Synthesis of novel azonia Helicenes containing terminal thiophene rings

The Knoevenagel condensation of the 9‐methyl derivatives of thieno[3,2‐a]‐ and thieno[2,3‐a]‐quinolizinium salts ( 2b and 3b ) with appropriate arylaldehydes yielded 9‐(arylvinyl)thieno[3,2‐a]‐ and 9‐(arylvinyl)thieno[2,3‐a]quinolizinium salts ( 4a‐c and 5a‐c ), respectively, which underwent photocyclization to give a series of novel hetero[5]helicenes ( 6a,b and 7a‐d ) containing quinolizinium and thiophene rings.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 6. Naphthothienonaphthyridines

Five novel polycyclic heterocyclic ring systems are reported via photocyclization. The specific final products in these ring systems are: naphtho[1′,2′:4,5]thieno[2,3-c][1,8]naphthyridin-6(5H)-one ( 5 ), naphtho-[1′,2′:4,5]thieno[2,3-c][1,6]naphthyridin-6(5H)-one ( 6 ), naphtho[1′,2′:4,5]thieno[2,3-c]-1,5-naphthyridine ( 9 ), naphtho[1′,2′:4,5]thieno[2,3-c][1,2,4]triazolo[4,3-a]-1,5-naphthyridine ( 12 ), and naphtho[2′,1′:4,5]thieno[2,3-c]-1,5-naphthyridine ( 17 ). The direction of photocyclization to produce 9 was established from a zero quantum two-dimensional nmr spectroscopy experiment (ZQCOSY) using 6-chloronaphtho[1′,2′:4,5]thieno[2,3-c]-1,5-naphthyridine ( 8 ) as the model compound.     

New polyheterocyclic series based on 4,5,6,7-tetrahydrothieno[2,3-c]pyridine

4,8-Dimethyl-6,7,8,9-tetrahydropyrido[4′,3′:4,5]thieno[2,3-e][1,2,4]triazolo[3,4-a]-4H-pyrimidin-5-ones, 7-methyl-2,3,6,7,8,9-hexahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrrolo[1,2-a]-1H, 10H-pyrimidin-10-one, 8-methyl-1,2,3,4,7,8,9,10-octahydropyrido[4′,3′:4,5]thieno[2,3-d]-11H-pyrimidin-11-one, and 9-methyl-2,3,4,5,8,9,10,11-octahydro[4′,3′:4,5]thieno[2,3-d]azepino-[1,2-a]-1H, 12H-pyrimidin-12-one which consist four new heterocyclic ring systems were synthesized from 2-amino-3-carbethoxy-5-methyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine.     

Synthesis and transformations of 3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridines

Reactions of 2,5-dimethoxytetrahydrofuran with 3-aminothieno[2,3-b]pyridines afford a number of substituted 3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridines. The possibility of the reaction and the yield of the product are determined by the character of a substituent in position 2 of thieno[2,3-b]pyridine. The Curtius rearrangement of 2-acylazido-3(1H-pyrrol-1-yl)thieno[2,3-b]pyridines yields 4,5-dihydropyrido[3",2":4,5]thieno[2,3-e]pyrrolo[1,2-a]pyrazin-4-ones. The molecular and crystal structures of ethyl 4-methoxymethyl-6-methyl-3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridine-2-carboxylate were determined by X-ray diffraction analysis.     

Synthesis and structure of some thienopyrimidine derivatives

A series of substituted thieno[2,3-d]pyrimidines was synthesized starting from ethyl-2-amino-4-isopropylthiophene-3-carboxlate. Reaction of 2-hydrazino-5-isopropyl-thieno[2,3-d]pyrimidin-4(3H)-one and its 3-methyl analogue with different reagents afforded thieno[2,3-d]triazolo[4,3-a]pyrimidines and thieno[3,2-e]triazolo[4,3-a]pyrimidines, beside open chain derivatives. Correspondence: Atef A. Hamed, Department of Chemistry, Faculty of Science, Menoufia University, Shebin El Koam, Egypt.     

Folate antagonists. 6. Synthesis and antimalarial effects of fused 2,4-diaminothieno[2,3-d]pyrimidines

2,4-Diamino-5,7-dihydro-6H-thiopyrano[4′,3′:4,5]thieno[2,3-d]pyrirnidine, 2,4-diamino-9H-mdeno[1′,2′:4,5]thieno[2,3-d]pyrimidine, 2,4-diamino-5H-indeno[2′,1′:4,5]thieno[2,3-d]pyrimidine, 9,11-diamino-5,6-dihydronaphtho[1′,2′:4,5]thieno[2,3-d]pyrimidine, 7,9-diamino-5,6-dihydronaphtho[2′,1′:4,5]thieno[2,3-d]pyrimidine, 2,4-diamino-7-benzy]-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidine, and various 2,4-diamino-5,6,7,8-tetrahydro-[1]benzothieno[2,3-d]pyrimidines were synthesized by cyclization of the requisite fused 2-aminothio-phenene-3-carbonitriles utilizing chloroformamidine hydrochloride in diglyme. Several compounds exhibited strong inhibitory effects against Streptococcus faecalis (MGH-2), Staphylococcus aureus (UC-76), Streptococcus faecium (ATCC 8043), Lactobacillus casei (ATCC 7469), and Pediococcus cerevisiae (ATCC 8081) in vitro, and three compounds displayed antimalarial activity against Plasmodium berghei in mice and P. falciparum (Uganda I) in vitro.     

Quinazolincs and 1,4-benzodiazepines. LXXXVI. The synthesis of imidazothienodiazepines and imidazopyrazolodiazepines

The thieno[3,2-e][1,4]diazepin-2-one ( 1a ), the thieno[2,3-e] [ 1,4] diazepin-2-one ( 1b ), the pyrazolo[3,4-e][1,4]diazepin-2-one ( 1c ) and a chloro analog of 1b , compound 1d , were each converted to derivatives of the novel tricyclic ring systems 4H-imidazo[1,5-a]thieno[2,3-f] [1,4]-diazepine, 4Himidazo[1,5a]thieno[2,3f][1,4]diazepine and 4H-imidazo[ 1,5-a]pyrazolo[4,3-f]-[1,4]diazepine. Depending on the substituents desired on the imidazo ring, two different synthetic pathways were employed.     

A facile one-pot synthesis of 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones

Abstract  

The reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one or its 2-methylthio derivative with hydrazonoyl halides, in the presence of triethylamine, yielded 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The structure of the latter compounds was further confirmed by reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one with the appropriate active chloromethylenes followed by coupling of the products with benzenediazonium chloride to afford the non-isolable azo-coupling products which converted, in situ, to 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The reaction mechanism was proposed and the products were screened for their biological activity. Some of the newly synthesized compounds had a moderate effect against some bacterial and fungal species.     

Synthesis of Substituted 1,3-Cyclohexadienes,Pyridine-2(1H)-thiones,and Thieno[2,3-d]pyrimidine- 4(3H)-thiones by the Michael Reaction

Cyclopentylidene- and cyclohexylidene(cyano)acetamides reacted with malononitrile and cyano-(thioacetamide) according to the Michael pattern with exchange of the methylene components to give substituted 1-amino-2,6,6-tricyano-1,3-cyclohexadienes and thieno[2,3-d]pyrimidine-4(3H)-thiones. Condensation of cyclopentylidene- and cyclohexylidene(cyano)acetamide with 1,3-dicarbonyl compounds afforded 4,6-di-methyl-3-cyanopyridine-2(1H)-thione and morpholinium 4-methyl-6-oxo-3-cyano-1,6-dihydropyridine-2-thiolate which were converted into substituted 2-alkylsulfanylpyridines, thieno[2,3-b]pyridines, thiazolo[3,2-a]pyridine, and 2H-[1,3]thiazino[3,2-a]pyridine.     

A convenient synthesis for some new pyrido[3′,2′:4,5]thieno-[3,2-d]pyrimidine derivatives with potential biological activity

Ready, convenient synthesis for 8-cyano-7-ethoxy-4-oxo-9-phenyl-2-substituted-1,2,3,-4-tetrahydropyrido-[3′,2′:,4,5]thieno[3,2-d]pyrimidines 5 , 8-cyano-7-ethoxy-4-oxo-9-phenyl-2-substituted-3,4-dihydropyrido[3′,2-: 4,5]thieno[3,2-d]pyrimidines 6 , 4-chloro-8-cyano-7-ethoxy-9-phenyl-2-substitutedpyrido[3′,2′:4,5]thieno[3,2-4 -pyrimidines 7 and 8-cyano-7-ethoxy-2-(2′-nitrophenyl)-9-phenyl-4-substitutedpyrido[3′,2′:4,5]thieno[3,2- d ]pyrimidines 8-18 from 2-chloro-3,5-dicyano-6-ethoxy-4-phenylpyridine 1 via 3,5-dicyano-6-ethoxy-2-mercapto-4-phenylpyridine 2 and aminocarboxamide 4 are reported. In addition, the reaction of hydrazino derivative 12 with reagents such as formic acid and triethyl orthoformate yielded the fused tetraheterocyclic 8-cyano-9- ethoxy-5-(2′-nitrophenyl)- 7-phenylpyrido[3′,2′:4,5]thieno[2,3-e]-1, 2,4-triazolo[4,3-c]pyrimidine system 19 .     

On the bromination of thieno[c]-fused 1,5-naphthyridines and their isomeric N-oxides using dibromoisocyanuric acid in fuming sulfuric acid

Thieno[2,3-c]-1,5-naphthyridine ( 3 ), thieno[2,3-c]1,5-naphthyridine 5-oxide ( 7 ), thieno[3,2-c]-1,5-naphthyridine ( 5 ) and thieno[3,2-c]-1,5-naphthyridine 5-oxide ( 9 ) could conveniently be brominated at room temperature using dibromoisocyanuric acid in fuming sulfuric acid. Bromination occurred in good to moderate yields at the β position in the thiophene ring. Thieno[2,3-c]-1,5-naphthyridine 9-oxide ( 12 ) and thieno[3,2-c]-1,5-naphthyridine 9-oxide ( 13 ) also gave substitution in the thiophene ring at 95°. It was also found that 12 was deoxygenated under these reaction conditions. Direct oxidation of the brominated thieno[c]naphthyridines with m-chloroperbenzoic acid gave the 5-oxides in high yield.     

Synthesis and nmr spectra of the six isomeric thieno[c]-fused 1,7- and 1,8-naphthyridines

Through the use of Pd(0)-catalyzed coupling between 2- and 4-formyl-3-thiopheneboronic acid and 4-iodo-3-aminopyridine ( 1 ) and 3-bromo-2-aminopyridine, convenient one-pot procedures for the preparation of thieno[2,3-c]-1,7-naphthyridine ( 2 ), thieno[3,4-c]-1,7-naphthyridine ( 3 ), thieno[2,3-c]-1,8-naphthyridine ( 6 ) and thieno[3,4-c]-1,8-naphthyridine ( 7 ) have been developed. Thieno[3,2-c]-1,7-naphthyridine ( 4 ) and thieno[3,2-c]-1,8-naphthyridine ( 8 ) were obtained through the coupling of 2-tri-n-butylstannyl-3-thiophenaldehyde with 2,2-dimethyl-N-(4-iodo-3-pyridinyl)propanamide and 3-bromo-2-acetamidopyridine ( 1 ). The yield of 8 was further increased when copper(II) oxide was used as the co-reagent. The ¹³C nmr spectra of the six isomeric thieno[c]-fused 1,7- and 1,6-naphthyridines are discussed.     

Novel Selected Tandem Transformations of the Amino and Carbonyl/Nitrile Groups in the Gewald Thiophenes

Novel transformations of the amino and carbonyl/nitrile groups in the Gewald thiophenes were studied for thienopyrimidine synthesis. It was found that 2-amino-thiophene-3-carboxamides and ethyl 2-(acetylamino)-4,5,6,7-tetrahydro-1-benzothiophene-3-carbo- xylate did not yield tetrazole derivatives, neither in the reaction with triethyl orthoformate and sodium azide, nor in the reaction with phosphorus oxychloride and sodium azide, correspondingly. On the contrary, derivatives of thieno[2,3-d]pyrimidin-4(3H)-one and thieno[2,3-d][1,3]oxazin-4-one were isolated. New 2-azidothiophenes [2-azido-4,5,6,7-tetra hydro-1-benzothiophene-3-carbonitrile and 2-azido-4,5,6,7-tetrahydro-1-benzothiophen-3-yl(phenyl)methanone] were synthesized and used in anionic domino reactions with activated acetonitriles to yield thieno[3,2-e][1,2,3]triazolo[1,5-a]pyrimidines and/or 2-(5-amino-1H-1,2,3-triazol-1-yl)thiophenes. Finally, a new ring system of thieno[3,2-e]pyrazolo[1,5-a]pyrimidine was synthesized via a domino reaction of ethyl 2-[(2Z)-2-(1-chloro-2-ethoxy-2-oxoethylidene)hydrazino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate with activated acetonitriles.     

Synthesis and Properties of 6-Amino-7-hetaryl-5-R-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles

We have established that when 5-chloro-6-[cyano(2,3-dihydro-1-R-benzo[d]azol-2-yl)methyl]-2,3-pyrazinedicarbonitriles are reacted with nucleophilic reagents (aliphatic and aromatic amines, hydrogen sulfide), annelation of the five-membered ring occurs on the [b] face of the pyrazine with formation of 6-amino-7-hetaryl-5-R-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles and 6-amino-7-(1H-benzo[d]imidazol-2-yl)thieno[2,3-b]pyrazine-2,3-dicarbonitrile respectively. Further heating with excess of acylating reagent leads to formation of a novel heterocyclic system 1H-benzo[4,5]imidazo[1,2-c]pyrazino[2',3':4,5]pyrrolo[3,2-e]pyrimidine. Reaction of vicinal dinitriles with hydrazine hydrate leads to the novel system 1H-pyrrolo[2',3':5,6]pyrazino[2,3-d]pyridazine.     

A facile one-pot synthesis of 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-<Emphasis Type="Italic">d</Emphasis>]-1,2,4-triazolo[4,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidin-5-ones

Abstract  The reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one or its 2-methylthio derivative with hydrazonoyl halides, in the presence of triethylamine, yielded 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The structure of the latter compounds was further confirmed by reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one with the appropriate active chloromethylenes followed by coupling of the products with benzenediazonium chloride to afford the non-isolable azo-coupling products which converted, in situ, to 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The reaction mechanism was proposed and the products were screened for their biological activity. Some of the newly synthesized compounds had a moderate effect against some bacterial and fungal species. Graphical abstract        

Synthesis of some pyrimido[4′,5′:4,5]thieno[2,3-b]quinolines and related heterocycles

Several thieno[2,3-b]quinolines 6a-i have been synthesized. These compounds were used as key intermediates in the synthesis of oxazino[4′,5′:4,5]thieno[2,3-b]quinoline 8 , pyrimido[4′,5′:4,5]-thieno[2,3-b]quinolines 9–12 , triazino[4′,5′:4,5]thieno[2,3-b] quinolines 14 and imidazo[4′,5′:4,5]-thieno[2,3-b]quinolines 17 .     

Synthesis,Reactions, and Antimicrobial Evaluation of Some Polycondensed Thienopyrimidine Derivatives

Some novel indeno[2,1-b]thiophenes, indeno[1′,2′:4,5]thieno[2,3-d][1,2,3]triazines, indeno[1′,2′:4,5]thieno[2,3-d]pyrimidines, indeno[1′,2′:4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidines, and indeno[1′,2′:4,5]thieno[2,3-d][1,2,4]triazolo[4,3-a]pyrimidines 2–16 were prepared starting with 2-aminoindeno[2,1-b]thiophene-3-carboxylic acid amide ( 1 ). Furthermore, the antimicrobial evaluation of the prepared products showed that many of them revealed promising antimicrobial activity.     

Synthesis of 2-Arylthiopyrano[2, 3-d]Pyrimidines and Thieno[2, 3-D]Pyrimidines

Diethyl thiopyrano[2,3-d]pyrimidine-6,7-dicarboxylates 2a, b ; thiopyrano[23-d]pyrimidines 3a-c and 4a-c thieno[2,3-d]pyrimidine-6-carbonitriles 5a-c and thieno[2, 3-d]pyrimidine-6-carboxamides 5d-f have been prepared.     

Thieno[2,3-d]pyrimidin-4-ones 1. Condensation of 2,3-dimethyl- and 2,3-tri-, 2,3-tetra-, and 2,3-pentamethylene-7,8-dihydro-pyrrolo[1,2-a]thieno[2,3-d]pyriminidin-4(6H)-ones with aromatic aldehydes and furfural

2,3-Dimethyl- and 2,3-tri-, 2,3-tetra-, and 2,3-pentamethylene-substituted 8-arylidene-6,7-dihydro-pyrrolo[1,2-a]thieno[2,3-d]pyrimidin-4-ones were synthesized by the reaction of 2,3-dimethyl- and 2,3-tri-, 2,3-tetra-, and 2,3-pentamethylene-7,8-dihydropyrrolo[1,2-a]thieno[2,3-d]pyrimidin-4(6H)-ones with benzaldehyde, its 4-dimethylamino-, 3,4-dimethoxy-, and 3,4-methylenedioxy derivatives and also furfural in the presence of NaOH.     

Chemistry of benzo[b]furan. V.. Synthesis of substituted thia-analogs and oxa-analogs of dihydrorutecarpine and evodiamine

Cycloaddition of 3,4-dihydrobenzo[b]thieno[2,3-c]pyridine ( 6 ) with the sulfinamide anhydride 9 (R = H) afforded the thia-analog of dihydrorutecarpine ( 2a ). Condensation of the imine 6 with the sulfinamide anhydride 9 (R = CH₃) gave the thia-analog of evodiamine ( 2b ). Starting from 1-methyl-3,4-dihydrobenzo[b]thieno[2,3-c]pyridine ( 12 ) and 1-methyl-3,4-dihydrobenzo[b]furo[2,3-c]pyridine ( 14 ), a series of 3-methyl derivatives of thia-analogs of dihydrorutecarpine and evodiamine ( 2c-2i ) and oxa-analogs of dihydrorutecarpine and evodiamine ( 1a-1g ) were similarly prepared.