Nitration of dithieno[3,4-b:3′,2′-d]pyridine and dithieno[2,3-b:3′,2′-d]pyridine

The nitration of dithieno[3,4-b:3′,2′-d]pyridine ( 2 ) and dithieno[2,3-b:3′,2′-d]pyridine ( 3 ) has been studied. Nitration of 2 occurred in both positions of the c-fused thiophene ring, while 3 was predominantly substituted in the 2-position. The structures of the nitro derivatives were proven by extensive use of ¹H and ¹³C nmr spectroscopy.     

Direct bromination of dithieno[3,4-b:3′,4′-d]pyridine and dithieno[2,3-b:3′,2′-d]pyridine

Bromination of dithieno[3,4-b:3′,4′-d]pyridine ( 1 ) and dithieno[2,3-b:3′,2′-d]pyridine ( 2 ) has been studied. Disubstitution occurred at both positions of the C ring. The substitution pattern is found to be similar to that of the nitration reaction. The structures of bromo derivatives were established by ¹H and ¹³C nmr spectroscopy.     

On the orientation in lithiation and bromination of dithieno[3,4-b:3′,2′-d]pyridine

The 3-position of dithieno[3,4-b:3′,2′-d]pyridine was found to be most reactive with regard to lithiation, bromination and halogen-metal exchange. The lithium compounds were trapped as the formyl derivatives by reaction with N,N-dimethylformamide.     

On the syntheses of 1,3-disubstituted dithieno[3,4-b:3′,2′-d]pyridines via halogen-metal exchange of 1,3-dibromodithieno[3,4-b:3′,2′-d]pyridine

Halogen-metal exchange of 1,3-dibromodithieno[3,4-b:3′,2′-d]pyridine with butyllithium under different conditions has been studied. Upon reaction with iodine, N,N-dimethylacetamide, N,N-dimethylformamide, dimethyl carbonate, dimethyl disulfide and thiuram disulfide, the 1,3-diiodo-, 1,3-diacetyl-, 1,3-diformyl-, 1,3-dicarbomethoxy, 1,3-di(thiomethyl)- and 1,3-di(N,N-dimethyldithiocarbamoyl)dithieno[3,4-b:3′,2′-d]-pyridines, respectively, were obtained in varying yields. 3-Monosubstituted derivatives were obtained in some cases. The formation of 3,7-disubstituted derivatives was sometimes also observed.     

Synthesis of 4-methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridine

4-Methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridine ( 3 ) was synthetized from 2-acetylfuro[3,2-f]benzo[b]furan ( 4 ) or from 2-acetyl-5,6-dihydrofuro[3,2-f]benzo[b]furan ( 10 ). The key step involves a rearrangement-cyclization of azides 6 and 12 to form 4-methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridin-1(2H) one ( 7 ) and 8,9-dihydro-4-methylfuro[3′,2′:5,6]benzofuro[3,2c]pyridin-1(2H)-one ( 13 ). Introduction of an aminoalkyl chain on carbon 1 was effected by substitution of 1-chloro-4-methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridine ( 8 ).     

Studies of thieno[2,3-b]pyrazines in preparation of pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidines and related molecules

A variety of 2,3-disubstituted derivatives of the previously unknown thieno[2,3-b]pyrazine ring system have been employed as a synthetic foundation for pyrazino[2′,3′:4,5]thieno[3,2-d]-pyrimidine and several of its derivatives.     

Synthesis and S-methylation of 2-thioxopyrido[3′,2′:4,5]thieno[3,2-d]-pyrimidin-4(3H)-ones with and without a phase transfer catalyst

A number of 2-thioxopyrido[3′,2′:4,5]thieno[3,2-H]pyrimdin-4(3H-ones (5) have been synthesized by cyclocondensation of 2-carbethoxy-3-amino-4-phenyl-6-substituted-thieno[2,3-b]pyridines (3) with various isothiocyanates. Compounds 5 were S-methylated routinely and the reactions compared under solid-liquid phase transfer conditions to obtain 2-methylthiopyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-^ones (6). The new triheterocyclic pyridothienopyrimidines were prepared with the objective to study their pharmacological properties.     

Synthesis of novel pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidines,pyrido[3″,2″:4′,5′]thieno[3′,2′:4,5]pyrimido[l,6‐a]benzimidazoles and related fused systems

3‐Amino‐4‐aryl‐5‐ethoxycarbonyl‐6‐methylthieno[2,3‐b]pyridine‐2‐carboxamides 3a‐c were prepared from ethyl 4‐aryl‐3‐cyano‐6‐methyl‐2‐thioxo‐1,2‐dihydropyridine‐5‐carbonylates 1a‐c and reacted with some carbonyl compounds to give tetrahydropyridothienopyrimidine derivatives 6a‐c, 7a‐c and 8a‐c , respectively. Treatment of compound 3c with chloroacetyl chloride led to the formation of a next key compound, ethyl 2‐chloromethyl‐4‐oxo‐3,4‐dihydropyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine‐8‐carboxylate 9 . Also, 3‐amino‐2‐benzimidazolylthieno[2,3‐b]pyridine‐5‐carboxylate 5 and 2‐(3′‐aminothieno [2,3‐b]pyridin‐2′‐yl)‐4‐oxo‐3,4‐dihydropyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine‐8‐carboxylate 17 were prepared from 1c. The compounds 5, 9 and 17 were used as good synthons for other pyridothienopyrimidines and pyridothienopyrimidobenzimidazoles as well as for related fused polyheterocyclic systems.     

Convenient synthesis and anticancer evaluation of novel pyrazolyl-thiophene,thieno[3,2-b]pyridine,pyrazolo[3,4-d]thieno[3,2-b]pyridine and pyrano[2,3-d]thieno[3,2-b]pyridine derivatives

The newly synthesized 3-(3-amino-5-(phenylamino)-4-(phenylcarbamoyl)thiophen-2-yl)-3-oxopropanoate was utilized as a precursor for the synthesis of pyrazolyl-thiophene derivative, which undergoes cyclization upon treatment with benzaldehyde derivatives to provide pyrazolo[3,4-d]thieno[3,2-b]pyridines. Basic treatment of pyrazolyl-thiophene derivative with phenyl isothiocyanate followed by subsequent addition of chloroacetone and/or ethyl bromoacetate yielded the thiazolylidene-pyrazolyl thiophenes. In addition, the building block 3-(3-amino-5-(phenylamino)-4-(phenylcarbamoyl)thiophen-2-yl)-3-oxopropanoate was converted into the corresponding thieno[3,2-b]pyridine compounds through its reactions with (DMF-DMA) and/or heating in sodium ethoxide. Moreover, the reaction of 7-hydroxy-5-oxo-N-phenyl-2-(phenylamino)-4,5-dihydrothieno[3,2-b]pyridine-3-carboxamide with 2-arylidenemalononitrile produced the new annulated pyrano[2,3-d]thieno[3,2-b]pyridines. The prepared thiophene-based compounds were evaluated against HepG2, PC3, and MCF-7 cancer cells, and normal fibroblast cell (WI38). The pyrazolo[3,4-d]thieno[3,2-b]pyridine and pyrano[2,3-d]thieno[3,2-b]pyridine compounds substituted with chlorophenyl group presented promising cytotoxic activities against HepG2 cancer cell line without any human toxicity. Docking study for the synthesized thiophene compounds delivered valuable insights about the binding interactions with the crystal structure of NS5B enzyme with PDB ID (4TLR).     

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 .     

Chemistry of the phenoxathiins VIII. Synthesis of 7-chlorobenzo[1″.2″:5,6:3″,4″:5′,6′] bis[1,4] oxathiino[3,2-b:3′.2′-b′]dipyridine

As a continuation of recent study on the synthesis of a bis[1,4]oxathiinodipyridine ring system, we would now like to report the preparation of 7-chlorobenzo[1″,2″:5,6:3″,4″:5′,6′]-bis[1,4]oxathiino[3,2-b: 3′,2′-b]dipyridine. Although a potentially complex reaction with several products possible, the title compound was formed exclusively, suggesting considerable mechanistic selectivity. The characterization of the product by FT-¹H-nmr as well as its mass spectral fragmentation pathways are also reported.     

New copolymers with thieno[3,2‐b]thiophene or dithieno[3,2‐b:2′,3′‐d]thiophene units possessing electron‐withdrawing 4‐cyanophenyl groups: Synthesis and photophysical,electrochemical, and electroluminescent properties

New monomers containing 4‐cyanophenyl (–PhCN) groups attached to a thieno[3,2‐b]thiophene (TT) or dithieno[3,2‐b:2′,3′‐d]thiophene (DTT) structure were synthesized and characterized as 4‐(2,5‐dibromothieno[3,2‐b]thiophen‐3‐yl)benzonitrile (Br–TT–PhCN) or 4,4′‐(2,6‐dibromodithieno[3,2‐b:2′,3′‐d]thiophene‐3,5‐diyl)dibenzonitrile (Br–DTT–PhCN). The Suzuki coupling of 9,9‐dioctylfluorene‐2,7‐diboronic acid bis(1,3‐propanediol)ester and the Br–TT–PhCN or Br–DTT–PhCN monomer was utilized for the syntheses of novel copolymers poly{9,9‐dioctylfluorene‐2,7‐diyl‐alt‐3‐(4′‐cyanophenyl)thieno[3,2‐b]thiophene‐2,5‐diyl} (PFTT–PhCN) and poly{9,9‐dioctylfluorene‐2,7‐diyl‐alt‐3,5‐bis(4′‐cyanophenyl)dithieno[3,2‐b:2′,3′‐d]thiophene‐2,6‐diyl} (PFDTT–PhCN), respectively. The photophysical, electrochemical, and electroluminescent (EL) properties of these novel copolymers were studied. Their photoluminescence (PL) exhibited the same emission maximum for both copolymers in solution. Red‐shifted PL emissions were observed in the thin films. The PL emission maximum of PFTT–PhCN was more significantly redshifted than that of PFDTT–PhCN, indicating more pronounced excimer or aggregate formation in PFTT–PhCN. The ionization potential (HOMO level) and electron affinity (LUMO level) values were 5.54 and 2.81 eV, respectively, for PFTT–PhCN and were 5.57 and 2.92 eV, respectively, for PFDTT–PhCN. Polymer light‐emitting diodes (LEDs) with copolymer active layers were fabricated and studied. Anomalous behavior and memory effects were observed from the current–voltage characteristics of the LEDs for both copolymers. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2629–2638     

Highly Fluorescent Conjugated Copolymers Containing Dithieno[3,2‐b:2′,3′‐d]pyrrole

Three copolymers that incorporate dithieno[3,2‐b:2′,3′‐d]pyrrole with fluorene, carbazole, or pyridine have been prepared by Suzuki reaction and characterized by NMR spectroscopy and GPC. A new homopolymer of dithieno[3,2‐b:2′,3′‐d]pyrrole was also synthesized for the comparison of their structure–property relationships. Their thermal, optical, and electrochemical properties have been investigated. All the polymers exhibit good thermal stability with decomposition temperatures around 400 °C. The fluorescence quantum efficiencies of all these polymers in solution are in the range of 33.5–55.5%. The copolymers also show high film fluorescence quantum efficiencies of about 20% while the fluorescence of the homopolymer film is almost quenched.

     

Synthesis of New Fused Pirano[4,3-b]pyridine Derivatives

A method was developed for the synthesis of pyrano[4,3-b]thieno[3,2-e]pyridine derivatives based on the reaction of 3-amino-7-ethyl-7-methyl-7,8-dihydro-5H-pyrano[4,3-b]thieno[3,2-e]pyridine-2-carboxylic acid ethyl ester with chloroacetic acid chloride, triethyl orthoformate, hydrazine hydrate, and also phenyl chloroformate. The synthesis of various new representatives of pyrano[2″,3″:5′,6′]pyrido[3′,2′:4,5]thieno[3,2-dl-pyrimidine series was carried out.

     

Synthesis of S-5-pyrrolo[2,3-b]pyridinemethyl and S-5- and S-6-pyrrolo[2,3-d]pyridinemethyl derivatives of 5′-deoxy-5′-thioadenosine

Reaction of 5-dimethylaminomethylpyrrolo[2,3-b]pyridine methiodide or 5-dimethylaminomethylpyrrolo[2,3-d]pyrimidin-4-one methiodide with 5′-deoxy-5′-S-thioacetyl-N⁶-formyl-2′,3′-O-isopropylideneadenosine in ethanolic sodium hydroxide solution, followed by deprotection of the resulting thioether in 80% formic acid, afforded 5′-deoxy-5′-(5-pyrrolo[2,3-b]pyridinemethylthio)adenosine or 5′-deoxy-5′-[5-(pyrrolo[2,3-d]pyrimidin-4-one)methylthio]adenosine, respectively. Similarly, the metiodide salt of the iso-gramine analog, 2-amino-6-dimethylaminomethylpyrrolo[2,3-d]pyrimidin-4-one afforded 5′-deoxy-5′-[6-(2-aminopyrrolo[2,3-d]pyrimidin-4-one)methylthio]adenosine.     

12H-naphtho[1′,2′:5,6]pyrano[2,3-d]pyrimidine derivatives

Reaction of 1-oxo-2-formyl-3-dimethylamino-1H-naphtho[2,1-b]pyran with amidines, guanidine, O-methylisourea, S-methylisothiourea afforded 9-substituted 12-oxo-12H-naphtho[1′,2′:5,6]pyrano[2,3-d]pyrimidines. When the reaction with O-methylisourea was carried out in anhydrous pyridine, 10,20-dioxo-10H,20H-dinaphtho[1,2-e:1′,2′-e′][1,5]diazocino[2,3-b:6,7-b′]dipyran was formed.     

Syntheses of 8-aminoimidazo[4′,5′:5,6]pyrido[2,3-d]pyrimiciines: Linear tricyclic analogs of adenine

The syntheses of 8-aminoimidazo[4′,5′:5,6]pyrido[2,3-d]pyrimidines (7), stretched-out versions of the naturally occuring nucleoside base adenine, are reported. Their preparation involves conversion of purine into 5-arninoimidazo[4,5-b]pyrimidine-6-carbonitrile ( 1 ) by reaction with malononitrile, followed by construction of the pyrimidine ring in two steps via the ethoxymethylene derivative 3 . 8-Azapurine can be converted to 8-amino-1,2,3-triazolo[4′,5′:5,6]pyrido[2,3-d]pyrimidines 8 in a similar fashion.     

New heterocyclic structures. [1,2,5]Thiadiazolo[3′,4′:4,5]pyrimido-[2,1-b][1,3]thiazine and thiazolo[3,2a][1,2,5]thiadiazolo[3,4-d]pyrimidine

Derivatives of two new molecular structures, namely, 7,8-dihydro-6H,10H-[1,2,5]thiadiazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-10-one and 6,7-dihydro-9H-thiazolo[3,2-a][1,2,5]thiadiazolo[3,4-d][pyrimidin-9-one, and derivatives of N-substituted sulfamic acid, namely, (8-amino-3,4-dihydro-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-on-7-yl)sulfamic acid and (7-amino-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidin-5-on-6-yl)sulfamic acid, were separated out as by-products in the reduction reaction of 8-amino-3,4-dihydro-7-nitroso-2H,6H-pyrimido[2,1- b][1,3]thiazin-6-one and 7-amino-2,3-dihydro-6-nitroso-5H-thiazolo[3,2-a]pyrimidin-5-one derivatives, respectively, with sodium hydrosulfite. A mechanism of reaction, which hypothesizes the action of sodium hydrosulfite in an asymmetic form, is proposed. The results of single-crystal X-ray investigation on 7,8-dihydro-6H,10H-[1,2,5]thiadiazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-10-one (R = 0.032 for 863 reflections) and (8-amino-3,4-dihydro-2H,6H-pyrimido[2,1-b]- [1,3]thiazin-6-on-7-yl)sulfamic acid, sodium salt (R = 0.028 for 3507 reflections) are reported.     

Polycyclic N‐Heterocyclic Compounds. Part 84: Reaction of N‐(pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4‐yl)amidines or N‐(pyrido[2′,3′:4,5]furo[3,2‐d]pyrimidin‐4‐yl)amidines with Hydroxylamine Hydrochloride

The reactions of nine N‐(pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4‐yl)amidines ( 3 ) with hydroxylamine hydrochloride produced new cyclization products. These were formed via ring cleavage of the pyrimidine component followed by a 1,2,4‐oxadiazole‐forming ring closure to give N‐[2‐([1,2,4]oxadiazol‐5‐yl)thieno[2,3‐b]pyridin‐3‐yl]formamide oximes ( 11 ). Reaction of six N‐(pyrido[2′,3′:4,5]furo[3,2‐d]pyrimidin‐4‐yl)amidines ( 12 ) with hydroxylamine hydrochloride gave similar results. Effects of the newly synthesized compounds on pentosidine formation were also evaluated.     

Furopyridines. XXIV. Nitration,chlorination, acetoxylation and cyanation of 2,3-dihydrofuro[2,3-b]-, -[3,2-b]-, -[2,3-c]- and -[3,2-c]pyridine N-Oxides

Nitration of 2,3-dihydrofuro[3,2-b]- N-oxide 3b and -[2,3-c]pyridine N-oxide 3c afforded the nitropyridine compounds 4b, 5b and 6 from 3b and 4c, 5c, 5′c and 7 from 3c , while -[2,3-b]- N-oxide 3a and -[3,2-c]pyridine N-oxide 3d did not give the nitro compound. Chlorination of 3b and 3c with phosphorus oxychloride yielded mainly the chloropyridine derivatives 15b, 15′b from 3b and 15c and 15′c from 3c , whereas 3a and 3d gave pyridine derivatives formed through fission of the 1–2 ether bond of the furo-pyridines 13a , 14 and 13d . Acetoxylation of 3b and 3c gave 3-acetoxy derivatives 18b and 18c and the parent compound 1b and 1c . Acetoxylation of 3a yielded compounds formed through fission of the 1–2 bond 16 and 17 and 3d gave furopyridones 19 and 19 ′. Cyanation of 3b and 3c yielded mainly the cyanopyridine compounds 20b, 20c and 20′c . Cyanation of 3a and 3d gave the cyanopyridine compounds 20a , 20d and 20′d accompanying formation of the pyridine derivatives 21a, 21d and 21′d .