Dicyclopentyl azodicarboxylate(DCpAD):A new alternative azo-reagent for the Mitsunobu reaction

Dicyciopentyl azodicarboxylate is introduced as a new azo-reagent which can be conveniently prepared in two steps and be used in the Mitsunobu reaction.Though there are no distinct difference of reactivity between DCpAD and DEAD,the former is a more preferable azo-reagent for its stability.     

Simplification of the Mitsunobu reaction. Di-p-chlorobenzyl azodicarboxylate: a new azodicarboxylate

Di-p-chlorobenzyl azodicarboxylate (DCAD) is introduced as a novel, stable, solid alternative to DEAD and DIAD for a variety of Mitsunobu couplings. DCAD/Ph(3)P-mediated reactions in CH(2)Cl(2) generate a readily separable hydrazine byproduct. [reaction: see text]     

Di-p-nitrobenzyl azodicarboxylate (DNAD): an alternative azo-reagent for the Mitsunobu reaction

Di-p-nitrobenzyl azodicarboxylate is prepared in 83.6% yield in two steps as a bright yellow solid, which can be used as an azo-reagent in the Mitsunobu reaction. When a chiral secondary alcohol was used, sufficient configurational inversion of alcohol occurred under Mitsunobu conditions. That the hydrazine produced from DNAD is semisoluble in some solvents such as THF and CH₂Cl₂ makes it separated easily from the reaction mixture just via filtration. Then the recovered hydrazine compound can be re-exposed to oxidant to produce DNAD. Because DNAD is more stable than DIAD at ambient temperatures and allows easy separation, it is a good alternative azo-reagent for the Mitsunobu reaction.     

DMEAD: a new dialkyl azodicarboxylate for the Mitsunobu reaction

Di-2-methoxyethyl azodicarboxylate (DMEAD) is prepared in 65% yield in two steps as a crystalline solid. Use of DMEAD in the Mitsunobu reaction of a variety of alcohols with pronucleophiles results in good yields of the products under sufficient stereospecificity of inversion, as conventional diisopropyl azodicarboxylate (DIAD) does. Isolation of the product is, however, much easier with DMEAD than that with DIAD, because the hydrazine produced from DMEAD is highly hydrophilic and is completely separable by a simple extraction into neutral water. Purification of the organic layer, after separation of the other by-product, triphenylphosphane oxide, by filtration, easily provides high purity of the product in a good yield. Concentration of the water layer yields the hydrazine, which can be reused for the preparation of DMEAD. One-step removal of the two by-products by the aqueous extraction was also possible when trimethylphosphane and DMEAD were employed.     

Reactivity of pyridines bearing EWG with bis-(TMS)ketene acetals. Substituent-induced lactonization reaction

The nucleophilic addition of bis-(TMS)ketene acetals to pyridines substituted by electron-withdrawing groups, activated with triflic anhydride, leads to their corresponding dihydropyridine carboxylic acids in a first instance. These acids can be efficiently turned into new bicyclic lactones by either of three different methods: first, bicyclic γ-lactones were successfully obtained by an unprecedented Michael-type ring closing procedure assisted by silica gel; second, bicyclic δ-bromolactones were achieved by a NBS-promoted process; and third, the unexpected spontaneous formation of new hydroxy γ-spirolactones was observed. Along the work presented herein, the scope, limitations, and regioselectivity of these lactonization reactions were studied, confirming the utility of bis-(TMS)ketene acetals as 1,3-dinucleophiles in this type of reactions, extending thus the range of synthesis of a wide variety of new aza-compounds.     

Association of poly-N-[tris(hydroxymethyl)methyl] acrylamide with a water soluble β-cyclodextrin polymer

An acrylic polymer with pendent adamantyl groups was synthesized and its properties in an aqueous solution with a β-cyclodextrin (βCD) epichlorhydrin polymer examined. Viscosity properties of precursor and modified polymers show differences at low concentrations, but not at higher concentration probably due to very important hydrogen bonds which prevent the formation of intermolecular hydrophobic bonds. The association of both complementary polymers through the inclusion of adamantyl groups is evidenced by phases separation occurrence. Phase diagrams were established at two different concentrations of polymers. We have shown a maximal association of both polymers at these two concentrations, for the same ratio βCD moles/adamantyl groups: 2.4. Salt addition favors this association and displaces the two phases zone to smaller concentrations of modified polymer. Further, 4-nitrophenol can be extracted by the concentrated phase resulting from mixture of solutions of guest and host polymers, pointing out the availability of the associated phase to trap organic molecules.     

Preparation of carbodiimides by the reaction of thioureas with diethyl azodicarboxylate

A new synthesis of disubstituted carbodiimides from N.N′-disubstituted thioureas, diethyl azodicarboxylate and triphenyl phosphine has been achieved. The intermediates of the reaction have been isolated and found to be 1:1 adducts of the thioureas and diethyl azodicarboxylate, N¹,N²-disubstituted—S—(N³,N⁴-biscarboethoxy)hydrazinoisothioureas which, on treatment with triphenyl phosphine at room temperature, afford the corresponding carbodiimides. Alternatively, the intermediates on heating under reflux in benzene or toluene, decompose to the carbodiimides, diethyl hydrazodicarboxylate and sulphur.     

Dinuclear Cu(II) complexes of isomeric bis-(3-acetylacetonate)benzene ligands: synthesis, structure, and magnetic properties

Highly versatile coordinating ligands are designed and synthesized with two β-diketonate groups linked at the carbon 3 through a phenyl ring. The rigid aromatic spacer is introduced in the molecules to orient the two acetylacetone units along different angles and coordination vectors. The resulting para, meta, and ortho bis-(3-acetylacetonate)benzene ligands show efficient chelating properties toward Cu(II) ions. In the presence of 2,2'-bipyridine, they promptly react and yield three dimers, 1, 2, and 3, with the bis-acetylacetonate unit in bridging position between two metal centers. X-ray single crystal diffraction shows that the compounds form supramolecular chains in the solid state because of intermolecular interactions. Each of the dinuclear complexes shows a magnetic behavior which is determined by the combination of structural parameters and spin polarization effects. Notably, the para derivative (1) displays a moderate antiferromagnetic coupling (J = -3.3 cm(-1)) along a remarkably long Cu···Cu distance (12.30 ?).     

Reactions at interfaces: oxygenation of n-butyl ligands anchored on silica surfaces with methyl(trifluoromethyl)dioxirane

The oxygenation of n-butyl and n-butoxy chains bonded to silica with methyl(trifluoromethyl)dioxirane (1) revealed the ability of the silica matrix to release electron density toward the reacting C(2)-H σ-bond through the Si-C(1) and Si-O(1) σ-bonds connecting the alkyl chain to the surface (silicon β-effect). The silica surface impedes neither the alkyl chain adopting the conformation required for the silicon β-effect nor dioxirane 1 approaching the reactive C(2) methylene group. Reaction regioselectivity is insensitive to changes in the solvation of the reacting system, the location of organic ligands on the silica surface, and the H-bonding character of the silica surface. Reaction rates are faster for those organic ligands either within the silica pores or bonded to hydrophilic silica surfaces, which evidence the enhanced molecular dynamics of confined dioxirane 1 and the impact of surface phenomena on the reaction kinetics. The oxygenation of n-butyl and n-butoxy chains carrying trimethylsilyl, trimethoxysilyl, and tert-butyl groups with dioxirane 1 under homogeneous conditions confirms the electronic effects of the silyl substituents and the consequences of steric hindrance on the reaction rate and regioselectivity. Orthosilicic acid esters react preferentially at the methylene group adjacent to the oxygen atom in clear contrast with the reactivity of the carboxylic or sulfonic acid alkyl esters, which efficiently protect this position toward oxidation with 1.     

Steric effects and competitive intra‐ and intermolecular host‐guest complexation between beta‐cyclodextrin and adamantyl substituted poly(acrylate)s in water: A 1H NMR,rheological and preparative study

A ¹H NMR and rheological study of host‐guest complexation interactions between three β‐cyclodextrin and three adamantyl substituted poly(acrylate)s, and also between them and adamantan‐1‐carboxylate and native β‐cyclodextrin, respectively, is reported. A close correllation between molecular level interactions and macroscopic characteristics of polymer networks in aqueous solution exists. It is found that intra‐ and intermolecular host‐guest complexation between the host β‐cyclodextrin and guest adamantyl substituents and the length of the aliphatic tether between them and the poly(acrylate) backbone have important roles. Dominantly, steric effects and competitive intra‐ and intermolecular host‐guest complexation are found to control poly(acrylate) isomeric interstrand linkage in polymer network formation. The preparations of five new 3% randomly substituted poly(acrylate)s are reported. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1818–1825, 2010     

Crystal and molecular structures of bis-(5-methyl-5-butoxy-hexanedionato-2,4) Copper(II) and bis-(2,2-dimethyl-5-cyclohexyl-pentanedionato-3,5) Copper(II)

Two new volatile complexes of Cu(II) containing methoxy groups were studied in a combined X-ray diffraction investigation of the mono- (KUMA automatic diffractometer, MoK_α radiation) and polycrystals (DRON-3M, CuK_α radiation). The structures are molecular and consist of the trans-complexes of bis-(5-methyl-5-butoxy-hexanedionato-2,4)copper(II), C₂₂H₃₈CuO₆, and bis-(2,2-dimethyl-5-cyclohexyl-pentanedionato-3,5) Copper(II), C₂₈H₄₆CuO₆. The crystal data of C₂₂H₃₈CuO₆: a = 8.939(1), b = 8.887(2), c = 8.326(1) å, α = 107.92(2), Β = 108.15(1), γ = 85.52(2)?, space group P1,V= 597.9(2) å³, Z = 1, d_x = 1.283 g/cm³. The crystal data of C₂₈H₄₆CuO₆: a = 18.625(3), b = 16.126(2), c= 13.613(3) å, Β = 132.19?, space group P2₁/n, V= 3029.3(9) å³, Z = 4, d_x= 1.189 g/cm³. In both cases, the square planar environment of the Cu atom with Cu...O distances of 1.90 å is completed by interactions with two carbon atoms of the terminal groups of the two neighboring molecules at Cu...C distances of 3.66 å (average).     

全衍生化羟丙基-β-环糊精固定相的制备及应用

研究了3, 5-二甲基苯基异氰酸酯对羟丙基-β-环糊精固定相的手性识别影响.通过异氰酸丙基三乙氧基硅烷作偶联剂,将羟丙基-β-环糊精键合到3-氨丙基硅烷化硅胶上,再用3, 5-二甲基苯基异氰酸酯对β-环糊精和硅胶其余羟基进行衍生化,制得一种新型的3, 5-二甲基苯基氨基甲酸酯全衍生化羟丙基-β-环糊精键合硅胶手性固定相.在反相色谱条件下,对9种手性药物进行了拆分,结果表明,3, 5-二甲基苯基氨基全衍生化固定相较之羟丙基-β-环糊精固定相有更好的分离效果.     

Synthesis of poly(ethylene glycol) (PEG)-grafted colloidal silica particles with improved stability in aqueous solvents

The known grafting procedures of colloidal silica particles with poly(ethylene glycol) (PEG) lead to grafting layers that detach from the silica surface and dissolve in water within a few days. We present a new grafting procedure of PEG onto silica with a significant improvement of the stability of the grafting layers in aqueous solvents. Moreover, the procedure avoids any dry states or other circumstances leading to strong aggregation of the particles. To achieve the improved water stability, St?ber silica particles are first pre-coated with a silane coupling agent (3-aminopropyl)triethoxysilane (APS) to incorporate active amine groups. The water solubility of the pre-coating layer was minimized using a combination of APS with bis-(trimethoxysilylpropyl)amine (BTMOSPA) or bis-(triethoxysilyl)ethane (BTEOSE). These pre-coated particles were then reacted with N-succinimidyl ester of mono-methoxy poly(ethylene glycol) carboxylic acid to form PEG-grafted silica particles. The particles form stable dispersions in aqueous solutions as well as several organic solvents.     

Binuclear carbonyl-containing complexes of Rh(i) with bis-(o-hydroxy)- and bis-(o-amino) quinones

Conclusions We synthesized a number of binuclear rhodium complexes that contain bis-(o-hydroxy)- and bis-(o-amino) quinones.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2630–2632, November, 1973.     

A novel sorbent for chromatographic separations: A silica matrix modified with non‐covalently bonded tetrakis(β‐cyclodextrin)–porphyrin conjugates

We prepared new phases for LC that consisted of silica modified with non‐covalently bonded tetrakis(β‐cyclodextrin)–porphyrin (where cyclodextrin is CD) conjugates. The effects of the porphyrin core, type of spacer and β‐CD moieties on the behaviours of the modified phases for the separation of aromatic compounds (benzene, toluene, ethylbenzene, propylbenzene, butylbenzene, pentylbenzene, o‐terphenyl, triphenylene, phenol and caffeine) and fluorinated aromatic compounds (pentafluorobenzonitrile, pentafluoronitrobenzene and hexafluorobenzene) were studied using the Tanaka test. The results indicate that the non‐covalent substitution of silica with CD‐based macromolecules that have a porphyrin core can be a very effective method for preparing novel sorbents with specific chromatographic properties for applications in LC.     

Synthesis of novel bis- and poly(aryldiazenylthiazoles)

A novel series of bis- and poly(arydiazenyl)thiazoles were prepared in good yields by the reaction of the appropriate α-keto-hydrazonoyl chlorides with the corresponding bis- and poly(hydrazinecarbothioamide) in refluxing EtOH/DMF in the presence of few drops of TEA. Based on elemental analyses as well as spectral data, the structures of the new compounds were confirmed.     

Hydrogels of β-cyclodextrin crosslinked by acylated poly(ethylene glycol): Synthesis and properties

Networks of β-cyclodextrin have been prepared by reaction with acylated poly(ethylene glycol) with a molar mass of 600 g/mol. Samples with different β-cyclodextrin/poly(ethylene glycol) ratios: 1/4, 1/6, 1/8 and 1/10 have been prepared. Both components are bonded by ester groups, resulting in a network that can be degraded by hydrolysis in basic and acidic media. The maximum stability of the hydrogels is reached at pH 4. The hydrogel percentage water content depends on β-cyclodextrin content ranging from 82 to 98, and the swelling data obtained for these hydrogels fit well with a second order kinetics. The sorption behavior of these hydrogels has been tested by employing 1-naphthol as model molecule. The sorption capacity is close to other cyclodextrin networks previously reported and depends on the hydrogel composition and the concentration of 1-naphthol.     

Potential DNA bis-intercalating agents. Bridged bis-(6-chloropurines) and related compounds

Two bis-(6-chloropurines) bridged by conformationally restricted tethers were synthesized as potential DNA bis-intercalating agents. Reduction of 4,6-dichloro-5-nitropyrimidine ( 1 ) afforded 5-amino-4,6-dichloropyrimidine ( 2 ) which was then used as the starting material. Reaction of 2 with 4,4′-diaminodiphenylmethane ( 3 ) and bis-(4-aminophenyl) ether ( 4 ) yielded bis-[4-(N-5-amino-4-chloro-6-pyrimidyl)aminophenyl]methane ( 5 ) and bis-[4-(N-5-amino-4-chloro-6-pyrimidyl)aminophenyl] ether ( 6 ), respectively. Acid-catalyzed condensation of the above pyrimidines, 5 and 6 , with triethyl orthoformate in N,N-dimethylacetamide gave bis-[4-(6-chloro-9-purinyl)phenyl]methane ( 7 ) and bis-[4-(6-chloro-9-purinyl)phenyl] ether ( 8 ). The spectral data on the new compounds will be discussed.     

Regioselective <Emphasis Type="Italic">N</Emphasis>-alkylation of (2-chloroquinolin-3-yl) methanol with <Emphasis Type="Italic">N</Emphasis>-heterocyclic compounds using the Mitsunobu reagent

The Mitsunobu reaction is a well-established fundamental reaction and has been widely applied in organic synthesis. In this paper, under Mitsunobu conditions dehydration proceeds between (2-chloroquinolin-3-yl)methanol and nitrogen heterocyclic compounds such as quinazolinone, pyrimidone, 2-oxoquinoline in dry THF in the presence of triethylamine, triphenylphosphane and diethyl azodicarboxylate to give the corresponding products. As part of our recent research, we attempted to couple two N-heterocyclic compounds under Mitsunobu reaction conditions to provide efficient building blocks for natural product synthesis.     

Synthesis and antispasmodic activity evaluation of bis-(papaverine) analogues

A new series of N-substituted bis-(tetrahydropapaverine) ring systems have been synthesised in expectation of better antispasmodic activity in comparison with papaverine. The synthesis of the targeted heterocycles is described along with a discussion of their structure activity relationship. The general synthetic methods of bis-(tetrahydropapaverine) analogues involve tetrahydropapaverine, various piperazines, diisocyanates and diisothiocyanates as starting materials. Pharmacological evaluation involves the in vitro antispasmodic activity on a freshly removed guinea pig ileum using a force displacement transducer amplifier connected to a physiograph. Among the analogues synthesized in the present study, N,N'-bis-[2-carbamoyl-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolinyl]piperazine (22), was found to be the most potent muscle relaxant (IC(50): 0.31 microM).