Reactions of <Emphasis Type="Italic">N</Emphasis>-and <Emphasis Type="Italic">C</Emphasis>-Alkenylanilines: VII. Synthesis of Indole Heterocycles from Products of Reaction between <Emphasis Type="Italic">N</Emphasis>-Mesyl-2-(1-alken-1-yl)anilines and Halogens

N-Mesyl-2-(1-methyl-1-butenyl)-6-methylaniline reacted with Br₂ to afford N-mesyl-2-(3-bromo-1-penten-2-yl)aniline that under treatment with NH₃ or amines underwent cyclization into N-mesyl-7-methyl-3-methylene-2-ethylindoline. The reaction of N-mesyl-2-(1-methyl-1-buten-1-yl)-4-methyl- and 2-(1-methyl-1-buten-1-yl)aniline with Br₂ gave rise to the corresponding N-mesyl-2-(2-bromo-1-methyl-1-buten-1-yl)anilines. Under the similar conditions N-tosyl-2-(1-cyclohexen-1-yl)aniline was converted into N-tosyl-2-(6-bromo-1-cyclohexen-1-yl)aniline that under treatment with NH₃ furnished N-tosyl-1,2,3,9a-tetrahydrocarbazole. The reaction of N-mesyl-1,2,3,9a-tetrahydrocarbazole with CuBr₂ in MeOH afforded N-mesyl-4-methoxy-1,2,3,4-tetrahydrocarbazole. N-Mesyl-6-methyl-2-(1-cyclopenten-1-yl)aniline in reaction with Br₂ in the presence of NaHCO₃ was oxidized into the corresponding cyclopentenone, and with NBS it gave N-mesyl-2-(2-bromo-1-cyclopenten-1-yl)aniline.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 5, 2005, pp. 730–737.Original Russian Text Copyright © 2005 by Gataullin, Sotnikov, Spirikhin, Abdrakhmanov.     

Transformations of Perfluorinated 2-Alkyl- and 2,2-Dialkylbenzocyclobutenones in SbF<Subscript>5</Subscript> and SiO<Subscript>2</Subscript>-SbF<Subscript>5</Subscript>

Perfluorinated 2-methyl- and 2-ethylbenzocyclobutenones on heating in SbF₅ underwent isomerization into perfluoroindan-1-one and perfluoro(2-methylindan-1-one), while their reaction with SiO₂—SbF₅ gave perfluorinated 3-methyl- and 3-ethylphthalides, respectively. Perfluorinated 2-ethyl-2-methyl- and 2,2-diethylbenzocyclobutenones reacted with SbF₅ to produce perfluorinated 2-(but-2-en-2-yl)- and 2-(pent-2-en-3-yl)-benzoic acids, and their transformations in SbF₅ over SiO₂ afforded 5,6,7,8-tetrafluoro-1-oxo-3-trifluoromethyl-1H-isochromene-4-carboxylic acid and perfluoro(4-ethyl-3-methyl-1H-isochromen-1-one), respectively.     

Synthesis of 2-Aryl-4-(R-sulfanylmethyl)-3-methyl-6,7-dihydro-2<Emphasis Type="Italic">H</Emphasis>-pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyridazin-7-ones

Bromination of ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazole-3-carboxylates gave ethyl 1-aryl-4-(bromoacetyl)-5-methyl-1H-pyrazol-3-carboxylates which were used to alkylate benzenethiol and heterocyclic thiones at the sulfur atom. Reactions of the resulting S-alkylation products with hydrazine or methylhydrazine involved closure of pyridazine ring to afford 2-aryl-3-methyl-4-[phenyl(or hetaryl)sulfanylmethyl]-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-7-ones.     

Synthesis and some properties of 6-di(tri)fluoromethyl-and 5-di(tri)fluoroacetyl-3-methyl-1-phenylpyrano[2,3-<Emphasis Type="Italic">c</Emphasis>]pyrazol-4(1<Emphasis Type="Italic">H</Emphasis>)-ones

Condensation of 4-acetyl-5-hydroxy-3-methyl-1-phenylpyrazole with R^FCO₂Et (R^F = CF₂H, CF₃) in the presence of LiH affords 4-di(tri)fluoroacetoacetyl-5-hydroxy-3-methyl-1-phenylpyrazoles from which 6-di(tri)fluoromethyl-and 5-di(tri)fluoroacetyl-3-methyl-1-phenylpyrano[2,3-c]pyrazol-4(1H)-ones were synthesized. The reactions of pyrano-pyrazoles with hydrazine hydrate, ethyl mercaptoacetate, or aromatic amines proceed at the C(6) atom with pyrone ring opening and formation of aminoenones, pyrazoles, or thiophenes with the 5-hydroxy-3-methyl-1-phenyl-4-pyrazolyl fragment. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2750–2754, December, 2005.     

Metabolites from the marine fungus <Emphasis Type="Italic">Eurotium repens</Emphasis>

1,8-Dihydroxy-6-methoxy-3-methyl-9,10-anthracenedione (physcion, 1), 3,4-dihydro-3,6,9-trihydroxy-8-methoxy-3-methyl-1(2H)-anthraceneone (asperflavin, 2), and 2,5-dihydroxy-3-(3-methyl-2-butenyl)-6-[(1E)-1-heptenyl]-benzaldehyde (tetrahydroauroglaucin, 3) were shown to be the main pigments of the marine isolate of the fungus Eurotium repens. In addition to the pigments, the fungal metabolites included the diketopiperazine alkaloid echinulin (4). The structures of the compounds were identified using NMR spectroscopy and mass spectrometry. The cytotoxic activity of 1–3 toward sex cells of the sea urchin Strongylocentrotus intermedius was determined. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 327–329, July–August, 2007.     

Hydrogenation and conformational analysis of (1<Emphasis Type="Italic">R</Emphasis>,2<Emphasis Type="Italic">R</Emphasis>,6<Emphasis Type="Italic">S</Emphasis>)-3-methyl-6-(1-methylethenyl)cyclohex-3-ene-1,2-diol

Hydrogenation of (1R,2R,6S)-3-methyl-6-(1-methylethenyl)cyclohex-3-ene-1,2-diol was studied. Nickel chloride-sodium tetrahydridoborate system turned out to selectively reduce the double bond in the isopropenyl group. The results of conformational analysis of (1R,2R,6S)-3-methyl-6-(1-methylethenyl)cyclohex-3-ene-1,2-diol and its partly and completely hydrogenated derivatives were in a good agreement with the NMR data.     

Synthesis and properties of pyrimido[4,5-<Emphasis Type="Italic">a</Emphasis>]- and pyrido[4,3-<Emphasis Type="Italic">a</Emphasis>]carbazole derivatives

Methods for the synthesis of substituted pyrimido [4,5-a]- and pyrido[4,3-a]carbazoles were proposed. Condensation of 2-(dimethylaminomethylene)-6-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-one with guanidine and thiourea afforded 2-amino-8-methyl-6,11-dihydro-5H-pyrimido[4,5-a]carbazole and 8-methyl-3,5,6,11-tetrahydro-2H-pyrimido[4,5-a]carbazole-2-thione, respectively. The reaction of cyano(6-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-ylidene)acetamide with dimethylformamide dimethyl acetal gave N-(dimethylamino-methylene)cyano(6-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-ylidene)acetamide. Cyclization of the latter yielded 1-cyano-8-methyl-3,5,6,11-tetrahydro-2H-pyrido[4,3-a]carbazol-2-one.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2740–2744, December, 2004.     

Synthesis and Reactions of 5-Amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-7-phenyl-7<Emphasis Type="Italic">H</Emphasis>-thiazolo[3,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine-6-carbonitrile

Summary. 5-Amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-7-phenyl-7H-thiazolo[3,2-a]pyrimidine-6-carbonitrile was synthesized via the reaction of 4-(2-aminothiazol-4-yl)-3-methyl-1-phenyl-2-pyrazolin-5-one with benzylidene malononitrile and was then transformed to related fused heterocyclic systems. The antifungal and antibacterial studies revealed in some cases excellent biocidal properties.     

Synthèses de produits organofluorés VI Solvolyse de chlorofluorocyclopropanes

Fluoro-organic Syntheses VI: The Solvolysis of Chlorofluoro-cyclopropanes 2-Fluoro-allylic carbocations, generated from 1-chloro-1-fluoro-cyclopropanes or 2-fluoro-allyl p-toluene-sulfonates in water or acetic acid, undergo either proton loss or addition of hydroxyl or acetoxyl. In the latter case, an alkyl-substituted 2-fluoro-allyl ion leads predominantly to the more branched product (e.g. 3-fluoro-2-methyl-3-buten-2-ol) which may be converted into the less branched one (e.g. 2-fluoro-3-methyl-2-buten-2-ol) through reversible reactions.     

Synthesis of 4<Emphasis Type="Italic">H</Emphasis>-imidazole-5-carbaldoxime 3-oxides and 4<Emphasis Type="Italic">H</Emphasis>-imidazole-5-carbonitrile 3-oxides

The condensation of 3-hydroxyamino-3-methylbutan-2-one or 3-ethyl-3-hydroxyamino-pentan-2-one with aldehydes and ammonia afforded a series of new 1-hydroxy-4-methyl-2,5-dihydroimidazoles, whose oxidation gave rise to the corresponding 5-methyl-4H-imidazole 3-oxides. The latter, like 1-hydroxy-4-methyl-2,5-dihydroimidazoles, react with PrⁱONO in the presence of bases to form 4H-imidazole-5-carbaldoxime 3-oxides, which are transformed into 4H-imidazole-5-carbonitrile 3-oxides in the reaction with TsCl in the presence of Et₃N. The by-products produced in different steps of the synthesis were isolated and characterized. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1487–1503, July, 2008.     

Effect of Temperature on Thermophysical Properties of Ethanol + Aliphatic Alcohols (C<Subscript>4</Subscript>–C<Subscript>5</Subscript>) Mixtures

Summary. Speeds of sound, densities, and refractive indices of the binary mixtures containing ethanol+(2-methyl-1-propanol, 2-methyl-1-butanol, 1-pentanol, or 3-methyl-1-butanol) were measured at 288.15 ≤ T/K ≤ 323.15 and atmospheric condition in the whole compositional range. The effect of temperature was analyzed by several chemical terms.     

Photochemische Cycloadditionen von 3-Phenyl-2H-azirinen mit kumulierten Doppelbindungen. Vorläufige Mitteilung

Irradiation of 2-methyl- ( 1c ) and 2,2-dimethyl-3-phenyl-2H-azirine ( 1d ) in benzene solution in the presence of carbon dioxide yields 2-methyl-4-phenyl- ( 3c ) and 2,2-dimethyl-4-phenyl-3-oxazolin-5-one ( 3d ), respectively. Similar cycloadducts are observed (see table) when 2,3-diphenyl-2H-azirine ( 1b ) and 1d are irradiated in the presence of phenylisocyanate, o-tolylisocyanate, phenylisothiocyanate or di-o-tolyl-carbodiimide.     

Structures and photochromic properties of fulgides based on naphtho[1,2-<Emphasis Type="Italic">b</Emphasis>]furan and benzo[<Emphasis Type="Italic">g</Emphasis>]indole

The novel heterocyclic fulgides, i.e. 3-isopropylidene-4-{1-[5-methoxy-1-(4-methoxy-phenyl)-2-methyl-1H-benzo[g]indol-3-yl]ethylidene}dihydrofuran-2,5-dione and 3-isopropylidene-4-[1-(1-benzyl-5-methoxy-2-methyl-1H-benzo[g]indol-3-yl)ethylidene]dihydrofuran-2,5-dione, were prepared and isolated as E-isomers. Photochromism, E-configuration, and high resistance to photocoloration—photobleaching of solutions of these fulgides as well as 3-isopropylidene-4-[1-(5-methoxy-2-methylnaphtho[1,2-b]furan-3-yl)ethylidene]dihydro-furan-2,5-dione and 3-isopropylidene-4-[1-(5-methoxy-2-methyl-1-phenyl-1H-benzo[g]indol-3-yl)ethylidene]dihydrofuran-2,5-dione synthesized previously were shown by X-ray diffraction analysis, ¹H NMR spectroscopy and electronic absorption spectroscopy. The novel fulgides show fluorescence and high thermal stability of photogenerated cyclic form. Repeated photo-coloration—photobleaching is accompanied by reversible photoinduced E—Z isomerization. Benzo[g]indolyl fulgides are characterized by the longer wavelength absorption of both original (E) and photoisomeric cyclic (C) forms as compared to naphthofuran fulgide.     

Amine-induced rearrangements of 2-bromo-1-(1H-indol-3-yl)-2-methyl-1-propanones: A new route to α-substituted indole-3-acetamides, β-substituted tryptamines, α-substituted indole-3-acetic acids and indole β-aminoketones

The reaction of 2-bromo-1-(1H-indol-3-yl)-2-methyl-1-propanone ( 1 ) and 2-bromo-1-(1-methyl-1H-indol-3-yl)-2-methyl-1-propanone ( 2 ) with primary amines proceeds in good yields to produce rearranged amides by a proposed pseudo-Favorskii mechanism. These amides in turn can either be reduced to produce β-substituted tryptamines or hydrolyzed to produce substituted indole-3-acetic acids. When the reaction is carried out using bulky primary or secondary amines, β-aminoketones are produced by elimination of hydrogen bromide followed by Michael addition. When hindered secondary amines or tertiary amines are used, elimination to the α,β-unsaturated ketones occurs.     

Photochemical reactivity of α,β-unsaturated δ-lactams: Synthesis of seco-steroids. Photochemical reactions. XIII [1]

The UV. irradiation of 17 β-hydroxy-2-aza-4-androsten-3-one (1) , N-methyl-17 β-hydroxy-2-aza-4-androsten-3-one (3) , 17 β-hydroxy-4-aza-5 β-androst-1-en-3-one (2) and N-methyl-17 β-hydroxy-4-aza-5 β-androst-1-en-3-one (4) , gives rise to 1,10-seco (from 1 and 3 ) and 5, 10-seco (from 2 and 4 ) steroids.     

Synthesis of 1-{4a,6-dimethyl-4a,9a-dihydropyrano-[3,4-<Emphasis Type="Italic">b</Emphasis>]indol-9(1<Emphasis Type="Italic">H</Emphasis>)-yl}ethanone

Heating of the bromination product of 4-methyl-3,6-dihydro-2H-pyran with 4-toluidine or 2-bromo-4-methylamiline in triethylamine gave 4-methyl-N-(4-methylphenyl)- and N-(2-bromo-4-methylphenyl)-4-methyl-3,6-dihydro-2H-pyran-3-amines which were converted into the corresponding amides by reaction with bromo- or chloroacetyl chloride. 1-{4a,6-Dimethyl-4a,9a-dihydropyrano[3,4-b]indol-9(1H)-yl} ethanone was synthesized in good yield by heating N-(2-bromo-4-methylphenyl)-N-(4-methyl-3,6-dihydro-2Hpyran-3-yl)acetamide in boiling toluene in the presence of palladium(II) acetate, triphenylphosphine, copper(II) acetate, triethylamine, and potassium carbonate.     

Synthesis of pyrrolidine and tetrahydroazonine derivatives from <Emphasis Type="Italic">N</Emphasis>-[bis(ethoxycarbonyl)methyl]tetrahydropyridinium bromide and methyl acetylenedicarboxylate

The reaction of N-methyl-N-(diethoxycarbonyl)methyltetrahydropyridinium bromide with dimethyl acetylenedicarboxylate in the presence of triethylamine at room temperature afforded 1,2-dimethyl 1-ethyl 2-[(3-vinyl-1-methyl-3-phenyl-2-ethoxycarbonyl)pyrrolidin-2-yl]-ethene-1,1,2-tricarboxylate in 25% yield. Its structure was proved by XRD analysis. At cooling to −20°C the pyrrolidine yield signifi cantly decreased and 3,4-dimethyl 2,2-diethyl 1-methyl-7-phenyl-1,5,8,9-tetrahydro-2H-azonine-2,2,3,4-tetratcarboxylate was obtained in 31% yield.     

Manufacturing synthesis of 5-hydroxy-2-methyl-1<Emphasis Type="Italic">H</Emphasis>-indole

The manufacturing synthesis of 5-hydroxy-2-methyl-1H-indole is described and two synthetic methods were used and the results discussed. Two small and three large runs with Nenitzescu’s method were analyzed and results reported with different reaction conditions. Manufacturing issues encountered were discussed. Production scale of more than 60 kg of the 5-hydroxy-2-methyl-1H-indole-3-carboxylic acid ethyl ester and over 20 kg of the 5-hydroxy-2-methyl-1H-indole were achieved. Based on these results, larger scale manufacturing of this product or similar products based on the optimized conditions is feasible.     

Acetylenchemie 12. Mitt.: Weitere studien über die phasentransfer-katalysierte umsetzung des 9(10H)-acridinons mil alkinylhalogeniden

By the phase transfer catalyzed reaction of 9(10H)-acridinone with 1-bromo-2-propyne, 10-(2-propynyl)-9(10H)-acridinone is synthesized. As prototropic rearrangement products of this 10-(1,2-propadienyl)-9(10H)-acridinone and 10-(1-propynyl)-9(10H)-acridinone are obtained, Under the given conditins 1-bromo-2butyne leads to 10-(2-butynyl)-9(10H)-acridinone and 2-chloro-3-butyne leads to 10-(1-methyl-1,2-propddienyl)-9(10H)-acridinone, 10-(1-methyl-2-propynyl)-9(10H)-acridinone, 9-(1-methyl-2-propynyloxy)acridine and 10-[1-methyl-3-(3,4-dimethylphenyl-2-propynyl)]-9(10H)-acridinone. The formation of the products is experimentally confirmed and with published work compared.     

Ringschlussreaktionen mit 2-(β-Styryl)benzylaminen 5-Phenyl-1H-2-benzazepine. 23. Mitteilung über siebengliedrige Heterocyclen

Cyclization reactions with 2-(β-styryl)benzylamines 5-Phenyl-1H-2-benzazepines Cyclization of the urea derivative 3 with POCl₃ to give 2-(4-methyl-1-piperazinyl)-4-phenylquinoline ( 4 ) was carried out in analogy to the quinoline synthesis of Foulds & Robinson. This reaction was used for the preparation of 2-benzazepines. The trisubstituted ureas 6 and 8 , derived from the 2-(β-styryl)-benzylamines 5 , were cyclized with POCl₃ to yield the 3-amino-5-phenyl-1H-2-benzazepines 7 and 9 , respectively. Similarly, cyclization of the corresponding acetyl-derivatives 10 gave the 3-methyl-5-phenyl-1H-2-benzazepines 12 . On the other hand, the disubstituted urea 15 , cyclized under the same conditions to the 1-methyl-1-phenylisoindoline derivative 16 , and 2-(β-styryl)benzylamine ( 5a ) on treatment with phosgene gave the isoindoline 17 in an analogous manner.