Reaction of 1,5-diarylpenta-1,4-dien-3-ones with methyl 1-bromocycloalkanecarboxylates and zinc

Methyl 1-bromocyclopentane-, 1-bromocyclohexane- and 1-bromocycloheptanecarboxylates react with zinc and 1,5-diarylpenta-1,4-dien-3-ones to form 10-aryl-8-(2-arylethenyl)-7-oxaspiro[4.5]dec-8-en-6-ones, 5-aryl-3-(2-arylethenyl)-2-oxaspiro[5.5]undec-3-en-1-ones, and 5-aryl-3-(2-arylethenyl)-2-oxaspiro[5.6]-dodec-3-en-1-ones, respectively.     

Synthesis of Several 2-Azafluorenones and 5H[1]Benzopyrano[3,4-c]Py Riding-Ones

Convenient syntheses of 2-azafluorenones 5a-f and 5H[1]benzopyrano[3,4-c]pyridin-5-ones 6a-b were performed by using intramolecular cyclization of 4-arylnicotinic acids 4a-F. 4a-f were obtained via permanganate oxidation from the corresponding of 4-arylpyridines 3a-f in good yields.     

Reaction of Reformatsky reagent prepared from methyl 1-bromocyclohexanecarboxylate and zinc with substituted chalcones

Methyl 1-bromocyclohexanecarboxylate reacts with zinc and substituted chalcones yielding the corresponding spiro-3,4-dihydropyran-2-one derivatives, 3-aryl-5-aryl-2-oxaspiro[5.5]undec-3-en-1-ones.     

Reaction of methyl 1-bromocycloalkanecarboxylates with zinc and ethyl 5-aryl-3-oxo-2,2-diethylpent-4-enoates

Methyl 1-bromoalkanecarboxylates react with zinc and ethyl 5-aryl-3-oxo-2,2-diethylpent-4-enoates to form ethyl 2-(10-aryl-6-oxo-7-oxaspiro[4.5]dec-8-en-8-yl)-2-ethylbutanoates and ethyl 2-(5-aryl-1-oxo-2-oxaspiro[5.5]undec-3-en-3-yl)-2-ethylbutanoates.     

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.     

On the reactions of aroylacetonitriles with acetoacetates

2,7-Diaryl-3-cyano-4-methylpyrano[4,3-b]pyridin-5-ones were synthesized by Ni(acac)₂-catalyzed condensation of aroylacetonitriles with acetoacetates. The competitive Knoevenagel reaction gave 6-aryl-5-cyano-4-methylpyran-2-ones as by-products. A preparative method for the synthesis of the latter compounds in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a catalyst was proposed.     

Studies on the total synthesis of streptazolin and its related natural products: first total synthesis of (+/-)-8alpha-hydroxystreptazolone

The intramolecular Pauson-Khand reaction of 2-oxazolone derivatives with a suitable heptynyl appendage gave exclusively the corresponding 4-hydroxy-6-substituted-9-oxa-1-azatricyclo[6.2.1.0(5,11)]undec-5-ene-7,10-diones. On the basis of this newly developed Pauson-Khand reaction of 2-oxazolone-alkyne derivatives, the first total synthesis of (+/-)-8alpha-hydroxystreptazolone was accomplished in a highly stereoselective manner. In addition, (+/-)-7-epi-8alpha-hydroxystreptazolone was also synthesized.     

Heterocyclizations of 5-methylpyrazol-3-amine with unsaturated arylaliphatic carboxylic acid derivatives

Cyclocondensation of 5-methylpyrazol-3-amine with methyl cinnamate and arylmethylidenemalonic acids in DMF and methanol leads to the formation of 7-aryl-2-methyl-6,7-dihydropyrazolo[1,5-a]-pyrimidin-5(4H)-ones. Arylmethylidenemalonic acids react with the title amine at a ratio of 1:2 in nitrobenzene to give 4-aryl-3,5-dimethyl-1,7-dihydrodipyrazolo[3,4-b:4′,3′-e]pyridines. Heterocyclizations of 5-methylpyrazol-3-amine with 5-arylmethylidene-2,2-dimethyl-1,3-dioxane-4,6-diones or their precursors, para-substituted benzaldehydes and 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum’s acid) in all solvents (methanol, DMF, and nitrobenzene) give the corresponding 4-aryl-3-methyl-2,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones. The structure of 3-methyl-4-(4-nitrophenyl)-2,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-one was proved by X-ray analysis.     

Fluorine-containing 3-arylhydrazono-2,4-dioxobutanoates in reactions with difunctional nucleophiles

3-Arylhydrazono-4-polyfluoroalkyl-2,4-dioxobutanoates reacted with hydrazines to give ethyl 4-aryldiazeno-3-polyfluoroalkyl-1H-pyrazole-5-carboxylates, while analogous reactions of ethyl 3-arylhydrazono-4-pentafluorophenyl-2,4-dioxobutanoates resulted in the formation of 4-aryldiazeno-3-pentafluorophenyl-1,2-dihydropyridazine-5,6-diones or 6-aryl-7,8,9,10-tetrafluoro-2-phenyl-2,4a,6,10b-tetradropyridazo[4,3-c]cinnoline-3,4-diones, depending on the conditions. Cyclocondensation of ethyl 3-arylhydrazono-4-polyfluoroalkyl(or pentafluorophenyl)-2,4-dioxobutanoates with ethylenediamine led to 3-[1-arylhydrazono-2-oxo-2-polyfluoroalkyl(or pentafluorophenyl)ethyl]-5,6-dihydropyrazin-2(1H)-ones, and 3-[1-arylhydrazono-2-oxo-2-polyfluoroalkyl(pentafluorophenyl)ethyl]benzoxazin-2-ones were formed in the condensation with o-aminophenol. Pentafluorophenyl-substituted heterocycles were found to undergo intramolecular ring closure to give 3-hetaryl-substituted 1-aryl-5,6,7,8-tetrafluoro-1,4-dihydrocinnolin-4-ones. The reactions of ethyl 3-arylhydrazono-4-pentafluorophenyl-2,4-dioxobutanoates with o-aminobenzenethiol gave 3-[7-(2-aminophenylsulfanyl)-1-aryl-5,6,8-trifluoro-4-oxo-1,4-dihydrocinnolin-3-yl]benzothiazin-2-ones; 8a-hydroxy-11,12,13,14-tetrafluoro-10-(4-methoxyphenyl)-2,3,4,5,6,7,8a,10-octahydropyrazino[1′,2′:4,5][1,4]diazepino[6,7-c]cinnolin-8-one was isolated in the condensation of ethyl 3-(4-methoxyphenylhydrazono)-4-pentafluorophenyl-2,4-dioxobutanoate with N-(2-aminoethyl)ethane-1,2-diamine.     

1-Aryl-1-chloro-2,2,2-trifluoroethylisocyanates—convenient reagents for synthesis of 2-aryl-2-trifluoromethyl-2,3-dihydro-4H-benzo[e][1,3]oxazin-4-ones

1-Aryl-1-chloro-2,2,2-trifluoroethylisocyanates react with 3-alkoxyphenols to form N-(1-aryl-2,2,2-trifluoroethylidene)-O-(3-alkoxyphenyl)urethanes, which undergo intramolecular thermal cyclization into derivatives of 2-aryl-2-trifluoromethyl-2,3-dihydro-4H-benzo[e][1,3]oxazin-4-ones.     

Synthesis of isochroman-fused pyrazolone and pyrimidine derivatives

Unsubstituted 5 , and 2-aryl- 6a-c , or 2-(2-benzothiazolyl)-substituted 1,3-dihydroisochromano[4,3-c]pyrazol-3(2H)-ones 7a-f were prepared by the reactions of 3-ethoxyoxalyl- 2 , or 3-ethoxycarbonylisochroman-4-one 3 with hydrazine derivatives. The reactions with amidines gave 2-substituted 4-hydroxyisochromano[4,3-d]-pyrimidines 8a-c .     

Synthesis and Transformations of 2-R-5-Aryl-5,6-dihydro-7H-[1,2,4]-triazolo[5,1-b][1,3]thiazin-7-ones

A new procedure for preparation of 2-R-5-aryl-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones by condensation of 5-R-1,2,4-triazole-3-thiones with 3-arylacryloyl chlorides was developed. The thiazine ring of the [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones is easily cleaved by treating with ammonia and hydrazine affording amides and hydrazides of 3-aryl-3-(1H-1,2,4-triazol-5-ylsulfanyl)propanoic acids. The latter react with isothiocyanates furnishing carbamoyl thiohydrazides of 3-aryl-3-(1H-1,2,4-triazol-5-ylsulfanyl)propanoic acids that in alkaline media undergo cyclization into 4-aryl-5-[2-(4H-1,2,4-triazol-5-ylsulfanyl)-2-phenylethyl]-2,4-dihydro-3H-1,2,4-triazole-5-thiones.     

Synthesis and reaction of 6-substituted 3-methoxycarbonyl-4-methylthio-2H-pyran-2-one derivatives

Reaction of aryl and styryl methyl ketones 1a-m with dimethyl bis(methylthio)methylenemalonate ( 2 ) in the presence of potassium hydroxide in dimethyl sulfoxide gave the corresponding methyl 6-aryl- and 6-styryl-4-methylthio-2-oxo-2H-pyran-3-carboxylates 3a-m . 6-Aryl derivatives 3a-d,g were treated with sodium methoxide in methanol to give the corresponding 6-aryl-4-methoxy-2H-pyran-2-ones 8a-d and 9. Phenylcoumalin ( 7a ) and paracotoin ( 7b ) were synthesized by the desulfurization of 6-aryl-4-methylthio-2H-pyran-2-ones 4a,b. Similarly, anibine ( 8e ) was also synthesized from 3g . Treatment of 3 with hydrogen peroxide or 3-chloroperoxybenzoic acid gave the corresponding 4-methylsulfiny-2H-pyran-2-ones 10a-f in good yields. Displacement reactions of 10a-f with nucleophilic reagents are also described.     

Reactions of 4-acyl-1-alkoxyaryl-5-aryl-3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones with nucleophilic reagents

4-Acetyl-1-alkoxyaryl-5-aryl-3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones reacted with amines to give 1-alkoxyaryl-5-aryl-4-(1-R-aminoethylidene)pyrrolidine-2,3-diones. Reactions of amines with 4-benzoyl-substituted analogs involve nucleophilic attack on the C³ atom in the heteroring to produce the corresponding 3-R-amino-1-alkoxyaryl-5-aryl-4-benzoyl-2,5-dihydro-1H-pyrrol-2-ones. Reactions of the title compounds with hydrazine hydrate, regardless on the substituent on C₄, afforded 4-aryl-3-methyl(phenyl)-5-[2(4)-methoxyphenyl]-4,6-dihydropyrrolo[3,4-c]pyrazol-6-ones.     

Synthesis of 3-(2H-Indazol-2-yl)-2H[1]-Benzopyran-2-Ones

Hitherto unknown 3-(2H-Indazol-2-yl)-2H[1] benzopyran-2-ones (4a-f) have been synthesized under the trithyl phosphite (TEP) mediated reaction conditions of 3-[[(2-nitro-phenyl)-methylene]amino]-2H-1-benzopyran-2-ones (3a-f), obtained by the condensation of 3-amino coumarins (1a-f) with 2-nitro-benzaldehyde (2).     

Synthesis and pharmacological activity of urea and thiourea derivatives of 4-azatricyclo[5.2.2.0(2,6)]undec-8-ene-3,5-dione

A series of nineteen new thiourea and urea derivatives of 10-isopropyl-8-methyl-4-azatricyclo[5.2.2.0(2,6)]undec-8-ene-3,5-dione, 1-isopropyl-7-methyl-4-azatricyclo[5.2.2.0(2,6)]undec-8-ene-3,5-dione and 1,7,8,9,10-pentamethyl-4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione have been prepared and studied by (1)H-NMR. The compound k1a (1-(1,7,8,9,10-pentamethyl-3,5-dioxo-4-aza-tricyclo[5.2.1.0(2,6)]dec-8-en-4-yl)-3-phenyl-urea) was tested for pharmacological activity on animal central nervous system (CNS). The activities of synthesized compounds were evaluated for their cytotoxicity and anti-HIV-1 activity in MT-4 cells. Antimicrobial activity of the newly obtained derivatives was tested against some Gram-positive and Gram-negative bacteria and fungi of the Candida species.     

The photochemistry of benzotriazole derivatives. Part 2: photolysis of 1-substituted benzotriazole arylhydrazones: new route to phenanthridin-6-yl-2-phenyldiazines

Irradiation of 1-substituted benzotriazole arylhydrazones 3a-c, 4a,b and 5a,b with a 16 W low pressure mercury arc-lamp (254 nm) for 24 h gave phenanthridin-6-yl-2-phenyldiazines 9a-c, phenanthridin-6(5H)-ones 10a-c, 1-anilinobenzimidazoles 11a-c, 2-aryl-1H-benzimidazoles 12a-c, 1-arylamino-1H-benzimidazol-2-carboxylic acid ethyl esters 14a,b, 1-aryl-1H, 9H-benzo [4,5][1,2,3] triazolo[1,2-a]tetrazole-3-carboxylic acid ethyl esters 16a,b, 1-arylamino-2-benzoylbenzimidazoles 18a,b and 2-benzoylbenzoxazole 21.     

Reactivity of N-(omega-haloalkyl)-beta-lactams with regard to lithium aluminium hydride: novel synthesis of 1-(1-aryl-3-hydroxypropyl)aziridines and 3-aryl-3-(N-propylamino)propan-1-ols

The reactivity of 4-aryl-1-(2-chloroethyl)azetidin-2-ones and 4-aryl-1-(3-bromopropyl)azetidin-2-ones with regard to lithium aluminium hydride has been evaluated for the first time. 4-Aryl-1-(2-chloroethyl)azetidin-2-ones were transformed into novel 1-(1-aryl-3-hydroxypropyl)aziridines through an unprecedented conversion of beta-lactams into 2,3-unsubstituted aziridine derivatives. Unexpectedly, 4-aryl-1-(3-bromopropyl)azetidin-2-ones underwent dehalogenation towards 3-aryl-3-(N-propylamino)propan-1-ols upon treatment with LiAlH(4). 1-(1-Aryl-3-hydroxypropyl)aziridines were further elaborated by means of ring opening reactions using benzyl bromide in acetonitrile towards 3-aryl-3-[N-benzyl-N-(2-bromoethyl)amino]propan-1-ols and using aluminium(iii) chloride in diethyl ether, affording 3-aryl-3-[N-(2-chloroethyl)amino]propan-1-ols.     

Stereoselective additions to the exocyclic CC bond of some α-alkylidene-(+)-camphor derivatives

Stereoselective additions to the exocyclic CC double bond of some (1R,3E,4S)-3-alkylidene-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones and (1R,4E,5S)-4-alkylidene-1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-ones were studied. All additions took place predominantly from the less hindered endo-face of the methylidene compounds to give the corresponding exo-adducts as the major isomers. Thus, catalytic hydrogenations afforded the α-alkylated (1R,3R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones and (1R,4R,5R)-1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-ones in 28–100% de. Similarly, 1,3-dipolar cycloadditions of 2,4,6-trisubstituted benzonitrile oxides gave the corresponding spiro cycloadducts in 66–100% de. The structures were determined by 2D NMR techniques, NOESY spectroscopy and X–ray diffraction.     

Reaction of methyl 1-bromocyclopentane- and 1-bromocyclohexanecarboxylates with zinc and 2-arylmethylidene-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-inden-1-ones or 2-arylmethylidene-3,4-dihydronaphthalen-1(2<Emphasis Type="Italic">H</Emphasis>)-ones

Methyl 1-bromocyclopentanecarboxylate and methyl 1-bromocyclohexanecarboxylate reacted with zinc and 2-arylmethylidene-2,3-dihydro-1H-inden-1-ones or 2-arylmethylidene-3,4-dihydronaphthalen-1(2H)-ones to give 4′-aryl-4′,5′-dihydro-2′H-spiro[cyclopentane(cyclohexane)-1,3′-indeno[1,2-b]pyran]-2′-ones or 4-aryl-5,6-dihydrospiro[benzo[h]chromene-3,1′-cyclopentane(cyclohexane)]-2(4H)-ones, respectively.