Reactions of 1,5-diaryl-4-heteroyl-3-hydroxy-3-pyrrolin-2-ones with arylamines and butylamine

1,5-Diaryl-4-[2-thienoyl(furanoyl)]-3-hydroxy-3-pyrrolin-2-ones reacted with aromatic amines to form arylamino-3-pyrrolin-2-ones. Reactions with butylamine occurred via intermediate salt formation followed by their transformation into 3-butylamino-3-pyrrolin-2-ones at heating.     

Reaction of 1,5-diaryl-3-hydroxy-4-methylsulfonyl-3-pyrrolin-2-ones with urea,hydrazine, ethylenediamine,and <Emphasis Type="Italic">o</Emphasis>-phenylenediamine

With urea 1,5-diaryl-3-hydroxy-4-methylsulfonyl-3-pyrrolin-2-ones form the 3-amino derivatives of pyrrolones. In reactions with hydrazine hydrate and ethylenediamine the corresponding salts are formed. With ethylenediamine at 180–185°C the double salt of 3-hydroxy-4-methylsulfonyl-1,5-diphenyl-3-pyrrolin-2-one forms N,N′-di(4-methylsulfonyl-1,5-diphenyl-3-pyrrolin-2-on-3-yl)-ethylenediamine. The reaction with o-phenylenediamine gives 2,3-diaryl-4-methylsulfonylpyrrolo-[2,3-b]quinoxalines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, 1631–1636, November, 2007.     

Amination of 5-Spiro-Substituted 3-Hydroxy-1,5-dihydro-2H-pyrrol-2-ones

The 3-hydroxy-1,5-dihydro-2H-pyrrol-2-one motif is a valuable scaffold in drug discovery. The replacement of the 3-oxy fragment in 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones-based compounds with a 3-amino one (3-amino analogs of 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones, 3-amino-1,5-dihydro-2H-pyrrol-2-ones) can play a crucial role in their biological effect. Thus, approaches to 3-amino-1,5-dihydro-2H-pyrrol-2-ones are of significant interest. We developed an approach to 5-spiro-substituted 3-amino-1,5-dihydro-2H-pyrrol-2-ones that could not be obtained using previously reported approaches (reactions of 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones with amines). The developed approach is based on the thermal decomposition of 1,3-disubstituted urea derivatives of 5-spiro-substituted 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones, which were prepared via their reaction with carbodiimides.     

Reactions of 1-(4-aminosulfonylphenyl)-5-aryl-4-aroyl-3-hydroxy-3-pyrrolin-2-ones with arylamines and hydrazine hydrate

Depending on the reaction condition, 1-(4-aminosulfonylphenyl)-5-aryl-4-aroyl-3-hydroxy-3-pyrrolin-2-ones reacted with aromatic amines to yield 3-arylamino-3-pyrrolin-2-ones or 4-[aryl (arylamino) methylene]tetrahydropyrrole-2,3-diones. Reactions of 1-(4-aminosulfonylphenyl)-5-aryl-4-aroyl-3-hydroxy-3-pyrrolin-2-ones with hydrazine hydrate afforded pyrrolo[3,4-c]pyrazol-6-ones.     

Reactions of ethyl methylsulfonylpyruvate and its sodium salt with a mixture of aromatic aldehyde and arylamine

The reactions of ethyl methylsulfonylpyruvate and its sodium salt with a mixture of aromatic aldehyde and arylamine afforded 1,5-diaryl-3-hydroxy-4-methylsulfonyl-3-pyrrolin-2-ones. The spatial structure of 1,5-diphenyl-3-hydroxy-4-methylsulfonyl-3-pyrrolin-2-one was established by X-ray diffraction analysis.     

Metaboliten der 1,5-Dihydroimidazo[2,1-b]chinazolin-2(3H)-one. Synthese und Reaktionen einiger 1,5-Dihydro-3-hydroxyimidazo[2,1-b]chinazolin-2(3H)-one

Metabolites of 1,5-Dihydroimidazo[2,1-b ]quinazolin-2(3H)-ones. Preparation and Reactions of Some 1,5-Dihydro-3-hydroxyimidazo[2,1-b]quinazolin-2(3H)-ones Hydroxylated 1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-ones 2–4 and 6 were isolated as metabolites of imidazoquinazolinones 1a and 1b , respectively. The synthesis of 1,5-dihydro-3-hydroxy-3-methylimidazo[2,1-b]quinazolin-2(3H)-ones 3 , 4 , and 6 , and the preparation of some derivatives thereof is described.     

Reactions of 5-aryl-4-acyl-1-(4-hydroxyphenyl)-3-hydroxy-3-pyrrolin-2-ones with arylamines

The reaction of 5-(4-chlorophenyl)-4-benzoyl-1-(4-hydroxyphenyl)-3-hydroxy-3-pyrrolin-2-one with aromatic amines affords the corresponding 3-arylamino derivatives, and the reactions of 5-aryl-4-acetyl-1-(4-hydroxyphenyl)-3-hydroxy-3-pyrrolin-2-ones with p-toluidine yield 5-aryl-4-(1-p-tolylamino)ethylene-1-(4-hydroxyphenyl)pyrrolidin-2,3-diones.     

Synthesis of derivatives of pyrazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidines and imidazo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidines proceeding from alkyl 2-benzylidene-3-oxo-3-fluoroalkylpropionates

Methods were developed of the synthesis of alkyl 2-hydroxy-2-fluoroalkyl-4-phenyl-1,2,3,4—tetrahydroimidazo-[1,5-a]pyrimidine-3-carboxylates and alkyl-5-hydroxy-2,7-diphenyl-5-fluoroalkyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-6-carboxylates by regioselective [3+3]-cycloaddition of 5-aminoimidazole or 5-aminopyrazole to alkyl 2-benzylidene-3-oxo-3-fluoroalkylpropionates at the fluoroacylvinyl fragment.     

Reactivity of pyrrole pigments. Part 5: Electrophilic substitution—Nitration and bromination—Of some pyrromethenones and 5-arylmethylene-3,4-dimethyl-3-pyrrolin-2-ones

Some 5-arylmethylene-3,4-dimethyl-3-pyrrolin-2-ones react with both bromine and nitronium tetrafluoroborate (NO₂BF₄) to give 5-(aryl)nitromethylene-3-pyrrolin-2-ones and 5-(aryl)bromomethylene-3-pyrrolin-2-ones, respectively. The use of bromine in methanol affords 5-(aryl)bromomethyl-3,4-dimethyl-5-methoxy-3-pyrrolin-2-ones. Whereas pyrromethenones react mainly on the pyrrole ring, ethyl 3,4-demethyl-5-[(3,4-dimethyl-5-oxo-3-pyrrolin-2-yl)methylene]-1H-pyrrole-2-carboxylate reacts as the aryl derivatives, however, with bromine in methanol the addition of two methoxy groups at the exocyclic double bond takes place. 3,4-Dimethyl-5-(2-pyridylmethylene)-3-pyrrolin-2-one does not react with bromine or NO₂BF₄, but reacts as the aryl derivatives with bromine in methanol. The reactivity patterns are in agreement with the theoretical ones obtained from MINDO/3 calculations, using theFukui frontier orbital model. The obtained results are used to explain the reactivity of rubins (biladienes-a,c) and verdins (bilatrienes-a,b,c) in front of electrophiles.Einige 5-Arylmethylen-3,4-dimethyl-3-pyrrolin-2-one reagieren sowohl mit Brom als auch mit Nitroniumtetrafloroborat (NO₂BF₄). Man erhält 5-(aryl)bromomethylen-oder 5-(aryl)nitromethylen-3-pyrrolin-2-one. Bei Verwendung einer methanolischen Bromlösung werden 5-(aryl)bromomethyl-3,4-dimethyl-5-methoxy-3-pyrrolin-2-one gebildet. Pyrromethenone reagieren hauptsächlich am Pyrrolring, Ethyl 3,4-dimethyl-5-[(3,4-dimethyl)-5-oxo-3-pyrrolin-2-yl)methylen]-1H-pyrrol-2-carboxylat hingegen verhält sich wie ein Arylderivat, mit methanolischen Bromlösung jedoch erfolgt Eintritt zweier Methoxygruppen an der exocyclischen Doppelbindung.5-(2-Pyridyl)methylen-3,4-dimethyl-3-pyrrolin-2-on reagiert nicht mit Brom oder NO₂BF₄, wohl aber mit einer methanolischen Bromlösung und verhält sich unter diesen Bedingungen wie ein Arylderivat; 3- und 4-Pyridylderivate verhalten sich analog. Die Reaktivität ist in Übereinstimmung mit theoretischen Werten aus MINDO/3-Rechnungen unter Verwendung des Fukui frontier orbital model. Die Reaktivität von Rubinen (Biladiene-a, c) und Verdinen (Bilatriene-a,b,c) gegenüber Elektrophilen werden im Zusammenhang mit den erhaltenen Resultaten diskutiert.

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Reaktivität der Pyrrolpigmente, 5. Mitt.: Elektrophile Substituierung (Nitrierung und Bromierung) von einigen Pyrromethenonen und 5-Arylmethylen-3,4-dimethyl-3-pyrrolin-2-onen

     

Synthesis of tetrahydroimidazo[1,5-c]oxazol-3-ones by aminomethylation of some oxazolidinones

Aminomethylation of 4,4-bis(nitrooxymethyl)oxazolidin-2-one and 4,4-bis(chloromethyl)-oxazolidin-2-one utilizing primary amines as the amino components yielded 6,7a-substituted tetrahydroimidazo[1,5-c]oxazol-3-ones.     

Synthesis of stereopure acyclic 1,5-dimethylalkane chirons: building blocks of highly methyl-branched natural products

An efficient synthetic method towards stereopure acyclic 1,5-dimethylalkane building blocks from methyl (2R)-3-hydroxy-2-methylpropionate (R)-1 (>99% ee) and methyl (2S)-3-hydroxy-2-methylpropionate (S)-1 (>99% ee) through a series of chemical transformations, including Julia–Kocienski olefination and diimide reduction, is described. Through this strategy, two fragments of β-d-mannosyl phosphomycoketide (C₃₂-MPM) and four stereopure 1,5-dimethylalkane C₁₀ chirons are prepared. These C₃₂-MPM fragments and C₁₀ chirons have shown great potential application as building blocks for the synthesis of highly methyl-branched natural products containing chiral oligoisoprenoid-like chains.     

Synthesis 5-(pyrazolin-3-ylmethylidene)-2-thiohydantoins and 2-alkylsulfanyl-5-(pyrazolin-3-ylmethylidene)-3,5-dihydro-4<Emphasis Type="Italic">H</Emphasis>-imidazol-4-ones

A reaction of 3-allyl- and 3-phenylthiohydantoins with 1,5-diphenyl- and 1-phenyl-substituted 3-formyl-2-pyrazolines was used to obtain a series of 5-(pyrazolin-3-ylmethylidene)-2-thioxotetrahydro-4H-imidazol-4-ones, the subsequent alkylation of which with methyl iodide or ethyl chloroacetate gave the corresponding 2-alkylthio-5-(pyrazolin-3-ylmethylidene)-3,5-dihydro-4H-imidazol-4-ones in the yields from 30 to 77%. The oxidation of (5Z)-3-phenyl-5-[(1,5-diphenylpyrazolin-3-yl)methylidene]-2-methylsulfanyl-4,5-dihydroimidazol-4-one with lead tetraacetate led to the corresponding pyrazole in 48% yield.     

Reactions of 1,5-diphenyl-2,4-dimethyl-1,5-pentanedione with hydrogen sulfide

1,5-Diphenyl-2,4-dimethyl-1,5-pentanedione reacts with hydrogen sulfide in the presence of boron trifluoride etherate or 70% perchloric acid to give the corresponding thiapyrylium salts and 2,6-diphenyl-3,5-dimethyldihydrothiopyran; complete disproportionation to give 2,6-diphenyl-3,5-dimethylthiacyclohexane and 2,6-diphenyl-3,5-dimethylthiapyrylium bromide occurs in the presence of hydrogen bromide. The possibility of catalytic hydrogenation in the presence of 10% Pd/C of compounds with a thiopyran ring was established.     

Synthesis of trifluoromethyl derivatives of pyrrole. Reaction of α,β-unsaturated trifluoromethyl ketones with sodium cyanide

An efficient preparative procedure was developed for the synthesis of 5-hydroxy-5-trifluoromethyl-2-pyrrolidones by the reaction of ,-unsaturated trifluoromethyl ketones with sodium cyanide. Dehydration of these reaction products under mild conditions afforded previously unknown 5-trifluoromethyl-3-pyrrolin-2-ones.     

Thermal,acid-catalyzed,and photolytic transformations of spirocyclic 3H-pyrazoles formed by reactions of methyl,phenyl, and p-tolyl phenylethynyl sulfones with 9-diazofluorene

Methyl, phenyl, and p-tolyl phenylethynyl sulfones react with 9-diazofluorene in diethyl ether at 20°C to give 1,3-dipolar cycloaddition products according to von Auwers’ rule, the corresponding spirocyclic 3H-pyrazoles. The spiro adducts undergo isomerization into 5-R-sulfonyl-3-phenylpyrazolo[1,5-f]phenanthridines on heating in boiling toluene for 2 h; heating of the same pyrazoles in boiling benzene, acetonitrile, or ethanol leads to mixtures of 5-R-sulfonyl-3-phenylpyrazolo[1,5-f]phenanthridines and 3-R-sulfonyl-3a-phenyl-3aH-dibenzo[e,g]indazoles, the latter prevailing. The indazoles are kinetically controlled thermolysis products which are quantitatively converted into phenanthridines on heating in toluene. Sulfonyl-substituted spirocyclic 3H-pyrazoles and indazoles in glacial acetic acid at 20°C in the presence of a catalytic amount of sulfuric acid are transformed into 3a-phenyl-2H-dibenzo[e,g]indazol-3(3aH)-one. Under analogous conditions, sulfonyl-substituted phenanhtridines give rise to 3-phenyl-1H-dibenzo[e,g]indazole. Photolysis of spirocyclic 3H-pyrazoles yields mixtures of sulfonylcyclopropenes and 2H-cyclopenta[j,k]fluorenes.     

Efficient domino strategy for synthesis of 3-substituted 1,5-dihydro-4H-pyrrolo[3,2-c]pyridin-4-one derivatives

A series of 1,5-dihydro-4H-pyrrolo[3,2-c]pyridin-4-one derivatives with 3-(4-hydroxy-2-oxo-2H-pyran-3-yl) groups were synthesized via a one-pot three-component reaction of 4-aminopyridin-2(1H)-ones, 2,2-dihydroxy-1-arylethan-1-ones, and 4-hydroxy-2H-pyran-2-ones in water. This strategy not only provides a valuable tool in the design and synthesis of new hydrogenated pyrrolo[3,2-c]pyridines but also has the advantages of inexpensive starting materials, atom and step economy, environmental friendliness, good to excellent yields, and operational simplicity. A total of 14 examples were examined to show a broad substrate scope and high yields.     

Lithium 1,5-bis[2-dioxyphosphinyl)phenoxy]-3-oxapentane hydrate: Synthesis,vibrational spectra,and crystal structure

The complex [Li(H₃L²)(H₂O)] _n (I), where H₄L² is 1,5-bis[2-(dioxyphosphinyl)phenoxy]-3-oxapentane, is synthesized. Its crystal and molecular structures are determined by X-ray diffraction analysis and vibrational spectroscopy. Complex I is an isolated chain polymer in which the Li⁺ cations bind anions (H₃L²)^? of the bridging ligand. The crystals are orthorhombic: a = 8.1860(3) Å, b = 9.9093(4) Å, c = 23.6293(8) Å, V = 1916.75(12) ų, Z = 4, space group Pna2 ₁. The framework of the polymer chain is stabilized by hydrogen bonds between two hydrogen atoms of the coordinated water molecule and two oxygen atoms of the ether and phosphone groups.     

Synthesis of 2,4,6,8-Tetrasubstituted 1,5-Naphthoquinones

Derivatives of N-aryl-5-hydroxy-1,4-naphthoquinone 4-imines react with primary amines to afford 2,4,6,8-tetrasubstituted 1,5-naphthoquinones.     

Chemistry of 1,5-diketones: V. Hydrazination of acyclic and heterocyclic (poly)carbonyl compounds

Reactions of 2-(1-aryl-3-oxo-3-phenylpropylidene)-3,4-dihydronaphthalen-1(2H)-ones, 3-(1-aryl-3-oxo-3-phenylpropyl)-3,4-dihydro-2H-chromene-2,4-diones, and 3,3'-(arylmethylene)bis(3,4-dihydro-2H-chromene-2,4-diones) with hydrazine hydrate have been studied. Depending on the substrate structure, these reactions involve intramolecular heterocyclization with participation of the exocyclic double bond and sidechain carbonyl group or both oxo groups to give new pyrazole, indazole, and diazepine derivatives, as well as hydrazones.     

Five-membered 2,3-dioxo heterocycles: LVI. Reaction of 3-aroyl-1<Emphasis Type="Italic">H</Emphasis>-pyrrolo[2,1-<Emphasis Type="Italic">c</Emphasis>][1,4]benzoxazine-1,2,4-triones with acyclic enamino ketones

3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones react with 4-arylaminopent-3-en-2-ones and 3-amino-1,3-diphenylprop-2-en-1-ones to give substituted 4-aroyl-3-hydroxy-1-(o-hydroxyphenyl)-1,7-diazaspiro[4.4]nona-3,8-diene-2,6-diones.