Facile syntheses of oxazolines and thiazolines with N-acylbenzotriazoles under microwave irradiation

Microwave reactions of 2-amino-2-methyl-1-propanol (2) or 2-aminoethanethiol hydrochloride (4) with readily available N-acylbenzotriazoles 1a-j in the presence of SOCl(2) produced 2-substituted 2-oxazolines 3a-j in 84-98% yields and 2-substituted thiazolines 5a-i in 85-97% yields, respectively. With use of this method chiral oxazoline 6, bisoxazoline 7, bisthiazoline 8, and 5,6-dihydro-4H-1,3-oxazines 9 or 10 have also been prepared in 82-96% yields. These results demonstrate a new application of N-acylbenzotriazoles in the preparation of oxazolines and thiazolines under mild conditions and short reaction times with microwave irradiation.     

含1-[二-(4-氟苯)甲基]哌嗪均三氮唑环的Mannich碱的合成及表征

微波辐射下,在冰醋酸中,3-甲基-4-氨基-1,2,4-三氮唑-5-硫酮1与芳香醛经微波辐射制得相应的中间体Schiff碱2(a~j),然后中间体2与1-[二-(4-氟苯)甲基]哌嗪于室温反应制得10个新的Mannich碱3(a~j).合成的10个目标化合物通过熔点测定和质谱、红外光谱、核磁共振氢谱分析、元素分析对其结构进行确证。     

Synthesis and antimicrobial study of linked heterocyclics containing Pyrazole-pyrimidine-thiazolidin-4-one

A new series of linked heterocyclics, 3-[4-(4-chlorophenyl)-6-(3,5-dimethyl-1-phenyl-1H-4-pyrazolyl)-2-pyrimidinyl]-2-(aryl/heteryl)-1,3-thiazolan-4-ones (6a-j), has been synthesized by the one-pot cyclo-condensation of 4-(4-chlorophenyl)-6-(3,5-dimethyl-1-phenyl-1H-4-pyrazolyl)-2-pyrimidinamine (5), aryl/heteroaryl aldehyde and thioglycolic acid. The structures of the synthesized compounds have been confirmed via IR, (1)H-NMR, (13)C-NMR, MS and elemental analyses. Further, all the newly synthesized compounds 6a-j have been assayed for their antimicrobial activity against Gram-positive and Gram-negative bacteria and fungi. The compounds containing moieties like 4-nitrophenyl (6c), 3-nitrophenyl (6d), 4-dimethylaminophenyl (6g), 2-furyl (6i) and 1,3-benzodioxole (6j), at 2-position of thiazolidin-4-one ring exhibited good inhibitory activity against all the tested organisms.     

Brφnsted acidic ionic liquid catalyzed highly efficient synthesis of chromeno pyrimidinone derivatives and their antimicrobial activity

A series of 8,9-dihydro-2-(2-oxo-2H-chromen-3-yl)-5-aryl-3/f-chromeno[2,3-(flpyrimidine-4,6(5ff,7//)-diones(5a-j) have been synthesized by the reaction of 2-amino-5,6,7,8-tetrahydro-5-oxo-4-aryl-4#-chromene-3-carbonitrile(4a-j) with couma-rin -3-catboxylic acid under neat conditions employing Br0nsted acidic ionic liquid(4-sulfobutyl)tris(4-sulfophenyl)phosphonium hydrogen sulfate as catalyst.Structures of all the compounds were established on the basis of analytical and spectroscopic data.All the compounds were evaluated for their in vitro antimicrobial activity against different bacterial and fungal strains.     

Synthesis and Fungicidal Activities of 2-Alkylthio-5-(3,4,5-tribenzyloxyphenyl)-l, 3,4-oxadiazoles

Ten novel 2-alkylthio-5-(3, 4, 5-tribenzyloxyphenyl)-1, 3, 4-oxadiazole derivatives (5a-j) were synthesized from methyl 3, 4, 5-trihydroxybenzoate by etherification, hydrazidation, cyclization and thioetherification reactions. The structures of 5a-j were confirmed by 1HNMR, MS spectra and elemental analysis. The results indicated that most of the compounds 5 exhibited good fungicidal activities. The activity of 5h is higher than 90% against Fusarium oxysporum and Botrytis cinereapers in 50 mg/L.     

Diels-Alder reactions of 4-triflyloxy-2,6,6-trimethyl-2,4-cyclohexadienone. An expedient methodology for the synthesis of bicyclo[2.2.2]oct-5-en-2-ones and bicyclo[2.2.2]octa-5,7-dien-2-ones

The synthesis of 4-triflyloxy-2,6,6-trimethyl-2,4-cyclohexadienone (13), bicyclo[2.2.2]octenones 1a-j and 15a-j, and bicyclo[2.2.2]octadienones 2a-f, 6a-d, and 11a-f is described. The 2,4-cyclohexadienones 4 and 13 were used for the first time as nondimerizing and easily accessible alternatives to 2,6,6-trimethyl-2,4-cyclohexadienone 12 in Diels-Alder reactions with acetylene derivatives 5a-d to prepare the adducts 6a-d and 11a-e in excellent yields. Compounds 11a-d were initially prepared by the alcoholysis of 6a-d to afford bicyclo[2.2.2]octene-2,5-diones 7a-dfollowed by treatment of 7a-d with N-phenyltriflimide in the presence of LHMDS at -78 degrees C. Diels-Alder reaction of 13 with an acetylene equivalent, phenyl vinyl sulfoxide, was also studied. A detailed study of the Diels-Alder reactions of various olefinic dienophiles 14a-j with 13 has been carried out to furnish cycloadducts 15a-j in high yields. Reductive removal of triflyloxy group of vinyl triflates 11a-f and 15a-j was performed in the presence of [Pd(PPh(3))(2)Cl(2)-Bu(3)N-HCO(2)H] to obtain the desired bicyclo[2.2.2]octadienones 2a-f and bicyclo[2.2.2]octenones 1a-j, respectively, in good overall yields.     

Synthesis and biological activities of nitro-hydroxy-phenylquinolines; validation of antibiotics effect over DNA gyrase inhibition and antimicrobial activity

A family of 11 nitrophenol 2-nitro-5-(4-substituted phenylquinolin-2-yl)phenol derivatives (4, 4a-j) was effectively synthesized as antimicrobial medications. A mixture of the substituted 3-hydroxy-4-nitrobenzaldehyde substituted aromatic amine and substituted phenylacetylenes were used to synthesis the title compounds 4, 4a-j. Antimicrobialactivity potential of 4, 4a-j was evaluated against Streptococcus pyogenes (MTCC 442), Staphylococcus aureus (MTCC 96), Pseudomonas aeruginosa (MTCC 424), and Escherichia coli (MTCC 443). DNA gyrase inhibition studies carried out to understand the mechanism ofaction of the antimicrobial effect of target compounds. HRBC membrane stabilization (in vitro) property was also assessed as a representative human cellular cytotoxic effect of 4, 4a-j since HRBC alike lysosomal cells and the lysozyme activity leads to inflammation and its adverse effects in cellular systems. Results reveal that compounds 4c and 4h have remarkable antibacterial activity and screened for further preclinical studies.     

Synthesis of a new series of N-substituted-3-[l-alkyl(aryl)- 4-piperidyl]azetidin-2-ones as possible muscarinic agents

A new series of N-substituted-3-[1-alkyl(aryl)-4-piperidyl]azetidin-2-ones 2a-j structurally related to the previously reported 2,7-diazaspiro[3.5]nonan-1-ones 1 have been synthesized and tested for their activity as muscarinic agents, both in vitro and in vivo. Preliminary pharmacological results showed that compounds 2 are devoid of significant cholinergic properties.     

Synthesis, anti-bacterial and anti-oxidant properties of thiadiazaphosphol-2-ones

4-Amino-5-phenyl-4H-1,2,4-triazole-3-thiol (1) underwent facile condensation with various phosphorus dichlorides (2a-j) in the presence of triethylamine in dry tetrahydrofuran at 60-65 degrees C and afforded corresponding thiadiazaphosphol-2-ones (3a-j). Their chemical structures were characterized using IR, (1)H-, (13)C-, (31)P-NMR and Mass spectral studies. All the title compounds were screened for antioxidant properties by radical scavenging methods such as 1,1-diphenyl-2-picryl hydrazyl (DPPH), hydroxyl and lipid peroxidation. They exhibited potent in vitro antioxidant activity dose dependently. Their bioassay showed them to possess significant antibacterial activity.     

Synthesis and antiproliferative activities of 5-azacytidine analogues in human leukemia cells

Twenty-six 5-azacytidine analogues have been synthesized, including 4-amino- 6-alkyl-1-pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 1a-j, 6-amino-4-alkyl/aryl-1- pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 2a-f and 4-amino-6-alkyl-1,3,5-triazin-2- yl-1-thio-pyranosides/ribofuranosides 3a-j. The antiproliferative activities of these synthetic analogues were investigated in human leukemia HL-60 cells. Ribofuranosyl S-nucleoside 3a, a bioisostere of 5-azacytidine, had a similar antiproliferative ability as that of the latter. Introduction of a methyl at the 6 position of 5-azacytidine and/or replacement of the ribofuranosyl moiety with pyranosyl sugars or disaccharides significantly decreased the antiproliferative activities of the 5-azacytidine derivatives. Several compounds with the replacement of pyranosyl sugars enhanced all-trans retinoic acid-induced differentiation ability in human leukemia HL-60 cells.     

Synthesis and antimicrobial agents of thiazolidinone derivatives from benzocyclohepetenone

A series of benzosuberone coupled piperazin-1-yl thiazolidin-4-one derivatives 6a-j were synthesized from 3-(2-[9-chloro-2,3-dimethyl-6,7-dihydro-5H-benzo[7]annulen-8-yl]-4-oxothiazolidin-3-yl)propanoic acid ( 4 ) and substituted piperazines/secondary amines 5a-j using 1-hydroxy benzotriazole, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and triethyl amine in good yields and their structures were characterized by ¹H NMR, ¹³C NMR, IR, and Mass spectra. The newly synthesized compounds were evaluated for their antimicrobial activity against bacterial strains and a fungal strain. Compounds 6f and 6g were indicated promising and broad spectrum antibacterial activity.     

Unprecedented catalytic asymmetric reduction of N-H imines

[Reaction: see text] Addition of lithium bis(trimethylsilyl)amide to perfluorinated ketones 1a-j affords (E)-N-TMS-ketimines 2a-j that are reduced in situ to afford racemic perfluoromethylated amine hydrochloride salts 3a-j in 54-97% yields. Solvolysis of the N-Si bond in MeOH leads to formation of bench-stable, isolable N-H imine Z/E isomer mixtures along with a methanol adduct. Enantioselective reduction of these three-component mixtures provides the first catalytic asymmetric synthesis of trifluoromethylated amines in 72-95% yields and 75-98% ee.     

Highly functionalized and stereocontrolled syntheses of 2-(2-methylenecycloalkyl)-furan derivatives by Pd-catalyzed cycloreduction

[structure: see text]. We have discovered a new method employing Pd-catalyzed cycloreduction of conjugated enynals 1 bearing an alkyne unit leading to the corresponding 2-(2-methylenecycloalkyl)-furans 2a-j and a related compound 7 in good to excellent yields.     

New Cantharidinimides from Cantharidin and 2-Arylethylamines: Efficient Synthesis under High Pressure

The new cantharidinimides 3a-j were prepared, in good to excellent yield, by heating the reactents 1 and 2a-j to 200 °C with toluene and triethylamine in a high pressure tube. The mixture was evaporated to dryness and furthermore heated to 180 °C-200 °C for 1 h.     

Analogs of alicyclic alpha-amino acids--effect of ring size and side chain on tumor accumulation

We studied the tumor-localizing characteristics of alicyclic alpha-amino acid analogs (a-j) without alpha-hydrogen, because of the selective affinity of synthetic nonmetabolizing amino acids such as 1-aminocyclopentanecarboxylic acid (ACPC) and alpha-aminoisobutyric acid alpha-AIB) to tumor tissues. Ten different alicyclic alpha-amino acids (a-j) were labeled with 14C using a modified Bücherer synthesis for amino acids. The tissue distributions and whole-body autoradiographic study of these 14C-labeled alicyclic alpha-amino acid analogs (a-j) were investigated in mice bearing Ehrlich tumor. These results showed that the tumor uptakes and tumor to tissue concentration ratios increased with decreasing ringsize in homologous series (8- through 4-membered ring systems) and alicyclic alpha-amino acid analogs containing 3- or 4-methyl group had the higher tumor to tissue concentration ratios. On the other hand, alicyclic alpha-amino acid analogs containing 2-methyl group and 4-phenyl group showed the lower tumor uptakes and the lower tumor to tissue concentration ratios. These results suggest that the small ringsize alicyclic alpha-amino acid analogs containing 3-methyl group such as 3-methyl-1-aminocyclopentanecarboxylic acid (3-MeACPC) may be effective for the early detection of tumors.     

A general and efficient synthesis of sulfonylbenzotriazoles from N-chlorobenzotriazole and sulfinic acid salts

One-pot reactions of sulfinic acid salts (produced from organometallic reagents with SO2) with N-chlorobenzotriazole gave the corresponding N-alkane-, N-arene-, and N-heteroenesulfonylbenzotriazoles 3a-j in 41-93% yields. Reagents 3a-j are efficient sulfonylating agents, reacting at 20-80 degrees C with various primary and secondary aliphatic amines to yield the corresponding sulfonamides in 64-100% yields.     

Enantioselective Baeyer-Villiger oxidation catalyzed by palladium(II) complexes with chiral P,N-ligands

Asymmetric Baeyer-Villiger reaction of symmetrical cyclobutanones 1a-j with urea-hydrogen peroxide (UHP) can be catalyzed by a complex of Pd(II) and the new terpene-derived P, N-ligand 7. The resulting lactones 2a-j were obtained in high yields and with good enantioselectivity (< or =81% ee).     

Electrochemically promoted C-N bond formation from amines and CO2 in ionic liquid BMIm-BF4: Synthesis of carbamates

A new electrochemical procedure for the synthesis of organic carbamates from amines and carbon dioxide has been developed using selective cathodic reduction of carbon dioxide in CO2-saturated room-temperature ionic liquid BMIm-BF4 solutions containing amines 1a-j, followed by addition of EtI as an alkylating agent. The synthesis was carried out under mild (PCO2 = 1.0 atm, t = 55 degrees C) and safe conditions, and the use of volatile and toxic solvents and catalysts (according to the growing demand for ecofriendly synthetic methodologies), as well as of any supporting electrolyte (for a very easy workup of the reaction mixture), was avoided. Carbamates 2a-j were isolated in good to high yields.     

Synthesis of substituted pyrimidine using ZnFe2O4 nanocatalyst via one pot multi-component reaction ultrasonic irradiation

A highly efficient, eco-friendly, recyclable heterogeneous ZnFe₂O₄ nanocatalyzed synthesis of 2-amino-4-substituted 1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carbonitrile (4a-j) derivatives via one pot multicomponent reaction of benzimidazole ( 1 ), substituted aromatic aldehyde ( 2a-j ) and malononitrile ( 3 ) under ultrasonic irradiations. Significance of this synthetic approach is short reaction time, easy handling, simplicity, efficiency, high yield, and recoverable catalyst.     

The synthesis and spectroscopic properties of 3-(2′,4′-Xylyl)-1H,3H-quinazoline-2,4-diones

The synthesis of 3-(2′,4′-xylyl)-1H,3H-quinazoline-2,4-diones ( 1a, 9a-j ) has been accomplished. Their pmr and ir spectra data for all compounds are presented.