Kinetics and mechanism of the defluorination of 8-fluoropurine nucleosides in basic and acidic media

For investigating the stability of C(8)-fluorine bond in 8-fluoropurine nucleosides some protected 8-fluoroguanosine, 8-fluoroinosine and 8-fluoroadenosine derivatives were prepared by direct fluorination of acetyl-protected purine nucleosides with elemental fluorine in solvents such as chloroform, acetonitrile and nitromethane. Fluorination reactions conducted in chloroform medium gave better yields of 8-fluoropurines. The fluorination yields were slightly lower when acetonitrile or nitromethane was used as solvent, but the product purification was found to be much easier. When the synthesized, protected fluoronucleosides were subjected to standard basic (NH₃ in methanol or 2-propanol) and acidic (HCl in methanol) deprotection conditions relevant to nucleoside chemistry, an efficient defluorination reaction took place. The kinetics of these defluorination reactions were conveniently followed, under pseudo-first-order reaction conditions, using ¹⁹F NMR spectroscopy. ¹H NMR, LC-MS and mass spectroscopy identified the products of the kinetic reaction mixtures. The defluorination reaction rate constants (k_obs) in basic media depended upon the electron density at C(8) while the k_obs data in acidic medium were determined by the pK_a of N⁷. An addition-elimination based mechanism (S_NAr) has been proposed for the defluorination reactions of these 8-fluoropurine nucleosides.     

Synthesis and photoluminescence properties of 8-hydroxyquinoline derivatives and their metallic complexes

Three new 8-hydroxyquinoline derivatives, i.e. 5-[(4-styryl-benzylidene)-amino]-quinolin-8-ol (1), 5-[(4-bromo-2-fluoro-benzylidene)-amino]-quinoline-8-ol (2) and 2-[2-(9-ethyl-9H-carbazol-2yl)-vinyl]-quinolin-8-ol (3), and their metallic complexes were synthesized and identified by ultraviolet-visible (UV-Vis), ¹H nuclear magnetic resonance (¹H NMR), Fourier transform infrared spectrometer (FTIR), mass spectrometry (MS) spectra and elemental analyses. Their fluorescence properties were studied by photoluminescence, which indicated that the luminescence wavelength of 5-and 2-substitued-8-hydroxyquinoline derivatives shifted to red in comparison with that of 8-hydroxyquinoline. Meanwhile, the fluorescence lifetime of 2-[2-(9-ethyl-9H-carbazol-2yl)-vinyl]-quinolin-8-ol and its zinc complex showed long lifetime in benzene solution. __________ Translated from Chinese Journal of Organic Chemistry, 2007, 27(3): 402–408 [译自: 有机化学]     

One-Pot,Facile, Highly Efficient,and Green Synthesis of Acridinedione Derivatives Using Vitamin B1

An efficient methodology for the synthesis of acridinedione derivatives 4a–o has been achieved by one-pot, multicomponent condensation of dimedone 1, various amines 2a–d, and substitute aromatic aldehydes 3a–k, in the presence of the easily available, inexpensive, and nontoxic catalyst vitamin B₁ (VB₁) as a versatile biodegradable. Synthesis of acridine-type compounds was performed in good yields in water as green solvent. Its high-yield efficiency; clean, ecofriendly, simple workup procedure; and easy purification are regarded as the main advantages of this method besides its green solvent. The synthesized compounds are characterized using spectroscopic analyses (FTIR, ¹H NMR, ¹³C NMR, and high-resolution mass spectrometry) techniques.     

Microwave assisted,sequential two-step,one-pot synthesis of novel imidazo[1,2-a]pyrimidine containing tri/tetrasubstituted imidazole derivatives

A series of novel imidazo[1,2- a ]pyrimidine containing tri/tetrasubstituted imidazole derivatives (1-10) has been synthesized via sequential two-step, one-pot, multicomponent reaction using imidazo[1,2- a ]pyrimidine-2-carbaldehyde, benzil, primary amines, and ammonium acetate catalyzed by p -toluenesulfonic acid under microwave-assisted conditions. The results showed that target compounds can be obtained from a wide range of primary amines bearing different functional groups with moderate to good yields (46%-80%) under optimum reaction conditions. This method provides a green protocol for imidazo[1,2- a ]pyrimidine containing tri/tetrasubstituted imidazole derivatives due to ethyl alcohol as a green solvent, microwave irradiation as a greener heating method and one-pot multicomponent reaction as a green technique. The synthesized compounds have been elucidated using various spectroscopic tools such as FT-IR, ¹H NMR, ¹³ C NMR, and MS.     

Synthesis,Reactions, and Anticancer Activity of Some 1,3,4-Thiadiazole/Thiadiazine Derivatives of Carbazole

A novel method for the synthesis of 1,3,4-thiadiazole and 1,3,4-thiadiazine derivatives bearing a carbazole moiety is described. Carbazole was transformed into carbazole-9-thiocarbohydrazide in two steps. This compound was allowed to react with various electrophiles to yield 1,3,4-thiadiazole derivatives. The reaction with bifunctional electrophiles led to 1,3,4-thiadiazines. 2-(Carbazol-9-yl)-5,6-dihydro-4H-1,3,4-thiadiazin-5-one reacted with piperidine and formaldehyde to yield the 4-(piperidin-1-ylmethyl) derivative. The reaction with aromatic aldehydes led to the corresponding 6-arylidene derivatives, which were transformed into pyrimidino[4,5-e]-1,3,4-thiadiazines and pyrazolo[3,4-e]-1,3,4-thiadiazines by a reaction with guanidine, acetamidine, or phenylhydrazine, respectively. Structures of the products were confirmed by ¹H NMR, ¹³C NMR, IR, and mass spectrometric measurements. Selected examples of products were screened for anticancer activity.     

Cu(I)-phosphine complex: An efficient catalyst for synthesis of 3-indole derivatives through one-pot MCR under mild conditions

An efficient copper (I) halotriphenylphosphine catalyzed one-pot multicomponent reaction (MCR) of 3-substituted indole derivatives has been developed using a variety of aldehydes (aromatic, aliphatic, and heteroaromatic), indole, and active methylene substrates such as malononitrile and ethyl 2-cyano acetate. This reaction proceeds smoothly and obtained good to excellent yields (68–93%) using water as green solvent under ambient conditions. The obtained products were confirmed by ¹H, ¹³C NMR, and mass spectroscopy techniques. The one-pot MCR occurs through formation of Knoevenagel adducts then followed by Michael addition of indole.     

An Efficient Synthesis of 1′,7′,8′,9′‐Tetrahydrospiro[indoline‐3,4′‐pyrazolo[3,4‐b]quinoline]‐2,5′(6′H)‐dione Derivatives in Aqueous Medium

An efficient and green reactions of isatins, 3‐amine‐1H‐pyrazole (5‐methyl‐1H‐pyrazol‐3‐amine) and 1,3‐diketone in aqueous medium for the synthesis of novel 1′,7′,8′,9′‐tetrahydrospiro[indoline‐3,4′‐pyrazolo[3,4‐b]quinoline]‐2,5′(6′H)‐dione derivatives were reported in this research. The advantages of this reaction are simple operation, mild‐reaction conditions, wide scope substrate, high yields, and friendly environment. The products were confirmed by IR, ¹H NMR, ¹³C NMR, and HRMS.     

Synthesis of new indolylpyrrole derivatives via a four-component domino reaction between arylglyoxals,acetylacetone, indole and aliphatic amines in aqueous media

A novel synthesis of indolylpyrrole derivatives is described by a four-component domino reaction between arylglyoxals, acetylacetone, indole and aliphatic amines in water as solvent at 60?°C without using any catalyst or promoter. The FT-IR, ¹H NMR, ¹³C NMR spectral and elemental analysis confirm the structures of the products.     

8-羟基喹啉共轭连接芳香杂环化合物的合成、荧光性质及生物活性的研究

设计合成了4个8-羟基喹啉共轭联接芳香杂环化合物来研究它们在有机发光材料和荧光探针的潜在应用。用IR, 1H NMR, 13C NMR, MS, UV确认了这些新化合物的结构。测定了化合物1-4的荧光性质,发光衰变时间和量子产率,并用密度泛函方法研究了4个化合物的几何结构和荧光发射波长的关系。在调控骨髓间充质干细胞增殖以及清除DPPH自由基的活性测试结果表明,这些化合物具有促进小鼠骨髓间充质干细胞的增殖的活性及良好的抗氧化性。     

NMR study of O and N,O‐substituted 8‐quinolinol derivatives

The ¹H and ¹³C NMR spectral study of several biologically active derivatives of 8‐quinolinol have been made through extensive NMR studies including homodecoupling and 2D‐NMR experiments such as COSY‐45°, NOESY, and HeteroCOSY. Electron donating resonance and electron withdrawing inductive effect of several groups showed marked changes in chemical shifts of nuclei at the seventh positions of O‐substituted quinolinols (2–15). Although in N‐alkyl, 8‐alkoxyquinolinium halides (16–21), ring A rightly showed low frequency chemical shift values. Copyright © 2013 John Wiley & Sons, Ltd.     

The Preparation of (8‐Hydroxyquinolinato)Bis(2‐Phenylpyridyl)Iridium Complexes and Their Photophysical Properties

Four derivatives of the titled compounds, (8‐hydroxyquinoline)bis(2‐phenylpyridyl)iridium ( IrQ(ppy)₂ ), were prepared. Two of them were confirmed by single crystal X‐ray diffraction analyses, in which solvent molecules were found to be incorporated in the crystal lattices. Their emission spectra display separated dual bands in de‐aerated solutions at about 515 and 645 nm upon excitation. These green and red emissions are attributed to the triplet metal‐to‐ligand charge transfer (³MLCT) and triplet ligand centered (³LC) transitions in Ir(ppy)₂ and IrQ, respectively. It is suggested that such a multiple emission is feasible by nearly orthogonal orientation between the ppy and quinoline ligands in the mixed‐ligand Ir‐compounds which prohibits energy transfer between the two different ligands. The electroluminescence (EL) of these compounds was examined by the fabrication of light‐emitting diodes (LEDs). Unlike the spectra in solutions, their EL spectra displayed only the red emission band. Devices displaying white light can be obtained by mixing the red emission of IrQ(ppy)₂ with a compatible blue emitter (NPB) in separated layers.     

Copper-immobilized ionic liquid as an alternative to organic solvents in the one-pot synthesis of bioactive dihydropyrano[2,3-c]pyrazole derivatives

In this study, a novel Cu-immobilized ionic liquid (IL)was designed, characterized, and employed as both promoter and solvent in the synthesis of some dihydropyrano[2,3-c]pyrazoles. The synthesized ionic liquid was characterized by ¹H NMR, ¹³C NMR, FTIR, ICP and EDX analysis and showed high catalytic activity to proceed the synthesis of bioactive dihydropyrano[2,3-c]pyrazole derivatives. This method has the advantage of using the IL as a green medium for the synthesize of the products in high to excellent yields within short reaction times.     

Ferrocene‐tagged ionic liquid stabilized on silica‐coated magnetic nanoparticles: Efficient catalyst for the synthesis of 2‐amino‐3‐cyano‐4H‐pyran derivatives under solvent‐free conditions

An advanced novel magnetic ionic liquid based on imidazolium tagged with ferrocene, a supported ionic liquid, is introduced as a recyclable heterogeneous catalyst. Catalytic activity of the novel nanocatalyst was investigated in one‐pot three‐component reactions of various aldehydes, malononitrile and 2‐naphthol for the facile synthesis of 2‐amino‐3‐cyano‐4H‐pyran derivatives under solvent‐free conditions without additional co‐catalyst or additive in air. For this purpose, we firstly synthesized and investigated 1‐(4‐ferrocenylbutyl)‐3‐methylimidazolium acetate, [FcBuMeIm][OAc], as a novel basic ferrocene‐tagged ionic liquid. This ferrocene‐tagged ionic liquid was then linked to silica‐coated nano‐Fe₃O₄ to afford a novel heterogeneous magnetic nanocatalyst, namely [Fe₃O₄@SiO₂@Im‐Fc][OAc]. The synthesized novel catalyst was characterized using ¹H NMR, ¹³C NMR, Fourier transform infrared and energy‐dispersive X‐ray spectroscopies, X‐ray diffraction, and transmission and field emission scanning electron microscopies. Combination of some unique characteristics of ferrocene and the supported ionic liquid developed the catalytic activity in a simple, efficient, green and eco‐friendly protocol. The catalyst could be reused several times without loss of activity.     

Reaction of aromatic aldehydes with β-dicarbonyl compounds in a catalytic system: Piperidinium acetate-1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid

Condensation of aromatic (heteroaromatic) aldehydes with 1,3-dicarbonyl compounds under the 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim][BF₄]) ionic liquid-piperidinium acetate catalytic system (0.2 equiv. of each component) in the absence of a solvent affords, depending on the structures of the reagents, 2-arylidene derivatives of methyl acetoacetate and acetylacetone, diethyl 2,4-bis(trifluoroacetyl)-3-phenylpentanedioate, or dimethyl 2-aryl-4-hydroxy-6-oxocyclohexane-1,3-dicarboxylates. The reactions of the resulting 2-arylidene derivatives with O-methylisourea in the [Bmim][BF₄] ionic liquid produced methyl 2-methoxy-4-methyl-6-aryldihydropyrimidine-5-carboxylates and 1-(2-methoxy-4-methyl-6-phenyldihydropyrimidin-5-yl)ethanone (mixtures of 3,6- and 1,6-dihydro isomers), which were transformed into the corresponding 3,4-dihydropyrimidin-2(1H)-one derivatives. Dedicated to Academician N. K. Kochetkov on the occasion of his 90th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1199–1204, May, 2005.     

Synthesis of 2-(4-amino substituted benzylidene) indanone analogues from aromatic nucleophilic substitution (SNAr) reaction

A novel, efficient and convenient procedure has been developed for the synthesis of 2-(4-amino-substituted benzylidene)indanone derivatives. In the first step, the reaction of 4-fluorobenzaldehyde with 5, 6-dimethoxy-2, 3-dihydro-1H-inden-1-one in the presence of NaOH in EtOH was described. In the next step, a variety of aliphatic and aromatic amines were reacted with 2-(4-fluorobenzylidene)-5, 6-dimethoxy-2, 3-dihydro-1H-Inden-1-one via aromatic substitution (S_NAr) reaction to produce 2-(4-aminobenzylidene)-5, 6-dimethoxy-2, 3-dihydro-1H-Inden-1-one derivatives as a novel class of 1-indanones. These products have been successfully prepared in good to excellent yields. ^1?H and ^13?C NMR, FT-IR spectroscopy and CHN analysis supported the proposed structures of the products.     

Development of an efficient,one-pot,multicomponent protocol for synthesis of 8-hydroxy-4-phenyl-1,2-dihydroquinoline derivatives

A one-pot quick and efficient multicomponent reaction has been developed for the synthesis of a new series of functionalized 8-hydroxy-4-phenyl-1,2-dihydroquinoline derivatives using 30 mol% ammonium acetate in ethanol as solvent. This economical protocol run smoothly to give variety of quinoline derivatives in 55% to 98% yield from inexpensive reagents and catalyst in mild reaction conditions. Various spectroscopic techniques like FTIR, ¹H NMR and ¹³C NMR, MALDI-TOF-MS, and EI-MS were used to study and confirm their structure.     

5-Arylidene Derivatives of Meldrum’s Acid as Synthons in Pyrano[4,3-b]pyran Synthesis

The reactions of 5-arylidene derivatives of Meldrum’s acid with ethyl vinyl ether or N-vinyl-2-oxazolidinone yielded trans-trans-(2,4:4,7)-pyrano[4,3-b]pyrans, cis-trans-(2,4:4,7)-pyrano[4,3-b]pyrans, or diastereoisomeric mixtures of pyrano[4,3-b]pyrans and reactions with 3,4-dihydro-2H-pyran afforded Michael adducts. The reactions of 5-arylidene derivatives of Meldrum’s acid with cyanoacetic acid derivatives do not provide appropriate pyrans.     

Ultrasound mediated green synthesis of pyrano[2,3-c]pyrazoles by using Mn doped ZrO2

Mn doped zirconia is utilized as an environmental-friendly and efficient catalyst for an ultrasound mediated four-component coupling reaction, containing dimethylacetylenedicarboxylate/ethyl acetoacetate, hydrazine hydrate, malononitrile, and aromatic aldehyde. These reactions were performed under green solvent conditions, to yield pyrano[2,3-c]pyrazole-3-carboxylate/pyrano[2,3-c]pyrazole-5-carbonitrile derivatives (5a–g and 7a–g) with good to excellent yields (88–98%). The structures of the compounds were identified and confirmed by ¹H NMR, ¹⁵N NMR, ¹³C NMR, FT-IR and HR-MS spectral data. The prepared catalyst Mn/ZrO₂ was synthesized and fully characterized by various techniques including P-XRD, BET, SEM and TEM analysis. The main benefits of this process are short reaction times, easy work-up, reusability of the catalyst and no chromatographic purifications.     

Confusing Quantitative Descriptions of BrønstedLowry AcidBase Equilibria in Chemistry Textbooks – A Critical Review and Clarifications for Chemical Educators

In chemistry textbooks, the pK value of water in the solvent water at 25 °C is sometimes given as 14.0, sometimes as 15.7. This is confusing. The particular chemical reaction considered is the one in which water as Brønsted? Lowry acid reacts with water as Brønsted? Lowry base in water as solvent to yield equal concentrations of hydrated oxonium and hydroxide ions, H₃O⁺(aq) and HO^?(aq), respectively. This reaction is also known as the ‘self‐ionization’ of water for which the equilibrium constant is abbreviated as K_w with its known value of 10^?14.0 at 25 °C, i.e., pK_w(25 °C)=14.0. Identical values for pK and pK_w at a fixed temperature appear reasonable, since K and K_w refer to one and the same reaction. Therefore, reasons for the apparent disagreement between the ‘thermodynamically correct’ pK_a value for water (14.0 at 25 °C) and the value reported in most organic chemistry textbooks (15.7) should be discussed when teaching acid? base chemistry. There are good arguments for introducing, from the very beginning, the concepts of activity and thermodynamic standard states when teaching quantitative aspects of chemical equilibria. This also explains in a straightforward way why all thermodynamic equilibrium constants, including K_w, are dimensionless, and why pK(25 °C)=0.