Syntheses with heterocyclic β-enaminonitriles: An expeditious synthetic approach to polyfunctionally substituted 5-phenylsulfonylthiophenes and their fused derivatives

Summary Phenylsulfonylacetophenones1 react with a mixture of elemental sulfur and malononitrile to yield the corresponding 2-amino-4-aryl-5-phenylsulfonylthiophene-3-carbonitriles2. Compound2a could be annelated to the corresponding thieno[2,3-d]pyrimidine and thieno[2,3-c]-pyrazole derivatives3 and5 upon reaction with nitrogen nucleophiles (cyanamide and hydroxylamine hydrochloride), respectively. The applicability and synthetic potency of5 to develop a facile convenient route to the polyfunctionally substituted thieno[2,3:3,4]pyrazolo[1,5-a]pyrimidines8, 14, 17, 20, and21 is reported. Chemical and spectroscopic evidences for the structures of the new compounds are presented.

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Synthesen mit heterocyclischen -Enaminonitrilen: Ein rascher synthetischer Zugang zu polyfunktionell substituierten 5-Phenylsulfonylthiophenen und ihren kondensierten Derivaten

Zusammenfassung Die Phenylsulfonylacetophenone1 reagieren mit einem Gemisch aus elementarem Schwefel und Malonsäurenitril zu den entsprechenden 2-Amino-4-aryl-5-phenylsulfonylthiophen-3-carbonitrilen2. Durch Umsetzung mit Stickstoffnucleophilen wie Cyanamid und Hydroxylaminhydrochlorid konnten aus Verbindung2a die entsprechenden Thieno[2,3-d]pyrimidin- und Thieno[2,3-c]pyrazolderivate erhalten werden. Das synthetische Potential und die Anwendbarkeit von5 zur Synthese polyfunktionell substituierter Thieno[2,3:3,4]pyrazolo[1,5-a]pyrimidine (8,14,17,20,21) werden beschrieben. Die Strukturen der neuen Verbindungen wurden durch chemische und spektroskopische Methoden abgesichert.

     

One-Pot Synthesis of Thieno[2,3-b]pyridine and Pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine Derivatives

Russian Journal of Organic Chemistry - 2-Acyl-4,5,6-trialkyl-3-aminothieno[2,3-b]pyridines,...     

Thieno[2,3-b]pyridine-2-carbohydrazide in Polyheterocyclic Synthesis: The Synthesis of Pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine,Pyrido[3′,2′:4,5]thieno[3,2-d][1,2,3]triazine,and Pyrazolyl,Oxadiazolylthieno[2,3-b]pyridine Derivatives

Pyrdine-2(1H)-thione 1 reacted with ethyl chloroacetate 2 to give 2-S-ethoxy-carbonylmethylpyridine derivative 3, which could be cyclized into thieno[2,3-b]-pyridine-2-carbohydrazide derivative 5 by boiling with hydrazine hydrate. The latter compound reacted with cinnamonitrile derivatives 6a, b, triethylorthoformate, formic acid, dimethylformamide-dimethylacetal, and diethyl carbonate to give the corresponding shiff base 7a, b and pyrido[3′,2′;-4,5]thieno[3,2-d]pyrimidine derivatives 10–13 in respective manner. On the other hand, compound 5 also reacted with carbondisulphide and phenyl isothiocyanate to afford the corresponding 2-(1,3,4-oxadiazolo-2-yl)thieno[2,3-b]pyridine derivatives 18 and 22. Finally, compound 5 reacted with some β-dicarbonyl compounds, such as ethyl acetoacetate, acetylacetone and ethyl β-arylazoacetoacetate, to yield the corresponding 2-(pyrazol-1-yl-carbonyl)thieno[2,3-b]pyridine derivatives 24, 25, and 27 respectively.     

New convenient synthesis of substituted 6,9-dihydropyrido[3′,2′:4,5]thieno[3,2-b]pyridines and 6,9-dihydropyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines

1,4-Dihydro-3-cyano-2-pyridinethiolates react with 2-bromo-l-(4-bromophenyl)ethylidenemalononitrile or N-cyanochloracetanudine to give 6, 9-dihydropyrido[3, 2': 4, 5]thieno[3. 2-b]pyridines or 6, 9-dihydropyrido-[3.2:4.5Jthieno(3,2-d]pyrimidines, respectively.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 553–556, April, 1996.     

Functionalization of α-Aminonicotinonitrile: A New Entry for Synthesis of Pyrazolo[3,4-b]pyridine,Pyrido[2,3-d]pyrimidine,and 1,8-Naphthyridine Derivatives

Russian Journal of General Chemistry - Functionalization of α-aminopyridine to a new series of pyridine and fused pyridine derivatives has been achieved via its reaction with a variety of...     

Vibrational spectra of the dithieno[3,2-b: 2′,3′-d] thiophene crystal

A normal mode analysis of dithieno[3,2-b:2′,3′-d]thiophene crystal was carried out using an intramolecular force field refined for the isolated molecule and an intermolecular potential described in terms of interactions among non-bonded atoms. Infrared and Raman data for internal and lattice vibrations are reported, including those for a deuterated isotopomer, which are satisfactorily accounted for by frequency calculations. Cartesian displacements for each normal mode of the isolated molecule are presented and frequency splittings and shifts analysed through calculations at k = 0 which include all crystal vibrational degrees of freedom.     

Synthesis,spectroscopic characterization,and in vitro antimicrobial activity of fused pyrazolo[4′,3′:4,5]thieno[3,2-d]pyrimidine

4-Amino-3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole-5-carboxamide ( 1 ), which had been previously synthesized according to literature, was used for synthesizing pyrazolothieno-pyrimidine ( 2 ) in the presence of triethyl orthoformate and acetic acid. Chlorination of the latter compound upon reflux with phosphorus oxychloride afforded the chloropyrazolothienopyrimidine ( 3 ), which underwent heterocyclization reaction with sodium azide to produce the tetrazolo-pyrazolothienopyrimidine ( 6 ). The chloropyrimidine ( 3 ) reacted with hydrazine hydrate to give the hydrazinopyrimidine derivative ( 4 ), which in turn underwent intramolecular condensation reactions with various 1,3-dicarbonyl compounds, namely ethyl acetoacetate, ethyl benzoylacetate, ethyl cyanoacetate, acetylacetone, diethyl malonate, and ethyl (ethoxymethylene) cyanoacetate, yielding new pyrazolyl pyrazolothienopyrimidine ring systems. Also triazolopyrazolothieno-pyrimidines and benzylidene Schiff's base compounds were obtained as a result of the reactions with carbon disulfide in pyridine and benzaldehyde, respectively. The chemical structures of the newly synthesized compounds were elucidated using elemental and spectroscopic analyses (FT-IR, ¹ H-NMR, ¹³ C-NMR, and mass spectroscopy). Some of the synthesized compounds possess high antibacterial and antifungal activities.     

Synthesis of Benzo[4,5]furo[3,2-b]thieno[2,3-d]pyridines —Derivatives of a New Heterocyclic System

Russian Journal of Organic Chemistry - Methyl 2-(bromomethyl)thiophene-3-carboxylates reacted with substituted 2-hydroxybenzonitriles to give methyl...     

Novel ferroelectric liquid crystals based on fused thieno[3,2‐b]furan and thieno[3,2‐b]thiophene cores

Several series of new benzofused thieno[3,2‐b]furan‐ and thieno[3,2‐b]thiophene‐based derivatives have been synthesized and their mesomorphic properties investigated. All the studied compounds exhibit a SmC* phase with very wide temperature interval. Additionally, some types of the compounds show the cholesteric, SmA or blue phase. In the ferroelectric SmC* phase we evaluated physical properties of relevance for possible applications.     

Syntheses with pyridinium and sulfonium salts of acylated β-enaminonitriles

Summary Pyridinium and sulfonium salts2a–e which can be prepared from 3-amino-2-(-haloacetyl)-crotonitriles and 3-amino-2-(-halo-acetyl)-3-phenyl-acrylonitriles react with malononitrile in the presence of a base to 3-amino-2-pyridinio-phenolates3a,b and 3-amino-2-sulfonio-phenolates3c–e. In an analogous way, 3-amino-2-(diethyloxyphosphoryl)-phenol5a and 3-amino-2-(p-tolyl-sulfonyl)-phenol5b have been prepared. 2,3-Diamino-phenoles6a,b are formed from the pyridinium salts3a,b. The behaviour of the pyridinium salts2a,b towards heterocumulenes has been investigated. Cyanamide leads to the (2-amino-4-hydroxy-pyrid-3-yl)-pyridinium salt8c. Phenylisothiocyanate gives the 3-pyridinio-2-thioxo-pyridin-4-olates9a,b. Carbon disulfide gives rise to 3-pyridinio-2-thioxo-pyridin-4-olate10 or 3-pyridinio-2-thioxo-thiopyran-4-olate11, depending on the substituent at the 6-position. Phenylisocyanate reacts to the pyrimidin-2,4-dione12 with loss of N-methyl-pyridinium chloride. S-methylation of9a and cleavage of the pyridine moiety yields the 3-amino-2-methylthio-pyrid-4-one14. The structures were investigated by¹H and¹³C NMR spectroscopy.

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Synthesen mit Pyridinium- und Sulfoniumsalzen von acetylierten -Enaminonitrilen

Zusammenfassung Pyridinium- und Sulfoniumsalze2a–e, die aus 3-Amino-2-(-halo-acetyl)-crotonsäurenitril und 3-Amino-2-(-halo-acetyl)-zimtsäurenitril hergestellt werden können, reagieren mit Malonsäuredinitril in Gegenwart einer Base zu 3-Amino-2-pyridinio-phenolaten3a,b und 3-Amino-2-sulfonio-phenolaten3c–e. In Analogie wurden 3-Amino-2-(diethyloxyphosphoryl)-phenol5a und 3-Amino-2-(p-tolyl-sulfonyl)-phenol5b erhalten. 2,3-Diamino-phenole6a,b werden aus den Pyridiniumsalzen3a,b gebildet. Das Verhalten der Pyridiniumsalze2a,b gegenüber Heterokumulenen ist untersucht worden. Cyanamid führt zum (2-Amino-4-hydroxy-pyrid-3-yl)-pyridiniumsalz8c. Phenylisothiocyanat liefert die 3-Pyridinio-2-thioxo-pyridin-4-olate9a,b. In Abhängigkeit vom Substituenten in der Position 6 entsteht bei der Reaktion mit Schwefelkohlenstoff ein 3-Pyridinio-2-thioxo-pyridin-4-olat10 oder ein 3-Pyridinio-2-thioxo-thiopyran-4-olat11. Phenylisocyanat reagiert zum Pyrimidin-2,4-dion12 unter Verlust von N-Methyl-pyridiniumchlorid. S-Methylierung von9a und Spaltung des Pyridiniumringes ergibt das 3-Amino-2-methylthio-pyrid-4-on14. Die Verbindungen wurden¹H- und¹³C-NMR-spektroskopisch untersucht.

     

Dianthra[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DATT): synthesis, characterization, and FET characteristics of new π-extended heteroarene with eight fused aromatic rings

A novel highly π-extended heteroarene with eight fused aromatic rings, dianthra[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DATT), was selectively synthesized via a newly developed synthetic strategy, fully characterized by means of single crystal X-ray structural analysis, and examined as an organic semiconductor in thin film transistors. Even with its highly extended acene-like π-system, DATT is a fairly air-stable compound with IP of 5.1 eV. Single crystal X-ray structural analysis revealed its planar molecular structure and the lamella-like layered structure with typical herringbone packing. Theoretical calculations of the solid state electronic structure based on the bulk single crystal structure suggest that DATT affords almost comparable intermolecular orbital couplings between HOMOs (t(HOMO)) with those of dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT), implying its good potential as an organic semiconductor for organic field-effect transistors. In fact, field-effect mobilities as high as 3.0 cm(2) V(-1) s(-1) were achieved with vapor-processed DATT-based devices, which is comparable with that of DNTT-based devices. The molecular ordering of DATT in the thin film state, however, turned out to be not completely uniform; as elucidated by in-plane and out-of-plane XRD measurements, the face-on molecular orientation was contaminated in the edge-on orientation, the former of which is not optimal for efficient carrier transport and thus could limit the mobility.     

Pyridine-2(1H)-thione in Heterocyclic Synthesis: Synthesis of Some New Nicotinic Acid Ester,Thieno[2, 3-b]pyridine,Pyrido[3′, 2′: 4, 5]thieno [3, 2-d]pyrimidine,and Thiazolylpyrazolo[3, 4-b]pyridine Derivatives

Nicotinic acid esters 3a–c were prepared by the reaction of pyridine-2(1H)-thione derivative 1 with α-halo-reagents 2a–c. Compounds 3a–c underwent cyclization to the corresponding thieno[2, 3-b]pyridines 4a–c via boiling in ethanol/piperidine solution. Compounds 4a–c condensed with dimethylformamide-dimethylacetal (DMF-DMA) to afford 3-{[(N,N-dimethylamino)methylene]amino}thieno[2, 3-b]- pyridine derivatives 6a–c. Moreover, compounds 4a–c and 6a–c reacted with different reagents and afforded the pyrido[3′,2′:4, 5]thieno[3, 2-d]pyrimidine derivatives 10a–d, 11a–c, 12a,b, 14a,b, 17, and 19. In addition, pyrazolo[3, 4-b]pyridine derivative 20 (formed via the reaction of 1 with hydrazine hydrate) reacted with ethylisothiocyanate yielded the thiourea derivative 21. Compound 21 reacted with α-halocarbonyl compounds to give the 3-[(3H-thiazol-2-ylidene)amino]-1H-pyrazolo[3, 4-b]pyridine derivatives 23a–c, 25, and 27a,b.     

New π-conjugated thieno[3,2-b]indole derivatives and charge carrier mobility in their thin films

New push-pull chromophores based on thieno[3,2-b]indole were synthesized. The energy levels of the outer molecular orbitals and the mobility of electrons and holes in thin films prepared from solutions of these compounds were determined experimentally.

     

Synthesis and characterization of some new pyridines,thieno[2,3-b] pyridines and pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine-4(3H)-ones bearing styryl moiety

3-Cyano-5-ethoxycarbonyl-6-methyl-4-styrylpyridine-2(1H)-thione ( 3 ) was prepared by reaction of 2-cyano-5-phenylpenta-2,4-dienethioamide ( 2 ) with ethyl acetoacetate or by multicomponent reaction of cinnamaldehyde ( 1 ), cyanothioacetamide and ethyl acetoacetate in a moderate yield. Reaction of compound 3 with some N-aryl-2-chloroacetamides, in the presence of sodium acetate, gave the corresponding 2-(N-arylcarbamoylmethylsulfanyl)-3-cyano-5-ethoxycarbonyl-6-methyl-4-styrylpyridines 4a-f . When compounds 4a-f were subjected to Thorpe-Ziegler reaction conditions, they converted into the corresponding 3-amino-5-ethoxycarbonyl-2-(N-arylcarbamoyl)-6-methyl-4-styrylthieno[2,3-b]pyridines 5a-f . Compounds 5a,e,f were reacted, in turn, with 2,5-dimethoxytetrahydrofuran to furnish the corresponding 3-(pyrrol-1-yl)thieno-pyridines 6a,e,f . Reactions of 5a-f with triethyl orthoformate or nitrous acid were also carried out and their products were identified. Structural formulas of all synthesized compounds was characterized and confirmed on the basis of their elemental and spectral analyses.     

Synthesis and antitumor activity of α-aminophosphonate derivatives containing thieno[2,3-d]pyrimidines

Two series of thieno[2,3-d]pyrimidine derivatives were designed and synthesized, in which bioactive a-aminophosphonate subunits were introduced at the N3 position through an N–N bond connection.The in vitro cytotoxic activity of the novel compounds was tested against human esophageal carcinoma cells(EC109), human hepatocarcinoma cells(Hep G2), human gastric carcinoma cells(MGC-803),respectively, by the MTT method. The evaluation results revealed that compounds 6mb, 6mf, 6mg, 6nd and 6nh exerted the most potent inhibition against Hep G2, MGC-803 and EC109 cells, respectively. In particular, compound 6mg presented excellent inhibitory effect against Hep G2(91.2%) and MGC-803(94.4%) cells.     

Synthesis of androsteno[17,16-d]pyrazoles and androsteno[17,16-d]-2′-pyrazolines with pyrazolo[3,4-d]pyrimidine fragments

Russian Chemical Bulletin - Reactions of pyrazolo[3,4-d]pyrimidine-containing hydrazines with pregnenolone derivatives were studied. The reaction of...     

New approaches to the synthesis of functionally substituted pyrido[3′,2′:4,5]thieno[3,2-b]pyridines and the structure of the products obtained

Substituted pyrido,[3',2':4,5]thieno[3,2-b]pyndines were obtained by the reaction of 3-amino-2-benzoylthieno [2,3-b]pyridines with malononitrile and the reaction of 3-cyanopyridine-2(IH)-thiones with 2-aryl-3-bromo-I,I-dicyanopropene. 2-Amino-4-(4-bromophenyl)-7, 9-dimethyl-3-cyanopyrido [3',2':4,5]thieno[3, 2-b]-pyridine was used for the synthesis of a derivative of pyrido[3",2":4', 5']thieno[2',3':5,6]pyrido[2,3-d]-pyrimidine. The structure of these compounds was confirmed by spectral data and x-ray diffraction structural analysis.Deceased.     

Synthesis,characterization, and biological activities of some novel thienylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines and related heterocycles

3-Cyano-5-ethoxycarbonyl-6-methyl-4-(2′-thienyl)-pyridine-2(1H)-thione ( 1 ) is synthesized and reacted with chloroacetamide or chloroacetonitrile to give 3-amino-5-ethoxycarbonyl-6-methyl-4(2′-thienyl)-thieno[2,3-b]pyridine-2-carboxamide 3a or its 2-carbonitrile analog 3b , respectively. Cyclocondensation of 3a with triethylorthoformate produced the corresponding pyridothienopyrimidineone 4 , which on heating with phosphorus oxychloride gave 4-chloropyrimidine derivative 5 . Compound 5 was used as key intermediate for synthesizing compounds 6 , 9 , 10 , 11 , and 12 upon treatment with some nucleophilic reagents such as thiourea, 5-phenyl-s-triazole-3(1H)-thione, piperidine, morpholine, or hydrazine hydrate, respectively. Reaction of pyridothienopyrimidinethione 6 with N-(4-tolyl)-2-chloroacetamide or ethyl bromoacetate afforded the corresponding S-substituted methylsulfanylpyrimidines 7 or 8 . The condensation of 3b with triethylorthoformate gave azomethine derivative 13 , which was reacted with hydrazine hydrate to give ethyl 3-amino-3,4-dihydro-4-imino-7-methyl-9-(2′-thienyl)pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine-8-carboxylate ( 14 ). Compounds 12 and 14 were used as precursors for synthesizing other new thienylpyridothienopyrimidines as well as isomeric thienyl-s-triazolopyridothieno- pyrimidines. All synthesized compounds were characterized by elemental and spectral analyses such as IR, ¹H NMR, and ¹³C NMR. In addition, majority of synthesized compounds were tested for their antifungal activity against five strains of fungi. Moreover, compounds 3a , 5 , 6 , 8 , and 22 were screened for their anticancer activity against HEPG-2 and MCF-7 cell lines.     

Synthesis of substituted pyrido[3´,2´:4,5]thieno[3,2-c]isoquinolin-5(6H)-ones and their sulfinyl and sulfonyl derivatives

A method for the synthesis of previously unknown pyrido[3´,2´:4,5]thieno[3,2-c]isoquinolin-5(6H)-ones was suggested, which includes a condensation reaction of substituted 3-cyanopyridine-2(1H)-thiones with methyl 2-(chloromethyl)benzoate and subsequent treatment of the condensation products with potassium tert-butoxide. The oxidation of the condensation products to sulfoxides or sulfones and subsequent treatment of these compounds with potassium tert-butoxide led to substituted pyrido[3´,2´:4,5]thieno[3,2-c]isoquinolin-5(6H)-one 11-oxides or substituted pyrido[3´,2´:4,5]thieno[3,2-c]isoquinolin-5(6H)-one 11,11-dioxides.

     

Synthesis of derivatives of pyrido[3′,2′:4,5]furo[3,2-c]isoquinoline heterocyclic system

An approach to the synthesis of derivatives of new heterocyclic system, pyrido[3′,2′:4,5]-furo[3,2-c]isoquinoline, was suggested. A condensation reaction of substituted 3-cyanopyridin-2(1H)-ones with methyl 2-(chloromethyl)benzoate and subsequent treatment of the condensation product with potassium tert-butoxide leads to substituted pyrido[3′,2′:4,5]furo[3,2-c]-isoquinolin-5(6H)-ones. Similarly, a condensation reaction of substituted 3-cyanopyridin-2(1H)-ones with 2-(chloromethyl)benzonitrile and subsequent treatment of the condensation product with potassium tert-butoxide gives substituted 5-aminopyrido[3′,2′:4,5]furo[3,2-c]-isoquinolines.