Malonyl Chloride Research Articles

Synthesis, spectral and structural characterization of iron chalcogenomalonato complexes CpFe(CO)2ECOCH2CO2R (E = S, Se)

The synthesis of CpFe(CO)2ECOCH2CO2R [E = S (1), Se (2); R = Me (a), Et (b)] was achieved by treating (µ-E x )[CpFe(CO)2]2 (E = S, x = 2–4, Se, x = 1) with alkyl malonyl chlorides at ambient temperature. The synthesized compounds were characterized by elemental analysis, FT-IR, 1H and 13C NMR spectroscopy as well as with UV–Vis spectroscopic techniques. The molecular structures of 1a and 2a were determined by single crystal X-ray diffraction studies and reveal that the two compounds are monomeric in the solid state with the iron center located in a distorted octahedral environment.

Four Routes to 3-(3-Methoxy-1,3-dioxopropyl)pyrrole, a Core Motif of Rings C and E in Photosynthetic Tetrapyrroles.

The photosynthetic tetrapyrroles share a common structural feature comprised of a β-ketoester motif embedded in an exocyclic ring (ring E). As part of a total synthesis program aimed at preparing native structures and analogues, 3-(3-methoxy-1,3-dioxopropyl)pyrrole was sought. The pyrrole is a precursor to analogues of ring C and the external framework of ring E. Four routes were developed. Routes 1-3 entail a Pd-mediated coupling process of a 3-iodopyrrole with potassium methyl malonate, whereas route 4 relies on electrophilic substitution of TIPS-pyrrole with methyl malonyl chloride. Together, the four routes afford considerable latitude. A long-term objective is to gain the capacity to create chlorophylls and bacteriochlorophylls and analogues thereof by facile de novo means for diverse studies across the photosynthetic sciences.

Divergent Sequential Reactions of β‐(2‐Aminophenyl)‐α,β‐ynones with Malonyl Chloride

AbstractA viable one‐pot synthesis of challenging 4H‐[3,4‐c]quinolone‐4,5(6H)‐diones by the reaction of β‐(2‐aminophenyl)‐α,β‐ynones with ethyl malonyl chloride is described. Their further elaboration in the presence of an excess of 40 % methyl amine aqueous solution in EtOH gives the benzo[c][2,7]naphthyridine‐4,5(3H,6H)‐diones of pharmacological interest in high yields. The product selectivity control of the divergent sequential condensation/C‐annulation/intramolecular transesterification vs condensation/O‐annulation/ring opening reactions of β‐(2‐aminophenyl)‐α,β‐ynones with malonyl chloride under metal free conditions has been addressed.

Studying spectroscopic, cyclic voltammetry, and electrical properties of novel 4-amino antipyrine derivative for photonic applications

The present work aims to synthesize a new antipyrine derivative and then study its optical properties in the form of thin films with the aim of using the obtained results in the fabrication and designing of new optoelectronic devices. A N1,N3-bis(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)malonamide, dpdp novel organic compound has been successfully synthesized in dimethylformamide (DMF) medium by the chemical reaction between 4-aminoantipyrine and malonyl chloride. The obtained dpdp compound is characterized quantitatively and qualitatively by using micro elemental analysis, FTIR spectroscopy, 1H– & 13C–NMR, and thermogravimetric measurements. Two steps weight loss of 84 % (calcd. mass loss 37.25 %) is recorded in the temperature range of 25 °C to 800 °C. Thin films of the novel organic dpdp were successfully grown by the thermal evaporation technique. FSEM images show the surface topology of the as-deposited thin film which is characterized by high quality, continuous, and crystalline granular surface with an average particle size of 70 nm. The cyclic voltammetric analysis showed that the energy difference between the HOMO and LUMO equals 2.43 eV. The calculated values of the optical band gap transitions deduced from the diffuse reflectance spectra are found to be 2.27 eV, and 3.44 eV for the powder and the as-deposited dpdp thin films, respectively. The photoluminescence spectra analysis showed that the as-deposited film dpdp is characterized by a main green peak centered at 530 nm. The optical transflection spectra showed that the calculated values of the indirect optical band gap transitions are found to be 3.53 eV for the as-deposited thin film which slightly increased to 3.63 eV after annealing at 373 K and 423 K for 4 h. Spectral variations of the refractive index and the specific polarizability showed one peak around 400 nm which fades by annealing treatment at 373 K and 423 K. The dc electrical resistivity activation energy of the free charge carriers was estimated.

Modulating the Asymmetry of the Active Layer in Pursuit of Nanofiltration Selectivity via Differentiating Interfacial Reactions of Piperazine.

Nanofiltration (NF), highly prospective for drinking water treatment, faces a challenge in simultaneously removing emerging contaminants while maintaining mineral salts, particularly divalent cations. To overcome this challenge, NF membranes possessing small pores concomitant with highly negatively charged surfaces were synthesized via a two-step fabrication strategy. The key is to generate a polyamide active layer having a loose and carboxyl group-abundant segment on top and a dense barrier segment underneath. This was achieved by restrained interfacial polymerization between trimesoyl chloride and partly protonated piperazine to form a highly depth-heterogeneous polyamide network, followed by second amidation in an organic environment to remove untethered polyamide fragments and associate malonyl chlorides with reserved amine groups to introduce more negative charges. Most importantly, on first-principle engineering the spatial architecture of the polyamide layer, amplifying asymmetric charge distribution was paired with the thinning of the vertical structure. The optimized membrane exhibits high salt/organic rejection selectivity and water permeance superior to most NF membranes reported previously. The rejections of eight emerging contaminants were in the range of 66.0-94.4%, much higher than the MgCl2 rejection of 41.1%. This new fabrication strategy, suitable for various diacyl chlorides, along with the new membranes so produced, offers a novel option for NF in potable water systems.

Regioselective Synthesis of 5- and 3-Hydroxy-N-Aryl-1H-Pyrazole-4-Carboxylates and Their Evaluation as Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase.

In silico evaluation of various regioisomeric 5- and 3-hydroxy-substituted alkyl 1-aryl-1H-pyrazole-4-carboxylates and their acyclic precursors yielded promising results with respect to their binding in the active site of dihydroorotate dehydrogenase of Plasmodium falciparum (PfDHODH). Consequently, four ethyl 1-aryl-5-hydroxy-1H-pyrazole-4-carboxylates and their 3-hydroxy regioisomers were prepared by two-step syntheses via enaminone-type reagents or key intermediates. The synthesis of 5-hydroxy-1H-pyrazoles was carried out using the literature protocol comprising acid-catalyzed transamination of diethyl [(dimethylamino)methylene]malonate with arylhydrazines followed by base-catalyzed cyclization of the intermediate hydrazones. For the synthesis of isomeric methyl 1-aryl-3-hydroxy-1H-pyrazole-4-carboxylates, a novel two-step synthesis was developed. It comprises acylation of hydrazines with methyl malonyl chloride followed by cyclization of the hydrazines with tert-butoxy-bis(dimethylamino)methane. Testing the pyrazole derivatives for the inhibition of PfDHODH showed that 1-(naphthalene-2-yl)-5-hydroxy-1H-pyrazole-4-carboxylate and 1-(naphthalene-2-yl)-, 1-(2,4,6-trichlorophenyl)-, and 1-[4-(trifluoromethyl)phenyl]-3-hydroxy-1H-pyrazole-4-carboxylates (~30% inhibition) were slightly more potent than a known inhibitor, diethyl α-{[(1H-indazol-5-yl)amino]methylidene}malonate (19% inhibition).

Maloplatin-B, a Cisplatin-Based BODIPY-Tagged Mito-Specific "Chemo-PDT" Agent Active in Red Light.

Maloplatin-B, a cisplatin-based complex, namely [Pt(A-BOD)(NH3)2](NO3) (Pt-A-BOD) with a pendant boron-dipyrromethene (BODIPY) moiety, where HA-BOD is a methyl malonyl chloride derived monostyryl BODIPY ligand, was designed and developed as near-IR light (600-720 nm) organelle-targeting photodynamic therapy agent. The complex [Pt(acac)(NH3)2](NO3) (Pt-Ac) was used as a control. Pt-A-BOD displayed an absorption band at 616 nm (ε = 2.9 × 104 M-1 cm-1) in 10% dimethyl sulfoxide/Dulbecco's Modified Eagle's Medium (DMSO/DMEM, pH 7.2). This complex displayed a broad emission band within 650-850 nm with a λem value of 720 nm in 10% DMSO-DMEM (pH 7.2) upon excitation (λex) at 615 nm with a large Stokes shift. The fluorescence quantum yield (ΦF) value for Pt-A-BOD is 0.032 and for the ligand HA-BOD is 0.24. The BODIPY complex and ligand showed the formation of singlet oxygen as the ROS (reactive oxygen species) on irradiation with near-IR red light of 660 nm, as evidenced from a 1,3-diphenylisobenzofuran (DPBF) assay. The complex displayed remarkable apoptotic NIR light-induced PDT activity with half-maximum inhibitory concentration values (IC50) of 1.6-2.4 μM in A549 lung and HeLa cervical cancer cells, while it was less active in the dark. The cellular ROS generation by the complex in red light was ascertained by a DCFDA (2',7'-dichlorofluorescein diacetate) assay. Cellular imaging showed its localization primarily in the mitochondria of A549 cancer cells. The JC1 and Annexin-V FITC/PI assays carried out for A549 cancer cells treated with the BODIPY complex showed the alteration of mitochondrial membrane potential and apoptotic cell death on near-IR red light (600-720 nm) irradiation, respectively.

Bio-Fe3O4-MNPs Promoted Green Synthesis of Pyrido[2,1-a]isoquinolines and Pyrido[1,2-a]quinolines: Study of Antioxidant and Antimicrobial Activity

In this work, synthesis of pyrido[2,1-a]isoquinolines and pyrido[1,2-a]quinolines in excellent yield using multicomponent reactions of isoquinoline, methyl malonyl chloride, alkyl bromides, and triphenylphosphine in the presence of catalytic amount of Fe3O4-MNPs in water at 80 °C were investigated. The reduction of ferric chloride solution with Clover Leaf water extract caused to synthesis of magnetic iron oxide nanoparticles (Fe3O4-NPs) as a green method. As well, antioxidant activity was studied for some newly synthesized compounds such as 6a, 6b, 8b, and 8c using the DPPH radical trapping and reducing of ferric ion experiments and comparing results with synthetic antioxidants (TBHQ and BHT). As a result, compounds 6a, 6b, 8b, and 8c show trace DPPH radical trapping and excellent reducing strength of ferric ion. These compounds have biological potential because of isoquinoline or quinoline core. For this reason, the antimicrobial activity of some synthesized compounds was studied employing the disk diffusion test on Gram-positive bacteria and Gram-negative bacteria. The results of disk diffusion test showed that compound 6a, 6c, 6d, 8a, and 8b prevented the bacterial growth. Highlights Organic solvents that are needed for performing some organic reactions are often toxic and expensive. For this reason, elimination of these solvents is a suitable work for nature. The present procedure avoids the use of toxic solvent. Isoquinoline or quinoline derivatives are one of the important heterocyclic compounds that have outstanding moiety in medicinal chemistry and display a broad variety of biological and pharmacological properties. This recoverable catalyst is very easy and performed by external magnet.

Introducing an α-Keto Ester Functional Group through Pt-Catalyzed Direct C-H Acylation with Ethyl Chlorooxoacetate.

Platinum-catalyzed selective C–H acylation of 2-aryloxypyridines with ethyl chlorooxoacetate provides an efficient way of introducing an α-keto ester functional group. The reaction is oxidant-free, additive-free, and, more significantly, free of any decarbonylative side reactions. The reaction tolerates a variety of substituents from strongly electron-donating to strongly electron-withdrawing groups. Double acylation is feasible for 2-phenoxypyridine and its derivatives with only one substituent at the para position. Although the reaction of 2-(2-methylphenoxy)pyridine with ethyl malonyl chloride did not produce the desired β-keto ester, the reaction with ethyl succinyl chloride proceeded smoothly to give the γ-keto ester. Ethyl chlorooxoacetate is much more reactive than ethyl succinyl chloride in this Pt-catalyzed C–H acylation reaction.

Synthesis of New 2-Substituted 5-Hydroxypyrano[2,3-d][1,3]oxazine-4,7-diones

The reaction of carboxylic acid amides with malonyl chloride in acetonitrile or tetrahydrofuran without heating leads to the formation of previously unknown 2-substituted 5-hydroxypyrano[2,3-d][1,3]oxazines. The structure of the obtained compounds was established by high resolution mass spectrometry, NMR spectroscopy, and X-ray analysis.

Green synthesis of pyrido[2,1‐a]isoquinolines and pyrido[1,2‐a]quinolins using Fe3O4‐MNPs as efficient nanocatalyst: Study of antioxidant activity

AbstractIn this work, synthesis of pyrido[2,1‐a]isoquinolines and pyrido[1,2‐a]quinolins in excellent yield using multicomponent reaction of phthalaldehyde, methyl amine, methyl malonyl chloride, alkyl bromides, and triphenylphosphine in the presence of catalytic amount of Fe3O4‐MNPs with aqueous sodium hydroxide at 80°C was investigated. The reduction of ferric chloride solution with Clover Leaf water extract caused to synthesis of magnetic iron oxide nanoparticles (Fe3O4‐MNPs) as a green method. As well, antioxidant activity was studied for the some newly synthesized compounds such as 6a, 6c, 9b, and 9c using the DPPH radical trapping and reducing of ferric ion experiments and comparing results with synthetic antioxidants (TBHQ and BHT). As a result, compounds 6a, 6c, 9b, and 9c show good DPPH radical trapping and excellent reducing strength of ferric ion.

Development of aryl-containing dipyrrolyldiketone difluoroboron complexes (BONEPYs): Tune the hydrogen bond o–C[sbnd]H···F for fluoride recognition

Dipyrrolyldiketone difluoroboron complexes (BONEPYs) were synthesized by condensation of the corresponding pyrroles and malonyl chloride followed by treatment with BF3·OEt2. The aryl-substituted pyrrole is introduced to form a cyclic system in order to investigate anion binding studies. In BONEPYs 1–3 the o-H of the aryl group forms hydrogen bonding with F− to give a more table complex. In contrast, the intramolecular hydrogen-bonded BONEPY endo-4 is more stable than its exo isomer. While adding F−, the hydrogen bonds must be broken first to give 4·(3)F−. Owing to the electron-rich group (-OMe), the o-H of the phenyl group can hardly interact with F−via hydrogen bonding to give the less stable complex 4·(5)F−. The energy differences between the different conformations were calculated using DFT methods, which is consistent to the experimental observations.

Синтез малонилди(1,2,4-триазола), изучение кинетических и термодинамических особенностей его гидролиза и прогнозирование биологической активности

This article describes a two-step method for the synthesis of malondyl (1,2,4-triazole) (1,3-di (1H-1,2,4-triazol-1-yl)propane-1,3-dione) of 1,2,4-triazole through 1-trimethylsilyl-1,2,4-triazole, followed by reaction with malonyl chloride; the yield of the final product is 85%. The kinetics of hydrolysis of malonyldi(1,2,4-triazole) in the acetonitrile – water system (9:1) at 25 °C and 35 °C was studied, and the activation energy of the hydrolysis of malonyldi(1,2,4-triazole). To study the thermodynamic features of the reactions of obtaining this compound in the Spartan’14 1.1.4 program, a number of thermodynamic characteristics were calculated, which determine the spontaneous and exothermic nature of the process. For the molecule malonyldi(1,2,4-triazole), the most and least stable conformers were found in the program Molecular Operating Environment 2009.10, for which the surfaces of nucleophilic susceptibility were calculated in the program SCIGRESS Modeling 3.1.4. It was shown that the most stable conformer of the malonyldi(1,2,4-triazole) molecule should have the highest reactivity in reactions with different nucleophiles and the lowest value of the heat of formation. In this case, the nucleophilic susceptibility of carbonyl carbon atoms is different, despite the symmetry of the structure of the molecules malonyldi(1,2,4-triazole), which suggests a stepwise interaction of malonyldi(1,2,4-triazole) with nucleophiles. The structure of malonyldi(1,2,4-triazole) was confirmed by IR, 1H NMR spectroscopy, individuality – by thin-layer chromatography. The proposed mechanism for the hydrolysis of malonyldi(1,2,4-triazole) is described. The program PASS Professional 2007 predicted the most likely types of biological activity of the studied compounds. The most significant types of biological activity are anti-diabetic, anti-ulcer, anti-ischemic, anti-oxidant. The obtained data allow us to choose the optimal conditions for the synthesis of malonyldi(1,2,4-triazole) and to conclude that it is highly hydrolytically stable in an aqueous acetonitrile medium.

Total synthesis of cyclopiamide A and speradine E

Described is a total synthesis of the related alkaloids, cyclopiamide A and speradine E, via a unified strategy that also delivers the natural product aspergilline A. Key steps include metal-free conversion of a malonyl chloride and propargylamine to an intermediate pyrrolinone and a palladium catalyzed decarboxylation/aromatization sequence that delivers the requisite tetracyclic core.

Total Synthesis of (±)-Aspergilline A.

The total synthesis of (±)-aspergilline A (1) is described. Key features of the synthesis include pyrrolinone formation via reaction of an intermediate propargyl amine with a methyl malonyl chloride derived ammonium enolate and a formal [3+2] cycloaddition between an imidate and cyclopropenone.

Solvent-Free Synthesis of Thiobarbituric Acids Using Amberlyst-15 as a Green Catalyst

Background: Solvent-free reaction for the synthesis of thiobarbituric acids (TBAs) by the reaction of 1,3-disubstituted thioureas and malonyl chloride using Amberlyst-15 as a green catalyst has been reported. Recyclability of the catalyst was possible up to five runs without loss of catalytic activity. Keywords: Thioureas, malonyl chloride, thiobarbituric acid, recyclability, amberlyst-15, plausible mechanism.

One-pot isocyanide-based five-component reaction: Synthesis of highly functionalized N-cyclohexyl-2-(2,4-dioxo-2,3,4,5 tetrahydro-1H-benzo[b][1,5]diazepin-3-yl)-2-phenylacetamides

ABSTRACTA new protocol has been developed for the efficient synthesis of structurally diverse N-cyclohexyl-2-(2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,5]diazepin-3-yl)-2-phenylacetamides through a one-pot, five-component condensation reaction of an aromatic diamine, an aromatic aldehyde, an isocyanide, ethyl malonyl chloride, and water in dichloromethane with good yields, at ambient temperature, in the presence of MgCl2 as a catalyst.

SOLVENT FREE SYNTHESIS OF MALONYL CHLORIDES: A GREEN CHEMISTRY APPROACH

Methyl malonyl chloride and ethyl malonyl chloride are the acid chlorides of malonic acid diester. The present study focuses on the study of the synthesis of monomethyl malonyl chloride and monoethyl malonyl chloride. The synthesis was a three step process of selective saponification of dialkyl malonate followed by hydrolysis and then chlorination of monoalkyl malonic acid. The reaction was studied in the presence of solvent and absence of solvent (which is methylene chloride). Kinetics of the process was studied. Reaction was found to be first order by integrated rate law. The green process was evaluated with maximum conversion. The conversion of methyl malonic acid in solvent process was found to be 78.67% and in without solvent process was found to be 93.08% from the experiments carried out. The conversion of ethyl malonic acid in solvent process was found to be 84.39% and in without solvent process was found to be 98.23% from the experiments carried out.

ChemInform Abstract: Base‐Switched Annuloselectivity in the Reactions of Ethyl Malonyl Chloride and Imines.

AbstractThe reaction of imines (I) with ethyl malonyl chloride (II) in the presence of 2‐chloropyridine affords exclusively trans‐β‐lactams (III) via a [2+2] cycloaddition pathway, whilst the reaction in the presence of the strong nucleophilic base N‐methylimidazole affords dihydrooxazinones [cf.

Synthesis of 3,5-isoxazolidinediones and 1H-2,3-benzoxazine-1,4(3H)-diones from aliphatic oximes and dicarboxylic acid chlorides.

The synthesis of the title compounds was carried out by reacting dicarboxylic acid chlorides with oximes in the presence of excess triethylamine. Disubstituted malonyl chlorides gave 2-alkenyl-4,4-dialkyl-3,5-isoxazolidinediones (8a–f) and 2,2′-ethylidene-bis[4,4-dialkyl-3,5-isoxazolidinedione]s (9a–f). Compounds 9 were formed from 8 and its N-unsubstituted 3,5-isoxazolidinedione decomposition product. Phthaloyl chlorides reacted with acetone oxime to yield 3-(1-methylethenyl)-1H-2,3-benzoxazine-1,4(3H)-diones (16a–e). Products 16 spontaneously decomposed to give N-unsubstituted 1H-2,3-benzoxazine-1,4(3H)-diones (17a–e) at rates that were dependent on temperature and solvent. Kinetic studies showed that two of the compounds decomposed by zero-order kinetics under neutral conditions. Butanedioyl chloride did not produce a cyclic product.