Synthesis and mass spectral fragmentations of new spiro heterocycles

The reaction of dichlorodiphenoxymethane (2) with ortho-functionlized benzoic acids 1a-c yielded the spiro derivatives of bezodioxinone 4a, benzoxazinone 4b and benzodioxepinone 4c. The same reaction with 1,8-diaminonaphthalene afforded the spiro perimidine 6, while with 1,1'-binaphthy1-2,2'-diol gave the semi-cyclized derivative 2,2-diphenoxydinaphthodioxepine 8.     

Synthesis of homochiral spiro[4.4] nonane-1,6-diols

Homochiral cis,cis-; cis,trans- and trans,trans-spiro[4.4]nonane-1,6-diols were prepared via diastereoselective reduction of enantiomerically pure spiro[4.4]nonane-1,6-dione (1) with the corresponding reducing agents: lithium n-butyldiisobutylaluminium hydride for cis,cis-diol (2) with 88% yield; BH3·THF for cis, trans-diol (3) with 91% yield; LiAlH4 for trans,trans-diol (4) with 15% yield.     

α-Cyclopropylalkyl cations of a spiro[2.4] heptane system

-Cyclopropylalkyl cations of a spiro[2.4]heptane system, which are possible intermediates in solvolytic reactions of the corresponding cyclopropylalkanol derivatives, have been generated from compounds of the spiro(indan-2,1-cyclopropane), spiro(indan-1,1-cyclo-propane), and spiro[acenaphthylene-1(2H),1-cyclopropane] classes under long life conditions (HSO{in3}F-SO{in2}FCl-CD{in2}Cl{in2}, –100 °C).Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2194–2198, December, 1994.This work was carried out with the financial support of the Russian Foundation for Basic Research (Project No. 93-03-4715).     

Synthesis of spiro[isoquinoline-4,4′-pyran]-3-imines

A method has been developed for the synthesis of 4-[2-(bromomethyl)phenyl] tetrahydro-2H-4-pyrancarbonitrile and a study was carried out on the reaction of this compound with primary amines, which, depending on the conditions, leads to either 4-[2-(R-aminomethyl)phenyl]tetrahydro-2H-4-pyrancarbonitriles or hydrobromides of 2-R-aryl-2,3,2,3,5,6-hexahydrospiro[isoquinoline-4(1H),4-pyran]-3-imines.Taras Shevchenko Kiev University, 252017 Kiev, Ukraine; e-mail: vkysil@mail.univ.kiev.ua. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1035–1041, August, 2000.     

A new rearrangement of spiro[indane-1,3′-thiophene] and spiro[naphthalene-1,3′-thiophene] derivatives accompanied by opening of the cycloalkane ring

Abstract  

The new thioamides 2-oxoindane-1-carbothioamides and 2-oxo-1,2,3,4-tetrahydronaphthalene-1-carbothioamides underwent conjugated addition to (E)-β-nitrostyrenes followed by cyclization to give products containing 5-hydroxyimino-2-aryliminothiophene rings spiro-annulated to the 2-indanone or 2-tetralone system. On treatment with hydrochloric acid in boiling methanol the compounds underwent a new rearrangement, involving transformation of the 2-aryliminothiophene ring to a pyrrole and an opening of the alicyclic ring in the proximity of the carbonyl group, affording 2-(1,3-diaryl-2-oxo-5-thioxopyrrol-4-yl)benzeneacetic or 2-(1,3-diaryl-2-oxo-5-thioxopyrrol-4-yl)benzenepropanoic acid methyl esters. The structures of two selected pyrrole derivatives were determined by X-ray crystal analyses. The thioamides derived from 2-indanone showed unexpected reactivity towards primary alcohols and underwent conversion to 2-hydroxy-1H-indene-3-thiocarboxylic acid O-esters.     

Thermal decomposition of strained spiro(1-pyrazoline-3,1′-cyclopropanes)

Pyrolysis (320–370 °C) of polycyclic 1-pyrazolines1 and2, obtained by 1,3-dipolar cycloaddition of diazocyclopropane to 3,3-dimethylcyclopropene and spiro[2,3]hex-1-ene, yields complex mixtures of isomeric hydrocarbons, substituted methylenecyclopropanes being the main components. Pyrolysis of 6-ethenyl- (4) and 6-methoxy-6-methylcarbonyl-4,5-diazaspiro[2,4]hept-4-enes (6) at 310–320 °C proceeds more unambiguously to give vinyl- (18) and 1-methoxy-1-methylcarbonylspiropentanes (20) in 85 and 95 % yields with respect to the transformed pyrazolines. Dediazotization of pyrazoline3 obtained from diazocyclopropane and benzvalene requires more drastic conditions (–440 °C) and produces indane.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2203–2207, November, 1995.This study was financially supported by the Russian Foundation for Basic Research (Grant No. 94-03-08902).     

Synthesis of new heterocyclic systems—substituted spiro[chromene-4,3′-indoles] and spiro[indole-3,4′-quinolines]

Methods have been developed for the synthesis of new heterocyclic systems, spiro[chromene-4,3′- indoles] and spiro[indole-3,4′-quinolines] by the base-catalyzed domino reaction of isatins with 5,5-dimethylcyclohexane- 1,3-dione (or 5,5-dimethyl-3-anilinocyclohex-2-en-1-one) and ethyl cyanoacetate.     

Synthesis of spiro[9,10-dihydro-10-sila-2-azaanthracene-9,1′-cyclopropanes

The Z- and E-isomers of 9,14dihydro-10,10-&-methyl-2-trimethylsilyl(2phenyl-3 fornryl)spiro[IO-sila-2-azaanthracene-9,1 -cyclopropane] have been obtained by heating 9-diazo-9,10-dihydro-10,10-dimethyl-10-sila-2azaanthracene with trimethylvinylsilane and with cinnanuaidehyde.     

Synthesis of spiro[pyrrole-2,5′-thiazoles] by heterocyclization of pyrrolobenzoxazinetriones with salicylaldehyde thiosemicarbazone

Russian Journal of Organic Chemistry - 3-Aroylpyrrolo[1,2-c][4,1]benzoxazine-1,2,4-triones reacted with salicylaldehyde thiosemicarbazone to give...     

Recyclization of spiro[3a-Hydroxypiperidin-4,2′-oxiranes] in basic medium

It is shown that heating spiro[3a-hydroxypiperidin-4,2-oxiranes] in aqueous base gives rearrangement into derivatives of 3,4-epoxypiperidines. The structures of the latter were confirmed by spectral data and by chemical informations.Belorussian State Technological University, Minsk 220030. Translated from Khimiya Geterotsiklicheskikh Soedineii, No. 9, pp. 1213–1215, September, 1994. Original article submitted July 29, 1994.     

Resonance-stabilized α-naphthylmethyl carbocations and derived spiro compounds 4. T-ansformations of 4-dimethylamino-5-methoxynaphthylmethyl carbocation in the presence of protic and Lewis acids. The formation of an asymmetrical spiro compound

4-Dimethy(amino-5-methoxynaphthylmethyl carbocation generated from 1-hydroxy methyl-4-dimethylamino-5-methoxynaphthalene in trifluoroacetic acid behaves as both diene and dienophile and undergoes (4 + 2) cycloaddition to give an asymmetrical spiro compound. The other reaction product is 4,4'-bis(dimethylamino)-5,5'-dimethoxy 1,l'-dinaphthylmethane, which is formedvia ipso-substitution of the hydroxymethyl group in the initial alcohol. When this cation is generated on Al₂O₃, 4-dimethylamino-5-methoxy 1-naphthaldehyde is formed along with the substituted dinaphthylmethane.For Part 3, see Ref. 1.Translated from Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 2039–2043, August, 1996.     

Investigation of regioselectivity in the synthesis of spiro [pyrrolidine-2,3′-oxindoles] by use of the Huisgen reaction

The Huisgen reaction has been used to synthesize five-membered heterocyclic compounds in high yield and with high regio and stereoselectivity. In the synthesis of spiro [pyrrolidine-2,3′-oxindole] derivatives from isatin, α-amino acids, and (E)-β-phenyl nitroolefins, two regioisomers were obtained in each reaction. The regioselectivity of the major product was found to be different from that in reported work, and was investigated at the B3LYP/6-311G* level of theory. On the basis of this new finding, several conditions, for example molar ratio, solvent, and temperature, which affect the regioselectivity of this reaction were investigated; the results obtained are discussed. It was found that the regioselectivity of this reaction was affected by solvent and temperature, irrespective of the ratio of the reactants. Low temperature and high solvent polarity leads to high regioselectivity, and protic solvents result in higher yield and regioselectivity. These results are of benefit for regioselective synthesis of some compounds.     

Construction of functionalized spiro 1,4-benzoxazine oxindole derivatives via domino Mannich-alkylation of α-halocarbonyl compounds with imines

A series of functionalized spiro 1,4-benzoxazine oxindole derivatives were obtained in moderate to good yields via a domino Mannich-alkylation of α-halocarbonyl compounds with imines under mild conditions.     

Synthesis of spiro(benzo[h]quinazoline-5,1′-cyclohexane) derivatives

3-p-Methoxyphenyl-4-oxo-2-mercapto-3, 4, 5, 6-tetrahydrospiro(benzo[h]quinazoline-4,1 -cyclohexane) wassynthesized by the reaction of 4-amino-3-ethoxycarbonvl-1, 2-dihydrospiro(naphthalene-2,1 '-cyclohexane) (1) with p-methoxyphenvl isothiocyanate without separation of the thioureido derivative. Amino ester 1 is transformed byacetamide and formamideinto 2-methyl-4-oxo-3, 4, 5, 6-tetrahydrospiro(benzo[h]quinazoline-5,1 -cyclohexane) and 4-oxo-3, 4, 5, 6-tetrahydrospiro(benzo[h]quinazoline-5,1-cyclohexane (11), respectively. Alkylation of quinazoline 11 with methyl iodide results in formation of 3-methyl-4-oxo-3, 4, 5, 6-tetrahydro-spiro (benzo[h]quinazoline-5,1 -cyclohexane). Amino ester 1 reacts with caprolactam with formation of 2, 3 pentamethylene-4-oxo-3, 4, 5, 6-tetrahydrospiro(benzo[h]quinazoline-5,1-cyclohexane). 4-Ethoxymethyleneamino-3-ethoxy-carbonyl-1,2-dihydrospiro(naphthalene-2,1-cyclohexane) was synthesized by the reaction of amino ester 1 with o-formic ester, and was converted into 3-amino-4-oxo-3, 4,5, 6-tetrahydro-spiro(benzo[h]quinazoline-5,1-cyclohexane) (VIII) by hydrazine hydrate. Aminoquinazoline VIII is acylated by acid chlorides with formation of 3-acylamino-4-oxo-3,4,5,6-tetrahydrospiro(benzo[h]quinazoline-5,1-cyclohexanes) and forms 3-benzyl-ideneamino-4-oxo-3,4,5,6-teirahydrospiro(benzo[h]quinazoline-5,1-cyclohexane) with benzaldehyde.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 530–533, April, 1996     

Efficient multicomponent synthesis of spiro[indoline-3,4′-thiopyran]-2-ones

Synthesis of new thiopyran fused spirooxindoles (spiro[indoline-3,4′-thiopyran]-2-ones) were achieved by a multicomponent reaction of N-methyl isatin, malononitrile/ethyl cyanoacetate, and β-oxodithioester using N,N′-dimethylaminopyridine as the catalyst.     

Synthesis of the substituted spiro segment of halichlorine--use of radical cyclization and stereospecific cuprate addition to an α,β-unsaturated lactam

Radical cyclization (26a,b → 27a,b+28) and cuprate addition (28 → 31) were used as key steps to construct the spiro core 4 of halichlorine.     

Electrophilic 1,5-addition of acyl chlorides to the azocyclopropane system of spiro(1-pyrazoline-3,1′-cyclopropanes)

1-Pyrazolines1–4, which contain a spiro cyclopropane fragment at the adjacent azo group, react selectively with acetyl (benzoyl) chloride or acetic anhydride in the presence of AlCl₃ to give high yields of the corresponding 1-acyl-3-(2-chloroethyl)-2-pyrazolines5–8, adducts of electrophilic 1,5-addition of acyl chlorides to the conjugated azocyclopropane system.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1993–1996, November, 1994.This study was financially supported by the Russian Foundation for Basic Research (grant No. 94-03-08902).     

Titanium-catalyzed cyclocodimerization of cyclohepta-1,3,5-triene with spiro[cyclopropane-1,7′-norborna-2,5-diene]

Russian Chemical Bulletin - Titanium complexes-catalyzed codimerization of cyclohepta-1,3,5-triene with spiro[cyclopropane-1,7′-norborna-2,5-diene] affords...     

Synthesis of novel non-natural spiro[2.3]hexane amino acids,the conformationally restricted analogs of γ-aminobutyric acid

3-Methylenecyclobutanecarboxylic acid and its methyl ester were used as the starting compounds for the synthesis of new spiro[2.3]hexane amino acids, the conformationally rigid analogs of γ-aminobutyric acid, namely, 5-aminospiro[2.3]hexanecarboxylic and 5-amino-spiro[2.3]hexanephosphonic acids, promising modulators of GABAergic cascades in the human central nervous system. The methods developed for the synthesis of the target amino acids are based on the reactions of catalytic [1+2] cycloaddition of diazoacetic and diazophosphonic esters to 3-substituted methylenecyclobutanes, as well as on a modified Curtius reaction for the transformation of a carboxy group to the amine one.     

Synthesis of spiro[furan-3,3′-indolin]-2′-ones by PET-catalyzed [3+2] reactions of spiro[indoline-3,2′-oxiran]-2-ones with electron-rich olefins

An efficient procedure for the synthesis of spiro[furan-3,3′-indolin]-2-ones and dispiro[cycloalkane-1,2′-furan-3′,3″-indolin]-2″-ones has been achieved in high yields and stereoselectivity by photoinduced electron transfer-catalyzed [3+2] reactions of substituted spiro[indoline-3,2′-oxiran]-2-ones with olefins. The reactions proceed by ring opening of spiro[indoline-3,2′-oxiran]-2-ones via C_β–O bond cleavage and subsequent cycloaddition with olefins by using 2,4,6-triphenylpyrylium tetarfluoroborate (TPT) as a sensitizer.