Reaction Of Ethyl Research Articles

Flexible green synthesis of 2-benzyl-3‑hydroxy-1H-pyrazolo([1,2-b]phthalazine and [1,2-a]pyridazine)‑dione derivatives using CuI@KSF nanocatalyst under solvent-free conditions

In the frame of research that examines the use of task CuI@KSF nanoparticles as an efficient catalyst, new 1H-pyrazolo[1,2-b]phthalazine-5,10‑dione (HPPhD) and 1H-pyrazolo[1,2-a]pyridazine-5,8‑dione (HPPyD) derivatives were prepared. Using the four-multicomponent condensation reaction (4MCRs) of phthalic anhydride, hydrazine monohydrate, aromatic aldehydes, and ethyl 3-oxo-3-phenylpropanoate under solvent free conditions at 80 °C. This method has several advantages, including, operational, simplicity, mild conditions, and maximum product yield. To monitor the progress of the reactions, new organic salty catalysts were used. New catalysts are cheap, benign, recyclable, and environmentally friendly. In addition, they are easy to prepare and use. They also showed good catalytic activity, which in conclusion led to the synthesis of new phthalazine derivatives with good to excellent yields. The new catalysts were characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR), thermal gravimetric analysis (TGA), and scanning electron microscopy (SEM). To check the possible effect of these compounds in anticancer therapy, two types of proteins were selected and examined through docking calculations. In the case of 1DHT as an oxidoreductase enzyme compound 7e with the score of amount -8.99 represent the highest tendency toward interaction with the desired enzyme, while in the case of 6LQA by the dominance hydrophobic character, compound 7c seems likely to be more efficient.

Synthesis of Novel 6H‐Furo[3,2‐e]Indole Derivatives via One‐Pot Three Component Reactions

ABSTRACTA one‐pot, three‐component reaction of ethyl 5‐aminobenzofuran‐2‐carboxylate, arylglyoxals and cyclic 1,3‐dicarbonyl compounds in the presence of acetic acid as an organocatalyst in ethanol medium under reflux conditions provided a series of new 6H‐furo[3,2‐e]indole derivatives in good yields.

Expanding the Horizons of Suzuki Reactions: Pd‐PEPPSI–Mediated Traditional and Decarbonylative Couplings With Diverse Assure Analogues

ABSTRACTWe have developed a highly efficient, ligand‐free Suzuki–Miyaura cross‐coupling protocol employing our lab‐prepared air and moisture‐stable Pd‐PEPPSI catalysts. The reaction of ethyl 2‐{4‐[(6‐chloroquinoxalin‐2‐yl)oxy]phenoxy}propionate (Assure) with various boronic acids afforded both traditional and decarbonylative coupling products in high yields. The catalyst's steric influence was assessed computationally using %Vbur calculations. The decarbonylative coupling pathway proved more efficient than the traditional Suzuki–Miyaura coupling under these conditions. Additionally, regioselectivity studies have been conducted on a variety of Assure analogues. This method excels in efficiency, requiring minimal catalyst, moderate temperatures, and rapid reaction completion.

Application of diffusive gradient in thin films probes to monitor trace levels of labile methylmercury in freshwaters.

This study aimed to optimize the methods for sampling and analyzing methylmercury (MeHg) concentrated within diffusive gradients in thin films (DGT) and its application to different water bodies. We explored the elution solution for MeHg, comprised of 1.13 mM thiourea and 0.1M HCl, optimizing its volume to 50 mL. In addition, we found that it is necessary to analyze the entire extraction solution after adjusting its pH, to ensure completion of the ethylation reaction. The DGT samplers were deployed in two distinct aquatic environments (i.e., Okjeong Lake and Nakdong River) for up to 6 weeks, and this study demonstrated to predict the time-weighted average concentration with a diffusion coefficient of 7.65 × 10-6 cm2 s-1 for MeHg in the diffusive gel. To assess the diffusive boundary layer (DBL) effects, the DGT samplers with different agarose diffusive gel thickness were deployed. The mass of MeHg accumulated in the DGT resin at a given time decreased with increasing diffusive gel thickness, because of creating longer diffusion pathways within thicker gels. The labile MeHg concentration estimated by the DGT in Okjeong Lake and Nakdong River are found in the range of 61-111 and 55-105 pg L-1, respectively, which were found to be similar to the grab sampling data. Additionally, this study evaluated depth-dependent MeHg in Okjeong Lake. The vertical profile results showed that the concentration of MeHg at the depth of 2.3 and 15.7 m are about 1.5 and 4.6 times of the DGT installed at 0.3 m of the surface layer, respectively, suggesting potential mercury methylation in deep waters. These findings have practical implications for predicting bioavailability, assessing risks, and formulating strategies for water body management and contamination remediation.

A Simple and Efficient Approach for the Synthesis of Aryl-3-(trifluoromethyl)-1H-1,2,4-triazol-5(4H)-one Derivatives

AbstractIn this work, a series of 4-aryl-3-(trifluoromethyl)-1H-1,2,4-triazol-5(4H)-one derivatives is synthesized through nucleophilic intramolecular cyclization reactions of ethyl 2-(2,2,2-trifluoro-1-(arylimino)ethyl)hydrazine-1-carboxylate intermediates, which are themselves prepared in high yields via reactions of ethyl chloroformate and N-aryl-2,2,2-trifluoroacetimidoyl chloride derivatives. Some of the merits of the reported procedure are an operationally simple and concise method, the ready availability of starting materials, excellent product yields, no formation of harmful by-products and easy purification of the products.

Synthesis of New Spiropyrrolo[3,4-b]Pyridine Derivatives Employed Multicomponent Reactions

In this research, novel derivatives of spiropyrrolo[3,4-b]pyridine derivatives were synthesized in high yields by using multicomponent reaction (MCR) of ninhydrin, ammonium acetate, ethyl 2,4-dioxo-4-arylbutanoates, primary amines, methyl propiolate, and triethyl amine (Et3N) in aqueous media. The antioxidant activity of new synthesized spiropyrrolo[3,4-b]pyridine derivatives is due to having OH group which was evaluated by two procedures. This employed procedure for preparation of spiropyrrolo[3,4-b]pyridine derivatives conveys benefits including reaction with low time, products with high yields, and easy separation of products using an easy procedure.

Expanding the Substrate Scope of N‐ and O‐Methyltransferases from Plants for Chemoselective Alkylation**

AbstractMethylation reactions are of significant interest when generating pharmaceutically active molecules and building blocks for other applications. Synthetic methylating reagents are often toxic and unselective due to their high reactivity. S‐Adenosyl‐l‐methionine (SAM)‐dependent methyltransferases (MTs) present a chemoselective and environmentally friendly alternative. The anthranilate N‐MT from Ruta graveolens (RgANMT) is involved in acridone alkaloid biosynthesis, methylating anthranilate. Although it is known to methylate substrates only at the N‐position, the closest relatives with respect to amino acid sequence similarities of over 60 % are O‐MTs catalysing the methylation reaction of caffeate and derivatives containing only hydroxyl groups (CaOMTs). In this study, we investigated the substrate range of RgANMT and a CaOMT from Prunus persica (PpCaOMT) using compounds with both, an amino‐ and hydroxyl group (aminophenols) as possible methyl group acceptors. For both enzymes, the reaction was highly chemoselective. Furthermore, generating cofactor derivatives in situ enabled the transfer of other alkyl chains onto the aminophenols, leading to an enlarged pool of products. Selected MT reactions were performed at a preparative biocatalytic scale in in vitro and in vivo experiments resulting in yields of up to 62 %.

Regioselective Suzuki–Miyaura Reactions of Ethyl 2,6-Dibromo­pyrazolo[1,5-a]pyrimidine-3-carboxylate

AbstractA variety of novel disubstituted pyrazolo[1,5-a]pyrimidine derivatives have been prepared via sequential site-selective cross-coupling reactions of ethyl 2,6-dibromopyrazolo[1,5-a]pyrimidine-3-carboxylate. The regiocontrolled Suzuki–Miyaura reaction proceeded with excellent selectivity in favor of position C6 after careful optimization of the cross-coupling conditions. The monobrominated compounds, obtained on a large scale, were subjected to a second arylation, alkynylation or amination, leading to a new series of ethyl 2,6-disubstituted pyrazolo[1,5-a]pyrimidine-3-carboxylates. These results constitute an efficient regioselective approach for diversification of the chemically and biologically interesting pyrazolo[1,5-a]pyrimidine heterocycle at C2 and C6 positions.

Synthesis of [(4-methyl-6-oxo-1,6-dihydropyrimidin2-yl)sulfanyl]acetamides

The reaction of ethyl-[(4-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)sulfanyl]acetate with aliphatic amines gives corresponding acetamides; the reaction with hydrazine hydrate and aniline leads to 2-hydrazinyl- and 2-anilinopyrimidine respectively.

Construction of 3,9-diazatetraasteranes and 3,9-diazatetracyclododecanes by photocycloaddition reaction of 1,4-dihydropyridines: Experimental and theoretical investigation

A photocycloaddition reaction of ethyl 1,4-diaryl-1,4-dihydropyridine-3-carboxylate for the construction of 3,9-diazatetraasteranes (P1) and 3,9-diazatetracyclododecanes (P2) is reported for the first time. The types of reaction product clearly differ with solvent, regardless of the irradiation wavelength. The difference in P1 and P2 lies in the second step of the intramolecular [2 + 2] photocyclization. In order to further investigate this phenomenon and gain a deeper understanding of the photochemical behavior of 1,4-dihydropyridines, DFT and TDDFT theoretical calculations are performed. The results provide a good explanation for the formation of 3,9-diazatetraasteranes and 3,9-diazatetracyclododecanes.

First Synthesis of the Novel Triazolo[3,4-b][1,3,4]Thiadiazoles and Triazolo[3,4-b][1,3,4]Thiadiazines Linked Chromeno[2,3-b]Pyridine

The novel 3-(4-amino-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-2H-chromeno[2,3-b]pyridine-2,5(1H)-dione (3) was efficiently synthesized from reaction of ethyl 2,5-dioxo-1,5-dihydro-2H-chromeno[2,3-b]pyridine-3-carboxylate (2) with thiocarbohydrazide. Compound 3 was utilize as building block for building a various heterocyclic systems linked chromeno[2,3-b]pyridine-2,5(1H)-dione. Reaction of compound 3 with some heterocyclic aldehydes afforded the condensation products 6 and 7. Treatment of compound 3 with some mono- and bi-electrophilic reagents afforded triazolo[3,4-b][1,3,4]thiadiazoles and triazolo[3,4-b][1,3,4]thiadiazines linked chromeno[2,3-b]pyridine, respectively. Finally, compound 3 reacted with 2,3-dichloroquinoxaline yielding the novel chromeno[2,3-b]pyridine bearing annulated triazolothiadiazinoquinoxaline 18. The obtained products were examined for their antimicrobial effectiveness appearing variable inhibitory action toward the used microorganisms.

One-pot synthesis of difluoromethyl-containing 1,2,3,4-tetrahydropyridines

Difluoromethyl-containing diethyl 1,2,3,4-tetrahydropyridine-3,5-dicarboxylate derivatives were synthesized in up to 90% yields by the Mannich reaction of ethyl 4,4-difluoroacetoacetate with formaldehyde and primary amine hydrochlorides. The effects of the reactant structure and reaction conditionson the efficiency of formation of 1,2,3,4-tetrahydropyridines and hexahydropyrimidines was studied. In the presence of NaCl in an acetate buffer (рН 4), the 1,2,3,4-tetrahydropyridine structure is formed selectively. When 4-aminophenol hydrochloride is used, the 3,4,5,6-tetrahydropyrimidin-1-ium difluoroacetate salt is produced, apart from the target product. The reactions with (S)-α-amino acid ester hydrochlorides afford mixtures of two diastereomeric 1,2,3,4-tetrahydropyridines.

Biginelli reaction in the synthesis of ethyl 4-(6-aryl-5-benzoyl-4-hydroxy-2-thioxohexahydropyrimidine-4-carboxamido)benzoates

Three-component Biginelli reaction of ethyl 4-(2,4-dioxo-4-phenylbutanamido)benzoate, aromatic aldehyde and thiourea in acetic acid in the presence of sodium acetate led to the formation of ethyl 4-(6-aryl-5-benzoyl4-hydroxy-2-thioxohexahydropyrimidine-4-carboxamido)benzoates. Structure of the obtained compounds was established by IR, 1H NMR, 13C spectroscopy methods.

Ru(II)-catalyzed synthesis of poly-substituted furans via intermolecular oxidative annulation reaction of ethyl 3-oxo-3-phenylpropanoates with aryl alkynes/heteroaryl alkynes.

The oxidative annulation reaction of ethyl 3-oxo-3-phenylpropanoates with internal alkynes proceeds efficiently in the presence of a Ru(II)-catalyst, a copper oxidant and an additive such as AgSbF6 to give poly-substituted furans, which offers a novel method for the selective construction of poly-substituted furans. The reaction has wider substrate scope with simple starting materials, and the desired tetrasubstituted furans were prepared in good to excellent yields.

Rapid characterization of isotopic purity of deuterium-labeled organic compounds and monitoring of hydrogen-deuterium exchange reaction using electrospray ionization-high-resolution mass spectrometry.

Deuterium-labeled organic compounds, reagents, and drugs are widely used in many scientific research fields. Isotopic purity as the feature parameter of deuterated compounds is of great importance. In this article, we used electrospray ionization with high-resolution mass spectrometry (ESI-HRMS) to study isotopic purity of deuterium-labeled organic compounds based on assigning and distinguishing the corresponding H/D (hydrogen-deuterium) isotopolog ions of deuterated compounds. We systematically considered the specific requirements of accuracy and resolution of ESI-HRMS when measuring isotopic purity and demonstrated some actual cases using ESI-HRMS and ultraperformance liquid chromatography (UPLC)-HRMS. Meanwhile, ESI-HRMS/MS of deuterated compounds was performed to obtain more information on deuterium-labeled position characterization. Two isotopic purity calculation methods based on the relative abundance in ESI-HRMS and UPLC-HRMS of H/D isotopolog ions (D0 -Dn ) were compared, which gave consistent isotopic purity values and were in good agreement with the certified isotopic purity values. We further studied and monitored the H/D exchange reaction of ethyl 3-(4-bromophenyl)-3-oxopropanoate (EBPO) by evaluating the dynamic isotopic purity changes in EBPO-D2 in the H/D exchange reaction in situ. The isotopic purity characterization methods using ESI-HRMS discussed in this article have some outstanding advantages: rapid, highly sensitive, very low sample consumption (even below nanogram level), and deuterated solvent-free. Thus, this low-impact analytical method requires less time and is cost effective and might have good application potential for in-situ isotopic purity analysis and for monitoring the H/D exchange reactions.

Synthesis and Investigation of Biological Activity of New Spiro Pyrrolo[3,4-d]Pyrimidine Derivatives

In this study a new and procedure was reported for the synthesis of Ag/TiO2/Fe3O4@MWCNTs MNCs as a new heterogeneous organometallic catalyst. XRD, FESEM, EDX and TEM analysis were used for confirming the structure of synthesized nanocatalyst. The Ag/TiO2/Fe3O4@MWCNTs MNCs as a high performance catalyst was employed for the preparation of a new family of functionalized spiro pyrrolo[3,4-d]pyrimidine via the one-pot condensation reactions of ethyl 2,4-dioxo-4-arylbutanoate, ammonium acetate, isatin, primary amines and tert-butyl isocyanide in water at room temperature. Also, antioxidant property of some prepared compounds was investigated using diphenyl-picrylhydrazine (DPPH) radical trapping experiment. Presently, bacteria that is not destroied with drug have generated many problems in the performance of many transferable disease. For this reason, discovering appropriate and new procedures for the dealing with these pathogens are important and recent study have focused on the investigation of the antibacterial effects on the prepared compounds.

Synthesis, photophysical properties, and biological activities of some new thienylpyridines, thienylthieno[2.3‐b]pyridines and related fused heterocyclic compounds

AbstractBoth 2‐(N‐arylcarbamoyl)methylsulfanyl‐3‐cyano‐5‐ethoxycarbonyl‐6‐methyl‐4‐(2′‐thienyl)pyridines 2a‐e and their isomers, 3‐amino‐2‐(N‐arylcarbamoyl)‐5‐ethoxy‐carbonyl‐6‐methyl‐4‐(2′‐thienyl)thieno[2,3‐b]pyridines 3a‐e were synthesized by reaction of ethyl 3‐cyano‐1,2‐dihydro‐6‐methyl‐4‐(2′‐thienyl)‐2‐thioxopyridine‐5‐carboxylate (1) with the respective N‐aryl‐2‐chloroacetamides in the presence of different basic catalysts. Compounds 3a‐e were used as precursors for synthesizing of pyridothienopyrimidinones 4a‐e, pyridothienotriazinones 5a‐e and tetrahydropyridothienopyrimidinones 6a‐c via treatment with triethyl orthoformate, nitrous acid, and/or 4‐chlorobenzaldehyde respectively. The photophysical properties of aminothienylthienopyridines 3a‐e and tetrahydropyridothieno‐pyrimidine‐4(3H)‐ones 6a‐c were studied and the fluorescence data revealed that all selected compounds possess AIE behaviors in solution and in solid state. Most of the prepared compounds were evaluated in vitro for their antibacterial and antifungal activities, and considerable results were obtained. Moreover, the cytotoxic activity of thienopyridines 3a‐d against MCF‐7 and HepG2 cell lines was evaluated and they showed moderate to very strong activity.

An Unexpended Stereocontrolled Rearrangement of Ethyl 4‐Hydroxy‐4‐(substituted phenyl)‐2‐butynoate to Tetrasubstituted Alkenes with MeSOCl 2

In this study, syn-selective tetrasubstituted alkene derivatives were synthesized from ethyl 4-hydroxy-4-(substituted phenyl)-2-butynoate under classical mesylation reaction conditions. The structures of the obtained products were determined by 1H-NMR,13C-NMR spectroscopy, HRMS, and X-ray analysis.

Thiophene Ring-Opening Reactions IV. Facile Generation of Novel Ethyl 4-hydroxy-6-thioxonicotinate-1,3,4-thiadiazoline Hybrids

: A set of triethylammonium 4-oxo-6-pyridinethiolate–1,3,4-thiadiazoline hybrids (3a-e) were prepared via the reaction of ethyl 2-chloro-6-cyclopropyl-3- nitro-4-oxothieno[2,3-b]pyridine- 5-carboxylate (2) with the appropriate thiobenzoyl- hydrazide (1a-e) in acetonitrile and triethylamine. These hybrids were readily converted, under neutral mild conditions, into the corresponding 4-hydroxy-6-thioxopyridine –thiadiazoline hybrids (5a-e). The structures of the latter set are supported by HRMS, 1H NMR, and 13C NMR spectral data and further confirmed by single-crystal X-ray diffraction studies. Alkylation of these hybrids in the presence of triethylamine occurred exclusively at the 6-thioxosulfur, yielding the respective 6-sulfanyl derivatives (6a-c).

Influence of the melting point on the deblocking reaction of methyl ethyl ketoxime‐blocked aromatic polyisocyanates

AbstractBlocked polyisocyanates are used in single component (1 K) water‐based and powder coatings to simplify coating synthesis and reduce waste. However, the relationship between the melting point and deblocking behavior of blocked polyisocyanates is not clear. We aim to determine the influence of the melting temperature on the deblocking of methyl ethyl ketoxime (MEKO)‐blocked aromatic polyisocyanates. A toluene‐2,4‐diisocyanate trimer grafted with different mass ratios of methoxypolyethylene glycol (MPEG) is used to achieve compounds with different melting points and is blocked with MEKO. The deblocking behaviors of the polymers are investigated using Fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, and thermogravimetric analysis. The results show that the deblocking temperature and average activation energy of the blocked polyisocyanates decrease with increase in melting point. Further, MEKO is more likely to be lost from blocked polyisocyanates having lower melting points. Furthermore, polyacrylic resins cured with blocked polyisocyanates having low melting points exhibit better properties than those having high melting points. The results reveal that the reduction in melting point induced by grafting with MPEG can significantly reduce the deblocking temperature of blocked polyisocyanates. The improvements in these properties may help achieve the low‐temperature crosslinking of blocked polyisocyanates for coating technologies.