Intramolecular Carbenoid Reactions of Pyrrole Derivatives Efficient Syntheses of Pyrrolizinone and Dihydroindolizinone

The copper-catalyzed pyrolysis of 1-diazo-3-(pyrrol-1-yl)-2-propanone (1a) and 1-diazo-4-(pyrrol-1-yl)-2-butanone (1b) in benzene solution gave 1 H-pyrrolizin-2-(3H)-one (4a) and 5,6-dihydroindolizin-7 (8H)-one (4b) , respectively, in quantitative yield. Similar pyrolysis of 1-diazo-4-(3-methylindol-1-yl)-2-butanone (9) was less efficient giving 1-methylbenzo[b]-5,6-dihydroindroindolizin-7 (8H)-one (10) and 4-(3-methylindol-1-yl)-but-l-en-3-one (11) in 7% and 24% yield, respectively.     

Synthesis of 3-[5-(biphenyl-4-yl)pyrrol-2-yl]-1-phenylprop-2-yn-1-ones by palladium-free cross-coupling between pyrroles and haloalkynes on aluminum oxide

Cross-coupling of 2-(biphenyl-4-yl)pyrroles derived from 1-(biphenyl-4-yl)ethanone oximes and acetylene with 3-bromo-1-phenylprop-2-yn-1-one on aluminum oxide gave 3-[5-(biphe-nyl-4-yl)pyrrol-2-yl]-1-phenylprop-2-yn-1-ones in 35–46% yields.     

Synthesis of 1H-pyrazolo[3,4-c]isoquinolin-1-ones by the condensation of cyclohexanone derivatives with 3-amino-1-phenyl-1H-pyrazol-5(4H)-one

The synthesis of 1H-pyrazolo[3,4-c]isoquinolin-1-ones was carried out by reacting 3-aryl(heteryl)-2,4-diacetyl-5-hydroxy-5-methylcyclohexanones with 3-amino-1-phenyl-1H-pyrazol-5(4H)-one. The structure of the 7-acetyl-2,4,6,7,8,9-hexahydro-8-hydroxy-5,8-dimethyl-2-phenyl-6-(fur-2-yl)-1H-pyrazolo[3,4-c]isoquinolin-1-one obtained was proved by X-ray diffraction analysis.     

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.     

类产碱假单胞菌全细胞催化前手性酮对映选择性还原合成西他列汀手性中间体

以苯乙酮为唯一碳源,从土壤中筛选出一株能够将4-氧-4-[3-(三氟甲基)-5,6-二氢[1,2,4]三唑并[4,3-a]吡嗪-7(8H)-基]-1-(2,4,5-三氟苯基)丁-2-酮(2)对映选择性还原为抗Ⅱ型糖尿病药物西他列汀关键手性中间体(S)-3-羟基-1-[3-(三氟甲基)-5,6-二氢[1,2,4]三唑并[4,3-a]吡嗪-7(8H)-基]-4-(2,4,5-,三氟苯基)丁-1-酮((S)-1)的细菌菌株,经鉴定并命名为类产碱假单胞菌(Pseudomonas pseudoalcaligenes)XW-40.系统研究了水溶性辅溶剂、温度、p H、底物浓度、细胞浓度、反应时间等反应条件对生物还原产率和对映选择性的影响.该菌株全细胞能够耐受浓度高达10 g/L的前手性酮2.在最优反应条件下,以制备规模合成了(S)-1,分离收率90%,ee99%.     

Bildung von 5,6-Dihydro-1,3(4H)-thiazin-4-carbonsäure-estern aus 4-Allyl-1,3-thiazol-5(4H)-onen

Formation of Methyl 5,6-Dihydro-l, 3(4H)-thiazine-4-carboxyiates from 4-Allyl-l, 3-thiazol-5(4H)-ones . The reaction of N-[1-(N, N-dimethylthiocarbamoyl)-1-methyl-3-butenyl]benzamid ( 1 ) with HCl or TsOH in MeCN or toluene yields a mixture of 4-allyl-4-methyl-2-phenyl-1,3-thiazol-5(4H)-one ( 5a ) and allyl 4-methyl-2-phenyl-1,3-thiazol-2-yl sulfide ( 11 ; Scheme 3). Most probably, the corresponding 1,3-oxazol-5(4H)-thiones B are intermediates in this reaction. With HCl in MeOH, 1 is transformed into methyl 5,6-dihydro-4,6-dimethyl-2-phenyl-1,3(4H)-thiazine-4-carboxylate ( 12a ). The same product 12a is formed on treatment of the 1,3-thiazol-5(4H)-one 5a with HCl in MeOH (Scheme 4). It is shown that the latter reaction type is common for 4-allyl-substituted 1,3-thiazol-5(4H)-ones.     

Novel synthesis of 5,6-dihydro-4H-thieno[3,2-b]pyrrol-5-ones via the rhodium(II)-mediated wolff rearrangement of 3-(thieno-2-yl)-3-oxo-2-diazopropanoates

[reaction: see text] Treatment of thioaryolketene S,N-acetals 12 with Hg(OAc)(2) followed by addition of 2-diazo-3-trimethylsilyloxy-3-butenoic acid alkyl esters 15 in CH(2)Cl(2) at room temperature gave 3-(3-alkylamino-5-arylthieno-2-yl)-3-oxo-2-diazopropanoates 16 in good yields. Subsequent reactions of 16 with a catalytic amount of Rh(2)(OAc)(4).2H(2)O in benzene at reflux afforded a mixture of 5,6-dihydro-4H-thieno[3,2-b]pyrrol-5-ones 18 and the corresponding enols 19 in excellent yields.     

Total synthesis of two novel 5,6,7,8-tetrahydroindolizine alkaloids, polygonatines A and B

The structures of polygonatines A and B, two simple but structurally novel alkaloids, have been substantiated by synthesis. Cyclisation of 4-(1H-pyrrol-1-yl)butanoic acid or its ethyl ester produced 6,7-dihydroindolizin-8(5H)-one , formylation of which at C-3 followed by reduction afforded polygonatine A . Acetylation of this alkaloid followed by displacement of the acetate with ethanol yielded polygonatine B , possibly via an azafulvenium cation.     

Reaction of 1,3-diaryl-2,3-dibromo-1-propanones with urea in basic and acidic medium. Synthesis of pyrimidine,imidazoline and imidazolidine derivatives

Reaction of 1,3-diaryl-2,3-dibromo-1-propanones 1 with urea in basic medium afforded 4,6-diaryl-5-bromo-5,6-dihydropyrimidine-2(1H)-ones 4 . Oxidation of these bromopyrimidines 4 in dimethylsulphoxide gave 4,6-diaryl-1,6-dihydropyrimidine-2,5-diones 6 , which were further converted to their thione analogues 7 . Reaction of 1,3-diaryl-2,3-dibromo-1-propanones 1 with urea, phenylurea and sym-diphenylurea in glacial acetic acid medium gave in appreciable yields 4-phenyl-5-α-(bromoarylmethyl)imidazolin-2-one 8 and 1,3-diphenyl-4-aroyl-5-arylimidazolidin-2-one 11 respectively.     

Azolyl-substituted 1,2,3-triazoles

Huisgen reaction of (E)-1,5-diarylpent-2-en-4-yn-1-ones and (E)-1,5-diarylpent-1-en-4-yn-3-ones afforded 1-aryl-3-(5-aryl-1H-1,2,3-triazol-4-yl)prop-2-en-1-ones and 3-aryl-1-(5-aryl-1H-1,2,3-triazol-4-yl)-prop-2-en-1-ones, respectively. (E)-1-Aryl-3-(5-phenyl-1H-1,2,3-triazol-4-yl)prop-2-en-1-ones reacted with hydrazine hydrate and phenylhydrazine to give 72–93% of 4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-5-phenyl-1H-1,2,3-triazoles which underwent dehydrogenation on heating in boiling acetic acid with formation of the corresponding pyrazole derivatives. The molecular structures of (E)-3-phenyl-1-(5-phenyl-1H-1,2,3-triazol-4-yl)prop-2-en-1-one and 4-[3-(4-methylphenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-5-yl]-5-phenyl-1H-1,2,3-triazole were studied by X-ray analysis. 4-(3-Aryl-4,5-dihydro-1H-pyrazol-5-yl)-5-phenyl-1H-1,2,3-triazoles showed toxicity against Daphnia magna.     

A novel push-pull Diels-Alder diene: reactions of 4-alkoxy- or 4-phenylsulfenyl-5-chalcogene-substituted 1-phenylpenta-2,4-dien-1-one with electron-deficient dienophiles

5-(phenylselenenyl)- and 5-(phenylsulfenyl)-4-ethoxy-1-phenyl-2,4-pentadien-1-ones (2) and (3) underwent [4+2] cycloaddition with N-methyl and N-phenylmaleimides and successive isomerization to give the 7-benzoyl-3a,4,5,7a-tetrahydro-1H-isoindole-1,3(2H)-diones 5, 8 and 9 in good yields. The 4-ethoxy group on the 2,4-pentadien-1-one was found to be effective to facilitate the cycloaddition with dienophiles. We also performed other [4+2] cycloadditions of 2,4-pentadien-1-ones with DMAD or naphthoquinone.     

Five-Membered 2,3-Dioxo Heterocycles: L. Synthesis and Thermolysis of 3-Aroyl- and 3-Hetaroyl-5-phenyl-1,2,4,5-tetrahydropyrrolo[1,2-<Emphasis Type="Italic">a</Emphasis>]quinoxalin-1,2,4-triones

(Z)-3-Phenacylidene- and (Z)-3-hetaroylmethylidene-1-phenyl-1,2,3,4-tetrahydroquinoxalin-2-ones react with oxalyl chloride to give 3-acyl-5-phenyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinoxaline-1,2,4-triones. Thermolysis of the latter generates acyl(3-oxo-4-phenyl-3,4-dihydroquinoxalin-2-yl)ketenes which are stabilized via [4 + 2]-cyclodimerization followed by [1,3]-acylotropic shift to afford 4-acyl-3-acyloxy-2-(3-oxo-4-phenyl-3,4-dihydroquinoxalin-2-yl)-6-phenyl-5,6-dihydro-1H-pyrido[1,2-a]quinoxaline-1,5-diones.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 7, 2005, pp. 1101–1108.Original Russian Text Copyright © 2005 by Bozdyreva, Smirnova, Maslivets.     

Intramolecular Carbenoid Reactions of Pyrrole Derivatives. A Total Synthesis of (±)-Ipalbidine

A new method for alkaloid synthesis is described. The rhodium(II)-acetate-catalyzed decomposition of 3-(4-acetoxyphenyl)-1-diazo-4-(pyrrol-1-yl)-2-butanone ( 5d ) gave 6-(4-acetoxyphenyl)-5,6-dihydro-7(8H)-indolizinone ( 6d ) in 82% yield via an intramolecular carbenoid reaction. The latter compound was converted in four steps in 13% overall yield to (±)-ipalbidine ( 1b ).     

Studies on the synthesis of heterocyclic compounds. Part IV. Further investigation of the pschorr reaction with some pyrazole derivatives

Thermal decomposition of the diazonium sulfate derived from N-methyl-(1-phenyl-3-methylpyrazol-5-yl)-2-aminobenzamide afforded products formulated as 1-phenyl-3-methyl[2]benzopyrano[4,3-c]pyrazol-5-one (yield 10%), 1,4-dimethyl-3-phenylpyrazolo[3,4-c]isoquinolin-5-one (yield 10%), N-methyl-(1-phenyl-3-methylpyrazol-5-yl)-2-hydroxybenzamide (yield 8%) and 4′-hydroxy-2,3′-dimethyl-1′-phenylspiro[isoindoline-1,5′-[2]-pyrazolin]-3-one (yield 20%). Decomposition of the diazonium sulfate derived from N-methyl-(1,3-diphenylpyrazol-5-yl)-2-aminobenzamide gave products formulated as 7,9-dimethyldibenzo[e,g]pyrazolo[1,5-a][1,3]-diazocin-10-(9H)one (yield 8%), 4-methyl-1,3-diphenylpyrazolo[3,4-c]isoquinolin-5-one (yield 7%) and 4′-hydroxy-2-methyl-1′,3′-diphenylspiro[isoindoline-1,5′-[2]pyrazolin]3-one (yield 10%). The spiro compounds 6a,b underwent thermal and acid-catalysed conversion into the hitherto unknown 2-benzopyrano[4,3-c]pyrazole ring system 7a,b in good yield. Analytical and spectral data are presented which supported the structures proposed.     

Synthesis,characterization, and antioxidant activity of heterocyclic Schiff bases

Schiff base derivatives have gained great importance due to revealing a great number of biological properties. Schiff bases were synthesized by treatment of 4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one ( 1 ) with various aldehydes in methanol at reflux. In addition, diamine was reacted with an aldehyde to yield the corresponding Schiff bases. The structures of synthesized Schiff bases were elucidated by spectroscopic methods such as microanalysis, ¹H-NMR, ¹³C-NMR, and FTIR. Antioxidant activities of synthesized Schiff bases were carried out using different antioxidant assays such as 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH^•) scavenging, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging, and reducing power activity. (E)-4-((1H-indol-3-yl)methyleneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one ( 3 ), (E)-1,5-dimethyl-4-((2-methyl-1H-indol-3-yl)methyleneamino)-2-phenyl-1H-pyrazol-3(2H)-one ( 5 ), (E)-1,5-dimethyl-2-phenyl-4-(thiophen-2-ylmethyleneamino)-1H-pyrazol-3(2H)-one ( 7 ), (E)-1,5-dimethyl-2-phenyl-4-(quinolin-2-ylmethyleneamino)-1H-pyrazol-3(2H)-one ( 9 ), (1S,2S,N1,N2)-N1,N2-bis((1H-indol-3-yl)methylene)cyclohexane-1,2-diamine ( 11 ), and (1S,2S,N1,N2)-N1,N2-bis((2-methyl-1H-indol-3-yl)methylene)cyclohexane-1,2-diamine ( 12 ) were synthesized in high yields. Compound 5 displayed a good ABTS^•+ activity. Compound 3 revealed the outstanding activity in all assays. Compound 7 has the best-reducing power ability in comparison to other synthesized compounds. Although compounds 5, 11, 12 are new, compounds 3, 7, 9 are known. Due to revealing a good antioxidant activity, the synthesized compounds ( 3, 5, 7 ) have the potential to be used as synthetic antioxidant agents.     

Reaction of polyfluorinated chalcones with guanidine

Reactions of polyfluorinated chalcones with guanidine in the presence of bases are accompanied by elimination of the polyfluorophenyl group. 3-(Pentafluorophenyl)-1-phenylprop-2-en-1-one and its derivatives reacted with guanidine under basic conditions to give 4-phenylpyrimidin-2-amine, polyfluorobenzenes, and Michael adducts, 3-(2-amino-4-phenylpyrimidin-5-yl)-3-(4-R-2,3,5,6-tetrafluorophenyl)-1-phenylpropan-1-ones. 1-(Pentafluorophenyl)-3-phenylprop-2-en-1-one and 1,3-bis(pentafluorophenyl)prop-2-en-1-one were converted into cinnamic acid derivatives whose reaction with guanidine afforded 2-amino-6-aryl-5,6-dihydropyrimidin-4(1H)-ones.     

Synthesis of triazafluoranthenones via silver(I)-mediated nonoxidative and oxidative intramolecular palladium-catalyzed cyclizations

Silver(I) fluoride (AgF)-mediated intramolecular nonoxidative and oxidative palladium-catalyzed cyclizations of 1,3-diphenyl- and 8-iodo-1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-ones 6a (R = H) and 7a (R = I) afford a new 'alkaloid like' ring system 2-phenyl-6H-[1,2,4]triazino[5,6,1-jk]carbazol-6-one 8a (triazafluoranthenone) in 86 and 100% yields, respectively. Furthermore, these cyclization protocols were used to prepare triazafluoranthenone analogues 8b-e bearing dialkylamino, methoxy, and phenylsulfanyl substituents at C-5, which were also independently synthesized from triazafluoranthenone 8a by regioselective nucleophilic addition. Similar AgF-mediated intramolecular nonoxidative and oxidative palladium-catalyzed cyclizations of 8,10-dihydro-1-iodo-10-phenylphenazin-2(7H)-ones 13 gave the new 'alkaloid like' ring system 8H-indolo[1,2,3-mn]phenazin-8-one 14 in 80 and 18% yields, respectively.     

The use of umbelliferone in the synthesis of new heterocyclic compounds

New coumarin derivatives, namely 7-[(5-amino-1,3,4-thiadiazol-2-yl)methoxy]-2H-chromen-2-one, 5-[(2-oxo-2H-chromen-7-yloxy)methyl]-1,3,4-thiadiazol-2(3H)-one, 2-[2-(2-oxo-2H-chromen-7-yloxy)acetyl]-N-phenylhydrazinecarbothioamide, 7-[(5-(phenylamino)-1,3,4-thiadiazol-2-yl)methoxy]-2H-chromen-2-one and 7-[(5-mercapto-4-phenyl-4H-1,2,4-triazol-3-yl)methoxy]-2H-chromen-2-one were prepared starting from the natural compound umbelliferone. The newly synthesized compounds were characterized by elemental analysis and spectral studies (IR, 1H-NMR and 13C-NMR).     

Synthesis of fluoroquinoxalin-2(1<Emphasis Type="Italic">H</Emphasis>)-one derivatives containing substituents in the pyrazine and benzene fragments

6,7-Difluoroquinoxalin-2-one reacted with indoles, 5,5-dimethylcyclohexane-1,3-dione, 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one, resorcinol, and pyrogallol on heating in acetic acid to give products of hydrogen substitution in the heterocyclic fragment. Heating of 6,7-difluoro-3-(1H-indol-3-yl)quinoxalin-2(1H)-ones with N-methylpiperazine gave the corresponding 7-(4-methylpiperazin-1-yl) derivatives.     

Microwave-assisted synthesis and antibacterial activity of some pyrazol-1-ylquinoxalin- 2(1H)-one derivatives

3-Hydrazinoquinoxalin-2(1H)-one was prepared from quinoxaline-2,3-dione and subsequently used for the synthesis of some potentially biologically active 3-(pyrazol-1-yl)quinoxalin-2(1H)-one derivatives. While 3-(3,5-dimethylpyrazol-1-yl)quinoxalin-2(1H)-one showed a comparative effect with streptomycin, 3-(5-oxo-3-phenyl-4,5-di- hydropyrazol-1-yl)quinoxalin-2(1H)-one was found to be the most active with an MIC value of 7.8 μg/ml.