Nitropyrazoles 22. On reactivity of 3,5-dinitro-4-(phenylsulfonyl)pyrazole and its N-methyl derivative

3,5-Dinitro-4-(phenylsulfonyl)pyrazole (5) obtained by oxidation of 3,5-dinitro-4-(phenylthio)pyrazole with 30% H₂O₂ in AcOH was involved into nucleophilic substitution reaction with thiophenol, which proceeded with substitution of the phenylsulfonyl group at position 4. N-Methyl-3,5-dinitro-4-(phenylsulfonyl)pyrazole obtained by methylation of 5 with dimethyl sulfate was involved into nucleophilic substitution reaction with thiophenol, p-bromophenol, and morpholine with the regioselective substitution of the nitro group at position 5 to form 5-R-3-nitro-4-(phenylsulfonyl)pyrazoles.     

Simple and efficient one-pot synthesis of N-phenyl-3,5-difunctionalized pyrazoles

A facile one-pot synthesis of N-phenyl-3,5-difunctionalized pyrazoles is described. The dialkyl 2-[(Z)-phenylhydrazono]succinate intermediate, which is prepared in situ from the mixture of phenylhydrazine and dialkyl acetylenedicarboxylate reacts with aroyl chloride or fumaryl chloride to afford the title compounds. Different types of compounds containing COCl functional group were used to investigate the scope and limitation of the reaction. Two -CO₂R and -O₂C groups at 3- and 5-position are potentially capable to convert to other functional groups. The reaction conditions are relatively mild and the yields are good.     

Synthese d'arylacetyl-3 carbethoxy ou acetyl-4 methyl-5 pyrazoles et de pyrazolo(3,4d)pyridazines : Action de l'hydrazine sur des carbethoxy ou acetyl-4 methyl-5 alkylidene-2 et n arylaminomethylene-2(2h)furannones-3

The reaction with hydrazine of 4-carbethoxy or acetyl 5-methyl(2H)furanones 2-substituted by arylmethine, alkenylmethine, arylaminomethine produces new 4,5-dihydro 3-methyl 4-oxo pyrazolo(3,4d)pyridazines or 3,4-dimethyl pyrazolo(3,4d)pyridazines. The preparation of 3-arylacetyl 4-carbethoxy or acetyl 5-methyl pyrazoles is described.     

1-(1-Carboxy-2-R-4-methylcyclohex-4-enyl)carbonyl- and 1-(2-R-4-Methylcyclohex-4-enyl)carbonyl-3,5-dimethyl(diphenyl)pyrazoles

1-(1-Carboxy-2-R-4-methylcyclohex-4-enyl)carbonyl- and 1-(2-R-4-methylcyclohex-4-enyl)carbonyl-3,5-dimethyl(diphenyl)pyrazoles have been obtained from the reaction of monohydrazides of 2-R-methyl-4-cyclohexen-1,1-dicarboxylic acids and hydrazides of 2-R-4-methyl-4-cyclohexen-1-monocarboxylic acids with acetylacetone and dibenzoylmethane. The conditions for the formation of the pyrazoles depend on the nature of the substituents in the hydrazide starting materials and the structure of the 1,3-diketone used.     

Regioselective synthesis of 1,3,5- and 1,3,4,5-substituted pyrazoles via acylation of N-Boc-N-substituted hydrazones

Acylation of N-Boc-N-methylhydrazones followed by TFA treatment affords regioselective access to substituted pyrazoles. Both regioisomers of 1-methyl-3,5-disubstituted-1H-pyrazoles can be selectively obtained. This procedure can also be employed for the regioselective preparation of fully substituted 1H-pyrazoles.     

Stereochemistry and reactivity of F- and H-vinyldiazocarbonyl compounds and their phosphazines: synthesis of pyrazoles and pyridazines

3-(Trifluoromethyl)-substituted (F) 2-vinyl-2-diazocarbonyl compounds, having cis-relationship of functional groups (AlkO₂C, CN₂), do not undergo 1,5-electrocyclization, but readily take part in the tandem Staudinger-diaza-Wittig reactions to produce trifluoromethyl-substituted pyridazines, whereas their non-fluorinated analogs (H), with trans-configuration, easily cyclize to pyrazoles, but remain intact under Staudinger-diaza-Wittig reaction conditions. The difference in the reactivity of H- and F-vinyldiazoketones, vinyldiazoacetates, and derived phosphazines is apparently caused by the different stereochemical arrangements of the AlkO₂C and CN₂ groups.     

Unusual reaction of chloroacetyl chloride with 1,2-dichloroethene. Synthesis and properties of 2-chlorovinyl dichloromethyl ketone

The reaction of chloroacetyl chloride with 1,2-dichloroethene in the presence of AlCl₃ unexpectedly led to the formation of (E)-1,1,4-trichlorobut-3-en-2-one whose structure was proved by ¹H and ¹³C NMR, IR, and mass spectra and independent synthesis. A probable reaction scheme was proposed, which involves transformation of initially formed 1,2,4-trichloro-3-oxobutan-2-yl cation by the action of AlCl₃. The high reactivity of the vinylic halogen atom in (E)-1,1,4-trichlorobut-3-en-2-one was demonstrated by its reactions with nitrogen-centered nucleophiles (triethylamine, aniline, 3,5-dimethyl-1H-pyrazole) and sodium sulfide. These reactions involved only the C-Cl bond in the vinyl fragment and afforded (4,4-dichloro-3-oxobut-2-en-1-yl)triethylammonium chloride, 1,1-dichloro-4-phenylaminobut-3-en-2-one, 1-(4,4-dichloro-3-oxobut-2-en-1-yl)-3,5-dimethyl-1H-pyrazole, and 4,4′-thiobis(1,1-dichlorobut-3-en-2-one), respectively. The reaction of 1,1,4-trichlorobut-3-en-2-one with benzylhydrazine gave a mixture of 1,3- and 1,5-disubstituted pyrazoles.     

New synthetic route to diaminonitropyrazoles as precursors of energetic materials

Treatment of nitropyrimidine derivatives with (N-substituted) hydrazines (2 equiv.) gave 1-(substituted)-3,5-diamino-4-nitropyrazole, providing a very mild conversion of pyrimidines into pyrazoles. This reaction provided a convenient route to precursors for new efficient and insensitive explosives.     

Unexpected course of rearrangement of substituted S-(1(3H)-isobenzofuranone-3-yl)isothiuronium bromides

Three series of S-(1(3H)-isobenzofuranone-3-yl)isothiuronium bromides differing in substitution at the isothiuronium moiety (none, one or two methyl groups) and at the benzene ring were prepared and characterized. These salts were then treated with various bases (acetate, triethylamine, Na₂CO₃) to give either 1-hydroxy-3-oxo-1,3-dihydro-2H-isoindol-2-carbothioamides or the product of S to N isobenzofuranone-3-yl migration, i.e., 1,3-dimethyl-1-(3-oxo-1,3-dihydro-2-benzofuran-1-yl)thioureas. If ammonia was used in reaction with N,N′-dimethyl isothiuronium salts then 3-hydroxy-2,3-dihydro-1H-isoindol-1-ones were formed together with 1,3-dimethyl-1-(3-oxo-1,3-dihydro-2-benzofuran-1-yl)thioureas in parallel reaction with the yields increasing with ammonia concentration. The formation of isoindolones takes place in two steps with an aldehyde intermediate, which can be trapped with N,N-dimethylhydrazine.     

4-(p-Chloro)phenyl-1,2,4-triazole-3,5-dione as a novel and reusable reagent for the oxidation of 1,3,5-trisubstituted pyrazolines under mild conditions

4-(p-Chloro)phenyl-1,3,4-triazole-3,5-dione is used as an effective oxidizing agent for the oxidation of 1,3,5-trisubstituted pyrazolines to their corresponding pyrazoles under mild conditions with moderate to good yields at room temperature.     

A concise synthesis of (−)-cytoxazone and (−)-4-epi-cytoxazone using chlorosulfonyl isocyanate

A concise synthesis of (−)-cytoxazone and its stereoisomer (−)-4-epi-cytoxazone, novel cytokine modulators, has been accomplished each in six steps from readily available p-anisaldehyde with good diastereoselectivity. Key steps in the synthesis include the regioselective and diastereoselective amination of anti- and syn-1,2-dimethyl ethers with chlorosulfonyl isocyanate and the subsequent regioselective cyclization of the diol to construct the oxazolidin-2-one core. The diastereoselectivity of amination reaction using CSI was explained by the Cieplak electronic model via S_N1 mechanism and neighboring group effect, leading to the retention of the configuration.     

Interaction of polyhedral boron hydride anions [B10H10] and [B12H12] with cyclic copper and silver 3,5-bis(trifluoromethyl)pyrazolate complexes

The interactions of cyclic trinuclear copper {[3,5-(CF₃)₂Pz]Cu}₃ and silver {[3,5-(CF₃)₂Pz]Ag}₃ complexes with polyhedral borate anions [B₁₀H₁₀]²⁻ and [B₁₂H₁₂]²⁻ in solvents of low-polarity were studied using IR spectroscopy (190-290 K). Two types of complexes were found in solution: {[((3,5-CF₃)₂PzM)₃][B_nH_n]}²⁻ and {[((3,5-CF₃)₂PzM)₃]₂[B_nH_n]}²⁻ (M = Ag, Cu; n = 10, 12). The stability constants of these complexes were determined from IR-spectra.     

Selective permeation of CO2 through poly 2-(N,N-dimethyl)aminoethyl methacrylate membrane prepared by plasma-graft polymerization technique

A membrane having an amine moiety was prepared by plasma-grafting 2-(N,N-dimethyl)aminoethyl methacrylate (DAMA) onto a microporous polyethylene substrate. Permselectivity of the membrane for CO₂ over N₂ was achieved in both dry and water swollen conditions. When the CO₂ partial pressure in the feed gas was 0.047 atm, the selectivity of CO₂ over N₂ reached 130 for the highly swollen water containing membrane. This value was found to agree with that obtained with a mobile carrier membrane (supported liquid membrane) using DAMA as the carrier. The effects of several experimental conditions such as degree of grafting, feed partial pressure and temperature on the membrane performance were studied. It was suggested that the membrane acted as a fixed carrier membrane for CO₂ facilitated transport in under the dry condition and acted as a fixed reaction site membrane in the water swollen condition. The carrier transport mechanism is discussed for dry and aqueous membranes.     

Synthesis and characterization of copper(II) and cobalt(II) complexes with two new potentially hexadentate Schiff base ligands. X-ray crystal structure determination of one copper(II) complex

Two new potentially hexadentate N₂O₄ Schiff base ligands 2-((z)-(2-(2-(2-((z)-3,5-di-tert-butyl-2-hydroxybenzylideneamino) phenoxy) phenoxy) phenylimino) methyl)-4,6-di-tert-butylphenol [H₂L¹] and 2-((z)-(2-(2-(2-((z)-3,5-di-tert-butyl-2-hydroxybenzylideneamino) phenoxy)-5-tert-butylphenoxy) phenylimino) methyl)-4,6-di-tert-butylphenol [H₂L²] were prepared from the reaction of 3,5-di-tert-butyl-2-hydroxy benzaldehyde with 1,2-bis(2′-aminophenoxy)benzene or 1,2-bis(2′-aminophenoxy)-4-t-butylbenzene, respectively. From the direct reaction of ligands [H₂L¹] and [H₂L²] with copper(II) and cobalt(II) salts in methanolic solution and in the presence of N(Et)₃ the neutral [CuL¹], [CuL²], [CoL¹] and [CoL²] complexes were prepared. All complexes were characterized by IR spectra, elemental analysis, magnetic susceptibility, mass spectra, molar conductance (Λ_m), UV-Vis spectra and in the case of [CuL²] with X-ray diffraction. X-ray crystal structure of [CuL²] showed that the complex contains copper(II) in a distorted square planar environment of N₂O₂ donors. Three CH/π interactions were observed in the molecular structure of latter complex.     

Reactions of some arenes and pyrazoles in MeCN under conditions of undivided-cell electrolysis

As exemplified for the first time by pyrazole and its 4-nitro and 3,5-dimethyl derivatives, N-arylation of pyrazoles can be performed under conditions of undivided-cell amperostatic electrolysis (Pt electrodes, MeCN) of systems containing the pyrazolate anion and (or) pyrazole, arene (benzene, 1,4-dimethoxybenzene, or xylene), and a supporting electrolyte. In the case of electrolysis involving 1,4-dimethoxybenzene as arene, N-arylation followed simultaneously three routes to form an ortho-substitution product (1,4-dimethoxy-2-(pyrazol-1-yl)benzene), an ipso-substitution product (4-methoxy-1-(pyrazol-1-yl)benzene), and an ipso-bisaddition product (1,4-dimethoxy-1,4-di(pyrazol-1-yl)cyclohexa-2,5-diene) in a total current yield of up to 50%. The acid-base properties of the pyrazoles under study affect the ratio of the N-arylation products and govern the required composition of the starting reaction mixture. In the case of a stronger base, such as 3,5-dimethylpyrazole, N-arylation with 1,4-dimethoxybenzene occurred even in the pyrazole—arene—tetraalkylammonium perchlorate system, whereas N-arylation of 4-nitropyrazole (a weaker base) proceeded only in the presence of the pyrazolate anion or another base, viz., sym-collidine. Oxidation of arene to the radical cation is the key anodic reaction. Not only the pyrazolate anion, but also highly basic pyrazole or a solvate complex of weakly basic pyrazole with collidine can serve as a nucleophilic partner in subsequent transformations of these radical cations.     

Effect of N1-substituted pyrazolic hybrid ligands on palladium catalysts for the Heck reaction

In this paper we have explored the influence of several linkers present on the [PdCl₂(L)] complexes, where L is 3,5-dimethylpyrazolic hybrid ligand N1-substituted by polyether chains and/or phenyl groups. These complexes have been used as pre-catalysts in the Heck reaction between phenyl halides and tert-butyl acrylate. The corresponding complexes efficiently catalyze the Heck olefination and provide good yields under phosphine-free conditions, even for aryl chlorides. Different reaction conditions were investigated and it was found that the nature of the ligand has an important influence on the effectiveness of the catalytic system. Ligand 1,8-bis(3,5-dimethyl-1H-pyrazol-1-yl)-3,6-dioxaoctane (L1), which has previously shown to be the most flexible and versatile, achieved high turnover numbers within very short reaction times and low catalyst loadings.     

Divergent synthesis of spirocyclopentene-pyrazolones and pyrano[2,3-c]-pyrazoles via Lewis base controlled annulation reactions

An effective Lewis base catalyst-controlled α-regioselective annulation reaction of γ-substituted allenoates with unsaturated pyrazolones has been developed, affording various spirocyclopentene-pyrazolones and pyrano[2,3-c]pyrazoles. The combination of PPh₃ and K₂CO₃ promoted the [3+2] annulation to access the spirocyclopentene-pyrazolones in moderate to good yields (up to 90%) with excellent diastereoselectivities (dr >19:1), while [4+2] annulations to generate pyrano[2,3-c]pyrazoles were successfully achieved by employing DBU as catalyst (in up to 92% yield). Of importance, the asymmetric synthesis of spirocyclopentene-pyrazolone was realized by using our previously reported chiral ferrocenylphosphine catalyst.     

2,6-Bis(3,5-di-tert-butyl-4-hydroxybenzyl)cycloalkanone: Synthesis and prospects for use as stabilizer for ethylene-propylene rubber

A phenolic antioxidant was synthesized by the reaction of N,N-dimethyl(3,5-di-tert-butyl-4-hydroxybenzyl) amine with cyclohexanone. The infl uence of temperature, reactant ratio, pressure, and time on the yield of the product, 2,6-bis(3,5-di-tert-butyl-4-hydroxybenzyl)cyclohexanone, was examined. The antioxidant obtained, taken both separately and in synergistic mixtures with alkylphenol and phosphites, showed high performance in inhibition of the thermal aging of ethylene-propylene rubber.     

Synthesis of new pyrazole-1,2,3-triazole dyads

An efficient two step synthetic methodology of new 5(4)-aryl-4(5)-[3(5)-(2-hydroxyphenyl)-1H-pyrazol-5(3)-yl]-1H-1,2,3-triazole dyads was established. The reaction of (E)-2-styryl-4H-chromen-4-ones, used as building blocks, with sodium azide, gave 4(5)-aryl-5(4)-(chromon-2-yl)-1H-1,2,3-triazoles bearing either electron-donating or electron-withdrawing substituents in their styryl moiety which upon reaction with hydrazine hydrate afforded the expected pyrazoles in moderate to very good yields.     

Efficient iodination of structurally varying pyrazoles in heterophase medium

A synthesis of 4-iodo-substituted pyrazoles by iodination of pyrazole and its derivatives in the heterophase (H₂O/CHCl₃ (CCl₄)) medium with the system KI-KIO₃ in the presence of H₂SO₄ additives was accomplished. The yields of 4-iodo-substituted pyrazoles in the iodination of pyrazole, 3,5-dimethylpyrazole, pyrazole-3(5)-carboxylic acid, 1-methylpyrazole-3-carboxylic acid, 1-methylpyrazole-5-carboxylic acid, 3-nitropyrazole, 1-methyl-3-nitropyrazole, 1-methylpyrazole, 1-ethylpyrazole, and 1-isopropylpyrazole were within 80–97%, whereas in the case of 3-nitropyrazole-5-carboxylic acid it was 32%.