Five-membered 2,3-dioxoheterocycles: LVIII. Reaction of methyl 1-Aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrol-2-carboxylates with substituted 1-methyl-3,4-dihydroisoquinolines. New approach to the synthesis of steroid 13-azaanalogs

Methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with substituted 1-methyl-3,4-dihydroisoquinolines with the formation of substituted 3-oxo-2,3,5,6-tetra-hydropyrrolo[2,1-a]-isoquinoline-2-spiro-2′-(1-aryl-3-aroyl-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrroles). A new approach was developed to the synthesis of 13-azagonanes, substituted benzo[f]pyrrolo[2,1-a]isoquinoline-9-spiro-2′-pyrroles.     

Three-Component Spiro Heterocyclization of Pyrrolediones with Malononitrile and Cyclic Enols

Ethyl 4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylates reacted with malononitrile and five-membered cyclic enols, indan-1,3-dione and cyclopentane-1,3-dione to give 1-substituted ethyl 2-amino-3- cyano-2′,5-dioxo-5′-phenyl-1′,2′-dihydro-5H-spiro[indeno[1,2-b]pyran-4,3′-pyrrole]-4′-carboxylates and ethyl 2-amino-3-cyano-2′,5-dioxo-5′-phenyl-1′,2′,6,7-tetrahydro-5H-spiro[cyclopenta[b]pyran-4,3′-pyrrole]-4′-carboxylates, respectively.     

New approaches to polysubstituted pyrroles and pyrrolinones from α-cyanomethyl-β-ketoesters

In this present paper, we report the efficient, regioselective one-pot synthesis of 5-alkoxy and 5-alkylsulfanylpyrrole-3-carboxylates in high yields via the zinc perchlorate-catalyzed addition of alcohols and thiols to the nitrile carbon of α-cyanomethyl-β-ketoesters followed by annulation. The addition-annulation process is undertaken in aqueous solution to give 4,5-dihydro-5-oxo-1H-pyrrole-3-carboxylates (pyrrolinones) in good yields. These 4,5-dihydro-5-oxo-1H-pyrrole-3-carboxylates are also obtained by the hydrolysis of 5-alkoxypyrrole-3-carboxylates.     

Five-membered 2,3-dioxo heterocycles: LV. Reaction of methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2-carboxylates with ethyl 3-arylaminobut-2-enoates

Methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with ethyl 3-aryl-aminobut-2-enoates to give the corresponding ethyl 1,7-diaryl-4-aroyl-3-hydroxy-8-methyl-2,6-dioxo-1,7-diazaspiro[4.4]nona-3,8-diene-9-carboxylates.     

Synthetic studies related to diketopyrrolopyrrole (DPP) pigments. Part 2: The use of esters in place of nitriles in standard DPP syntheses: Claisen-type acylations and furopyrrole intermediates

Ethyl 2-aryl-4,5-dihydro-5-oxopyrrole-3-carboxylates react with esters or acyl halides in the presence of a strong base to give 4-acyl derivatives, which exist predominantly as either E- or Z-enols. These are cyclised, either in solution at temperatures >200 °C or by microwave irradiation, to 3,6-disubstituted 1H-furo[3,4-c]pyrrolediones which, after N-protection, are convertible by reaction with primary amines into novel N,N′-disubstituted DPP derivatives.     

Redox Transformation of Adducts from Cycloaddition of Diazoacetic Ester to β-Arylacryloyloxiranes

It was established that, in addition to ethyl 4-aryl-3-(2,3-epoxyalkanoyl)-4,5-dihydro-1H-pyrazole-5-carboxylates, the reaction of diazoacetic ester with β-arylacryloyloxiranes also gives ethyl 4-aryl-3(5)-(3-hydroxy-2-methylalkanoyl)-1H-pyrazole-5(3)-carboxylates. The latter are formed from the tautomeric ethyl 4-aryl-5-(2,3-epoxyalkanoyl)-4,5-dihydro-1H-pyrazole-3-carboxylates as a result of intramolecular oxidative-reductive disproportionation. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, 1150–1160, August, 2005.     

Reaction of methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2-carboxylates with arylhydrazines. synthesis of isomeric 5-arylcarbamoyl-4-aroyl- and 5-aryl-4-aryloxamoyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazoles

Methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with arylhydrazines to give methyl 3-aroyl-1-aryl-2-(2-arylhydrazinyl)-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylates which underwent thermal recyclization into isomeric methyl 1-aryl-5-(arylcarbamoyl)-4-aroyl-1H-pyrazole- 3-carboxylates and methyl 1,5-diaryl-4-[2-oxo-2-(arylamino)acetyl]-1H-pyrazole-3-carboxylates.     

Synthesis of substituted 2,3,5,6,7,8-hexahydropyrazolo[4,3-d][1,2]diazepine-8-carboxylates

Substituted 2,3,5,6,7,8-hexahydropyrazolo[4,3-d][1,2]diazepine-8-carboxylates were prepared in good to excellent yields from ethyl (2E)-3-(dimethylamino)-2-{(4Z)-4-[(dimethylamino)methylidene]-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl}propenoate with 1,2-disubstituted hydrazines by heating in an alcohol.     

Reactions of Substituted Ethyl 1,2,3,4,4′,5′-Hexahydrospiro-[naphthalene-2,5′-pyrazole]-3′-carboxylates with Halogens

Substituted ethyl 1,2,3,4,4′,5′-hexahydrospiro[naphthalene-2,5′-pyrazole]-3′-carboxylates react with chlorine or N-bromosuccinimide to give spirocyclic substituted 3-halo-4,5-dihydro-3H-pyrazoles which lose nitrogen molecule on heating with formation of substituted spirocyclic 1-halocyclopropane-1-carboxylates. Heating of the title compounds with bromine in acetic acid results in opening of the spiro-fused six-membered ring to afford ethyl 4-aryl-5-[2-(2-carboxyphenyl)ethyl]pyrazole-3-carboxylates.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 7, 2005, pp. 1058–1063.Original Russian Text Copyright © 2005 by Molchanov, Korotkov, Kopf, Kostikov.     

Unexpected pathway of the reaction of N-[(β-halogeno-α-tosyl)alkyl]ureas with β-oxoester enolates. Synthesis of ethyl 5-ureido-4,5-dihydrofuran-3-carboxylates and N-carbamoylpyrrole-3-carboxylates

Reaction of β-halogeno-α-tosyl-substituted N-alkylureas with sodium enolates of β-oxoesters proceeds predominantly via nucleophilic substitution of the halogen rather than the tosyl group followed by spontaneous cyclization to give ethyl 5-ureido-4,5-dihydrofuran-3-carboxylates. The latter are transformed into ethyl N-carbamoylpyrrole-3-carboxylates under acidic conditions.     

Synthesis of spiro[imidazole-2,2′-pyrroles] by reaction of 4,5-dioxo-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2-carboxylates with urea

Substituted alkyl 4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with urea to give alkyl 2-(carbamoylamino)-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylates which underwent intramolecular cyclization to 8-hydroxy-1,3,6-triazaspiro[4.4]non-8-ene-2,4,7-triones by the action of sodium methoxide.     

Five-membered 2,3-dioxo heterocycles: LXX. Spiro heterocyclization of 1H-pyrrole-2,3-diones by the action of 1,5-binucleophiles. Crystalline and molecular structure of ethyl 1′-benzyl-7-methoxy-3,3-dimethyl-1,2′-dioxo-5′-phenyl-1′,2,2′,3,4,10-hexahydro-1H-spiro[acridine-9,3′-pyrrole]-4′-carboxylate

Ethyl 1-alkyl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylates reacted with 3-arylamino-5,5-dimethylcyclohex-2-en-1-ones as carbon-centered 1,5-binucleophiles to give the corresponding substituted ethyl 1′-alkyl-3,3-dimethyl-1,2′-dioxo-5′-phenyl-1′,2,2′,3,4,10-hexahydro-1H-spiro[acridine-9,3′-pyrrole]-4′-carboxylates whose structure was proved by X-ray analysis.     

2H-Azirines as dipolarophiles

2H-Azirine-3-carboxylates unsubstituted at C-2 act as dipolarophiles in the reaction with diazomethane giving new 4,5-dihydro-3H-pyrazole derivatives. The synthesis of a pyrimidine was also achieved via 1,3-dipolar cycloaddition of methyl 2-bromo-3-phenyl-2H-azirine-2-carboxylate with an azomethine ylide.     

Microwave assisted synthesis of some new thiazolopyrimidine, thiazolodipyrimidine and thiazolopyrimidothiazolopyrimidine derivatives with potential antioxidant and antimicrobial activity

Biginelli reaction of ethyl acetoacetate, thiourea and the appropriate aromatic aldehyde was used to produce ethyl 4-aryl-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylates, that reacted with bromomalononitrile to give ethyl 3-amino-5-aryl-2-cyano-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylates rather than the isomeric 7H-thiazolo[3,2-a]pyrimidines. Thiazolopyrimidine derivatives reacted with carbon disulphide to yield ethyl 9-aryl-7-methyl-2,4-dithioxo-2,3,4,9-tetrahydro-1H-thiazolo[3,2-a:4,5-d']dipyrimidine-8-carboxylates, that reacted with phenacyl bromide to produce ethyl 8-methyl-10-(4-methoxyphenyl)-3-substituted-5-thioxo-2(un)subatituted-10H-thiazolo[3',2':1',2']pyrimido[4',5':4,5]thiazolo[3,2-a]pyrimidine-9-carboxylates. The aforementioned reactions were carried out using both conventional chemical methods and with the assistance of microwave irradaition. Comparison between both methods showed that the microwave assisted method is preferable because of the time reduction and yield improvements achieved. The new compounds were tested for their biological activity as antioxidants, antibacterial or antifungal agents. Some of the new compounds were found to have moderate to good antioxidant and antimicrobial activities.     

Five-membered 2.3-dioxo heterocycles: LXVIII. Three pathways in the reaction of methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates with 3-amino-5,5-dimethylcyclohex-2-en-1-one

Methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with 3-amino-5,5-dimethylcyclohex-2-en-1-one having no substituent on the nitrogen atom to give 3-aroyl-4-arylamino-6′,6′-dimethyl-6′,7′-dihydro-5H-spiro[furan-2,3′-indole]-2′,4′,5′(1′H,5′H)-triones or methyl 12-aroyl-11-aryl-9-hydroxy-5,5-dimethyl-3,10-dioxo-8,11-diazatricyclo[7.2.1.0^2,7]dodec-2(7)-ene-1-carboxylates. The latter underwent thermal recyclization to 3′-aroyl-1′-aryl-4′-hydroxy-6,6-dimethyl-6,7-dihydrospiro[indole-3,2′-pyrrole]-2,4,5′(1H,1′H,5H)-triones.     

Microwave-induced generation and reactions of nitrile sulfides: an improved method for the synthesis of isothiazoles and 1,2,4-thiadiazoles

The 1,3-dipolar cycloaddition reactions of nitrile sulfides, generated by microwave-assisted decarboxylation of 1,3,4-oxathiazol-2-ones, have been investigated. By this approach ethyl 1,2,4-thiadiazole-5-carboxylates 3 were prepared in good yield by cycloaddition of the nitrile sulfides to ethyl cyanoformate. Similarly, reaction of benzonitrile sulfide with dimethyl acetylenedicarboxylate (DMAD) afforded dimethyl 3-phenylisothiazole-4,5-dicarboxylate (5). In contrast, o-hydroxybenzonitrile sulfide, generated from the corresponding oxathiazolone 2d, reacted with DMAD to give methyl 4-oxo-4H-[1]benzopyrano[4,3-c]isothiazole-3-carboxylate (8) in high yield. A ca. 1:1 mixture of ethyl 3-phenylisothiazole-4- and 5-carboxylates (6,7) was formed from benzonitrile sulfide and ethyl propiolate. The corresponding reaction with diethyl fumarate gave diethyl trans-4,5-dihydro-3-phenylisothiazole-4,5-dicarboylate (10). 3-Arylisothiazoles, unsubstituted at both the 4- and 5-positions, were prepared from the reaction of 5-aryl-1,3,4-oxathiazolones with norbornadiene by a pathway involving cycloaddition of the nitrile sulfide to the norbornadiene, followed by retro-Diels-Alder extrusion of cyclopentadiene from the resulting isothiazoline cycloadduct 12. In summary, the use of microwave irradiation, rather than conventional heating methods, allows nitrile sulfide generation and reactions to be carried out in shorter times, with easier work-up and, in some cases, in higher yields.     

Five-membered 2,3-dioxo heterocycles: CV. Reaction of methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates with methyl 2-arylamino-4-(2-naphthyl)-4-oxobut-2-enoates. Crystal and molecular structure of substituted 1,7-diazaspiro[4.4]nonane

Methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with methyl 2-arylamino-4-(2-naphthyl)-4-oxobut-2-enoates to give methyl 1,7-diaryl-4-aroyl-3-hydroxy-9-(2-naphthalen-2-ylcarbonyl)-2,6-dioxo-1,7-diazaspiro[4.4]nona-3,8-diene-8-carboxylates.     

A convenient synthesis of 3,4-dihydro-2-methyl-3-oxo-2H-1,4-benzoxazine-2-carboxylic acids and 3,4-dihydro-2-methyl-3-oxo-2H-pyrido[3,2-b]-1, 4-oxazine-2-carboxylic acid

A convenient one pot synthesis of ethyl 3,4-dihydro-2-methyl-3-oxo-2H-1,4-benzoxazine-2-carboxylates and 3,4-dihydro-2-methyl-3-oxo-2H-pyrido[3,2-b]-1,4-oxazine-2-carboxylates and their conversion into the respective carboxylic acids are described.     

Synthesis and properties of ethyl 1-aryl-5-methyl-4-[1-(phenylhydrazinylidene)ethyl]-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-3-carboxylates

Ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazole-3-carboxylates reacted with phenylhydrazine to give the corresponding hydrazones, ethyl 1-aryl-5-methyl-4-[1-(phenylhydrazinylidene)ethyl]-1H-pyrazole-3-carboxylates, which were converted to ethyl 1′-aryl-4-formyl-5′-methyl-1-phenyl-1H,1′H-3,4′-bipyrazole-3′-carboxylates by treatment with the Vilsmeier–Haack reagent. No indole derivatives were formed from the same hydrazones under the Fischer reaction conditions, but cyclization to 2-aryl-3,4-dimethyl-6-phenyl-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-ones was observed.     

Potential antidiabetic zinc(II) complexes of novel 5-oxo-2-thioxopyrrolidine derivatives synthesized via an unprecedented reaction

We have developed a synthetic route to novel ethyl 1-arylmethyl-5-oxo-2-thioxopyrrolidine-3-carboxylates (1a–e) via an unprecedented reaction of ethyl 1-arylmethyl-4-acetoxy-5-oxo-2,5-dihydro-1H-pyrrole-3carboxylates with potassium thioacetate. Synthesized products 1a–e were further converted into their zinc(II) complexes (10a–e), having an S₂O₂-type coordination mode, that showed improved insulin-mimetic activities compared to ZnSO₄, a positive standard, and also the previously reported zinc(II) complexes of ethyl 1-benzyl-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxylates with O₄-type coordination mode.