Synthesis and mass spectral studies of 1-[5-chloro-1-substituted-2(1H)-pyrazin-2-on-3-yl]-5-aryl-3-methylpyrazoles

Sixteen new 1-[5-chloro-1-substituted-2(1H)-pyrazin-2-on-3-yl]-5-aryl-3-methylpyrazoles V have been synthesized by condensation of 5-chloro-1-substituted-3-hydrazino-2(1H)-pyrazin-2-ones III and 1-aryl-1,3-butanediones IV in dry 1,4-dioxane. The general mass spectral fragmentation mode of these compounds has been studied.     

Novel syntheses of 3-cyano-3,4-dihydroquinolin-2(1H)-one and derivatives of 2,3-dicarbomethoxy-2-hydroxycyclopenta[b]quinoline

A facile solid phase conversion of 2-chloro-3-cyano-4-substituted-1,4-dihydroquinolines to 3-cyano-4-substituted-3,4-dihydroquinolin-2(1H)-ones in almost quantitative yields and a novel synthesis of 2,3-dicarbomethoxy-2-hydroxycyclopenta[b]quinoline are described.     

有生物活性的哒嗪酮-氨基甲酸酯类衍生物的合成

氨基甲酸酯衍生物;有生物活性的哒嗪酮-氨基甲酸酯类衍生物的合成     

嘧啶酮衍生物的微波合成

在微波辅助下,Baylis-Hillman加成物与4-氨基-6-氯嘧啶或2-氨基-噻唑反应,快速合成了两类嘧啶酮衍生物——3-取代-7-氯-4H-嘧啶[1,2-b]哒嗪-4-酮和6-取代-5H-噻唑[3,2-a]嘧啶-5-酮,收率81%～98%,其结构经1H NMR,13C NMR,IR和MS确证。     

Synthesis of nucleosides of 5-substituted-1,2,4-triazole-3-carboxamides

Nucleosides of 5-substituted-1,2,4-triazole-3-carboxamides were prepared by the acid-catalyzed fusion procedure and by glycosylation of the appropriate trimethylsilyl derivative. The following nucleosides were obtained in two steps starting from methyl 4-substituted-1,2,4-triazole-3-carboxylates: 5-chloro-1-β- D -ribofuranosyl-1,2,4-triazole-3-carboxamide ( 6 ), 3-chloro-1-β- D -ribofuranosyl-1,2,4-triazole-5-carboxamide ( 5 ), 3-nitro-1-β- D -ribofuranosyl-1,2,4-triazole-5-carboxamide ( 12 ), 3-amino-1-β- D -ribofuranosyl-1,2,4-triazole-5-carboxamide ( 13 ), 5-methyl-1-β- D -ribofuranosyl-1,2,4-triazole-3-carboxamide ( 15 ), and 3-methyl-1-β- D -ribofuranosyl-1,2,4-triazole-5-carboxamide ( 16 ). In addition, 5-amino-1-β- D -ribofuranosyl-1,2,4-triazole-3-carboxamide ( 7 ), and 1-β- D -ribofuranosyl-1,2,4-triazole-3-carboxamide-5-thiol ( 8 ) were prepared from 6 .     

Synthesis and bioactivity of pyrazole acyl thiourea derivatives

Sixteen novel pyrazole acyl thiourea derivatives 6 were synthesized from monomethylhydrazine (phenylhydrazine) and ethyl acetoacetate. The key 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl chloride intermediates 4 were first generated in four steps through cyclization, formylation, oxidation and acylation. Thess were then reacted with ammonium thiocyanate in the presence of PEG-400 to afford 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl isothiocyanates 5. Subsequent reaction with fluorinated aromatic amines resulted in the formation of the title compounds. The synthesized compound were unequivocally characterized by IR, 1H-NMR, 13C-NMR and elemental analysis and some of the synthesized compounds displayed good antifungal activities against Gibberella zeae, Fusarium oxysporum, Cytospora mandshurica and anti-TMV activity in preliminary antifungal activity tests.     

Synthesis and biological evaluation of novel dabigatran derivatives as thrombin inhibitors

Research on Chemical Intermediates - A novel series of 3-[{2-[(4-carbamimidoylphenylamino)methyl]-1-substituted-1H-benzoimidazole-5-carbonyl}(3-chloro-4-fluorophenyl)amino]propionic derivatives of...     

1-Benzenesulfonyl-2-trimethylsilylethane and 1-benzenesulfonyl-1-chloro-2-trimethylsilylethane; efficient reagents for sulfonyl-α-vinylation

1-Benzenesulfonyl-2-trimethylsilylethane and 1-benzenesulfonyl-1-chloro-2-trimethylsilylethane are convertable to 1-benzenesulfonyl-1-chloro-1-substituted-2-trimethylsilylethanes which undergo elimination by fluoride ion to give phenyl $\text{α}$-substituted-vinyl sulfones.     

Preparation of 1,3-Disubstituted-5-cyano-4,5-dihydropyrazoles via 1,3-Dipolar Cycloaddition of Nitrile Imine with Acrylonitrile

Ｉｎｔｒｏｄｕｃｔｉｏｎ4 ,5 Ｄｉｈｙｄｒｏｐｙｒａｚｏｌｅｄｅｒｉｖａｔｉｖｅｓｈａｖｅｂｅｅｎｓｔｕｄｉｅｄｅｘｔｅｎｓｉｖｅｌｙｄｕｅｔｏｔｈｅｉｒｄｉｖｅｒｓｅｃｈｅｍｉｃａｌｒｅａｃｔｉｖｉｔｙ ,ｂｒｏａｄｓｐｅｃｔｒｕｍｏｆｂｉｏｌｏｇｉｃａｌａｃｔｉｖｉｔｙａｎｄｖａｒｉｅｔｙｏｆｉｎｄｕｓｔｒｉａｌａｐ ｐｌｉｃａｔｉｏｎ .1Ｉｎａｄｄｉｔｉｏｎ ,ｉｔｉｓｋｎｏｗｎｔｈａｔ 4 ,5 ｄｉｈｙｄｒｏｐｙｒａ ｚｏｌｅｄｅｒｉｖａｔｉｖｅｓｗｅｒｅｕｓｅｆｕｌｃｏｍｐｏｕｎｄｓｎｏｔｏｎｌ…     

A novel preparation of chlorophospholenium chlorides and their application in the synthesis of phospholene boranes

A novel preparation of 1-chloro-3-methyl-3-phospholenium chlorides was developed by reacting 1-substituted-3-methyl-3-phospholene 1-oxides with oxalyl chloride. The obtained cyclic chlorophosphonium salts were reacted with LiBH₄ to afford the corresponding 1-substituted-3-methyl-3-phospholene boranes. The latter protocol involves a silane-free deoxygenation, and borane complex formation. In one instance, a 2-phospholene borane and the corresponding P-oxide were synthesized via rearrangement of the double bond in the cyclic chlorophosphonium salt. This double bond migration was investigated by quantum chemical calculations.     

Synthesis of some 7-substituted 3-chloro-3,4-dihydro-1-hydroxycarbostyrils by the reduction cyclization of α-chloro-β-(4-substituted-2-nitrophenyl)propionic acids

A new method was developed for the synthesis of some 7-substituted 3-chloro-3,4-dihydro-l-hydroxycarbostyrils 3c-g in which α-chloro-β-(4-substituted-2-nitrophenyl)propionic acids 2c-g were reductively cyclized by catalytic hydrogenation over platinum-on-carbon sulfided catalyst. In particular, this method was applied to α-chloro-β-(2-nitrophenyl)propionic acids bearing 4-methyl 2c , 4-ethyl 2d , 4-ethoxy 2e , 4-(n-butyl 2f and 4-phenyl 2g substituents to afford good yields of the corresponding 7-methyl 3c , 7-ethyl 3d , 7-ethoxy 3e , 7-(n-butyl) 3f , and 7-phenyl 3g substituted 3-chloro-3,4-dihydro-l-hydroxycarbostyrils. The various 4-substituted α-chloro-β-(2-nitrophenyl)propionic acids 2c-q were synthesized by reacting the in situ diazotized salts of the appropriate 4-substituted-2-nitroanilines in aqueous acetone with acrylic acid in the presence of cuprous chloride and hydrochloric acid. All compounds prepared in this study were characterized by microanalytical and ir and nmr spectral data.     

The preparation and characterization of 5-substituted-4-chloro-1,2,3-dithiazolium salts and their conversion into 4-substituted-3-chloro-1,2,5-thiadiazoles

A series of monosubstituted acetonitriles were treated with disulfur dichloride at room temperature in CH2Cl2 to afford 5-substituted-4-chloro-1,2,3-dithiazolium chlorides 1.Where the 5-substituent was not a good leaving group the chloride salts were converted into the corresponding perchlorate salts 2 which were sufficiently stable and soluble to provide both (1)H- and (13)C-NMR and cyclic voltammetry data. Several of the dithiazolium chlorides were converted into their corresponding 4-substituted-3-chloro-1,2,5-thiadiazoles 13 on treatment with aqueous ammonia. Mechanisms for all reactions are proposed.     

Synthesis and antimicrobial activity of some novel 5-alkyl-6-substituted uracils and related derivatives

6-chloro-5-ethyl-, n-propyl- and isopropyluracils 5a-c were efficiently prepared from the corresponding 5-alkybarbituric acids 3a-c via treatment with phosphorus oxychloride and N,N-dimethylaniline to yield the corresponding 5-alkyl-2,4,6-trichloro-pyrimidines 4a-c, which were selectively hydrolyzed by heating in 10% aqueous sodium hydroxide for 30 minutes. The reaction of compounds 5a-c with 1-substituted piperazines yielded the corresponding 5-alkyl-6-(4-substituted-1-piperazinyl)uracils 6a-j. The target 8-alkyltetrazolo[1,5-f]pyrimidine-5,7(3H,6H)-diones 7a-c were prepared via the reaction of 5a-c with sodium azide. Compounds 6a-j and 7a-c were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compound 6h displayed potent broad-spectrum antibacterial activity, while compound 6b showed moderate activity against the Gram-positive bacteria. All the tested compounds were practically inactive against Candida albicans.     

Two efficient cascade reactions to synthesize substituted furocoumarins

We have developed two efficient one-pot reactions to generate furo[3,2-c]coumarins and chlorofuro[3,2-c]coumarins through addition/cyclization/oxidation and chlorination. One cascade addition/cyclization/oxidation sequence of 1 with H(2)O in the presence of 20% CuCl as Lewis acid under an air atmosphere generated the 2-substituted-4 H-furo[3,2-c]chromen-4-one 2. Another sequence in the presence of 10% CuBr and excess CuCl(2) as the oxidant afforded the 3-chloro-2-substituted-4 H-furo[3,2- c]chromen-4-one 3.     

Transformations in the 2-quinolone series

The treatment of 1-substituted-1,2-dihydro-4-hydroxy-2-oxo-3-quinoline carboxylic acid esters and 4-hydroxy-1-methyl-3-nitro-2-(1H)quinolinone with phosphorus oxychloride resulted in the formation of the corresponding 4-chloro-2-quinolones. Their reactions with a variety of carbon, nitrogen, oxygen, and sulfur nucleophiles is described.     

Study of conventional versus microwave-assisted reactions of 3,4-epoxyalcohols by CeCl3·7H2O: Synthesis of tetrahydrofurans and 1-chloro-3-substituted-2-propanols

3,4-Epoxyalcohols undergo regioselective cyclization in the presence of CeCl₃·7H₂O in ref1uxing acetonitrile to afford tetrahydrofuran derivatives in good yields. On the other hand epoxyalcohols afforded 1-chloro-3-substituted-2-propanols under microwave irradiation using CeCl₃·7H₂O supported on SiO₂ under solvent-free conditions.     

A FACILE SYNTHESIS OF 3-GLYCOSYL-5-SUBSTITUTED-2-ISOXAZOLES

The 1,3-dipolar cycloaddition reaction between a 2-deoxy-D-aldose oxime (D-gluco or D-ribo) and an alkyne as dipolarophile (phenylacetylene, 2-propyn-1-ol, 3-chloro-1-propyne, or 3-bromo-1-propyne) is described. The new 3-glycosyl-5-substituted-2-isoxazoles are characterized physically and spectroscopically.     

Multistep, microwave assisted, solvent free synthesis and antibacterial activity of 6-substituted-2,3,4-trihydropyrimido[1,2-c]9,10,11,12-tetrahydrobenzo[b]thieno[3,2-e]pyrimidines

A novel, efficient, microwave assisted route for the synthesis of 6-substituted-2,3,4-trihydropyrimido[1,2-c]-9,10,11,12-tetrahydrobenzo[b]thieno[3,2-e]pyrimidines in good yields has been developed. The intermediates, 2-substituted-4-[3-hydroxy(propyl-1-amino)]5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidines were obtained by irradiating 2-substituted-4-chloro-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidines with 1-amino-propanol under basic conditions in a microwave oven. 4-Chlorothieno[2,3-d]pyrimidines were synthesized by microwave irradiation of equimolar mixture of 4-hydroxythieno[2,3-d]pyrimidines and phosphorus oxychloride. The final compounds were screened for antibacterial activity by Kirby Bauer's method using amicacin as the standard against various gram positive and gram negative bacteria. All the compounds showed antibacterial activity comparable with the standard.     

Reinvestigation of the Reaction of Sodium Borohydrate with Benzhydryl Halides under Solvolytic Conditions

Solvolysis of benzhydryl halides in aqueous diglyme containing sodium borohydride was studied. Contrary to the literature, sodium borohydride was found not to be a convenient trap for benzhydryl carbocations, especially for those containing electron-withdrawing substituent, and it decomposed appreciably in 80% aqueous diglyme at 45 °C. In addition, significant acceleration of reactions due to the presence of sodium borohydride was realized in the solvolysis of 3-chloro- and 3-trifluoromethyl-benzhydryl chlorides.     

The preparation and some chemistry of 2,2-dimethyl-1,2-dihydroquinolines

The cyclisation of N-(1,1-dimethylpropargyl) anilines, using cuprous chloride in refluxing toluene, yields 6-substituted-2,2-dimethyl-1,2-dihydroquinolines. The reactivity of the double bond in the heterocyclic ring of these products is exemplified by chlorination, to yield 6-substituted-3,4-cis-dichloro-2,2-dimethyl-1,2,3,4-tetrahydroquinolines which can be selectively dechlorinated to provide 6-substituted-3-chloro-2,2-dimethyl-1,2,3,4-tetrahydroquinolines; epoxidation to yield an epoxide, which can be hydrogenolysed to the corresponding 3-hydroxy product and in turn oxidised to the 3-keto derivative; and oxymercuration to provide a 4-hydroxy product and hence a 4-keto derivative. Dehydrochlorination of a 3,4-dichloro product provides a 3-chloro-1,2-dihydroquinoline which can be hydrolysed to a 3-keto system. The formation of cis 3,4-dichloro products from the chlorination, as well as the formation of a cis chlorohydrin from the chlorination of N-acetyl-2,2,6-trimethyl-1,2-dihydroquinoline in partially aqueous solution, suggests that N-acetyl, or N-trifluoroacetyl groups, participate in the addition process.