Abstract  The problems of liquid-liquid extraction and solids dissolution in stirred tanks are classic mass transfer problems which have been studied extensively in the literature. An analogous problem, that of dissolution of pure drops close to their solubility limit, has been almost completely neglected. This problem has practical application in the dissolution and dispersion of small amounts of surface active additives, particularly in the water treatment industry and in oil field applications where the cost of the chemical additive is one of the major process costs. The question is also of interest for some chemical reactions, such as the third Bourne reaction (diethylmalonate in water) and the hydrolysis of acetic anhydride to acetic acid. In this paper, the drop size distribution and solute concentration in the bulk are measured throughout the dissolution period and the dissolution process is successfully modelled using an Eulerian-Lagrangian approach. The validated model is used to identify the key variables driving the dissolution rate. The approach to saturation, the impeller rotational speed, and the continuous phase viscosity all play an important role. When the solute is injected close to the impeller, the role played by surface tension is surprisingly small.

Abstract  The synthesis and structure of Rh(I) and Pd(II) complexes of chiral P,C-chelating phosphino-(alpha-sulfinylalkyl)phosphonium ylide ligands with a trisubstituted asymmetric ylidic center P(+)-C*(S*(O)p-Tol)-M (R = alkyl group) have been investigated, and compared to those of the analogous disubstituted ylide complexes (R = H). Reaction of the ethyl onium ylide of o-bis(diphenylphosphino)benzene with (-)-menthyl-(S)-p-tolylsulfinate afforded the corresponding racemic erythro phosphino-(alpha-sulfinylethyl)phosphonium in 90% de (R = Me). The racemization process is interpreted by a Berry-like pseudorotation mechanism driven by the steric repulsion between the alpha-methyl substituent and the bulky menthyloxy S-substituent or sulfur lone pair in the intermediate ylide-sulfinyl adduct. The ylide of phosphino-(alpha-sulfinylethyl)phosphonium reacts with [Rh(cod)(2)][PF(6)] and PdCl(2)(MeCN)(2) to afford the corresponding PC-chelated threo-Rh(I) and erythro-Pd(II) mononuclear complexes in 70% yield and total diastereoselectivity. These respective complexes act as efficient catalytic precursors for the hydrogenation of (Z)-alpha-acetamidocinnamic acid and allylic substitution of 3-acetoxy-1,3-diphenyl-1-propene with sodium dimethyl malonate. The bonding features of the erythro-Pd(11) complex exhibiting a sulfinyl O center dot center dot center dot Pd interaction are studied theoretically at the DFT level using ELF and MESP analyses. The eta(2)-P,C haptomeric form of the ylide ligand is estimated to compete at 19% with the eta(1)-C haptomeric form dominating at 81%. (C) 2010 Elsevier Ltd. All rights reserved.

Abstract  Copper(II)-directed condensation of 1,9-diamino-3,7-dithianonan-5-ol with nitroethane or diethyl malonate yields (6-methyl-6-nitro-1,11-dithia-4,8-diazacyclotetradecan-13-ol)copper(II) and (diethyl 13-hydroxy-1,11-dithia-4,8-diazacyclotetradecane-6-6-dicarboxylate)copper(II) respectively in good yields, with the latter readily converted by decarboxylation into the complex of ethyl 13-hydroxy-1,11-dithia-4,8-diazacyclotetradecane-6-carboxylate. Analogues without the alcohol group based on 3,7-dithianonane-1,9-diamine are also described. The pendant alcohol group fused directly to a macrocyclic ring carbon can act as an axial donor group, as illustrated in the X-ray crystal structure analysis of (diethyl 13-hydroxy-1,11-dithia-4,8-diazacyclotetradecane-6,6-dicarboxylate) copper(II)) perchlorate. This complex crystallizes in the P 2(1)/c space group, a 12 . 650(3), b 8 . 620(1), c 24 . 382(4) Angstrom, beta 96 . 10(2)degrees. The copper ion lies in a distorted square-based pyramidal environment of two sulfur donors (average Cu-S 2 . 338 Angstrom), two nitrogen donors (average Cu-N 2 . 035 Angstrom) and the pendant alcohol donor [Cu-O 2 . 319(6) Angstrom], with the copper ion displaced slightly (0 . 043 Angstrom) out of the macrocycle donor plane towards the pendant alcohol donor.

Abstract  Chiral spiro diphosphines (SDP) are efficient ligands for the Pd-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate and related nucleophiles. The newly synthesized ligand DMM-SDP (1e) with 3,5-dimethyl-4-methoxy groups on the P-phenyl rings of the phosphine shows the highest enantioselectivity (up to 99.1% ee). Diethylzinc as a base is critical for obtaining high enantioselectivity in the allylic alkylation using beta-dicarbonyl nucleophiles. The structure of catalyst [PdCl(2)((S)-SDP)] was determined by single crystal X-ray diffraction. The SDP ligands create an effective asymmetric environment around the palladium, resulting in high enantioselectivities for the asymmetric allylic alkylation reaction.

Abstract  The most difficult and costly step in the industrial manufacturing of antimicrobial quinolones is the synthesis of ethoxymethylene malonate (EMME), which is influenced by three main parameters: ethyl orthoformate/diethyl malonate molar ratio, acetic anhydride/diethyl l malonate molar ratio and time. In order to establish the optimum reaction conditions a planned factorial experiment of second-degree order was accomplished, in which the real values of the parameters and their limits Of variation were chosen arbitrarily. Feedforward neural networks with a single hidden layer were used in direct and inverse modeling of the process, to predict the yield of the reaction for different reaction conditions or the reaction conditions for a pre-established yield. Both mathematical modeling and the neural modeling of EMME obtaining process enabled to settle the optimum values of the parameters for a maximum yield in EMME.

Abstract  [image omitted] The article describes an efficient, economical, and environmentally friendly approach for Michael addition of diethyl malonate to ferrocenyl substituted chalcones in the presence of microwave irradiation under solvent-free conditions, affording the corresponding Michael adducts in moderate to good yields of 53-94%.

Abstract  Octan-1-ol, acetophenone, ethyl butanoate (ethyl butyrate), ethyl pentanoate (ethyl valerate), and 1,3-diethyl propanedioate (diethyl malonate) were used as solvents for determining the ternary liquid phase diagrams of aqueous mixtures consisting butyric acid, with the intention of bringing more effective and environmental friendly solvents into use. The liquid-liquid equilibrium (LLE) data for water + butyric acid + solvent ternary systems were investigated at 298.15 K and atmospheric pressure. The ternary phase diagrams composed of solubility data and tie-lines were presented graphically. The reliability of the experimental tie-lines was tested by Othmer-Tobias correlation. The experimental tie-line data were compared with the results correlated by means of UNIQUAC model, and predicted by the UNIFAC method. It is concluded that the used solvents may be adequate extractants to extract butyric acid from its dilute aqueous solutions

Abstract  Allylation of dimethyl malonate with 1-(4-chlorophenyl)prop-2-enyl methyl carbonate in the presence of [Pd(All)Cl](2), [Rh(COD)Cl](2), [Ir(COD)Cl](2) (COD is cycloocta-1,5-diene), and a chiral ferrocenyl-containing phosphite ligand based on (R)-BINOL (BINOL is 2,2'-dihydroxy-1,1'-binaphthyl) in CH2Cl2 gave a mixture of linear and branched cross-coupling products, the latter having a moderate optical purity (below 51%). The rhodium-and iridium-catalyzed reactions were very highly regioselective (regiospecific in the case of Ir), giving a branched product. In ionic liquids ([bmim][BF4] and [bdmim][BF4]) (bmim is 1-butyl-3-methylimidazolium and bdmim is 1-butyl-2,3-dimethylimidazolium), the Ir-catalyzed reaction regiospecifically afforded a branched product as a racemate. The same result was obtained with [Ir(COD)Cl](2) as a catalyst; this reaction easily occurred in ionic liquids even without a base.

Abstract  A convenient one-pot synthesis of stable phosphorus ylides by the condensation of triphenylphosphine with dialkyl acetylenedicarboxylate and CH acids, such as penta-2,4-dione or diethyl propane-1,3-dioate, in the presence of beta-cyclodextrin as a catalyst (to increase the solubility of the reactants in water) without using toxic organic solvents was proposed. This methodology is of interest due to the use of water as a solvent, thus minimizing such factors as the cost, operational hazards, and environmental pollution.

Abstract  Complexation of the chiral P,N-bidentate ferrocene- and cymantrene-based iminoarylphosphites with [Rh(CO)(2)O-12, [Rh(COD)(THF)(2)]BF4, [Pd(allyl)Cl](2), [Pt(allyl)Cl](4), [Pd(COD)Cl-2] and [Pt(COD)Cl-2] was found to give chelate complexes [Rh(CO)(eta(2)-PN)Cl], [Rh(COD)(eta(2)-PN)]BF4, [M(allyl)(eta(2)-PN)]BF4 (M = Pd, Pt) and cis-[M(eta(2)-PN)Cl-2)] (M = Pd, Pt), correspondingly. With the new P,N-ligands, up to 97% ee was achieved in the asymmetric Pd-catalysed alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate. In the enantioselective amination of 1,3-diphenyl-2-propenyl acetate with sodium diformylamide, up to 96% enantioselectivity was achieved. (c) 2006 Elsevier B.V. All rights reserved.

Abstract  Dimethyl 4-methoxycarbonylcyclopenta-1,3-diene-1,2-diacetate has been prepared from benzyl methyl malonate by reaction with 2-propynyl bromide, followed by palladium-catalyzed ring-forming oxidative carbonylation and by elimination of the benzyloxycarbonyl group and double bonds isomerization. The anion of the diacetate readily reacts with transition metal complexes, to give the corresponding cyclopentadienyl derivatives. We describe here some complexes, obtained from [{RhCl(L)(2)}(2)] [L = CO, C2H4, or 1,5-cyclooctadiene (COD)], which are efficient catalysts for the alkyne-nitrile co-cyclization to pyridines and for the hydroformylation of styrene and 1-hexene.

Abstract  alpha -Enones 1a,b react additively with hydrazine hydrate, thiourea, diethyl malonate, malononitrile, as well as ethyl cyanoacetate. Simultaneous cyclisation of the resulting 1:1 adducts yields indazole, thiazine, chromene and quinoline derivatives. The structures of all the synthesised compounds were confirmed by micro analytical and spectral data. The antimicrobial activity of some of the synthesised compounds were tested.

Abstract  Skeletal structure of copiamycin (C sub(54)H sub(95)N sub(3)O sub(17)), a potent antifungal antibiotic, was determined from the physicochemical properties of this compound and of its degradation products. This compound consists of 32-membered polyhydroxy lactone ring, an alpha , beta -unsaturated ester group, as well as a side chain with a disubstituted guanidine moiety as its terminal. One of the hydroxyl groups (presumably at C-19) forms a hemiketal ring with the keto group at C-15, and another (at either C-21 or C-23) forms a hemiester with a malonic acid moiety.

Abstract  The s-cis-[Cr(S,S-eddv)L]-complexes (1,2) (S,S-eddv = (S,S)-ethylenediamine-N,Na2-di-2-(3-methyl)butanoato ion; L = oxalate or malonate ion) were prepared. The complexes were purified by ion-exchange chromatography. The geometry of the complexes has been supposed on the basis of the infrared and electronic absorption spectra, and the absolute configurations of the isolated s-cis-[Cr(S,S-eddv)L]-complexes have been predicted on the basis of their circular dichroism (CD) spectra. Also, the results of thermal decomposition have been discussed. Antimicrobial activity of the prepared complexes (1a4) was investigated against 28 species of microorganisms. Testing was performed by microdilution method and minimum inhibitory concentrations (MIC) and minimum microbicidal concentration (MMC) have been determined. Complexes demonstrated in generally low antibacterial and antifungal activity.

Abstract  Cerium(IV) ammonium nitrate (CAN) has recently emerged as a versatile reagent for oxidative electron transfer; the overwhelming number of reports serve as a testimony to the unparalleled utility of CAN in a variety of transformations of synthetic importance. Our recent work has uncovered novel carbon-carbon bond-forming reactions leading to the one-pot synthesis of dihydrofurans, tetrahydrofurans, and aminotetralins. In addition, we have developed a number of facile carbon-heteroatom bond-forming reactions by the CAN-mediated oxidative addition of soft anions to alkenes. A mechanistic rationale has been provided for the reactions explored. As might be expected of very powerful one-electron oxidants, the chemistry of cerium(IV) oxidation of organic molecules is dominated by radical and radical cation chemistry.

Abstract  The new steroidal pyrimidine derivatives (4-6) were synthesized by the reaction of steroidal thiosemicarbazones with (2-methyl) diethyl malonate in absolute ethanol. After characterization by spectral and analytical data, the DNA interaction studies of compounds (4-6) were carried out by UV-vis, fluorescence spectroscopy, hydrodynamic measurements, molecular docking and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 2.31×103M-1, 1.93×103M-1 and 2.05×103M-1, respectively indicating the higher binding affinity of compound 4 towards DNA. Gel electrophoresis demonstrated that compound 4 showed a strong interaction during the concentration dependent cleavage activity with pBR322 DNA. The molecular docking study suggested the intercalation of steroidal pyrimidine moiety in the minor groove of DNA. During in vitro cytotoxicity, compounds (4-6) revealed potential toxicity against the different human cancer cells (MTT assay). During DAPI staining, the nuclear fragmentations on cells occurred after treatment with compounds 4 and 5. Western blotting analysis clearly indicates that compound 4 causes apoptosis in MCF-7 cancer cells. The results revealed that compound 4 has better prospectus to act as a cancer chemotherapeutic candidate, which warrants further in vivo anticancer investigations.

Abstract  A novel series of N-substituted-benzimidazolyl linked para substituted benzylidene based molecules containing three pharmacologically potent hydrogen bonding parts namely; 2,4-thiazolidinedione (TZD: a 2,4-dicarbonyl), diethyl malonate (DEM: a 1,3-diester and an isooxazolidinedione analog) and methyl acetoacetate (MAA: a β-ketoester) (6a-11b) were synthesized and evaluated for in vitro α-glucosidase inhibition. The structure of the novel synthesized compounds was confirmed through the spectral studies (LC-MS, 1H NMR, 13C NMR, FT-IR). Comparative evaluation of these compounds revealed that the compound 9b showed maximum inhibitory potential against α-amylase and α-glucosidase giving an IC50 value of 0.54 ± 0.01 μM. Furthermore, binding affinities in terms of G score values and hydrogen bond interactions between all the synthesized compounds and the AA residues in the active site of the protein (PDB code: 3TOP) to that of Acarbose (standard drug) were explored with the help of molecular docking studies. Compound 9b was considered as promising candidate of this series.

Abstract  A straightforward synthetic pathway allowing the access to anti or syn 2-amino-1,3-diol scaffolds is presented. The strategy relies on a diastereoselective organocatalyzed decarboxylative aldol reaction of a N-Boc-hemimalonate that is easily formed from commercial N-Boc-diethyl malonate. Although this method has been optimized previously with the N-Bz-hemimalonate analogue, this key step was reinvestigated with the N-Boc derivative to improve the required reaction time, the yield, and the diastereoselectivity. The new conditions enhance this transformation, and quantitative yields and anti/syn ratios up to 96:4 can be obtained. The anti aldol product was easily isolated in pure form and then taken forward as the key precursor in the preparation of both a set of ten N-/O-alkylated anti 2-amino-1,3-diol derivatives and the syn congeners.

Abstract  Brain damage is a leading cause of death in patients with cardiac arrest (CA). The accumulation of succinate during ischemia by succinate dehydrogenase (SDH) is an important mechanism of ischemia-reperfusion injury. It was unclear whether inhibiting the oxidation of accumulated succinate could also mitigate brain damage after CA. In this study, rats were subjected to a 6 min of CA, and cardiopulmonary resuscitation (CPR) was performed with administration of normal saline or dimethyl malonate (DMM, a competitive inhibitor of SDH). After the return of spontaneous circulation, neurological function of the rats was assessed by a tape removal test for 3 days. The rats were then sacrificed, and their brains were used to assess neuronal apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Hippocampal tissues were used for Western blotting analysis and biochemical detection. In addition, hippocampal mitochondria during CA and CPR were isolated. The relative mitochondrial membrane potential (MMP) and cytochrome C in the cytosol were detected. Our results show that DMM promoted ROSC and neurological performance in rats after CA. The TUNEL assay showed that DMM reduced neuronal apoptosis. Western blotting analysis showed that DMM inhibited the activation of caspase-3 and enhanced the expression of HIF-1α. Moreover, DMM inhibited excessive hyperpolarization of MMP after CPR, and prevented the release of cytochrome C. Therefore, inhibiting SDH by DMM alleviated brain damage after CA, and the main mechanisms included inhibiting the excessive hyperpolarization of MMP, reducing the generation of mtROS and stabilizing the structure of HIF-1α.

Abstract  A homogeneous C60 tri-diethyl malonate membrane was fabricated by a facile electro-spinning method. Comprehensive characterizations of its assembling structure, such as SEM, TEM, TGA, UV-vis, and FTIR, were carried out. Different fullerene derivatives show different assembling characters during the electrospining process. Notably, C60 tri-diethyl malonate with close-knite structures can form a stable structure after removing the assistant polymer of PVP. The antibacterial experiments of C60 tri-diethyl malonate membrane were performed, and the results revealed that this membrane owns excellent antibacterial activity.

Abstract  Raman spectroscopic detection is one of the suitable methods for the detection of chemical warfare agents (CWAs) and simulants. Since the 1980s, many researchers have been dedicated to the research of chemical characteristic of CWAs and simulants and instrumental improvement for their analysis and detection. The spatial heterodyne Raman spectrometer (SHRS) is a new developing instrument for Raman detection that appeared in 2011. It is already well-known that SHRS has the characteristics of high spectral resolution, a large field-of-view, and high throughput. Thus, it is inherently suitable for the analysis and detection of these toxic chemicals and simulants. The in situ and standoff detection of some typical simulants of CWAs, such as dimethyl methylphosphonate (DMMP), diisopropyl methylphosphonate (DIMP), triethylphosphate (TEP), diethyl malonate (DEM), methyl salicylate (MES), 2-chloroethyl ethyl sulfide (CEES), and malathion, were tried. The achieved results show that SHRS does have the ability of in situ analysis or standoff detection for simulants of CWAs. When the laser power was set to as low as 26 mW, the SHRS still has a signal-to-noise ratio higher than 5 in in situ detection. The standoff Raman spectra detection of CWAs simulants was realized at a distance of 11 m. The potential feasibility of standoff detection of SHRS for CWAs simulants has been proved.

Abstract  A series of novel pyridine and fused pyridine derivatives have been prepared starting from 6-(3,4-dimethylphenyl)-2-hydrazinyl-4-(thiophen-2-yl)-pyridine-3-carbonitrile 1 which on treatment with appropriate formic acid, acetic acid/ acetic anhydride, benzoyl chloride and/or carbon disulfide afforded the corresponding triazolopyridine derivatives 2⁻5. Also, treatment of hydrazide 1 with diethyloxalate, chloroacetyl chloride, chloroacetic acid and/or 1,2-dichloroethane yielded the corresponding pyridotriazine derivatives 7⁻10. Further transformation of compound 1 with a different active methylene group, namely acetyl acetone, diethylmalonate, ethyl cyanoacetate, ethyl benzoylacetate and/or ethyl acetoacetate, produced the pyridine⁻pyrazole hybrid derivatives 11⁻15. These newly synthesized compounds (1⁻15) were subjected to in silico molecular docking screenings towards GlcN-6-P synthase as the target protein. The results revealed moderate to good binding energies of the ligands on the target protein. All the newly prepared products exhibited antimicrobial and antioxidant activity.

Abstract  A discrete tetranuclear thiourea-based metal-organic macrocycle (MOM) with a large size was constructed by a well-designed organic ligand and nickel(ii) ions via self-assembly. Incorporating thiourea groups as hydrogen-bond donors into a metal-organic complex system leads to a new approach for synthesizing functionalized heterogeneous catalysts, as this not only introduces coordination sites serving as chelators, but also overcomes the issues of self-association via intermolecular H-bonding, often occurring in homogeneous systems. The packing structure of this material formed a confined environment suitable for the access of substrate molecules dragged by the strong hydrogen-bond interactions from the thiourea groups, thus achieving a high catalytic performance in Michael additions of nitrostyrenes to nitroalkanes, with remarkable yields and size-selectivity in heterogeneous phase. Moreover, a comparison of the IR spectrum of Ni-SPT with the spectra of dimethyl malonate- and β-nitrostyrene-impregnated Ni-SPT indicated that both substrate molecules, β-nitrostyrene and dimethyl malonate, were able to access the cavity of the trimeric subunit.

Abstract  A photocatalytic process for 1,7-enyne bicyclizations with α-bromo diethyl malonate has been established via synergistic domino bicyclizations. This protocol provides an efficient and practical method for the synthesis of various cyclopenta[c]quinolines and benzo[j]phenanthridines under operational simplicity and mild reaction conditions.