The Homoconjugated Electron-Releasing Carbonyl Group of 1-Methylbicyclo[2.2.1]hept-5-en-2-one. Regioselective syntheses of 5-chloro- and 6-chloro-1-methylbicyclo[2.2.1]hept-5-en-2-one

Syntheses of (±)-2-exo-cyano-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl acetate ( 1 ) and of (±)-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 2 ) are reported. The additon of PhSeCl to 1 afforded (±)-5-endo-chloro-2-exo-cyano-1-methyl-6-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1]hept-2-endo-yl acetate ( 6 ), whereas 2 added to PhSeCl with the opposite regioselectivity giving (±)-6-endo-chloro-1-methyl-5-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1]heptan-2-one ( 7 ). These adducts were converted into 5-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 9 ) and 6-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 10 ), respectively.     

A Diastereoselective Preparation of 7-Ethyl-7-methylbicyclo[3.2.0]HEPT-2-en-6-one(1)

Alkylation of 7-endo-ethylbicyclo[3.2.0]hept-2-en-6-one (2a) and 7-endo-methylbicyclo[3.2.0]hept-2-en-6-one (2b) with lithium diisopropylamide (LDA) and the appropriate alkyl iodide (methyl and ethyl iodide, respectively) afforded the title compound such that alkylation had occurred exclusively on the exo face of the bicyclo[3.2.0] system.     

Condensation of 1-Substituted 1,2,3,9a-Tetrahydro-9H-imidazo[1,2-a]indol-2-one Derivatives with Aromatic Aldehydes

Condensation of 1-alkyl-, 1-allyl-, and 1-benzyl-1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones with benzaldehydes in acetic acid and subsequent treatment of the reaction mixture with potassium hydroxide afforded 1-substituted 9a-(2-phenylethenyl)-1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-one derivatives. 1-Methyl- and 1-ethyl-9a-[2-(4-dimethylaminophenyl)ethenyl]-1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones were synthesized by alkylation of 9a-[2-(4-dimethylaminophenyl)ethenyl]-1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-one with methyl- and ethyl iodides in DMF in the presence of a strong base.     

Unambiguously confirmed structure of 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one

To determine the structures of two isomeric products, 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (2) and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (3) obtained by condensation of 2,3-diaminopyridine (1) with ethyl benzoylpyruvate [1–3], these compounds were hydrolyzed to give 2-methyl-4H-pyrido[2,3-b]pyrazin-3-one (4) and 3-methyl-1H-pyrido[2,3-b]pyrazin-2-one (5) , respectively [4,5]. Both hydrolysates 4 and 5 were hydrogenated to afford 2-methyl-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (6) and 3-methyl-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (7) . The latter compound was identical with an unequivocally synthesized compound providing proof for the structures of all these compounds.     

Synthesis of some 5H-benzo[a]phenothiazin-5-one derivatives

Several substituted 6-anilino-5H-benzo[a]phenothiazin-5-one derivatives were prepared by condensation of substituted 1,4-naphthoquinones with 2-aminobenzenethiol in pyridine. The reduction and acetylation of the resulting compounds were also investigated.

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Synthese einiger 5H-Benzo[a]phenothiazin-5-on-Derivate

Zusammenfassung Es wurden mittels Kondensation substituierter 1,4-Naphthochinone mit 2-Aminothiophenol in Pyridin einige substituierte 6-Anilino-5H-benzo[a]phenothiazin-5-one dargestellt. Die Reduktion und Acetylierung der resultierenden Verbindungen wurde ebenfalls untersucht.

     

Synthesis of cis-1,5-Dimethyl-2,4-dinitro-2,4-diazabicyclo[3.1.0]hexan-3-one and cis-1,5-dimethyl-2,4-dinitro-2,4-diazabicyclo[3.2.0]heptan-3-one

cis-1,5-Dimethyl-2,4-dinitro-2,4-diazabicyclo[3.2.0]heptan-3-one and cis-1,5-dimethyl-2,4-dinitro-2,4-diazabicyclo[3.1.0]hexan-3-one were both synthesized in three steps each from a common precursor, 1,3-diacetyl-4,5-dimelhyl-4-imidazolin-2-one.     

Chiral exo-Alkylidenecyclopentanes from (1S,4R)-7,7-Dimethyl-1-vinylbicyclo[2.2.1]heptan-2-one

(1S,4R)-7,7-Dimethyl-1-vinylbicyclo[2.2.1]heptan-2-one oxime in the system (CF₃CO)₂O-CF₃COOH and (1S,4R)-1-(1,2-dibromoethyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-one in the system MeONa-MeOH undergo fragmentation to give exo-alkylidenecyclopentane derivatives, (4R)-4-cyanomethyl-5,5-dimethyl-1-[(1E)-trifluoroacetoxyethylidene]cyclopentane and isomeric (4R)-4-carboxymethyl-1-[(1ZE)-2-methoxyethylidene]-5,5-dimethylcyclopentanes, respectively. The trifluoroacetate derivative undergoes unusual rearrangement, yielding an equilibrium mixture of two isomers with endo- and exocyclic double bond.     

Unexpected formation of a 11H-pyrido[2,1-b]quinazolin-11-one derivative from 5,11-dihydro-6H-pyrido[2,3-b]-1,4-benzodiazepin-6-one

The unexpected formation of 11H-pyrido[2,1-b]quinazolin-11-one derivative 6 from 5,11-dihydro-6H-pyrido[2,3-b]-1,4-benzodiazepin-6-one (2) has been observed. Its structure 6 was determined by X-ray crystallography. Detailed nmr study provided a complete set of proton and carbon-13 nmr parameters of compound 6 in solution.     

New synthesis of chalcogenolactones. 1H,3H-benzo[c]selenophen-1-one, 1H,3H-benzo[c]tellurophen-1-one and the related 3,4-dihydro-1H-2-benzoselenin-1-one and 3,4-dihydro-1H-2-benzotellurin-1-one

The synthesis of three new basic heterocyclic systems namely, 1H,3H-benzo[c]tellurophen-1-one (2-tellurophthalide), 3,4-dihydro-1H-2-benzoselenin-1-one (3,4-dihydro-2-isoselenocoumarin) and 3,4-dihydro-1H-2-benzotellurin-1-one (3,4-dihydro-2-isotellurocoumarin), is reported through the cyclisation of o-(bromoalkyl)benzoyl chlorides.     

Synthesis of Indolo phenothiazin-6-one derivatives

Summary 5H-Indolo[3,2-a]-6H-phenothiazin-6-one and its regioisomer 1H-Indolo[2,3-a]-6H-phenothiazin-6-one were prepared by the condensation of 2-aminobenzenethiol with carbazole-1, 4-dione or with isomeric mixture of bromo-carbazole-1,4-diones.

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Synthese von Indolo-Phenothiazin-6-on-Derivaten (Kurze Mitteilung)

Zusammenfassung 5H-Indolo[3,2-a]-6H-phenothiazin-6-on und sein Regioisomer 1H-Indolo[2,3-a]-6H-phenothiazin-6-on wurden mittels Kondensation von 2-Aminobenzolthiol mit Carbazol-1,4-dion oder mit einer isomeren Mischung von Bromcarbazol-1,4-dionen hergestellt.

     

Synthesis of pyrido[2,3-d]pyrimidin-4-one derivatives

This paper describes one-pot synthesis of 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidin-5-one 4 , 5H-dipyri-do[1,2-a:3′,2′-e]pyrimidin-5-one 10 and 5H-pyrido[3,2-e]pyrimido[1,2-a]pyrimidin-5-one 15 and some of their derivatives, starting with 2-chloro-3-pyridine carboxilic acid 1. Compounds 4 and 10 reacted with phosphorus pentasulfide to give the respective 5-thione analogues, 5 from 4 and 11 from 10 . Boiling the 5-thione derivatives with hydrazine hydrate, the respective 5-hydrazono derivatives 6 from 5 and 12 from 11 were obtained. The 5-acetyl hydrazono, 7 , and the 5-isopropylidenehydrazono, 8 , derivatives were also prepared from 6 , and the 5-propionylhydrazono derivatives, 13 , from 12 . Compound 4 reacted with hydrazine to give an adduct with two molecules of hydrazine and the probable structure 16 . Treating this adduct with acetone a monohydrazone 17 was obtained. Boiling a suspension of this adduct in DMF, it gave 6,10-dihydro-6H-pyrido[3′,2′:5,6]pyrimido[2,1-c][1,2,4]triazin-5-one 20 .     

Reinvestigation of the Nazarov cyclization of 1-(3-hydroxypropynyl)cyclododecan-1-ol to bicyclo[10.3.0]pentadec-1(12)-en-13-one

Reinvestigation of the acid-catalyzed cyclization of 1-(3-hydroxypropynyl)cyclododecan-1-ol under the conditions of the Nazarov reaction demonstrated that this conversion yields two isomeric bicyclic ketones, namely, bicyclo[10.3.0]pentadec-1(12)-en-13-one and bicyclo[10.3.0]pentadec-1-en-3-one. The latter compound is thermodynamically less stable. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1325–1327, July, 1997.     

5,5,6-Trimethylbicyclo[2.2.1]heptan-2-one in the Synthesis of Carbocyclic Analogs of Prostaglandin Endoperoxides

1,3-Dipolar cycloaddition of nitrile oxides to 5,5,6-trimethyl-exo-2-ethynylbicyclo[2.2.1]heptan-endo-2-ol yields the corresponding 2-(isoxazol-5-yl) derivatives. Opening of the isoxazole ring in the latter gives rise to prostanoid precursors with partially built up or completed side chain. 5,5,6-Trimethyl-3-methylenebicyclo[2.2.1]heptan-2-one reacts with nitromethane in the presence of tetramethylguanidine to afford 5,5,6-trimethyl-exo-3-(2-nitroethyl)bicyclo[2.2.1]heptan-2-one which can be converted into the corresponding nitrile oxide by the action of phenyl isocyanate in benzene in the presence of triethylamine as catalyst. 1,3-Dipolar cycloaddition of the nitrile oxide to ethyl 4-pentynoate yields 3-exo-[5-(2-ethoxycarbonylethyl)isoxazol-3-ylmethyl]-5,5,6-trimethylbicyclo[2.2.1]heptan-2-one. Treatment of the latter with hydroxyl amine leads to formation of the corresponding Z-oxime whose reaction with n-hexyl bromide results in transalkylation of the ester group to afford 3-exo-[5-(2-hexyloxycarbonylethyl)isoxazol-3-ylmethyl]-5,5,6-trimethylbicyclo[2.2.1]heptan-2-one oxime.     

Synthesis of azolo[a]pyridines from 5-(bromomethyl)hept-4-en-3-one and 5-bromopent-3-en-2-one derivatives

Alkyl derivatives of 1H-imidazo[1,2-a]pyridin-4-ium, 5H-pyrido[1,2-a]benzimidazol-10-ium, 1H-[1,2,4]-triazolo[4,3-a]pyridin-4-ium, and 3-methylthiazolo[3,2-a]pyridin-4-ium bromides were obtained in two stages from (4Z)-5-(bromomethyl)-2,2,6,6-tetramethylhept-4-en-3-one, 5-bromo-4-methylpent-3-en-2-one, or (3E)-5-bromopent-3-en-2-one by alkylation of 1-alkyl-1H-imidazoles, 1-alkyl-1H-benz-imidazoles, 1-methyl-1H-1,2,4-triazole, and 4-methylthiazole and subsequent cyclization of the quaternary azolium salts in the presence of bases.     

Synthesis of 5H-pyrido[2,3-a]phenoxazin-5-one and 5H-pyrido[3,2-a]phenoxazin-5-one derivatives

The 5H-pyrido[2,3-a]phenoxazin-5-one derivatives and 5H-pyrido[3,2-a]phenoxazin-5-one derivatives were prepared by the condensation of substituted 2-aminophenols with 6,7-dibromo-5,8-quinolinequinone followed by dehalogenation in the presence of sodium hydrosulfite dissolved in aqueous pyridine under a nitrogen atmosphere.     

Synthesis of 3- and 4-(β-D-ribofuranosyl)-s-triazolo[2,3-a] pyrimid-7-one,isomers of inosine containing a bridgehead nitrogen atom

The first synthesis of a purine nucleoside analog containing a bridgehead nitrogen atom is here reported. The direct glycosylation of the trimethylsilyl derivative of s-triazolo[2,3-a] pyrimid-7-one has been shown to give 3-(β-D-ribofuranosyl)-s-triazolo[2,3-a]pyrimid-7-one (V) and 4-(β-D-ribof'uranosyl)-s-lriazolo[2,3-α]pyrimid-7-one (VII). The nueleoside V may he considered a close analog of inosine in which the nitrogen N₁ and C₅ of inosine have been interchanged. Bro-minalion of the tri-O-acelyl derivative IV gave, after deblocking, 6-bromo-3-(β-D-ribofurnaosyl)-s-triazolo[2,3-a] pyrimid-7-one (IX). Structural assignments of the nucleosides were made on the basis of comparison of the ultraviolet absorption spectral characteristics with 3-methyl-s-triazolo-[2,3-a]pyrimid-7-one (XI) and 4-methyl-s-lriazolo[2,3-a Jpyrimid-7-one (XII) prepared by a standard procedure from 7-methoxy-s-triazolo(2,3-a] pyrimidine (X).     

Fused imidazoacridines: Synthesis of 1,3-dihydroimidazo[4,5-b]-acridin-2-one and 1,3-dihydroimidazo[4,5-a]acridin-2-one

The synthesis of new 1,3-dihydroimidazo[4,5-a]acridin-2-one and 1,3-dihydroimidazo[4,5-b]acridin-2-one derivatives is reported. The yield and the structure of each isomer were determined by nmr spectroscopy.     

Stereoselective 1,3-Dipolar Cycloadditions to (S)-1-Benzoyl-3-(cyanomethylidene)-5-(methoxycarbonyl)pyrrolidin-2-one

(5S)-1-Benzoyl-3-[(E)-cyanomethylidene]-5-(methoxycarbonyl)pyrrolidin-2-one ( 5 ) was prepared in four steps from L -pyroglutamic acid ( 1 ). 1,3-Dipolar cycloadditions of diazomethane ( 6 ) and 2,4,6-trimethoxybenzonitrile oxide ( 7 ) gave substituted 1,2,7-triazaspiro[4.4]non-1-en-6-one 12 and 1-oxa-2,7-diazaspiro[4,4]non-1-en-6-one 13 in 38 and 20% de, respectively. On the other hand, reaction of 5 with N-phenylbenzonitrile imines 8 and 9 , generated in situ from the corresponding hydrazonoyl chlorides 10 and 11 , respectively, and Et₃N, furnished racemic pyrrolo[3,4-c]pyrazoles 14 and 15 in 61 and 56% de, respectively. Cycloaddition of nitrile oxide 7 , when performed in the presence of Et₃N, led to pyrrolo[3,4-d]isoxazole 16 in 85% de.     

Specifically (π → π*)-Induced Cyclohexenone Reactions 4a-(Z-1-Propenyl)-bicyclo[4.4.0]dec-1 (8a)-en-2-one and 4a-Z-1-Propenyl-bicyclo[4.4.0]deca-1(8a), 7-dien-2-one

4a-(Z-1-Propenyl)-bicyclo[4.4.0]dec-1(8a)-en-2-one ( 6 ) and 4a-(Z-1-propenyl)-bicyclo[4.4.0]deca-1(8a), 7-dien-2-one ( 17 ) undergo an intramolecular hydrogen transfer from the methyl group of the propenyl substitutent to the α-carbon atom of the enone group, and cyclization to the [4.4.3]propellane derivatives 9 and 30 , respectively, when excited in the π → π* wavelength region. The quantum yield for (Z)- 6 → 9 under optimum conditions is 0.29 at 254 nm. These reactions occur specifically from the S₂ (π,π*) state, competing with the S₂ → T decay. The triplet reactions of 6 are E–Z double-bond isomerization, double-bond shift to (E,Z)- 8 , and rearrangement to (E)- 10 . Further investigations concern some structural limitations in the scope of the reaction type 6 → 9 and enone S₂ reactivity in general.     

Synthesis of 11-aza-5H-benzophenoxazin-5-one and 11-Aza-5H-pyridophenoxazin-5-one derivatives

The 1,6-disubstituted- and 4,6-disubstituted-11-aza-5H-benzo[a]phenoxazin-5-one as well as 6-substituted-11-aza-5H-pyrido[a]phenoxazin-5-one derivatives were prepared by the condensation of 2-amino-3-hydroxypyridine with 5-substituted-2,3-dihalogeno-1,4-naphthoquinones and 6,7-dibromo-5,8-quinolinequinone respectively. The resulting compounds were subjected to reduction, acetylation, dehalogenation and reaction with aniline.