Synthesis of 3-amino-3,4-dihydroquinazolin-4-one derivatives from anthranilic acid hydrazide and dicarboxylic acids

Treatment of anthranilic acid hydrazide with 2 equiv of ethoxalyl chloride gave the corresponding diester which underwent cyclization in acetic anhydride to produce ethyl 3-(ethoxalylamino)-4-oxo-3,4-dihydroquinazoline-2-carboxylate. Acylation of anthranilic acid hydrazide first with succinic anhydride and then with ethoxalyl chloride led to the formation of 4-[2-(2-{[ethoxy(oxo)acetyl]amino}benzoyl)hydrazino]-4-oxobutanoic acid whose cyclization in acetic acid afforded N-(2-ethoxycarbonyl-4-oxo-3,4-dihydroquinazolin-3-yl)succinamic acid, while in acetic anhydride ethyl 3-(2,5-dioxopyrrolidin-1-yl)-4-oxo-3,4-dihydroquinazoline-2-carboxylate was obtained. The latter was brought into reactions with amines and hydrazine hydrate and alkaline hydrolysis. Acylation of 2-[2-(2-aminobenzoyl)hydrazinocarbonyl]benzoic acid with ethoxalyl chloride gave ethyl N-[2-(phthalimidocarbamoyl)phenyl]oxamate, and with succinic anhydride, 3-[4-oxo-3-phthalimido-3,4-dihydroquinazolin-2-yl]propionic acid. 4-[2-(2-Aminobenzoyl)hydrazino]-4-oxobutanoic acid reacted with phthalic anhydride in boiling acetic acid to give phthalazino[1,2-b]quinazoline-5,8-dione via elimination of succinic acid residue.     

Features of the reaction of 3,4-dihydroxy-6-oxo-2,4-alkadienoic acid esters with acetone and <Emphasis Type="Italic">p</Emphasis>-toluidine

Three-component reactions of 3,4-dihydroxy-6-oxo-2,4-alkadienoic acids with acetone and p-toluidine were studied; their specific feature was the formation of the regioisomeric esters of 4-hydroxy-2,2-dimethyl-1-(4-methylphenyl)-5-(2-oxoalkyliden)-2,5-dihydro-1H-pyrrole-3-carboxylic acids and [4-alkanoyl-3-hydroxy-5,5-dimethyl-1-(4-methylphenyl)-1,5-dihydro-2H-pyrrol-2-ylidene]acetic acid. Structure of the synthesized compounds was discussed based on the data of IR and ¹H NMR spectroscopy and X-ray diffraction analysis.     

Reaction of 3,4,6-trioxoalkanoic acid esters with 2,4-dinitrophenylhydrazine

Methyl 3,4,6-trioxoalkanoates (3,4-dihydroxy-6-oxo-2,4-alkadienoates) reacted with 2,4-dinitrophenylhydrazine to give methyl 3,6-bis[(2,4-dinitrophenyl)hydrazinylidene]-4-oxoalkanoates or methyl {5-alkyl-2-hydroxy-1-(2,4-dinitroanilino)-3-oxo-2,3-dihydro-1H-pyrrol-2-yl }acetates. Alkyl 3,6-bis[(2,4-dinitrophenyl) hydrazinylidene]-4-oxoalkanoates were also synthesized by reaction of disodium 1-alkoxy-1,6-dioxoalka-2,4-diene-3,4-diolates with 2,4-dinitrophenylhydrazine.     

Reaction of methyl 3,4-dihydroxy-6-oxo-2,4-alkadienoates with 2-aminophenol

Methyl [(3Z)-2-hydroxy-3-(2-oxoalkylidene)-3,4-dihydro-2H-1,4-benzoxazin-2-yl]acetates were prepared by reacting methyl 3,4-dihydroxy-6-oxo-2,4-alkadienoates with 2-aminophenol.     

Synthesis and reactions of 3-(3-ethoxycarbonyl-1-phenyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-4-yl)propenic acid

The reaction of ethyl 4-formyl-1-phenyl-1H-pyrazole-3-carboxylate with the malonic acid led to the formation (2E)-3-(3-ethoxycarbonyl-1-phenyl-1H-pyrazol-4-yl)propenic acid. In reactions of this acid chloride with 4-amino-5-aryl(hetaryl)-4H-1,2,4-triazole-3-thiols were obtained ethyl 4-[(E)-2-{3-aryl(hetaryl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl}ethenyl]-1-phenyl-1H-pyrazoe-3-carboxylates, with 5-aryltetrazoles, ethyl 4-[(E)-2-(5-aryl-1,3,4-oxadiazol-2-yl)-ethenyl]-1-phenyl-1H-pyrazole-3-carboxylates, with 1-(2-hydroxy-3,5-dimethylphenyl) followed by the Baker-Venkataraman rearrangement and the cyclization, ethyl 4-[(E)-2-(6,8-dimethyl-4-oxo-4Hchromen-2-yl)ethenyl]-1-phenyl-1H-pyrazole-3-carboxylate.     

Synthesis of <Emphasis Type="Italic">N</Emphasis>-(4-oxo-3,4-dihydroquinazolin-3-yl)succinimide and <Emphasis Type="Italic">N</Emphasis>-(4-oxoquinazolin-3-yl)succinamic acid derivatives based thereon

The reaction of anthranilic acid hydrazide with diethyl oxalate under microwave irradiation was accompanied by decarboxylation with formation of 3-amino-3,4-dihydroquinazolin-4-one, and acylation of the latter with succinic anhydride gave N-(4-oxo-3,4-dihydroquinazolin-3-yl)siccinimide which was converted into various N-(4-oxo-3,4-dihydroquinazolin-3-yl)succinamic acid derivatives.     

Reaction of polychloroacetaldehyde arylsulfonylimines with 2-amino-6<Emphasis Type="Italic">H</Emphasis>-1,3-thiazine-6-thiones and 2-amino-4-phenyl-6<Emphasis Type="Italic">H</Emphasis>-1,3-thiazin-6-one

2-Amino-4-R-6H-1,3-thiazine-6-thiones and 2-amino-4-phenyl-6H-1,3-thiazin-6-one react with highly electrophilic N-arylsulfonylimines of chloral and phenyldichloroacetic aldehyde at the exocyclic amino group affording in good yields products of nucleophilic addition to the azomethine group of imines: N-[2-polychloro-1-(6-thioxo-4-R-6H-1,3-thiazin-2-ylamino)ethyl]- or -[2-polychloro-1-(6-oxo-4-phenyl-6H-1,3-thiazin-2-ylamino)ethyl]arenesulfonamides.     

Chemistry of Acyl(imidoyl)ketenes: IX. Synthesis and Thermolysis of 3-Aroyl-8-chloro-1,2-dihydro-4<Emphasis Type="Italic">H</Emphasis>-pyrrolo[2,1-<Emphasis Type="Italic">c</Emphasis>][1,4]benzoxazine-1,2,4-triones

Reactions of 3-Z-aroylmethylene-6-chloro-3,4-dihydro-2H-1,4-benzoxazine-2-ones with oxalyl chloride afford 3-aroyl-8-chloro-1,2-dihydro-4H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones and Z-3-(2-aryl-2-chlorovinyl)-6-chloro-2H-1,4-benzoxazine-2-ones. Aroyl(imidoyl)ketenes generated by decarbonylation of pyrrolobenzoxazinetriones undergo dimerization through [4+2]-cycloaddition to form 4-aroyl-3-aroyloxy-2-(2-oxo-2H-1,4-benzoxazin-3-yl)-1H, 5H-pyrido[2,1-c][1,4]benzoxazine-1,5-diones.     

Polyfunctional Derivatives of Isocytosine: I. Intramolecular Rearrangement of 6-Methyl-4-oxo-2-[2-(phenylcarbamoyloxy)ethyl]aminodihydro-3<Emphasis Type="Italic">H</Emphasis>-pyrimidine

The reaction of 2-(2-hydroxyethyl)amino-6-methyl-4-oxodihydro-3H-pyrimidine with phenyl isocyanate yields 6-methyl-4-oxo-2-[2-(phenylcarbamoyloxy)ethyl]dihydro-3H-pyrimidine, which rearranges into 2-(2-hydroxyethyl)amino-6-methyl-4-oxo-5-phenylcarbamoyldihydro-3H-pyrimidine under the action of HCl.     

Multicomponent condensation of 6-acetyl-5,7-dihydroxy-4-methylchromen-2-one with aldehydes and Meldrum´s acid

Previously unknown 6-acetyl-10-aryl-5-hydroxy-4-methyl-9,10-dihydropyrano[2,3-f]-chromene-2,8-diones were synthesized by multicomponent condensation of 6-acetyl-5,7-dihydroxy-4-methylchromen-2-one, aromatic aldehydes, and Meldrum´s acid. A fundamen-tal possibility of interconversion of substituted 6-acetyl-10-aryl-5-hydroxy-4-methyl-9,10-dihydropyrano[2,3-f]chromene-2,8-diones and methyl 3-(6-acetyl-5,7-dihydroxy-4-meth-yl-2-oxo-2H-chromen-8-yl)-3-arylpropionates was demonstrated.     

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.     

Synthesis,structure, and antimicrobial activity of methyl (4-alkanoyl-1,5-diaryl-2-hydroxy-3-oxo-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrol-2-yl)acetates

Reactions of methyl 3,4,6-trioxoalkanoates (3,4-dihydroxy-6-oxo-2,4-alkadienoates) with mixtures of aromatic aldehydes and arylamines or with the corresponding N-(arylmethylidene)anilines afforded methyl (4-alkanoyl-1,5-diaryl-2-hydroxy-3-oxo-2,3-dihydro-1H-pyrrol-2-yl)acetates. The product structure was discussed on the basis of their IR, ¹H NMR, and mass spectra and X-ray diffraction data, and their antimicrobial activity against Staphylococcus aureus P-209 and Escherichia coli M₁₇ was evaluated.     

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.     

Reactions of 1,3-Dialkyl-5-amino-1,3-dihydro-2<Emphasis Type="Italic">H</Emphasis>-imidazo-[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-2-ones with acetylacetone and ethyl acetoacetate

1,3-Dialkyl-5-amino-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones reacted with acetylacetone to give the corresponding 4-(1,3-dialkyl-2-oxo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-5-ylamino)pent-3-en-2-ones which underwent intramolecular cyclization to 1,3-dialkyl-5,7-dimethyl-1,3-dihydro-2H-imidazo[4,5-b]-[1,8]naphthyridin-2-ones on heating in polyphosphoric acid or diphenyl ether. Analogous reaction of 1,3-dialkyl-5-amino-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones with ethyl acetoacetate led to the formation of ethyl 3-(1,3-dialkyl-2-oxo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-5-ylamino)but-2-enoates whose cyclization afforded 1,3-dialkyl-8-hydroxy-7-methyl-1,3-dihydro-2H-imidazo[5,4-b][1,8]naphthyridin-2-ones.     

Reaction of 3,4-dioxohexane-1,6-dioic acid esters with 2,4-dinitrophenylhydrazine

Reaction was studied of 3,4-dihydroxyhexa-2,4-diene-1,6-dioic acid esters with 2,4-dinitrophenylhydrazine that led to the formation of esters of (3E)-3-[2-(2,4-dinitrophenyl)-hydrazinylidene]-4-oxohexane-1,6-dioic and (3E,4E)-3,4-bis[2-(2,4-dinitrophenyl)hydrazinylidene]-hexane-1,6-dioic acids. The structural features of compounds synthesized were established from the data of IR and NMR spectra and X-ray diffraction (XRD) analysis.     

Modified synthesis of some 1-(pyrimidin-2-yl)-3-methyl-4-arylidenepyrazol-5(4<Emphasis Type="Italic">H</Emphasis>)-ones

2-[3-Methyl-4(4-dialkylaminobenzylidene)-5-oxo-4,5-dihydropyrazol-1-yl]cyclopenta[d]pyrimidin-4(3H)-ones were synthesized by consecutive transformation of 2-hydrazinocyclopenta[d]pyrimidin-4(3H)-one prepared from benzylideneaminoguanidine and ethyl 2-oxocyclopentanoate.     

Reaction of anthranilic acid 2-<Emphasis Type="Italic">N</Emphasis>-phenylhydrazide with cyclic anhydrides

In the reaction with cyclic anhydrides the anthranilic acid 2-N-phenylhydrazide depending on conditions yielded either anthranilic acid 2-N-acyl-2-N′-phenylhydrazides, 2-R-3-anilinoquinazolin-4(3H)-ones, or derivatives of 1-phenylpyridazino[3,2-b]quinazoline-2,10-dione.     

Synthesis and antimicrobial activity of novel fused [1,2,4]triazino[5,6-<Emphasis Type="Italic">b</Emphasis>]indole derivatives

Synthesis of new fused systems of triazino[5,6-b]indole starting with preparation of 3-amino[1,2,4]-triazino[5,6-b]indole 1 by reaction of isatin with 2-aminoguanidinium carbonate in boiling acetic acid is presented [1]. Intermediate compound 1 reacted with aldehyde, ethyl chloroformate, triethyl orthoformate, and ninhydrine and gave new heterotetracyclic nitrogen systems, such as 3-(N ²-guanidinylimino)indole-2(1H)-one 2, 3-(N-ethoxycarbonylamino)-4H-[1,2,4]triazino[5,6-b]indole 3, 3-(N-ethoxymethyleneamino)-4H-[1,2,4]-triazino[5,6-b]indole 4, 3-(hydrazinothiocarbonylamino)-4H-[1,2,4]triazino[5,6-b]indole 5, respectively. N-(1,3-dioxoindene-2-ylidene)-4H-[1,2,4]triazino[5,6-b]indol-3-amine 6 was synthesized by reaction of compound 1 with aldehyde, ethyl chloroformate, triethyl orthoformate, and ninhydrine. New fused indole systems, pyrimido[2′,1′:3,4][1,2,4]triazino[5,6-b]indol-3(4H)-one 8, 9, 11, 12 and 1H-imidazo[2′,1′:3,4][1,2,4]triazino-[5,6-b]indol-2(3H)-one 10, were synthesized in the reaction of the intermediate 1 with bifunctional compounds. Structures of the products were elucidated from their elemental analysis and spectral data (IR, ¹H and ¹³C NMR and mass spectra). Antimicrobial activity of some synthesized compounds was tested.     

Synthesis,Structure, and Biological Activity of Products of Reactions of 3,4-Dioxohexane-1,6-dioic Acid Esters with 2-Aminophenol

Bioactive derivatives of 1,4-benzoxazine have been prepared via reactions of 3,4-dioxohexane-1,6- dioic (ketipic) acid esters with 2-aminophenol. (2'Z)-2,2'-(2-Hydroxy-2H-1,4-benzoxazin-2-yl-3-ilidene)diacetic acid esters or (2Z)-[2-oxo-2H-1,4-benzoxazin-3(4H)-ylidene]acetic acid esters can be formed depending on the conditions. The structures of the products of dialkyl ketipate esters reactions with 2-aminophenol were determined by means of X-ray diffraction. It has been demonstrated that the prepared compounds exhibit antimycotic activity against test cultures of plant pathogenic fungi (Fusauium sp., Alternarium sp., and Bipolaris soraciniana).     

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.