An improved Balz-Schiemann reaction enabled by ionic liquids and continuous processing

A Balz-Schiemann reaction was developed to convert 2-cyano-5-aminopyridine to 2-cyano-5-fluoropyridine. The use of an ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate, BMIMBF₄) as a solvent was found to be critical in achieving high assay yields and high selectivity for the fluorination vs. protonation. A process was developed to recycle and reuse the ionic liquid enabling its cost-effective use as a solvent. Finally, the optimal conditions were demonstrated under as a continuous process to address process safety risks associated with diazonium intermediates and the product was used to access a key intermediate in the synthesis of β-amyloid cleaving enzyme 1 inhibitor, verubecestat.     

An efficient approach for the total synthesis of balticolid

An efficient stereoselective total synthesis of balticolid has been accomplished starting from known aldehyde. The key steps involved in this synthesis are Sharpless asymmetric epoxidation, Wittig olefination, alkylation of 1,3-dithiane and Yamaguchi macrolactonization.     

Thiamine hydrochloride(VB1):An efficient catalyst for one-pot synthesis of α-aminophosphonates under ultrasonic irradiation

An efficient synthesis of novelα-aminophosphonates by the reaction of aldehydes and amines with triethyl phosphite in the presence of the easily available,inexpensive,and nontoxic catalyst thiamine hydrochloride(VB1).This method affords theα-aminopho-sphonates under the influence of ultrasound irradiation in aqueous medium,in short reaction times(4-6 min),high yields(85-95%), with improved purity.The process is green,mild,inexpensive and excellent yields are the main compensation of this procedure.     

An efficient aldol-based approach for the synthesis of dihydrokawain-5-ol

An efficient and simple aldol-based convergent approach toward the total synthesis of (+)- and (?)-dihydrokawain-5-ol is described. The key features of this synthetic strategy include Evans’ aldol reaction and an ethyl acetate addition reaction for the formation of the six-membered ring.     

Redox polymerization process: An efficient tool for the synthesis of block copolymers

The synthesis of poly(acrylonitrile)-block-poly-(ethylene glycol)-block-poly(acrylonitrile) copolymers has been carried out using a redox system consisting of ceric ion and poly(ethylene glycol)s of various molecular weights in aqueous medium. The generation of intermediate radicals in the redox process has been confirmed by ESR spectroscopy and the polymerization progressing through ‘blocking from’ mechanism has been postulated. The formation of the block copolymers has been confirmed by chemical tests and fractional precipitation technique as well as by FT-IR and FT-NMR [¹H and ¹³C–(¹H)] spectroscopic techniques. The triblock nature of the block copolymers has been ascertained through the cleavage of ether linkage of the PEG segment. TG/DTA studies of the block copolymers with PEG molecular weights of 1000 and above revealed two-stage decomposition, while their DSC traces exhibited a shift in the melting peak of PEG. GPC investigations of the block copolymers manifested a high homogeneity with unimodal distribution of molecular weights. SEM studies indicated significant changes in the morphological characteristics of the block copolymers. © 1995 John Wiley & Sons, Inc.     

微波等离子体常压解吸电离质谱法快速检测化学药剂中的活性成分

构建了一种新型电离源--微波等离子体常压解吸电离源, 等离子体由微波等离子体炬产生, 工作气体为Ar气, 微波频率为2450 MHz, 该离子源可在大气压下产生稳定的等离子体. 将该电离源与具有大气压接口的Corsair API-TOF型飞行时间质谱仪结合, 实现了化学药剂中单一或多种主要活性成分的快速分析, 在手动进样条件下, 检测速度可达每小时360次. 在微波等离子体环境下, 活性物质成盐时母体化合物上结合的酸性物质可被直接除掉, 谱图中主要离子为母体化合物的准分子离子[M+H]⁺, 便于识别. 微波等离子体常压解吸电离质谱法无需化学试剂, 具有实时、 快速及无污染等特点, 为药剂研发及化学工业提供了一种新的检测技术.     

An efficient ultrasound-promoted method for the synthesis of bis(indole) derivatives

In this paper, the reaction of indole with electron-deficient alkenes in aqueous media is reported. This procedure allows the synthesis of bis(indole) derivatives in good to high yields at 90 °C under silent and ultrasound irradiation conditions. Short reaction times and high yields of desired products are the main advantages of the presented procedure. This reaction catalyzed by 12-tungstophosphoric acid is operationally simple and considers environmental aspects by avoiding toxic catalysts and solvents.     

An efficient and general synthesis of pyrroles

We have discovered that a wide range of 3-alkynyl-hydroxyalkanamine derivatives undergo 5-endo-dig cyclisations when exposed to silver nitrate supported on silica gel. Subsequent in situ dehydration of the resulting and sometimes isolable hydroxy-dihydropyrroles leads to pyrroles in essentially quantitative yields using this recoverable and reusable heterogeneous catalyst.     

An efficient approach to the stereoselective synthesis of 2,6-disubstituted dihydropyrans via stannyl-Prins cyclization

A general method has been developed for the stereoselective construction of 2,6-disubstituted dihydropyrans based on the Lewis acid-catalyzed intramolecular reactions of oxocarbenium ions with vinylstannanes. This novel methodology was applied to the enantioselective total synthesis of (−)-centrolobine.     

An efficient synthesis of 3,4-dihydropyrimidin-2(1H)-ones catalyzed by thiamine hydrochloride in water under ultrasound irradiation

An environmentally benign aqueous Biginelli protocol for the synthesis of substituted 3,4-dihydropyrimidin-2(1H)-ones using thiamine hydrochloride as a catalyst has been achieved. These ultrasound-assisted reactions proceed efficiently in water in the absence of organic solvent. Utilization of ultrasound irradiation, simple reaction conditions, isolation, and purification makes this manipulation very interesting from an economic and environmental perspective.     

Stannous oxalate: An efficient catalyst for poly(trimethylene terephthalate) synthesis

A complete study on the catalytic activity of stannous oxalate for poly(trimethylene terephthalate) (PTT) synthesis via esterification method is carried out by comparison to the well known catalysts (tetrabutyl titanate (TBT), dibutyltin oxide (Bu2SnO), and stannous octoate (SOC)). Their catalytic activity in the esterification process is monitored by measuring the amount of water generated, while intrinsic viscosity (IV) and content of terminal carboxyl groups (CTCG) are used as the index in the polycondensation process. Stannous oxalate shows higher activity than the other catalysts. Decrease in reaction time and improvements in PTT property are observed. The higher catalytic activity of stannous oxalate is attributed to its chelate molecular structure.     

An efficient method for the solid-phase synthesis of fluorescently labelled peptides

Fluorescent labelling of peptides is necessary in a wide range of cell biological applications. In the last decade, the application of cell-penetrating molecules has been advanced by the use of peptides, which have proven efficient in aiding nonpermeant molecules to cross the cell membrane. Currently, the development of new cell-penetrating peptides based on the design and synthesis of labelled peptide libraries is becoming critically important. Here we report an improved method for the solid-phase labelling of peptides, mediated by the activation of 5(6)-carboxyfluorescein with PyAOP/ HOAt.     

An efficient non-catalytic, regioselective approach to the synthesis of angularly fused polycyclic systems

A novel approach to the synthesis of partially reduced different ring sizes of PAH analogs with sec.amino and nitrile functionalities is delineated through base-induced ring transformation of 4-sec.amino-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles by a carbanion, generated in situ from cyclopentanone, cyclohexanone, cycloheptanone, and cyclooctanone separately in good yields. An increase in the size of cycloalkanone ring beyond cyclooctanone restricts the ring transformation under analogous reaction conditions possibly due to bulky conformation of higher homologs. The synthetic method provides an efficient general route for the construction of angularly fused partially reduced polycyclic aromatic hydrocarbons: 5-sec.amino-2,3,6,7-tetrahydro-1H-cyclopenta[c]phenanthrene-4-carbonitriles, 6-sec.amino-2,3,4,7,8-pentahydro-1H-benzo[c]phenanthrene-5-carbonitriles, 7-sec.amino-2,3,4,5,8,9-hexahydro-1H-cyclohepta[c]phenanthrene-6-carbonitriles, and 8-sec.amino-2,3,4,5,6,9,10-heptahydro-1H-cycloocta[c]phenanthrene-7-carbonitriles.     

An efficient approach for total synthesis of aminopropyl functionalized ganglioside GM1b

A highly efficient protocol for the synthesis of aminopropyl functionalized ganglioside GM1b has been described. The full protected ganglioside GM1b was obtained in 71% yield within 5 h. The key feature of the synthetic approach was the use of sialic acid donor that was with a C-5 trichloroacetamide moiety and with a dibenzyl phosphite residue as leaving group at the anomeric carbon. The sialyl donor gave high yields and excellent α-anomeric selectivities with a wide variety of glycosyl acceptors ranging from C-3 or C-6 hydroxyls of galactoside to C-6 hydroxyl of glucosaminoside by using TMSOTf as catalyst in a mixture solution of acetonitrile and methylene chloride.     

An efficient method for the synthesis of lignans

An efficient approach for the synthesis of several types of lignans (dibenzylbutanediols, dibenzylbutanes, substituted tetrahydrofurans, aryldihydronaphthalenes, arylnaphthalenes, and aryltetralins) was developed. The regioselective oxidative coupling of ethyl ferulate was used as the key step.     

An efficient method for the synthesis of gem-difluoroolefins

A series of gem-difluoroolefin derivatives were synthesized in moderate to good yields by the reaction of α,α-difluoro-β-carbonyl benzothiazol-2-yl sulfones (DFBTs) with various carbon nucleophiles. Using dl-proline as organocatalyst, the reaction of DFBT with acetone gave a tertiary alcohol, which could be further converted to the corresponding difluoroolefin by LDA.     

An efficient approach to the synthesis of 3-vinylidene tetrahydropyrans via Prins-type cyclization

Lewis acid-catalyzed intramolecular reactions of oxocarbenium ions with propargylsilanes are described. The results obtained indicate that trimethylsilyl trifluoromethanesulfonate (TMSOTf) efficiently catalyses cyclization leading to the corresponding 3-vinylidene tetrahydropyrans in high yield as single isomers.     

An efficient stereoselective synthesis of six stereoisomers of 3, 4-diaminocyclohexane carboxamide as key intermediates for the synthesis of factor Xa inhibitors

An efficient stereoselective route for the preparation of six stereoisomers of tert-butyl ((1R, 2S, 5S)-2-amino-5-(dimethylcarbamoyl)cyclohexyl)carbamate 1 starting from simple 3-cyclohexene-1-carboxylic acid has been described. Stereochemistry of the title compounds was controlled at C2 center by Mitsunobu reaction and at C5 via a base-catalyzed epimerization. Only a limited usage of column chromatography has provided a direct and scalable route for the six stereoisomers.     

An efficient synthesis of pyrazole chalcones under solvent free conditions at room temperature

An easy,safe,solvent free and effective method for the synthesis of pyrazole-substituted chalcones has been achieved by grinding pyrazole aldehydes and acetophenones in the presence of activated barium hydroxide(C-200) in high yield within short span of time.All reactions were carried out just by grinding the two reactants in the presence of activated barium hydroxide(C-200). Results are also compared with sodium hydroxide and potassium hydroxide.