Synthesis and transformations of polyhedral compounds. Synthesis of 2-[quinolin-3(2)-yl]-1,3-diazaadamantanes

A number of new 1,3-diazaadamantane derivatives containing quinoline fragments on C² have been synthesized by condensation of 1,5-dialkyl-3,7-diazabicyclo[3.3.1]nonan-9-one, 1,5-dimethyl-3,7-diazabicyclo-[3.3.1]nonan-9-ol, and 1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane with 2-oxo-1,2-dihydroquinoline-3-carbaldehyde, 2-chloro- and 2-iodoquinoline-3-carbaldehyde, and quinoline-2-carbaldehyde.     

Reactions of 3,5-dibromo-1-(thiiran-2-ylmethyl)-1,2,4-triazole with NH-azoles

Reactions of 3,5-dibromo-1-(thiiran-2-ylmethyl)-1,2,4-triazole with 3,5-dimethylpyrazole, 1,3-dimethyl-3,7-dihydropurine-2,6-dione, 3,5-dibromo-1,2,4-triazole, 2,4,5-tribromoimidazole, and 2-chlorobenzimidazole lead to the formation of 5-azolylmethyl-2-bromo-5,6-dihydrothiazolo[3,2-b]-1,2,4-triazoles. In the case of 8-bromo-1,3-dimethyl-3,7-dihydropurine-2,6-dione the intermediate thiolate anion undergoes cyclization into 7-[(3,5-dibromo-1,2,4-triazol-1-yl)methyl]-1,3-dimethyl-6,7-dihydrothiazolo[2,3-f]purine-2,4(1H,3H)-dione. The structure of reaction products depends on the relative rate of substitution of leaving groups in the reagents.     

7-Substituted 8-vinyl-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-diones and their broncholytic activity

Summary Alkylation of 8-vinyl-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (1) with alkyl halides inDMF in the presence of potassium carbonate, or alternatively, alkylation of its sodium salt (2) with alkyl iodide or hydroxyalkyl iodide afforded the 7-alkyl- or 7-(-hydroxyalkyl)-8-vinyl-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-diones3. 2-Substituted oxiranes reacted with1 catalyzed by2 or Triton B to yield 7-(2-hydroxyalkyl)-8-vinyl-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-diones4. Compounds3 and4 were tested for broncholytic activity. The most effective derivatives were3c and4b.

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7-Substituierte 8-Vinyl-1,3-dimethyl-3,7-dihydro-1H-purin-2,6-dione und ihre broncholytische Wirkung

Zusammenfassung Alkylierung von 8-Vinyl-1,3-dimethyl-3,7-dihydro-1H-purin-2,6-dion (1) mit Halogenalkanen in Gegenwart von Kaliumkarbonat inDMF oder Alkylierung seines Natrium-Salzes (2) mit Iodalkanen beziehungsweise Iodalkanolen führte zu den 7-Alkyl- bzw. 7-(-Hydroxyalkyl)-8-vinyl-1,3-dimethyl-3,7-dihydro-1H-purin-2,6-dionen3. 2-Substituierte Oxirane reagierten mit Verbindung1 unter Katalyse durch2 oder Triton B zu den entsprechenden 7-(2-Hydroxyalkyl)-derivaten4. Die Substanzen3 und4 wurden auf ihre broncholytische Wirkung geprüft. Die höchste Aktivität wurde bei den Derivaten3c und4b festgestellt.

     

Synthesis and Reactions of Polyhedral Compounds. 27. Development of a Synthetic Route for 2- Spiro-substituted 6-Hydroxy-5,7-dimethyl-1,3-diazaadamantanes

Alternative methods for the synthesis of 2-spiro-substituted 6-hydroxy-5,7-dimethyl-1,3-diazaadamantanes have been developed. These are the reduction of the ketone group to hydroxyl in the corresponding 6-oxo-1,3-diazaadamantanes and the condensation of 9-hydroxy-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane (obtained by different routes from 5,7-dimethyl-6-oxo-1,3-diazaadamantane) in reaction with cyclic ketones.     

Alkylations of tricyclo[5.2.1.0]deca-4,8-dien-3-one by a cuprate reaction

Alkylation at C₆ of tricyclo[5.2.1.0^2,6]deca-4,8-dien-3-one (R=H) was achieved by treatment of 6-bromotricyclo[5.2.1.0^2,6]deca-4,8-dien-3-one with lithium dimethylcuprate and subsequently with an appropriate electrophile. The best results were obtained in THF as the solvent. A wide range of alkyl halides, bromo ketones and esters, and acetyl chloride resulted in C₆-tricyclo[5.2.1.0^2,6]deca-4,8-dien-3-ones in moderate to good yields. This alkylation reaction proceeds via a C₆-carbanionic Cu intermediate, which is likely stabilized by the enone olefinic bond. 6-Bromo-endo-tricyclo[5.2.1.0^2,6]dec-8-en-3-one, which lacks this double bond, behaves differently. Treatment with lithium dimethylcuprate leads to dehydrobromination to give tricyclo[5.2.1.0^2,6]deca-2(6),8-dien-3-one in high yield.     

Sigmatropische Umlagerungen von Aryl-propargyläthern; Synthese von 1, 5-Dimethyl-6-methylen-tricyclo[3, 2, 1, 02,7]-oct-3-en-8-on-Derivaten. Vorläufige Mitteilung

2, 6-Dimethylphenyl propargyl ether ( 10 ) and its derivatives 12–15 rearrange thermally to 1, 5-dimethyl-6-methylene-tricyclo [3.2.1.0^2,7]oct-3-en-8-one ( 9 ) and related compounds 16–19 . The ethers undergo first an aromatic [3, 3]-sigmatropic rearrangement to ortho-allenyldienones 11 , which then undergo ring closure to the tricyclic products by an electrocyclic reaction. Only in the case of the γ-methylpropargyl ether 13 , the ortho-dienone 11 is further rearranged in low yield to the para-butynylphenol 20 , but the tricyclic ketone 17 is again the main product. New data show that the known thermal cyclisation of aryl propargyl ethers to chromenes (e. g. 4 → 8 ) involves a preliminary [3, 3]-sigmatropic rearrangement.     

Photochemistry synthesis. Part 1: Syntheses of xanthine derivatives by photolysis of 1-(5′-oxohexyl)-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione (pentoxifylline): an ambident chromophore

We investigated the use of photochemistry to make novel derivatives of pentoxifylline. Under conditions that favour singlet excited states, we obtained 1-allyl-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione, (R^∗,R^∗)-(±)-1-{[2-hydroxy-2-methylcyclobutyl]methyl}-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione and 1-(5-hydroxyhexyl)-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione. Naphthalene or molecular oxygen increases the yields and triplet sensitisers (acetophenone, benzophenone and acetone) decrease the yields. Efficient intramolecular triplet energy transfer from the carbonyl to the xanthine moiety allows the carbonyl moiety to react from a singlet excited state only. In solvents with an α-hydroxyalkyl hydrogen under conditions that favour triplet excited states, we obtained 8-substituted pentoxifylline derivatives: 8-(1-hydroxy-1-methylethyl)-3,7-dimethyl-1-(5-oxohexyl)-3,7-dihydro-1H-purine-2,6-dione in isopropanol, 8-(1-hydroxymethyl)-3,7-dimethyl-1-(5-oxo-hexyl)-3,7-dihydro-1H-purine-2,6-dione in methanol and 8-(1-hydroxyethyl)-3,7-dimethyl-1-(5-oxohexyl)-3,7-dihydro-1H-purine-2,6-dione in ethanol. The xanthine moiety reacts from a triplet state via a radical mechanism and yields are considerably improved by the addition of catalytic amounts of di-tert-butyl peroxide.     

Synthesis,structural, and biochemical study of a series of methyl 2,6-diaryl-1-methyl-4-oxopiperidine-3,5-dicarboxylates and a series of methyl 2,4-diaryl-3,7-dimethyl-9-oxo-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarboxylates

A series of methyl-2,6-diaryl-1-methyl-4-oxopiperidine-3,5-dicarboxylates Ia-c and 2,4-diaryl-3,7-dimethyl-1,5-dimethoxycarbonyl-9-bispidinones IIa-c have been synthesized and studied by ir, ¹H and ¹³C nmr spectroscopy and the crystal structure of methyl 2,4-diphenyl-3,7-dimethyl-9-oxo-3,7-diazabicyclo[3,3.1]nonane-1,5-dicarboxylate (IIa) has been determined by X-ray diffraction. The enolic form of compound Ia (I'a) was also studied.     

Total synthesis of the sesquiterpene (±)-hirsutene using an organoselenium-mediated cyclization reaction

Cyclization of 2-carbomethoxy-3-(4',4'-dimethylcyclopent-2-enylmethyl)cyclopentanone (4) with N-phenylselenophthalimide and tin(IV) chloride affords cis-syn-cis-1β-carbomethoxy-4,4-dimethyl-3β-phenylselenotricyclo [6.3.0.0^2,6]undecan-11-one (8) and cis-anti-cis-1β-carbomethoxy-4,4-dimethyl-3α-phenylselenotricyclo [6.3.0.0^2,6]undecan-11-one (9). Both of these selenides can be elaborated to cis-anti-cis-4,4-dimethyl-1β-methyltricyclo [6.3.0.0^2,6]undecan-11-one (13) which upon treatment with CH₂Br₂/ TiCl₄/Zn affords the sesquiterpene (±)-hirsutene (1) in 20% overall yield.     

Synthesis of Some Spirooxazolidinones

In this communication, we wish to report the synthesis of some new spiro-4-oxazolidinones. Treatment of the potassium salt of 2-methyl-cyclohexane-1,3-dione (1) with α-chloroacetanilides (2 a-c) gave 4-aryl-6-methyl-1-oxa-4-aza-spiro [4,5] deca-3,7-diones (3 a-c); and with α-halopropionanilides (2 d,e), the corresponding 4-aryl-2,6-dimethyl-1-oxa-4-aza-spiro [4,5] deca-3,7-diones (3 d, e) were obtained.     

Synthetic access of new 6-purineselenyl and 8-(1,3,4-thiadiazolyl)-7-benzyl-1, 3-dimethyl-1H-purine-2,6-(3H,7H)-dione derivatives

Abstract

New 6-purineselenyl, 1, 3, 4-thiadiazols bearing 7-benzyl-1,3-dimethyl-1H-purine-2,6-(3H,7H)-diones and (8-[2-(3-phenyl-5-substituted-1,3,4-thiadiazol-2(3H)-ylidene) hydrazinyl)-7-benzyl-1,3-dimethyl-1H-purine-2,6-(3H,7H)-diones derivatives were synthesized. The structures of the newly synthesized compounds were elucidated by spectroscopic methods (1H-NMR, 13C-NMR, and MS spectrometry) and elemental analysis.     

The Use of 4-(Bromomethylene)-5,5-dimethyl-1,3-dioxolan-2-one as “Masked” α-Bromo-α'-Hydroxy Ketone in the Synthesis of Heterocyclic Systems

4-(Bromomethylene)-5,5-dimethyl-1,3-dioxolan-2-one was obtained on the basis of the readily obtainable 4-methylene-5,5-dimethyl-1,3-dioxolan-2-one. It forms 2-imidazo[1,2-a]pyridin-2-yl-2-propanol with 2-aminopyridine, 11a-hydroxy-1,1-dimethyl-3-oxo-1,5,11,11a-tetrahydro[1,3]oxazolo[3,4-a]pyrido[1,2-d]-10-pyrazinium bromide with 2-(aminomethyl)pyridine, and the corresponding derivative of 4-hydroxyoxazolidin-2-one with 2-(3,4-dimethoxyphenyl)ethylamine. The last product was converted by intramolecular amidoalkylation without isolation into 10b-(bromomethyl)-8,9-dimethoxy-1,1-dimethyl-1,5,6,10b-tetrahydro[1,3]oxazolo[3,4-a]isoquinolin-3-one.     

Products active on mosquitoes,IV: Synthesis and biological activity of 8-propargyloxy-3,7-dimethyl-2,6-octadienyl/6-octenyl ethers

Summary A series of 8-proparglyoxy-3,7-dimethyl-2,6-octadienyl and 8-propargyloxy-3,7-dimethyl-6-octenyl ethers were prepared from 8-hydroxygeranyl and 8-hydroxycitronellyl ethers, respectively. Almost all compounds showed high toxicity toCulex quinquefaciatus larvae at 1 mgl^–1 dose level.

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Gegen Mücken aktive Produkte, 4. Mitt.: Synthese und biologische Aktivität von 8-Propargyloxy-3,7-dimethyl-2,6-octadienyl/6-octenyl-ethern

Zusammenfassung Eine Reihe von 8-Propargyloxy-3,7-dimethyl-2,6-octadienyl- und 8-propargyloxy-3,7-dimethyl-6-octenyl-ethern wurden aus 8-Hydroxygeranyl- bzw. 8-Hydroxycitronellyl-ethern hergestellt. Fast alle Verbindungen zeigten hoch Toxizität gegenüber Larven vonCulex quinquefaciatus in einer Dosierung von 1 mgl^–1.

     

Reactions of 1,2,4-triazole derivatives with a “model” thiirane

Reactions of 3-mono- and 3,5-disubstituted 1,2,4-triazoles with a “model” thiirane, 8-bromo-1,3-dimethyl-7-(thiiran-2-ylmethyl)-3,7-dihydro-1H-purine-2,6-diones proceed at the positions N¹ and N² of the triazole ring and yield 7-(5-R-3-R′-1,2,4-triazol-1-yl)methyl- and/or 7-(5-R′-3-R-1,2,4-triazol-1-yl)methyl-1,3-dimethyl-6,7-dihydro[1,3]thiazolo[2,3-f]-purine-2,4-(1H,3H)-diones. 3-Methylsulfonyl-1,2,4-triazole reacted regiospecifically at the position N¹ forming 1,3-dimethyl-7-[(3-methyl-sulfonyl-1,2,4-triazole-1-yl)-methyl]-6,7-dihydro[1,3]thiazolo-[2,3-f]purine-2,4(1H,3H)-dione.     

Synthesis of glutarimide antibiotics and their analogs through 1,3-cycloaddition of 3-glutarimidylacetonitrile oxide to 2-cyclohexenones

A mixture of 4,4-dimethyl-9-(3-methylglutarlmidyl)-2-oxo-7-oxa-8-azabicyclo[4.3.0] non-8-ene and 3-(3-methylglutarimidyl)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydrobenz-[d]isoxazole was obtained by in situ 1,3-dipolar cycloaddition of 3-glutarimidyl-acetonitrile oxide to 5,5-dimethylcyclohex-2-en-1-one. Reductive cleavage of these compounds by catalytic hydrogenation over Pd catalysts gives 3-[2-amino-2,2-(4,4-dimethyl-2-oxocyclohexylene)ethyl]glutarimide and the known 3-[2-amino-2,2-(4,4-dimethyl-2,6-dioxocyclohexylene)ethyl]glutarimide, respectively, in quantitative yield. Hydrolysis of the latter leads to 3-[2-oxo-2-(4,4-dimethyl-2,6-dioxocyclo-hexyl)ethyl]glutarimide. The ketones obtained are analogs of glutarimide antibiotics and polyfunctional intermediates in their synthesis.See [1] for a preliminary communication.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 230–234, February, 1979.     

Heterocyclische und carbocyclische 12-π- and 14-π-Molekülsysteme, 47. Mitteilung. Herstellung von 7, 9-Dimethyl-4, 5-dihydro-3 H-benz [cd]- azulen-3-on and 7,9-Dimethyl-3H-benz [cd]azulen-3-on. Eine einfache Synthese eines Azulenopseudophenalenons

Heterocyclic and Carbocyclic 12-π-and 14-π-Systems, 47th Commnunication¹. Synthesis of 7,9-Dimethyl-4,5-dihydro-3H-benz[cd]azualene-3-one and 7,9-Dimethyl-3H-benz[cd]azulene-3-one. A Simple Synthesis of Azulenopseudophenalenons 4, 6, 8-Trimethylazulene ( 3 ) reacts after metalation with lithiumdiisopropyl-amide in ether with bromoacetic acid to the 6, 8-dimethylaltulene-4-propionic acid ( 4 ), which undergoes cyclization to the 7, 9-dimethyl-4, 5-dihydro-3H-benz [cd]-azulene-3-one ( 5 ) in the presence of p-toluenesulfonic acid; oxidation of 5 with 2, 3-dichloro-5, 6-dicyanobenzoquinone yields 7, 9-dimethyl-3H-benz [cd]azulene-3--one ( 1b ). Alkylation of 1b with triethyloxonium tetrafluoroborate in CH₂C1₂ gives the 3-ethoxy [cd]benzazulenium tetrafluoroborate ( 6 ).     

[f]-Fused purine-2,6-diones: Synthesis of new [1,3,5]- and [1,3,6]-thiadiazepino-[3,2-f]-purine ring systems

Summary 6-Phenyl-1,3-dimethyl-2,4-dioxo-1,2,3,4,8,9-hexahydro-[1,3,5]-thiadiazepino-[3,2-f]-purine (5) was obtained by a three-step synthesis from 8-mercapto-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (1) and 2-(benzoylamino)-ethyl chloride (2)via 8-(benzoylaminoethylthio)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (3) and its chloromido derivative4. The analogous 9-phenyl-1,3-dimethyl-2,4-dioxo-1,2,3,4,6,7-hexahydro-[1,3,6]-thiadiazepino-[3,2-f]-purine (7) was synthesized either from compound1 and N-(2-chloroethyl)-benzimido chloridevia N-(chloroethyl)-S-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-7H-purin-8-yl)-benzothioimide (6), or alternatively from 7-(2-benzoylaminoethyl)-8-bromo-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (9), its 8-mercapto derivative10 and the corresponding chloroimido compound11 being the intermediates.Part of this paper was presented as a preliminary report at the Congress of Czech and Slovak Chemical Societies, Olomouc, Czech Republic, September 13–16, 1993     

Electron Ionization Mass Spectra of Organophosphorus Compounds Part I: The Mass Fragmentation Pathways of Cyclic α-Aminophosphonates Monoester Containing 1,2,4-Triazinone Moiety

Abstract

The electron impact induced fragmentation reactions of 3-(4-chlorophenyl)-3,4- dihydro-2-ethoxy-2-oxido-7-methyl-2H,6H-[1,2,4]triazino[4,3-e][1,4,5,2]thiadiazaphosphin in-6-one (1), 3,7-dimethyl-2-ethoxy-2-oxido-1,2,3,4-tetrahydro-6H-[1,2,4]triazino[4,3-b][1,2,4,5]triazaphosphinin-6-one (2), and 9-amino-3,7-dimethyl-4-ethoxy-4-oxido-2,3,4,9-tetrahydro-8H-[1,2,4]triazino[3,2-c][1,2,4,5]triazaphosphinin-8-one (3) are presented and compared. The 1,2,4-triazine rings have almost identical fragmentation routes. The 1,2,4-triazine rings are rather stable relative to the phosphorus rings. Therefore, fragmentation of the phosphorus rings is more favorable for the compounds than the stable 1,2,4-triazine rings.     

Facile syntheses of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones and the corresponding 6-substituted 4-hydroxy-2-pyrones

A variety of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones 5a-l and the corresponding 6-substituted 4-hydroxy-2-pyrones 3a-l were prepared in high yields under mild reaction conditions by the reaction of 2,2,6-trimethyl-1,3-dioxin-4-one 4 with 1-acylbenzotriazoles 9 in the presence of LDA followed by thermal cyclization of 5a-l to 3a-l. Synthesis of novel 6-(1-benzoylalkyl)-2,2-dimethyl-1,3-dioxin-4-ones 12a-c was achieved by alkylation of dioxinone 5a and their subsequent cyclization gave 5-alkyl-4-hydroxy-2-pyrones 13a-c.     

Reactive species from aromatics and oxa-di-π-methane rearrangement: a stereoselective synthesis of (±)-hirsutene from salicyl alcohol

A total synthesis of hirsutene, a triquinane sesquiterpene, from salicyl alcohol is reported. Oxidation of salicyl alcohol in the presence of cyclopentadiene gave 9-spiroepoxy-endo-tricyclo[5.2.2.0^2,6]undeca-4,10-dien-8-one which was elaborated to the 3-hydroxy-2-methyl-endo-tricyclo[5.2.2.0^2,6]undeca-10-en-8-one containing major structural and functional features of hirsutene. Photochemical sigmatropic 1,2-acyl shift in 3-hydroxy-2-methyl-endo-tricyclo[5.2.2.0^2,6]undeca-10-en-8-one followed by radical induced cleavage of peripheral cyclopropane bond, olefination and Simmon-Smith reaction furnished 11-hydroxy-1-methyl-4-spirocyclopropanetricyclo[6.3.0.0^2,6]undecane that upon treatment with hydrogen on PtO₂ and PCC oxidation gave 1,4,4-trimethyltricyclo[6.3.0.0^2,6]undecan-11-one, a known precursor. Wittig methylenation on this precursor gave hirsutene.