Convenient procedure of Horner-Wadsworth-Emmons olefination for the synthesis of simple and functionalized α,β-unsaturated nitriles

A mild and practical procedure of Horner-Wadsworth-Emmons olefination promoted by lithium hydroxide and α-cyano phosphonates has been set up for the synthesis of α,β-unsaturated nitriles. The reaction conditions are tolerated by functionalized ketones and the exclusive formation of E-γ-hydroxy α,β-unsaturated nitriles has been observed.     

New, diastereoselective synthesis of 1-alkyl-5-alkylidene-3-methylidenepyrrolidin-2-ones

The diastereoselective synthesis of 1-alkyl-5-alkylidene-3-methylidenepyrrolidin-2-ones was readily accomplished in a two-step reaction sequence consisting of the reaction of 2-diethoxyphosphoryl-4-oxoalkanoates with amines followed by Horner-Wadsworth-Emmons olefination of formaldehyde using the intermediate 1-alkyl-5-alkylidene-3-diethoxyphosphorylpyrrolidin-2-ones.     

Preparative synthesis of 3-cyano-4-difluoromethyl- and 3-cyano-4-trifluoromethyl-2(1H)-pyridones

An efficient procedure for the synthesis of 3-cyano-4-difluoromethyl- and 3-cyano-4-trifluoromethyl-2(1H)-pyridones was developed. The structure of one of the resulting compounds was established by X-ray diffraction analysis.     

A simple and expedient method for the stepwise synthesis of 2-ethoxy-(4H)-3,1-benzoxazine-4-ones

A simple and practical route is described for the synthesis of 2-efhoxy-(4H)-3,1 -benzoxazine-4-ones using the coupling reaction of anthranilic acid derivatives with diethyl dicarbonate following with fast cyclization of the carbamate adduct with a dehydrocyclization agent such as cyanuric chloride and N,N′-dicyclohexylcarbodiimide in PEG at room temperature.High yields of the products obtained under mild reaction conditions with simple work-up of the reaction mixture.     

Design, synthesis and antifibrotic activities of carbohydrate-modified 1-(substituted aryl)-5-trifluoromethyl-2(1H) pyridones

Pirfenidone, a pyridone compound, is an effective and novel antifibrotic agent. In this article, we describe the design, synthesis and activity evaluation of novel antifibrotic agents, 1-(substituted aryl)-5-trifluoromethyl-2(1H) pyridones modified with carbohydrate. Most of the title compounds exhibited comparable or better inhibitory activity than fluorofenidone. Notably, compound 19a demonstrated the highest cell-based inhibitory activity against NIH 3T3 (IC(50) = 0.17 mM).     

Synthesis, Crystal Structure and Antibacterial Activity of 1-（（2-Chloroquinolin-3-yl）-methyl）-pyridin-2（1H）-one

On the basis of the interesting structures and biological activities exhibited by several heterocyclic systems possessing the pyridone nucleus such as mappcine and camptothecin, we have planed to design the synthesis, crystal studies and antibacterial activity of the new 1-((2- chloroquinolin-3yl)-methyl)-pyridine-2(1H)-one building block. An X-ray analysis has provided valuable insight into the effect of steric factors on the three-dimensional shape of this compound which serves as a useful advanced intermediate in the synthesis of these biologically active molecules. A multistep synthesis of camptothecin (5) has been designed by retrosynthetic analysis as part of an ongoing program on lead anticancer drug.     

Synthesis and antibacterial activity of some 5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-thiocarboxamides, 3-trifluoromethylpyrazol-1-thiocarboxamides and 4-aryl-2-(5(3)-trifluoromethyl-1-pyrazolyl)thiazoles

5-Hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-thiocarboxamides 3 and 3-trifluoromethylpyrazol-1-thiocarboxamides 4, regioselectively obtained by the condensation of trifluoromethyl-β-diketones with thiosemicarbazide under neutral and acidic conditions, on further reaction with phenacyl bromides 5 afforded 4-aryl-(5-trifluoromethyl-pyrazol-1-yl)thiazoles 6 and 4-aryl-(3-trifluoromethyl-pyrazol-1-yl)thiazoles 7, respectively. Five 4,5-dihydropyrazoles (3a–e) and two pyrazolylthiazoles (6a and 6c) were tested against one Gram-positive and one Gram-negative bacteria to assess their in vitro antibacterial activity. Compounds 3a, 3b and 3e showed moderate antibacterial activity against Gram-positive bacterium, Bacillus pumilus.     

A highly enantioselective synthesis of 5-(l-menthyloxy )-4-substituted-3-chloro-2(5H )-furanones

In this paper, stereocontrolled tandem Michael addition-elimination reaction of the novel chiral source, 5-(l-menthyloxy)-3,4-dichloro-2(5H)-furanone, with various thiols and amines has been investigated. A series of new enantiomerically pure compounds, 5–(l-menthyloxy)-4-substituted-3-chloro-2(5H)-furanones, were obtained in good yields with d. e. ? 98% under mild conditions.     

Novel synthesis of 2-amino-3-hetaryl-4(5H)-oxothiophenes

3-Cyano-3-hetaryl-2-oxopropyl thioacetates were obtained by the acylation of hetarylacetonitriles with acetylmercaptoacetyl chloride. Their reaction with amines led to the formation of 2-amino-3-hetaryl-4(H)-oxothiophenes. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 680–685, May, 2006.     

A CONVENIENT SYNTHESIS OF NEW PYRIDOTHIENOPYRIMIDIN-4 (3H) ONES AND PYRIDOTHIENOPYRIMIDIN-2, 4(1H, 3H) DIONES

New derivatives of 2-substituted pyrido[3′,2′:4,5]thieno[3,2-d]pyri-midin-4(3H) ones and 3-substituted pyrido[3′,2′:4,5]thieno[3,2-d]pyri-midin-2,4(1H,3H) diones have been prepared by base catalyzed cyclocondensation of ethyl-3-aminothieno[3,2-b]pyridine-2-carboxylate with aryl nitriles and aryl- or alkyl isocyanates respectively.     

Tandem reduction-olefination for the stereoselective synthesis of (Z)-α-fluoro-α,β-unsaturated esters

A tandem stereoselective reduction-olefination reaction of ethyl 2-acyl-2-fluoro-2-diethylphosphonoacetate employing NaBH₄ in EtOH was developed. The one-pot reaction gave α-fluoro-α,β-unsaturated esters with excellent (Z)-selectivity. A plausible mechanism involving a diastereoselective reduction predicted by the Felkin-Anh model, followed by olefination similar to the Horner-Wadsworth-Emmons reaction, has been proposed.     

1-(2,6-二氯-4-三氟甲基苯基)-3-氰基-5-氨基吡唑及其磺酰胺的合成及晶体结构

2,6-二氯-4-三氟甲基苯胺经重氮化后与2,3-二氰基丙酸酯反应合成了1-(2,6-二氯-4-三氟甲基苯基)-3-氰基-5-氨基吡唑(1), 1与苯磺酰氯、对甲基苯磺酰氯、甲基磺酰氯反应, 得到1的苯磺酰胺2a、对甲基苯磺酰胺2b和双甲基磺酰胺2c. 通过元素分析、红外光谱、核磁共振氢谱、核磁共振碳谱、质谱等手段对其结构进行了表征. 用X射线单晶衍射测定了化合物1, 2a和2c的晶体结构. 1属于正交斜方晶系, Pbca空间群, 晶胞参数 a＝1.61739(7) nm, b＝1.62480(7) nm, c＝3.10857(13) nm, ＝＝＝90, V＝8.1691 nm³, Z＝24, R＝0.1089, wR＝0.2545. 2a属于单斜晶系, C2/c空间群, 晶胞参数 a＝3.35144(18) nm, b＝0.97948(5) nm, c＝2.44717(12) nm, β＝102.460(1), V＝7.8440(7) nm³, Z＝8, R＝0.1831, wR＝0.2600. 2c属于三斜晶系, P-1空间群, 晶胞参数 a＝0.84681(7) nm, b＝0.89652(83) nm, c＝1.43497(12) nm, α＝75.198(2), β＝87.918(1), γ＝65.395(1), V＝0.9546 nm³, Z＝2, R＝0.049, wR＝0.135.     

A facile and efficient method for the synthesis of N-substituted isoindolin-1-one derivatives under Pd(OAc)2/HCOOH system

A facile and efficient method for the synthesis of N-substituted isoindolin-1-one derivatives from 2-formylbenzoic acid and amine under Pd(OAc)₂/HCOOH system has been described. The whole process is carried out in ligand-free conditions and furnished the desired products by reductive intramolecular cyclization. Furthermore, this procedure is applied successfully for the modification of natural products, such as vindoline and estrone.     

2-[3-Phenyl-5-(m-Chlorophenyl)-2-Pyrazolin-1-yl]-3-Methyl-4(3H)-Quinazolinone

There are two molecules in the asymmetric unit (I and II). The structure consists of a 2-pyrazoline ring and three aromatic rings two of which are free and the third one is condensed with a 3-methyl-4(3H)-pyrimidine ring (4(3H)-Quinazolinone). While the pyrazoline ring is in the distorted envelope conformation, the free aromatic rings are planar and the pyrimidine ring deviates from the planarity. The crystal structure is stabilized by C–HO inter and intramolecular bonds.     

New synthesis of 2-trifluoromethyl-2,3-dihydro-1H-quinolin-4-ones

N-(1-Ethoxy-2,2,2-trifluoroethyl)anilines 2a-2f, prepared from trifluoroacetaldehyde ethyl hemiacetal and aniline, readily reacted with diethyl malonate in the presence of sodium hydride, giving substituted products 5a-5f in high yields. Compounds 5a-5f subjected to hydrolysis and decarboxylation under specified conditions yielded the 4,4,4-trifluorobutyric acids 6a-6e or 7. Direct ring-closure of 6a-6e with polyphosphoric acid gave 2-trifluoromethyl-2,3-dihydro-1H-quinolin-4-ones 9a-9e.     

Synthesis, spectroscopic properties and crystal structure determination of 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole derivatives

Substituted 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole derivatives 2, 3 and 6 were synthesized. 2-(2-Pyridin-4-yl-vinyl)-1H-benzimidazole 2 and 6-methyl-2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole 3 were prepared by condensation reaction from 3-pyridin-4-yl-acrylic acid and corresponding 1,2-phenylenediamines in polyphosporic acid (PPA). 2,7,11-b-Triaza-benzo[c]fluorene 4 was prepared by photochemical dehydrocyclization reaction of ethanolic solution of 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole 2. 2-(2-Pyridin-4-yl-vinyl)-3H-benzimidazole-6-carbonitrile 6 was prepared by condensation reaction from 3-pyridin-4-yl-propenal and 4-cyano-1,2-phenylenediamine using p-benzoquinone as oxidants. The structure of novel benzimidazole derivatives has been studied by ¹H and ¹³C NMR, IR, MS, UV/Vis and fluorescence spectroscopy. The structure of 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole 2 was confirmed by X-ray single crystal structure analysis. The conformation of the molecule is E in regard to substituents position around vinyl double C=C bond. The non-planar molecules are mutually connected via the N–H···N and C–H···N type of intermolecular hydrogen bonds into infinite chains spreading along y axis.     

New Method of Synthesis of 2-Amino-4(5H)-oxothiophenes

A new method is proposed for the synthesis of 2-amino-4(5H)-oxothiophenes with aryl and hetaryl substituents in position 3 of the molecule by the acylation of aryl- and 2-azahetarylacetonitriles with mercaptoacetic acid ethyl ester.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 202–205, February, 2005.