Condensed pyridine bases synthesis of some benzo[b]furo[2,3-c]-, benzo[b]- thieno[2,3-c]-, and benzo[b]selenopheno[2,3-c]-quinolines

Summary Condensation of benzo[b]furan-3(2H-one, benzo[b]thiophen-3(2H)-one and benzo[b]selenophen-3(2H)-one with dimedone gives 2-(3-heteryl)dimedones. Acylation of the latter leads to the corresponding tetracyclic pyrylium salts, from which condensed quinolines are obtained. Some condensed quinoline derivatives are obtained by reaction of 1-oxo-1,2,3,4-tetrahydroheterene[2,3-c]quinolines with sodium borohydride, hydrazine, and hydroxylamine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 321–326, March, 1994.     

Synthesis of 3-amino derivatives of benzo[b]furo[2,3-c]pyridines

The reaction of 1,7-dimethyl-3(2H)-benzo[b]furo[2,3-c]pyridone with phosphoric acid amides gave 1,7-dimethyl-3-dimethylamino (morpholino)benzo[b]furo[2,3-c]pyridines. A method for the synthesis of 3-amino derivatives of 4-nitrobenzo[b]furo[2,3-c]pyridines, which consists in heating 1,7-dimethyl-4-nitro-3(2H)-benzo[b]furo[2,3-c]pyridone with hexamethyldisilazane and secondary or primary amines in pyridine, was developed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1552–1555, November, 1991.     

Photochemical Reactions of Benzo[b]Thiophene-2,3-Diones with 2,3-Dimethylbut-2-Ene

Abstract

Photochemical reactions of benzo[b]thiophene-2,3-diones with 2,3-dimethylbut-2-ene gave dioxene derivatives in excellent yields.     

Synthesis and application of ethyl 2-arylazo-4,9-dioxonaphtho[2,3-b]thiophene-3-carboxylate

Synthesis of ethyl 2-arylazo-4,9-dioxonaphtho[2,3-b]thiophene-3-carboxylate was achieved by diazotization of ethyl 2-amino-4,9-dioxonaphtho[2,3-b]thiophene-3-carboxylate and coupling with selected N,N-dialkylanilines. The key intermediate ethyl 2-amino-4,9-dioxonaphtho[2,3-b]thiophene-3-carboxylate was synthesized by the condensation of sodium salt of ethyl cyanoacetate with 2,3-dichloro-1,4-naphthoquinone. Ethyl 2-arylazo-4,9-dioxonaphtho[2,3-b]thiophene-3-carboxylate were applied on polyester fibers as disperse dyes and their dyeing properties were studied.     

A new synthesis of naphtho[2,3-C]pyrroles. Conversion of naphtho[2,3-C]thiophene-4,9-diones to naphtho[2,3-C]pyrrole-4,9-diones

A series of 2-substituted-4,9-dihydronaphtho[2,3-c]pyrrole-4,9-diones was prepared by the reaction of 4,9-dihydronaphtho[2,3-c]thiophene-4,9-diones with primary amines under mild conditions. The presence of halogen in the naphtho[2,3-c]thiophene-4,9-dione and the presence of hydroxyl, ether, or tertiary amine functions in the amine reagent do not interfere with the course of the reaction.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 8 . [1]Benzothieno[2,3-c]naphtho[1,2-h]quinoline and [1]benzothieno[2,3-c]naphtho[1,2-h][1,2,4]triazolo[4,3-a]quinoline

The previously unknown polycyclic heterocyclic ring systems, namely, [1]benzothieno[2,3-c]naphtho[1,2-h]-quinoline and [1]benzothieno[2,3-c]naphtho[1,2-h][1,2,4]triazolo[4,3-a]quinoline were synthesized via photocyclization of 3-chloro-N-(1′-phenanthryl)benzo[b]thiophene-2-carboxamide.     

The synthesis of [1]benzothieno[2,3-c]quinolines, [1]benzothieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline,and [1]benzothieno[2,3-c]tetrazolo[1,5-a]quinoline

Photocyclization of 3-chloro-N-phenylbenzo[b]thiophene-2-carboxamide 10 afforded [1]benzothieno[2,3-c]-quinolin-6(5H)-one 11 which was chlorinated to 6-chloro[1]benzothieno[2,3-c]quinoline 12 followed by dechlorination to give [1]benzothieno[2,3-c]quinoline 5 . A series of 6-substituted alkoxy and thioalkoxy[1]benzothieno[2,3-c]quinoline derivatives were prepared along with the N-methyl quaternary salt 13 of 5 . 6-Chloro[1]-benzothieno[2,3-c]quinoline 12 was converted into 6-hydrazino[1]benzothieno[2,3-c]quinoline 23 which upon treatment with formic acid yielded [1]benzothieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline 6 . Treatment of 23 with nitrous acid resulted in [1]benzothieno[2,3-c]tetrazolo[1,5-a]quinoline 7 . Compounds 6 and 7 are novel heterocyclic ring systems.     

Thiophene chemistry—XXII : Some reactions of benzo[b]thiophene-2(3H)one

Benzo[b]thiophene-2(3H)one has been prepared from 2-t-butoxybenzo[b]thiophene by dealkylation. Alkylation of sodium, thallium and tetrabutylammonium salts of benzo[b]thiophene-2(3H)one produces both C- and O-alkylation along with products due to ring-opening. At elevated temperatures benzo[b]thiophene-2(3H)one reacts with HMPA (hexamethylphosphorictriamide) to give 2-dimethylaminobenzo[b]thiophene. Other 2-aminobenzo[b]thiophenes are produced by refluxing benzo[b]thiophene-2(3H)one in HMPA in the presence of excess of the corresponding amine.     

Synthese von 2,4-Diamino-thieno[2,3-d]pyrimidin-Derivaten

Synthesis of 2,4-Diamino-thieno[2,3-d]pyrimidines Condensation of 2-aminothiophene-3-carbonitrile ( 4 ) with guanidine or sequential addition of CS₂ and NH₃ to 4 provides 2,4-diaminothieno[2,3-d]pyrimidine ( 7 ). This compound yields, after sequential addition of sec-BuLi and either [3-(trifluoromethyl)benzene]sulfenyl chloride ( 8 ) or the corresponding disulfide 9 , followed by acidic work up, 2,4-diamino-6-{[3-(trifluoromethyl)phenyl]thio}thieno[2,3-d]pyrimidine ( 10 ). In another approach, 2-amino-5-{[3-(trifluoromethyl)phenyl]thio}thiophene-3-carbonitrile ( 11 ) obtained from 4 and 8 is transformed to 10 by condensation with guanidine. Corresponding to the second route, 2,4-diamino-6-[(naphth-2-yl)thio]thieno-[2,3-d]pyrimidine ( 16 ) is synthesized. Oxidation of 10 with m-chloroperbenzoic acid gives 2,4-diamino-6-{[3-(tri-fluoromethyl)phenyl]sulfinyl}thieno[2,3-d]pyrimidine ( 13 ).     

K-region oxides and imines of benzo[b]phenanthro[2,3-d]thiophene and benzo[b]phenanthro[3,2-d]thiophene

The syntheses of the K-oxides and K-imine derivatives of benzo[b]phenanthro[2,3-d]thiophene and benzo-[b]phenanthro[3,2-d]thiophene are described. The parent hydrocarbons 1 and 2 were oxidized with osmium tetroxide and sodium metaperiodate, and the dialdehydes 12 and 18 so formed, cyclized to the corresponding epoxides 1a,12b-dihydrobenz[b]oxireno[9,10]phenanthro[2,3-d]thiophene ( 7 ) and 1a,12b-dihydrobenz-[b]oxireno[9,10]phenanthro[3,2-d]thiophene ( 13 ). Reaction of the oxiranes with sodium azide gave mixtures of azido-alcohols that, in turn, were transformed to the thiaarene imines 1a,12b-dihydro-1H-benz[b]azirino-[9,10]phenanthro[2,3-d]thiophene ( 8 ) and 1a,12b-dihydro-1H-benz[b]azirino[9,10]phenanthro[3,2-d]thiophene ( 14 ), respectively, with the aid of tri-n-butylphosphine.     

Toluene dioxygenase-catalyzed cis-dihydroxylation of benzo[b]thiophenes and benzo[b]furans: synthesis of benzo[b]thiophene 2,3-oxide

Enzymatic cis-dihydroxylation of benzo[b]thiophene, benzo[b]furan and several methyl substituted derivatives was found to occur in both the carbocyclic and heterocyclic rings. Relative and absolute configurations and enantiopurities of the resulting dihydrodiols were determined. Hydrogenation of the alkene bond in carbocyclic cis-dihydrodiols and ring-opening epimerization/reduction reactions of heterocyclic cis/trans-dihydrodiols were also studied. The relatively stable heterocyclic dihydrodiols of benzo[b]thiophene and benzo[b]furan showed a strong preference for the trans configuration in aqueous solutions. The 2,3-dihydrodiol metabolite of benzo[b]thiophene was utilized as a precursor in the chemoenzymatic synthesis of the unstable arene oxide, benzo[b]thiophene 2,3-oxide.     

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.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 5. [1]Benzothieno[2,3-c]naphtho[2,1-f]-quinoline and [1]benzothieno[2,3-c]naphtho[1,2-g]quinoline

Two previously unknown heterocyclic ring systems, namely, [1]benzothieno[2,3-c]naphtho[2,1-f]quinoline ( 4 ) and [1]benzothieno[2,3-c]naphtho[1,2-g]quinoline ( 5 ) were synthesized via photocyclization of 3-chloro-N-(2-phenanthryl)benzo[b]thiophene-2-carboxamide ( 8 ) followed by chlorination and dechlorination. The total assignment of their ¹H- and ¹³C-nmr spectra was determined by utilizing inverse-detected HMQC and HMBC two-dimensional nmr spectroscopic methods.     

Derivate des 3-Phenyl-benzo[b]thiophens

Zusammenfassung 2-Methylthio-benzophenon reagierte mit Chloressigsäure zu 3-Phenyl-benzo[b]thiophen-2-carbonsäure und mit -Chlorphenylessigsäure zu 2,3-Diphenyl-benzo[b]thiophen. 3-Phenyl-5-methoxy-benzo[b]thiophen-2-carbonsäure wurde aus 3-Phenyl-5-amino-benzo[b]thiophen-2-carbonsäure durch Verkochen des Diazoniumsalzes und Methylierung erhalten; ihr N-Methylpiperazid sowie 3 basisch substituierte Ester wurden dargestellt.

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Derivatives of 3-phenylbenzo[b]thiophene

2-Methylthio-benzophenone reacted with chloroacetic acid to 3-phenyl-benzo[b]thiophene-2-carboxylic acid and with -chloro-phenylacetic acid to 2,3-diphenyl-benzo[b]thiophene. 3-Phenyl-5-methoxy-benzo[b]thiophene-2-carboxylic acid was prepared by diazotation of 3-phenyl-5-amino-benzo[b]thiophene-2-carboxylic acid and hydrolysis to the hydroxy compound followed by methylation; its N-methylpiperazide and three esters with basic substituents were synthesized.

     

The synthesis of monomethoxy[1]benzothieno[2,3-c]quinolines

A series of monomethoxy[1]benzothieno[2,3-c]quinolines 24-28 were prepared by photocylization of the appropriate 3-chloro-N-phenylbenzo[b]thiophene-2-carboxamides 9–13 to [1]benzothieno[2,3-c]quinolin-6(5H)-ones 14-18 followed by chlorination to 6-chloro[1]benzothieno[2,3-c]quinolines 19-23 then dechlorination resulting in the title compounds except for 25 which was achieved by direct reduction of 15 . Reaction of 24-28 with methyl iodide provided the corresponding N-methyl quaternary salts 29-33 . Also, conversion of 4-meth-oxy[1]benzothieno[2,3-c]quinolin-6(5H)-one 16 to 4-methoxy-6-methylthio[1]benzothieno[2,3-c]quinoline 35 and 4,6-dimethoxy[1]benzothieno[2,3-c]quinoline 36 is described.     

The synthesis of dimethoxy- and trimethoxy[1]benzothieno[2,3-c]quinolines

Three dimethoxy[1]benzothieno[2,3-c]quinolines 24–26 were prepared by photocyclization of the appropriate 3-chloro-N-phenylbenzo[b]thiophene-2-carboxamides 15–17 to [1]benzothieno[2,3-c]quinolin-6(5H)-ones 18–20 followed by chlorination to 6-chloro[1]benzothieno[2,3-c]quinolines 21–23 and then dechlorination resulting in the title compounds. Reaction of 24–26 with methyl iodide furnished the corresponding N-methyl quaternary salts 27–29 . Sodium methoxide readily converted 21–23 to trimethoxy[1]benzothieno[2,3-c]quinolines 30–32 .     

Synthesis,photochemical synthesis and antitumor evaluation of novel derivatives of thieno[3',2':4,5]thieno[2,3-c]quinolones

The novel derivatives of thieno[3',2':4,5]thieno[2,3-c]quinolones 6a, 6b, 7, 10a and 10b were synthesized in multistep synthesis starting from thiophene-3-carboxaldehyde and malonic acid reacting in aldol condensation or from 3-bromothiophenes or methyl 4-bromothiophene-2-carboxylate reacting in Heck reaction. They resulted in corresponding substituted thienylacrylic acids 3a-c, which were cyclized into thieno[2,3-c]thiophene-2-carbonyl chlorides 4a-c and converted into thieno[2,3-c]thiophene-2-carboxamides 5a-d. Prepared carboxamides were photochemically dehydrohalogenated into corresponding substituted thieno[3',2':4,5]thieno[2,3-c]quinolones 6a-d. Compound 7 was prepared from 6d by alkylation with N-[3-(dimethylamino)propyl]chloride hydrochloride in the presence of NaH. Compounds 10a and 10b were prepared from 6c in the multistep synthesis over acid 8 and acid chloride 9. Compounds 6a, 6b, 7, 10a and 10b were found to exert cytostatic activities against malignant cell lines: pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7), cervical carcinoma (HeLa), laryngeal carcinoma (Hep2), colon carcinoma (CaCo-2), melanoma (HBL), and human fibroblast cell lines (WI-38). The compound 6b, which bears the 3-dimethylaminopropyl substituent on quinolone nitrogen and methoxycarbonyl substituent on position 9, exhibited marked antitumor activity. On the contrary, compound 7, which also bears the 3-dimethylaminopropyl substituent on the quinolone nitrogen but anilido substituent on position 9, exhibited less antitumor activity than the others.     

Synthesis of 2-N-(benzo[b]thiophen-2-yl)benzo and heterofused-1,2,3-triazoles

A novel efficient synthesis of 2-N-(benzo[b]thiophen-2-yl)benzo and heterofused-1,2,3-triazoles was achieved by the diazotisation of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile and ethyl-2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate and coupling with selected aromatic and heterocyclic amines followed by air oxidation in the presence of cupric acetate.     

Nucleophilic addition to benzo[b]thieno[2,3-b]benzo[b]thiophene S,S,S′,S′-tetroxide

The reaction of benzo[b]thieno[2,3-b]benzo[b]thiophene S,S,S′,S′-tetroxide with primary and secondary amines and with alcohols gave 10 b-amino- and 10 b-alkoxy-5a, 10b-dihydro-benzo[b]thieno[2,3-b]benzo[b]thiophene S,S,S′,S′-tetroxides. These nucleophilic reagents do not add to benzo[b]thieno[2,3-b]benzo[b]thiophene S,S-dioxide.     

Synthesis and reactions of benzo[b]furo[2,3-c]pyrylium salts

A method has been developed for the synthesis of 3-acetonyl- and 3-phenacylben-zo[b]furans by cyclization of 1-arloxy-2,4-pentanediones and 1-phenyl-4-aryloxy-1,3-butanediones in polyphosphoric acid. Acylation of 3-acetonyl(phenyl-benzo-[b]furans with aliphatic acid anhydrides in the presence of perchloric acid gives the benzo[b]furo[2,3-c]pyrylium perchlorates. The recyclization of the pyrylium salts with ammonia, aqueous alkali, and morpholine has been examined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 889–893, July, 1987.