Reformatsky Reaction of Methyl α-Bromoisobutyrate with 2-Arylmethylidenemalonic Acid Derivatives

Reformatsky reagent obtained by treatment of methyl α-bromoisobutyrate with zinc reacts with dimethyl 2-arylmethylidenemalonates to give trimethyl 2-aryl-3-methylbutane-1,1,3-tricarboxylates. The reaction of the same compound with ethyl 3-aryl-2-(4-methylphenylcarbamoyl)acrylates yields cyclic products, ethyl 4-aryl-5,5-dimethyl-1-(4-methylphenyl)-2,6-dioxopiperidine-3-carboxylates. Treatment of the latter with morpholine and phenylhydrazine leads to the corresponding 4-aryl-5,5-dimethyl-1-(4-methylphenyl)-2,6-dioxopiperidine-3-carboxylic acid morpholides and phenylhydrazides. The products are formed as a single diastereoisomer.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 7, 2005, pp. 1034–1038.Original Russian Text Copyright © 2005 by Shchepin, Fotin.     

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.     

Synthesis of 4,6-diaryl-1-benzyl-6-hydroxy-5,5-dimethyl-2-oxopiperidine-3-carbonitriles and their analogs via a modified Reformatsky reaction

Organozinc compounds obtained from 1-aryl-2-bromo-2-methylpropanone and zinc react with N-benzyl-3-aryl-2-cyanoacrylamides or N-[6-(2-cyano-1-oxo-3-phenylprop-2-enylamino)hexyl]-2-cyano-3-phenylacrylamide to give 4,6-diaryl-1-benzyl-6-hydroxy-5,5-dimethyl-2-oxopiperidine-3-carbonitriles or 1,6-bis(6-aryl-3-cyano-6-hydroxy-5,5-dimethyl-2-oxo-4-phenylpiperidyl)hexanes as a single isomer with trans-located piperidine hydrogen atoms.     

Cyclization of ortho-cyclopropylphenyl benzamides in gas and liquid phases

The electron ionization (EI) and collision-induced dissociation (CID) spectra of substituted N-(ortho-cyclopropylphenyl)benzamides 1-7 and N-[ortho-(1-methylcyclopropyl)phenyl]benzamides 8-12 were recorded. In addition to routine bond cleavages, the molecular ions (M+) of 1-12 undergo cyclization into the corresponding 3-aryl-1-alkyl-1-ethyl-1H-benzoxazines and isomeric 5-ethyl-2-oxodibenzoazepines. The presence of a methyl group in the cyclopropyl ring (compounds 8-12) makes the formation of 5-ethyl-2-oxodibenzoazepine less favorable. In accord with mass spectrometric predictions, compound 13 (3-p-tolyl-1-ethyl-1H-benzoxazine) was obtained as a major product of the reaction of N-(ortho-cyclopropylphenyl)-4-methylbenzamide 1 with sulfuric acid. Traces of 5-ethyl-2-oxodibenzoazepine were also detected in gas chromatography-mass spectrometry (GC-MS) analysis of the reaction mixture although the yield was too low to allow its isolation.     

Five-membered dioxo heterocycles: CIV. Reaction of methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates with cyclic enehydrazines. Crystal and molecular structure of N-[3′-benzoyl-1′-(4-chlorophenyl)-4′-hydroxy-6,6-dimethyl-2,4,5′-trioxo-1′,4,5,5′,6,7-hexahydrospiro-[indole-3,2′-pyrrol]-1(2H)-yl]benzamide

Methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with N′-(5,5-dimethyl-3-oxocyclohex-1-en-1-yl)benzohydrazides and N′-(5,5-dimethyl-3-oxocyclohex-1-en-1-yl)-2,2-diphenylacetohydrazide to give substituted N-[1′-aryl-3′-benzoyl-4′-hydroxy-6,6-dimethyl-2,4,5′-trioxo-1′,4,5,5′,6,7-hexahydrospiro[indole-3,2′-pyrrol]-1(2H)-yl]benz- and -diphenylacetamides.     

The use of anilinodihydrofurans in the synthesis of novel heterocyclic compounds

Alkyl 4-oxo-2-phenylamino-4,5-dihydrofuran-3-carboxylates were used for the preparation of alkyl 5-amino-7-aryl-2-{[aryl(hydroxy)methyl](phenyl)amino}-4,6-dicyano-1-benzofuran-3-carboxylates, 4-oxo-2-phenylamino-N-(p-tolyl)-4,5-dihydrofuran-3-carboxamide, and ethyl 4-chloro-5-formyl-2-(phenylamino)furan-3-carboxylate. The latter was used for the synthesis of ethyl 4-chloro-5-(hydrazinylidenemethyl)-2-(phenylamino)furan-3-carboxylate and diethyl 5,5'-(hydrazine-1,2-di-ylidenemethylylidene)bis[4-chloro-2-(phenylamino)furan-3-carboxylate].     

Chemistry of iminofurans: V. Synthesis,structure, and cyclization of 4-R-4-oxo-2-[2-(2-oxo-1,2-diphenylethylidene)hydrazino]but-2-enoic acids

Reactions of 1,2-diphenylethane-1,2-dione hydrazone with 4-aryl-2-hydroxy-4-oxobut-2-enoic and 2-hydroxy-5,5-dimethyl-4-oxohex-2-enoic acids provided 4-aryl-4-oxo-2-[2-(2-oxo-1,2-diphenylethylidene) hydrazino]but-2-enoic and 5,5-dimethyl-4-oxo-2-[2-(2-oxo-1,2-diphenylethylidene)hydrazino]hex-2-enoic acids. The acids derivatives can exist in solutions as Z- and β-enehydrazino-or β-ketohydrazone forms, and under the treatment with acetic anhydride they undergo cyclization into 5-aryl- and 5-tert-butyl-3-[2-(2-oxo-1,2-diphenylethylidene)hydrazono]-2,3-furandiones.     

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.     

Reformatsky reaction of methyl 1-bromocycloalkane-1-carboxylates with phenyl-and benzoylhydrazones derived from aromatic aldehydes

Reformatsky reagents obtained from methyl 1-bromocyclohexane-and 1-bromocyclopentane-1-carboxylates reacted with aromatic aldehyde phenyl-and benzoylhydrazones to give 3-aryl-2-phenylamino-2-azaspiro[3.5]nonan-, 3-aryl-2-phenylamino-2-azaspiro[3.4]octan-, 3-aryl-2-benzoylamino-2-azaspiro[3.5]-nonan-, and 3-aryl-2-benzoylamino-2-azaspiro[3.4]octan-1-ones, respectively. The reaction of furan-2-carbaldehyde phenylhydrazone with methyl 1-bromocyclohexane-1-carboxylate and zinc led to the formation of 4-(2-furyl)-2-phenyl-2,3-diazaspiro[4.5]decan-1-one.     

Reaction of alkyl 5,5-dimethyl-2-oxo-2,5-dihydrofuran-3-carboxylates with zinc enolates prepared from zinc and 1-arul-2-bromo-2-phenylethanones, 2 bromoindanone, and 2-bromo-6-methyltetralone

Alkyl 5,5-dimethyl-2-oxo-2,5-dihydrofuran-3-carboxylates react with zinc enolates prepared from 1-aryl-2-bromo-2-phenylethanones, 2-bromo indanone, 2-bromo-6-methyltetralone and zinc with formation of ethyl 4-(2-aryl-2-oxo-1-phenyl-ethyl)-5,5-dimethyl-2-oxotetrahydrofuran-3-carboxylates, alkyl 5,5-dimethyl-2-oxo-4-(1-oxoindan-2-yl)tetrahydrofuran-3-carboxylates, and ethyl 5,5-dimethyl-4-(6-methyl-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)-2-oxotetrahydrofuran-3-carboxylates respectively, mainly as single diastereomers.     

Cyclopropanation of N-substituted 3-aryl-2-cyanoprop-2-enamides and derivatives of 5,5-Dimethyl-2-oxo-2,5-dihydrofuran-3-carboxylic acid and 2-oxochromene-3-carboxylic acid with bromine-containing zinc enolates

Zinc enolates derived from 1-aryl-2,2-dibromoalkanones react with N-substituted 3-aryl-2-cyanoprop-2-enamides and 5,5-dimethyl-2-oxo-2,5-dihydrofuran-3-carboxylic and 2-oxochromene-3-carboxylic acid derivatives to give, respectively, N-substituted 2-alkyl-3-aryl-2-aroyl-1-cyanocyclopropane-1-carboxamides, 6-(4-bromobenzoyl)-4,4,6-trimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylic acid ethyl ester and morpholide, and 1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropla[c]chromene-1a-carboxylic acids as a single geometric isomer. Treatment of 1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxylic acids with carboxylic acid anhydrides leads to the formation of the corresponding 9c-alkyl-1-aryl-3,4-dioxo-9b,9c-dihydro-2,5-dioxacyclopenta[2,3]cyclopropa[1,2-a]naphthalen-1-yl carboxylates.     

Reaction of 4-thioxo-1,3-benzothiazines with thiocarbohydrazine: Synthesis and reactivity of 1,3,4-triazolo[3,2-c]quinazoline derivatives

2-Aryl-4-thioxo-1,3-benzothiazines react with thiocarbohydrazide to give the new mesoionic compounds an-hydro 1-amino-5-aryl-2-mercapto-1,3,4-triazolo[3,2-c]quinazolin-4-ium hydroxides. These compounds react with methyl iodide, aldehydes and phenacyl bromides to give 1-amino-5-aryl-2-methylthio-1,3,4-triazolo-[3,2-c]quinazolin-4-ium iodides, 4-arylidenamino-3-(o-aroylamino)phenyl-1H-1,2,4-triazolin-5-thiones and 3-(o-aroylamino)phenyl-6-aryl-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines, respectively. These latter compounds by sequential treatment with methyl trifluoromethanesulphonate and triethylamine lead to 3-(o-aroylamino)-phenyl-6-aryl-1-methyl-7-mercapto-1H-pyrazolo[5,1-c]-1,2,4-triazoles.     

Reaction of Zinc and Sodium Enolates of 3-Alkyl-6-aryl-5,5-dimethyl-2,3,5,6-tetrahydropyrane-2,4-diones with Acyl Chlorides or Benzyl Bromides

Zinc enolates of 3-alkyl-6-aryl-5,5-dimethyl-2,3,5,6-tetrahydropyrane-2,4-diones react with acyl chlorides to form O-acylation products, 4-acyloxy-3-alkyl-6-aryl-5,5-dimethyl-5,6-dihydropyrane-2-ones. Sodium enolates of these pyranediones react in DMSO with substituted benzyl bromides to give mainly C-alkylation products, 3-alkyl-6-aryl-3-(4-R-benzyl)-5,5-dimethyl-2,3,5,6-tetrahydropyrane-2,4-diones, as single geometric isomers. In some cases, O-alkylation products, 4-alkoxy-3-alkyl-6-aryl-5,5-dimethyl-5,6-dihydropyrane-2-ones, are formed as by-products (10-15%).     

Synthesis of methyl 4-aryl-4-oxo-2-[(4-sulfamoylphenyl)amino]but-2-enoates and their reaction with ninhydrin

The reaction of methyl 4-aryl-2,4-dioxobut-2-enoates with 4-aminobenzenesulfonamide in acetic acid–ethanol (1: 1) afforded methyl (2Z)-4-aryl-4-oxo-2-(4-sulfamoylanilino)but-2-enoates which reacted with ninhydrin in glacial acetic acid to give 3-aroyl-4-(4-sulfamoylanilino]-5H-spiro[furan-2,2′-indene]-1′,3′,5-triones.     

Synthesis of Alkyl 4-(1-Alkyl-2-aryl-2-oxoethyl)-5,5-dimethyl-2-oxotetrahydrofuran-3-carboxylates

Zinc enolates derived from 1-aryl-2-bromoalkanones react with alkyl 5,5-dimethyl-2-oxo-2,5-dihydrofuran-3-carboxylates to give alkyl 4-(1-alkyl-2-aryl-2-oxoethyl)-5,5-dimethyl-2-oxotetrahydrofuran-3-carboxylates. Reactions of the latter with amines, such as p-toluidine, cyclohexylamine, and piperidine, lead to the corresponding carboxamides.     

Reformatsky Reaction of Methyl 1-Bromocycloalkanecarboxylates with α-Dicarbonyl Compounds

Reformatsky reactions of methyl 1-bromocyclohexanecarboxylate and methyl 1-bromocyclo-pentanecarboxylate with 2-aryl-2-oxoacetaldehydes involve both carbonyl groups of the latter and result in formation of 3a-aryl-3,3 : 6,6-bis(pentamethylene)- and 3a-aryl-3,3 : 6,6-bis(tetramethylene)tetrahydrofuro-[3,2-b]furan-2,5-diones. The reaction with 2-(2,4-dimethylphenyl)-2-oxoacetaldehyde gives acyclic products, methyl 1-[1-hydroxy-2-(2,4-dimethylphenyl)-2-oxoethyl]cyclohexanecarboxylate and methyl 1-[1-hydroxy-2-(2,4-dimethylphenyl)-2-oxoethyl]cyclopentanecarboxylate, while with benzil methyl 1-(4-hydroxy-1-oxo-3,4-diphenyl-2-oxaspiro[4.5]dec-3-yl)cyclohexanecarboxylate and methyl 1-(4-hydroxy-1-oxo-3,4-diphenyl-2-oxaspiro[4.4]non-3-yl)cyclopentanecarboxylate are obtained.     

Synthesis and Transformations of 5-Substituted 2-Aryl-7H-[1,2,4]triazolo[3,2-b][1,3]thiazin-7-ones and 2-Aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones

3-Aryl-1,2,4-triazole-5-thiones react with dimethyl acetylenedicarboxylate and methyl 3-phenyl-propynoate to afford the corresponding 5-substituted 2-aryl-7H-[1,2,4]triazolo[3,2-b][1,3]thiazin-7-ones. Treatment of 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones with alkalies leads to formation of 3-(benzimidazol-2-ylsulfanyl)-3-arylpropionic acids, their reaction with methyl p-toluenesulfonate yields 1-(3-methyl-2-thioxo-2,3-dihydro-1N-benzimidazol-1-yl)-3-phenyl-2-propen-1-one, and oxidation with hydrogen peroxide gives benzimidazole-2-sulfonic acid and 3-aryl-2-propenoic acids.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 1, 2005, pp. 109–114.Original Russian Text Copyright © 2005 by Britsun, Esipenko, Chernega, Lozinskii.     

Chemistry of Iminofuran: XVI. Synthesis,Structure, Biological Activity,and Cyclization of 4-Oxo-2-(2-phenylaminobenzoylhydrazono)butanoic Acids

The reaction of (2-phenylaminobenzoyl)hydrazine with 4-aryl-2-hydroxy-4-oxobut-2-enoic and 2-hydroxy-5,5-dimethyl-4-oxohex-2-enoic acids results in the formation of 4-aryl-2-(2-phenylaminobenzoyl-hydrazono)-4-oxobutanoic and 5,5-dimethyl-2-(2-phenylaminobenzoylhydrazono)-4-oxohexanoic acids. The products in solutions are present as mixtures of a Z,E-hydrazono form and a cyclic pyrazolinic form, and under the action of acetic anhydride they cyclize in 5-aryl- and 5-tert-butyl-3-(2-phenylaminobenzoylhydrazono)-furan-2,3-diones. 4-Aryl-2-(2-phenylaminobenzoylhydrazono)-4-oxobutanoic and 5,5-dimethyl-2-(2-phenyl-aminobenzoylhydrazono)-4-oxohexanoic acids were tested for antinociceptive and anti-inflammatory activity.

     

Chemistry of 2-ylidenefuran-3(2<Emphasis Type="Italic">H</Emphasis>)-ones: XIX. Reaction of 5-aryl-2(oxoylidene)furan-3(2<Emphasis Type="Italic">H</Emphasis>)-ones with carboxylic acid hydrazides

2-[2-(4-Chlorophenyl)-2-oxoethylidene]-5-phenylfuran-3(2H)-one and methyl (5-aryl-3-oxo-2,3-dihydrofuran-2-ylidene)acetates react with carboxylic acid hydrazides to give the corresponding 3-substituted 2-acyl-6-aryl-3-hydroxy-2,3-dihydropyridazin-4(1H)-ones. Specificities of the product structure are discussed.     

Five-membered 2,3-dioxo heterocycles: LIV. Double spiro heterocyclization of methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2-carboxylates with 3-arylamino-5,5-dimethylcyclohex-2-en-1-ones

Methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with 3-arylamino-5,5-dimethylcyclohex-2-en-1-ones in boiling benzene to give the corresponding 1,1′-diaryl-3′-benzoyl-4′-hydroxy-6,6-dimethyl-1,1′,2,4,5,5′,6,7-octahydrospiro[indole-3,2′-pyrrole]-2,4,5′-triones and 1′-aryl-4-arylamino-3-benzoyl-6′,6′-dimethyl-1′,2′,4′,5′,6′,7′-hexahydro-5H-spiro[furan-2,3′-indole]-2′,4′,5-triones whose structure was proved by X-ray analysis.