Abstract  The production and use pattern of Diethylmalonate (DEM) and Dimethylmalonate (DMM) are comparable. The two chemicals have very similar physico-chemical properties and both esters are hydrolyzed via a two step reaction to malonic acid and the corresponding alcohol, methanol or ethanol. It is likely that unspecific esterases in the body catalyze the hydrolysis. The alcohols and malonic acid are physiological substances that are metabolized via physiological pathways. Ethanol (CAS No. 64-17-5) and methanol (CAS No. 67-56-1) were assessed at SIAM 19. For ethanol it was concluded that the chemical is currently of low priority for further work, because the hazardous properties of ethanol are manifest only at doses associated with consumption of alcoholic beverages. As it is impossible to reach these exposure levels as a consequence of the manufacture and use of malonates, it can be expected that malonic acid will be the metabolite that determines the toxicity of DEM. For methanol, SIAM 19 decided that this chemical is a candidate for further work. Methanol exhibits potential hazardous properties for human health (neurological effects, CNS depression, ocular effects, reproductive and developmental effects, and other organ toxicity). The effects of methanol on the CNS and retina in humans only occur at doses at which formate accumulates due to a rate-limiting conversion to carbon dioxide. In primates, formate accumulation was observed at methanol doses greater than 500 mg/kg bw (which would require a DMM dose of more than 1000 mg/kg bw). As there were no indications of a methanol associated toxicity from a well performed repeated dose toxicity study with DMM in rodents (which are, however, known to be less sensitive to methanol toxicity than humans), and because methanol toxicity would not be expected up to doses as high as 1000 mg DMM/kg bw/day, it was concluded that methanol does not make a relevant contribution to the toxicity profile of DMM. A possible mode of action for systemic toxicity of DMM and DEM can only be deduced from the repeated dose study with DMM, indicating a reversible liver hypertrophy at the cellular level at high doses of 1000 mg/kg bw/day. This effect can be an indication of an induction of metabolism in the liver rather than a clear systemic toxicity.

Abstract  The complexation of lanthanides (Ln) with dicarbonyl compounds (acetylacetone, acac; ethyl acetoacetate; 3-ethyl-2,4-pentanedione; 2,4-hexanedione; 3-methyl-2,4-pentanedione; and diethyl malonate) was investigated using a potentiometric titration technique. The ability of a dicarbonyl compound to complex with the lanthanide elements was greatly dependent on its pK(a) and on the pH of the titrated solution. Selected lanthanide complexes (Ln complexes) were incorporated into spherical poly(L-lactic acid) (PLA) matrices and irradiated in a nuclear reactor with neutrons to produce short-lived high-energy beta-particle-emitting radioisotopes. The lanthanides investigated (Ho, Dy, Sm, and La) were chosen on the basis of their physical and nuclear properties. A transition element (Re) was also studied. The small decrease in the ionic radii of the lanthanides with increasing atomic number led to (a) greater ability to extract and complex from an aqueous solution with complexing agents, (b) larger formation and stability constants for the Ln complexes, (c) increased solubility of the Ln complexes in chloroform, and (d) increase in the maximum percent incorporation of the stable lanthanides in PLA spheres. Ho(acaC)3 was found to be the most promising candidate of the complexes studied on the basis of the above observations and due to the favorable physical properties of Ho-165 and nuclear properties of Ho-166.

Abstract  In this work, voltammetric, spectroelectrochemical, and electrocatalytic properties of the metallophthalocyanines bearing four chloro and four biphenyl-malonic ester bulky groups were investigated. Voltammetric and spectroelectrochemical measurements of the metallophthalocyanines show that while cobalt phthalocyanine presents both metal-based and ring-based redox processes, all other complexes give only ring-based reduction and oxidation processes. The redox processes have generally diffusion-controlled, reversible and one-electron transferred mechanisms. Cobalt phthalocyanine electrocoated easily on the glassy carbon working electrode during the repeating cycles, a very useful feature for application in fabrication of thin films. Electrocatalytic activity of cobalt phthalocyanine to hydrogen evolution reaction was studied in solution titrated with perchloric acid and on glassy carbon electrode modified with cobalt phthalocyanine in aqueous solution. Electrocatalytic measurements show that cobalt phthalocyanine has significant catalytic activities towards hydrogen evolution reaction. Moreover, the catalytic activity of the complex enhanced significantly when the complex was incorporated into the cation exchange Nafion polymeric matrix.

Abstract  Fullerenes could potentially play a valuable role in radioimmunotherapy by more stably encapsulating radionuclides, especially where conventional chelation chemistry is inadequate due to the physical and/or chemical properties of the radionuclide. One of the therapeutically useful radionuclides that requires improved containment in vivo is Pb-212 (tau(1/2) = 10.6 h), the beta-emitting parent to alpha-emitting Bi-212 (tau(1/2) = 60.6 min). Myelotoxicity resulting from the accumulation of Pb-212 in the bone marrow has limited the use of this radionuclide despite its favorable decay characteristics. In this work, Pb-212@C-60 and its malonic ester derivatives were prepared for the first time by allowing the Pb-212 to recoil into C-60 following alpha-decay from its parent, 0.15-s Po-216, generated in situ from the decay of Ra-224 (tau(1/2) = 15 days). Repeated washing of the organic phase containing the Pb-212@C-60 malonic esters with challenge solutions containing cold Pb2+ ions demonstrated that some of the Pb-212 could not be exchanged and was apparently inside of the fullerenes. Malonic esters of endohedral alpha-emitting Bi-213 (tau(1/2) = 45 min) fullerenes were prepared by an analogous procedure. Following acidification of the esters, a preliminary biodistribution study in mice was performed with the untargeted water-soluble radiofullerenes. It was found that Pb-212 did not accumulate in bone after being administered as an endohedral fullerene, in contrast to results with polyhydroxylated radiofullerenes and conventional polyaminocarboxylate chelators for Pb-212. The results indicate that Pb-212 is held more tightly in the fullerene than in other methods and suggest that fullerenes may have an important role in the targeted delivery of Pb-212.

Abstract  For the functional enhancement of chelating resins containing carboxylic acids, copolymer beads were prepared by suspension polymerization of styrene (St), methyl methacrylate (MMA), and divinylbenzene (DVB) in the presence of toluene as diluent. The phenyl rings of the beads were directly chloromethylated, and the carboxylic ester groups of the beads were converted into hydroxymethyl groups by reduction followed by chlorination to give chloromethyl groups, respectively. The chelating resins containing a pair of neighboring carboxylic acid groups (NCAGs) were obtained by the alkylation of chloromethyl groups in copolymer beads with diethyl malonate in the presence of sodium hydride followed by hydrolysis using aqueous alkali solution. Accordingly, the structural effects of the resins on the adsorption of heavy metal ions were investigated. Poly(St- co -DVB)-based chelating resin containing NCAGs showed adsorption abilities toward heavy metal ions like Pb 2+ , Cd 2+ , and Cu 2+ , whereas poly(MMA- co -DVB)-based chelating resin containing NCAGs showed adsorption abilities toward heavy metal ions like Cu 2+ , Cd 2+ , and Co 2+ . On the other hand, poly(St- co -MMA- co -DVB)-based chelating resin containing NCAGs showed adsorption abilities toward heavy metal ions like Pb 2+ , Cd 2+ , Hg 2+ , Co 2+ , and Cu 2+ : a synergistic effect on the adsorption of heavy metal ions like Pb 2+ , Cd 2+ , Hg 2+ , and Co 2+ was observed. The adsorption ability of poly(St- co -MMA- co -DVB)-based chelating resin among three kinds of chelating resins was relatively good.

Abstract  Mesoporous silica MCM-41 was successfully prepared by flow synthesis in a microreactor at shorter reaction times (i.e., minutes versus day) at high yield (i.e., 60% calcined sample) to give particles of more uniform size and shape compared to MCM-41 prepared by conventional batch synthesis. Magnetic iron oxide nanoparticles were incorporated and organic amines (i.e., propylamine and propyl diethylene amine) were grafted to obtain magnetic mesoporous catalysts for the Knoevenagel condensation reactions of benzaldehyde with ethyl cyanoacetate, ethyl acetoacetate and diethyl malonate. The incorporation of magnetic nanoparticles and large organic amines can hinder reactants access to the catalyst resulting in lower reactivity. NH2-magMCM-41 showed superb catalyst activity and selectivity for the all three Knoevenagel condensation reactions studied. The catalyst can be easily dispersed into solution and rapidly removed by a magnet for recovery and reuse. (c) 2012 Elsevier B.V. All rights reserved.

Abstract  Synthetic routes to potent bicyclic nonsteroidal sulfamate-based active-site-directed inhibitors of the enzyme steroid sulfatase (STS), an emerging target in the treatment of postmenopausal hormone-dependent diseases, including breast cancer, are described. Sulfamate analogs 9-27 and 28-46 of the core in vivo active two-ring coumarin template, modified at the 4- and 3-positions, respectively, were synthesized to expand structure-activity relationships. α-Alkylacetoacetates were used to synthesize coumarin sulfamate derivatives with 3-position modifications, and the bicyclic ring of other parent coumarins was primarily constructed via the Pechmann synthesis of hydroxyl coumarins. Compounds were examined for STS inhibition in intact MCF-7 breast cancer cells and in placental microsomes. Low nanomolar potency STS inhibitors were achieved, and some were found to inhibit the enzyme in MCF-7 cells ca. 100-500 more potently than the parent 4-methylcoumarin-7-O-sulfamate 3, with the best compounds close in potency to the tricyclic clinical drug Irosustat. 3-Hexyl-4-methylcoumarin-7-O-sulfamate 29 and 3-benzyl-4-methylcoumarin-7-O-sulfamate 41 were particularly effective inhibitors with IC50 values of 0.68 and 1 nM in intact MCF-7 cells and 8 and 32 nM for placental microsomal STS, respectively. They were docked into the STS active site for comparison with estrone 3-O-sulfamate and Irosustat, showing their sulfamate group close to the catalytic hydrated formylglycine residue and their pendant group lying between the hydrophobic sidechains of L103, F178, and F488. Such highly potent STS inhibitors expand the structure-activity relationship for these coumarin sulfamate-based agents that possess therapeutic potential and may be worthy of further development.

Abstract  Bulky, electron-rich phosphine ligands with a biphenyl backbone, when combined with Pd(OAc)(2), give highly active catalysts for the alpha-arylation of ketones. The ligand 2-methyl-2'-dicyclohexylphosphinobiphenyl is particularly effective, and with 0.1-1.0 mol % Pd, a large variety of aryl halides and ketones react efficiently and with high selectivity. For two types of substrates, the ligands BINAP and Xantphos are more effective than the biphenyl-based ligands. It is also shown that K3PO4 can be used as the base in these reactions, and that base-sensitive functional groups are better tolerated if this is used instead of NaO'Bu or NnHMDS. In some cases, alpha-aryl ketones can be produced without adding a ligand to the reaction. Although the substrate scope of the ligandless conditions is limited, some combinations react in high yield, and in one case, 100 000 turnovers were obtained. The results of experiments on the Pd-catalyzed arylation of diethyl malonate, cyclic 1,3-diketones, and nitroalkanes are also reported.

Abstract  Methods for enantioselective transfer of carbenes starting from precursors carrying two carbonyl groups have been elaborated. A one-pot procedure for olefin cyclopropanation with CH-acidic precursors via intermediate phenyliodonium ylides has been developed. The structure of the [Rh-2{(S)-nttl}4] catalyst was optimized to produce up to 98% ee in olefin cyclopropanations with dimethyl malonate or Meldrum's acid. Highly selective Rh(II)-catalyzed olefin cyclopropanations could be observed upon replacement of methyl diazoacetoacetate by methyl (silyloxyvinyl)diazoacetate. Enantioselective dipolar cycloadditions of diazopyruvate to polar olefins have been realized with Ru(II)-pybox catalysts.

Abstract  Treatment of (phenylsulfonyl)-1,2-propadiene (1) with bis(phenylsulfonyl)methane in the presence of sodium hydride affords 2,4,4-tris(phenylsulfonyl)-1-butene in 94% yield. Similar rearranged products were obtained using other soft nucleophiles and related allenes. The formation of these products involves addition of benzenesulfinate anion onto allene 1. The initially formed carbanion undergoes proton transfer with bis(phenylsulfonyl)methane followed by a S(N)2' reaction of the resulting anion with 2,3-bis(phenylsulfonyl)-1-propene. Supporting evidence for the proposed mechanism is provided by the observation that the reaction of dimethyl malonate with the activated allene in the presence of sodium benzenesulfinate gives mostly abnormal products. When allene 1 is allowed to react with olefins bearing an electron-withdrawing group in the presence of sodium benzenesulfinate, a substituted cyclopentenyl sulfone is formed. The reaction proceeds in a stepwise fashion by addition of the initially produced carbanion onto the activated pi-bond of the olefin followed by a 5-endo-trig cyclization and elimination of benzenesulfinate. This approach represents a mild and versatile anionic [3 + 2] route to five-membered unsaturated sulfones.

Abstract  A Pd/(R)-BINAP-catalyzed asymmetric benzylic substitution of secondary benzyl carbonates with amides and amines proceeds to form the corresponding optically active benzylamines in good yields with a high enantiomeric ratio. The reaction occurs in a dynamic kinetic asymmetric transformation (DYKAT) manner. Additionally, the asymmetric Pd catalysis can also be applicable to phenol nucleophiles, thus delivering chiral ethers with acceptable yields and enantioselectivity.

Abstract  In this study, biodegradable rigid cellular materials were synthesized from the reaction of malonic acid with epoxidized soybean oil. Malonic ester reacts with two epoxy reaction, initially formed malonic acid monoester (MAME) can decarboxylate and produce CO2, which acts as the blowing agent leading to in situ foaming of the polymer. Epoxide addition and decarboxylation reactions of MAME occur competitively and simultaneously and by controlling their relatives rates, foams of controlled density were produced. H-1 NMR spectrum of the synthesized foams showed that increasing the temperature increases the rate of decarboxylation reaction of MAME and decreases crosslink dencity leading to softer and lower density foams. Addition of 1,4-diazabicyclo[2.2.2]octane (DABCO) as a catalyst also increases the rate of decarboxylation. Load deflection curves of the cellular materials showed that decreasing the temperature and addition of DABCO increase compressive modulus of samples. Cell morphology was studied by microscopic images of foam samples that showed that foam samples have a closed cell structure and a wide distribution of cell volume. Soil burial test was done todetermine rate of biodegradation of foam samples. A half-life of 815 days showed that foam samples are highly biodegradable. (c) 2008 Wiley Periodicals, Inc.

Abstract  A series of chiral aminophosphine ligands with N,N-disubstituted 2-diphenylphosphinoaniline backbone are designed and readily prepared from (R)-2-(methoxymethyl)pyrrolidine or (S)-prolinol. The reactivity and selectivity in the palladium-catalyzed asymmetric allylic alkylation (AAA reaction) of 1, 3-diphenyl-2-propenyl acetate with a dimethyl malonate-BSA-LiOAc system using these chiral ligands are evaluated. Furthermore, chiral fluorous aminophosphine bearing two fluorous ponytails was prepared from (S)-prolinol. Chiral fluorous palladium catalyst from this ligand was easily reused in palladium-catalyzed AAA reaction with good enantioselectivity.

Abstract  The complexing capability of beta-diketone-3-substituted phthalides (isobenzofuranone) or isoindolinones toward Cu(II), Fe(III), Al(III), and Zn(II) salts has been highlighted by UV-vis spectroscopic studies. Conversely, heterocyclic analogs substituted with dimethyl malonate showed no complexing ability. Further insights have been given by the determination of equilibrium constants and distribution diagram, while the synthesis, isolation, and characterization of Cu(II)-beta-diketonate-isoindolinone complex has been achieved via a convenient modification of standard procedures. Moreover, in silico evaluation of bioavailability of the ligands is also discussed for potential pharmacological applications.

Abstract  Poly(vinylidene fluoride) (PVF2) produces thermoreversible gels in diesters. By variation of the number of intermittent carbon atoms (n = 0-7) of the diesters, the physical properties of the gels are studied. The morphology of the PVF2/diethyl oxalate (DEO) gel is spheroidal, but the morphology of PVF2-diethyl malonate (DEM) gel is a mixture of both spheroidal and fibrillar. The PVF2/diethyl succinate (DES), PVF2/diethyl gluterate (DEG), PVF2/diethyl pimelate (DEP), and PVF2/diethyl azelate (DEAZ) gels are "fibrillar-like" as evidenced from scanning electron microscopy (SEMI and transmission electron microscopy (TEM). The X-ray and solvent subtracted FT-IR spectra indicate the presence of a-polymorph PVF2 in all the gels. The enthalpy of gel formation and the enthalpy of gel fusion, measured from differential scanning calorimetry (DSC), show linear plot with PVF2 concentration for PVF2-DEO gels but others exhibit positive deviation from linearity. From the deviation vs PVF2 weight fraction (W-PVF2) plot, the compositions of the polymer solvent complexes are found to be 1:3, 1:2, 1:4, 1:4, and 1:3 in the molar ratio of the diester and PVF2 repeating unit, for gels in DEM, DES, DEG, DEP, and DEAZ, respectively. The phase diagrams of PVF2-DEM, PVF2-DES, and PVF2-DEP gels indicate polymer-solvent compound formation with a singular point while those of the PVF2-DEG and PVF2-DEAZ gels indicate compound formation with an incongruent melting point. The polymer solvent compound formation is also studied by molecular mechanics calculations using MMX program. The pairs of alpha-PVF2 and diester molecules with appropriate conformation to match the composition of the complex are energetically minimized. The distances between the >CF2 group and the carbonyl oxygen are lower than the summation of their van der Waals radii for all the diesters. The discrepancy between molecular modeling and morphology of the PVF2-DEO gels and the borderline morphology of PVF2-DEM gels have been explained from molecular mobility of the solvent and enthalpy of complexation (Delta H-c). The gel melting temperature and gelation temperature increases with increase in intermittent length (n) for a particular PVF2 concentration. Also, Delta H-c increases with "n", and this indicates that the intermittent length of diesters has both enthalpic and entropic contribution on gel behavior of PVF2.

Abstract  New iminophosphines have been synthesized from (R,R)-1-amino-2-diphenylphosphino cyclohexane (R.R)-1 in good to excellent yields. The catalysts obtained from iminophosphines 3a-g and [Pd(C3H5)Cl](2) promote the enantioselective allylic substitution of 1,3-diphenyl-2-propenyl acetate (6) with diethyl malonate with good enantioselectivity. The air-stable complex PdCl2[K-2-P,N-(R,R)-2-Ph2PC6H10N=CHPh] (4) has been prepared and structurally characterized by X-ray crystallography. (C) 2004 Elsevier B.V. All rights reserved.

Abstract  Three hydrometallurgical processes for industrial wastes treatment are presented. ?The main separation techniques are: solvent extraction, leaching-precipitation, electro-oxidation, and ion exchange. Recovery of gold from solid wastes generated in the electronic and jewellery industries consists of thermal degradation, two-stage leaching with nitric acid solution to remove silver and other metals and then with aqua regia to dissolve gold, selective solvent extraction of gold with diethyl malonate, and reduction of gold from the organic phase.

Vanadium recovery from residue ashes after burning heavy oil fractions consists of alkaline leaching of vanadium, filtration, neutralization of sodium vanadate solution, precipitation of ammonium metavanadate, drying of the precipitate, and adsorption of the remaining vanadium from the filtrate on an anionite. From the remaining ashes nickel is recovered using acidic leaching, filtration, precipitation of ammonium-nickelous sulphate, filtration, and drying.

The third process concerns processing of electroplating sludges and waste waters containing chromium and copper. The waste waters are electro-oxidized to transform Cr(III) into chromate. Then metal cations are separated on a cationite. The purified electroplating baths are recycled directly to electroplating; other solutions are first concentrated using anionite, followed by sodium chromate eluate conversion into concentrated chromic acid solution. The sludges accumulated from waste water processing by hydroxide precipitation are re-dissolved in chromic acid solution generated progressively by circulation between the dissolving and electro-oxidation steps. The concentrated chromic acid solution obtained is purified on the cationite and recycled.

Abstract  Using a malonic ester route, the first branched tandem intramolecular Diels-Alder (TIMDA) precursor, 3, was synthesized from sorbic acid in seven steps (15% overall yield). Treatment with Lewis acid catalysts (e.g., boron trifluoride etherate) affects the TIMDA reaction to afford a new fused-tetracyclic, 4, as two diastereomers (1:1). An alternative synthetic route to key intermediates used in the synthesis of linear TIMDA precursors has also been achieved.

Abstract  Tetracarboxylic acid ester was synthesized with diethyl malonate and methyl acrylate, and an amino terminated hyperbranched polymer (HBP-NH2) was prepared by reaction of a tetracarboxylic acid ester with diethylenetriamine (DETA). Hyperbranched polymer grafted chitosan (HBP-g-chitosan), a novel adsorbent material for Cr(VI) removal, was prepared from HBP-NH2 and chitosan with epichlorohydrin as crosslinking agent. The adsorbent was characterized by thermogravimetric analysis, Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray photoelectron spectrophotometry, and X-ray diffraction. The influence of the initial concentration of Cr(VI), the dosage of adsorbent, pH value and the coexisting anions on the adsorption performance were studied. An isotherm of the adsorption process was generated and studied by Langmuir and Freundlich models. The results showed that the Freundlich model proved to be more suitable than the Langmuir model. The adsorption kinetics were determined by pseudo-first order and pseudo-second order kinetics. In doing so, it was found that the pseudo-second order kinetic model was more reliable than the pseudo-first order kinetic model.

Abstract  A new and efficient method for the direct conversion of N-acyl oxazolidinones to a beta-keto ester is disclosed. The one-pot transformation is effected by the utilization of an excess of Lewis acid along with base and potassium ethyl malonate. This methodology has been applied to the large scale preparation of ethyl (R)-5-methyl-3-oxooetanoate. (c) 2008 Elsevier Ltd. All rights reserved.

Abstract  We describe a specific procedure for the synthesis of deuterium-labelled 2-(1-methylalkyl)succinate established via alkylation of diethyl malonate, Krapcho decarboxylation reaction with D2O and hydrolysis reaction. Two novel compounds, 2-[H-2]-2-ethylsuccinic acid and 2-(H-2-2-(1-methylheptyl)succinic acid were prepared via this synthetic route and characterized by mass spectrometry and H-1 NMR. The results showed that the 2-(1-methylalkyl)succinic acids were deuterated at the beta-position, which is considered as an important reaction centre in the anaerobic degradation of n-alkanes. (C) 2015 Chinese Chemical Society and Institute of Materia Medics, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

Abstract  Diffusion, permeation, and equilibrium sorption coefficients have been determined using a sorption gravimetric technique for methyl acetoacetate, ethyl acetoacetate, methyl benzoate, ethyl benzoate, methyl salicylate, isobutyl salicylate, and diethyl malonate into tetrafluoroethylene/propylene copolymer membranes in the temperature range 25-70 degrees C. The sorption kinetics process has been characterized by first-order rate constants and penetration velocities. From a temperature dependence of the transport coefficients, the activation parameters have been estimated. It is observed that the values of the transport coefficients for the systems of this study depend on the nature of the penetrant molecules rather than on their molecular sizes. On the whole, the mechanism of solvent transport into the copolymer membranes used here follows nearly the Fickian trend. (C) 1994 John Wiley and Sons, Inc.

Abstract  The reaction of barium or strontium metal in ammonia gas-saturated THF with two equivalents of dimethyl malonate (dmalH) in the presence of tetraethylene glycol dimethyl ether (tetraglyme) or 1,1,4,7,7-pentamethyldiethylenetriamine (pmdt) yields Ba(dmal)(2)(tetraglyme) (1), Ba(dmal)(2)(pmdt) (2). Sr(dmal)(2)(tetraglyme) (3). and Sr(dmal)(2)(pmdt) (4) as colorless crystals in reasonable yields (45-52%). These complexes have been characterized by spectroscopic methods (IR and H-1- and C-13-NMR) and elemental analysis data. Molecular structures of 1, 3, and 4 have been determined by X-ray diffraction studies and have revealed that they are monomeric and the tetraglyme or pmdt ligand wraps around a central metal atom in a meridional plane with the dmal ligands on opposite sides of this plane. (C) 2002 Elsevier Science B.V. All rights reserved.