Direct Ferrier rearrangement on unactivated glycals catalyzed by indium(III) chloride

Anhydrous InCl₃ has been shown to efficiently catalyze the Ferrier rearrangement by a direct allylic substitution of the hydroxyl group at C-3 position of glycals to afford the corresponding 2,3-unsaturated glycosides in high yields at ambient temperature. This methodology obviates the need for protecting and/or activating the C-3 hydroxyl group of glycals. The reaction works in equal ease with both 4,6-di-O-benzyl-d-glucal and 4,6-di-O-benzyl-d-galactal. The mildness of InCl₃ makes this approach compatible for glycosyl acceptors with acid labile groups. The generality of the reaction has been demonstrated with a diversity of alcohols, phenols, and sugar nucleophiles.     

One-step novel synthesis of methylene bisphenols and methylene bisnaphthols using Lewis acid mediated rearrangement

Mono- and di-substituted isomeric methylene bisphenols and methylene bisnaphthols have been synthesized by rearrangement of the corresponding O-methoxyacetyl derivatives of phenols and naphthols, respectively, in presence of aluminium chloride under dry conditions. The chemistry observed is different from the usual Fries rearrangement reaction and involves an intermolecular rearrangement. The reactions reported here also reflect the influence of substituents present in the substrate as is supported by the substitution of the bridging methylene at a position meta to the phenolic hydroxyl in some of the minor products formed along-side the majorly formed ortho substituted products.     

一水硫酸氢钠无溶剂催化合成4-甲基香豆素

NaHSO4•H2O(摩尔分数为0.1)催化下, 取代酚与乙酰乙酸乙酯(物质的量比1∶1.2)在无溶剂条件下, 通过Pechmann缩合反应, 合成了9个4-甲基香豆素衍生物, 反应时间3～5 h, 产率23%～91%, 反应条件温和、操作简便有效. 研究结果表明, 当苯酚环上取代基为一个羟基或氨基能显著加速反应, 提高产率, 苯环上更多的取代基则对反应没有促进作用; 当苯酚环上取代基为吸电子基团时, 则不发生反应或者产率很低.     

Synthesis of 4-(2-hydroxyaryl)-3-nitro-4H-chromenes

A combinatorial library of 4-(2-hydroxyaryl)-3-nitro-4H-chromenes was synthesized in high yield by C4-SMe substitution in N-alkyl/phenyl 4-(methylthio)-3-nitro-4H-chromen-2-amines with a variety of phenols. The reaction always provided C2 substitution in the phenol ring, dictated by hydrogen bond interactions between the phenolic hydroxyl group and the nitro group in 3-nitro-4H-chromenes. Reduction of the nitro group with concomitant hydrolysis of the enamine in 4-(2-hydroxyaryl)-3-nitro-4H-chromenes with Zn, Ac₂O in AcOH furnished hybrid amino-acid lactone incorporating ortho-tyrosine and phenyl alanine moieties.     

Synthesis of Partially Fluorinated Organic Compounds from Perfluoro-2-methyl-2-pentene and Phenol Derivatives

The reactions of perfluoro-2-methyl-2-pentene with substituted phenols and some heterocyclic compounds containing OH group result in the substitution of the fluorine atom either exclusively at the internal multiple bond or at the terminal multiple bond of perfluoro-2-methyl-1-pentene formed by isomerization of the starting perfluoroolefin in the course of the reaction. The reaction pathway depends on the reaction conditions, base used, and substituents in the benzene ring. The structures of the compounds were confirmed by ¹H, ¹³C, and ¹⁹F NMR and IR spectroscopy.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 3, 2005, pp. 430–437.Original Russian Text Copyright © 2005 by Furin, Zhuzhgov, Chi, Kim.     

Synthesis and characterization of non-aggregating octa-substituted azaphthalocyanines bearing bulky phenoxy substituents

The synthesis and characterization of two novel series of octaazaphthalocyanines (AzaPc) bearing bulky phenoxy substituents are described. Target precursors to AzaPcs derivatives were prepared by using a nucleophilic aromatic substitution reaction between sterically hindered phenols (2,6-di-iso-propylphenol and 2,6-diphenylphenol) and 5,6-dichloropyrazine-2,3-dicarbonitrile. UV-vis and ¹H NMR analyses confirm that steric isolation of the AzaPcs cores enforced both in the solution and in the solid state. This study explores the effectiveness of the steric factor imposed by the applied bulky phenoxy substituents on the packing behaviour of azaphthalocyanines and thereby improving their solubility and photo-physical properties.     

Structural examination of some polychlorinated 2-phenoxyphenols by 1H and 13C nuclear magnetic resonance

Carbon-13 NMR spectra of some polychlorinated 2-phenoxyphenols have been obtained. The substituent chemical shifts obtained by varying the chlorine substitution pattern of one ring are very similar to those reported for the corresponding diphenyl ethers. Thus, the replacement of a 2-chlorine atom by a hydroxyl group only induces minor shielding changes at the adjacent aryl moiety and the ¹³C chemical shift changes are mainly determined by the preferred conformations governed by the steric demand of the ortho substituents. An ¹H NMR/IR study revealed an equilibrium between intermolecular aggregates and intramolecular OH…π species in the concentration interval 2-0.005 M. Any hydrogen bonding effects on ¹³C NMR shieldings are, therefore, minor compared to shielding variations caused by steric perturbations.     

Mechanistic Insights into Rhenium-Catalyzed Regioselective C-Alkenylation of Phenols with Internal Alkynes

A (μ-aryloxo)rhenium complex was isolated and confirmed as a key precatalyst for rhenium-catalyzed ortho-alkenylation (C-alkenylation) of unprotected phenols with alkynes. The reaction exclusively provided ortho-alkenylphenols; the formation of para or multiply alkenylated phenols and hydrophenoxylation (O-alkenylation) products was not observed. Several mechanistic experiments excluded a classical Friedel–Crafts-type mechanism, leading to the proposed phenolic hydroxyl group assisted electrophilic alkenylation as the most plausible reaction mechanism. For this purpose, the use of rhenium, a metal between the early and late transition metals in the periodic table, was key for the activation of both the soft carbon–carbon triple bond of the alkyne and the hard oxygen atom of the phenol, at the same time. ortho-Selective alkenylation with allenes also provided the corresponding adducts with a substitution pattern different from that obtained by the addition reaction with alkynes.     

Synthesis of polyoxyethylene grafting nylon 6 and the selective separation of cyclohexane/cyclohexanone/cyclohexanol mixture through its membranes

A polymer membrane having polyoxyethylene grafting nylon 6 was prepared by reacting of nylon 6 and ethylene oxide. The chemical compositions of the polyoxyethylene grafting nylon 6 were determined by ¹H NMR. Degree of substitution for amide group, x, and degree of polymerization for polyoxyethylene, n, in bulk polymerization at 80°C for 4–9.5 h were evaluated: x = 0.32 ± 0.01–0.56 ± 0.02 and n = 2.8 ± 0.1–6.0 ± 0.3. The polyoxyethylene grafting nylon 6 membrane showed a selective separation of cyclohexanol from a cyclohexane/cyclohexanone/cyclohexanol mixture by a pervaporation technique. The FTIR and flux analyses verified that the selectivity for cyclohexanol was attributed to the hydrogen-bonding interaction between hydroxyl group in cyclohexanol and the hydroxyl group in polyoxyethylene grafting chain. The pervaporation and an adsorption experiment of cyclohexanol through the present membrane showed that hydroxyl group in graft chain acted as a carrier for cyclohexanol.     

Late-Stage Direct o-Alkenylation of Phenols by PdII-Catalyzed C−H Functionalization

o-Alkenylation of unprotected phenols has been developed by direct C−H functionalization catalyzed by Pd^II. This work features phenol group as a directing group and realizes highly site-selective C−H bond functionalization of phenols to achieve the corresponding products in moderate to excellent yields at 60 °C. The advantages of this reaction include unprecedented C−H functionalization using phenol as a directing group, high regioselectivity, good substrate scope, mild reaction conditions, and high efficiency. To the best of our knowledge, this is the first example of a regioselective C−H alkenylation of unprotected phenols utilizing phenolic hydroxyl group as a directing group. The alkenylation of unprotected tyrosine and intramolecular cyclization are also successfully carried out under this catalytic system in good yields. Furthermore, this novel method enables a late-stage modification of complex phenol-containing bioactive molecules toward a diversity-oriented drug discovery.     

Enantiomeric discrimination of aromatic-containing anionic substrates using cationic cyclodextrins

Cationic α-, β-, and γ-cyclodextrins were prepared by reacting the corresponding native cyclodextrin (CD) with glycidyltrimethylammonium chloride (GTAC). The reaction conditions were varied in order to alter the degree of substitution of GTAC units on the cyclodextrin. The CD-GTAC derivatives, which retain a positive charge independent of pH, were evaluated as water-soluble chiral NMR solvating agents for anionic substrates. The CD-GTAC derivatives are considerably more effective at causing enantiomeric discrimination in the ¹H NMR spectra of aromatic-containing anionic substrates than the neutral native cyclodextrins. Derivatives with a degree of substitution of about 1.5 were more effective than those with lower or higher degree of substitution. Not one of the α-, β-, and γ-CD-GTAC derivatives was consistently the most effective at causing enantiomeric discrimination for all of the substrates examined herein.     

Synthesis of purpurin-18 imide derivatives from chlorophyll-a and -b by modifications and functionalizations along their peripheries

The methyl pheophorbide-a and methyl pheophorbide-b were used as starting materials and converted to purpurin-18 ester by ring-opening and rearrangement reaction in their exocyclic ring. N-Substituted purpurin-18 imides were obtained from purpurin-18 ester through amidation reaction of six-membered cyclic anhydride. Further chemical modifications along their peripheries were carried out by a variety of common reactions, including electrophilic substitution, Wittig reaction, allomerization and Vilsmeier reaction, to afford the title compounds with long-wavelength absorption. The structures of all new chlorins were characterized by elemental analysis, IR, UV–vis and ¹H NMR spectra.     

Oxetane ethers are formed reversibly in the lithium-catalyzed Friedel–Crafts alkylation of phenols with oxetanols: Synthesis of dihydrobenzofurans,diaryloxetanes, and oxetane ethers

Studies on the mechanism and intermediate products in the Friedel–Crafts reaction between oxetanols and phenols are presented. The formation of O-alkylated intermediates is identified using ¹H NMR spectroscopy, in a reversible formation of the kinetic oxetane ether products. An interesting relationship between the electronic nature of the nucleophile and the degree of O-alkylation is uncovered. For phenols substituted with an electron withdrawing group such as CN, oxetane ethers are the only products isolated regardless of reaction time. Increasing the electron rich nature of the phenol leads to an increased proportion of the thermodynamic C-alkylated Friedel–Crafts products after just 1?h and as the sole product/s after extended reaction times. These studies have enabled a more complete catalytic cycle to be proposed. Using the same lithium catalyst and carefully selected reaction times, several examples of oxetane ethers are successfully isolated as novel bioisosteres for ester groups.     

One step from nitro to oxime: a convenient preparation of unsaturated oximes by the reduction of the corresponding vinylnitro compounds

A series of novel unsaturated oximes were conveniently prepared from the corresponding vinylnitro compounds by reduction with SnCl₂·2H₂O. The structures of the oximes were characterized by ¹H and ¹³C NMR, IR and HRMS, and X-ray crystallography analysis of 1-(6-chloro-pyridin-3-ylmethyl)-4,5-dihydro-1H-imidazole-2-carbaldehyde oxime 2a reveals that, the hydroxyl group is arranged in a trans configuration. Some evidences from a brief investigation suggest that these oximes seem to be formed by reduction of the aci form of nitro aliphatic compounds.     

Asymmetric synthesis and absolute configuration of a planar chiral phosphapalladacycle with a ferrocenyl framework

A monodentate optically active tertiary α-ferrocenylethylphosphine was prepared from the corresponding tertiary α-ferrocenylethylamine; Me₂N group substitution by a tert-Bu₂P group occurs with complete retention of the enantiomeric composition and absolute configuration of the α-carbon stereocentre. The cyclopalladation of this phosphine ligand results in the formation of a phosphapalladacycle bearing the elements of central and planar chirality with a high diastereoselectivity. The enantiomeric composition of the CP-palladacycle was determined by ³¹P{¹H} NMR spectroscopy using (S)-prolinate as a chiral derivatizing agent. The structure and absolute configuration of the phosphapalladacycle were established using NMR spectroscopy and an X-ray diffraction study of its (S)-prolinate derivative.     

Synthesis of δ-cyclohexyl- and δ,δ-alkylene-α,α-dicarbonyl-substituted dienes and study of their valence isomerization

β-Cyclohexylacrolein, β-cyclohexylmethacrolein, or α-cycloalkylidenalkanals were condensed with methyl acetoacetate or dimethyl malonate to give the δ-cyclohexyl- and δ,δ-alkylene-substituted α,α-dicarbonyl-containing α,β∶γ,δ-dienes. The structures of the reaction products were studied using¹H NMR,¹³C NMR, and UV spectroscopy. The diene keto esters bearing no substituents at the γ-position were shown to be in fact three-component equilibrium mixtures comprised ofE- andZ-isomers of the diene (at the α,β bond) and a corresponding 2H-pyran. On the other hand, for keto esters with a Me group at the γ-position the equilibrium is shifted entirely to the 2H-pyrans. In contrast with the keto esters, dienic diesters exist only in the open form.     

Comprehensive characterization of surface-functionalized poly(amidoamine) dendrimers with acetamide,hydroxyl, and carboxyl groups

Terminal amine groups of poly(amidoamine) (PAMAM) dendrimers can be substituted with different functional groups for various applications. In this study, PAMAM derivatives with acetamide, hydroxyl, and carboxyl termini were synthesized from ethylenediamine (EDA) core generation 4 and 5 primary amine-terminated PAMAM dendrimers. The reaction products were purified with dialysis and subsequently characterized by polyacrylamide gel electrophoresis (PAGE), capillary electrophoresis (CE), size exclusion chromatography (SEC), matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, potentiometric titration, ¹H NMR, and ¹³C NMR. PAGE and CE electropherograms provide data regarding the purity, charge distribution, and electrophoretic mobility of the dendrimers and their derivatives. SEC and MALDI-TOF mass spectrometry detect the average absolute molar mass and the individual mass fractions, respectively. The combination of SEC with potentiometric titration provides quantitative evidence of the degree of the functional group substitution, while NMR techniques (both ¹H NMR and ¹³C NMR) confirmed the changes in dendrimer surface functionalization. This study provides a general example for the comprehensive characterization of surface-functionalized PAMAM dendrimer nanoparticles. The synthesized dendrimer derivatives hold promise for environmental and medical applications.     

Synthesis,DFT calculations,cyclic voltammetry and antibacterial activities of a new blue-violet dye and a new blue-green fluorescent heterocyclic system

The new blue-violet dye 2-(3-hydroxyimino-2,3-dihydroimidazo[1,2-a]pyridin-2-yliden)-2-(2-thienyl)acetonitrile was prepared in high yield from the reaction of 3-nitroimidazo[1,2-a]pyridine with 2-(2-thienyl)acetonitrile by nucleophilic substitution of hydrogen. Acylation of the hydroxyl group led to a new heterocyclic system, (pyrido[2′,1′:2,3] imidazo[4,5-b]thieno[2,3-e]pyridine-11-carbonitrile) with very strong blue-green fluorescent properties. Physical, spectral and analytical data have confirmed the structures of the synthesized dyes. The optical and solvatochromic properties of these compounds were investigated and showed interesting photophysical properties. Density functional theory calculations of blue-violet and fluorescent dyes were performed to provide the optimized geometries, Mulliken atomic charges, relevant frontier orbitals and the prediction of ¹H NMR chemical shifts. The electrochemical properties of these dyes were investigated by cyclic voltammetry and an oxidation wave was observed at a half-wave potential of −0.143 V versus SCE for the blue-violet dye. Also, these new compounds exhibited potent antibacterial activity against Gram positive and negative bacterial species.     

5-苄氧亚氨基-5-脱氧阿维菌素B1a的合成

以阿维菌素B1a为原料经过选择性氧化合成5-氧代-5-脱氧阿维菌素B1a, 再与O-取代羟胺盐酸盐反应合成了5个5-苄氧亚氨基-5-脱氧阿维菌素B1a (4a～4e), 通过¹H NMR, ¹³C NMR, MS, IR确证了它们的结构. 生测结果表明它们对于棉铃虫和甜菜夜蛾有一定的杀虫活性.     

Thermodynamics of complexation of tauro- and glyco-conjugated bile salts with two modified ��-cyclodextrins

The interaction between two modified ??-cyclodextrins and bile salts, common for rat, dog and man, was studied using isothermal titration calorimetry. The structural differences in the interaction were investigated by ¹³C NMR. The two modified ??-cyclodextrins were chosen because of their frequent use as oral excipients in drug formulation and in marketed products. All the investigated bile salts had an affinity for the ??-cyclodextrins, although there were large variations in the stability constants. The variations in the enthalpic and entropic contributions to the overall Gibbs free energy revealed differences in the binding mode to the investigated bile salts, i.e. the bile salts with a hydroxyl group at C12 interacted differently than bile salts without this hydroxyl group. These observations were supported by ¹³C NMR, which suggested binding to the D-ring of the steroid structure for bile salts with a hydroxyl group at C12 and to the C-ring for the bile salts without this hydroxyl group. The type of substitution of ??-cyclodextrin had significant effects on the thermodynamics of the interaction where especially the entropic changed were affected.