Reactions of N- and C-alkenylanilines: IX. Synthesis, oxidation, and nitration of some 7-methyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles

Heating of 4-acyl-3-iodo-7-methyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indoles in piperidine gave 4-acyl-7-methyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles which were oxidized with KMnO4 to obtain the corresponding 4-acyl-7-methyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-1,2-diols. Oxidation of 4-acyl-7-methyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles at the olefinic double bond with hydrogen peroxide in acetonitrile in the presence of formic acid afforded stereoisomeric epoxides with cis and trans orientation of the nitrogen-containing and oxirane rings. Nitration with a mixture of ammonium nitrate and trifluoroacetic anhydride produced 5-nitro derivatives. The structure of 1-{(1aR*,1bR*,6bS*,7aS*)-5-methyl-1a,1b,2,6b,7,7ahexahydrooxireno[4,5]cyclopenta[1,2-b]indol-2-yl}ethanone was determined by X-ray analysis.     

Synthesis of 3-substituted cyclopenta[b]indoles

When reacting with I₂, 2-(cyclopent-2-enyl)anilines undergo cyclization into 3-iodo-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indoles in high yields. The minor reaction products were 3,5- or 3,7-diiodoindolines. Ammonolysis of 3-iodo-5-methyl-1,2,3,3a,4,8b-hexahydro-cyclopenta[b]indole or itsN-chloroacetyl derivative results in 3-amino-5-methyl-1,2,3,3a,48b-hexahydro- and 5-methyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles. Published inIzvestiya Akademii Nauk. Seriya Khimischeskaya, No. 10, pp. 1789–1793, October, 2000.     

Reactions of N- and C-Alkenylanilines: V. Synthesis of Iodo-Substituted Heterocycles from o-Cycloalkenylanilines and Their Transformations

Iodination of N-isopropyl- and N-benzyl-2-(2-cyclohexenyl)anilines gave the corresponding 1-iodo-hexahydrocarbazoles which underwent quantitative isomerization into 3-iodo-2,4-propano-1,2,3,4-tetrahydro-quinolines. Nucleophilic substitution in 1-iodohexahydrocarbazoles and 3-iodo-2,4-propano-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole was studied. N-Allylation of the latter via reaction with allyl bromide is accompanied by replacement of the iodine atom by bromine.     

Cyclization ofN-acetyl-ortho-cycloalkenylanilines on treatment with bromine andN-bromosuccinimide

The reaction ofN-acetyl-2-(cyclohex-1-enyl)aniline with Br₂ orN-bromsuccinimide at 20°C is accompanied by intramolecular cyclization to give brominated 3,1-benzoxazines or 4-acetyl-(3-bromo-5-methyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 118–120, January, 2000.     

Cyclization ofN-acetyl-ortho-cycloalkenylanilines on treatment with bromine andN-bromosuccinimide

The reaction ofN-acetyl-2-(cyclohex-1-enyl)aniline with Br₂ orN-bromsuccinimide at 20°C is accompanied by intramolecular cyclization to give brominated 3,1-benzoxazines or 4-acetyl-(3-bromo-5-methyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 118–120, January, 2000.     

Synthesis of (3RS)- and (3SR)-acetoxy-(3aRS,8bSR)-N-acetyl-5-methoxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indoles

Stereoisomeric 3-acetoxy-5-methoxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indoles differing by the configuration of the C³ atom were synthesized. The reaction of N-acetyl-6-(cyclopent-2-en-1-yl)-2-methoxyaniline with 50% hydrogen peroxide in the presence of Na₂WO₄-H₃PO₄ in AcOH gave (3RS,3aRS,8bSR)-N-acetyl-3-hydroxy-5-methoxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole which was converted into the corresponding 3-O-acetyl derivative by treatment with acetic anhydride in pyridine. N-Acetyl-6-(cyclopent-2-en-1-yl)-2-methoxyaniline reacted with iodine in methylene chloride in the presence of NaHCO₃ to produce (3SR,3aRS,8bSR)-3-acetoxy-5-methoxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole which was subjected to acetylation at the nitrogen atom by reaction with acetic anhydride. The structure of (3RS,3aRS,8bSR)-N-acetyl-3-hydroxy-5-methyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole was proved by X-ray analysis. Original Russian Text ? N.A. Likhacheva, A.A. Korlyukov, R.R. Gataullin, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 3, pp. 406–409.     

Reactions of N - and C -alkenylanilines: VIII. Synthesis of functionalized cycloalka[ b ]indoles from o -(cycloalk-2-en-1-yl)anilines

N-Acyl-2-(cyclohex-2-en-1-yl)anilines react with molecular iodine to give the corresponding N-acyl-1-iodo-1,2,3,4,4a,9a-hexahydrocarbazoles which undergo isomerization into 1-R-2a,3,4,5,5a,10a-hexahydro[1,3]oxazolo[5,4,3-j,k]carbazol-10-ium iodides; no isomerization occurs with N-acetyl-3-iodo1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole. The reaction of N-p-tolylsulfonyl-3,4,4a,9a-tetrahydrocarbazoles with hydrogen peroxide leads to the formation of a single 1,2-epoxy derivative with trans orientation of the nitrogen-and oxygen-containing rings. N-p-Tolylsulfonyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles give rise to the corresponding 2,3-epoxy derivatives with both trans and cis orientation of the dihydropyrrole and oxirane fragments. The resulting epoxides undergo trans-opening with formation of N-p-tolylsulfonyl-1-hydroxy-2-methoxy-1,2,3,4,4a,9a-hexahydrocarbazoles and N-p-tolylsulfonyl-3-hydroxy-2-methoxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indoles on heating in methanol in the presence of KU-2 cation exchanger. Mutual orientation of the oxirane and nitrogen-containing rings in the epoxides derived from cyclopenta[b]-indoles was proved by X-ray analysis. Original Russian Text ? R.R. Gataullin, N.A. Likhacheva, K.Yu. Suponitskii, I.B. Abdrakhmanov, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 9, pp. 1316–1326. For communication VII, see [1].     

Reaction of the N-mesylates of 1,3a,4,8b-tetrahydrocyclopenta[b]indoles and 3,4,4a,9a-tetrahydrocarbazoles with dimethyldioxirane and bromine

In reaction with dimethyldioxirane N-mesyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles and N-mesyl-3,3,4a,9a-tetrahydrocarbazoles mostly form the trans-epoxide. The reaction with molecular bromine leads to the product from halogenation in the aromatic ring, i.e., the corresponding N-mesyl-7-bromo-1,3a,4,8b-tetrahydrocyclopenta[b]indole or N-mesyl-6-bromo-3,4,4a,9a-tetrahydrocarbazole. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1306–1313, September, 2006.     

Synthesis of N-acetyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]indoles from N- and 2-(cyclopent-2-en-1-yl)anilines

Reactions of 2-bromo-N-(cyclopent-2-en-1-yl)-4-methylaniline and N-(cyclopent-2-en-1-yl)-2-iodo-4,6-dimethylaniline with acetyl bromide in the presence of potassium carbonate gave mixtures of syn and anti atropisomers of the corresponding N-acetyl derivatives at ratios of 1: 1 and 3: 2 respectively. Heating of these mixtures in toluene in the presence of Pd(OAc)₂, PPh₃, Et₃N, and K₂CO₃ (KOAc) afforded mixtures of isomeric N-acetyl-7-methyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]indoles at a ratio of 3: 1 or N-acetyl-5,7-dimethyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]indoles at a ratio of 2: 3. N-Acetyl-3,3a,4,8b-tetrahydrocyclopenta[b]indole was found to undergo thermal isomerization into N-acetyl-1,3a,4,8btetrahydrocyclopenta[b]indole.     

Synthesis of hydrogenated 2,7-dimethylpyrrolo[3,4-<Emphasis Type="Italic">b</Emphasis>]indoles – analogs of dimebon

A schemes have been proposed for the synthesis of novel 4-substituted 2,7-dimethyl-3,4-dihydro-1H- and previously unknown 2,7-dimethyl-cis-1,2,3,3a,4,8b-hexahydropyrrolo[3,4-b]indoles. In the case of the Dimebon structural analog 2,7-dimethyl-4-[2-(6-methylpyridin-3-yl)ethyl]-3,4-dihydro-1H-pyrrolo-[3,4-b]indole a broad spectrum of pharmacological activity was found in the hydrogenated pyrroloindoles suitable for the development of medicines via the “magic bullet” concept. A strong dependence of the antagonist relationship of the synthesized compounds towards histamine H₁ and serotonin 5-HT₆ receptors with the nature of the substituent in the 4 position and the degree of hydrogenation of the pyrrolo[3,4-b]indoles was demonstrated.     

Syntheses and radical ring-opening polymerization behavior of vinylcyclopropanone cyclic acetals having exomethylene and phenyl groups

Syntheses and radical ring-opening polymerizations of vinylcyclopropanone derivertives having cyclic six-membered acetal, exomethylene, and phenyl groups; 1-vinyl-6-methylene-4,8-dioxaspiro[2.5&]octane ( 2b ), 1-vinyl-5,7-dimethyl-6-methylene-4,8-dioxaspiro[2.5]octane ( 2c ), 1-vinyl-5-phenyl-4,8-dioxaspiro[2.5]octane ( 2d ), and 1-vinyl-5,7-diphenyl-4,8-dioxaspiro[2.5]octane ( 2e ), were carried out. The monomers were prepared by reactions of 1,1-dichloro-2-vinylcyclopropane and the corresponding diols in DMF in the presence of sodium hydride. Radical polymerizations of 2b – 2e were carried out at 60, 80, and 120°C in the presence of an appropriate initiator (3 mol % vs. monomer) in degassed sealed ampoules for 20 h. Although colorless transparent polymers (M̄_n 2300–13,500) were isolated by preparative HPLC for the most monomers, a crosslinked polymer was obtained in the case of 2b . The structures of the polymers were determined to consist of single and double ring-opening units. The content of the double ring-opened unit was 25–75% by comparison of IR spectra to a model compound. It is suggested that the double ring-opened propagating chain end is stabilized by the substituents on the cyclic acetal rings. The two-center energies of the cyclopropane ring and activation energy of ring-opening calculated by molecular orbital methods may explain the selectivity in the cleavage of the cyclopropane ring, and the degree of double ring-opening. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 2501–2512, 1997     

Nenitzescu synthesis of carbamate indole derivatives from <Emphasis Type="Italic">N,N′</Emphasis>-bis(methoxycarbonyl)-<Emphasis Type="Italic">p</Emphasis>-benzoquinone diimine

N,N′-Bis(methoxycarbonyl)-p-benzoquinone diimine reacted with 4-(cyclohex-1-en-1-yl)-and 4-(cyclopent-1-en-1-yl)morpholines in methylene chloride at room temperature to give morpholino-substituted cyclohexane-and cyclopentane-fused indole derivatives. Heating of the latter in boiling 10% hydrochloric acid led to the formation of methyl 6-(methoxycarbonylamino)-1,2,3,4,4a,9a-hexahydro-9H-carbazole-9-carboxylate and methyl 7-(methoxycarbonylamino)-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-4-carboxylate, respectively. The reaction of N,N′-bis(methoxycarbonyl)-p-benzoquinone diimine with 4-benzylaminopent-3-en-2-one in CH₂Cl₂ in the presence of BF₃·Et₂O on heating gave methyl 3-acetyl-2-methyl-(5-methoxy-carbonylamino)-1H-indole-1-carboxylate.     

Synthesis of oxo derivatives of <Emphasis Type="Italic">N</Emphasis>-(<Emphasis Type="Italic">p</Emphasis>-tolysulfonyl)hexahydrocycloalka[<Emphasis Type="Italic">b</Emphasis>]indoles

Hydroxymercuration-demercuration of N-p-tolysulfonyl-4,4a,9,9a-tetrahydro-3H-carbazoles and N-p-tolyl(or methyl)sulfonyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles leads to the formation of the corresponding N-p-tolylsulfonyl-2,3,4,4a,9,9a-hexahydro-1H-carbazol-2-ols and N-p-tolyl(or methyl)sulfonyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indol-2-ols. The latter are oxidized to 2-oxo derivatives with potassium dichromate. The oxidation of 2-methoxy-8-methyl-N-p-tolylsulfonyl-2,3,4,4a,9,9a-hexahydro-1H-carbazol-1-ol under analogous conditions gives 2-methoxy-8-methyl-N-p-tolysulfonyl-2,3,4,4a,9,9a-hexahydro-1H-carbazol-1-one.     

Palladium-Catalyzed Coupling Reaction of Iodouracil Having Acetamidine Moiety with Olefins

The reaction of 6-[1-Aza-2-(dimethylamino)prop-l-enyl]-5-iodo-1,3-dimethyluracil (3) with various olefins in the presence of a catalytic amount of Pd(OAc)₂ and 1.5 equiv. of K₂CO₃ in DMF at 120 °C gave the pyrido[2,3-d]pyrimidine derivatives (5a-b and 7a-d) in moderate to high yield.     

Etudes photochimiques—XIII : Reactions de photoaddition du benzo[b]thiophene avec des amines et avec le pyrrole

The photochemical behavior of benzo[b]thiophene is different from that of thiophene. The former does not undergo photoisomerization and is not converted into an indole when irradiated in the presence of a primary amine; its photochemical behavior resembles that of naphthalene. Thus photoexcited benzo[b]thiophene gives adducts with primary amines (1(H)), secondary amines (2), and pyrrole (3(H)): an exciplex is an intermediate. The existence of the exciplex is supported by the formation of aldehyde 7 when benzo[b]thiophene is irradiated in aqueous propylamine, the finding that photoexcited benzo[b]thiophene does not react with an alcohol and that photoexcited indole benzo[b]furan, 2-methylbenzo[b]thiophene, and 3-methylbenzo[b]thiophene do not react with propylamine or with piperidine. The results are interpreted in terms of spin densities calculated for the anion radicals of the compounds under study.     

N‐Methyl‐N‐(1‐phenyl­sulfonyl­indol‐2‐ylmethyl)­aniline

In the title compound, 2‐[(methylphenylamino)methyl]‐1‐(phenylsulfonyl)indole, C₂₂H₂₀N₂O₂S, the indole system is not strictly planar and the dihedral angle between the fused rings is 2.7 (1)°. The angles around the S atom of the sulfonyl substituent deviate significantly from the ideal value for tetrahedral geometry. The pyramidalization at the indole N atom is very small. Of the two C—H?O interactions, one influences the orientation of indole with respect to the sulfonyl group and the other determines the orientation of the phenyl bound to sulfonyl. The phenyl ring of the sulfonyl substituent makes a dihedral angle of 89.6 (1)° with the best plane of the indole. The molecular packing is stabilized by C—H?π and C—H?O hydrogen bonds.     

Dense compounds of C,H, N,and O atoms: Nitramine derivatives of diimino- and dioxodecahydro-1 h,5h-diimidazo-[4,5-b:4′,5′-e]pyrazine

Guanidine condensed with 1,4-diformyl-2,3,5,6-tetrahydroxypiperazine 1 to give 2,6-diiminodecahydro-1H,5H-diimidazo[4,5-b:4′,5′-e]pyrazine 3 isolated as the tetrahydrochloride salt. nitric acid (100%) at −40°C converted the bisguanidine 3 to 2,6-dinitrimino-4,8-dinitrodecahydro-1H,5H-diimidazo[4,5-b:4′,5′-e]- pyrazine 8 isolated as a dihydrate, whereas nitration by nitronium tetrafluoroborate at 0° to 25°C afforded 2,6-diimino-4,8-dinitrodecahydro-1H,5H-diimidazo[4,5-b:4′,5′-e]pyrazine 9 isolate as the monohydrated bistetrafluoroborate salt, and treatmetn with nitric acid (100%) and acetic anhydride or phosphorus pentoxide converted the bisguanidine 3 to 2,6-dioxo-1,3,4,5,7,8-hexanitrodecahydro-1H,5H-diimidazo[4,5-b:4′,5′-e]pyrazine 4 , also obtained from the tetra N-nitro compound 8 · 2 H₂O and from the dinitramine 9 · 2 BHF₄ · H₂O after similar treatment. The cis-syn-cis- configuration of the tricyclic bisurea 4 and bisguanidine 9 was confirmed by X-ray crys-tallographic analysis. Nitrosation by nitrous acid or by dinitrogen tetroxide converted the bisguanidine 3 to a hydrated 2,6-dinitrosimino-4,8-dinitrosodecahydro-1H,5H-diimidazo[4,5-b:4′,5′-]pyrazine 10 · 2.5 H₂O, whereas treatment with nitrosonium tetrafluo-roborate afforded the bistetrafluoroborate salt of 4,8-dinitroso derivative 11 · 2 BHF 4 . The nitrosamines 10 and 11 were converted to the tetranitro compound 8 · 2 H₂O on treatment with nitric acid (100%) at −40°C. Treatmnt with fluoroboric acid etherate in acetonitrile converted nitroimino groups in compound 8 · 2 H₂O and nitrosimino groups in compound 10 · 2.5 H₂O to imino groups in compounds 9 · 2 BHF₂ · H₂O and 11 · 2 HBF₄ respectively.     

Molecular structure of methyl 1-isopropenyl-5a,5b,8,8,14a-pentamethyl-1,2,3,3a,4,5,5a,5b,6,7,7a,8,9,14,14a,14b,15,16,16a,16b-icosahydrocyclopenta[7,8] phenanthro[2,1-b]carbazole-3a-carboxylate

The molecular and crystal structure of methyl 1-isopropenyl-5a,5b,8,8,14a-pentamethyl-1,2,3,3a,4,5,5a,5b, 6,7,7a,8,9,14,14a,14b,15,16,16a,16b-icosahydrocyclopenta[7,8]phenenthro[2,1-b]carbazole-3a-carboxylate is determined. Compound C₃₇H₅₁NO₂ II crystallizes in the C2 chiral space group: a = 27.0380(5) ?, b = 7.9817(15) ?, c = 18.1980(3) ?, β = 123.580(3)°.     

Intramolecular Diels-Alder Reactions via 3-(Phenylthio)-4-(Trimethylsilyl)-3-Sulfolene

Deprotonation of the title compound 2 followed by treatment with 5-iodo-1-pentene or 6-iodo-l-hexene gave the alkylated products 3 and 4 which upon refluxing in toluene yielded the dienes 8a and 8b. Intramolecular Diels-Alder reactions were achieved by heating the dienes 8a and 8b in toluene in a sealed tube at 160–180°C to give bicyclo[4.3.0]nonene 9 and bicyclo[4.4.0]decene 10, respectively, in good yield. The stereochemistry of the cyclization products was determined, and was rationalized by comparison of the possible transition states involved.     

Condensed isoquinolines 23. Reaction of <Emphasis Type="Italic">o</Emphasis>-bromomethylphenyl-acetonitrile with anthranilic acids: Synthesis of 6H, 12H,17H-dibenzo[3,4:6,7][1,8]-naphthyridino[1,8-<Emphasis Type="Italic">ab</Emphasis>]quinazoline-6,17-diones

The direction of the reaction of anthranilic acids with o-bromomethylphenylacetonitrile upon fusion depends on the temperature and nature of the substituent in the anthranilic acid. The reaction may lead to three types of products: Derivatives of 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones below 150°C and to 6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-one or derivatives of 6H,12H,17H-dibenzo[3,4:6,7][1,8]naphthyridino[1,8-ab]quinazoline-6,17-diones above 150°C depending on the nature of the substituent in the anthranilic acid. A study was carried out on the mechanism for the formation of 6H,12H,17H-dibenzo[3,4:6,7][1,8]naphthyridino[1,8-ab]quinazoline-6,17-diones, which permitted the preparation of 6-(4-methylphenyl)-6,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1059–1067, July, 2007.