Synthesis and Antimicrobial Evaluation of Some Chalcones and Their Derived Pyrazoles, Pyrazolines, Isoxazolines, and 5,6-Dihydropyrimidine-2-(1 H )-thiones

Chalcones were synthesized by a base catalyzed Claisen-Schmidt condensation reaction. Bromination of chalcones afforded the dibromo derivatives. Monobromo derivatives could be obtained by treating the corresponding dibromochalcones with dry benzene in the presence of triethylamine. Pyrazole derivatives were obtained by refluxing of dibromochalcones with phenylhydrazine or 2,4-dinitrophenylhydrazine in dry pyridine. Chalcones were treated with hydrazine hydrate or phenyl hydrazine in ethanol to afford Δ ²-pyrazolines and N-phenyl-Δ ²-pyrazolines. Condensation of chalcones with hydroxylamine hydrochloride or thiourea in ethanolic sodium hydroxide solution gave 4,5-dihydroisoxazoles and 5,6-dihydropyrimidine-2-(1H)-thiones. The prepared compounds were tested for antimicrobial activity against four different bacterial species displaying different degrees of antibacterial activities or inhibitory actions.     

Synthesis of 1,5-Disubstituted 3-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines

Summary. A series of 1,5-disubstituted 3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines were synthesized by the reaction of α,β-unsaturated ketones derived from dehydroacetic acid and hydrazine in hot acetic acid or propionic acid. The structures of all new compounds were elucidated by microanalyses, ¹H and ¹³C NMR, IR, and mass spectroscopic measurements.     

1H and 13C NMR spectral assignments of chalcones bearing pyrazoline–carbothioamide groups

Chalcones are known to act on various physiological targets. As a result, structural modifications of chalcones have been studied extensively. Benzochalcones, in which the A‐ring of chalcone is substituted with a naphthalene unit, inhibits breast cancer resistance protein. Chalcones in which the α,β‐unsaturated carbonyl group is switched with a pyrazoline moiety are potent cytotoxic agents against various cancer cell lines, and chalcones with a pyrazoline‐1‐carbothioamide group instead of an α,β‐unsaturated carbonyl group exhibit antimicrobial activities. The present report describes hybrid molecules designed from benzochalcone and pyrazoline–carbothioamide. Methoxylation of plant‐derived polyphenols alters their hydrophobicity, resulting in changes in biological function and intracellular compartmentation. In the current study, 22 novel methoxylated 3‐(naphthalen‐2‐yl)‐N,5‐diphenyl‐pyrazoline‐1‐carbothioamide derivatives were prepared. This report provides complete assignments of their ¹H and ¹³C NMR data, which can be used to subsequently identify chalcones bearing pyrazoline–carbothioamide groups. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis of 1,5-Disubstituted 3-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines

A series of 1,5-disubstituted 3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines were synthesized by the reaction of α,β-unsaturated ketones derived from dehydroacetic acid and hydrazine in hot acetic acid or propionic acid. The structures of all new compounds were elucidated by microanalyses, ¹H and ¹³C NMR, IR, and mass spectroscopic measurements.     

Synthesis of thiophene analogs of 1, 3, 5-triphenylpyrazoline derivatives

Nineteen ²-pyrazolines hitherto undescribed in the literature are prepared by reacting thiophene and selenophene analogs of chalcones with phenylhydrazine or p-nitrophenylhydrazine. It is shown that thiophene and selenophene chalcones can be more easily cyclized than their furan analogs. The 2, 4, 6-trimethoxy group when present in the 1-(thienyl-2)-3-arylpropenone-1 molecule causes steric hindrance in the corresponding pyrazoline.     

Synthesis of furan analogs of 1, 3, 5-triphenylpyrazoline derivatives

Furan analogs of chalcones are condensed with phenylhydrazine to give a number of ²-pyrazolines hitherto not described in the literature. It is shown that in , -unsaturated ketones, a nitro-group in the nucleus and remote from the carbonyl group makes cyclization to the corresponding ²-pyrazolines more difficult than does one adjacent to the carbonyl.     

Action of Hydrazines on 2‐(2‐Oxindolin‐3‐ylidene)malononitrile, (E,Z)‐Ethyl 2‐cyano‐2‐(2‐oxindolin‐3‐ylidene)acetate and Isatin‐β‐thiosemicarbazone as a Source of Spiro Indoline‐pyrazole Systems

2‐(2‐Oxindolin‐3‐ylidene)malononitrile ( 1a ) or (E,Z)‐ethyl 2‐cyano‐2‐(2‐oxindolin‐3‐ylidene)acetate ( 1b ) or isatin‐β‐thiosemicarbazone ( 1c ) undergoes reactions with prototype hydrazine hydrate itself and some of its simple congeners to give hydrazone derivatives bearing indoline‐2‐one moiety ( 2 ). The hydrazone derivatives ( 2 ) when heated with acetyl acetone or ethyl acetoacetate in dry pyridine afforded the spiro indoline derivatives ( 3a , 3b ). Also, cinnoline derivative ( 9 ) is obtained by action of hydrazine hydrate on the N‐acetyl derivative of ( 6a ). The structures of the newly synthesized compounds were evaluated by IR, ¹H‐NMR spectroscopy, mass spectra and elemental analyses.     

Isomeric composition of pyrazolines obtained from unsaturated carbonyl compounds and hydrazine

The ²-pyrazolines synthesized under the usual conditions from unsaturated aldehydes and hydrazine contain from 2 to 3% of the ¹-isomers and considerable amounts of the isomeric 3-alkyl-²-pyrazolines, which are formed as a consequence of migration of the double bond. Mixtures of the stereoisomeric ²-pyrazolines are formed from ,-dialkyl-substituted acroleins. Migration of the double bond does not occur in the condensation of unsaturated ketones with hydrazine, and ²-pyrazolines that are free from admixtures of the structural isomers are obtained.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1225–1229, September, 1971.     

Kinetics of hydrolysis of five-membered <Emphasis Type="Italic">C</Emphasis>-nitroheterocycles: pyrazole,imidazole, 1,2,4-triazole,and isoxazole derivatives

Alkaline hydrolysis of mono-and dinitro derivatives of five-membered heterocycles, viz., pyrazole, imidazole, 1,2,4-triazole, and isoxazole, is accompanied by the elimination of the nitro group in the form of a nitrite anion. The hydrolysis kinetics was studied by the polarographic and photometric methods. The experimentally determined hydrolysis rate constants depend on the nature of the heterocycle. A possible mechanism for hydrolytic transformations of the compounds under study was proposed on the basis of the calculated thermodynamic parameters of the reaction (Δ G ^≠, ΔH ^≠, ΔS ^≠). Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2719–2725, December, 2005.     

1H and 13C NMR spectral assignments of 2′‐hydroxychalcones

Chalcones are of interest to medicinal chemists because their structures can be easily modified with various functional groups. The syntheses and biological activities of chalcones from natural sources are well known. In this study, 24 2′‐hydroxychalcones bearing methoxy substituents were synthesized, among which five are new. The NMR data for all synthesized chalcones are described for the first time. The complete assignments of the ¹H and ¹³C NMR data can be used for the identification of newly discovered and widely isolated, synthesized chalcones. Copyright © 2013 John Wiley & Sons, Ltd.     

Thermodynamic characteristics of the complexation between Pb<Superscript>2+</Superscript> and <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-Bis(carboxymethyl)aspartic acid in aqueous solution

The enthalpies of complexation between N,N-bis(carboxymethyl)aspartic acid (H₄Y) and the Pb²⁺ ion at 298.15 K were determined from calorimetric data for a wide range of the ionic strengths (KNO₃). The thermodynamic characteristics ΔH, ΔG, and ΔS, of formation of the complexes PbHY⁻ and PbY²⁻ were calculated for zero and fixed ionic strengths. The results obtained were interpreted.     

Theoretical Study of the Interactions between Isolated <Emphasis Type="Italic">DNA</Emphasis> Bases and Various Groups IA and IIA Metal Ions by <Emphasis Type="Italic">Ab Initio</Emphasis> Calculations

Summary. Interactions of the DNA bases adenine (A), guanine (G), cytosine (C), and thymine (T) with various metal ions (M) of groups IA and IIA of the periodic table of the elements were studied at the HF, MP2, and DFT levels of theory. The structures and thermodynamic stabilities of these species were studied at the gas phase. The calculations uphold that there exist two active sites in G and one in A, C, and T. The calculations also show that the O² atom in T is a more active site for metal ion bindings than that in C. The stability energies for G … M complexes are larger than those for A … M complexes and the stability energies for T … M complexes are larger than those for C … M complexes. As z/r ratio for the metal ion increases, the interaction energy for the complex increases systematically. Thermodynamic quantities such as ΔH, ΔG, ΔS, and ln K were determined for each complexation reaction, [Base+M ⁿ⁺ →(Base … M) ⁿ⁺]. A, G, and C complexation reactions except for C … Rb⁺ are exothermic. The situation is quite different for T complexation reactions and all except for T … Be²⁺ and T … Mg²⁺ are endothermic.     

Reactions of fluoroalkyl-containing bis-β-diketones with hydrazine and hydroxylamine

Polyfluoroalkyl-containing bispyrazoles, bis(5-hydroxy-Δ²-isoxazolines), and bisisoxazoles were synthesized for the first time by reactions of polyfluoroalkyl-containing bis-β-diketones with hydrazine, phenylhydrazine, and hydroxylamine, respectively. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 762–764, April, 1999.     

Enthalpies of Dehydrations of Oxalate,Sulfate and Chloride Hydrates by Transpiration Method and DSC

Transpiration method was used to measure the equilibrium water vapor pressures of the dehydration of the respective hydrates, such as oxalates, sulfates,chlorides and acetate, and the enthalpies of dehydrations (ΔH _Tr ⁰) of these hydrates were obtained. The heats of dehydrations (ΔH _DSC ⁰) were also determined by TG-DSC method. From the comparison with ΔH _Tr ⁰ of ΔH _DSC ⁰, the relation of ΔH _DSC ⁰/ΔH _Tr ⁰=R (=dehydration molar number determined by TG-DSC peak/stoichiometric dehydration molar number) was yielded. From these results, the following relations were found: ΔH _DSC ⁰(corrected)=ΔH _DSC ⁰/R=ΔH _Tr ⁰ This revised version was published online in July 2006 with corrections to the Cover Date.     

Rearrangement products of some 1R,4R-2-arylidene-p-menthan-3-ones in acidic media, their structures, and conformational analysis

1R,4R-2-(4-Phenylbenzylidene)-p-menthan-3-one in acidic media undergoes rearrangement with migration of the exocyclic double bond to the cyclohexane ring to form three 2-(4-phenylbenzyl) derivatives ofp-menthen-3-ones. The reaction products differ in the location of the endocyclic double bond (Δ¹ or Δ⁴) and in the configuration of the new chiral C(2) center in the resultingp-menth-4-en-3-ones. The configurations of the 1R,2R- and 1R,2S-2-(4-phenylbenzyl)-p-menth-4-en-3-ones were established based on analysis of their¹H NMR spectra in combination with calculations by molecular mechanics. The molecular conformations of these compounds as well as of some racemic 2-benzyl-p-menth-1-en-3-one derivatives were studied.     

Solid-Solute Phase Equilibria in Aqueous Solutions XIV [1]. Thermodynamic Analysisof the Solubility of Hellyerite in Water

Summary.  The solubility of hellyerite, NiCO₃ · 6H₂O, in water was studied at different temperatures. From the experimental data obtained, a preliminary set of the thermodynamic quantities Δ_f G ^⊖, Δ_f H ^⊖, and S ^⊖ for hellyerite was derived using the ChemSage optimizer routine. Received January 16, 2001. Accepted January 18, 2001     

Thermochemical study of processes of complex formation of Cu<Superscript>2+</Superscript> ions with L-glutamine in aqueous solutions

Heats of the interaction of Cu(NO₃)₂ solutions with L-glutamine solutions were measured directly by calorimetry at a temperature of 298.15 K and ionic strength values of 0.5, 1.0, and 1.5 (KNO₃). Using RRSU universal software, the experimental data were subjected to rigorous mathematical treatment with allowances made for several concurrent processes in the system. The heats of formation of the CuL⁺ and CuL₂ complexes were calculated from the calorimetric measurements. The standard heats of the complex formation of Cu²⁺ with L-glutamine were obtained by extrapolation to zero ionic strength. The complete thermodynamic characteristic (Δ_r H ^o, Δ_r G ^o, Δ_r S ^o) of the complex formation processes in a Cu²⁺—L-glutamine system was obtained.     

Rearrangements in the formation of pyrazolines from alkyl hydrazines and unsaturated carbonyl compounds

The isomeric composition of the 2-pyrazolines obtained by the condensation of croton aldehyde and methyl vinyl ketone with C₁–C₄ monoalkyl hydrazines has been studied by the GLC method. It has been shown that in the reaction of croton aldehyde with isopropyl hydrazine, isobutyl hydrazine, and, to a smaller extent, with methyl hydrazine, in addition to the 1-alkyl-5-methyl-2-pyrazolines the 1, 3-isomers are formed. In other cases, only one pyrazoline, corresponding to the structure of the carbonyl compound, is formed. Eight previously-unknown dialkyl-2-pyrazolines are described.     

Synthesis,Antimicrobial Studies,and Docking Simulations of New Bis(4,5‐dihydropyrazole) Derivatives

A novel series of bis(3‐thienyl‐4,5‐dihydropyrazoles) has been synthesized by the cyclization reactions of bischalcones with phenyl hydrazine in basic medium. The O‐alkylation reactions of chalcones with suitable 1,ω‐dibromoalkanes in the presence of anhydrous K₂CO₃, dry acetone, and Bu₄N⁺I⁻ as PTC lead to the formation of bischalcones in good yields. The chalcone required was obtained from the Claisen–Schmidt condensation reaction of 2‐acetylthiophene with 3‐hydroxybenzaldehyde. Structures of prepared compounds were elucidated from their IR, ¹H‐NMR, ¹³C‐NMR, and ESI‐MS spectral data. Newly synthesized compounds were screened for their antimicrobial potencies against Gram‐positive, Gram‐negative bacterial strains, and fungal strains using serial tube dilution method. Docking simulations have also been carried out to visualize the possible interaction of synthesized scaffold 2(a – g) and 3(a – g) at the active sites of Escherichia coli .     

Volumetric and Viscometric Studies on Sodium Nitrate and Potassium Nitrate in Aqueous and H<Subscript>2</Subscript>O-urea Solutions

Summary.  Density and viscosity of NaNO₃ and KNO₃ in aqueous and in H₂O-urea solutions were determined as a function of electrolyte concentrations at 308, 313, 318, 323, and 328 K, respectively. The apparent molal volume (φ _v ) of the electrolytes were found to be linear functions of the square root of the solute molality (b). The φ _v and data were fitted to the Masson equation [1] by the least square method to obtain the apparent molar volume at infinite dilution (φ _v ^{^}), which is practically equal to the partial molar volume . The viscosity coefficients A and B were calculated on the basis of the viscosity of the solutions and the solvent concerned using the Jones–Dole [2] equation. The activation parameters for viscous flow (ΔG ^≠, ΔS ^≠, and ΔH ^≠) were calculated according to Eyring [3]. The values of for the two systems were also calculated from B-coefficient data. The results were found to be of opposite nature in the two electrolyte systems. Where sodium nitrate showed structure making behaviour both in aqueous and in H₂O-urea solutions, KNO₃ showed structure breaking behaviour in aqueous solutions and structure making behaviour in 5 molal H₂O-urea solutions in the studied temperature range. The behaviour of these two electrolytes in aqueous binary and in aqueous-urea ternary systems are discussed in terms of charge, size, and hydrogen bonding effects. Corresponding author. E-mail: chemistry_ru@yahoo.com Received January 24, 2002; accepted (revised) April 5, 2002