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.     

Synthesis of new imidazo[2,1-<Emphasis Type="Italic">b</Emphasis>][1,3]thiazole derivatives from 2-amino-4-(2,2-dichlorovinyl)-1,3-thiazole and <Emphasis Type="Italic">N</Emphasis>-(2,2-dichloro-2-phenylethylidene)arenesulfonamides

2-Amino-4-(2,2-dichlorovinyl)-1,3-thiazole reacted with highly electrophilic N-(2,2-dichloro-2-phenylethylidene)- and N-(2,2,2-trichloroethylidene)arenesulfonamides through the exocyclic amino group to give products of nucleophilic addition to the azomethine bond, N-[2,2-di(or 2,2,2-tri)chloro-1-(1,3-thiazol-2-ylamino)ethyl]arenesulfonamides in good yields. Intramolecular heterocyclization of the latter afforded N-[3-(2,2-dichloroethyl)-6-phenylimidazo[2,1-b][1,3]thiazol-5-yl]arenesulfonamides.     

Regioselectivity in the reactions of <Emphasis Type="Italic">N</Emphasis>-(polychloroethylidene)-sulfonamides with 1<Emphasis Type="Italic">H</Emphasis>-pyrrole and 1-methyl-1<Emphasis Type="Italic">H</Emphasis>-pyrrole

N-(2,2,2-Trichloroethylidene)arenesulfonamides react with 1H-pyrrole and 1-methyl-1H-pyrrole to give the corresponding N-[2,2,2-trichloro-1-(1H-pyrrol-2-yl)ethyl]arenesulfonamides. The reaction of N-(2,2,2-trichloroethylidene)trifluoromethanesulfonamide with pyrrole leads to a mixture of 2-mono-and 2,5-disubstituted pyrroles, whereas in the reaction with 1-methyl-1H-pyrrole only the 2-substituted compound is formed. N-(2,2-Dichloro-2-phenylethylidene)-4-methylbenzenesulfonamide reacts with 1H-pyrrole to form N-[2,2-dichloro-2-phenyl-1-(1H-pyrrol-2-yl)ethyl]-4-methylbenzenesulfonamide, and its reaction with 1-methyl-1H-pyrrole gives a mixture of 2-and 3-monosubstituted derivatives. The results of quantum-chemical calculations of the initial reactants and products indicate that the process is orbital-controlled. A good agreement is observed between the experimental data and theoretical conclusions concerning the dependence of the reaction regioselectivity on the nature of substituents in the electrophile molecule.     

Reaction of <Emphasis Type="Italic">N</Emphasis>-aryl-3-oxobutanethioamides with 2-amino-1,3-thiazole and 2-amino-1,3-benzothiazole

N-Aryl-3-oxobutanethioamides react with 2-amino-1,3-thiazole (2-amino-1,3-benzothiazole) in acetic acid to give mixtures of 7-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidine-5-thione (2-methyl-4H-pyrimido-[2,1-b][1,3]benzothiazole-4-thione) and 5-arylimino-7-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidines (4-arylimino-2-methyl-4H-pyrimido[2,1-b][1,3]benzothiazoles), whose ratio depends on the nature of the aryl substituent in the initial butanethioamide.     

Electrophilic cyclization of <Emphasis Type="Italic">N</Emphasis>-allyl(propargyl)-5-amino-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-4-carboxamides. Synthesis of 4-[(dihydro)oxazol-2-yl]-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-5-amines

N-Allyl-5-amino-1H-pyrazole-4-carboxamides in reactions with polyphosphoric acid, with N-halosuccinimides in chloroform, and with (chlorosulfanyl)benzenes in nitromethane in the presence of lithium perchlorate underwent cyclization involving the N-allylamide fragment to give 4-[5-methyl(halomethyl)-4,5-dihydrooxazol-2-yl]-1H-pyrazol-5-amines and 2-(5-amino-1H-pyrazol-4-yl)-5-[(arylsulfanyl)methyl]-4,5-dihydro-1,3-oxazolium perchlorates, respectively. Analogous reactions of N-propargyl-5-amino-1H-pyrazole-4-carboxamides with polyphosphoric acid afforded 4-(5-methyloxazol-2-yl)-1H-pyrazol-5-amines, and with (chlorosulfanyl) benzenes, 2-(5-amino-1H-pyrazol-4-yl)-5-[(arylsulfanyl)methylidene]-4,5-dihydro-1,3-oxazolium perchlorates.     

Nitration of 1,3-dihydro-2<Emphasis Type="Italic">H</Emphasis>-imidazo[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-2-one derivatives

Nitration of 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one and its N-methyl derivatives at 0–5°C and 60°C gives 5-nitro-and 5,6-dinitro-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones, respectively. The latter can also be obtained by nitration of 5-mononitro derivatives under similar conditions. The nitration of 6-chloro-and 6-bromo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones and their N-methyl-substituted analogs leads to the formation of the corresponding 6-chloro(bromo)-5-nitro compounds. The same products are formed in the nitration of 5,6-dichloro-and 5,6-dibromo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones. In this case, the process involves replacement of the halogen atom in position 5 of the pyridine fragment by nitro group. The nitration of 6-bromo-5-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one is accompanied by oxidation of the 5-methyl group to carboxy.     

Recyclization of 1,3-dialkyl-6-nitro-1<Emphasis Type="Italic">H</Emphasis>-imidazo[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridine-2,5(3<Emphasis Type="Italic">H</Emphasis>,4<Emphasis Type="Italic">H</Emphasis>)-diones into imidazole derivatives

Treatment of 5-amino-1,3-dialkyl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones with sodium nitrite in aqueous HCl gave 1,3-dialkyl-1H-imidazo[4,5-b]pyridine-2,5(3H,4H)-diones which were nitrated with potassium nitrate in sulfuric acid to 6-nitro derivatives, and the latter underwent recyclization into 4-amino-1,3-dialkyl-5-(1H-pyrazol-5-yl)-2,3-dihydro-1H-imidazol-2-ones by the action of hydrazine hydrate.     

Cycloaminomethylation of dihydric phenols catalyzed by <Emphasis Type="Italic">d</Emphasis>- and <Emphasis Type="Italic">f</Emphasis>-metal compounds

An efficient method has been developed for the synthesis of 7,16,25-triaryl-7,8,16,17,25,26-hexahydro-6H,15H,24H-tribenzo[f,m,t][1,5,8,12,15,19,3,10,17]hexaoxatriazacyclohenicosines, 3,8-diaryl-2,3,4,7,8,9-hexahydrobenzo[1,2-e:4,3-e′]bis[1,3]oxazines, 3,9-bis(chlorophenyl)-3,4,9,10-tetrahydro-2H,8H-benzo[1,2-e:3,4-e′]bis[1,3]oxazines, and 2,9-bis(chlorophenyl)-1,2,3,8,9,10-hexahydrobenzo[1,2-e:6,5-e′]bis-[1,3]oxazines via cycloaminomethylation of pyrocatechol, resorcinol, and hydroquinone with N,N-bis(methoxymethyl) anilines in the presence of samarium catalysts.     

Features of Reaction of 2-(5-Methyl-2-phenyl-2<Emphasis Type="Italic">H</Emphasis>-1,2,3-diazaphosphol-4-yl)-4<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">e</Emphasis>]-1,3,2-dioxaphosphorin-4-one with 1,2-Dicarbonyl Compounds

2-(5-Methyl-2-phenyl-2H-1,2,3-diazaphosphol-4-yl)-4H-benzo[e]-1,3,2-dioxaphosphorin-4-one reacts with perfluorodiacetyl, 3,6-di(tert-butyl)-1,2-benzoquinone and phenanthrenequinone only with the participation of a three-coordinated phosphorus atom to form spirophosphoranes containing acyclic 5-methyl-2- phenyl-2H-1,2,3-diazaphosphol-4-yl substituent, whereas the interaction with tetrachloro-1,2-benzoquinone proceeds via expanding the six-membered heterocycle to the nine-membered one to form 2-(2-phenyl-2H-1,2,3-diazaphosphol-4-yl)-2,9-dioxo-4,5,6,7-tetrachlorodibenzo[d,h]-1,3,8-trioxaphosphonine.     

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 2-(halomethyl)-3,4-dihydro-2<Emphasis Type="Italic">H</Emphasis>-pyrido[2,1-<Emphasis Type="Italic">b</Emphasis>][1,3]oxazinium halides

Alkylation of pyridin-2(1H)-one and 5-nitropyridin-2(1H)-one with 4-bromobut-1-ene afforded a mixture of N- and O-butenyl derivatives. 1-(But-3-en-1yl)pyridin-2(1H)-one and 1-(but-3-en-1-yl)-5-nitropyridin- 2(1H)-one reacted with bromine and iodine to give 2-(halomethyl)-3,4-dihydro-2H-pyrido[2,1-b][1,3]-oxazinium halides.     

<Emphasis Type="Italic">N</Emphasis>-acylimino-substituted 2-oxa-7-azaspiro[4.4]nona-3,6,8-trienes in the synthesis of 3-(1<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazol-3-yl)-3<Emphasis Type="Italic">H</Emphasis>-pyrrole-4-carbonitriles

Reaction with phenylhydrazine of 3Н-pyrroles spirobound to a furan ring, N-acylimino-substituted 2-oxa-7-azaspiro[4.4]nona-3,6,8-trienes, occurs with a diasteroselective formation of previously unknown derivatives of 1,2,4-triazole: 5-amino-3-(5-alkyl-1-phenyl-1H-1,2,4-triazol-3-yl)-2-morpholin-4-yl-3H-pyrrole-4-carbonitriles.     

Synthesis of 2-Methyl-7-phenyl-5,8-dihydro-4<Emphasis Type="Italic">H</Emphasis>-pyrzylo-[5,1-<Emphasis Type="Italic">d</Emphasis>][1,2,5]triazepin-4-one

An approach is developed to the synthesis of 2-methyl-7-phenyl-5,8-dihydro-4H-pyrazolo[5,1-d]-[1,2,5]triazepin-4-one, based on the recyclization of 2-methyl-6-phenyl-4H-pyrazolo[5,1-c][1,4]oxazin-4-one with hydrazine.     

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.     

Atropisomeric <Emphasis Type="Italic">N</Emphasis>-acyl-<Emphasis Type="Italic">N</Emphasis>-(cyclopentenylphenyl)glycines in the synthesis of oxazolo[3,4-<Emphasis Type="Italic">a</Emphasis>]benzoxazocinones

Intramolecular [3+2]-cycloaddition was studied of munchnones generated at heating syn- and anti-atropisomers of N-acyl-N-[6-methyl-2-(cyclopent-2-en-1-yl)phenyl]glycines with acetic anhydride. By spectral and X-ray diffraction analysis syn-isomers of acids and tetrahydro-1,4,7-methanetriyl[1,3]oxazolo[3,4-a][1]- bensazocin-3(3aH)-ones were identified.     

Alkylation of 2-(methylsulfanyl)-6-polyfluoroalkylpyrimidin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones with haloalkanes

The alkylation of ambident anions of 2-(methylsulfanyl)-6-(polyfluoroalkyl)pyrimidin-4(3H)-ones with 4-bromobutyl acetate leads to concurrent formation of O- and N-(4-acetoxybutyl) derivatives. Polar aprotic solvents favor formation of the O-isomer, and weakly polar dioxane favors N-alkylation. The reaction of 2-(methylsulfanyl)-6-(trifluoromethyl)pyrimidin-4(3H)-one with an equimolar amount of 1,2-dibromoethane in polar acetonitrile gives a mixture of N,N-, O,O-, and N,O-bridged bis-pyrimidines, as well as N- and O-[2-(methylsulfanyl)ethyl] derivatives, whereas in the presence of 10 equiv of 1,2-dibromoethane the N,O-isomer is formed as the only product. The reaction in weakly polar tetrahydrofuran yields N,N- and N,O-bispyrimidines.     

Synthesis and biotests of 2-aryl-5-arylmethylidene-substituted 1,3-oxazol-5(4<Emphasis Type="Italic">H</Emphasis>)-ones and <Emphasis Type="Italic">N</Emphasis>-methyl-3,5-dihydro-4<Emphasis Type="Italic">H</Emphasis>-imidazol-4-ones as combretastatin A-4 analogs

A series of 2-aryl-5-arylmethylidene-1,3-oxazol-5(4H)-ones and 2-aryl-5-arylmethylidene-N-methyl-3,5-dihydro-4H-imidazol-4-ones was synthesized as structural analogs of combret- astatin A-4 (a compound possessing antitumor activity). (5Z)-5-[(4-Methoxyphenyl)methyl-idene]-3-methyl-2-(4-methylphenyl)-3,5-dihydro-4H-imidazol-4-one was found to exhibit the highest cytotoxicity against cells of human A549 lung carcinoma line (EC₅₀ = 6±0.8 μmol L^?1).     

Cyclization of trifluoro-<Emphasis Type="Italic">N</Emphasis>-(prop-2-yn-1-yl)methanesulfonamides to <Emphasis Type="Italic">N</Emphasis>-(hydroxymethyl)-1,2,3-triazoles

Three-component heterocyclizations of trifluoro-N-(prop-2-yn-1-yl)methanesulfonamide, trifluoro-N-pheny-N-(prop-2-yn-1-yl)methanesulfonamide, and trifluoro-N,N-di(prop-2-yn-1-yl)methanesulfonamide with formaldehyde and sodium azide afforded N-{[2-(hydroxymethyl)-2H-1,2,3-triazol-4-yl]methyl}-, N-{[2-(hydroxymethyl)-2H-1,2,3-triazol-4-yl]methyl}-N-phenyl-, and N,N-bis{[2-(hydroxymethyl)-2H-1,2,3-triazol-4-yl]methyl}trifluoromethanesulfonamides as the major products together with minor 1-(hydroxymethyl)-1H-1,2,3-triazole isomers.     

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.     

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.