Furan derivatives. Part 10. Synthesis of cyclohepta[cd]benzofuran

Cyclohepta[cd]benzofuran 2 was synthesized by heating (5-oxo-5H-benzocyclohepten-4-yloxy)acetic acid 16 with sodium acetate in acetic anhydride or by photocyclization of 16 in acetonitrile. Several reactions of cyclohepta[cd]benzofuran 2 were examined. Protonation of 2 with trifluoroacetic acid occurred at the 2-position to give a tropylium ion 17 . Catalytic hydrogenation of 2 with palladium on charcoal proceeded smoothly to give tetrahydrocyclohepta[cd]benzofuran 18 . The Diels-Alder reaction of 2 with tetracyano-ethylene produced an adduct 19 . Formylation of 2 with phosphorus oxychloride and dimethylformamide occurred easily at the 2-position to afford compound 20 . Cyclohepta[cd]benzofuran 2 has both properties of heptafulvene and benzofuran.     

Furan derivatives. Part 13 . Synthesis of thiopyrano[4,3,2-cd]benzofuran

Thiopyrano[4,3,2-cd]benzofuran 9 possessing benzofuran and methylenethiopyran structures in the molecule was synthesized starting from 1-chloro-4-methoxy-2-nitrobenzene 11. Some reactions (formylation, protonation and catalytic hydrogenation) on 9 were examined. The 2-position of 9 was highly reactive toward electrophilic reagents and the furan ring was readily reduced by catalytic hydrogenation with palladium-charcoal. Thiopyrano[4,3,2-cd]benzofuran 9 has both properties of methylenethiopyran and benzofuran.     

Furan derivatives. Part 9. Synthesis and properties of cyclohepta[cd]benzofurans

Cyclohepta[cd]benzofurans 1a-c were synthesized by heating (5-oxo-5H-benzocyclohepten-4-yloxy)acetic acids 7a-c with sodium acetate in acetic anhydride or by irradiation of 7a-c in acetonitrile. Several reactions such as protonation, catalytic hydrogenation, Diels-Alder reaction, acylation, and photoreaction were examined for 1a-b . The results show that cyclohepta[cd]benzofurans have both properties of heptafulvene and benzofuran. The carbon-carbon double bond in the furan ring of 1a has aromatic character, however, the carbon-carbon double bonds in the seven-membered ring have olefinic character.     

v-triazolines. Part XVI. Synthesis of benzothiepino[4,5-d]-v-triazole derivatives

The cycloaddition reaction of some arylazides to enamines 4a-f afforded v-triazolines 5a-i ; by subsequent acid-catalyzed hydrolysis v-triazoles 6a-c were obtained. The reversibility of the cycloaddition was demonstrated on the basis of spectroscopic or chemical evidences.     

Furan derivatives. Part 8 On substituent effects in the synthesis of 4,5-dihydro-3H-naphtho[1,8-bc]furans

4,5-Dihydro-3H-naphtho[1,8-bc]furans 4 and 6 which have various substituents (R¹ and R²) have been synthesized from 8-oxo-5,6,7,8-tetrahydro-1-naphthyloxyacetic acids 1 and 3 or their ethyl esters 2 . The reaction of acids 1 and 3 with sodium acetate in acetic anhydride gave a mixture of furans 4 and 6 and lactones 5 and 7 . The ratios of the products were varied according to the types of substituents (R¹ and R²) in acids 1 and 3 . As the substituent R¹ (R² = hydrogen) in acids 1 was changed from hydrogen to a methyl, ethyl or isopropyl group, production of furans 4 became more difficult. However, when a phenyl group was used as the substituent, furan 4 was obtained in good yield. Similarly, as the substituent R² (R¹ = hydrogen) in acids 1 was changed from hydrogen to a methyl, ethyl or isopropyl group, furan formation was more difficult. In contrast, acids 3 which had electron-withdrawing substituents such as chlorine, bromine or a nitro group at the 4-position afforded furans 6 in good yield. 4,5-Dihydro-3H-naphtho[1,8-bc]furans 4 and 4,5-dihydro-3H-naphtho[1,8-bc]furan-2-carbocylic acids 8 were synthesized from the reaction of esters 2 and potassium hydroxide in dioxane. When the substituents R¹ or R² in esters 2 were varied from hydrogen to a methyl, ethyl or isopropyl group the total yields of furans 4 and furancarboxylic acids 8 were reduced.     

Benzolactams. II. Synthesis of tetrahydrobenz[d]indeno-[1,2-b]azepines and their 12-Oxo derivatives

Aromatic methoxy and/or methylenedioxy substituted 7-methyltetrahydrobenz[d]indeno[1,2-b]-azepines 7 and their 12-oxo derivatives 8 were efficiently synthesized by the general method consisting of two types of intramolecular dehydrative cyclizations, as follows. N-Methyl-N-β-phenethylacetamides 1 were cyanomethylated in the two-step process of chloromethylation and treatment of the resultant benzyl chlorides with sodium cyanide. The condensation of the benzyl cyanides 2 with the appropriate benzaldehydes, followed by reduction of the benzylidene function, gave α,β-diphenylpropionitriles 3 . Successively, hydrolysis to the amino acids 4 and the thermal cyclization converted 3 to the benzylbenzazepinones 5 , which were also prepared by benzylation of the benzazepinones 6 smoothly by heating of 5 with phosphoryl chloride to afford the title azepines 7 . Further, these tetracyclic enamines 7 underwent autoxidation to the corresponding 12-oxo derivatives 8 , on exposure to oxygen in the presence of Triton B.     

Synthesis and cytotoxic activity of 2,5-disubstituted pyrimido[5,4-c]quinoline derivatives

A series of 2,5-disubstituted pyrimido[5,4-c]quinoline derivatives were synthesized and their cytotoxic activity against H460, HT-29 and MDA-MB-231 cell lines was evaluated in vitro.It was found that most of the tested compounds especially compound 17, shown stronger activity to the selected three cell lines than ZM447439.     

Synthesis of substituted 2,5-diazabicyclo[2.2.1]heptanes

A new method is proposed for the synthesis of substitituted 2,5-diazabicyclo[2.2.1]heptanes from 1-(tert-butoxycarbonyl)-4-tosyloxy-2-(tosyloxymethyl)pyrrolidine.¹H NMR spectroscopy indicated multiple conformations of 2-(tert-butoxycarbonyl)-2,5-diazabicyclo[2.2.1]heptanes in solution.St. Petersburg State University, 198904 St. Petersburg, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 501–503, April, 2000.     

Some derivatives of benz[f]azepine. Part III

We report the synthesis by two routes, of hitherto unknown 3, 4-epoxy-2, 3, 4, 5-tetrahydrobenz[f]azepine-2, 5-dione and hence a new route to 2, 3, 4, 5-tetrahydrobenz[f]azepine-2, 4, 5-triones which are precursors of 2-quin-olonecarboxylic acids.     

Synthesis of [1,5]benzothiazepine derivatives

Various derivatives of 2,3-dihydro[1,5]benzothiazepin-4(5H)-ones were synthesized. Alternative route for the synthesis of 5-dimethylaminoethyl-2,3-dihydro[1,5]benzothiazepin-4(5H)-ones and 4-dimethylaminopro-poxy-(2H,5H)-[1,5]benzothiazepines are described.     

Synthesis and polymerization of 2,5-dimethylene-2,5-dihydrothieno[3,2-b]thiophene derivatives: The structure and reactivity of quinonoid monomers

Novel 2,5-dimethylene-2,5-dihydrothieno[3,2-b]thiophene derivatives such as 2,5-bis[di(ethylthio)methylene]-2,5-dihydrothieno[3,2-b]thiophene ( 4b ) and 2,5-bis[cyano(ethylthio)methylene]-2,5-dihydrothieno[3,2-b]thiophene ( 4c ) were successfully synthesized as isolable crystals. Polymerization behavior of 2,5-bis(dicyanomethylene)-2,5-dihydrothieno[3,2-b]thiophene ( 4a ), 4b , and 4c was investigated. 4a , 4b , and 4c are not homopolymerizable with any initiators and also not copolymerizable with vinyl monomers such as styrene (St), methyl methacrylate, and acryronitrile except for an alternating copolymerization of 4a with St. 4a , 4b , and 4c did not copolymerize with 7,8-bis(butoxycarbonyl)-7,8-dicyanoquinodimethane (BCQ) as a highly conjugated comonomer and instead only homopolymer of BCQ was obtained, indicating that they are much less reactive than BCQ. To obtain the relative reactivity among 1c , 2c , and 4c , the rate of addition reaction of 2,2′-azobis(isobutyronitrile) (AIBN) with 4c was compared with those of AIBN with 7,8-bis(ethylthio)-7,8-dicyanoquinodimethane ( 1c ) and with 2,5-bis[cyano(ethylthio)methylene]-2,5-dihydrothiophene ( 2c ) by NMR spectroscopy and analyzed with the first-order kinetics. The relative reactivity among 1c , 2c , and 4c was found to be as follows: 1c > 4c > 2c . The relationship between structure and reactivity for the quinonoid compounds was discussed. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3027–3039, 1999     

Studies on the syntheses of heterocyclic compounds. Part DLXXXII . Synthesis of benzo[a] quinolizine derivatives and pyrrolo[2,1-a] isoquinoline derivatives by phenolic cyclization

Phenolic cyclization of 3-hydroxy phenethylamine with acylbutyric acid and acylpropionic acid afforded the lactam of the corresponding benzol[a] quinolizine and pyrrolo[2, 1-a]isoquinoline derivatives, which were reduced with lithium aluminum hydride to give the benzol[a]quinolizine and pyrrolo[2,1 -a] isoquinoline derivatives, respectively. The configurations of acetyl derivatives of these products were determined.     

Furan derivatives. part 11 [1]. on substituent effects in the synthesis of 3,4,5,6-tetrahydrocyclohepta[cd]benzofurans

Tetrahydrocyclohepta[cd]benzofurans 7a-e were synthesized by the treatment of ( 5 -oxo-tetrahydro-5H-benzocyclohepten-4-yloxy)acetic acids 5a-e with sodium acetate in acetic anhydride or by heating of their esters 6a-e with sodium hydroxide or sodium hydride in dioxane. The yield of furans 7 decreased as a substituent R of acids 5 or esters 6 was changed from hydrogen to a methyl, ethyl, or isopropyl group. When R was a phenyl group furan 7e was always prepared in good yield. Sodium hydride was a useful base for synthesis of tetrahydrocyclohepta[cd]benzofurans.     

Synthesis of the 2,5-di-t-butyl-cyclopenta[a]pentalenide ion: A novel 12π-electron system

The resonance destabilized, paratropic lithium 2,5-di-t-butyl-cyclopenta [a] pentalenide has been prepared as the first derivative of the cyclopenta [a] pentalenide ion.     

Saturated heterocycles,Part 172. Synthesis of 2,6-disubstituted-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine derivatives

The title compounds were synthesized via the addition of methyl acrylate to benzylamine or to α-aminopyridine, which gave the corresponding diesters, e.g. 12 , followed by Dieckmann condensation of the latter to yield the keto-esters 13 , which were condensed with amidines and guanidines, 3, 14 . Removal of the benzyl group by hydrogenolysis and subsequent alkylation of the nitrogen atom at position 6 in the resulting compound 5 , with variation of the substituents on C-2, gave a number of products with potential biological action; some of them gave analgesic and anti-inflammatory effects.     

Synthesis and reactivity of thieno[2,3-b]quinoline derivatives (Part II)

As a continuation of our previous review entitled “Vilsmeier-Haack cyclisation as a facile synthetic route to thieno[2,3-b]quinolines (Part I).” This review describes the methods of preparation and the chemical reactivity of thieno[2,3-b]quinolines, which might show interesting biological activities.     

Synthesis of benzo[g]quinoline derivatives

In the condensation of 1, 2, 3, 4-tetrahydro-4-oxobenzo[g]quinollne with ammonia, which leads to the formation of 4-aminobenzo[g]quinoline, the by-products are benzo[g]quinoline (V) and 1, 2, 3, 4-tetrahydrobenzo]quinoline (VI), which are also obtained from 1, 2, 3, 4-tetrahydro-4hydroxybenzo[g]quinoline by its dehydration and the subsequent disproportionation of the dihydrobenzo[g]quinoline formed.For communication II, see [1].     

Synthesis of benzo[g]quinoline derivatives. XI. 2,4-Diamino-substituted benzo[g]quinolines

Previously unknown 2,4-diamino-substituted benzo[g]quinolines were synthesized from 2,4-dihydroxybenzo[g]quinoline.