Unusual Reaction of Tetrachlorocyclopentadienone Dimer with Secondary Amines

Tetrachlorocyclopentadienone dimer reacts with secondary amines to afford unusual products, tricyclic 6-oxo-1,1a,3a,6-tetrahydrocyclopropa[c]pentalene-1-carboxamide derivatives.     

Novel annulated products from aminonaphthyridinones

2-(4-Methoxyphenyl)-1-oxo-1,2-dihydro-1,6-naphthyridine-4-carboxamide (4c) underwent Hofmann rearrangement with iodobenzene diacetate in methanol to give the corresponding 4-amino compound (6c). This, when reacted with 2,4-pentanedione and then hot phosphoryl chloride (attempted Combes synthesis) gave a new heterocyclic system, 6-(4-methoxyphenyl)-2-methylpyrido[3,2-c]pyrrolo[2,3-e]azocin-7(6H)-one (9c). This showed typical pyrrole-type reactivity at the 3-position. Alternatively, an attempt to convert the 4-NH₂ in 6c to 4-OH by diazotization gave, instead, a [1,2,3]triazolo[1,5-a]pyridine-3-carboxaldehyde (16c). The same series of reactions on a benzo analog, 2-methyl-1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carboxamide (4a), gave the same results.     

Reaction of perfluorinated 1-ethyl-, 1,1-diethyl-, and 1,2-diethylcyclobutabenzenes with pentafluorobenzene in SbF<Subscript>5</Subscript>

Perfluoro(1-ethyl-1,2-dihydrocyclobutabenzene) reacts with pentafluorobenzene in SbF5 to give perfluoro(1-ethyl-2-phenyl-1,2-dihydrocyclobutabenzene). Analogous reaction of a mixture of perfluoro(1,1-diethyl-1,2-dihydrocyclobutabenzene) and perfluoro(1,2-diethyl-1,2-dihydrocyclobutabenzene) leads to the formation (after hydrolysis of the reaction mixture) of perfluorinated 7-phenyl-8,8-diethylbicyclo[4.2.0]octa-1,4,6-trien-3-one, 1,1-diethyl-2-(4-oxocyclohexa-2,5-dienylidene)-1,2-dihydrocyclobutabenzene, and 2-(pent-2-en-3-yl)benzophenone (from the 1,1-isomer) and perfluorinated (E)-1,2-diethyl-1-phenyl-1,2-dihydrocyclobutabenzene, 7,8-diethyl-8-phenylbicyclo[4.2.0]octa-1,4,6-trien-3-one, and 1-[2-(1-phenylprop-1-en-1-yl)-phenyl]propan-1-one (from the 1,2-isomer).     

α-Thioureidoalkylation of functionally substituted ureas: I. Tandem cyclization and esterification in reactions of <Emphasis Type="Italic">N</Emphasis>-(carboxyalkyl)ureas with 1,3-dialkyl-4,5-dihydroxy-4,5-diphenylimidazolidine-2-thiones in alcohols

Acid-catalyzed reactions of N-(carboxyalkyl)ureas with 1,3-dialkyl-4,5-dihydroxy-4,5-diphenylimidazolidine-2-thiones in methanol or propan-2-ol led to the formation of previously unknown ω-(4,6-dialkyl-2-oxo-3a,6a-diphenyl-5-thioxooctahydroimidazo[4,5-d]imidazol-1-yl)alkanoic acids and their methyl and isopropyl esters. The structure of some esters was proved by X-ray analysis. Methyl (4,6-diethyl-2-oxo-3a,6adiphenyl-5-thioxooctahydroimidazo[4,5-d]imidazol-1-yl)acetate showed anxiolytic effect.     

Cyclopropanation of N-Substituted 2-Oxochromene- and 6-Bromo-2-oxochromene-3-carboxamides with Zinc Enolates Derived from 1-Aryl-2,2-dibromoalkanones

Zinc enolates derived from 1-aryl-2,2-dibromoalkanones react with N-cyclohexyl-2-oxochromene-3-carboxamides to give N-cyclohexyl-1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxamides mainly as cis isomers with respect to the substituents in positions 1 and 1a. Reactions of the same zinc enolates with N-benzyl-2-oxochromene-3-carboxamide and N-benzyl-6-bromo-2-oxochromene-3-carboxamide lead to formation of 1-aryl-2-benzyl- and 1-aryl-2-benzyl-6-bromo-1-hydroxy-9c-alkyl-1,2,9b,9c-tetrahydro-5-oxa-2-azacyclopenta[2,3]cyclopropa[1,2-a]naphthalene-3,4-diones. The reaction of zinc enolates with N-aryl-2-oxochromene-3-carboxamides in a weakly polar solvent (diethyl ether or ethyl acetate) affords mixtures of cis-N-aryl-1-aroyl-1-alkyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxamides and their cyclic isomers, 9c-alkyl-1,2-diaryl-1-hydroxy-1,2,9b,9c-tetrahydro-5-oxa-2-azacyclopenta[2,3]cyclopropa[1,2-a]naphthalene-3,4-diones, the latter prevailing. N-Substituted 1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxamides in which the aroyl group on C¹ and the carboxamide group on C^1a are arranged trans are formed by reactions of zinc enolates with the corresponding 2-oxochromene-3-carboxamides in the presence of hexamethylphosphoric triamide.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 4, 2005, pp. 539–546.Original Russian Text Copyright © 2005 by V. Shchepin, Silaichev, R. Shchepin, Ezhikova, Kodess.     

Synthesis of 2-thioxo-6-trifluoromethyl-1,2-dihydropyridine-3-carbonitrile and ethyl 5-cyano-6-thioxo-1,6-dihydropyridine-2-carboxylate by the S<Subscript>N</Subscript>Vin reaction

Ethyl 5-cyano-6-thioxo-1,6-dihydropyridine-2-carboxylate and 2-thioxo-6-trifluoromethyl-1,2-dihydropyridine-3-carbonitrile were obtained by the S_NVin reaction. The latter compound was used in the synthesis of 2-alkylsulfanyl-6-trifluoromethylpyridin-3-carbonitriles, 3-amino-5-trifluoromethylthieno[2,3-b]pyridin-2-carboxamide, and 7-thifluoromethyl-2-spirocyclopentane-1,2,3,4-tetrahydropyrido[2′,3′:2,3]thieno[4,5-d]pyrim-idin-4-one.     

Fluorine-containing 3-arylhydrazono-2,4-dioxobutanoates in reactions with difunctional nucleophiles

3-Arylhydrazono-4-polyfluoroalkyl-2,4-dioxobutanoates reacted with hydrazines to give ethyl 4-aryldiazeno-3-polyfluoroalkyl-1H-pyrazole-5-carboxylates, while analogous reactions of ethyl 3-arylhydrazono-4-pentafluorophenyl-2,4-dioxobutanoates resulted in the formation of 4-aryldiazeno-3-pentafluorophenyl-1,2-dihydropyridazine-5,6-diones or 6-aryl-7,8,9,10-tetrafluoro-2-phenyl-2,4a,6,10b-tetradropyridazo[4,3-c]cinnoline-3,4-diones, depending on the conditions. Cyclocondensation of ethyl 3-arylhydrazono-4-polyfluoroalkyl(or pentafluorophenyl)-2,4-dioxobutanoates with ethylenediamine led to 3-[1-arylhydrazono-2-oxo-2-polyfluoroalkyl(or pentafluorophenyl)ethyl]-5,6-dihydropyrazin-2(1H)-ones, and 3-[1-arylhydrazono-2-oxo-2-polyfluoroalkyl(pentafluorophenyl)ethyl]benzoxazin-2-ones were formed in the condensation with o-aminophenol. Pentafluorophenyl-substituted heterocycles were found to undergo intramolecular ring closure to give 3-hetaryl-substituted 1-aryl-5,6,7,8-tetrafluoro-1,4-dihydrocinnolin-4-ones. The reactions of ethyl 3-arylhydrazono-4-pentafluorophenyl-2,4-dioxobutanoates with o-aminobenzenethiol gave 3-[7-(2-aminophenylsulfanyl)-1-aryl-5,6,8-trifluoro-4-oxo-1,4-dihydrocinnolin-3-yl]benzothiazin-2-ones; 8a-hydroxy-11,12,13,14-tetrafluoro-10-(4-methoxyphenyl)-2,3,4,5,6,7,8a,10-octahydropyrazino[1′,2′:4,5][1,4]diazepino[6,7-c]cinnolin-8-one was isolated in the condensation of ethyl 3-(4-methoxyphenylhydrazono)-4-pentafluorophenyl-2,4-dioxobutanoate with N-(2-aminoethyl)ethane-1,2-diamine.     

Synthesis of 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones from 4-aryl-3-carbethoxy-6-(trifluoromethyl)-2-pyrones and their reaction with sodium azide leading to new carbostyril derivatives

Treatment of ethyl 4-aryl-6-(trifluoromethyl)-2-oxo-2H-pyran-3-carboxylates, prepared from 4,4,4-trifluorobutane-1,3-diones, PCl₅ and sodium diethyl malonate, with sulfuric acid afforded the intramolecular Friedel–Crafts acylation products, 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones, from which 2-(trifluoromethyl)-6H-pyrano[3,4-c]quinoline-4,5-diones were obtained via the Schmidt reaction in moderate yields. The latter reacted with sodium azide to give 2-oxo-4-(5-trifluoromethyl-1,2,3-triazol-4-yl)-1,2-dihydroquinoline-3-carboxylic acids in good yields.     

Synthesis of novel spiro[indole-3,3′-pyrrolidin]-2(1H)-ones

Diastereoselective [3+2] cycloaddition of azomethine ylide to 1,3-dimethyl-6-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)-3a,9a-diphenyl-3,3a,9,9a-tetrahydroimidazo[4,5-e]thiazolo[3,2-b]-[1,2,4]triazine-2,7(1H,6H)-dione yields hitherto unknown 1,1′,3-trimethyl-3a,9a-diphenyl-3,3a,9,9a-tetrahydrodispiro(imidazo[4,5-e]thiazolo[3,2-b][1,2,4]triazine-6,3′-pyrrolidine-4′,3″-indole)-2,2″,7(1H,1″H)-triones.     

Reaction of organozine reagents derived from dialkyl 2,2-dibromomalonates and methyl 4,4-dibromo-3-oxoalkanoates with 2-oxochromene-3-carboxamides

Organozinc compounds obtained by treatment of dialkyl 2,2-dibromomalonates with zinc reacted with N-substituted 2-oxochromene-3-carboxamides to give dialkyl 1a-R-carbamoyl-2-oxo-1a,7b-dihydro-2H-cyclopropa[c]chromene-1,1-dicarboxylates or alkyl 2-R-1,3,4-trioxo-2,3-dihydro-1H,9bH-chromeno[3′,4′:1,3]-cyclopropa[1,2-c]pyrrole-9c-carboxylates. Reactions of N-substituted 2-oxochromene-3-carboxamides with zinc enolates derived from methyl 4,4-dibromo-3-oxoalkanoates led to the formation of the corresponding 9c-alkyl-2-R-2,3-dihydrochromeno[3′,4′:1,3]cyclopropa[1,2-c]pyrrole-1,3,4-triones.     

Synthesis of some 5-Aryl-4,5-dihydro[1]benzoxepin-3(2H)-ones and 5-aryl-5,6,8,9-tetrahydro-7H-benzocyclohepten-7-ones from benzoxepinoisoxazolone and benzocycloheptaisoxazolone derivatives

Some 5-aryl-4,5-dihydro[1]benzoxepin-3(2H)-ones and 5-aryl-5,6,8,9-tetrahydro-7H-benzocyclohepten-7-ones were synthesized by hydrogenolytic cleavage of the isoxazole ring of 4-aryl-3-oxo-3,3a,4,10-tetrahydro[1]-benzoxepino[3,4-c]isoxazoles or 4-aryl-3-oxo-3a,4,9,10-tetrahydro-3H-benzo[4,5]cyclohepta[1,2-c]isoxazoles which in turn were prepared from ethyl 3-oxo-4-phenoxybutanoate or ethyl 3-oxo-5-phenylpentanoate by simple methods.     

Synthesis of 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide

The reaction of methyl 2-bromo-6-(trifluoromethyl)-3-pyridinecarboxylate ( 1 ) with methanesulfonamide gave methyl 2-[(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridine-carboxylate ( 2 ). Alkylation of compound 2 with methyl iodide followed by cyclization of the resulting methyl 2-[methyl(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridinecarboxylate ( 3 ) yielded 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 4 ). The reaction of compound 4 with α,2,4-trichlorotoluene, methyl bromopropionate, methyl iodide, 3-trifluoromethylphenyl isocyanate, phenyl isocyanate and 2,4-dichloro-5-(2-propynyloxy)phenyl isothiocyanate gave, respectively, 4-[(2,4-dichlorophenyl)methoxy]-1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazine 2,2-dioxide ( 5 ), methyl 2-[[1-methyl-2,2-dioxido-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4-yl]oxy]propanoate ( 6 ), 1,3,3-trimethyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 7 ), 4-hydroxy-1-methyl-7-(trifluoromethyl)-N-[3-(trifluoromethyl)phenyl]-1H-pyrido[2,3-c][1,2]thiazine-3-carboxamide 2,2-dioxide ( 8 ), 4-hydroxy-1-methyl-7-(trifluoromethyl)-N-phenyl-1H-pyrido[2,3-c][1,2]thiazine-3-carboxamide 2,2-dioxide ( 9 ) and N-[2,4-dichloro-5-(2-propynyloxy)phenyl]-4-hydroxy-1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2] thiazine-3-carboxamide 2,2-dioxide ( 10 ).     

Five-membered 2,3-dioxo heterocycles: LXXXVIII. Reaction of 3-aroylpyrrolo[1,2-d][1,4]benzoxazine-1,2,4(4H)-triones with N,N′-dicyclohexylcarbodiimide under thermolysis conditions

Thermolysis of 3-aroylpyrrolo[1,2-d][1,4]benzoxazine-1,2,4(4H)-triones generates aroyl(2-oxo-1,4-benzoxazin-3-yl)ketenes which react as dienes at the aroylketene fragment in [4 + 2]-cycloaddition at the C=N bond of N,N??-dicyclohexylcarbodiimide with formation of 3-[6-aryl-4-oxo-3-cyclohexyl-2-cyclohexylimino-3,4-dihydro-2H-1,3-oxazin-5-yl]-2H-1,4-benzoxazin-2-ones. Thermolysis of the latter is accompanied by elimination of N,N??-dicyclohexylcarbodiimide, and aroyl(2-oxo-1,4-benzoxazin-3-yl)ketenes thus generated undergo cyclodimerization to produce 7-aroyl-6,10-dioxo-9-(2-oxo-2H-1,4-benzoxazin-3-yl)-6,10-dihydrobenzo[b]pyrido[1,2-d][1,4]oxazin-8-yl benzoates.     

About the synthesis of [1,2]diazepinoindole derivatives from ethyl 2-(1-methylindole)acetate, 2-indole and 3-indoleacetohydrazones

The Vilsmeier-Haack reaction with ethyl 2-(1-methylindole)acetate and N,N-Dimethylamides/phosphorus oxychloride gave (65–85%) of ethyl 2-(3-acyl-1-methylindole)acetates 2 , which when boiled with hydrazine yielded about 90% of 4,5-dihydro-6-methyl-4-oxo-3H[1,2]diazepino[5,6-b]indoles 3. The attempted cyclization of 2-(1-methylindole)acetohydrazones 6 with acyl (acetyl and benzoyl) chlorides/triethylamine, to [1,2]diazepino[5,6-b]indole derivatives was fruitless and the bis(acyl)hydrazones 9 were obtained. Several transformations of 9 are reported. Similarly, the attempted cyclization of 3-indoleacetohydrazones 14 with acetyl chloride/triethylamine to [1,2]diazepino[4,5-b]indole derivatives was also fruitless and the bis(acyl)hydrazones 16 were again obtained.     

‘Higher-order’ azomethine ylides in the synthesis of functionalized pyrroles and 5-oxo-5H-pyrrolizines

Azafulvenium methides generated by the thermal extrusion of SO₂ from 1-methyl- and 1,1-dimethyl-1H,3H-pyrrolo[1,2-c]thiazole-2,2-dioxides undergo [1,8]H sigmatropic shifts to give vinylpyrroles. Flash vacuum pyrolysis of the C-vinylpyrroles affords 5-oxo-5H-pyrrolizines or C-allyl-1H-pyrroles.     

Reactions of 3,4-Dichloro-N-R-maleimides with Substituted 2-Thiouracils

Reactions of 3,4-dichloro-N-R-maleimides with substituted thiouracils at 40°C gave a 1:1 mixture of isomers of pyrrolothiazolopyrimidinetriones. Under conditions of thermodynamic control (100°C, 5 h) only pyrrolo[3',4':4,5]thiazolo[3,2-a]pyrimidine-4,6,8-triones were formed, hydrolysis of which followed by decarboxylation gave 5-oxo-5H-thiazolo[3,2-a]pyrimidine-2-carboxamide. The structure of N²-phenyl-6-methyl-5-oxo-5H-thiazolo[3,2-a]pyrimidine-2-carboxamide was confirmed by X-ray crystallography. Analogous cyclization of 3,4-dichloro-N-R-maleimides with 2-thioxoquinazol-4-one also gave a mixture of two isomers which were successfully separated by fractional crystallization.     

Synthesis of optically active hydridocarbonyl triosmium clusters with terpene derivatives as ligands. Molecular structure and absolute configuration of a cluster with a bridging dihydroimidazole ligand

Reactions of the triosmium clusters Os₃(CO)₁₁(NCMe) (1) and Os₃(CO)₁₀(NCMe)₂ (2) with terpene derivatives,viz., (1S,3S,4R,6R)-3-(N,N-dimethylamino)-4-amino-3,7,7-trimethylbicyclo [4.1.0]heptane (3). (3bR,4aR)-(3,4,4-trimethyl-3b,4,4a,5-tetrahydrocyclopropa [3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetic acid (4a), and (3bR,4aR)-3-(3,4,4-trimethyl-3b, 4,4a,5-tetrahydrocyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)propionic acid (4b), were studied. A complex with the terminally coordinated ligand is formed in the first step of the reaction of diamine3 with cluster1. Heating of the resulting complex is accompanied by activation of one of the methyl groups of the ligand to form diastereomers with the bridging tricyclic dihydroimidazole ligand. One of these diastereomers was studied by X-ray diffraction analysis and its absolute configuration was established. Pyrazolycarboxylic acids react with cluster2 as simple organic acids and are coordinated as a bridge at the Os—Os bond through the carboxyl group. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1447–1454, August, 2000.     

Bis-Pyrazolones as azodienophiles

Lead tetraacetate oxidations of 2,3,3a,4,6,7,7a,8-octahydrobenzo[1,2-c:4,5-c']dipyrazolo-3,7-dione and 2,3,3a,4,5,5a,6,7-octahydrobenzo[2,1-c:3,4-c']dipyrazolo-3,6-dione in the presence of 1,3-cyclopentadiene, 1,3-cyclohexadiene, 2,3-dimethyl-1,3-butadiene or 1,4-diphenyl-1,3-butadiene have yielded octahydrodipyridazino[1,2-a:1,2-a']benzo[1,2-c:4,5-c']dipyrazolo-6,14-diones and octahydrodipyridazino[1,2-a:1,2-a']benzo[2,1-c:3,4-c']dipyrazolo-6,9-diones. In one of the eight Diels-Alder reactions two isomeric products were isolated.     

Synthesis and transformations of new 3-oxo(thioxo)-1-phenyl-2,3,5,6,7,8-hexahydroisoquinoline-4-carboxylic acid derivatives

By condensation of 2-benzoyl-1-(morpholin-4-yl)-1-cyanohexene with cyanoacetanilides and monothiomalonodiamide the corresponding 2-substituted 3-oxo-1-phenyl-2,3,5,6,7,8-hexahydroisoquinoline-4-carbonitriles and 3-thioxo-1-phenyl-2,3,5,6,7,8-hexahydroisoquinoline-4-carboxamide were obtained. The latter was used in the synthesis of 3-alkylthio-1-phenyl-5,6,7,8-hexahydroisoquinoline-4-carboxamides and 3,3-dimethyl-1-oxo-6-phenyl-1,2,7,8,9,10-hexahydro-3H-[1,3]thiazino[6,5-c]isoquinoline.     

Cyclopropanation of N-substituted 3-aryl-2-cyanoprop-2-enamides and derivatives of 5,5-Dimethyl-2-oxo-2,5-dihydrofuran-3-carboxylic acid and 2-oxochromene-3-carboxylic acid with bromine-containing zinc enolates

Zinc enolates derived from 1-aryl-2,2-dibromoalkanones react with N-substituted 3-aryl-2-cyanoprop-2-enamides and 5,5-dimethyl-2-oxo-2,5-dihydrofuran-3-carboxylic and 2-oxochromene-3-carboxylic acid derivatives to give, respectively, N-substituted 2-alkyl-3-aryl-2-aroyl-1-cyanocyclopropane-1-carboxamides, 6-(4-bromobenzoyl)-4,4,6-trimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylic acid ethyl ester and morpholide, and 1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropla[c]chromene-1a-carboxylic acids as a single geometric isomer. Treatment of 1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxylic acids with carboxylic acid anhydrides leads to the formation of the corresponding 9c-alkyl-1-aryl-3,4-dioxo-9b,9c-dihydro-2,5-dioxacyclopenta[2,3]cyclopropa[1,2-a]naphthalen-1-yl carboxylates.