Chemical and photochemical synthesis of substituted dihydro-thieno[2',3':4,5]thieno[2,3-c]quinolin-6-ones and tetrahydro-dithieno[2,3-b:2',3'-d]thieno[2'',3''c:2'',3''c']diquinolin-6,14-dione

Some new substituted dihydrothieno[2',3':4,5]thieno[2,3-c]quinolin-6-ones 9- 12 and tetrahydrodithieno[2,3-b: 2',3'-d]thieno[2',3'-c:2',3'-c']diquinolin-6,14-dione (17) were prepared from the corresponding new anilides 5-8 and from the corresponding dianilide 15, respectively, by a multistep combination of chemical and photochemical reactions. All the prepared compounds are of particular interest because they might serve as DNA intercalators in anticancer therapy.     

Synthesis and Reactions of Some New Heterocyclic Compounds Containing Cycloalka[e]thieno[2,3‐b]pyridine Moiety

Hydrolysis of ethyl 3-amino-4-aryl-cycloalka[e]thieno[2,3-b]pyridine-2-carboxylates ( 3a-d) gave the corresponding o-aminocarboxylic acids 4a-d . Heating the latter compounds ( 4a-d) with acetic anhydride furnished the oxazinone derivatives 5a-d which, in turn, underwent recyclization reaction to give the corresponding pyrimidinones 6a-d upon treatment with ammonium acetate in acetic acid. Reaction of 3-amino-4-aryl-cycloalka[e]thieno[2,3-b]pyridine-2-carboxamides ( 3f,h ) with triethyl orthoformate gave pyrimidinone derivatives 7a,b . Reaction of 3-amino-4-phenyl-cycloalka[e]thieno[2,3-b]pyridine-2-carboxamides 3e,h with aromatic aldehydes furnished tetrahydropyridothienopyrimidinones 8a-d . Chlorination of 7a,b and 6a-d by using phosphorous oxychloride produced 4-chlorocycloalka[5′,6′]pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine derivatives 9a-f which were used as key intermediates in the synthesis of several new cycloalkapyrido-thienopyrimidines 10a-f ˜ 14a-f . Moreover, some cycloalkapyridothienotriazinones 15a,b-17a,b were synthesized.     

Facile synthesis of some novel pyrido[3',2':4,5]thieno[2,3-b][1,4]thiazine-8-carboxylic acids

Model tetrahydropyrido[3',2':4,5]thieno[2,3-b][1,4]thiazines 9a-c were synthesized via reductive lactamization, using sodium dithionite, of the respective 2-[(carboxyalkyl)thio]-3-nitro-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acids 7a-c. The latter derivatives were made via interaction of 2-chloro-7-cyclopropyl-3-nitro-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid (6) with each of alpha-mercaptoacetic, alpha-mercaptopropionic, and alpha-mercaptosuccinic acids and triethylamine in aqueous acetone at room temperature. The structures of 7a-7c and 9a-9c are supported by microanalytical and spectral (IR, MS, NMR) data. Compounds 9a and 9c showed potent inhibitory activity against the IGROV1 (Ovarian Cancer) cell line.     

Tetracyclic systems: Synthesis of isoindolo[1,2-b]thieno-[2,3(3,2 or 3,4)-e][1,3]thiazocines and Isoindolo[2,1-a]thieno-[2,3(3,2 or 3,4)-f][1,4] and [1,5]diazocines

Cyclization of thioglycolic acids derivatives 3a-d gave isoindolo[1,2-b]thieno[2,3(3,2 or 3,4)-e][1,3]-thiazocines 4a-d . Isoindolo[2,1-a]thieno[2,3(3,2 or 3,4)-f][1,4] or [1,5]diazocines 10b or 11a-c were synthesized from Beckmann or Schmidt rearrangement of the ketones 7a-c .     

Synthesis of thiopyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]furo[3,2-d]pyrimidines

<正>Reactions of the 6-hydroxy-thiopyrano[3,4-c]pyridine-5-carbonitrile derivative 1 withα-halo-carbonyl compounds gave the ortho-substituted intermediates 2a-c which were converted into furo[2,3-b]thiopyrano[4,3-d]pyridines 3a-c by fusion of a furan moiety under basic conditions.Further cyclization of 3a-c led to a fusion of a pyrimidine ring,yielding the tetracyclic products 6,7 and 8.In addition,condensation of 6 with various aromatic aldehydes afforded the corresponding imines 9a,b.Mannich reaction of 7 gave products 10a,b.     

Synthesis and reactions of benzo[b]thieno[2,3-c]pyrylium pairs

Benzo[b]thieno[2,3-c]pyrylium perchlorates were obtained in high yields in the acylation of benzo[b]thien-3-ylacetone with aliphatic acid anhydrides in the presence of 70% perchloric acid. Treatment of the products with ammonia converts them to benzo[b]thieno[2,3-c]pyridines (in yields higher than 90%), whereas hydroxy and dialkylamino derivatives of dibenzothiophene were obtained in up to 50% yields by treatment of the products with alkalis or secondary amines, respectively.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1351–1354, October, 1981.     

Novel Synthesis of Thieno[2,3-c]Pyridazine and Pyrimido[4',5':4,5]thieno[2,3-c]pyridazine Derivatives

Abstract

Novel series of thieno[2,3-c]pyridazines and pyrimido[4′,5′:4,5] thieno-[2,3-c]pyridazines have been synthesized from the readily accessible 4-cyano-5,6-dimethylpyridazin-3(2H)-thione 3b.     

An efficient synthesis of novel benzo[b]pyrido[3',2':4,5] thieno[2,3-e][1,6]naphthy-ridine-8-ones

An efficient method for the synthesis of novel benzo[b]pyrido[3',2':4,5] thieno[2,3-e][1,6] naphthyridine-8-one derivatives has been developed using a Pictet-Spengler reaction between 4-(3-aminothieno[2,3-b]pyridin-2-yl)quinoline-2-ones, which could be obtained from the alkylation of 4-bromomethylquinoline-2-ones with 3-cyanopyridine-2-thione followed by a Thorpe-Ziegler isomerization, and aromatic aldehydes under p-TsOH as catalysis in good yields.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 19. Thieno[3′,2′:4,5]thieno[2,3-c]-naphtho[1,2-f]quinoline,thieno[3′,2′:4,5]thieno[2,3-c]naphtho-[1,2-f][1,2,4]triazolo[4,3-a]quinoline and thieno[3′,2′:4,5]-thieno[2,3-c]naphtho[1,2-f]tetrazolo[1,5-a]quinoline

Photocyclization of 3-chloro-N-(3-phenanthryl)thieno[2,3-b]thiophene-2-carboxamide ( 5 ) yielded only one of the two possible structural isomers, thieno[3′,2′:4,5]thieno[2,3-c]naphtho[1,2-f]quinolin-6(5H)-one ( 6 ), which was further elaborated to afford the unsubstituted ring system 10 , its triazole 11 and tetrazole 12 . The structural confirmation of 10 was achieved by the total assignment of its ¹H and ¹³C nmr spectra by the concerted utilization of two-dimensional nmr spectroscopic methods.     

Synthesis of Hexa- and Octahydropyrido[3'2':4,5]thieno[3,2-d]pyrimidines

The reaction of N-methylmorpholinium 4-(2-chlorophenyl)-5-cyano-2-oxo-1,2,3,4-tetrahydropyridine-6-thiolate with chloroacetamide in DMF in the presence of an excess of KOH gave 3-amino-2-carbamoyl-4-(2-chlorophenyl)-6-oxo-4,5,6,7-tetrahydrothieno[2,3-b]pyridine. Refluxing the latter with acyl chlorides in AcOH or heating in formic acid gave hexahydropyrido[3',2':4,5]thieno[3,2-d]pyrimidine derivatives and reaction with cyclohexanone gave a spiro-linked octahydropyrido[3',2':4,5]thieno[3,2-d]pyrimidine.     

Multistep, microwave assisted, solvent free synthesis and antibacterial activity of 6-substituted-2,3,4-trihydropyrimido[1,2-c]9,10,11,12-tetrahydrobenzo[b]thieno[3,2-e]pyrimidines

A novel, efficient, microwave assisted route for the synthesis of 6-substituted-2,3,4-trihydropyrimido[1,2-c]-9,10,11,12-tetrahydrobenzo[b]thieno[3,2-e]pyrimidines in good yields has been developed. The intermediates, 2-substituted-4-[3-hydroxy(propyl-1-amino)]5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidines were obtained by irradiating 2-substituted-4-chloro-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidines with 1-amino-propanol under basic conditions in a microwave oven. 4-Chlorothieno[2,3-d]pyrimidines were synthesized by microwave irradiation of equimolar mixture of 4-hydroxythieno[2,3-d]pyrimidines and phosphorus oxychloride. The final compounds were screened for antibacterial activity by Kirby Bauer's method using amicacin as the standard against various gram positive and gram negative bacteria. All the compounds showed antibacterial activity comparable with the standard.     

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.     

Condensed Thienopyrimidines. 14. Synthesis of 10H-Thiopyrano[4',3':4',5']thieno[2',3':4,5]pyrimido[2,3-c]-1,2,4-triazines

Reaction of a substituted 2-aminothienothiopyran with methyl(phenyl) isothiocyanate, intramolecular cyclization of the obtained N'-methyl(phenyl) thioureido derivatives, and work up of the cyclization products with hydrazine hydrate gave 2-hydrazinodihydrothiopyranothienopyrimidines. Treatment of the latter with pyruvic acid gave the novel 10H-thiopyrano[4',3':4',5']thieno[2',3':4,5]pyrimido[2,3-c]-1,2,4-triazines.     

Synthesis of novel benzo[b]pyrimido[4',5':5,4]thieno[2,3-e][1,6]naphthyridine-8-ones via Pictet–Spengler cyclization

An efficient method for the synthesis of novel benzo[b]pyrimido[4',5':5,4]thieno[2,3e]-[1,6]naphthyridine-8-one derivatives via Pictet–Spengler cyclization is reported. The reaction of 4-(3-aminopyrimido[4,5-d]thieno-2-yl)quinoline-2-ones, which could be obtained from Thorpe–Ziegler isomerization of 4-bromomethylquinoline-2-ones and 5-cyano-1,6-dihydro-4-methyl-2-phenyl-6-thioxopyrimidine,with aromatic aldehydes in the presence of BF_3·OEt_2 gives pyrimidothieno[1,6]naphthyridines in good yields.     

A convenient approach to heterocyclic building blocks: synthesis of novel ring systems containing a [5,6]Pyrano[2,3-c]pyrazol-4(1H)-one moiety

Starting from commercially available educts, a straightforward synthetic route to new heterocyclic building blocks is exemplified with the one- or two-step synthesis of tri-, tetra-, or pentacyclic ring systems. Representatives of the following novel ring systems are prepared from 3-methyl-1-phenyl-2-pyrazolin-5-one and the corresponding o-halo-arenecarbonyl chloride using calcium hydroxide in refluxing 1,4-dioxane: pyrimidino[4',5':5,6]pyrano[2,3-c]pyrazol-4(1H)-one, thieno[3',2':5,6]pyrano[2,3c]pyrazol- 4-(1H)-one, thieno[3',4':5,6]pyrano[2,3-c]pyrazol-4(1H)-one, thieno[3',2':4',5']thieno[2',3':5,6]-pyrano[2,3-c]pyrazol-4(1H)-one, [1,3]dioxolo[5',6'][1]benzothieno[2',3':5,6]pyrano-[2,3-c]- pyrazol-4(1H)-one, pyridazino[4',3':5,6]pyrano[2,3-c]pyrazol-4(1H)-one and pyrazolo-[4',3':5',6']pyrido[3',4':5,6]pyrano[2,3-c]pyrazol-4(1H)-one. While the latter two ring systems are directly obtained due to a spontaneous intramolecular substitution reaction, in the other reactions uncyclised 4-aroylpyrazol-5-ols are produced, which are cyclised into the target heterocycles in a subsequent synthetic step (i.e. treatment with NaH in DMF). Detailed NMR spectroscopic investigations ((1)H-, (13)C-, (15)N-) with the obtained compounds were undertaken to unambiguously prove the new structures.     

Synthesis and Properties of Derivatives of the new Heterocyclic System Benz[4,5]imidazo[1,2-c]pyrido[3',2';4,5]thieno[2,3-e]pyrimidine

Derivatives of a new heterocyclic system - benz[4,5]imidazo[1,2-c]pyrido[3',2';4,5]thieno[2,3-e]pyrimidine have been obtained by successive reactions in three stages - alkylation of 3-cyanopyridine-2(1H)-thiones with 2-chloromethylbenzylimidazole to give 2-benzimidazolylmethylthio-3-cyanopyridines, closing the thiophene ring in the latter to form 3-amino-2-(benzimidazolyl-2)thieno[2,3-b]pyridines, and cyclization of the pyrimidine ring by acylation with carboxylic acid anhydrides or chlorides.     

Efficient Synthesis of 3,5,6,8-Tetrahydro-4H-thiopyrano[4',3':4,5]thieno[2,3-d]pyrimidin-4-ones via an Iminophosphorane

3,5,6,8-Tetrahydro-4H-thiopyrano[4',3':4,51thieno[2,3-d]pyrimidin-4-ones(7) were synthesized via the base catalytic reactions of amines or phenols with carbodiimides(5),which were obtained from the aza-Wittig reactions of iminophosphoranes(4) with aromatic isocyanates.     

Derivatives of Condensed Thienopyrimidimines. 13. Synthesis and Structure of Pyrano[4',3':4,5]thieno[3,2-e]-1,2,4-triazolo[2,3-c]pyrimidines

Methods for the synthesis of 5-substituted 10,10-dimethyl-10,11-dihydro-8H-pyrano[4',3':4,5]thieno[3,2-e]-1,2,4-triazolo[2,3-c]pyrimidines have been developed. An X-ray crystallographic study of 5-(2-ethoxymethylhydrazino)-10,10-dimethyl-10,11-dihydro-8H-pyrano[4',3':4,5]thieno[3,2-e]-1,2,4-triazolo[2,3-c]pyrimidine has been carried out.     

Structural effects on the electronic properties of extended fused-ring thieno[3,4-b]pyrazine analogues

The synthesis and characterization of the extended thieno[3,4-b]pyrazine analogues acenaphtho[1,2-b]thieno[3,4-e]pyrazine (3a), 3,4-dibromoacenaphtho[1,2-b]thieno[3,4-e]pyrazine (3b), 3-octylacenaphtho[1,2-b]thieno[3,4-e]pyrazine (3c), dibenzo[f,h]thieno[3,4-b]quinoxaline (4), and thieno[3',4':5,6]pyrazino[2,3-f][1,10]phenanthroline (5) are reported. Comparison of structural, electrochemical, and photophysical properties to those of simple thieno[3,4-b]pyrazines are provided in order to provide structure-function relationships within this series of compounds.     

Condensed pyridine bases. A new approach to the synthesis of 3-phenacylbenzo[b]thiophenes and 3-phenacyl-5-ethylthieno[2,3-b]thiophene. Synthesis of new derivatives of benzothieno[2,3-c]pyrylium and thieno[2′,3′:5,4]thieno-[2,3-c]pyrylium and pyridine bases

A new method is proposed for the production of substituted 3-phenacylbenzo[b]thiophenes by the intramolecular cyclization of 1-phenyl-4-phenylthio-1,3-butanediones in polyphosphoric acid. The analogous cyclization of 1-phenyl-4-(5-ethyl-2-thienylthio)-1,3-butanedione leads to 3-phenacyl-5-ethylthieno[2,3-b]thiophene. The acylation of substituted 3-phenacylbenzo[b]thiophenes and 3-phenacyl-5-ethylthieno[2,3-b]thiophene by the anhydrides of aliphatic acids in the presence of perchloric acid leads to 1-alkyl-3-phenylbenzothieno[2,3-c]pyrylium perchlorates and 2-ethyl-5-phenyl-7-methylthieno[2′,3′:5,4]thieno[2,3-c]pyrylium perchlorate. The action of ammonium acetate on the obtained salts gives the corresponding pyridine bases. L. M. Litvinenko Institute of Physical Organic Chemistry and Coal Chemistry, National Academy of Sciences of Ukraine, Donetsk 340114. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1335–1339, October, 1998.