Dimethyl Malonate Research Articles

Dimerization/Elimination of β-Styrylmalonates under Action of TiCl4.

A new type of dimerization of dimethyl (β-styryl)malonates in the presence of TiCl4 accompanied by elimination of a methanol molecule was discovered. Selective methods for the synthesis of substituted trimethyl 4-hydroxy-[1,1'-biaryl]-3,3,5(2H)-tricarboxylates and trimethyl 7-hydroxy-9,10-dihydro-5,9-methanobenzo[8]annulene-6,8,8(5H)-tricarboxylates were developed. The regularities of the occurring processes were determined and a similar reaction of β-styrylmalonate with benzylidenemalonate in the presence of TiCl4 was performed in the scope of the suggested mechanism.

Succinate level is increased and succinate dehydrogenase exerts forward and reverse catalytic activities in lipopolysaccharides-stimulated cardiac tissue: The protective role of dimethyl malonate

This study aimed to investigate the alterations of myocardial succinate and fumarate levels with or without succinate dehydrogenase (SDH) inhibitor dimethyl malonate during 24 h of lipopolysaccharides (LPS) challenge, as well as the effects of dimethyl malonate on the impaired cardiac tissue. Myocardial succinate and fumarate levels were increased in the initial 9 h of LPS challenge. During this time, dimethyl malonate increased the succinate level, decreased the fumarate level, aggravated the cardiac dysfunction, reduced the oxidative stress, had little effect on interleukin-1β production, promoted interleukin-10 production and bothered the ATP production. Co-treatment with exogenous succinate significantly increased interleukin-1β production in this period. After 12 h of LPS challenge, myocardial the succinate level increased sharply, while the fumarate level gradually decreased. During 12–24 h of LPS challenge, dimethyl malonate effectively reduced the succinate level, increased the fumarate level, improved cardiac dysfunction, inhibited interleukin-1β production, and had little effect on oxidative stress, interleukin-10 production, and ATP production. LPS challenge also significantly increased the myocardial succinate receptor 1 expression and circulating succinate level. Inhibition of succinate receptor 1 significantly reduced the mRNA expression of interleukin-1β. In conclusion, the current study suggests that myocardial succinate accumulates during LPS challenge, and that SDH activity may be transformed (from forward to reversed) and involved in a line of stress response. Dimethyl malonate inhibits SDH and, depending on the time of treatment, reduces LPS-induced cardiac impairment. Furthermore, accumulated succinate exerts pro-inflammatory effects partly via succinate receptor 1 signaling.

P,S-Bidentate Phosphoramidites with (Ra)-BINOL Core in Palladium-Catalyzed Asymmetric Allylic Substitution

New P,S-bidentate phosphoramidite ligands, including these having a stereogenic phosphorus atom in the 1,3,2-dioxaphosphepine ring, have been synthesized on the basis of (Ra)-BINOL and its adamantanyl derivatives. With their participation in the Pd-catalyzed asymmetric allylic alkylation of (E)-1,3-diphenylallyl acetate with dimethyl malonate and the amination with pyrrolidine involving these ligands have afforded selectivity up to 84 and 75% ee, respectively.

Excess Thermodynamic Properties of Binary Mixtures of Dimethyl Malonate with some Branched Alkanols

The intermolecular hydrogen bond interactions in the dimethyl malonate with some branched alkanols (2-methyl-1-propanol, 2-propanol, and 2-butanol) binary mixture have been studied experimentally and theoretically. The ultrasonic velocities U, densities ρ of binary mixtures of dimethyl malonate with 2-methyl-1-propanol, 2-propanol, 2-butanol from 303.15 K to 318.15 K were measured. Excess molar volume (VE), deviation in adiabatic compressibility (Δβad) and excess intermolecular free length ( LEf) have been calculated from the measured experimental data. It is observed that the order of interactions in dimethyl malonate – branched alkanols mixtures is 2-methyl-1-propanol > 2-propanol > 2-butanol.

Asymmetric Total Synthesis of (+)-Alstonlarsine A.

The first asymmetric total synthesis of (+)-alstonlarsine A has been realized. The prominent features of the current synthesis include the following: (i) a Pd/self-adaptable ligand complex-catalyzed asymmetric allylic alkylation of 2-methyl-2-cyclopentenyl carbonate with 2-indolylsubstituted dimethyl malonate to establish the key stereocenter of C15, (ii) an intramolecular nitrile oxide-alkene [3 + 2] cycloaddition (INOC [3 + 2]) to construct the cyclohepta[b]indole backbone with the installment of the requisite stereochemistry of the all-carbon quaternary center of C20, and (iii) a late-stage interrupted Pictet-Spengler reaction (IPSR) to rapidly assemble the core structure of (+)-alstonlarsine A.

Effects of Different Gasoline Additives on Fuel Consumption and Emissions in a Vehicle Equipped With the GDI Engine

Fuel additives are considered to be a cost-effective and simple approach to improve combustion and reduce the harmful emissions of internal combustion engines. In addition to the use of conventional fuel additives, some unconventional fuel additives also have potential to improve fuel properties. Exploring the effects of different unconventional additives can provide a valuable reference to improve vehicle performance by fuel optimization. In this study, five unconventional gasoline additives (i.e., isopropyl ether, aniline, diethylamine, dimethyl malonate and p-tert-butylphenol) were blended with the baseline gasoline (G92). The five blended fuels are referred to as G92-1, G92-2, G92-3, G92-4, and G92-5, respectively. Fuels with different additives were tested on a compact passenger vehicle with a 1.4-L gasoline direct injection engine to assess the effects of these additives on performance and emission characteristics, and G92 gasoline was compared as a baseline. The new European drive cycle (NEDC), which is representative for passenger car and light duty vehicles, was chosen in the tests. The experimental results show little or slight improvement in fuel consumption for fuels blended with additives. With respect to gaseous emissions, the vehicle obtains the lowest and highest NOx emissions by fueling G92-5 (blended with p-tert-butylphenol) and G92-3 (blended with diethylamine), respectively; the lowest and highest CO emission is acquired using G92-2 (blended with aniline) and G92-4 (blended with dimethyl malonate), respectively; the vehicle reaches the lowest and highest THC emissions when fueling G92-3 (blended with diethylamine) and G92-4 (blended with dimethyl malonate), respectively; and the lowest and highest CO2 emission using G92-3 (blended with diethylamine) and G92-2 (blended with aniline), respectively. Compared with the baseline gasoline fuel, all of the fuels with additives show improved engine-out PM emissions. Furthermore, all five additives can improve the acceleration performance slightly. In brief, diethylamine is potential gasoline additive to reduce carbon emissions, improve fuel consumption, and enhance performance.

Catalytic [2+2+2] Tandem Cyclization with Alkyl Substituted Methylene Malonate Enabling Concise Total Synthesis of Four Malagasy Alkaloids

Catalytic [2+2+2] Tandem Cyclization with Alkyl Substituted Methylene Malonate Enabling Concise Total Synthesis of Four Malagasy Alkaloids

Synthesis of Ester-Substituted Indolizines from 2-Propargyloxypyridines and 1,3-Dicarbonyls.

Two new complementary Au(I)-catalyzed methods for the preparation of ester-substituted indolizines from easily accessible 2-propargyloxypyridines and either acetoacetates or dimethyl malonate are reported. These reactions tolerate a wide range of functionality, allowing for diversification at three distinct positions of the product (R, R1, R2). For electron-poor substrates, the highest yields are observed upon reaction with acetoacetates, while neutral and electron-rich substrates give higher yields upon treatment with dimethyl malonate.

“Stacked-arene”-type organocatalysts: Utilization of π-π interaction as an electron tuning tool

We have developed a novel type of organocatalyst having a 1,8‑diarylnaphthalene core, namely, a “Stacked-arene”-type organocatalyst. The key point of the catalyst design is the π-π interaction based electron tuning. This through space electron tuning effect is effective enough for the improvement of the catalytic activity (reducing the catalyst loading), and this tendency was evaluated by the Michael addition reaction between nitrostyrene and dimethyl malonate. Additional experiments suggest that the expected improvement of the hydrogen bonding ability plays a critical role in the high performance of the designed catalyst.

Synthesis, Reactivity, and Properties of Benz[a]azulenes via the [8 + 2] Cycloaddition of 2H-Cyclohepta[b]furan-2-ones with an Enamine.

Starting with the reaction of 2H-cyclohepta[b]furan-2-ones with an enamine, which was prepared from 4-tert-butylcyclohexanone and pyrrolidine, benz[a]azulenes having both formyl and tert-butyl groups were obtained in the three-step sequence. Subsequently, both the formyl and tert-butyl groups were eliminated by heating the benz[a]azulene derivatives in 100% H3PO4 to give benz[a]azulenes without these substituents in high yields. In terms of product yield, this method is the best one ever reported for the synthesis of the parent benz[a]azulene so far. The conversion of the benz[a]azulene derivatives with a formyl group into cyclohept[a]acenaphthylen-3-one derivatives was also investigated via Knoevenagel condensation with dimethyl malonate, followed by Brønsted acid-mediated intramolecular cyclization. The structural features including the bond alternation in the benz[a]azulene derivatives were revealed by NMR studies, NICS calculations, and a single-crystal X-ray structural analysis. The optical and electrochemical properties of a series of benz[a]azulene derivatives were evaluated by UV/Vis, fluorescence spectroscopy, and voltammetry experiments. As a result, we found that some benz[a]azulene derivatives showed remarkable luminescence in acidic media. In addition, the benz[a]azulene derivatives with the electron-withdrawing group and cyclohept[a]acenaphthylen-3-one derivative displayed good reversibility in the spectral changes under the electrochemical redox conditions.

Continuous Flow Biocatalysis: Synthesis of Coumarin Carboxamide Derivatives by Lipase TL IM from Thermomyces lanuginosus

Coumarin carboxamide derivatives are important building blocks for organic synthesis and chemical biology due to their excellent biopharmaceutical properties. In this paper, we demonstrate for the first time a two-step enzymatic synthesis of coumarin carboxamide derivatives. Salicylaldehyde and dimethyl malonate were reacted to obtain coumarin carboxylate methyl derivatives, which were then reacted with various amines under the catalysis of lipase TL IM from Thermomyces lanuginosus to obtain coumarin carboxamide derivatives in continuous flow reactors. We studied various reaction parameters on the yields. The important features of this method include mild reaction conditions, a short reaction time (40 min), reduced environmental pollution, higher productivity (STY = 31.2941 g L−1 h−1) and enzymes being relatively easy to obtain.

Dimethyl malonate based organic compounds bearing different aromatic substituents: Synthesis, photophysics and application in anti-blue light lenses

Five new organic conjugated molecules (TM1–TM5) based on the electron-withdrawing unit (dimethyl malonate) were synthesized and studied. Among them, TM1–TM4 exhibited intense absorption bands from ultraviolet to blue region, which were mainly arisen from the π–π* transitions, mixed with intramolecular charge transfer (ICT) characters. The absorption bands in the region of 360–450 nm for TM5 might be assigned to ICT transitions, mixed with the π–π* feature. Meanwhile, the increasing electron-donating ability of the substituents caused a bathochromic shift of emission. The different electron-donating substituents in the molecular structure make a slight difference in oxidation potential. Furthermore, there is almost no mass loss up to 200 °C for these compounds and all of them exhibit the satisfactory photostability. In addition, the anti-blue light performance of these compounds doped in optical films was studied and TM5 exhibited the best anti-blue light performance. These photophysical, photochemical and electrochemical properties indicated that organic conjugated small molecules containing dimethyl malonate unit are excellent optical functional materials for anti-blue light applications.

Dimethyl malonate slows succinate accumulation and preserves cardiac function in a swine model of hemorrhagic shock.

Succinate (SI) is a citric acid cycle metabolite that accumulates in tissues during hemorrhagic shock (HS) due to electron transport chain uncoupling. Dimethyl malonate (DMM) is a competitive inhibitor of SI dehydrogenase, which has been shown to reduce SI accumulation and protect against reperfusion injury. Whether DMM can be therapeutic after severe HS is unknown. We hypothesized that DMM would prevent SI buildup during resuscitation (RES) in a swine model of HS, leading to better physiological recovery after RES. The carotid arteries of Yorkshire pigs were cannulated with a 5-Fr catheter. After placement of a Swan-Ganz catheter and femoral arterial line, the carotid catheters were opened and the animals were exsanguinated to a mean arterial pressure (MAP) of 45 mm. After 30 minutes in the shock state, the animals were resuscitated to a MAP of 60 mm using lactated ringers. A MAP above 60 mm was maintained throughout RES. One group received 10 mg/kg of DMM (n = 6), while the control received sham injections (n = 6). The primary end-point was SI levels. Secondary end-points included cardiac function and lactate. Succinate levels increased from baseline to the 20-minute RES point in control, while the DMM cohort remained unchanged. The DMM group required less intravenous fluid to maintain a MAP above 60 (450.0 vs. 229.0 mL; p = 0.01). The DMM group had higher pulmonary capillary wedge pressure at the 20-minute and 40-minute RES points. The DMM group had better recovery of cardiac output and index during RES, while the control had no improvement. While lactate levels were similar, DMM may lead to increased ionized calcium levels. Dimethyl malonate slows SI accumulation during HS and helps preserve cardiac filling pressures and function during RES. In addition, DMM may protect against depletion of ionized calcium. Dimethyl malonate may have therapeutic potential during HS.

Itaconate and Its Derivatives Repress Early Myogenesis In Vitro and In Vivo.

A Krebs cycle intermediate metabolite, itaconate, has gained attention as a potential antimicrobial and autoimmune disease treatment due to its anti-inflammatory effects. While itaconate and its derivatives pose an attractive therapeutic option for the treatment of inflammatory diseases, the effects outside the immune system still remain limited, particularly in the muscle. Therefore, we endeavored to determine if itaconate signaling impacts muscle differentiation. Utilizing the well-established C2C12 model of in vitro myogenesis, we evaluated the effects of itaconate and its derivatives on transcriptional and protein markers of muscle differentiation as well as mitochondrial function. We found itaconate and the derivatives dimethyl itaconate and 4-octyl itaconate disrupt differentiation media-induced myogenesis. A primary biological effect of itaconate is a succinate dehydrogenase (SDH) inhibitor. We find the SDH inhibitors dimethyl malonate and harzianopyridone phenocopie the anti-myogenic effects of itaconate. Furthermore, we find treatment with exogenous succinate results in blunted myogenesis. Together our data indicate itaconate and its derivatives interfere with in vitro myogenesis, potentially through inhibition of SDH and subsequent succinate accumulation. We also show 4-octyl itaconate suppresses injury-induced MYOG expression in vivo. More importantly, our findings suggest the therapeutic potential of itaconate, and its derivatives could be limited due to deleterious effects on myogenesis.

Clinico-Biochemical Presentation of Classical Organic Aciduria Presenting as Intoxication in Tertiary Care Hospital of Peshawar

Background: About 5 million children died in 2017 in developing countries alone, amongst them 15-20% are due to inherited metabolic disorders. Inherited metabolic disorders like Methyl Malonic Aciduria, Isovaleric aciduria, Glutaric Aciduria type 1, Urea cycle defects, Maple syrup urine disease & multiple carboxylase deficiency present mostly as intoxication, ataxia and convulsions Objective:To find the pattern of classical organic aciduria in children of different age and gender Methodology: This cross-sectional descriptive study was conducted at Paediatrics department of Town Women & Children Hospital, Peshawar from Aug 2018- Aug 2020. Patients aged 0-24 months were included in the study based on inclusion criteria.Clinical data, preliminary investigations and urinary organic acids profile were collected. Data were analysed using SPSS version 21. Results: Out of 178 total patients, 36 patients were diagnosed with classical Organic aciduria in this present study. Mean age of the study population was 0.865+/- 1.07654 years and range of 1 - 2 years. About 20(53%) cases were males, while 16(47%) cases were females. Major clinical and biochemical findings included seizures, feeding difficulties, developmental delay, neurological impairment, and motor weakness, hypoglycemic and metabolic acidosis. Conclusion: The cases positive for inherited metabolic disorder showed a significant prevalence. Methyl Malonic Aciduria was the commonest of the OAs found in Northern areas of Pakistan followed by 3- Methyl Glutaconic aciduria.Simple heel prick test alongside blood gas analysis and confirmatory test by urinary Gas Chromatography Mass Spectrometry were helpful in diagnosis of such inherited metabolic disorder. Keywords: Intoxication; Organic aciduria;Ethyl Malonic aciduria; Fumaric Aciduria

Homogeneous Catalytic Hydrogenation of Dimethyl Malonate into 1,3-Propanediol

Homogeneous Catalytic Hydrogenation of Dimethyl Malonate into 1,3-Propanediol

The Preparation and Resolution of Novel Axially Chiral Pyrazine‐Containing P,N Ligands for Asymmetric Catalysis and Their Application in Palladium‐Catalysed Allylic Substitution

AbstractThe design and synthesis of two novel pyrazine‐containing ligands, 3,6‐diisopropyl‐Pyrazinap and Np−Cy‐Pyrazinap, has been described. Their synthesis was accomplished in six and nine steps, respectively, in which the key steps were the formation of the biaryl linkage through a Suzuki cross‐coupling reaction and the formation of the aryl to phosphorus bond employing nickel catalysis. Both ligands were resolved through the formation of diastereomeric palladacycles and in the case of the isolated diastereomer formed from 3,6‐diisopropyl‐Pyrazinap, an X‐ray crystal structure showed the axial chirality to possess (S)‐configuration. The two enantiopure ligands were applied to the palladium‐catalysed allylic alkylation of 1,3‐diphenylprop‐2‐enyl acetate with dimethyl malonate and afforded conversions of up to 100 % and 99 % with enantioselectivities of up to 92 % ee and 78 % ee, respectively. A series of 1,1,3‐triphenylallyl and 1,3‐diphenylallyl palladium complexes were prepared and their solution structures and dynamic behaviour elucidated by 2D‐COSY and NOESY NMR spectroscopic experiments.

Dimethyl 2-(2,4-Diamino-3-cyano-5H-chromeno[2,3-b]pyridin-5-yl)malonate

Dimethyl sulfoxide (DMSO) is widely used as a solvent in organic synthesis and in pharmacology because of its low cost, stability, and non-toxicity. Multicomponent reactions are a powerful synthetic tool for the rapid and efficient construction of complicated molecular frameworks. In this communication, the multicomponent transformation of salicylaldehyde, malononitrile dimer, and dimethyl malonate in DMSO at room temperature was carefully investigated to give dimethyl 2-(2,4-diamino-3-cyano-5H-chromeno[2,3-b]pyridin-5-yl)malonate with good yield. The structure of the new compound was established by means of elemental analysis and mass, nuclear magnetic resonance, and infrared spectroscopy.

Enantioselective Nitro‐Michael Addition Catalyzed by N‐Terminal Guanidinylated Helical Peptide

AbstractEnantioselective Michael addition of β‐dicarbonyl compounds toward nitroalkenes were realized by using an immobilized, N‐terminal‐guanidinylated peptide, H2N−C(=NH)−Trp−Trp−(Leu−Leu−Aib)3−PEG−PS‐resin (Aib=2‐aminoisobutyric acid), as catalyst. Viable nucleophiles were acetylacetone, dimethyl malonate, and β‐ketoesters. The electrophiles include the β‐nitrostryrenes with various substituents on the benzene ring and the aliphatic nitroalkenes. Sterically congested α‐ethoxycarbonyl‐β‐nitrostryrene also successfully reacted. The resin‐supported catalyst could be recycled for five times.magnified image

Sequential Knoevenagel Condensation/Cyclization for the Synthesis of Indene and Benzofulvene Derivatives.

Sequential Knoevenagel condensation/cyclization leading to indene and benzofulvene derivatives has been developed. The reaction of 2-(1-phenylvinyl)benzaldehyde with malonates gave benzylidene malonates, cyclized indenes, and dehydrogenated benzofulvenes. The product selectivity depends on the reaction conditions. The reaction with piperidine, AcOH in benzene at 80 °C for 1.5 h gave a benzylidene malonate in 75% yield as a major product. The reactions with piperidine, AcOH in benzene at 80 °C for 17 h and with TiCl4-pyridine at room temperature gave an indene derivative in 56 and 79% yields, respectively, as a major product. The reaction with TiCl4-Et3N gave a benzofulvene in 40% yield selectively. Indene was transformed to a benzofulvene derivative using the reagents TiCl4-Et3N and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The reaction of variously substituted aryl derivatives with dimethyl malonate gave indene and benzofulvene derivatives. The reactions of 2-(1-phenylvinyl)benzaldehyde with Meldrum’s acid or malononitrile also gave cyclized compounds in the suitable sequential or stepwise conditions. Furthermore, the reaction of 2-arylbenzaldehydes has been investigated. The limitation and scope have been described. The reaction mechanism of the cyclization steps has been examined by DFT calculations.