Ring Opening Closure Research Articles

Evaluation of ferrocenyl-containing γ-hydroxy-γ-lactam-derived tetramates as potential antiplasmodials

A series of ferrocenyl-containing γ-hydroxy-γ-lactam tetramates were prepared in 2–3 steps through ring opening-ring closure (RORC) process of γ-ylidene-tetronate derivatives in the presence of ferrocenyl alkylamines. The compounds were screened in vitro for their antiplasmodial activity against chloroquine-sensitive (3D7) and chloroquine-resistant (W2) clones of P. falciparum, displaying activity in the range of 0.12–100 μM, with generally good resistance index. The most active ferrocene in these series exhibited IC50 equal to 0.09 μM (3D7) and 0.12 μM (W2). The low cytotoxicity of the ferrocenyl-containing γ-hydroxy-γ-lactam tetramates against Human Umbilical Vein Endothelial (HUVEC) cell line demonstrated selective antiparasitic activity. The redox properties of these ferrocene-derived tetramates were studied and physico-biochemical studies evidenced that these derivatives can exert potent antimalarial activities via a mechanism distinct from ferroquine.

Synthesis, DFT studies and photovoltaic characteristics of 2-amino-N-cyclohexyl-5-oxo-5H-chromeno[2,3-b]pyridine-3-carboxamide (ACCP)

Base catalysed ring opening ring closure (RORC) reaction of chromone-3-carbonitrile (1) with 2-cyano-N-cyclohexylacetamide afforded 2-amino-N-cyclohexyl-5-oxo-5H-chromeno[2,3-b]pyridine-3-carboxamide (ACCP). Mullikan atomic charges and EHOMO-ELUMO highest occupied and lowest unoccupied energies have been discussed from density functional theory DFT/B3LYP/6-311G(d,p). The surface topography of the prepared samples by electron microscopy introduces an indication for the presence of micro-rods with various directions and the measured size, by particle size analyzer was found to be 1100 nm. The optical band transitions were estimated to be directly allowed with energy gap values of 1.16 and 3.31 eV for the onset and fundamental energy gaps, respectively. The single-oscillator model was applied to obtain the main dispersion parameters. The current density-voltage characteristics in dark and under various illuminations of 20–100 were applied to obtain the main photovoltaic parameters. The results of the illuminated current density-voltage characteristics confirm that ACCP based heterojunction can be used as a photodiode in optoelectronic device applications.

Synthesis, molecular, electronic structure, linear and non-linear optical and phototransient properties of 8-methyl-1,2-dihydro-4H-chromeno[2,3-b]quinoline-4,6(3H)-dione (MDCQD): Experimental and DFT investigations

Base catalysed ring opening ring closure (RORC) reaction of 6-methylchromone-3‑carbonitrile (1) with 1,3-cyclohexanedione afforded 8-methyl-1,2-dihydro-4H-chromeno[2,3-b]quinoline-4,6(3H)-dione (MDCQD). Theoretical calculations by Density Functional Theory (DFT) at the B3LYP/6-311G (d,p) level of theory was utilized to illustrate the equilibrium geometries of MDCQD. Also, the nonlinear optical properties, simple harmonic vibrational frequencies, thermo-chemical parameters and Mullikan atomic charges were calculated. In addition, the electronic absorption spectra in polar and non polar solvents were discussed on the basis of TD-DFT calculations. A nanofiber-like structure with high aggregation was resolved by using scanning electron microscopy images and its particle sizes were measured by particle size analyzer. The spectroscopic characteristics of the prepared thin film of MDCQD were studied in a wide spectral range of 200–2500nm. The analysis of the absorption edges affords two direct optical band gaps with energies of 1.00 and 2.76eV. A characteristic emission peak of photoluminescence spectrum in the visible region was detected and has a red-shift as a result of solvent polarity. The MDCQD film based heterojunction showed rectification behavior and diode-like characteristics. The photovoltaic characteristics under illumination of 100mW/cm2 were studied. The open-circuit voltage and short-circuit current were found to be 0.22V and 4.25×10−7A/cm2, respectively. Moreover, the prepared heterojunction showed remarkable phototransient characteristics which afford the probability for the operation as a photodiode.

7-Chloro-4-aminoquinoline γ-hydroxy-γ-lactam derived-tetramates as a new family of antimalarial compounds

In this Letter we report on an efficient and short 2–3 steps synthesis of γ-hydroxy-γ-lactam derived-tetramates bearing a 7-chloro-4-aminoquinoline skeleton and their evaluation as potent antimalarials. These molecules were obtained through ring opening-ring closure (RORC) process of γ-ylidene-tetronate derivatives in the presence of 7-chloro-4-aminoquinoline-derived amines. In vitro antimalarial activity of these new γ-lactams was evaluated against Plasmodium falciparum clones of variable sensitivity (3D7 and W2) and they were found to be active in the range of 14–827nM with generally good resistance index. A preliminary SAR study is also presented to explain these results. Finally, the most active compounds did not show in vitro cytotoxicity when tested against Human Umbilical Vein Endothelial Cells (HUVEC) up to concentration of 50μM and they were stable at pH 7.4 for at least 48h.

Flavylium based dual photochromism: addressing cis-trans isomerization and ring opening-closure by different light inputs.

The multistate system of 4',7-dihydroxy-3-methoxyflavylium is constituted by a multiequilibrium involving trans-chalcone, cis-chalcone, hemiketal, flavylium cation and quinoidal base. This system possesses two independently addressable inter-connected photochromic systems based on the cis-trans isomerization and ring opening-closure of the hemiketal.

ChemInform Abstract: “Ring Opening—Ring Closure” Strategy for the Synthesis of Aryl‐C‐glycosides.

A new “ring-opening–ring closure” strategy for the synthesis of aryl-C-glycosides was described. This strategy exploited the nickel-catalyzed regioselective β-O elimination of glycals by reactions with various aryl boronic acids or potassium aryltrifluoroborates to yield the ring-opened products, which underwent the Lewis acid, protonic acid, PhSeCl, or NBS mediated ring closure reactions to afford diverse aryl-C-glycosides. After Lewis acids and protonic acids were screened, it was found that, starting from the ring-opened substrates, the Ph3PHBr or Sc(OTf)3 mediated ring closure reaction provided α- or β-preferred aryl-C-Δ2,3-glycosides, respectively. Furthermore, β-d-phenyl-C-glycosides were successfully prepared via the PhSeCl-mediated cyclization reaction, whereas the α-d-phenyl-C-glycoside was obtained via the NBS-mediated cyclization reaction. After removal of the 2-substituted functionalities by Bu3SnH/AIBN, the synthesis of 2-deoxy-aryl-C-glycosides was ultimately realized in a stereoselective ma...

"Ring opening-ring closure" strategy for the synthesis of aryl-C-glycosides.

A new "ring-opening-ring closure" strategy for the synthesis of aryl-C-glycosides was described. This strategy exploited the nickel-catalyzed regioselective β-O elimination of glycals by reactions with various aryl boronic acids or potassium aryltrifluoroborates to yield the ring-opened products, which underwent the Lewis acid, protonic acid, PhSeCl, or NBS mediated ring closure reactions to afford diverse aryl-C-glycosides. After Lewis acids and protonic acids were screened, it was found that, starting from the ring-opened substrates, the Ph3PHBr or Sc(OTf)3 mediated ring closure reaction provided α- or β-preferred aryl-C-Δ(2,3)-glycosides, respectively. Furthermore, β-D-phenyl-C-glycosides were successfully prepared via the PhSeCl-mediated cyclization reaction, whereas the α-D-phenyl-C-glycoside was obtained via the NBS-mediated cyclization reaction. After removal of the 2-substituted functionalities by Bu3SnH/AIBN, the synthesis of 2-deoxy-aryl-C-glycosides was ultimately realized in a stereoselective manner.

Substituted quinolinones, Part 23. Synthesis of 6-ethyl-4,5-dioxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carboxaldehyde and its chemical behavior towards hydroxylamine hydrochloride

The synthesis of novel 6-ethyl-4,5-dioxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carboxaldehyde is described via Vilsmeier-Haack reaction of 3-acetyl-1-ethyl-4-hydroxyquinolin2(1H)-one. The reaction of titled aldehyde with hydroxylamine hydrochloride, under different conditions, revealed its distinctive chemical behavior and a variety of products were obtained. This study revealed existence of ring-opening ring-closure (RORC) on treatment with hydroxylamine hydrochloride in both acetic acid and/or ethanolic potassium hydroxide. The structure of the new products was deduced on basis of their analytical and spectral data.

New route to the 5-((arylthio- and heteroarylthio)methylene)-3-(2,2,2-trifluoroethyl)-furan-2(5H)-ones—Key intermediates in the synthesis of 4-aminoquinoline γ-lactams as potent antimalarial compounds

In this Letter we report on a multi-step synthesis of 5-((arylthio- and heteroarylthio)-methylene)-3-(2,2,2-trifluoroethyl)furan-2(5H)-ones starting from γ-keto thiolester or γ-keto carboxylic acid. The key intermediate γ-lactones were then reacted with 4-aminoquinoline-derived amines via ring opening—ring closure (RORC) process affording the corresponding γ-hydroxy-γ-lactams in moderate to good yields. In vitro antimalarial activity of the resulting new 4-aminoquinoline γ-lactams were evaluated against Plasmodium falciparum clones of variable sensitivity (3D7 and W2) and were found to be active in the range of 89–1600nM with good resistance index and did not show cytotoxicity in vitro when tested against human umbilical vein endothelial cells (HUVEC) up to concentration of 50μM.

Nucleophilic substitution and ring transformation reactions with 4-chloro-6-ethyl-3-nitropyrano[3,2-c]quinoline-2,5(6H)-dione

Chloro-6-ethyl-3-nitropyrano(3,2-c)quinoline-2,5(6H)-dione (3) was obtained by nitration followed by chlorination of 4-hydroxypyranoquinoline-2,5-dione 1. Substitution reactions of compound 3 with various nucleophiles, namely: sodium azide, amines, thiophenol and malono- nitrile, led to a series of novel 4-sustituted-3-nitropyranoquinolinones. Also, nucleophilic reactions of compound 3 with hydrazine, cyanoguanidine and S-methylisothiourea, involving ring opening-ring closure of the pyranoquinolinedione nucleus, are described.

Application of Noble Metal Nanoparticles in Organic Reactions

In current organic synthesis, choice of appropriate catalysts is becoming more and more important. Among these catalysts, noble metal nanoparticles catalyst is one of the most important catalysts which has been successfully applied in hydrogenation, dehydrogenation, selective oxidation, alkylation and other reactions. At the same time, recent advances in nanotechnology allow the researchers to prepare noble metal nanoparticles with appropriate size and shape, and interestingly, properties of nano-sized noble metals are different from those of bulk metals. Therefore, noble metal nanoclusters or colloids have been attracting much attention in catalytic reactions due to their special physical and chemical properties. In this review, the applications of noble metal nanoparticles with different sizes and structures in organic reactions are described; and all the sections in this review have been subdivided according to the reaction types. Besides, the mechanism will be also briefly mentioned. Keywords: Alkylation, catalysis, catalyst, colloidal particles, coupling reaction, cycloaddition, dehydrogenation, hydrogeneration, hydroformylation, nanoparticles, noble metal nanoparticles, nanotechnology, organic synthesis, oxidation, rearrangement reaction, ring openingring closure reaction

ChemInform Abstract: Reactivity of 3-Alkyl-4-arylazomethylene-3,4-dihydro-1,2,3-benzotriazines in Protic Solvents: 1,4-Addition Reactions and Dimroth Rearrangement.

3-Alkyl-4-arylazomethylene-3,4-dihydro-1,2,3-benzotriazines 5a and 5b undergo facile 1,4-addition of methanol or ethanol to afford stable crystalline hydrazones, 6 and 8 which have been characterised by spectroscopic analysis. In particular, the nmr spectrum of 8 shows novel features due to the diastereotopic nature of the CH2 protons in the two O-ethyl groups. Compound 5b shows a property unique to the compounds in this series; refluxing this arylazomethylenetriazine in ethanol affords a rearranged product, characterised as the 1-aryl-2-cinnolinylhydrazine (9). The formation of 9 is rationalised as a ring opening-ring closure process analogous to the Dimroth rearrangement. The cinnoline 9 displays some novel chemistry arising from the facility of the arylhydrazino substituent to react with acid to give a fragmentation product, 3-methylindazole (7).

Substituted Quinolinones. Part 11. Efficient Synthesis of Different 3‐(4‐Arylidene and Hetarylidene‐5‐oxopyrazolin‐3‐yl)quinolin‐2‐ones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Substituted Quinolinones, Part 11: Efficient Synthesis of Different 3‐(4‐Arylidene and Hetarylidene‐5‐oxopyrazolin‐3‐yl) quinolin‐2‐ones

Several 3‐(4‐arylidene and hetarylidene‐5‐oxopyrazolin‐3‐yl)quinolin‐2‐ones 6–26 were synthesized in an efficient methodology utilizing both pyrazolinylquinolinone 2 and its chromenylmethylene derivative 10. Compound 2 was derivatized by Knoevenagel condensation with different carbonyl compounds. Nucleophilic ring opening–ring closure (RORC) of the compound 10 furnished the desired 4‐methylenepyarzolinone bearing novel five‐, six‐, and seven‐membered heterocycles, in good yields.

The Mechanism of Nucleophilic Substitution of 1-Alkyl-2-(tosyloxymethyl)-aziridines

The stereochemical course of nucleophilic substitution of 1-alkyl-2-(tosyloxymethyl)aziridines has been elucidated by a study using a chiral substrate, which confirmed that no initial ring opening and subsequent ring closure occurred but that instead direct substitution at the exocyclic methylene function took place. Consequently, these N-alkylaziridines exhibit a totally different reactivity towards nucleophiles as compared to the corresponding activated aziridines with an electron-withdrawing group at nitrogen, which has important stereochemical implications.

Ring Opening-Ring Closure of 4-Phenyl-1,2-dithiole-3-thione: Reaction with α,β-Unsaturated Nitriles

4-Phenyl-1,2-dithiole-3-thione ( 1 ) reacts with unsaturated nitriles including g -arylacrylo-nitrile and crotonitrile derivatives. Thiinthione ( 8 ) was the only product obtained in all cases, which resulted from initial nucleophilic attack at C-5 of the dithiole ring. On the other hand compound ( 1 ) reacted with bromine followed by some selected amino- f , g -unsaturated nitriles to afford isothiazolo[3,2-b]-[1,3]thiazine derivatives mainly from nucleophilic attack at either C-3 or ring sulfur atom.

Hetero-Diels–Alder additions to pent-4-enofuranosides: concise synthesis of hydroxylated pyrrolizidines

A new facile method for the synthesis of hydroxylated pyrrolizidines of the alexine family has been developed, which involves hetero-Diels–Alder addition of ethyl 2-nitrosoacrylate to pent-4-enofuranosides and a further two-step reductive ring opening-ring closure treatment of the cycloadduct.

Vinylphosphirane-phospholene rearrangements: pericyclic [1,3]-sigmatropic shifts or not?

The conversion of "free" and Cr(CO)(5)-complexed 2-vinylphosphiranes into 3-phospholenes via [1,3]-sigmatropic shifts was studied with density functional theory and compared with the corresponding hydrocarbon system, that is, the vinylcyclopropane-cyclopentene rearrangement. All three systems behave similarly with subtle but important differences. No intermediate was found on any of the potential energy surfaces. 2-Vinylphosphiranes have smaller rearrangement barriers than vinylcyclopropane, and those carrying the Cr(CO)(5) group have still smaller ones. The rearrangement of both anti- and syn-2-vinylphosphiranes occurs in a concerted pericyclic manner with inversion of configuration at the migrating phosphorus, requiring, respectively, 29.3 and 36.7 kcal/mol, much in contrast to the 44.6 kcal/mol demanding diradical-like process for the hydrocarbon analogue. Epimerization at the phosphorus center (syn right arrow over left arrow anti) requires approximately 32.0 kcal/mol and occurs in a single step, reflecting a diradical-like ring opening-ring closure process that can occur in both a clockwise and counterclockwise fashion. Complexation of the phosphorus center by Cr(CO)(5) results in the substantial stabilization of reagents and products and further reduces the barriers for rearrangement. The anti isomer has the lowest barrier for the [1,3]-shift (DeltaE = 20.5 kcal/mol), which is slightly less than that needed for P-epimerization and for conversion of the syn isomer, both of which are nonpericyclic processes. When a P-phenyl group is introduced, the diradical-like conversion of the syn isomer is favored over the anti isomer, in agreement with experimental reports. The influence of torquoselectivity is discussed for the rearrangements of these structures with their heavy substituents. The origin of the stabilization rendered by the Cr(CO)(5) group and its influence on the [1,3]-conversion are also analyzed. The DFT activation energies for the diradical-like [1,3]-sigmatropic shifts were verified with a multireference method.

A novel ring transformation of 5-azidothiazoles

The 4-oxoalkyl- and 4-iminoalkyl-5-azidothiazoles undergo a ring transformation with nitrogen loss at relatively low temperatures to afford 4-cyanooxazoles and 4-cyanoimidazoles, respectively. The mechanism, which is thought to involve a ring opening-ring closure process, is discussed.

Conversion of a thiohydantoin to the corresponding hydantoin via a ring-opening/ring closure mechanism

The treatment of activated N, N′ disubstituted arylthiohydantoins with methyl or ethyl iodide and sodium methoxide in DMF at room temperature affords the corresponding hydantoins in good yield. The mechanism involves an unusual ring opening-ring closure sequence which can be exploited for a novel (thio) hydantoin to (thio) urea rearrangement.