Dimethyl Itaconate Research Articles

Compositional design and Taguchi optimization of hardness properties in silicone-based ocular lenses

A multi-component acrylate-based copolymer system especially designed for application as ocular lenses is developed through free-radical, bulk polymerization of a system containing hydroxyethyl methacrylate, methyl methacrylate, triethylene glycol dimethacrylate, dimethyl itaconate, 3-(trimethoxysilyl) propylmethacrylate, Polyhedraloligomeric silsesquioxane-acrylate (POSS-acrylate) and AIBN as an initiator. The progress of the reaction was monitored by Fourier transform infrared spectroscopy (FTIR). The effect of increasing concentration of the components on the hardness of the synthesized lenses was measured by Shore Durometer before and after immersion in PBS solutions. Extraction test method was performed to analyze the biocompatibility of the fabricated lenses. In this research the Taguchi method was employed to achieve the optimal hardness property which plays a critical role in final application of the lens materials. The Taguchi trial for ocular lens hardness was configured in an L16 orthogonal array, by five control factors, each with four level settings. The results showed that 3-(trimethoxysilyl) propyl methacrylate decreases and 2-hydroxyethylmethacrylate increases, polyhedraloligomeric silsesquioxane with a cage-like structure, methyl methacrylate and dimethyl itaconate increase the hardness. Proliferation and growth of the cells showed that there is no toxic substance extracted from the lenses which can interfere with the cell growth.

Rhodium-catalyzed hydroformylation in γ-valerolactone as a biomass-derived solvent

Rhodium-catalyzed hydroformylation of styrene, α-methylstyrene, dimethyl itaconate, and (R)-limonene was performed in gamma-valerolactone (GVL) as a proposed biomass-based environmentally benign solvent for hydroformylation referring to toluene as a generally used conventional solvent. Both achiral (triphenylphosphine, 1,3-bis(diphenylphoshino)propane) and enantiopure bidentate phosphine ligands ((S,S)-BDPP, (R)-BINAP, (R)-QUINAP, (R,R)-DIOP, (Rc),(Sp)-JOSIPHOS, (S)-SEGPHOS, (S)-(DM)-SEGPHOS) were investigated in in situ generated Rh-diphosphine catalyst systems. In general, the catalysts' activity in GVL was lower than in toluene; however, remarkable chemo- (>99%) and regioselectivities (>95%) were achieved in GVL under identical conditions. The BDPP-modified Rh-catalyst was recycled for three consecutive cycles; however a decrease in its activity was detected.

Effect of tacticity on the cyclization of polyacrylonitrile copolymers

This work investigated polyacrylonitrile copolymers synthesized using methyl acrylate (MA) and dimethyl itaconate (DMI) as second monomers by bulk polymerization in the presence of magnesium chloride as a reagent to control the tacticity of polyacrylonitrile copolymers. The copolymers synthesized by solution polymerization were used as a control group to study the tacticity effect. The 13C-NMR results confirm that the isotacticity by bulk polymerization is increased approximately double for either P(AN-co-MA) or P(AN-co-DMI). The X-ray diffraction (XRD) and the isothermal DSC results show that the P(AN-co-MA) produced by bulk process, as compared to that by solution polymerization, has higher domain size (L c ) and crystallinity (CI); moreover, its cyclization period is decreased significantly. It indicates that the increase of isotacticity for P(AN-co-MA) makes the crystalline domain larger and the cyclization takes place more easily. However, such positive correlations do not hold good for the P(AN-co-DMI) system. It is due to the high steric-hindrance effect for the DMI monomer, which has long reactive branches on both sides of the vinyl DMI monomer, complicating the mechanisms of crystallization and cyclization and resulting in diminishing the contribution of high isotacticity to lower the barrier of cyclization reaction.

Dimethyl Itaconate Is Not Metabolized into Itaconate Intracellularly

Itaconic acid is an important metabolite produced by macrophages after stimulation with LPS. The role of itaconate in the inflammatory cascade is unclear. Here we used [13C]itaconate and dimethyl [13C]itaconate (DMI) to probe itaconate metabolism, and find that [13C]DMI is not metabolized to itaconate. [13C]Itaconate in the cell culture medium leads to elevated intracellular levels of unlabeled succinate, with no evidence of intracellular uptake. The goal of this study is to encourage the development of effective pro-drug strategies to increase the intracellular levels of itaconate, which will enable more conclusive analysis of its action on macrophages and other cell and tissue types.

Asymmetric Allylic Alkylation and Hydrogenation with Transition Metal Complexes of Diphosphite Ligands Based on (1S,2S)-Trans-1,2-cyclohexanediol

The preparation of new palladium complexes in situ that were composed of a series of chiral diphosphite ligands, which were derived from (1S,2S)-trans-1,2-cyclohexanediol, have been described. It was found that (1S,2S)-bis[(S)-1,1′-binaphthyl-2,2′-diyl]phosphite-cyclohexanediol was the suitable ligand in the Pd-catalyzed allylic alkylation, and up to 75% ee for (E)-dimethyl 2-(1,3-diphenylallyl)malonate was obtained. In compared with the results of the asymmetric allylic alkylation, (1S,2S)-bis[(R)-1,1′-binaphthyl-2,2′-diyl]phosphite-cyclohexanediol was proved to be the most efficient ligand in the Rh-catalyzed asymmetric hydrogenation of dimethyl itaconate and enamides with up to 99% ee. The stereochemically matched combinations between the diol skeleton and diaryl moieties of the ligands were essential for inducing high enantioselectivities in the two transformations. It was found that the sense of the enantiodiscrimination of the products was mainly determined by the configuration of the binaphthyl phosphite moieties.

Tail-to-tail dimerization and Rauhut-Currier reaction of disubstituted Michael acceptors catalyzed by N-heterocyclic carbene

The N-heterocyclic carbene (NHC)-catalyzed dimerizations of a variety of disubstituted Michael acceptors have been investigated. In addition to the tail-to-tail dimerization of methacrylates reported previously, the scope of vinylidene substrates expands to γ-methyl-α-methylene-γ-butyrolactone, dimethyl 2-methylenepentanedioate, dimethyl itaconate, methacrylamides, and 2-isopropenylbenzoxazole, none of which have been dimerized by metal-catalyzed counterparts. In contrast, vinylene substrates, such as crotononitrile, methyl crotonate, and 2-cyclohexen-1-one, do not undergo the dimerization probably due to the steric hindrance of the β-substituent. Instead, the Rauhut-Currier (RC) reaction of these was found to proceed. The stoichiometric reaction of crotononitrile with NHC indicates that this RC reaction also involves the deoxy-Breslow intermediate and the reversible proton transfer.

Correlation between the Selectivity and the Structure of an Asymmetric Catalyst Built on a Chirally Amplified Supramolecular Helical Scaffold.

For the first time, supramolecular helical rods composed of an achiral metal complex and a complementary enantiopure monomer provided a good level of enantioinduction in asymmetric catalysis. Mixtures containing an achiral ligand monomer (BTA(PPh2), 2 mol %) and an enantiopure ligand-free comonomer (ester BTA, 2.5 mol %), both possessing a complementary benzene-1,3,5-tricarboxamide (BTA) central unit, were investigated in combination with [Rh(cod)2]BArF (1 mol %) in the asymmetric hydrogenation of dimethyl itaconate. Notably, efficient chirality transfer occurs within the hydrogen-bonded coassemblies formed by BTA Ile and the intrinsically achiral catalytic rhodium catalyst, providing the hydrogenation product with up to 85% ee. The effect of the relative content of BTA Ile as compared to the ligand was investigated. The amount of chiral comonomer can be decreased down to one-fourth of that of the ligand without deteriorating the enantioselectivity of the reaction, while the enantioselectivity decreases for mixtures containing high amounts of BTA Ile. The nonlinear relationship between the amount of chiral comonomer and the enantioselectivity indicates that chirality amplification effects are at work in this catalytic system. Also, right-handed helical rods are formed upon co-assembly of the achiral rhodium complex of BTA(PPh2) and the enantiopure comonomer BTA Ile as confirmed by various spectroscopic and scattering techniques. Remarkably, the major enantiomer and the selectivity of the catalytic reaction are related to the handedness and the net helicity of the coassemblies, respectively. Further development of this class of catalysts built on chirally amplified helical scaffolds should contribute to the design of asymmetric catalysts operating with low amounts of chiral entities.

Flexible synthesis of diverse N-heterocycles from substrates attainable from biomass

A suite of structurally diverse N-heterocycles have been prepared from pyrrole and dimethyl itaconate, two compounds attainable from biomass.

Chiral diphosphites derived from (1R,2R)-trans-1,2-cyclohexanediol: a new class of ligands for asymmetric hydrogenations

A series of novel chiral diphosphite ligands was easily prepared in a few steps from commercial (1R,2R)-trans-1,2-cyclohexanediol as the chiral source, and successfully employed in the Rh-catalyzed asymmetric hydrogenation of α,β-unsaturated carboxylic acid derivatives and enamides with up to 99% ee for dimethyl itaconate and enamides and with up to 94% ee for α-dehydroamino acid esters. The stereochemically matched combination of (1R,2R)-trans-1,2-cyclohexanediol backbone and (S)-binaphthyl in the ligand (1R,2R)-bis[(S)-1,1′-binaphthyl-2,2′-diyl]phosphitecyclohexanediol, was essential for inducing high enantioselectivity. Moreover, the sense of enantiodiscrimination of the products was mainly determined by the configuration of the binaphthyl moieties.

Synthesis of P‐Stereogenic Phosphoramidite and Phosphorodiamidite Ligands and Their Application in Asymmetric Catalysis

AbstractA series of P‐stereogenic monodentate phosphoramidite (PNO2) and phosphorodiamidite (PN2O) ligands based on chiral Betti bases has been prepared by modular synthetic procedures. The chirality at the phosphorus can be controlled to a large extent by the synthetic route, leading to stereoselective access to single P‐epimers. The absolute configuration of the P‐atom was assigned by X‐ray diffraction analysis. The new ligands were evaluated in asymmetric catalysis and the influence of the exocyclic amine or alcohol moiety as well as the interplay between the P‐chirality and the stereocenters in the backbone were investigated. Enantioselectivities of up to 85 and 83 % ee were obtained in the Rh‐catalyzed hydrogenation of dimethyl itaconate and in the Pd‐catalyzed allylic amination of (rac)‐(E)‐1,3‐diphenylallyl acetate with benzylamine, respectively. In the Ni‐catalyzed hydrovinylation of styrene, ee values of up to 68 %, excellent chemoselectivities, and high activities (TOFav up to 3000 h–1) were achieved.

Radical polymerization of acrylonitrile under the action of catalytic systems based on zero-valent copper

Specific features of the (co)polymerization of acrylonitrile in the presence of a catalytic system based on zero-valent copper and 2,2-bipyridyl in various solvents was studied. It is shown that these systems can be successfully used in the presence of halogen-containing initiators to obtain homo- and copolymers of acrylonitrile with dimethyl itaconate and methyl acrylate in the controlled mode. It was found that introduction of comonomers (methyl acrylate and dimethyl itaconate) in low concentrations has no effect on parameters of the acrylonitrile polymerization process, but strongly affects some properties and characteristics of samples being synthesized.

Synthesis of new N-substituted chiral phosphine–phosphoramidite ligands and their application in asymmetric hydrogenations and allylic alkylations

Phosphine–phosphoramidite ligands containing a 2,4-pentanediyl backbone, BINOL moieties, and Me, Bn or Ph substituent on the nitrogen were synthesized and fully characterized. The electronic effect of the N-substituents was examined by 31P NMR of their corresponding seleno-phosphate-amide and phosphine–selenide derivatives. The new ligands together with their earlier reported derivatives were tested in the palladium catalyzed asymmetric allylic alkylation of rac-(E)-1,3-diphenylallyl acetate. Remarkably high activity (up to 1780h−1 turnover frequency) and first order kinetics were observed by facilitating nucleophile formation. The substituent at the nitrogen and the configuration of chiral moieties had a high impact on the enantioselectivity. The new ligands were also tested in the rhodium-catalyzed asymmetric hydrogenation of methyl (Z)-α-acetamidocinnammate, dimethyl itaconate (up to 99.9% ee’s) and methyl 2-acetamidoacrylate (up to 99.5% ee).

Understanding Potentials and Restrictions of Solvent‐Free Enzymatic Polycondensation of Itaconic Acid: An Experimental and Computational Analysis

AbstractItaconic acid is a chemically versatile unsaturated diacid that can be produced by fermentation and potentially it can replace petrol‐based monomers such as maleic and fumaric acids in the production of curable polyesters or new biocompatible functionalized materials. Unfortunately, due to the presence of the unsaturated CC bond, polycondensation of itaconic acid is hampered by cross reactivity and isomerization. Therefore, enzymatic polycondensations would respond to the need of mild and selective synthetic routes for the production of novel bio‐based polymers. The present work analyses the feasibility of enzymatic polycondensation of diethyl itaconate and, for the first time, provides comprehensive solutions embracing both the formulation of the biocatalyst, the reaction conditions and the choice of the co‐monomers. Computational docking was used to disclose the structural factors responsible for the low reactivity of dimethyl itaconate and to identify possible solutions. Surprisingly, experimental and computational analyses revealed that 1,4‐butanediol is an unsuitable co‐monomer for the polycondensation of dimethyl itaconate whereas the cyclic and rigid 1,4‐cyclohexanedimethanol promotes the elongation of the oligomers.magnified image

The Mechanical Properties of a Poly(methyl methacrylate) Denture Base Material Modified with Dimethyl Itaconate and Di-n-butyl Itaconate

This study investigates a wide range of clinically relevant mechanical properties of poly(methyl methacrylate) (PMMA) denture base materials modified with di-methyl itaconate (DMI) and di-n-butyl itaconate (DBI) in order to compare them to a commercial PMMA denture base material. The commercial denture base formulation was modified with DMI and DBI by replacing up to 10 wt% of methyl methacrylate (MMA) monomer. The specimens were prepared by standard bath curing process. The influence of the itaconate content on hardness, impact strength, tensile, and thermal and dynamic mechanical properties was investigated. It is found that the addition of di-n-alkyl itaconates gives homogenous blends that show decreased glass transition temperature, as well as decrease in storage modulus, ultimate tensile strength, and impact fracture resistance with increase in the itaconate content. The mean values of surface hardness show no significant change with the addition of itaconates. The magnitude of the measured values indicates that the poly(methyl methacrylate) (PMMA) denture base material modified with itaconates could be developed into a less toxic, more environmentally and patient friendly product than commercial pure PMMA denture base material.

ChemInform Abstract: Cu(I)/TF—BiphamPhos‐Catalyzed Asymmetric 1,3‐Dipolar Cycloaddition of Azomethine Ylides with Dimethyl Itaconate and 2‐Methyleneglutarate.

Catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides with dimethyl itaconate and 2-methyleneglutarate was realized with the Cu(I)/TF–BiphamPhos complex as the catalyst for the efficient construction of pyrrolidine derivatives bearing one unique all carbon-quaternary and two tertiary stereogenic centers. The current catalytic system exhibited excellent diastereoselectivity (> 20:1), good enantioselectivity (88–>99% ee) and broad substrate scope under mild conditions.

Synthesis of 2,3-di- and 2,2,3-trisubstituted-3-methoxycarbonyl-γ-butyrolactones as potent antitumor agents.

Various 2,3-substituted γ-butyrolactones have been synthesized by three-component reaction of aryl bromides, dimethyl itaconate and carbonyl compounds. The in vitro cytotoxic activity of these products was evaluated against a representative panel of cancer cell lines (KB, HCT116, MCF7, MCF7R, PC3, SK-OV3, HL60 and HL60R). One compound (4x) displays a good anti-proliferative activity with IC50 in the sub-micromolar range. The mechanism of action has been investigated using flow cytometry.

Recent developments in hydrogenation and hydroformylation in surfactant systems

We investigate surfactant systems for catalytic gas/liquid reactions, namely the hydrogenation of dimethylitaconate (DMI) and the hydroformylation of the long-chain olefin 1-dodecene. We show that surfactant selection is crucial to obtain a high activity and selectivity. Choosing an appropriate surfactant results in comparable selectivity's as in conventional organic solvents, but usually at lower activities. For microemulsion systems, the activity is strongly influenced by the phase behavior. For both reactions we present a concept of catalyst recycling based on the specific properties of the surfactant system. The efficiency for catalyst recycling is >97% with minor loss in activity.

New chiral diphosphoramidite rhodium(I) complexes for asymmetric hydrogenation

Chiral 1,5‐cyclooctadiene rhodium(I) cationic complexes with C2‐symmetric chelate diphosphoramidite ligands containing (R,R)‐1,2‐diaminocyclohexane as the backbone and two atropoisomeric biaryl units were easily synthesized and fully characterized by multinuclear one‐ and two‐dimensional NMR spectroscopy and elemental analysis. These complexes were used as catalysts in the asymmetric hydrogenation of dimethyl itaconate, methyl 2‐acetamidoacrylate and (Z)‐methyl‐2‐acetamido‐3‐phenylacrylate. The rhodium complexes derived from diphosphoramidite ligands that contain two (R) or (S) BINOL (2,2′‐dihydroxy‐1,1′‐binaphthyl) units proved to be efficient catalysts, giving complete conversion and very good enantioselectivity (up to 88% ee). An uncommon positive H2 pressure effect on the enantioselectivity was observed in the hydrogenation of dimethyl itaconate catalyzed by Rh‐complex with diphosphoramidite ligand that contains two (S)‐binaphthol moieties. Copyright © 2014 John Wiley & Sons, Ltd.

N-Alkylated dinitrones from isosorbide as cross-linkers for unsaturated bio-based polyesters.

Isosorbide was esterified with acryloyl chloride and crotonic acid yielding isosorbide diacrylate (9a) and isosorbide dicrotonate (9b), which were reacted with benzaldehyde oxime in the presence of zinc(II) iodide and boron triflouride etherate as catalysts to obtain N-alkylated dinitrones 10a/b. Poly(isosorbide itaconite -co- succinate) 13 as a bio-based unsaturated polyester was cross-linked by a 1,3-dipolar cycloaddition with the received dinitrones 10a/b. The 1,3-dipolar cycloaddition led to a strong change of the mechanical properties which were investigated by rheological measurements. Nitrones derived from methyl acrylate (3a) and methyl crotonate (3b) were used as model systems and reacted with dimethyl itaconate to further characterize the 1,3-dipolaric cycloaddition.

Asymmetric Hydrovinylation and Hydrogenation with Metal Complexes of C3‐Symmetric Tris‐Binaphthyl Monophosphites

AbstractNeutral allyl–palladium complexes stabilised by bulky tris‐binaphthyl monophosphite ligands have been prepared and fully characterised in solution by NMR spectroscopy, which evidenced a dynamic equilibrium between two diastereomeric species. The new allyl–palladium phosphite complexes have been evaluated as catalytic precursors in the asymmetric hydrovinylation of styrene; they show moderate activity and good to excellent chemo‐ and enantioselectivity depending on the substituent at the ligand 2′‐binaphthyl position. Remarkably, the palladium complex bearing the ligand with an adamantyl ester substituent led to 92 % ee toward (R)‐3‐phenyl‐1‐butene, which suggests that the ester functionality might provide a secondary hemilabile interaction with the metal, thus favouring the enantioselectivity control. Rhodium(I) complexes formed in situ with the same ligands were further applied in the hydrogenation of dimethyl itaconate, but gave limited activity. The best enantioselectivity (62 %) was achieved with the same ligand that contained the adamantyl ester substituent.