Synthesis Of Thiophenes Research Articles

Synthetic Utility of Arylmethylsulfones: Annulative π-Extension of Aromatics and Hetero-aromatics Involving Pd(0)-Catalyzed Heck Coupling Reactions.

A straightforward and general method for the synthesis of annulated thiophene, dibenzothiophene, and carbazoles analogues has been achieved involving alkylation of 2-bromo-1-(phenylsulfonylmethyl)arene/heteroarene with arylmethyl bromides/heteroarylmethyl bromides using t-BuOK as a base in DMF, followed by Pd(0)-mediated intramolecular Heck coupling in the presence of K2CO3 in DMF at 80-140 °C. The attractive feature of this protocol is that a wide variety of π-conjugated heterocycles could be readily accessed by an appropriate choice of arylmethylsulfones and benzylic bromides.

Short Review on the Synthesis of Thiophene, Pyrazole, and Thiazole Derivatives

The review summarizes the synthesis of different thiophene, pyrazole, and thiazole derivatives by refluxing 9a in ethanol with a catalytic amount of TEA or leaving it in DMF containing potassium carbonate at room temperature overnight to afford the corresponding thiophene derivative 10a. In addition, cyclization of Schiff bases with thioglycollic acid in the presence of a catalytic amount of ZnCl2 yielded novel thiophene derivatives. Condensation of 2‐substituted‐4‐methylythio semi‐carbazides 92 with carbonyl compounds under strong acidic conditions afforded 2‐thiazolines. Also, carboxylic acid reacted with 2‐thioethylamine in the presence of triphenylphosphine and triethylamine to afford 2‐thiazolines 98.

Synthesis of Thiophene-Based Optical Ligands That Selectively Detect Tau Pathology in Alzheimer's Disease.

The accumulation of protein aggregates is associated with many devastating neurodegenerative diseases and the development of molecular ligands able to detect these pathological hallmarks is essential. Here, the synthesis of thiophene based optical ligands, denoted bi-thiophene-vinyl-benzothiazoles (bTVBTs) that can be utilized for selective assignment of tau aggregates in brain tissue with Alzheimer's disease (AD) pathology is reported. The ability of the ligands to selectively distinguish tau deposits from the other AD associated pathological hallmark, senile plaques consisting of aggregated amyloid-β (Aβ) peptide, was reduced when the chemical composition of the ligands was altered, verifying that specific molecular interactions between the ligands and the aggregates are necessary for the selective detection of tau deposits. Our findings provide the structural and functional basis for the development of new fluorescent ligands that can distinguish between aggregated proteinaceous species consisting of different proteins. In addition, the bTVBT scaffold might be utilized to create powerful practical research tools for studying the underlying molecular events of tau aggregation and for creating novel agents for clinical imaging of tau pathology in AD.

Synthesis of thiophene and N-substituted thieno[3,2-d] pyrimidine derivatives as potent antitumor and antibacterial agents.

A novel series of carbamothioylamino-benzene-sulfonamide-thiophene-carboxylates 4a-c and thieno[3,2-d]pyrimidin-2-yl-amino-benzene-sulfonamides 5a-c were synthesized in a series of synthetic steps and were used as key intermediates for the synthesis of thienotriazolopyrimidine-benzene-sulfonamide derivatives 6a-c and 7a-c. Thieno[3,2-d]pyrimidinones (8 and 9) were also prepared. Compound 9 was used as an intermediate for the synthesis of imidazole/1,2,4-triazole and tetrazine functionalized thieno[3,2-d]pyrimidine derivatives (10-12). Pyrrole derivatives/pyrrolopyrimidine/pyrrolotriazolopyrimidine functionalized thiophenes (15-19) were also synthesized. Structures of the newly synthesized compounds were established by elemental analysis and spectral data. Most of the newly synthesized compounds were evaluated for their in vitro activity against three human tumor cell lines, namely, liver cancer (HepG-2), colon cancer (HT-29) and lung cancer (NCI-H460), using doxorubicin as standard. Compounds 16 (GI50 = 0.02, 0.04 and 0.06 μmol L-1, resp.) and 19b (GI50 = 0.02, 0.03 and 0.05 μmol L-1, resp.) showed higher activity against all cell lines than doxorubicin. Most of the compounds were also screened for antibacterial activity using ciprofloxacin as standard drug. Compounds 4b and 6b, both containing benzenesulfonamide linked to N-, 10 bearing imidazole moiety, and 15 and 19b,c with a thiophene-2-carboxylic acid chain, exhibited high activity against Gram-positive and Gram-negative bacteria.

A facile synthesis and characterization of some new thiophene based heterocycles

Synthesis of some new pyrazole, pyridazine, pyridine, chalcone, hydrazone derivatives containing thiophene ring has been carried out by simple, efficient and good yielding routes starting from the versatile and readily accessible ethyl 5-acetyl-4-phenyl- 2-(phenylamino)thiophene-3-carboxylate (1). The structure of the products has been elucidated from their spectral and elemental analyses. X-ray crystallography of compound 1 confirmed its structure.

Synthesis, characterization and photovoltaics studies of 3-alkylthienyl thiophene based polymers prepared via direct arylation polymerization

Synthesis, characterization and photovoltaics studies of 3-alkylthienyl thiophene based polymers prepared via direct arylation polymerization

A convenient synthesis of new 5,11-dihydroindolo[3,2-b]carbazoles bearing thiophene, 2,2′-bithiophene or 2,2′:5′,2″-terthiophene units at C-2 and C-8 positions

A series of new 5,11-dihydroindolo[3,2-b]carbazole derivatives, containing functional thiophene, 2,2′-bithiophene or 2,2′:5′,2″-terthiophene moieties at both C-2 and C-8 positions of their fused scaffolds, have been obtained from 2,8-diacetyl-substituted 5,11-dihydroindolo[3,2-b]carbazole compounds through the effective strategy, which is based on the sequence of two reactions, namely the Vilsmeier–Haack formylation and the Fiesselmann thiophene synthesis. The starting acetyl substituted materials have been transformed into the corresponding 3-chlorocrylaldehyde-containing compounds by treatment with POCl3-DMF complex, followed by the reaction with alkyl thioglycolates or α-mercaptoacetone in the presence of triethylamine to afford 2-carboalkoxythiophene- or 2-acetylthiophene-linked derivatives. 2-Acetylthiophene derivatives have further been involved into the same sequence of reactions to obtain 2,2′-bithiophene-, and 2,2′:5′,2″-terthiophene-linked 5,11-dihydroindolo[3,2-b]carbazole compounds.

Design and environmentally benign synthesis of novel thiophene appended pyrazole analogues as anti-inflammatory and radical scavenging agents: Crystallographic, in silico modeling, docking and SAR characterization

Oxidative-stress induces inflammatory diseases and infections caused by drug-resistant microbial strains are on the rise necessitating the discovery of novel small-molecules for intervention therapy. The current study presents an effective and new green protocol for the synthesis of thiophene-appended pyrazoles through 3+2 annulations method. Chalcones 3(a-g) were prepared from 5-chloro-2-acetylthiophene and aromatic aldehydes by Claisen-Schmidt approach. The reaction of chalcones 3(a-g) with phenylhydrazine hydrochlorides 4(a-b) in acetic acid (30%) medium and also with freshly prepared citrus extract medium under reflux conditions produced the thiophene appended pyrazoles 5(a-l) in moderate yields. Structures of synthesized new pyrazoles were confirmed by spectral studies, elemental analysis and single crystal X-ray diffraction studies. Further, preliminary assessment of the anti-inflammatory properties of the compounds showed that, amongst the series, compounds 5d, 5e and 5l have excellent anti-inflammatory activities. Further, compounds 5c, 5d, 5g, and 5i exhibited excellent DPPH radical scavenging abilities in comparison with the standard ascorbic acid. Furthermore, using detailed structural modeling and docking efforts, combined with preliminary SAR, we show possible structural and chemical features on both the small-molecules and the protein that might contribute to the binding and inhibition.

Synthesis and Characterisation of Novel Thiophene Based Azomethine Polymers and Study of Their Liquid Crystalline, Electrochemical and Optoelectronic Properties

This work reports the synthesis, structural characterisation, liquid crystallinity, luminescence and electroluminescence of novel thiophene azomethine polymers. The polymers under study were prepared via oxidative polymerisation of four novel monomers at room temperature using iron (III) chloride. The chemical structures of the prepared monomers and polymers were confirmed by infrared and 1H and 13CNMR spectroscopy. Molecular masses were determined for monomers and polymers by gas/liquid chromatography-mass spectrometry (GC/LC-MS) and by gel-permeation (size exclusion) chromatography (SEC), respectively. Thermal stability studies of the prepared materials were achieved by thermogravimetric analysis (TGA), and the onset of weight loss To and the endset Tmax were calculated from the thermograms. Liquid crystalline mesophases and phase changes of the monomers and polymers were studied by differential scanning calorimetry (DSC) and polarised optical microscopy (POM), and the glass transition temperatures Tg of the polymers were determined from the DSC curves. The electrochemical band gaps, HOMO and LUMO energy levels were measured by cyclic voltammetry. UV-visible absorption-emission spectra (liquid and solid films) of the polymers were obtained at room temperature with different solvents. Optical band gaps were calculated from the absorption edges, and were in good agreement with those estimated from cyclic voltammetry. Mixing the polymers with lanthanide salts such as EuCl3 and YbCl3 gave modified fluorescence, and the light emitted was much more intense than that from the pure polymers. Polymer based light-emitting diodes (PLEDs) were fabricated by spin coating, and their current-voltage characteristics were measured. In preliminary work, the polymer devices were found to produce electroluminescent spectra similar to the PL spectra of the corresponding samples. Molecular modelling studies were performed both on polymer segments and monomer molecules; the absorption spectra of the prepared polymers, HOMO and LUMO energy levels were calculated with ZINDO using AMI geometry optimisation.

Synthesis of Fused Furans and Thiophenes via Ruthenium-Catalyzed Atom-Transfer [2+2+1] Cycloadditions of α,ω-Diynes

Furans and thiophenes are important five-membered heterocyclic compounds that are found in natural products, functional materials, and pharmaceutics. This account outlines our studies on ruthenium-catalyzed atom-transfer [2+2+1] cycloadditions toward the synthesis of fused furans and thiophenes.1 Introduction2 Synthesis of Furans using Dimethyl Sulfoxide as the Oxygen ­Donor3 Synthesis of 2-Silylfurans Using Nitrones as Oxygen Donors4 Synthesis of Thiophenes Using Thiocarbonyls as Sulfur Donors5 Conclusions

Synthesis, Cytotoxic and Anti-proliferative Activity of Novel Thiophene, Thieno[2,3-b]pyridine and Pyran Derivatives Derived from 4,5,6,7-tetrahydrobenzo[b]thiophene Derivative.

Novel tetrahydrobenzo[b]thienopyrole derivatives are synthesized from 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene (1) through its reaction with α-chloroacetone to give the corresponding N-alkyl derivative 3. Compound 3 undergoes ready cyclization in sodium ethoxide solution to give the tetrahydrobenzo[b]thienopyrrole 4. The latter compound 4 is used as the key starting material for the synthesis of thiophene, thieno[2,3-b]pyridine and pyran derivatives. The cytotoxicity of the synthesized products towards the human cancer cell lines namely gastric cancer (NUGC), colon cancer (DLD-1), liver cancer (HA22T and HEPG-2), breast cancer (MCF-7), nasopharyngeal carcinoma (HONE-1) and normal fibroblast (WI-38) cell lines are measured. Compounds 4, 7a, 7b, 8a, 8b, 10c, 10d, 10f, 12a, 12b, 14b and 15b exhibit the optimal cytotoxic effect against cancer cell lines. Compounds 7b and 14b show the maximum inhibitory effect and these are much higher than the reference CHS-828 (pyridyl cyanoguanidine). On the other hand, the anti-proliferative evaluations of these compounds with high potency against the cancer cell lines L1210, Molt4/C8, CEM, K562, K562/4 and HCT116 show that compounds 7b and 8b give IC50's against Molt4/C8 and CEM cell lines higher than that of the reference, doxorubicin.

Synthesis of Novel Five- and Six-Membered Ferrocene-Containing Heterocycles and Heteroaromatics via Cyclocondensation of 1-Ferro­cenyl-3,3-bis(methylthio)prop-2-en-1-one with Various Bifunctional Nucleophiles

Synthesis and reactions of 1-ferrocenyl-3,3-bis(methylthio)prop-2-en-1-one as a versatile 1,3-bielectrophilic synthon leading to a range of novel ferrocene-containing five- and six-membered heterocycles and heteroaromatics has been reported. Thus its cyclocondensation with various bifunctional heteronucleophiles, such as hydrazine­, phenylhydrazine, hydroxylamine, guanidine, and amidine, affords­ a range of ferrocene-substituted pyrazoles, oxazoles, and pyrimidines in highly regioselective manner. Synthesis of few ferrocenyl-substituted pyridines and thiophenes has also been described. Similarly cycloaromatization of this ferrocene-substituted α-oxoketene dithioacetal with anions generated from (het)arylacetonitriles provides a facile entry to ferrocene-substituted heteroaromatics in good yields. Synthesis of a few 2-ferrocenylvinyl-substituted heterocycles, such as pyrazoles, isoxazoles, and pyrimidines, via cyclocondensation of a novel 5-ferrocenyl-1,1-bis(methylthio)penta-1,4-dien-3-one with phenylhydrazine, hydroxylamine, and guanidine has also been reported.

Synthesis and Cytotoxicity of Thiophene, Thieno[2,3-C]Pyrazole, Thieno[2,3-D]Pyrimidine and Pyridine Derivatives Derived from 2-Acetylfuran

This work deals with the synthesis and cytotoxicity of some heterocyclic compounds starting from 2-acetylfuran. The title compound was used for the synthesis of thiophene derivative 3 through its reaction with elemental sulfur and ethyl cyanoacetate. Compound 3 was used for the synthesis of thiophene, thieno[2,3-c]pyrazole, thieno[2,3-d]pyrimidine and pyridine derivatives through its reaction with different reagents. The newly synthesized compounds were screened through three cancer cell lines. Compound 13b showed the highest potency among the synthesized compounds.

3-Cyanoallyl boronates are versatile building blocks in the synthesis of polysubstituted thiophenes.

We report the preparation of hitherto unprecedented 3-cyanoallyl boronates using condensation of the parent α-boryl aldehyde and nitriles. The resulting allyl boronates have been used to generate a wide range of borylated thiophenes, which represent a valuable class of heterocycles in modern drug discovery. Subsequent Suzuki-Miyaura cross-coupling enabled the synthesis of pharmaceutically important 3,5-disubstituted aminothiophenes. Moreover, late stage functionalization gave access to borylated bromothiophene and thieno[2,3-b]pyridines.

Synthesis of Some Novel Thiophene and Thiazole Derivatives and Their Antimicrobial Evaluation

Synthesis of Some Novel Thiophene and Thiazole Derivatives and Their Antimicrobial Evaluation

Synthesis and properties of thiophene- and quinoxaline-based random copolymers for organic photovoltaics

In this study, a series of polymers (denoted as PTQxFs) were prepared from random copolymers—poly[(5,8-(6,7-difluoro-2,3-dihexylquinoxaline))-alt-(2,5-thiophene)]-ran-[(2,5-(3-dodecylthiophene))-alt-(2,5-thiophene)]—via Pd(0)-catalyzed Stille polymerization using thiophene as the electron-rich unit and 6,7-difluoro-2,3-dihexylquinoxaline as an electron-deficient unit, which is newly synthesized by our group. This series of polymers were utilized for organic photovoltaics, and their absorption spectra, energy levels, and photovoltaic properties were investigated. The two fluorine atoms in the 6,7-difluoro-2,3-dihexylquinoxaline unit, exhibiting strong electron-withdrawing properties, enhanced the open-circuit voltage of solar cell devices due to the decrease of HOMO energy levels. With increasing number of 6,7-difluoro-2,3-dihexylquinoxaline units in the random copolymers, the HOMO energy levels decreased from −5.33 eV for PTQxF1 to −5.50 eV for PTQxF9, resulting in increased open-circuit voltage.

Regioselective Synthesis of Dihydrothiophenes and Thiophenes via the Rhodium-Catalyzed Transannulation of 1,2,3-Thiadiazoles with Alkenes.

A method for the regioselective synthesis of a wide range of dihydrothiophenes was developed from the rhodium-catalyzed transannulation of 1,2,3-thiadiazoles with aliphatic, aromatic, and heteroaromatic alkenes. Tandem rhodium-catalyzed transannulation of 1,2,3-thiadiazoles with alkenes followed by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) oxidation was also demonstrated for the one-pot regioselective synthesis of various thiophenes. Advantages of the present method include a broad substrate scope, wide functional group compatibility, and high regioselectivity.

ChemInform Abstract: Synthesis of Thiophenes in a Deep Eutectic Solvent: Heterocyclodehydration and Iodocyclization of 1‐Mercapto‐3‐yn‐2‐ols in a Choline Chloride/Glycerol Medium.

AbstractThe deep eutectic solvent system can be recycled and reused several times without any loss in yields.

Utility of β-diketones in heterocyclic synthesis: Synthesis of new tetrahydro-pyrimidinethione, pyrazole, thiophene, dihydropyridine, dihydropyrane, pyridazine derivatives and investigation of their antimicrobial activity

A series of many important diverse number of fused heterocyclic systems were prepared from the reaction of 1-(2-hydroxynaphthalen-1-yl)-3-phenylpropane-1,3-dione with some bifunctional nucleophiles, these reactions mainly proceed via condensation of 1-(2-hydroxynaphthalen-1-yl)-3-phenylpropane-1,3-dione with the aldehydic function followed by nucleophilic attack. Structures of the new compounds were established by elemental analyses and spectral data. Some of the products were also screened in vitro for their antimicrobial activity.

ChemInform Abstract: A New General Method for the Synthesis of Thiophenes Through Acid Mediated Cyclization of Mixed Acetals Derived from β‐Oxodithiates and Bromoacetaldehyde Acetal.

β-oxodithioates react with bromoacetaldehyde diethylacetal in the presence of anhydrous potassium carbonate in dimethyl formamide at 80 °C to yield the corresponding mixed acetals. These acetals undergo smooth cyclization in the presence of ethanolic orthophosphoric acid to afford the corresponding 2-methylthio-3-acyl/aroyl/heteroaroyl thiophenes in 64–85% high overall yields.