Acetoacetate Research Articles

The synthesis, characterization, antioxidant and antimicrobial activity of some novel amides of the esters of substituted 1,4-dihydropyridines

The esters of substituted 1,4-dihydropyirdines (1,4-DHP) are formed in the reaction of an appropriate aldehyde and ethyl acetoacetate in the presence of concentrated water solution of ammonia. The esters form the amides by the reaction with primary amines. The series of the amides has been synthesized with the aim to analyze their chemical characteristics, antioxidant and antimicrobial activity. The amine used in this research is 2-aminothiazole. The antioxidant activity is analysed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) methods and the antimicrobial activity screening was performed by broth microdilution method, using different microbial strains. The characterization of the obtained amides was done by melting points, FTIR, NMR and elemental analysis. The possibilities for further research was suggested, which could lead to the application of selected compounds.

Preparation and characterization of magnetic microgels with linear thermosensitivity over a wide temperature range

Abstract Hybrid nanogels that are both thermosensitive and superparamagnetic, and have good biocompatibility are expected to have applications in the biomedical field. In this article, a linearly thermosensitive magnetic microgel was prepared by a radical copolymerization reaction in aqueous dispersion. In this reaction, poly(ethylene glycol) diacrylate was used as a crosslinker, polyvinylpyrrolidone was used as a stabilizer, and 2-methoxyethyl acrylate, poly(ethylene glycol)methyl ether acrylate, and 2-(methacryloyloxy)ethyl acetoacetate were used as copolymer monomers. The thermosensitive magnetic microgel displays a linear volume phase transition in water upon heating over a wide range of temperatures. Transmission electron microscopy, scanning electron microscopy, and dynamic light scattering were used to characterize the morphology and dimensions of the thermosensitive magnetic microgel. This material is expected to be used in magnetically targeted drug delivery systems that require linear drug release.

A Practical Synthesis of Homoallylic Diene Halides: Versatile Synthons for the Preparation of the Taxane A-Ring System

AbstractA concise and efficient synthesis of two homoallylic halides, which are useful precursors for the preparation of the taxane A-ring system is reported. Contrary to the synthetic routes reported in the literature, this procedure does not employ expensive tetramethylethylene as a starting material. The synthetic route uses readily available and inexpensive ethyl acetoacetate, 1,2-dibromoethane, methyltriphenylphosphonium iodide and methylmagnesium bromide as starting materials. The key step in the synthesis is the acid-mediated ring opening of a cyclopropyl tertiary alcohol to afford the corresponding homoallylic diene halides. The corresponding Grignard reagent, derived from the bromide, is used in the synthesis of an enone previously used as a precursor of taxadienone by reaction with the enol ethyl ether of 1,3-cyclohexanedione.

Green synthesis of novel pyrano[2,3-c]pyrazole-5-carbonitrile analogues by using Fe5(PW10V2O40)3 nanocatalyst through a one-pot Knoevenagel condensation and Michael addition mechanism

A swift and green one-pot method was improved for the preparation of new pyranopyrazole analogues using iron-doped heteropoly acid [(Fe5(PW10V2O40)3] (FePWV) as an efficient catalyst at room temperature and ethanol as the solvent. The one-pot, multi-component reaction combining substituted aldehyde, malononitrile,ethyl acetoacetate, and hydrazine hydrate produces remarkable yields (varying from 88 % to 98 %) for this highly selective technique. Using P-XRD, TGA, BET, FT-IR, TEM, and SEM studies, the synthesized FePWV catalyst was fully characterized. Several spectroscopic methods, including 1H NMR, 15N NMR, 13C NMR, and HRMS, were used to confirm the target molecules' structural information.This environmentally benign method also has other benefits, such as operational simplicity, a stable catalyst with great reusability (up to 7 times), quick reaction times (<20 min), and the absence of chromatographic separations. The proposed method is sustainable and affordable as a result of these properties taken together.

DIFFERENT ROUTES FOR THE SYNTHESIS OF BENZALDEHYDE-BASED DIHYDROPYIMIDINONES VIA BIGINELLI REACTION

Multicomponent reactions involving three or more reactants are commonly used to prepare dihydropyrimidinone with various bioactivities. This study reports the different routes for the synthesis of benzaldehyde-based dihydropyrimidinone via the Biginelli reaction and investigates the yield of the obtained products. The synthesis was performed via routes A, B, C, D, and E based on the formation of iminium, enamine, and Knoevenagel intermediates between urea, benzaldehyde, and ethyl acetoacetate. Route A, through a one-pot reaction via iminium, produced dihydropyrimidinone with a yield of 58%. The product from route B via iminium was obtained in 62% yield. Route C and D occurred via enamine at room temperature, and reflux gave the product 31% and 40% yield, respectively. Route E involving Knoevenagel intermediate provided the product in a 38% yield. 1H NMR, FTIR, and MS spectroscopic techniques were used for structure elucidation.

Synthesis, Spectroscopic, Computational Structure Analysis, Molecular Docking, in vitro Antibacterial and in vivo Antipyretic Investigations of Transition Metal(II) Complexes

Unsymmetrical Schiff base hydrazone complexes of cobalt(II), nickel(II) and zinc(II) were synthesized from oxalic dihydrazide, salicylaldehyde and ethyl acetoacetate. The ligand and its metal(II) complexes were characterized by elemental analysis, UV-visible, FT-IR, molar conductivity. To determine the biological activity, in vivo antipyretic as well as in vitro antibacterial activities were conducted along with molecular docking simulation, HOMO-LUMO and MEP calculations. The findings from the experimental and molecular docking investigations demonstrated that the ligand and all the metal(II) complexes has an ability to interact with E. coli 24kDa domain protein (PDB: 1KZN). Furthermore, these interactions were accompanied by favourable docking score values, indicating potential therapeutic implications. The quantum parameters and geometric optimization of the ligand and complexes were performed using DFT simulations.

Natural Surfactant Mediated Synthesis of 4-Aryl Substituted 3,4-Dihydropyrimidinones

Present work describes the synthesis of 4-aryl substituted 3,4-dihydropyrimidinones (DHPMs) using aqueous extract of pericarp of Sapindus trifoliatus fruit as a green catalyst. The reaction is a one-pot reaction, similar to classical Biginelli reaction employing an aromatic aldehyde, urea and active methylene compound (ethyl acetoacetate) as substrates. Desired DHPMs were yielded within 2 h at room temperature. The key advantage of the present strategy was its low dependence on organic solvents as green synthesis.

Conjugates of tacrine with aminomethylidene derivatives of ethyl acetoacetate as promising agents for the treatment of Alzheimer’s disease

Conjugates of tacrine with aminomethylidene derivatives of ethyl acetoacetate as promising agents for the treatment of Alzheimer’s disease

Synthesis, characterization, and thermal decomposition performance of 1,2,3-triazolyl-substituted 1,3,5-triazines with carbonyl, ester, and azide functional groups

Based on the organocatalytic reaction of enamine azide addition of 2,4,6-triazido-1,3,5-triazine to acetylacetone acetoacetic ester, we synthesized a series of previously unknown mono-, di-, and tri(1,2,3-triazolyl)-substituted-1,3,5-triazines that additionally carried carbonyl, ester, and azide groups. The structure of the obtained compounds was proved by NMR (1H, 13C) and IR spectroscopy, and the composition was confirmed by elemental analysis. With the aid of differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) coupled to mass spectrometry (TG-MS), we obtained data on the thermal behavior and decomposition mechanism for these compounds. We demonstrated that di(1,2,3-triazolyl)-substituted 1,3,5-triazines have an increased thermal stability and have higher values of decomposition onset temperature (220–250 °C) in comparison with tri(1,2,3-triazolyl)-substituted 1,3,5-triazines (180 °C and 160 °C, respectively).

Efficient microwave synthesis of coumarin derivatives with evaluation of their antioxidant and anti-inflammatory properties

Microwave radiation, an electromagnetic radiation, is used as a source of heating in organic synthesis. Coumarin, a benzopyrone derivative, shows various pharmacological activities such as anticoagulant, antimicrobial, analgesic, anti-inflammatory. The prime objective was to compare the synthesis of some coumarin derivatives by microwave assisted methods. Two different coumarin derivatives were synthesized and evaluated for their anti-inflammatory activity and anti-oxidant activity. 3-Acetylcoumarin (3-acetyl-2H-Chromen-2- one) was synthesized by reaction with salicylaldehyde and ethyl acetoacetate in presence of piperidine and the 3-acetyl-6-bromocoumarin (3-acetyl-6-bromo-2H-chromen-2-one) was synthesized by using 5-bromo-salicyladehyde. The synthesized compounds were characterized by MP, TLC, IR and NMR. The antioxidant activity of the compounds was done by reducing power by ferric chloride, nitric oxide and hydrogen peroxide scavenging method. The anti-inflammatory activity of the compounds was done by protein denaturation using BSA method. Out of the two compounds synthesized, bromine-substituted acetyl coumarin showed more anti-oxidant and anti-inflammatory activity when compared to standard.

Caffeine: An efficient and Reusable catalyst for the multicomponent synthesis of 2-amino-3-cyano-6-methyl-4-aryl-4H-pyrans

An efficient procedure for the synthesis of various 2-amino-3-cyano-6-methyl-4-aryl-4H-pyrans is reported. It has been found that Caffeine catalyse the condensation reaction of aromatic aldehydes, malononitrile and ethyl acetoacetate efficiently under EtOH-H2O (1:1) at reflux conditions. This approach provides many merits such as high yields of products, clean, simple work-up, waste free, mild reaction conditions and commercially available catalyst.

Visible light mediated eosin-Y catalysed synthesis of benzylidene-methylisoxazolone

An eco-friendly green and metal-free visible light mediated approach for the synthesis of biologically potent 4-benzylidene-3-methylisoxazol-5(4H)-one through multifactorial reaction of aryl aldehydes, ethyl acetoacetate and hydroxylamine hydrochloride catalysed by eosin-Y and water as a solvent has been developed with wide range of applications in pharmaceutical industries and agriculture. The aim of this work is to investigate an economical, safe, easy and convenient method for the synthesis of some derivatives of its with high yield, applied in biological studies.

Novel Nano-Size Inorganic-Bioorganic Hybrids Based on Graphene Oxide and Arginine-Derived Ionic Liquids (GO@Mono-Arg Malonate and GO@di-Arg Malonate): Versatile Catalysts to Prepare Spiro[Indeno[1,2-d]Pyrimidineindoline]Ones, Spiro[Indoline-Pyrimido[4,5-d]Pyrimidine]Ones, and Dihydro-Spiro[Indoline-Pyrimidine]-Carboxylates under Solvent-Free Conditions

In this research, two novel nano-size inorganic-bioorganic hybrids based on graphene oxide were prepared via a two-step process. The ionic liquids obtained through the reaction of arginine and malonic acid, in a 1:1 and 1:2 molar ratio, afford mono-Arg malonate and di-Arg malonate, respectively. These two bio-based ILs characterized via FT-IR, 1H-NMR, 13C-NMR, and GC-MASS techniques. In the second part, they embedded on graphene oxide core to gain the final nano-size inorganic-bioorganic hybrids (GO@mono-Arg malonate and GO@di-Arg malonate), which were identified through, FT-IR, FESEM, EDAX, and TGA/DSC, analysis. The catalytic efficacy of two obtained nanostructures examined in the synthesis a wide range of spiro[indeno[1,2-d]pyrimidineindoline]ones, spiro[indoline-pyrimido[4,5-d]pyrimidine]ones, and dihydro-spiro[indoline-pyrimidine]-carboxylates via the reaction of 1,3-cyclic/linear dicarbonyls (1,3-indanedione, barbituric acid, Meldrum’s acid, ethyl acetoacetate, and 4-hydroxycoumarin), heterocyclic 1,2-dicarbonyls (isatin, 5-chloroisatin, 5-bromoisatin, acenaphthenequinone, and ninhydrin), and urea/thiourea/guanidine under solvent-free conditions at 80 °C. The results affirmed that the GO@di-Arg malonate accelerated the reactions faster than GO@mono-Arg malonate. The recovery and reusability of the GO@di-Arg malonate was examined within two cycles successfully. The recovered GO@di-Arg malonate was determined by FESEM analysis.

Antimicrobial Potency and E. coli β-Carbonic Anhydrase Inhibition Efficacy of Phenazone-Based Molecules.

In this investigation, 4-antipyrinecarboxaldhyde was reacted with methyl hydrazinecarbodithioate to afford the carbodithioate derivative 3. The as-prepared carbodithioate derivative 3 is considered to be a key molecule for the preparation of new antipyrine-1,3,4-thiadiazole-based molecules (4-9) through its reaction with the appropriate hydrazonoyl halides. Furthermore, a typical Biginelli three-component cyclocondensation reaction involving ethyl acetoacetate, 4-antipyrinecarboxaldhyde, and thiourea under the standard conditions is carried out in the presence of sulfuric acid to afford the corresponding antipyrine-pyrimidine hybrid molecule (10). The latter was submitted to react with hydrazine monohydrate to provide the corresponding hydrazide derivative (11) which, under reaction with ethyl acetoacetate in refluxing ethanol containing catalytic amount of acetic acid, afforded the corresponding derivative (12). The structure of the newly synthesized compounds was affirmed by their spectral and microanalytical data. We also screened for their antimicrobial potential (ZOI and MIC) and conducted a kinetic study. Additionally, the mechanism of biological action was assessed by a membrane leakage assay and SEM imaging technique. Moreover, the biological activities and the binding modes of these compounds were further supplemented by an in silico docking study against E. coli β-carbonic anhydrase. The amount of cellular protein released by E. coli is directly correlated to the concentration of compound 9, which was found to be 177.99 µg/mL following treatment with 1.0 mg/mL of compound 9. This finding supports compound 9's antibacterial properties and explains how the formation of holes in the E. coli cell membrane results in the release of proteins from the cytoplasm. The newly synthesized compounds represent acceptable antimicrobial activities with potential action against E. coli β-carbonic anhydrase. The docking studies and antimicrobial activity test proved that compound (9) declared a greater activity than the other synthesized compounds.

Synthesis, Antibacterial Activities and Theoretical Study of Polyhydroquinoline Derivatives

AbstractIn the present study, novel bis‐Schiff base derivatives of polyhydroquinoline were synthesized through Hantzsch condensation reaction in excellent yields. Initially, a mixture of dimedone, ethyl acetoacetate, ammonium acetate and esterified aldehydes were refluxed in ethanol for 7–9 hrs. Then, hydrazine hydrate was treated with obtained polyhydroquinoline to form bis‐hydrazide of corresponding polyhydroquinoline. Finally, the bis‐hydrazide was independently refluxed with substituted aromatic aldehydes to get desired bis‐Schiff base derivatives of polyhydroquinoline. The new derivatives were confirmed by modern spectroscopic techniques such as 1H‐NMR, 13C‐NMR and HR‐ESI‐MS. The targeted compounds were evaluated for their antibacterial activity using disc diffusion method. The derivative with four OH‐group was found more effective against Bacillus megaterium, Bacillus subtilis IM, Bacillus subtilis ATCC, Salmonella enterica and Proteus vulgaris FMC II with zone of inhibition 8.3, 7.6, 7.3, 6.6 and 6.3 mm, respectively. DFT study of targeted compounds were performed on both materials studio and Gaussian 09 package, which showed good agreement with experimental data. The NLO of synthesized compounds were calculated and consider good candidates for NLO. The global reactivity, NBO and 1H‐NMR correlation were also studied, which showed good agreement. The cheap reagents, short reaction time and excellent yields are some features of current work.

Biological Evaluation of Anti-Cholinesterase Activity, in Silico Molecular Docking Studies, and DFT Calculations of Green Synthesized Thiadiazolo[3,2-a]pyrimidine Derivatives.

A series of [1,3,4] thiadiazolo[3,2-a]pyrimidine-6-carboxylate derivatives 4(a-n) have been designed and synthesized as inhibitors of acetylcholinesterase (AChE). Synthesizing of thiadiazolo[3,2-a] pyrimidines was carried out in a single step, one-pot reaction using aromatic aldehydes, ethyl acetoacetate and different derivatives of 1,3,4-thiadiazoles (with molar ratio of 1 : 2 : 1, respectively) in conjunction with the catalyst, anhydrous iron(III) chloride by a grinding method under solvent-free conditions at room temperature. The in-vitro studies exhibited good potency for inhibiting AChE comparable with donepezil as the reference drug. The best results were obtained by Ethyl 2-(4-nitroophenyl)-7-methyl-5-(pyridin-3-yl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidine-6-carboxylate 4n with IC50 value of 0.082±0.001 μM which was comparable with AChE inhibitory effects of donepezil (IC50 =0.079 μM).

Synthesis, Antimicrobial, Antioxidant Evaluation, and DFT Estimation of some New Cyclohexenone Derivatives Derived from Benzyloxy Chalcones.

New cyclohexenone derivatives candidates were designed to discover their antioxidant and antibacterial activity potentials, respectively. Aldehydes with the diverse functional group were prepared from 4-hydroxy benzaldehyde and benzyl bromide and converted to chalcones by reaction with 4-substituted benzophenones and 2-acetyl naphthalene. When chalcone derivatives were subjected to ethyl acetoacetate, it produced new cyclohexenone derivatives through NaOH- catalyzed addition-ring closure reaction. The new compound structures were strengthened by their spectral information. The new compounds are examined for in vitro antifungal and antibacterial actions through broth microdilution technique, and they exhibited potential responses against various bacteria and fungi. As a result, composites with (-F) group as a substituent on para position were established to be the forceful derivatives against S. aureus, E. coli organism, and C Albicans since this compound could inhibit the microbial and Fungai growth at lower concentrations compared to the standards (Ciprofloxacin HCl, and Fluconazole). DPPH radical scavenging experiments were used to evaluate proton donating antioxidant effects; it was exposed that compound 7c has the most significant antioxidant activity, while less than the standard ascorbic acid. Finally, HOMO-LUMO was calculated, which represents the quantum mechanical calculations of energies and conducted by the theory of density functional (DFT) method based on the level of (B3LYP) with 6-31G (d, p) basis set.

Gas-Phase Alkali-Metal Cation Affinities of Stabilized Enolates.

The chemistry of alkali-metal enolates is dominated by ion pairing. To improve our understanding of the intrinsic interactions between the alkali-metal cations and the enolate anions, we have applied Cooks' kinetic method to determine relative M+ (M=Li, Na, K) affinities of the stabilized enolates derived from acetylacetone, ethyl acetoacetate, diethyl malonate, ethyl cyanoacetate, 2-cyanoacetamide, and methyl malonate monoamide in the gas phase. Quantum chemical calculations support the experimental results and moreover afford insight into the structures of the alkali-metal enolate complexes. The affinities decrease with increasing size of the alkali-metal cations, reflecting weaker electrostatic interactions and lower charge densities of the free M+ ions. For the different enolates, a comparison of their coordinating abilities is complicated by the fact that some of the free anions undergo conformational changes resulting in stabilizing intramolecular interactions. If these complicating effects are disregarded, the M+ affinities correlate with the electron density of the chelating functionalities, that is, the carbonyl and/or the nitrile groups of the enolates. A comparison with the known association constants of the corresponding alkali-metal enolates in solution points to the importance of solvation effects for these systems.

Bioinspired Fe(II)‐Mediated Halogenative C−C Bond Activation of Ozonides: Temporary Installment of a Peroxide Bridge Allows Selective C−C Scissions for Replacement of a Carbonyl Group by a Halogen

AbstractA selective reaction of bridged ozonides with Fe(II) salts proceeds through the sequence of O−O, C−C scissions and halogenation to form α‐halogen substituted δ‐ketoesters and δ‐diketones in 15–72% yields. The overall sequence shows how a temporary installation of a peroxide functionality can be used to replace the acyl group within an acetoacetic ester unit with a halogen.

4-Methyl/Phenyl-1,2,5,6-tetraazafluoranthen-3(2H)-ones Synthesis: Mechanistic Pathway Study and Single-Crystal X-ray Analysis of the Intermediates

The synthesis of 4-methyl/phenyl-1,2,5,6-tetraazafluoranthen-3(2H)-one 4 and 7 has been reported with ninhydrin via a reaction first with ethyl acetoacetate or ethyl benzoylacetate and then a reaction of the resultant esters with hydrazine hydrate. The mechanism of hydrazinolysis and cyclization to obtain tetraazafluoranthen-3(2H)-ones is ambiguous, and the previously proposed mechanism was not based on facts because the actual intermediates were not isolated. Herein, the important intermediates involved in the hydrazinolysis–cyclization mechanistic pathway were isolated and characterized using NMR and X-ray single-crystal analysis. The intermediates demonstrate that the reaction carried out via two hydrazinolysis–cyclization reactions, the first of which includes the condensation of one hydrazine molecule with two ketone groups and the second of which includes the reaction of another hydrazine molecule with the ester and then condensation with the other ketone group. The stability of hydrazide 11 enabled the hydrazine to reduce the carbonyl of the ketone group to form 12 via a Wolff–Kishner-like reduction. The structure of the three intermediates was confirmed using X-ray crystallographic analysis. It was found that the three fused ring systems deviated from planarity to different extents, with their deviation from being coplanar reaching up to 5.3°. The possible non-covalent interactions which control the molecular packing of these intermediates were elucidated with the aid of Hirshfeld analysis.