazoles in different tautomeric forms: DFT and QTAIM study

On the basis of X-ray crystallographic data on molecular crystals of zinc complexes with 3-(pyridin-2-yl)-5-(arylideneiminophenyl)-1H-1,2,4-triazoles, quantum-chemical analysis of the electron density distribution function for these complexes has been performed by Bader’s atoms in molecules method. Topological parameters of electron density at the critical points of coordination and noncovalent bonds have been interpreted, and the bond energies have been estimated using the Espinosa equation. For the solvated complex Zn[(L3)(OAc)₂] · i-PrOH (L3 = 3-(pyridin-2-yl)-5-(benzylideneiminophenyl)-1H-1,2,4-triazole), a variable coordination number of the Zn²⁺ ion has been predicted as a result of dynamic dissociation/formation of an unstable Zn-O coordination bond. For the binuclear [Zn₂(L2)₂] complex (L2 = 3-(pyridin-2-yl)-5-(salicylideneiminophenyl)-1H-1,2,4-triazole), an orbital interpretation of the decrease in the fluorescence quantum yield in tetrahydrofuran and dimethyl sulfoxide as compared with free L2 ligand is presented.