Position of the equilibrium during the migration of double bonds in the pyrazoline ring

Data characterizing the position of the equilibrium between Δ²- and Δ¹-pyrazolines with alkyl substituents in different positions, which is established under the influence of potassium tertbutoxide in tert-butyl alcohol at 90°C, were obtained. 3-Alkyl-Δ²-pyrazolines are thermodynamically more stable than their isomers with different positions of the double bond, so that the fraction of the latter in equilibrium mixtures does not exceed 1–2%, and they are practically completely isomerized to the 3-Alkyl-Δ²-substituted derivatives. If the position of the side chains excludes the possibility of the formation of 3-alkyl-Δ²-pyrazolines by migration of the double bond (4-alkyl- and 5,5-dialkyl-substituted compounds), the fraction of Δ¹-pyrazolines in the equilibrium rises appreciably and reaches 12% for 3,3-diethyl-Δ¹-pyrazoline.     

Dárivás C-glycosyliques. IX. Syntháse de spiro-Δ2-isoxazolines et de spiro-Δ1-pyrazolines à partir du dásoxy-3-di-O-isopropylidène 1, 2: 5, 6-máthylène-3-α-D-ribo-hexofurannose. Communication práliminaire

Treatment of 3-deoxy-1, 2:5, 6-di-O-isopropylidène-3C-méthylene-α-D -ribo-hexofuranose with aromatic nitrile oxides led to spiro-Δ₂-isoxazolines, whereas a Δ₁-pyrazoline was obtained by reacting the same C-methylenic sugar with diazomethane. Properties of these compounds, a new class of carbohydrates, and 5, 6-di-O-acetyl derivatives thereof are described.     

Photoreaktionen von 5-Phenyl-pyrazolinen. Vorläufige Mitteilung

On irradiation in benzene 1-methyl-5-phenyl-Δ²-pyrazoline ( 1 ) is partly converted into trans- and cis-1-methylazo-2-phenyl-cyclopropanes ( 2 and 3 ) in the ratio of 23:77. Both 2 and 3 on thermal treatment are reconverted to 1 . A concurrent thermal equilibration of 2 and 3 is also observed. 1, 3-Dimethyl-5-phenyl-Δ²-pyrazoline ( 5 ) on irradiation in benzene yields the corresponding trans- and cis-1-methylazo-1-methyl-2-phenyl-cyclopropanes ( 6 and 7 ). In contrast similar treatment of 5-phenyl-Δ²-pyrazoline gives benz- and cinnamaldazine ( 9 and 11 ) along with the corresponding mixed aldazine ( 10 ).     

2,3,7,8-Tetraazaspiro[4.4] nonane, 2,3,7,8-tetraazaspiro-[4.4] nona-2,7-diene and derivatives

Synthetic routes to the title compounds ( 4, 12 ) are described. Chiral derivatives of these, 2,7-bis(phenylcarbamoyl)-2,3,7,8-tetraazaspiro[4.4]nonane ( 7 ) and 3,8-dicarbomethoxy-2,3,7,8-tetraazaspiro[4.4]nona-1,6-diene ( 10 ) were prepared. Synthetic routes to diketo derivatives of other tetraazaspiro[4.4]nonanes were explored. 3,3-Dicarbethoxy-1-pyrazoline ( 24 ) and 3,3-dicarbethoxypyrazolidine ( 25 ) were prepared and their reactions with hydrazine examined. Proton and ¹³C nuclear magnetic resonance spectra of new compounds, including some 5-substituted 3-hydroxypyrazoles, are discussed in relation to structure.     

Reaktionen von Steroiden mit Dialkylaminoschwefeltrifluoriden. I. 11β-Hydroxysteroide. Über STeroide, 233. Mitteilung

Reactions of Steroids with Dialkylaminosulfur Trifluorides. I. 11β-Hydroxysteroids. Reactions of three types of 11β-hydroxy steroids with dialkylaminosulfur trifluorides (DAST) have been studied. 9Δ-unsubstituted 11-alcohols are dehydrated with DAST to Δ⁹⁽¹¹⁾-unsaturated compounds under very mild conditions. 9α-Chloro-11β-hydroxy steroids are quantitatively fluorinated in position 11 yielding the known 9α-chloro-11β-fluoro derivatives. Finally, 9α, 11Δ-fluorohydrins at 0–25° are selectively transformed with DAST into Δ¹¹-9α-fluorides. When the latter reaction is run at lower temperature, the corresponding 11-piperidinesulfinates, products of partial hydrolysis of the alkoxy-dialkylaminosulfur difluoride intermediates postulated by Middleton, can be isolated in high yields. A rational explanation of the results is presented.     

Reactions of 4-phenyl-1,2,4-triazoline-3,5-dione with 2-pyrazolines

4-Phenyl-1,2,4-triazoline-3,5-dione (PTAD) acts as an efficient Michael acceptor in reactions with 1-unsubstituted 2-pyrazolines, giving substituted (3,5-dioxo-4-phenyl-1,2,4-triazol-idin-1-yl)-1-pyrazolines in quantitative yields. Through elimination of molecular nitrogen, the latter are easily transformed into the corresponding cyclopropanes. A reaction of methyl 5-methyl-2-pyrazoline-5-carboxylate with a twofold excess of PTAD leads to an intermediate bisadduct, which undergoes dediazotization to form a 1,3,5-triazabicyclo[3.3.0]octane-2,4-dione derivative. 1-Substituted 2-pyrazolines also add to PTAD with the exception that the 2-pyrazoline structure is retained in the product because of the migration of the C(3)H proton to PTAD.     

Novel four-component route to the synthesis of spiro[indoline-3,4′-pyridine]-3′-carboxylate derivatives

An effective route to spiro[indoline-3,4′-pyridine]-3′-carboxylate derivatives is described. This involves reaction of isatin, 1-phenyl-2-(1,1,1-triphenyl-λ⁵-phosphanylidene)-1-ethanone, and benzylamine derivatives or aliphatic amines in the presence of alkyl acetoacetate (1,3-dicarbonyl compounds) in dry methanol under reflux conditions. The reactive 1:1 enaminone, which is obtained from the addition of the amine to 1,3-dicarbonyl compound, adds to the α,β-unsaturated ketone, which is formed from the reaction of isatin and 1-phenyl-2-(1,1,1-triphenyl-λ⁵-phosphanylidene)-1-ethanone, to produce the alkyl 1′-benzyl-2′-methyl-2-oxo-6′-phenyl-1′H-spiro[indoline-3,4′-pyridine]-3′-carboxylate derivatives in excellent yields.     

19-Nor-steroids V. New synthesis of 6-dehydro-19-nor-steroids

A new efficient approach to the synthesis of Δ^4,6-3-oxo-19-norsteroids is described. Starting from 3β, 17α-diacyloxy-20-oxo-Δ⁵-pregnenes, the derivatives VIIIa and VIIIb of 6-dehydro-19-norprogesterone have been synthesized, which exhibit high progestational activity. Modification of the procedure leads to the new group of steroidal Δ^5(10),6-dienes.     

Reaction of bis(2-chloroethyl)-2-nitroethynylphosphonate with diazoacetic ester

Reactions of 1,3-dipolar cycloaddition of bis(2-chloroethyl)-2-nitroethenylphosphonate to methyl and ethyl diazoacetates proceed with the formation of a mixture of regioisomers of phosphorylated nitropyrazoline carboxylates that under the reaction conditions undergo isomeric transformations and denitration and afford a mixture of Δ¹- and Δ²-pyrazoline- and pyrazolecarboxylates. Structures of the synthesized substances are studied by the methods of IR and ¹H, ³¹P NMR spectroscopy and partially by X-ray structural analysis.     

Experimental and theoretical comparative studies on two 2-pyrazoline derivatives

Two 2-pyrazoline derivatives of 1-phenyl-3-(4-methylphenyl)-5-phenyl-2-pyrazoline (1) and 1-phenyl-3-(4-methylphenyl)-5-(2,4-dichlorophenyl)-2-pyrazoline (2) have been synthesized and characterized by elemental analysis, IR, UV–vis and fluorescence spectroscopy. The crystal structure of 2 has been determined by X-ray single crystal diffraction. For the two compounds, density functional theory (DFT) calculations of the structures and natural population atomic charge analysis have been performed at B3LYP/6-311G** level of theory. By using TD-DFT method, electron spectra of 1 and 2 have been predicted, which suggests the B3LYP/6-311G** method can approximately simulate the electron spectra for the system presented here. Comparative studies on 1 and 2 indicate that the change of substituent in 5-phenyl ring of pyrazoline ring influences the peak location and intensity in electronic and fluorescence spectra.     

Synthesis and antitumor activity of 1-acetyl-3-(4-phenyl)-4,5-dihydro-2-pyrazoline-5-phenylursolate and 4-chalcone ursolate derivatives

New 4-chalcone ursolate and 1-acetyl-3-(4-phenyl)-4,5-dihydro-2-pyrazoline-5-phenyl ursolate derivatives were synthesized by esterification of UA and chalcone or pyrazoline. The compounds were structurally confirmed by IR, ¹H NMR, ¹³C NMR, and HR-MS spectroscopy. The cytotoxicity of ten derivatives was evaluated against A549, SKOV3, and HepG2 cell lines by MTT assay. The result showed that several compounds were more potent than UA against A549 and SKOV3 cells; however, none of them were more potent than UA against HepG2.     

Comparative study on two 2-pyrazoline derivatives with experimental and theoretical methods

Two 2-pyrazoline derivatives of 1-phenyl-3-(4-chlorophenyl)-5-(2-chlorophenyl)-2-pyrazoline (1) and 1-phenyl-3-(4-methylphenyl)-5-(2-chlorophenyl)-2-pyrazoline (2) have been synthesized and characterized by elemental analysis, IR, UV–Vis, and fluorescence spectra. The crystal structure of 2 has been determined by X-ray single crystal diffraction. For the two compounds, density functional theory (DFT) calculations of the structures and natural population atomic charge analysis have been performed at B3LYP/6-311G** level of theory. By using TD-DFT method, electron spectra of 1 and 2 have been predicted, which are in good agreement with the experimental ones. Comparative studies on 1 and 2 indicate that the change of substituted groups in 3-phenyl ring of pyrazoline ring will change the peak intensity and peak locations both in electron spectra and fluorescence spectra.     

Bridgehead nitrogen heterocycles from 2,4,6-triphenyl- pyrylium cation and thiosemicarbazide or thiocarbohydrazide

2,4,6-Triphenylpyrylium with thiosemicarbazide and thiocarbohydrazide, gives 2-pyrazolines $\text{3a}$ and $\text{3b}$ which undergo cyclization yielding pyrazolo(1,5-c]pyrimidine 5 and pyrazolo [2,3-d]-1,2,4-triazepine $\text{7}$ derivatives, respectively. Reaction of $\text{7}$ with phenacyl bromides gave 1,3-thiazolo[3,2-b]pyrazolo [2,3-d]-1,2,4-triazepin-4-iums $\text{10}$. Compound $\text{3a}$ on treatment with phenacyl bromides gave 1-(4'-aryl-thiazol-2'-yl)-2-pyrazoline derivatives $\text{6}$. Compound $\text{3b}$ reacts with acyl chlorides to give pyrazolo[1,5-c]pyrimidine derivatives $\text{14}$, and with aromatic aldehydes giving the 2-(Δ^2'1 pyrazolin-1-yl)-5-aryl-1,3,4-Δ²-thiadiazolines $\text{12}$ which were easily converted to the corresponding 2-(Δ²-pyrazolin-1-yl)-5-aryl-1,3,4-thiadiazoles $\text{13}$.     

Synthesis, structure characterization and preliminary biological evaluation of novel 5-alkyl-2-ferrocenyl-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives

A series of novel 5-alkyl-2-ferrocenyl-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives were synthesized by the reaction of ethyl 1-(2-bromoethyl)-3-ferrocenyl-1H-pyrazole-5-carboxylate with non-aromatic primary amines in one-pot procedure and characterized by ¹H NMR, ¹³C NMR, IR, HRMS and X-ray diffraction analysis. The effects of all the compounds on A549 cell growth were investigated. The results showed that all compounds had almost inhibitory effects on the growth of A549 cells.     

A study of chemiluminescence from reaction of bis(2,4,6-trichlorophenyl)oxalate, hydrogen peroxide and diethyl-2-(cyclohexylamino)-5-[(E)-2-phenyl-1-ethenyl]-3,4-furandicarboxylate as a novel fluorescer

The chemiluminescence (CL) arising from reaction of bis(2,4,6-trichlorophenyl)oxalate (TCPO) with hydrogen peroxide in the presence of a diethyl-2-(cyclohexylamino)-5-[(E)-2-phenyl-1-ethenyl]-3,4-furandicarboxylate as a novel fluorescer (Flu) has been studied. The relationship between the chemiluminescence intensity and concentrations of TCPO, sodium salicylate, hydrogen peroxide and fluorescer is reported. The chemiluminescence parameters including intensity at maximum CL, time at maximum intensity, total light yield, theoretical maximum level of intensity and pseudo-first-order rate constants for the rise and fall of the CL burst (k_r and k_f) were evaluated from computer fitting of the resulting intensity-time plots. The activation parameters E_a, ΔH^Δ, ΔS^Δ and ΔG^Δ for the rise and fall steps were evaluated from the temperature dependence of k_r and k_f values.     

Synthesis and biological activity of some new pyrazoline and pyrrolo[3,4-c]pyrazole-4,6-dione derivatives: reaction of nitrilimines with some dipolarophiles

Several 1,3-diaryl-5-(cyano-, aminocarbonyl- and ethoxycarbonyl-)-2-pyrazoline, pyrrolo[3,4-c]pyrazole-4,6-dione and 1,3,4,5-tetraaryl-2-pyrazoline derivatives were prepared by the reaction of nitrilimine with different dipolarophilic reagents. The new compounds were characterized using IR, (1)H-NMR, (13)C-NMR and mass spectra. Biological screening of some compounds is reported.     

Simultaneous determination of the activation energy and the reaction kinetic model from the analysis of a single curve obtained by a novel method

It has been demonstrated that a single plot of the values of Δlnα^1/2/Δln(1-α) (taken from a single α?T curve obtained under a controlled linear increase of the reaction rate) as a function of the corresponding values of Δ(1/T)/Δln(1?α) permits the simultaneous determination of both the activation energy and the kinetic model in accordance with a solid state reaction.     

Arylation of halogenated thiophene carboxylate via Suzuki–Miyaura reaction: Anti-bacterial study against clinically isolated extensively drug resistant Escherichia coli sequence type 405 and computational investigation

In present study, Pd(0) catalysed Suzuki-Miyaura cross coupling reaction was used to synthesize 2,4-biarylphenyl-5-arylthiophene-2-carboxylate (7a–7f) and 2-aryl-4-chlorophenyl-5-arylthiophene-2-carboxylate derivatives (8a–8l) in moderate to good yields. While 2,4-dibromophenyl-5-bromothiophene-2-carboxylate (4) and 2-bromo-4-chlorophenyl-5-bromothiophene-2-carboxylate (5) were synthesized via Steglich esterification of 5-bromothiophene-2-carboxylic acid (1) with 2,4-dibromo phenol (2) and 2-bromo-4-chlorophenol (3) in the presence of N, N?-dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP). ¹H and ¹³C NMR were used to confirm all of the compounds. To screen out the most active lead compounds, binding interactions of all synthesized compounds with MurD and MurE Escherichia coli proteins were evaluated theoretically via molecular docking studies indicating the good binding affinities. DFT calculations were performed out by using DFT-B3LYP/3-21g and structural and reactivity parameters were calculated. Compounds 5, 8b, 8e, 8h, and 8j have demonstrated potential reactivities and charge distributions that indicate their efficiency towards biological targets. These chemicals were tested in vitro for antibacterial activity against Gram-negative bacteria (Escherichia coli) at different concentrations based on theoretical results. The total results were quite close to the theoretical predictions and compound 8j was found to be having the greatest potential value, strongest binding affinities, and a promising antibacterial agent with MIC value of 50 mg/ml against Escherichia coli.     

5-Imino-Δ3-1,2,4-thiadiazoline derivatives with a linear N-S…O grouping. Synthesis and crystal structures

A series of carbonyl derivatives of 5-imino-Δ³-1,2,4-thiadiazolines has been prepared and shown by X-ray analysis of a selected example to have a trithiapentalene-like structure. When diphenylketene was used as acylating reagent, the primary product ( 14 ), obtained at room temperature, rearranged on heating in a polar solvent into a Δ²-thiazolin-4-one ( 15 ). The structure of 15 has been confirmed by X-ray analysis, and shown to be a zwitterion. Rearranged products (i.e., 16 and 20-22 ) were also obtained when 3 was reacted with dimethyl acetylenedicarboxylate or methanesulfonyl chloride, whereas tosyl chloride gave normal tosylated derivatives ( 17-19 ). The latter have also a nearly linear N-S…O arrangement, but the interaction between S and O is weak.     

A multireference configuration interaction study with singles and doubles of some mesoionic rings: reaction and activation free energies for the ring-opening reaction

For the first time, multireference configuration interaction with singles and doubles (MR-CISD) calculations (including extensivity corrections, MR-CISD+Q) have been performed to study the ring-opening reactions of the following mesoionic rings and their 2, 3, and 4 methyl-substituted derivatives: ( a ) 1,3-oxazol-5-one, ( c ) 1,3-oxazol-5-thiolate, and ( d ) 1,3-thiazol-5-thiolate. The ring-opening reaction of the parent 1,3-thiazol-5-one mesoionic ring ( b ) has also been studied. The effect of methyl and S replacement on the reaction and activation free energies (ΔG and ΔG^†, respectively) is studied. For a , the effect of methyl replacement on C2 is almost negligible, while on N3 and C4, it is significantly larger, especially in the latter position. The open structure (ketene form) of a is considerably more stable, and the replacement of the exocyclic O by S stabilizes the ketene tautomer even more and increases ΔG^† considerably. On the other hand, replacement of the endocyclic O by S (yielding b ) completely prevents the formation of the open structure, while replacement of both endo and exo atoms strongly stabilizes the cyclic structure and leads to a remarkably high value of ΔG^†. In some cases, the relative polarity of the stationary points is used to estimate how ΔG and ΔG^† are expected to change as one goes from the gas phase to aprotic polar solvents. A linear correlation between the multiconfigurational character of the mesoionic rings and ΔG^† has been observed, and such correlation is used to estimate the ΔG^† values for the methyl-substituted c and d . The largest barrier (13.78 kcal/mol) has been obtained for the 4-methyl-1,3-thiazol-5-thiolate (4-m- d ).