A facile carbene route to 2-fluoro-2-pyrrolines via fluorinated azomethine ylides

2-Fluoro-2-pyrrolines have been prepared by a domino reaction of difluorocarbene with N-substituted ketimines in the presence of fumaronitrile, malenitrile or dimethyl maleate, involving azomethine ylide formation, 1,3-dipolar cycloaddition, and dehydrofluorination. The reactions of 1H-dibenzo[b,e]azepine and 3,4-dihydroisoquinolines with difluorocarbene in the presence of fumaronitrile proceed with the formation of fluorinated 1H-dibenzo[c,f]pyrrolo[1,2-a]azepine and pyrrolo[2,1-a]isoquinoline derivatives. The yields of 2-fluoro-2-pyrrolines depend mostly on their resistance to chromatographic work-up and are higher for 5,5-disubstituted pyrrolines compared to 5-monosubstituted derivatives.     

Reactions of 3-Aroylpyrrolo[1,2-<Emphasis Type="Italic">a</Emphasis>]quinoxaline-1,2,4(5<Emphasis Type="Italic">H</Emphasis>)-triones with 2,3-Dihydrofuran and 3,4-Dihydro-2<Emphasis Type="Italic">H</Emphasis>-pyran

3-Aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones reacted with 2,3-dihydrofuran and 3,4-dihydro-2H-pyran to give mixtures of the corresponding hetero-Diels–Alder (furo- and pyrano[3″,2″: 5′,6′]pyrano- [4′,3′: 2,3]pyrrolo[1,2-a]quinoxalines) and Michael adducts (furyl- and pyranylpyrrolo[1,2-a]quinoxalines).     

Synthesis of New Heterocyclic Systems on the Basis of 7-Benzyl-3-chloro-1-(morpholin-4-yl)-5,6,7,8-tetrahydro-2,7-naphthiridine-4-carbonitrile

Methods have been developed for the synthesis of new 8-amino-3-benzyl-5-(morpholin-4-yl)-1,2,3,4-tetrahydropyrimido[4′,5′: 4,5]thieno[2,3-c][2,7]naphthyridine starting from 7-benzyl-3-chloro-1-(morpholin-4-yl)-5,6,7,8-tetrahydro-2,7-naphthyridine-4-carbonitrile. 8-Hydrazinyl-3-benzyl-5-(morpholin-4-yl)-1,2,3,4-tetrahydropyrimido[4′,5′: 4,5]thieno[2,3-c][2,7]naphthyridine has been converted to isomeric pentacyclic structures with a triazole ring fused through the [c] side of the pyrimidine ring, and their Dimroth rearrangement has been accomplished in both acidic and basic media. New heterocyclic systems containing pyrrolo[1,2-a]pyrimidinone and pyrimido[1,2-a]azepinone fragments were obtained on the basis of the thieno-[2,3-c][2,7]naphthyridine derivative.     

Electrophilic heterocyclization of 6-alken(yn)ylsulfanyl-pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4(5<Emphasis Type="Italic">H</Emphasis>)-ones

6-Allylsulfanyl-1-arylpyrazolo[3,4-d]pyrimidin-4(5H)-ones react with iodine and sulfuric acid to give angular pyrazolothiazolopyrimidine derivatives. The reaction of 6-(prop-2-yn-1-ylsulfanyl)-1-(4-tolyl)-pyrazolo[3,4-d]pyrimidin-4(5H)-one with sulfuric acid gives angularly fused pyrazolo[4,3-e][1,3]thiazolo-[3,2-a]pyrimidin-4-one, whereas in the reaction with sodium methoxide linearly fused pyrazolo[3,4-d][1,3]-thiazolo[3,2-a]pyrimidin-4-one was formed. Linearly fused pyrazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazole derivatives were also obtained by reaction of 1-aryl-6-(3-phenylprop-2-en-1-ylsulfanyl)pyrazolo[3,4-d]pyrimidin-4(5H)-ones with sulfuric acid.     

Synthesis of Pyrano[4′,3′:2,3]pyrrolo[1,2-<Emphasis Type="Italic">a</Emphasis>]quinoxalines by Reaction of Aroylpyrroloquinoxalines with Alkyl Vinyl Ethers

Thermally induced [4 + 2]-cycloaddition of 3-aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones with alkyl vinyl ethers afforded mixtures of diastereoisomeric (5S*,6aR*)- and (5R*,6aR*)-5-alkoxy-3-aryl-5,6-dihydropyrano[ 4′,3′: 2,3]pyrrolo[1,2-a]quinoxaline-1,2,7(8H)-triones.     

Diastereoselective 1,3-Dipolar Cycloaddition of Nitrones to 1<Emphasis Type="Italic">H</Emphasis>-Pyrrole-2,3-diones. Synthesis of pyrrolo[3,2-<Emphasis Type="Italic">d</Emphasis>]isoxazoles

1H-pyrrol-2,3-diones react with nitrones affording substituted pyrrolо[3,2-d]isoxazoles. The structures of ethyl (3R*,3aR*,6aR*)-6-benzyl-3-(4-bromophenyl)-4,5-dioxo-2,6a-diphenylhexahydro-3aHpyrrolo[ 3,2-d]isoxazole-3a-carboxylate and dimethyl (3R*,3aR*,6aS*)-3-(4-bromophenyl)-4,5-dioxo-2,6-diphenyltetrahydro-3aH-pyrrolo[3,2-d]isoxazole-3a,6a(4H)-dicarboxylate were proved by single-crystal X-ray analysis.     

Synthesis of 1-(1,3-dialkyl-2-oxo-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-imidazo-[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acids

Nitration of 2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-one gave its 5-nitro derivative which was subjected to alkylation with dimethyl sulfate, diethyl sulfate, and benzyl(dimethyl)phenylammonium chloride. The resulting 1,3-dimethyl-, 1,3-diethyl-, and 1,3-dibenzyl-5-nitro-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones were reduced to the corresponding 1,3-dialkyl-5-amino-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones, and the latter reacted with itaconic acid to produce 1-(1,3-dialkyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acids. 1-(2-Oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acid was obtained by analogous reaction with 5-amino-2,3-dihydro-1H-imidazo[4,5-b]-pyridin-2-one.     

Synthesis of 5,8-Diamino-Substituted Pyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]thieno[3,2-<Emphasis Type="Italic">d</Emphasis>]pyrimidines and Pyrimido[4′,5′:4,5]thieno[2,3-<Emphasis Type="Italic">c</Emphasis>]isoquinolines

Ethyl 1-amino-8,8-dimethyl-5-(piperidin-1-yl)-8,9-dihydro-6H-pyrano[4,3-d]thieno[2,3-b]pyridine-2-carboxylate and ethyl 1-amino-5-(piperidin-1-yl)-6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline-2-carboxylate reacted with benzoyl isothiocyanate to give the corresponding 1-thioureido derivatives which underwent cyclization to 2,2-dimethyl-5-(piperidin-1-yl)-10-thioxo-1,4,10,11-tetrahydro-2H-pyrano[4″,3″:4′,5′]pyrido-[3′,2′:4,5]thieno[3,2-d]pyrimidin-8(9H)-one and 5-(piperidin-1-yl)-10-thioxo-1,2,3,4,10,11-hexahydropyrimido-[4′,5′:4,5]thieno[2,3-c]isoquinolin-8(9H)-one. The cyclization products were converted into 8-chloro derivatives, and the chlorine atom therein was replaced by various amines.     

Hetero-Diels–Alder Reaction of Aroylpyrrolo[1,2-<Emphasis Type="Italic">a</Emphasis>]quinoxalinetriones with Styrene

Hetero-Diels–Alder reaction of 3-aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones with styrene afforded diastereoisomeric (5R*,6aR*)- and (5S*,6aR*)-3,5-diaryl-5,6-dihydropyrano[4′,3′:2,3]pyrrolo[1,2-a]-quinoxaline-1,2,7(8H)-triones.     

New approach to the synthesis of pyrrolo[3,4-<Emphasis Type="Italic">c</Emphasis>]pyridines

Strategies of synthesis of pyrrolo[3,4-c]pyridines were developed based on cyclization of 3-phenacyl-4-ethoxycarbonyl(acetyl)pyrrole derivatives reacting with N-methylformamide or formamide, and also on recyclization of pyrrolo[3,4-c]pyrylium salts under the action of ammonium acetate and hydrazine acetate. The influence of substituents in initial reagents on composition of reaction products was studied.     

Oxidation of reaction products of <Emphasis Type="Italic">p</Emphasis>-aryl-<Emphasis Type="Italic">С</Emphasis>,<Emphasis Type="Italic">С</Emphasis>-disubstituted nitrones and dimethyl 3-methylenecyclopropane-1,2-dicarboxylate

Oxidation with 2,3-dichloro-4,5-dicyanobenzoquinone of 2,4-dihydro-1Н-azeto[1,2-a]quinoline-3,4 -dicarboxylates obtained in the reaction of N-aryl-С,С-disubstituted nitrones with Feist’s acid ester resulted in the formation of 2-vinylquinoline-3,4-dicarboxylates in good yields.     

Synthesis of benzo[<Emphasis Type="Italic">f</Emphasis>]quinoline derivatives by three-component condensation of tetronic acid with naphthalen-2-amine and formaldehyde

New derivatives of benzo[f]furo[3,4-b]quinoline, spiro[benzo[f]quinoline-2,3′-furan], and benzo[f]-quinoline-2-carboxylic acid were synthesized with high selectivity by three-component condensation of tetronic acid with naphthalen-2-amine and formaldehyde.     

Reactions of 2-(2-propynylsulfanyl)-5,6,7,8-tetrahydrobenzo[<Emphasis Type="Italic">b</Emphasis>]thieno[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4(<Emphasis Type="Italic">3H</Emphasis>)-one with arylsulfenyl chlorides

2-(2-propynylsulfanyl)-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidin-4(3H)-one with arylsulfenyl chlorides in chloroform gave products of anti-Markownikoff Ad _E-addition. The use of nitromethane as solvent in the presence of lithium perchlorate additives favored intramolecular electrophilic cyclization into 1-arylsulfanyl-1,2,6,7,8,9-hexahydro-4H-benzo[4,5]thieno[3,2-e][1,3]thiazolo[3,2-a]-pyrimidin-5-one.     

Synthesis of substituted 3-acyl-1-hydroxyindoles and azoles on their basis

A general approach to the synthesis of new 3-acetyl-substituted pyrrolo[3,4-f]indole-5,7-diones, 3-[3-(dimethylamino)acryloyl]-1-methoxypyrrolo[3,4-f]indole-5,7-diones and similar indole-5,6-dicarbonitriles has been developed. Dimethylaminoacryloyl derivatives synthesized on their basis regioselectively reacted with hydrazine hydrochlorides and hydroxylamine with the formation of the corresponding 5-substituted azoles.     

Convenient Way to the Synthesis of Polycyclic Fused Benzimidazole Derivatives with a Bridgehead Nitrogen Atom

Effective synthesis was developed for 1,2,3,4-tetrahydropyrido- and pyrido[1,2-a]benzimidazole-7,8-diamines that underlie the preparation of new polyazaheterocycles: pyrido[1,2-а]imidazo[4,5-f]-benzimidazole, 7Н-pyrido[1,2-а]imidazo[4,5-f]benzotriazole, pyrido[1,2-а]imidazo[4,5-g]quinoxaline.     

Synthesis and Antimycobacterial Activity of Hydrazides Based on Pyridoxine Derivatives

Pyridoxine derivatives, 3-hydroxy-2-methylpyridine-4- and -5-carbohydrazides, were synthesized according to optimized known procedures, and a method for the synthesis of 5-(hydroxymethyl)-2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine-6-carbohydrazide was developed. The hydroxymethyl groups in positions 5 and 6 of 2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine showed different reactivities, and only the 6-hydroxymethyl group was selectively oxidized to aldehyde under mild conditions. The lactone ring in 5,6-dihydrofuro[3,4-b]pyridin-7(5H)-one was found to be stable to nucleophiles. The synthesized hydrazides showed no antimycobacterial activity.     

Thienooxazolopyrimidinium salts. Reaction of 1-bromomethyl-5-oxo-4-phenyl-1,2,4,5,6,7,8,9-octahydro[1]benzothieno-[3,2-<Emphasis Type="Italic">e</Emphasis>][1,3]oxazolo[3,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidin-11-ium bromide with oxygen-centered nucleophiles

Reactions of [1]benzothieno[3,2-e][1,3]oxazolo[3,2-a]pyrimidin-11-ium bromide with oxygen-containing nucleophiles involve opening of the dihydrooxazole ring and lead to the formation of new functionally substituted thieno[2,3]-d]pyrimidine derivatives.     

Fluorine-containing heterocycles: XVI. Reactions of tetrafluorobenzoyl isothiocyanate with hydrazines and their derivatives

Fluorinated derivatives of 4H-1,3-benzothiazin-4-one, [1,2,4]triazolo[4,3-a]pyrimidine, [1,2,4]triazolo[3,4-b][1,3]benzazoles, and 1,5-dihydro-1,2,4-triazole-5-thione were synthesized by addition of hydrazines and their derivatives to tetrafluorobenzoyl isothiocyanate, followed by cyclization of intermediate thiosemicarbazides.     

Synthesis and properties of 1-aroyl-5,5-dialkyl-2,3,5,6-tetrahydropyrrolo[ 2,1-<Emphasis Type="Italic">a</Emphasis>]isoquinoline-2,3-diones

Acylation of 1-methyl-3,3-dialkyl-3,4-dihydroisoquinolines with acid chlorides afforded enaminoketones. Enaminophenylketones from the obtained series were reacted with oxalyl chloride to provide 1-benzoyl-5,5-dialkyl-2,3,5,6- tetrahydropyrrolo[2,1-a]isoquinoline- 2,3-diones. The reaction of the latter with binucleophiles leads to the opening of the pyrrole ring and to the heterocyclization: Under the effect of o-phenyldiamine qinoxaline is formed, 1,2-cyclohexanediamine provides the hexahydro-benzimidazole system, о-aminophenol gives benzoxazole, 3-hydroxy-2-amino-pyridine furnishes oxazolo[4,5-b]pyridine. In the reaction with hydrazine hydrate the acylation occurs with hydrazide formation.     

[4 + 2]-Cycloaddition of vinyl acetate to pyrrolobenzoxazinetriones. Diastereoselective synthesis of angularly fused pyrano[4,3-<Emphasis Type="Italic">b</Emphasis>]pyrroles

[4 + 2]-Cycloaddition of vinyl acetate to 3-aroylpyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones afforded (10R*,11aR*)-8-aryl-6,7,12-trioxo-6,7,10,11-tetrahydropyrano[4′,3′:2,3]pyrrolo[2,1-c][1,4]benzoxazin-10-yl acetates with high diastereoselectivity.