Synthesis and properties of novel 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-triones: methodology for synthesizing cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates

Novel condensation reaction of tropone with N-substituted and N,N′-disubstitued barbituric acids in Ac₂O afforded 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (8a-f) in moderate to good yields. The ¹³C NMR spectral study of 8a-f revealed that the contribution of zwitterionic resonance structures is less important as compared with that of 8,8-dicyanoheptafulvene. The rotational barriers (ΔG^‡) around the exocyclic double bond of mono-substituted derivatives 8a-c were obtained to be 14.51-15.03 kcal mol⁻¹ by the variable temperature ¹H NMR measurements. The electrochemical properties of 8a-f were also studied by CV measurement. Upon treatment with DDQ, 8a-c underwent oxidative cyclization to give two products, 7 and 9-substituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates (11a-c·BF₄⁻ and 12a-c·BF₄⁻) in various ratios, while that of disubstituted derivatives 8d-f afforded 7,9-disubstituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborate (11d-f·BF₄⁻) in good yields. Similarly, preparation of known 5-(1′-oxocycloheptatrien-2′-yl)-pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (14a-d) and novel derivatives 14e,f was carried out. Treatment of 14a-c with aq. HBF₄/Ac₂O afforded two kinds of novel products 11a-c·BF₄⁻ and 12a,c·BF₄⁻ in various ratios, respectively, while that of 14d-f afforded 11d-f. The product ratios of 11a-c·BF₄⁻ and 12a-c·BF₄⁻ observed in two kinds of cyclization reactions were rationalized on the basis of MO calculations of model compounds 20a and 21a. The spectroscopic and electrochemical properties of 11a-f·BF₄⁻ and 12a-c·BF₄⁻ were studied, and structural characterization of 11c·BF₄⁻ based on the X-ray crystal analysis and MO calculation was also performed.     

Atom-efficient and environment-friendly multicomponent synthesis of amidoalkyl naphthols catalyzed by P2O5

An atom-efficient and environment-friendly approach for the synthesis of amidoalkyl naphthols (4a-x) via multicomponent one-pot reaction of 2-naphthol (1), aromatic aldehyde (2) and amide (3) catalyzed by P₂O₅ has been developed. The present approach offers several advantages such as reduced reaction times, moderate temperature, higher yields, eco-friendly reaction condition, easy purification and economic availability of the catalyst.     

Synthesis and properties of bis(heteroazulen-3-yl)methyl cations and bis(heteroazulen-3-yl)ketones

The synthesis and properties of a novel type of bis(heteroazulen-3-yl)methyl cations, bis(2-oxo-2H-cyclohepta[b]furan-3-yl)methyl cation salt and nitrogen analogues, (9a-c·PF₆⁻) and (9a-c·BF₄⁻), as well as bis(heteroazulen-3-yl)ketones (12a-d) are studied. The synthetic method was based on a TFA-catalyzed electrophilic aromatic substitution on the heteroazulenes (6a-d) with paraformaldehyde to afford the corresponding disubstituted methane derivatives 7a-d, followed by oxidative hydrogen abstraction with DDQ, and subsequent exchange of the counter-anion by using aq. HPF₆ or aq. HBF₄. In addition, the reaction of 7a-d with 2.2 equiv. amounts of DDQ afforded carbonyl compounds 12a-d. The delocalization of the positive charge of 9a-c was evaluated by the ¹H and ¹³C NMR spectral data. The thermodynamic stability of cations 9a-c was evaluated to be in the order 9a<9b<9c on the basis of their reduction potentials measured by cyclic voltammetry (CV) and pK_R+ values (2.6-10.3) obtained spectrophotometrically. The reduction waves of cations 9a-c were irreversible, suggesting the dimerization of the radical species generated by one-electron reduction. This was demonstrated by the reduction of 9a·BF₄⁻ with Zn powder to give dimerized product 14a. In addition, the quenching of 9a·BF₄⁻ with MeOH/NaHCO₃ gives ether derivative 15a, which is proposed for the precursor for synthesizing tris(heteroazulene)-substituted methyl cations bearing two different heteroazulene-units.     

Synthesis and structure of {{amino(triorganosilyl)carbene}pentacarbonyltungsten(0)} complexes and attempted synthesis of {[2-bis(trimethylsilyl)methyl-3-triorganosilyl-2H-azaphosphirene-κP]pentacarbonyltungsten(0)}

First examples of tungsten aminocarbene complexes [(OC₅)W{C(SiR¹_nR²_3-n)NH₂}] 2a-d (R¹ = Ph, R² = Me) were synthesized via ammonolysis of the corresponding methoxycarbene complexes 1a-d. They were characterized by NMR spectroscopy, MS, IR, UV/Vis and elemental analysis, and in the case of the C-triphenylsilyl derivative 2a by single-crystal X-ray structure analysis. The reaction of P-chloro alkylidenephosphane 3 with complexes 2a-d, meant to give 2H-azaphosphirene complexes, was monitored by ³¹P NMR spectroscopy to reveal the formation of the products 4-7, which were presumably formed via decomposition of the transient complexes 10a-d.     

Synthesis and hybridization affinity of oligodeoxyribonucleotides incorporating 4-N-(N-arylcarbamoyl)deoxycytidine derivatives

Modified oligodeoxynucleotides incorporating 4-N-(N-arylcarbamoyl)-dC derivatives 1a-c were synthesized. The ¹H NMR spectra of 1a-c suggest that the carbamoyl group forms an intramolecular hydrogen bond with the cytosine ring nitrogen atom so that formation of a Watson-Crick base pair with the complementary guanine base is inhibited. The hybridization properties of oligodeoxynucleotides containing 1a-c were investigated by use of T_m analysis. The hybridization properties of 4-N-(N-phenylcarbamoyl)-dC (1a) were similar to those of 4-N-(N-alkylcarbamoyl)-dC derivatives reported previously. In sharp contrast to 1a, it turned out that 4-N-(N-napht-1-yl) and (N-quionol-5-yl)-dC (1b,c) have a unique property as a universal base.     

Carbonylation studies of Pd-methyl complexes modified with 1,4-Cs-symmetrical diphosphine ligands

Neutral palladium methyl chloride 2a-d [PdCH₃(PˆP′)Cl] and cationic palladium methyl acetonitrile mono-triflate 3a-d [PdCH₃(PˆP′)(CH₃CN)](CF₃SO₃) complexes were synthesized and fully characterized (PˆP′ = 1a-d). All the neutral and cationic complexes containing a C_s-symmetric diphosphine exist in solution as a mixture of geometric isomers. The carbonylation at atmospheric pressure of the neutral and cationic complexes revealed that migratory insertion of carbon monoxide is not stereospecific in these systems. The neutral and cationic acyl complexes were formed in situ as mixtures of stereoisomers, which were characterized by means of NMR spectroscopy.The crystal structures of [Pd(1a)Cl]₂(OTf)₂ and 2d are described.     

Assembly of diverse structural types of organotellurium compounds in the reactions of (4-MeO-C6H4)2TeO with pyridine carboxylic acids

The reactions of Ar₂TeO (Ar = 4-MeO-C₆H₄) with 2-, 3- and 4-pyridine carboxylic acids (LH) afforded different organotelluroxane structural types depending on the stoichiometry of the reactants and the conditions of the reaction. Ar₂Te(L)OH (1a-1c) are formed in a 1:1 reaction of Ar₂TeO with LH in the presence of water. On the other hand a 1:2 reaction under anhydrous conditions leads to the formation of Ar₂TeL₂ (2a-2c). A 2:2 reaction under anhydrous conditions affords the ditelluroxanes Ar₂Te(L)OTe(L)Ar₂ (3a-3c) while tritelluroxanes Ar₂Te(L)OTeAr₂OTe(L)Ar₂ (4a-4c) are formed in 3:2 reactions. Interestingly, 3a-3c are formed in the reaction of 2a-2c with Ar₂TeO. The former can be hydrolyzed to 1a-1c while the latter upon reaction with Ar₂TeO lead to the formation of the tritelluroxanes 4a-4c. Attempts to metalate 2a with PdCl₂(MeCN)₂ leads to a transfer of the carboxylate ligand to palladium affording Ar₂TeCl₂ and PdL₂. X-ray crystal structures of representative examples of the family of 1, 2 and 3 reveal interesting supramolecular structures and the formation of a novel [TeO]₂ structural unit. The latter results from intermolecular secondary Te?O interactions.     

An efficient microwave assisted synthesis of novel class of Rhodanine derivatives as potential HIV-1 and JSP-1 inhibitors

(Z)-5-(2-(1H-Indol-3-yl)-2-oxoethylidene)-3-phenyl-2-thioxothiazolidin-4-one (7a-q) derivatives have been synthesized by the condensation reaction of 3-phenyl-2-thioxothiazolidin-4-ones (3a-h) with suitably substituted 2-(1H-indol-3-yl)-2-oxoacetaldehyde (6a-d) under microwave condition. The thioxothiazolidine-4-ones were prepared from the corresponding aromatic amines (1a-e) and di-(carboxymethyl)-trithiocarbonyl (2). The aldehydes (6a-h) were synthesized from the corresponding acid chlorides (5a-d) using HSnBu₃.     

Structure of N,C,N-chelated organotin(IV) fluorides

The set of starting tri-, di- and monoorganotin(IV) halides containing N,C,N-chelating ligand (L^NCN = {1,3-[(CH₃)₂NCH₂]₂C₆H₃}⁻) has been prepared (1-5) and two compounds structurally characterized ([L^NCNPh₂Sn]⁺I₃⁻ (1c), L^NCNSnBr₃ (5)) in the solid state. These compounds were reacted with KF with 18-crown-6, NH₄F or L^CNnBu₂SnF to give derivatives containing fluorine atom(s). Triorganotin(IV) fluorides L^NCNMe₂SnF (2a) and L^NCNnBu₂SnF (3a) revealed monomeric structural arrangement with covalent Sn-F bond both in the coordinating and non-coordinating solvents, except the behaviour of 3a that was ionized in the methanol solution at low temperature. The products of fluorination of L^NCNSnPhCl₂ (4) and 5 were described by NMR in solution as the ionic hypervalent fluorostannates or the oligomeric species reacting with chloroform, methanol or moisture to zwitterionic monomeric stannate L^NCN(H)⁺SnF₄⁻ (5c), which was confirmed by XRD analysis in the solid state.     

Facile synthesis of 4-phenylquinolin-2(1H)-one derivatives from N-acyl-o-aminobenzophenones

An efficient synthesis of 4-phenylquinolin-2(1H)-one derivatives has been achieved in a one-pot reaction from N-acyl-o-aminobenzophenones 1a-c (a: acyl=acetyl; b: acyl=propanoyl; c: acyl=heptanoyl) using NaH as a base. Treatment of 1 with NaH provided the quinolones 2a-c with 62-83% yields, whereas the reaction in the presence of alkyl iodide (alkyl=methyl, ethyl, n-octyl) gave the corresponding N-alkylated quinolones 3a-g in 75-95% yields. The alkylation reaction of 4-phenylquinolin-2(1H)-one 2a with alkyl halide gave a mixture of N-alkylated and O-alkylated products. Comparison of IR and NMR data of the N-alkylated and O-alkylated compounds with those of 2a-c indicated that 2a-c exist as the lactam form.     

A highly stereoselective preparation of CF3-substituted 1-aryl-1,2-diphenylethenes: application to the synthesis of panomifene

β-CF₃-α,β-diphenylvinyl sulfide 3a was prepared stereoselectively in 77% yield from the reaction of 2 with phenyllithium at room temperature for 5 h. Oxidation of 3a with MCPBA afforded the corresponding vinyl sulfone 4a, in which (E)-4a can be crystallized in a mixture of CH₂Cl₂ and hexane. The addition-elimination reaction of (E)-4a with phenyllithium having substituents on the benzene ring provided 5a-j in 51-82% yields stereospecifically. Similarly, the treatment of (E)-4a with p-chloroethoxyphenyllithium in the presence of 12-crown-4 (20 mol %) at −10 °C, followed by slowly warming to room temperature, resulted in the formation of the corresponding panomifene precursor 6 in 82% yield.     

Synthesis, crystal structure and non-linear optical properties of boronates derivatives of salicylideniminophenols

The condensation in one step of a series of salicylaldehydes and 2-amino-5-nitrophenol with 1-naphthylboronic acid, 2-naphthylboronic acid, and o-tolylboronic acid to give the corresponding boronates 1a-3a, 1b-3b and 1c-3d, is reported. The X-ray crystal structures of 1a, 2b and 3b allowed determining the α- and β-angle between the stilbene skeleton and the aryl or naphthylboronic fragments; these values are indicative of different conformations for the aryl moieties around the (B-C) boron-carbon bond which could potentially modulate the electronic properties on the boron stilbene compounds. All compounds were characterized by ¹H, ¹¹B and ¹³C NMR spectroscopy, UV, IR and mass spectrometry. Second- and third-order non-linear optical characterizations were also performed by EFISH and THG Maker Fringe techniques, respectively. Compounds 3a-3d containing an -N(Et)₂ donor group gave the best NLO response in second- and third-order.     

SEAr-SNAr couplings of indolizines and related pyrrole derivatives with superelectrophilic nitrobenzoxadiazoles

The nucleophilic aromatic substitutions of 7-chloro-4,6-dinitrobenzofurazan (DNBZ-Cl) and 7-chloro-4,6-dinitrobenzofuroxan (DNBF-Cl) with a series of differently substituted indolizines (5a-f) and a series of dihyropyrroloisoquinolines (11a-f) have been investigated. In accord with previous reports emphasizing the superelectrophilic character of these compounds in σ-complexation processes, DNBZ-Cl and DNBF-Cl react very readily and quantitatively with the weak carbon nucleophiles 5a-f and 11a-f at room temperature in acetonitrile. In the case of DNBZ-Cl, the resulting products (7Z,a-f and 12Z,a-f) are those expected from the displacement of the chlorine atom through a S_EAr-S_NAr mechanism. A significant result is that these compounds, despite the lack of coplanarity of the two rings, are characterized by an intense intramolecular charge transfer between the donor pyrrole-type moiety and the electron-deficient acceptor DNBZ moiety. Contrasting with this behaviour, the DNBF-Cl reactions show a totally different pattern, proceeding with loss of the N-oxide functionality and expansion of the pyrrole moiety to afford stable zwitterionic spiro adducts (8F,a-f and 13F,a-f) of a so far unknown type. Rapid NMR recordings have revealed that the formation of these adducts occurs after initial formation of the expected substitution products 7F,a-f and 12F,a-f. A mechanism accounting for the overall rearrangement leading to the spirobenzofurazan adducts is suggested. It is based on an initial nucleophilic attack of the oxygen atom of the N-oxide functionality at the electron-deficient and strongly olefinic C-C coupling bond generated by the aforementioned intramolecular charge transfer. This results in the formation of an unstable five-membered isoxazole ring whose decomposition goes along with loss of the N-oxide functionality and enlargement of the pyrrole moiety into a pyridine one. Also discussed are the factors accounting for the high thermodynamic stability of the spiro adducts, and their relevance to the stability of previously reported spiro adducts.     

Hydrogen-bonded networks from η-semiquinone complexes of manganese tricarbonyl

The cationic manganese tricarbonyl complexes containing η⁶-2-methylhydroquinone (2a), η⁶-2,3-dimethylhydroquinone (3a), η⁶-2-t-butylhydroquinone (4a), η⁶-tetramethylhydroquinone (5a) and η⁶-4,4′-biphenol (6a) are readily deprotonated to the corresponding neutral (η⁵-semiquinone)Mn(CO)₃ (2b-6b) and anionic (η⁴-quinone)Mn(CO)₃⁻ (2c-5c) complexes. The X-ray structures of 2b-6b feature strong intermolecular hydrogen bonding interactions that result in the formation of supramolecular organometallic networks. Significantly, the substitution pattern at the semiquinone ring affects the stereochemistry of the hydrogen bonding interactions. NMR spectra of 2b, 3b and 5b reveal dynamic hydrogen bonding in solution.     

Quinoxalines. Part 12: Synthesis and structural study of 1-(thiazol-2-yl)-1H-pyrazolo[3,4-b]quinoxalines—the dehydrogenative cyclization with hydroxylamine hydrochloride

Starting with 2-acetylquinoxaline a novel class of heterocyclic compounds, the 1-(thiazol-2-yl)-1H-pyrazolo[3,4-b]quinoxalines 4, were prepared by following two different synthetic procedures: 2-acetylquinoxaline reacted with thiosemicarbazide to the thiosemicarbazones 1a which was (i) cyclized with α-halogeno ketones to the thiazoles 3. These compounds were dehydrogenated in acidic medium to the title compounds 4. (ii) The thiosemicarbazone 1a could be also dehydrogenated using NH₂OH·HCl to the thioamide 5a and these, finally, were cyclized with α-halogeno ketones to the title compounds 4. Only thiazole 3a was isolated, the other thiazoles 3 were dehydrogenated in a one-pot procedure. From the thioamide 5a also both the compounds 9, by reacting with dibromodiacetyl, and 10, by treatment with dimethyl acetylenedicarboxylate, were obtained. The analysis of both the ¹H and ¹³C NMR spectra was not straightforward but could be attained finally by employing the whole arsenal of 1D and 2D NMR spectroscopy.     

Synthesis, properties, and oxidizing function of 6-substituted 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]pyrrole-8(7H),10(9H)-dionylium tetrafluoroborates

Uracil-annulated heteroazulenes, 6-substituted 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]pyrrole-8(7H),10(9H)-dionylium tetrafluoroborates 7a,b·BF₄⁻, which are the isoelectronic compounds of 5-dezazaflavin, were synthesized. X-Ray crystal analysis and MO calculations were carried out to clarify the structural characteristics of 7a,b·BF₄⁻. The stability of cations 7a,b is expressed by the pK_R+ values which were determined spectrophotometrically to be 10.9 and 11.2, respectively. The electrochemical reduction of 7a,b exhibited high reduction potentials at −0.84 and −0.87 (V vs Ag/AgNO₃) upon cyclic voltammetry (CV). A good linear correlation between the pK_R+ values and reduction potentials (E1_red) of 7a,b·BF₄⁻ and reference compounds 4·BF₄⁻ and 5·BF₄⁻ was obtained. In a search of the reactivity, reactions of 7a,b·BF₄⁻ with some nucleophiles, hydride and diethylamine, were carried out to clarify that the introduction of nucleophiles to give regio-isomers is dependent on the nucleophile. The photo-induced oxidation reactions of 7a,b·BF₄⁻ toward some alcohols under aerobic conditions were carried out to give the corresponding carbonyl compounds in more than 100% yield [based on compounds 7a,b·BF₄⁻], suggesting the oxidizing function of 7a,b·BF₄⁻ toward alcohols in the autorecycling process.     

A simple and highly efficient method for the synthesis of chalcones by using borontrifluoride-etherate

Chalcones are secondary metabolites of terrestrial plants, precursors for the biosynthesis of flavonoids and exhibit various biological activities. Condensation of substituted acetophenones (2a-12a) with various aromatic aldehydes (1b-7b) in the presence of BF₃-Et₂O at room temperature gave chalcones in 75-96% yield.     

Syntheses, spectroscopic and structural characterizations and metal ion binding properties of Schiff bases derived from 4′-aminobenzo-15-crown-5

A series of benzyloxybenzaldehyde derivatives (1-4) were synthesized by the reactions of 4-(bromomethyl)benzonitrile with 4-hydroxy-3-methoxybenzaldehyde (vanillin), 2-hydroxy-3-methoxybenzaldehyde (o-vanillin), 2-hydroxy-4-methoxybenzaldehyde and 2-hydroxy-5-methoxybenzaldehyde. Condensation reactions among the new benzyloxybenzaldehyde derivatives (1-4) with 4′-aminobenzo-15-crown-5 yielded the new Schiff base compounds (5-8). Sodium complexes (5a-8a) and potassium complexes (5b-8b) were prepared with NaClO₄ and KI, respectively. All of these synthesized compounds were characterized on the basis of FT-IR, ¹H and ¹³C NMR, mass spectrometry and elemental analyses data. The solid state structures of compounds 8 and 5a were determined by X-ray crystallography. The extraction abilities of compounds 5-8 were also evaluated in CH₂Cl₂ by using several main group and transition metal picrates, such as Na⁺, K⁺, Pb²⁺, Cr³⁺, Ni²⁺, Cu²⁺ and Zn²⁺.     

One pot synthesis of new benzopyranopyridines via Friedlander condensation

A facile, green synthetic route to new benzopyrano [2,3-b] pyridines in excellent yield via Friedlander condensation has been developed by the reaction of 2-amino-3-formylchromone 1a-b and cyclic active methylene compounds 2a-e in the presence of Zn(l-proline)₂ as an efficient, stable, and inexpensive Lewis acid catalyst in water. The present methodology offers several advantages such as shorter reaction time, mild reaction conditions, simple operational procedure, recyclable catalyst, and safe to the environment.     

Chemically modified oximato complexes of titanium(IV) isopropoxide as new precursors for the sol-gel preparation of nano-sized titania: Crystal and molecular structure of [Ti{ONC10H16}4·2CH2Cl2]

Reactions of [Ti(OPrⁱ)₄] with various oximes, in anhydrous refluxing benzene yielded complexes of the type [Ti{OPrⁱ}_4−n{L}_n], where, n = 1-4 and LH = (CH₃)₂CNOH (1-4), C₉H₁₆CNOH (5-8) and C₉H₁₈CNOH (9-12). The compounds were characterized by elemental analyses, molecular weight measurements, FAB-mass, FT-IR and NMR (¹H, ¹³C{¹H}) spectral studies. The FAB-mass spectra of mono- (1), and di- (2), (6), (10) substituted products indicate their dimeric nature and that of tri- (3) and tetra- (4), (8) substituted derivatives suggest their monomeric nature. Crystal and molecular structure of [Ti{ONC₁₀H₁₆}₄·2CH₂Cl₂] (8A) suggests that the oximato ligands bind the metal in a dihapto η²-(N, O) manner, leading to the formation of an eight coordinated species. Thermogravimetric curves of (3), (6) and (10) exhibit multi-step decomposition with the formation of TiO₂ as the final product in each case, at 900 °C. Low temperature (∼600 °C) sol-gel transformations of (2), (3), (4), (6), (7) and (8) yielded nano-sized titania (a), (b), (c), (d), (e) and (f), respectively. Formation of anatase phase in all the titania samples was confirmed by powder XRD patterns, FT-IR and Raman spectroscopy. SEM images of (a), (b), (c), (d), (e) and (f) exhibit formation of nano-grains with agglomer like surface morphologies. Compositions of all the titania samples were investigated by EDX analyses. The absorption spectra of the two representative samples, (a) and (f) indicate an energy band gap of 3.17 eV and 3.75 eV, respectively.