Microwave assisted synthesis of novel imidazo [2,1-b]thiazole derivative attached to quinoxalinones

3-(6-Phenylimidazo[2,1-b]thiazol-5-yl)quinoxalin-2(1H)-ones (qunoxalinone) (6a-q) have been synthesized by the reaction of ethyl 2-oxo-2-(6-phenylimidazo[2,1-b]thiazol-5-yl)acetates (4a-e) with suitably substituted o-phenylenediamines (5a-f) under microwave heating. The ethyl 2-oxo-2-(6-phenylimidazo[2,1-b]thiazol-5-yl)acetates (4a-e) were prepared by the reaction of 6-phenylimidazo[2,1-b]thiazoles (3a-e) with ethyl chlorooxoacetate in refluxing 1,4-dioxane whereas the thiazoles (3a-e) were synthesized by the reaction of 2-bromo-1-phenylethanones (2a-e) with thiazol-2-amine in refluxing acetone.     

Efficient stepwise and one pot three-component synthesis of 2-amino-4-(2-oxo-2H-chromen-3-yl)thiophene-3-carbonitriles

Environmentally benign conditions have been developed for the synthesis of 2-amino-4-(2-oxo-2H-chromen-3-yl)thiophene-3-carbonitriles (3) starting from 3-acetyl-2H-chromen-2-one (1) through the intermediacy of 2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)malononitrile (2) using the Knoevenagel condensation followed by the Gewald reaction. Alternatively, 3 could also be prepared in a one pot method by treating equimolar amounts of 1, malononitrile, and elemental sulfur. The merits of this preparation are mild reaction conditions, easy work-up procedure, and good yields.     

Synthesis,structure elucidation and plants growth promoting effects of novel quinolinyl chalcones

The readily synthesized 3-(4-Hydroxy-1-methyl-1,2-dihydro-2-oxoquinolin-3-yl)-1-phenyl-1H-pyrazole-4-carbaldehyd (5) and 3-(2-Oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde (6) were utilized as a convenient starting precursor materials for synthesis of novel enone system 4-hydroxy-1-methyl-3-(4-(2H-2-oxo-chromen-3-yl)prop-2-enoyl)-1-phenyl-1H-pyrazol-4-yl)quinolin-2(1H)-one (7) and4-hydroxy-1-methyl-3-(2E)-3-(3-(2-oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazol-4-yl)acryloyl)quinolin-2(1H)-one (8). Simple homonuclear NOE experiment (NOESY 1D) method was performed for structure elucidation of the novel quinolinyl chalcones. The synthesized compounds have been estimated for their effect of growth on some selective crop of plants (Hibiscus, Mint and Basil).     

Synthesis, reactions and antineoplastic activity of 3-(2-oxo-2H-chromen-3-yl)-2-oxo-2H,5H-pyrano[3,2-c]chromene derivatives

The key 3-(2-oxo-2H-chromen-3-yl)-2-oxo-2H,5H-pyrano[3,2-c]chromen-5-yl acetates 3 were synthesized in high yields by cyclocondensation of 4-oxo-4H-chromen-3-carbaldehydes 1 with coumarin-3-acetic acids 2 under mild conditions. The reaction pathway involves aldol condensation and subsequent intramolecular lactonization to afford 2-oxo-2H,5H-pyrano[3,2-c]chromene skeleton 3. Further treatment of acetates 3 with alcohols, water or nitrogen containing compounds led to 5-alkoxy-, 5-hydroxy- or 5-acylamino-2H,5H-pyrano[3,2-c]chromen-2-ones 4-6 via nucleophilic substitution of acetyloxy group at C-5. Acetates and hydroxyl derivatives 3 and 5 undergo facile rearrangement in an acid medium yielding 5-hydroxypyrano[2,3-b]chromen-2(10aH)-ones 7. Twelve prepared compounds were evaluated on their antineoplastic activities on 60 human tumour cell line panels in NCI USA. The obtained biological results confirmed that 3-(2-oxo-2H-chromen-3-yl)-2H,5H-pyrano[3,2-c]chromen-2-one represents a new leading skeleton suitable for further antitumour activity study.     

Intramolecular amidation: synthesis of novel imidazo[2,1-b][1,3,4]thiadiazole and imidazo[2,1-b][1,3]thiazole fused diazepinones

Novel heterocyclic systems 2-alkyl/aryl-9-(2-hydroxybenzylidene)-7,9-dihydro-8H-[1,3,4]thiadiazolo[2′,3′:2,3]imidazo[4,5-d][1,2]diazepin-8-one and 9-(2-hydroxy-benzylidene)-3,3-dimethyl-3,4,7,9-tetrahydro-2H-11-thia-4b,6,7,10-tetraazaindeno[1,2-a]azulene-1,8-dione are synthesized via an intramolecular amidation reaction. An interesting ring opening and cyclization of 2-alkyl/aryl-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde and 6,6-dimethyl-8-oxo-2-(2-oxo-2H-chromen-3-yl)-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazole-3-carbaldehyde are discussed.     

Microwave-assisted Hantzsch thiazole synthesis of N-phenyl-4-(6-phenylimidazo[2,1-b]thiazol-5-yl)thiazol-2-amines from the reaction of 2-chloro-1-(6-phenylimidazo[2,1-b]thiazol-5-yl)ethanones and thioureas

N-Phenyl-4-(6-phenylimidazo[2,1-b]thiazol-5-yl)thiazol-2-amines (6a-q) have been synthesized by the Hantzsch thiazole reaction of 2-chloro-1-(6-phenylimidazo[2,1-b]thiazol-5-yl)ethanones (4a-e) with suitably substituted thioureas using microwave heating. The ethanones (4a-e) were prepared by the reaction of 6-phenylimidazo[2,1-b]thiazoles (3a-e) with chloroacetylchloride in refluxing 1,4-dioxane whereas the thiazoles (3a-e) were synthesized by the reaction of 2-bromo-1-phenylethanones (2a-e) with thiazol-2-amine in refluxing acetone.     

Novel thiosemicarbazone derivatives containing benzimidazole moiety: Green synthesis and anti-malarial activity

A series of (E)-2-[5-chloro-1-(1H-benzo[d]imidazol-2-yl)ethylidene] N-(substituted) hydrazine carbothioamide (7a–7t) and (E)-2-[1-(1H-benzo[d]imidazol-2-yl)ethylidene] N-(substituted) hydrazine carbothioamide (8a–8t) were prepared via the synthesis of 1-(substituted-1H-benzimidazol-2-yl) ethanol (3a–3b) which was synthesized by the condensation of substituted o-phenylenediamine (2a–2b) with dl-lactic acid (1) followed by oxidation with sodium hypochlorite in mild acidic condition to form the corresponding ketones 4a–4b. Final compounds were formed by condensation of 4a–4b with different thiosemicarbazides 6a–6t. A total of 40 compounds were synthesized and characterized by FT-IR, ¹H NMR, ¹³C NMR, Mass spectral technique and elemental analysis, in addition they were evaluated for anti-malarial properties. Among the compounds tested 7o, 7p, 7q, 7r, 7s, 8e and 8h exhibited good antimalarial activity in vitro.     

An efficient microwave assisted synthesis of novel class of Rhodanine derivatives as potential HIV-1 and JSP-1 inhibitors

(Z)-5-(2-(1H-Indol-3-yl)-2-oxoethylidene)-3-phenyl-2-thioxothiazolidin-4-one (7a-q) derivatives have been synthesized by the condensation reaction of 3-phenyl-2-thioxothiazolidin-4-ones (3a-h) with suitably substituted 2-(1H-indol-3-yl)-2-oxoacetaldehyde (6a-d) under microwave condition. The thioxothiazolidine-4-ones were prepared from the corresponding aromatic amines (1a-e) and di-(carboxymethyl)-trithiocarbonyl (2). The aldehydes (6a-h) were synthesized from the corresponding acid chlorides (5a-d) using HSnBu₃.     

Chemoenzymatic synthesis of both enantiomers of 3-hydroxy-2,3-dihydro-4H-chromen-4-one

4-Oxo-3,4-dihydro-2-chromen-3-yl acetate is synthesized using manganese(III)acetate starting from 2,3-dihydro-4H-chromen-4-one. K₂CO₃ mediated hydrolysis of 4-oxo-3,4-dihdro-2-chromen-3-yl acetate furnished 3-hydroxy-2,3-dihydro-4H-chromen-4-one in high yield.The enantioselective hydrolysis of (±)-4-oxo-3,4-dihydro-2-chromen-3-yl acetate in various organic solvent-phosphate buffer (pH7) systems and enantioselective transesterification of (±)-3-hydroxy-2,3-dihydro-4H-chromen-4-one in organic solvents was investigated by screening a range of lipases. The lipase Amano PS, PPL, PLE and CCL-catalyzed asymmetric ester hydrolysis and transesterification afforded the enantiomers of 3-hydroxy-2,3-dihydro-4H-chromen-4-one and 4-oxo-3,4-dihydro-2-chromen-3-yl acetate with high enantiomeric excess (up to 97% ee) and in good yields.     

Synthesis of Some New Thiazoles and Pyrazolo[1,5-a]pyrimidines Containing an Antipyrine Moiety

Ethyl 2-{2-[4-(2,3-dimethyl-5-oxo-1-phenyl-3-(pyrazolin-4-yl)]-2-cyano-1-(phenylamino)vinylthio}-acetate, 2-[4-(2,3-dimethyl-5-oxo-1-phenyl-(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]2-(4-oxo-3-phenyl-(1,3-thiazoilidin-2-ylidene))ethanenitrile, 2-[4-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]-2-(4-methyl-3-phenyl(1,3-thiazolin-2-ylidene))ethanenitrile, 2-(5-acetyl-4-methyl-3-phenyl(1,3-thiazolin-2-ylidene))-2-[4-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]ethanenitrile, and ethyl 2-(cyano(4-(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)thiazol-2-yl)methylene)-2,3-dihydro-4-methyl-3-phenylthiazole-5-carboxylate were synthesized by treatment of 2-(4-(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)thiazol-2-yl)-3-mercapto-3-(phenylamino)-acrylonitrile with appropriate halo ketones or halo esters. Also, 4-{2-[5,7-dimethyl-2-(phenylamino)(7a-hydropyrazolo[1,5-a]pyrimidin-3-yl](1,-thiazol-4-yl)}-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one derivatives were synthesized via reaction of 4-{2-[5-amino-3-(phenylamino)pyrazolin-4-yl](1,3-thiazol-2-yl)}-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one with β-diketone or β-keto ester. All synthesized compound were established by elemental analysis, spectral data, and alternative synthesis whenever possible.     

An efficient synthesis of 4-substituted coumarin derivatives via a palladium-catalyzed Suzuki cross-coupling reaction

An efficient Pd-catalyzed Suzuki cross-coupling reaction of sterically crowded 4-chlorocoumarin derivatives with air- and moisture-stable potassium organotrifluoroborates is developed. This methodology has been used to generate a series of novel alkyl, aryl, and vinyl substituted coumarin derivatives in good to excellent yields. The twisted conformation of the vinyl groups in the X-ray crystal structures of (2-oxo-4-vinyl-2H-chromen-3-yl)methyl acetate (2) and (2-oxo-4-vinyl-2H-chromen-3-yl)methyl 2,2,2-trichloroacetimidate (3), along with the atropisomerism of 3-(hydroxymethyl)-4-(2-methoxyphenyl)-2H-chromen-2-one (1d), are evidence of the steric crowding in these adducts.     

Synthesis and Spectral Characterization of Some New 4-(2,6-Diarylpyridin-4-yl)-2H-chromen-2-ones

Some new 4-(2,6-diarylpyridin-4-yl)-2H-chromen-2-one derivatives 5a–l have been synthesized by reacting 4-(3-oxo-3-arylprop-1-enyl)-2H-chromen-2-ones 3a–c with appropriate 1-(2-oxo-2-arylethyl)pyridinium bromide salt 4a–d in the presence of ammonium acetate in refluxing glacial acetic acid. The newly synthesized compounds have been characterized by elemental and spectral analysis.     

Synthesis and antioxidant evaluation of some new 2-benzoylamino-5-hetaryl-1,3,4-oxadiazoles

A series of new functionalized 2-benzoylamino-5-hetaryl-1,3,4-oxadiazoles were efficiently synthesized via the reaction of the versatile key intermediates, 2-benzoylamino-5-cyanomethyl-1,3,4-oxadiazole (1) and N-(5-(5-amino-3-phenylamino)-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)-benzamide (13), with some appropriate electrophilic reagents. The structures of the newly synthesized compounds were established on the basis of elemental analyses, spectral data, and by alternative synthesis wherever possible. The mechanisms of the studied reactions are discussed. Also, we evaluate the antioxidant activity of some representative examples of the newly prepared compounds. Among the synthesized compounds, 2-benzoylamino-5-cyanomethyl-1,3,4-oxadiazole (1) and N-(5-(7-methyl-5-oxo-2-(phenylamino)-4,5-dihydropyrazolo[1,5-a]pyrimidin-3-yl)-1,3,4-oxadiazol-2-yl)benzamide (17) showed excellent antioxidant activity and exhibited high protection against DNA damage induced by the Bleomycin iron complex.     

Synthesis of arylated highly congested indans using a domino sequence

A novel and efficient regioselective synthesis of various arylated highly congested 7-aryl-5-methylsulfanylindan-4-carbonitriles (3a-f), methyl 7-aryl-5-methylsulfanylindan-4-carboxylates (10a-e) and 7-aryl-5-methylsulfanylindan-4-carboxylic acids (11a-e) through base-catalyzed reaction of 6-aryl-4-methylsulfanyl-2-oxo-2H-pyran-3-carbonitriles (1a-f) and methyl 6-aryl-4-methylsulfanyl-2-oxo-2H-pyran-3-carboxylates (9a-e) by cyclopentanone (2) has been delineated. The synthetic potential of 2-pyranone was explored further to generate molecular diversity using 6-aryl-4-sec-amino-2-oxo-2H-pyran-3-carbonitriles (7a-h), 5,6-diaryl-4-methylsulfanyl-2-oxo-2H-pyran-3-carbonitriles (5a,b) and methyl 5,6-diaryl-4-methylsulfanyl-2-oxo-2H-pyran-3-carboxylates (12a,b) as precursors for the ring transformation by cyclopentanone to assess the effects of substituents on the course of the reaction to obtain highly congested indans, 6,7-diaryl-5-methylsulfanylindan-4-carbonitriles (6a,b), 7-aryl-5-(piperidin-1-yl)indan-4-carbonitriles (8a-h) and methyl 6,7-diaryl-5-methylsulfanylindan-4-carboxylates (13a,b).     

Transformations of enaminones. A simple one-pot synthesis of imidazolone derivatives

Ethyl (5-benzoyl-2-oxo-3-substituted-2,3-dihydro-1H-imidazol-1-yl)carbamates 7 were prepared by the Michael addition of diethyl azodicarboxylate (3) to (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one (2) followed by substitution of the dimethylamino group with primary amines 5a–n to afford a mixture of (E) and (Z) diethyl 1-(1-(substituted)amino)-3-oxo-3-phenylprop-1-en-2-yl)hydrazine-1,2-dicarboxylates (6a–n), followed by cyclization to give final products 7a–n. The intermediate 6i was isolated and characterized and transformed into 7i. All imidazolones 7a–n were synthesized in one pot reaction sequences with individual reactions being very clean.     

Synthesis and characterization of new thiazolidinones containing coumarin moieties and their antibacterial and antioxidant activities

New coumarin derivatives, namely (2-(4-methyl-2-oxo-2H-chromen-7-yloxy)-N-(4-oxo-2-phenylthiazolidin-3-yl)acetamide, N-(2-(3-methoxyphenyl)-4-oxothiazolidin-3-yl)-2-(4-methyl-2-oxo-2H-chromen-7-yloxy)acetamide, 2-(4-methyl-2-oxo-2H-chromen-7-yloxy)-N-(4-oxo-2-(2,3,4trimethoxyphenyl)thiazolidin-3-yl)acetamide and N-(2-(4-bromophenyl)-4-oxothiazolidin-3-yl)-2-(4-methyl-2-oxo-2H-chromen-7-yloxy)acetamide) were synthesized starting from 4-methyl-7-hydroxycoumarin. The structures of the obtained compounds were confirmed by analytical IR and NMR spectra to elucidate the different positions of protons and carbons and as well as theoretical studies (DFT/B3LYP). The new compounds were screened for antibacterial activity. Most of them are more active against E. coli S. aureus and B. subtilis than standard references.     

Five-membered 2,3-dioxoheterocycles: XCVI. Reactions of 3-aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5h)-triones with substituted 1,3,3-trimethyl-2-azaspiro[4.5]dec-1-enes

3-Aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones react with 1,3,3,7,9-pentamethyl-2-azaspiro-[4.5] deca-1,6,9-trien-8-one and 2′,5′,5′-trimethyl-4′,5′-dihydro-4H-spiro[naphthalene-1,3′-pyrrol]-4-one providing 3-aroyl-2-hydroxy-3a-{(3,3,7,9-tetramethyl-8-oxo-2-azaspiro[4.5]deca-1,6,9-trien-1-yl)methyl}pyrrolo[1,2-a-quinoxaline-1,4(3a H,5H)-diones and 3-aroyl-2-hydroxy-3a-{(5′,5′-dimethyl-4-oxo-4′,5′-dihydro-4H-spiro[naphthalene-1,3′-pyrrol]-2′-yl)methyl}pyrrolo[1,2-a]-quinoxaline-1,4(3aH,5H)-diones.     

Five-membered 2,3-dioxo heterocycles: LXXIV. Recyclization of 3-aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones by the action of benzohydrazides. Crystalline and molecular structure of N-[2,4-dihydroxy-5-oxo-3-(3-oxo-3,4-dihydroquinoxalin-2-yl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]benzamide

Recyclization of 3-aroyl-1H-pyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones by the action of benzoic acid hydrazides gave N-[2,4-dihydroxy-5-oxo-3-(3-oxo-3,4-dihydroquinoxalin-2-yl)-2-aryl-2,5-dihydro-1H-pyrrol-1-yl]benzamides whose structure was proved by X-ray analysis.     

Microwave-assisted synthesis of novel bis(2-thioxothiazolidin-4-one) derivatives as potential GSK-3 inhibitors

(5Z,5′Z)-3,3′-(1,4-Phenylenebis(methylene)-bis-(5-arylidene-2-thioxothiazolidin-4-one) derivatives (5a-r) have been synthesized by the condensation reaction of 3,3′-(1,4- or 1,3-phenylenebis(methylene))bis(2-thioxothiazolidin-4-ones) (3a,b) with suitably substituted aldehydes (4a-f) or 2-(1H-indol-3-yl)2-oxoacetaldehydes (8a-c) under microwave conditions. The bis(2-thioxothiazolidin-4-ones) were prepared from the corresponding primary alkyl amines (1a,b) and di-(carboxymethyl)-trithiocarbonyl (2). The 2-(1H-indol-3-yl)-2-oxoacetaldehydes (8a-c) were synthesized from the corresponding acid chlorides (7a-c) using HSnBu₃.     

Reaction of 4-hydroxycoumarin with arylglyoxals and ureas

One-pot condensation of 4-hydroxycoumarin with arylglyoxals and ureas gave 4-aryl-5-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1H-imidazol-2(3H)-ones. The same compounds may be obtained from aroylbis(4-hydroxy-2-oxo-2H-chromen-3-yl)methanes and urea. The reaction of 4-bromobenzaldehyde with 4-hydroxycoumarin in the presence of urea led to the formation of the corresponding Michael adduct without participation of urea.