Thermodynamic functions of Ni(II) complexes with 5-(2-hydroxyphenyl)-pyrazole derivatives. A potentiometric study

Proton-ligand dissociation constants of five biologically important pyrazole derivatives, viz. [5-(2-hydroxyphenyl)-3-(pyridin-3-yl)-4-benzoyl]-pyrazol (HPPBP), [5-(2-hydroxyphenyl)-3-(3-nitrophenyl)-4-(3-pyridinoyl)]-pyrazol (HPNPPP), [5-(2-hydroxyphenyl)-3-(3-nitrophenyl)-4-benzoyl]-pyrazol (HPNPBP), [5-(2-hydroxyphenyl)-3-phenyl-4-(3-pyridinoyl)]-pyrazol (HPPPP), and [5-(2-hydroxyphenyl)-3-(3-nitrophenyl)-4-(2-furoyl) pyrazol (HPNPFP) and metal ligand stability constants of their Ni(II) complexes in 70% (v/v) dioxane-water and 0.1 M KNO₃ were determined at 298.15, 303.15, and 308.15 K by potentiometric method. Thermodynamic functions, such as, free energy change (ΔG ^○), enthalpy change (ΔH ^○) and entropy (ΔS ^○) change for dissociation and complex formation have been estimated form temperature dependence of proton-ligand and metal-ligand stability constants and interpreted in terms of feasibility of these processes.     

Preparation of 4-nitrostyrene

The interaction of D,L-1-(4-nitrophenyl)ethanol with SOCl₂ and P₄O₁₀ has been studied. In the reaction of D,L-1-(4-nitrophenyl)ethanol with SOCl₂ a mixture of 1-(4-nitrophenyl)-1-chloroethane, 1,1′-bis-(4-nitrophenyl)diethyl ether, and 4-nitrostyrene (yield 21%) has been formed. The direction of reaction of D,L-1-(4-nitrophenyl)ethanol with P₄O₁₀ in toluene has been affected significantly by the order of reagents addition and the solution concentration. 4-Nitrostyrene has been obtained in the only case: the addition of P₄O₁₀ to diluted solution of D,L-1-(4-nitrophenyl)ethanol and subsequent refluxing. Also the procedure of 4-nitrostyrene preparation via the cleavage of 2-(4-nitrophenyl)ethyl nitrate with alkoxy anion in the alcoholic solution has been upgraded.     

Temperature dependence of density, viscosity, ultrasonic velocity, and other properties of substituted pyrazoles in acetone-water mixtures

The density, viscosity and ultrasonic velocity of some substituted pyrazoles viz. 5-(2-hydroxyphenyl)-3-(pyridin-3-yl)-4-benzoylpyrazol, 5-(2-hydroxyphenyl)-3-(3-nitrophenyl)-4-(3-pyridinoyl)-pyrazol, 5-(2-hydroxyphenyl)-3-(3-nitrophenyl)-4-benzoylpyrazol and 5-(2-hydroxyphenyl)-3-phenyl-4-(3-pyridinoyl)-pyrazole have been measured in 70: 30 (vol/vol) acetone-water mixture at 298, 303, 308, and 313 K for 0.01 mol dm^?3 concentration of pyrazoles. The acoustical parameters such as adiabatic compressibility (??_s), relative association (R _A), specific acoustic impedance (Z), apparent molar volume (?_v), apparent molar adiabatic compressibility (?_K), and intermolecular free length (L _f) were calculated from the experimental densities and velocities. The changes in acoustical properties have been used to interpret the molecular interactions in solutions. The activation energies of viscous flow of pyrazole solutions were determined from the data of viscosity at different temperature.     

Exploratory chemistry of 3-aroylformamido-4-aryl-1,2,5-thiadiazoles

Apart from the previous report, the reaction of 3-(4-nitrobenzoylformamido)-4-(4-nitrophenyl)-1,2,5-thiadiazole ( 2a ) with m-chloroperbenzoic acid in chloroform at room temperature did not proceed, whereas at reflux temperature the same reaction gave 4-nitrobenzoic acid ( 5 ) (86%) and a minute amount of a mixture of 4-nitrobenzoylformamide ( 6 ) and 3-amino-4-(4-nitrophenyl)-1,2,5-thiadiazole ( 7a ). On the other hand the same reaction in a mixture of ethanol and chloroform (1:4) at room temperature gave 3-ethoxycarbamoyl-4-(4-nitrophenyl)-1,2,5-thiadiazole ( 8a ) (24%) as an isolable product. When 3-aroylformamido-4-aryl-1,2,5-thiadiazoles 2 in tetrahydrofuran were treated with various alkoxides in the corresponding alcohols at room temperature, 3-amino-4-aryl- 7 , 3-alkoxycarbamoyl-4-aryl- 8 , and 3-aryl-4-(aryl)(hydroxy)acetamido-1,2,5-thiadiazoles 9 were isolated. The ratios of which were dependent on the kind of bases and the solvent employed. Selected compounds 2 were allowed to react with phosphorus pentasulfide in the presence of pyridine at reflux to give 3-aryl-4-arylacetarnido-1,2,5-thiadiazoles 17 (55–64%), which were also produced by the reaction of 2 with either Lawesson's reagent or hydrogen sulfide gas in the presence of pyridine at reflux.     

Synthesis and hydrogenation of (E)-γ-aryl-γ-morpholino-α-trifluoromethylated allyl alcohols through the reaction of trifluoroacetaldehyde ethyl hemiacetal with enamines

Treatment of trifluoroacetaldehyde ethyl hemiacetal with enamines, derived from acetophenone derivatives, at room temperature gave (E)-1,1,1-trifluoro-4-morpholino-4-aryl-but-3-en-2-ols, which are intermediates for preparation of the β-trifluoromethylated aldol products, 4,4,4-trifluoro-3-hydroxy-1-aryl-butan-1-ones. The structure of the intermediate (E)-1,1,1-trifluoro-4-morpholino-4-(4-nitrophenyl)-but-3-en-2-ols could be assigned by ¹H, ¹³C NMR, IR, and X-ray crystallography. Furthermore, hydrogenation and reductive deamination of the intermediate (E)-1,1,1-trifluoro-4-morpholino-4-aryl-but-3-en-2-ols with hydrogen in the presence of a catalytic amount (10 mol %) of palladium on carbon in trifluoroethanol proceeded smoothly at room temperature to give 1,1,1-trifluoro-4-aryl-2-butanols in good to excellent yields.     

Protophilic isotopic hydrogen exchange of 1-ferrocenyl-2-(nitrophenyl)ethylenes

cis-1-Ferrocenyl-2-(4-nitrophenyl)ethylene enters into the protium/deuterium exchange in basic medium at the expense of hydrogens of the phenyl ring, at ortho positions in respect of the nitro group. The homoaromatic analogue, 4-nitrostilbene, under the same conditions, undergoes isotopic exchange occurring exclusively at the vinylic CH fragment attached to the nitrophenyl group. The difference is eliminated as a result of the shift of the nitro group from position 4 into position 2 of the phenyl ring: cis-1-ferrocenyl-2-(2-nitrophenyl)ethylene enters into H⁺/D⁺ exchange in the same manner as 4-nitrostilbene. Correspondence to: Professor Z.V. Todres.     

A new and efficient method for the synthesis of 3-(2-nitrophenyl)pyruvic acid derivatives and indoles based on the Reissert reaction

The formation of 3-(2-nitrophenyl)pyruvic acid and its amide and ester derivatives – key compounds for the Reissert indole synthesis – was achieved under various reaction conditions via the acid catalyzed hydrolysis of 5-(2-nitrobenzyliden)-2,2-dimethyl-1,3-oxazolidin-4-one, which is readily available from 3-(2-nitrophenyl)oxirane-2-carboxamide. A new and highly efficient method for the synthesis of indole-2-carboxylic acid derivatives via the intramolecular reductive cyclization of o-nitrophenylpyruvic acid and its amide and ester derivatives was developed using Na₂S₂O₄ in dioxane/water at reflux.     

偶氮苯取代吡唑啉衍生物PMMA薄膜的光诱导双折射性质研究

芳香族偶氮化合物的顺反异构化反应长期以来一直受到人们的关注 [1,2 ] .当把偶氮生色团引入到聚合物中时 ,在线性偏振光的激发下 ,偶氮生色团能发生“反 -顺 -反”光异构化循环 ,并且偶氮发色团会沿着偏振光偏振方向的法线重新取向 ,从而导致光致双折射现象的发生 [3 ] .因此 ,这类聚合物在光学存储 [4 ] 、光学开关和全息光栅 [5] 等方面具有重要的应用价值 .为研究偶氮苯的结构对光诱导双折射性质的影响 ,本文制备了偶氮苯取代的三苯基吡唑啉衍生物 ,并把其掺杂入 PMMA中 ,研究了薄膜的偏振光诱导光致双折射性质 ,讨论了温度对其光致双…     

Albumin-mediated asymmetric nitroaldol reaction of aromatic aldehydes with nitromethane in water

We succeeded in the asymmetric nitroaldol (Henry) reaction of aromatic aldehydes with nitromethane using human serum albumin (HSA) in water at neutral pH. The reaction of 4-nitrobenzaldehyde smoothly proceeded for 24 h at 30 °C to afford the corresponding (R)-2-nitro-1-(4-nitrophenyl)ethanol (27% ee). Lowering the reaction temperature to 0 °C improved the enantioselectivity (53% ee). Although the denatured HSA also catalyzed the coupling reaction, no enantioselectivity was observed. The reaction was also applicable to other substrates bearing various substitutions on the benzene ring, and the ee of (R)-1-(biphenyl-4-yl)-2-nitroethanol was up to 79% ee.     

Effects of steric bulk and stereochemistry on the rates of diketopiperazine formation from N-aminoacyl-2,2-dimethylthiazolidine-4-carboxamides (Dmt dipeptide amides)—a model for a new prodrug linker system

A peptide-like self-immolative molecular clip is required for release of active drugs from prodrugs by endopeptidases. Upon cleavage from the carrier, this clip must collapse and release the drug rapidly. A series of aminoacyl-5,5-dimethylthiaproline (Aaa-Dmt) N-(2-(4-nitrophenyl)ethyl)amides were designed. Boc-l-aminoacyl fluorides were coupled with R-DmtOH to give Boc-l-Aaa-R-DmtOH, which were converted to the Boc-l-Aaa-R-Dmt N-(2-(4-nitrophenyl)ethyl)amides. The l,S diastereomeric series was prepared by the reaction of Boc-Aaa PFP esters with S-DmtOH. The l-Aaa-Dmt N-(2-(4-nitrophenyl)ethyl)amides were allowed to cyclise to diketopiperazines (DKPs) in aqueous buffers, expelling 2-(4-nitrophenyl)ethylamine as a model for amine-containing drugs. Reaction rates were dependant on pH. In the l,R diastereomeric series, increasing steric bulk of the Aaa side-chain (Gly, Ala, Phe, Val) led to decrease in the reaction rate. However, in the l,S series, the greatest rate of reaction was observed for the most bulky amino-acid (Val), with t_½=15 min at pH 8.0. The effects of steric bulk and stereochemistry are rationalised through conformational analysis (NMR and X-ray crystallography) of the starting dipeptide amides, the product diketopiperazines and key analogues. Since the dipeptides are (almost) exclusively in the cis-amide conformation, trans-cis interconversion is not relevant. The data suggest that steric interactions in the reacting conformations of the dipeptide amides, as they form the tetrahedral intermediates, are the controlling factors. Thus, l-Aaa-S-Dmt amides are shown to be excellent candidates for incorporation into the design of novel prodrugs.     

Stereochemical studies—75 : Saturated heterocycles—62. connection between the diastereoselectivity and the dominant conformation in the formation of condensed- skeleton 1,3-oxazines,first X-ray diffraction evidence of N-outside conformation

The rapid, spontaneous epimerization occurring at the C(2) chirality centre of a new diastereomeric (r-4,c-2,c-5)-2-(p-nitrophenyl)-3-methyl-4,5-tetramethylenetetrahydro-1,3-oxazine led to the conclusion that the configuration at C(2) of the bicyclic 1,3-oxazines formed by the cyclization of alicyclic 1,3-aminoalcohols with aldehydes is determined by the dominant conformation of the product. The first X-ray diffraction evidence is given for the N-outside conformation of compounds of this type.     

Cross effects of structure and temperature in the reactions of <Emphasis Type="Italic">trans</Emphasis>-2,3-diaryloxiranes with arenesulfonic acids

Cross effects of the reagent structure and the temperature on the rate and activation parameters of the reactions of symmetrically X-substituted trans-2,3-diaryloxiranes with Y-substituted arene-sulfonic acids have been investigated in the temperature range 265–298 K. The isokinetic temperature of 265 K was reached, at which the rate and the free energy of the ring-opening reaction of trans-2,3-bis(3-bromo-5-nitrophenyl)-oxirane practically do not depend on substituent Y. The transition through the isoparametric points on substituent Y was realized with the inversion of the temperature effect on the free energy of activation for the reactions of oxiranes with X = 4-NO₂ and 3-Br-5-NO₂.     

A convenient approach towards 2- and 3-aminobenzo[b]thiophenes

Reaction of 1-(2-chloro-5-nitrophenyl)ethanone via Willgerodt-Kindler route with primary or secondary amines and sulfur allows a simple, efficient one-pot synthesis of 3-aminobenzo[b]thiophenes. Base-catalyzed transformation of 4-(2-chloro-5-nitrophenyl)-1,2,3-thiadiazole in the presence of primary and secondary amines offers a convenient approach towards 2-aminobenzo[b]thiophenes.     

Remarkable Chichibabin-type cyclotrimerisation of 3-nitrotyrosine, tyrosine and phenylalanine to 3,5-diphenylpyridine derivatives induced by hypochlorous acid

Reaction of 3-nitrotyrosine with HOCl in aqueous phosphate buffer (pH 7.4) leads to a mixture of extractable products, including 3,5-di(4-hydroxy-3-nitrophenyl)pyridine (15% isolated yield) and 3,5-di(4-hydroxy-3-nitrophenyl)-2-(4-hydroxy-3-nitrophenylmethyl)pyridine (3%) arising by a Chichibabin-like pyridine synthesis via N-chloroimine intermediates. Under the same conditions, phenylalanine gives 3,5-diphenylpyridine in 9% isolated yield, while tyrosine leads to 3,5-di(4-hydroxyphenyl)pyridine (3%) and 3-(3-chloro-4-hydroxyphenyl)-5-(4-hydroxyphenyl)pyridine (3%).     

Synthetic entry to 8-(o-nitrophenyl-2-azabicyclo[3.3.1]nonan-7-ones. Intermediates for the synthesis of strychnos-type systems.

The first synthetic route to 8-aryl-2-azabicyclo-[3.3.1]nonan-7-ones (e.g. 5) is reported. The synthesis involves acid cyclization of an appropriate 4-acetonyl-2-piperidinecarbonitrile (4) which, in turn, is obtained from the corresponding piperidine (3) by a modified Polonovski reaction. The o-nitrophenyl substituent of 3 is introduced by arylation of 4-piperidineacetoacetate 1 with o-fluoronitrobenzene followed by acid hydrolysis. The conversion of α-(o-nitrophenyl)ketone 5 to the bridged azocinoindole 7, an intermediate in the synthesis of deethyltubifolidine, is also reported.     

Syntheses and fluorescence of RNA conjugates having pyrene-modified adenosine and nitrobenzene-modified uridine base pairs

We prepared RNA duplexes possessing 2′-O-(1-pyrenylmethyl)adenosine and 5-(4-nitrophenyl)uridine base pairs. In the duplexes, pyrene serves as a photo-excitable electron donor and 5-(4-nitrophenyl)uridine acts as an electron acceptor. The donor-acceptor-modified RNA duplexes showed very weak fluorescence originating from the pyrene monomer and excimer emissions, which occur due to electron transfer from the excited pyrene to the nitrobenzene acceptor.     

Poly(4-nitrophenyl)quinoxalines

Via the reaction of 4,4-bis(4-nitrophenylglyoxalyl)diphenyl ether with different bis(o-phenylenediamine)s, new poly(4-nitrophenyl)quinoxalines were synthesized, which are of interest as precursors for polymers containing protogenic groups. Some properties of the obtained polymers were studied. It was shown that the solubility of poly(4-nitrophenyl)quinoxalines in organic solvents and their viscosity characteristics are comparable with the parameters of polyphenylquinoxalines that do not bear nitro groups. A study of the thermal properties of the polymers showed that the introduction of nitro groups into polyphenylquinoxalines is accompanied by some increase in the glass transition temperature and a decrease in the onset temperature of runaway thermal degradation.     

Asymmetric reduction of ketones by employing Rhodotorula sp. AS2.2241 and synthesis of the β-blocker (R)-nifenalol

A broad range of prochiral ketones were efficiently reduced to the corresponding optically active secondary alcohols using resting cells of Rhodotorula sp. AS2.2241. The microbial reduction system exhibited high activity and enantioselectivity in the reduction of various aromatic ketones and acetylpyridines (>97% ee), but moderate to high enantioselectivity in the reduction of α- and β-keto esters. (R)-Nifenalol, a β-adrenergic blocker, was also synthesized using 2-bromo-1(R)-(4-nitrophenyl)ethanol (97% ee) which was prepared through the asymmetric reduction of 2-bromo-1-(4-nitrophenyl)ethanone employing Rhodotorula sp. AS2.2241. The simple preparation and the high activity of the biocatalyst turned this system into a versatile tool for organic synthesis.     

Synthesis and Anticancer Activity Evaluation of 5-[2-Chloro-3-(4-nitrophenyl)-2-propenylidene]-4-thiazolidinones

A series of novel 5-[(Z,2Z)-2-chloro-3-(4-nitrophenyl)-2-propenylidene]-thiazolidinones (Ciminalum–thiazolidinone hybrid molecules) have been synthesized. Anticancer activity screening toward the NCI60 cell lines panel, gastric cancer (AGS), human colon cancer (DLD-1), and breast cancer (MCF-7 and MDA-MB-231) cell lines allowed the identification of 3-{5-[(Z,2Z)-2-chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}propanoic acid (2h) with the highest level of antimitotic activity with mean GI₅₀/TGI values of 1.57/13.3 μM and a certain sensitivity profile against leukemia (MOLT-4, SR), colon cancer (SW-620), CNS cancer (SF-539), melanoma (SK-MEL-5), gastric cancer (AGS), human colon cancer (DLD-1), and breast cancers (MCF-7 and MDA-MB-231) cell lines. The hit compounds 2f, 2i, 2j, and 2h have been found to have low toxicity toward normal human blood lymphocytes and a fairly wide therapeutic range. The significant role of the 2-chloro-3-(4-nitrophenyl)prop-2-enylidene (Ciminalum) substituent in the 5 position and the substituent’s nature in the position 3 of core heterocycle in the anticancer cytotoxicity levels of 4-thiazolidinone derivatives have been established     

Reinvestigation of the reported preparation of 3-(4-nitrophenyl)thiazolo[2,3-c][1,2,4]triazepines

2-(1H-Pyrazol-1-yl)-4-(4-nitrophenyl)thiazoles 2a and 2b , resulting from the condensation of 2-hydrazino-4-(4-nitrophenyl)thiazole ( 1 ) and acetylacetone and dibenzoylmethane, respectively, were previously [4] misas-signed as 3-(4-nitrophenyl)thiazolo[2,3-c][1,2,4]triazepines 3a and 3b . The assignments were corrected by authentic syntheses of 2a and 2b from 2-chloro-5-(4-nitrophenyl)thiazole ( 6 ) and 3,5-dimethyl-1H-pyrazole and 3,5-diphenyl-1H-pyrazole, respectively. In addition, the mass spectrum of 2a is reported. An apparent ionmolecule reaction produces an ion of significant intensity at m/e 394.