Synthesis and reactions of 4-(arylhydrazino)coumarins

The interaction of 4-hydroxycoumarin with phenyl-, 2-chlorophenyl- and 4-bromophenyhydrazine hydrochlorides in the presence of triethylamine led in all cases to the corresponding 4-(arylhydrazino)-coumarins and 1-aryl-3-(2-hydroxyphenyl)-2H-pyrazolin-5-ones. 4-(Arylhydrazino)coumarins reacted with 4-chlorobenzaldehyde in the presence of piperidine acetate to give the corresponding 2-aryl-3-(4-chlorophenyl)[1]benzopyrano[4,3-b]pyrazol-4-ones. The reaction of 4-(4-bromophenylhydrazino)-coumarin with 4-chlorobenzaldehyde in the presence of piperidine acetate and an excess of piperidine gave 2-(4-bromophenyl)-5-(4-chlorophenyl)-3-(2-hydroxyphenyl)-4-(piperidinocarbonyl)pyrazole, but the reaction of phenyl- and 4-(2-chlorophenylhydrazino)coumarins with 4-chlorobenzaldehyde gave 1-aryl-5-(4-chlorophenyl)-3-(2-hydroxyphenyl)-4-(1-piperidino)carbonyl-4,5-dihydropyrazoles.     

Ensembles of rings with a coumarin unit 1. Synthesis of 3-(2-R-thiazol-4-yl)-and 3-(4-R-thiazol-2-yl)coumarins

We have synthesized 3-(2-R-thiazol-4-yl)coumarins (R=H, CH₃, CH₂CN, Ar) by condensation of 3-(-bromoacetyl)coumarins with thioamides. We obtained 3-(4-R-thiazol-2-yl)coumarins (R=H, Ar) by several methods. By reaction of 2-cyanomethyl-4-phenylthiazole with 2-hydroxybenzaldehydes, we synthesized 2-imino-3-(4-phenylthiazol-2-yl)coumarins, which were converted to the corresponding coumarins by acid hydrolysis. For 3-(2-R-thiazol-4-yl)coumarins (R=CH₂CN), we carried out reactions with aromatic aldehydes. We propose alternative methods for synthesis of 2-[2-aryl(hetaryl)-1-cyanoethenyl]-4-(coumarin-3-yl)thiazoles.Ukrainian Pharmaceutical Academy, Kharkov 310002. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1345–1355, October, 1997.     

Synthesis and properties of 4-(3-aminothieno-[2,3-b]pyridin-2-yl)coumarins

Substituted 4-[(3-cyanopyridin-2-yl)thiomethyl]coumarins have been synthesized by the alkylation of 2-mercapto-4,6-dimethylnicotinonitrile with 4-chloromethylcoumarins. Substituted 4-(3-amino-thieno[2,3-b]pyridin-2-yl)coumarins have been obtained by a subsequent intramolecular condensation of the methylene and cyano groups. 6H-Chromeno[4,3-d]thieno[3,2-b:5,4-b']dipyridin-6-ones were isolated as a result of the interaction of these compounds with aldehydes, and their aminomethyl derivatives were synthesized.     

3-(2-Pyridyl)coumarins

3-(2-Pyridyl)coumarins were prepared by reaction of substituted salicylaldehydes and 2-pyridylacetonitrile. Benzylation, acylation, and aminomethylation of 7-hydroxy-3-(2-pyridyl)coumarin was studied. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 428–431, September–October, 2005.     

3-(2-Quinolyl)- and 3-(5-carbethoxyfuryl-2)coumarins

3-(2-Quinolyl)- and 3-(5-carbethoxyfuryl-2)coumarins were prepared by reaction of substituted salicylaldehydes and hetarylacetonitriles. Alkylation and acylation of 3-hetaryl-7-hydroxycoumarins were studied. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 432–434, September–October, 2005.     

Synthesis,luminescence, and spectral characteristics of 7-diethylamino-3-(2-arylethenyl)coumarins

By condensation of 7-diethylamino-3-formylcoumarin with aromatic compounds containing an active methyl or methylene group, a number of previously unreported 7-diethylamino-3-(2-arylethenyl)coumarins have been obtained. The reaction conditions depend on the activity of the methyl (or methylene) component. The spectral and luminescent properties of the synthesized compounds have been investigated.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, 1171–1175, September, 1992.     

Photocyclisation of 3-alkoxy-6-chloro-2-(3-methylthiophen-2-yl)-4H-chromen-4-ones

Photocyclisation of 3-alkoxy-6-chloro-2-(3-methylthiophen-2-yl)-4H-chromen-4-ones in methanol with pyrex filtered UV-light lead to the formation of tetracyclic compounds through intramolecular γ-hydrogen abstraction. The methyl group on the thiophenyl ring does not interfere in the photocyclisation although it does effect the product formation.     

Synthesis of 4-(2-hydroxymethylaryl)coumarins

New 4-(2-hydroxymethylaryl)coumarins were prepared using the Suzuki—Miyaura cross-coupling at the key step. According to X-ray diffraction data, the compounds obtained are structural analogs of the natural stilbene combretastatin A-4, which exhibits potent antitumor activity.     

Microwave promoted one-pot synthesis of 3-(2''-amino-3''-cyano-4''-arylpyrid-6''-yl) coumarins

A facile procedure for the synthesis of 3-(2'-amino-3'-cyano-4'-arylpyrid-6'-yl) coumarins are being reported starting from 3-acetylcoumarin, aromatic aldehydes and malononitrile. The reactions were carded out on microwave irradiation in good yield with short time and easy work-up. The structures of all the compounds have been confirmed on the basis of their analytical, IR,1H NMR,and mass spectral data.     

An Efficient One-Pot Synthesis of 3-(2-Benzothiazolyl)coumarins

Some 3-(2-benzothiazolyl)coumarin imines and 3-(2-benzothiazolyl)coumarins are prepared from 2-benzothiazolylacetonitrile and 2-hydroxybenzaldehydes in ethanol in the presence of catalytic amount of NaOH.     

Synthesis and spectral-luminescence properties of 7-diethylamino-4-(2-arylethenyl)coumarins

A number of 7-diethylamino-4-(2-arylethenyl)coumarins were obtained by condensation of 7-diethylamino-4-methylcoumarin with aromatic aldehydes, while only a product of addition to the carbon—nitrogen double bond is formed with benzalaniline. The spectral-luminescence properties of the compounds obtained were investigated.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 319–322, March, 1991.     

Synthesis of 4-(thien-2-yl)-substituted coumarins through Lewis acid catalyzed Michael addition of thiophenes to 3-benzoylcoumarins followed by oxidation

3-Benzoyl-4-(thien-2-yl)coumarins have been obtained in good yields according to the S_N^H addition–oxidation protocol, involving the diastereoselective addition of thiophenes at C-4 of 3-benzoylcoumarins under BBr₃ catalysis, followed by oxidation of the intermediate 3,4-trans-3-benzoyl-4-(thien-2-yl)-3,4-dihydrocoumarins with DDQ. This two-step procedure can be regarded as nucleophilic substitution of hydrogen (S_N^H) on the heterocyclic ring of coumarins.     

Condition-controlled selective synthesis of coumarins and flavones from 3-(2-hydroxyphenyl)propiolates and iodine

2H-Chromen-2-ones (coumarins) and 4H-chromen-4-ones (flavones) were selectively prepared via the reaction of 3-(2-hydroxyphenyl)propiolates with iodine in toluene and N,N-dimethylformide, respectively.     

Synthesis,characterization and antibacterial activity of 1-([6-bromo-2-hydroxy-naphthalen-1-yl]arylphenyl)methyl)-3-chloro-4-(arylphenyl)-azetidin-2-one

One-pot synthesis of 1-([6-bromo-2-hydroxy-naphthalen-1-yl]-aryl-phenyl)methyl)-3-chloro-4-(aryl-phenyl)azetidin-2-ones has been reported in the present research work via Staudinger [2 + 2] ketene-imine cycloaddition reaction pathway. The reaction of 1-((Benzylideneamino)(aryl)methyl)-6-bromo-naphthalen-2-ols with chloroacetic acid and triethylamine afforded 1-([6-bromo-2-hydroxynaphthalen-1-yl]aryl-phenyl)methyl)-3-chloro-4-(aryl-phenyl)azetidin-2-ones. For the structural elucidation of series of compounds, different analytical and spectroscopic techniques such as elemental analysis, IR spectra, ¹H-NMR spectra and mass spectra were used. All the newly synthesized compounds were tested for their anti-bacterial activity studies. It revealed that some of the compounds possesses moderate to good activities as compared to standard drugs. The widest spectrum of anti-bacterial activities against both gram-positive and gram-negative bacterial strains among the examined compounds possessed having more hydroxyl group along with β-lactam ring compared to other substituted azetidinones.     

Synthesis of halosulfuron-methyl via selective chlorination at 3- and/or 5-position of pyrazole-4-carboxylates

Reactions of methyl pyrazole-4-carboxylates 4b-d with N-chlorosuccinimide under heating conditions without a solvent gave methyl 3,5-dichloro-1-methylpyrazole-4-carboxylate 4a in good yields. The reaction of 4a with sodium hydrosulfide led to a nucleophilic substitution on the 5-position regioselectively to afford methyl 3-chloro-1-methyl-5-mercaptopyrazole-4-carboxylate 6a, which was followed by oxidative chlorination and amination to obtain 3-chloro-1-methyl-5-sulfamoylpyrazole-4-carboxylate 2a. Finally, the reaction of 2a with phenyl 4,6-dimethoxypyrimidin-2-yl carbamate 7 provided methyl 3-chloro-5-(4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoyl)-1-methylpyrazole-4-carboxylate (halosulfuron-methyl) 1a promising herbicide in com.     

2-Polyfluoroalkylchromones. 14. Synthesis of 4-chloro-3(5)-(2-hydroxyaryl)-5(3)-polyfluoroalkylpyrazoles

3-Chloro-2-polyfluoroalkyl- and 3-chloro-6-nitro-2-polyfluoroalkylchromones were synthesized. These compounds react with N₂H₄·2HCl on boiling in ethanol to form 4-chloro-3(5)-(2-hydroxyaryl)-5(3)-polyfluoroalkylpyrazoles.     

Condensation of methyl 2-chloro-3-(3-nitrophenyl)-2,3-epoxypropionate with 1,2-phenylene diamine

It is established that the -chloroepoxide methyl 2-chloro-3-(3-nitrophenyl)-2, 3-epoxypropionate, in contrast to its a-chloroketone isomer methyl 3-(3-nitrophenyl-3-chloro-2-oxopropionate, forms 2-(3-nitrophenyl-3methoxycarbonylquinoxaline in reaction with 1,2-phenylene diamine, whereas the condensation of the achloroketone with 1,2 phenylene diamine gives 3-(-chloro-3-nitrophenyl)-2-oxo-1,2-dihydroquinoxaline.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1105-1108, August, 1994.     

Co-crystal structure of mixed molecules of methyl 2-(3-chloro-4-methyl-2-oxo-2H-chromen-7-yloxy)acetate and 2-(2-aminophenyl)benzothiazole

A co-crystal is obtained in a methanolic solution from methyl 2-(3-chloro-4-methyl-2-oxo-2H-chromen-7-yloxy)acetate and 2-(2-aminophenyl)benzothiazole. In the crystal these molecules are connected via usual N-H…O and weak C-H…O H-bonds. The co-crystals are very stable.     

Synthesis and reactivity of 3-(2-chloroalkyl)-2,2-dihaloaziridines

3-(2-Chloroalkyl)-2,2-dihaloaziridines were synthesized via cycloaddition of dihalocarbenes to the CN double bond of β-chloroimines. Under the action of Lewis acids or HCl, N-C³ bond cleavage occurred, giving rise to N-substituted 2,4-dichloro-3,3-dimethylbutanamides, which were further converted to 3-chloropyrrolidin-2-ones under alkaline conditions. When 2,2-dichloro-3-(2-chloro-1,1-dimethylethyl)-1-phenylaziridine was reacted with sodium methoxide, aziridine ring opening with N-C² bond cleavage took place, leading to methyl 4-chloro-3,3-dimethyl-2-(phenylamino)butanoate.     

Chemistry of 3-hetarylcoumarins. 2. 3-(2-thiazolyl)coumarins

3-(2-Thiazolyl)coumarins were obtained by the reaction of substituted salicylaldehydes with 2-thiazolylacetonitriles. Methylation, acylation, and aminomethylation were studied for the 7-hydroxy-substituted products.For Communication 1, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1632–1644, November, 2004.