Work-up Procedure Research Articles

One-pot synthesis of chromenes in the presence of magnetic nanocomposite based on NH2-UiO-66(Zr), graphene oxide and Fe3O4

In this research, GO/Fe3O4/UiO‑66-NH2, a new magnetically recoverable heterogeneous catalyst, was prepared and characterized using various spectroscopic techniques and elemental analysis methods. The promoting ability of GO/Fe3O4/UiO‑66-NH2 was studied in the synthesis of chromenes via one-pot three-component condensation of 4‐hydroxycoumarin, 2‐hydroxynaphthalene‐1,4‐dione and aromatic aldehydes at 110 °C under solvent-free conditions. This new protocol is included some important features such as lower loading of the catalyst, excellent yields (88%–98%), short reaction times (5–10 min), easy work-up procedure, and easy recovery using a simple magnet. The catalyst was characterized by SEM, XRD, EDX, BET, TGA and FT-IR analysis.

One-pot multicomponent synthesis approach for tetrahydropyridines using polyaniline-zirconium oxide composites

Tetrahydropyridines, one-pot five-component green synthesis from aldehydes, anilines, and β-keto esters by cyclo-condensation using polyaniline-zirconium oxide catalyst. It is an efficient protocol due to the simplicity in reaction conditions, simple catalyst generation, and excellent product yield. The catalyst can be effortlessly recovered from the reaction mixture and reused up to the seven catalytic cycles without losing substantial catalytic activity. The present protocol offers prominent advantages over other reaction conditions in terms of a simple workup procedure, exceptional atomic economy, affordability, and wide substrate scope.

FeCl3 as an efficient catalyst for the synthesis of styrylquinoxalin-2(1H)-ones

The synthesis of (E)-3-substituted styrylquinoxalin-2(1H)-ones was achieved by the reaction of 3-methylquinoxalinone and aromatic aldehydes using FeCl3 as a catalyst in toluene under microwave irradiation. The protocol is endowed with milder reaction conditions, high yields of product, and easy workup procedures.

Deep Eutectic Solvent (DES) Mediated Multicomponent Synthesis of 4- thiazolidinone-5-carboxylic Acid: A Green Chemistry Approach

Background: The 4-thiazolidinone-5-carboxylic acid and its derivatives have diverse applications in agriculture, industrial and pharmaceutical fields. Therefore, the synthesis of this heterocyclic compound attracted much attention from researchers with green chemistry protocols. In this research work, we have introduced the green protocol for the synthesis of 4-thiazolidinone- 5-carboxylic acid by keeping the parameters in mind like cost-effective, environmentally benign, short reaction time and easy work-up procedure. Methods: Initially, we irradiated the mixture of substituted aldehyde, thiosemicarbazide and furan 2-5-dione in the presence of choline chloride-thiourea-based Deep Eutectic Solvent [DES] as a green medium. The reaction optimization was performed in different solvents like ethanol, glycerol, and PEG-400. Results: The DES, which was used as a green solvent, produced an excellent result in context to short reaction time, yield, easy workup, mild reaction condition and cost-effective protocol. All the results are discussed. Conclusion: The DES-mediated synthesis of 4-thiazolidinone-5-carboxylic acid is found to be an excellent protocol, which followed green chemistry principles. This method has specific features like mild reaction conditions, environmentally benign, cost-effective and easy workup procedure.

Applications of Choline Chloride-Based Deep Eutectic Solvents as Sustainable Media and Catalyst in the Synthesis of Heterocyclic Scaffolds

Abstract:Deep eutectic solvents (DESs), also referred to as low transition temperature mixtures (LTTMs), have emerged as sustainable and cheap alternatives to conventional organic solvents in organic synthesis. This is attributed to their exceptional characteristics viz. easy preparation with readily available cheap materials, water compatibility, non-flammability, non-toxicity, biocompatibility, biodegradability, etc. All these properties label them as versatile and cost-effective green solvents. The first reported DES, choline chloride urea mixture has appeared as an innocuous solvent and catalyst in many organic transformations. This prospective DES combination has been applied extensively to the synthesis of a wide range of heterocyclic compounds including quinolones, spirooxindoles, etc. The conditions employed are relatively mild and do not require additional acid catalysts or organic solvents. This ecofriendly blend for the synthesis of heterocycles reports excellent yields of products with shorter reaction times and a simple workup procedure. Evaluating these merits, this review focuses on the recent literature published on the use of choline chloride-based DESs in the synthesis of a few important heterocyclic compounds.

Direct conversion of white phosphorus to versatile phosphorus transfer reagents via oxidative onioation

The main feedstock for the value-added phosphorus chemicals used in industry and research is white phosphorus (P4), from which the key intermediate for forming P(III) compounds is PCl3. Owing to its high reactivity, syntheses based on PCl3 are often accompanied by product mixtures and laborious work-up procedures, so an alternative process to form a viable P(III) transfer reagent is desirable. Our concept of oxidative onioation, where white phosphorus is selectively converted into triflate salts of versatile P1 transfer reagents such as [P(LN)3][OTf]3 (LN is a cationic, N-based substituent; that is, 4-dimethylaminopyridinio), provides a convenient alternative for the implementation of P-O, P-N and P-C bonds while circumventing the use of PCl3. We use p-block element compounds of type RnE (for example, Ph3As or PhI) to access weak adducts between nitrogen Lewis bases LN and the corresponding dications [RnELN]2+. The proposed equilibrium between [RnELN]2+ + LN and [RnE(LN)2]2+ allows for the complete oxidative onioation of all six P-P bonds in P4 to yield highly reactive and versatile trications [P(LN)3]3+.

Continuous-Flow Synthesis of the Nucleobase Unit of Remdesivir

In this work, the nucleobase unit of the antiviral drug remdesivir, 7-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine, was synthesized through five-step continuous flow. By adapting batch synthetic chemistry, 7-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine was successfully produced through sequential flow operations from the widely available and inexpensive starting material pyrrole. Under optimal flow conditions, 7-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine was obtained in 14.1% isolated yield in a total residence time of 79 min with a throughput of 2.96 g·h−1. The total residence time was significantly shorter than the total time consumed in batch procedures (> 26.5 h). In flow, the highly exothermic Vilsmeier–Haack and N-amination reactions involving hazardous and unstable intermediates, oxidative liquid–liquid biphasic transformation, and a bromination reaction requiring strict cryogenic conditions are favorably facilitated. The salient feature of this synthesis is that the workup procedures are fully integrated into the reaction sequences by deploying dedicated equipment and separation units, thus forming a streamlined continuous-flow system that maximizes the overall process efficiency. This method represents a greener and more sustainable process to prepare this nucleobase unit with high efficiency and safety.

Sustainable and Scalable Two-Step Synthesis of Thenfadil and Some Analogs in Deep Eutectic Solvents: From Laboratory to Industry

A sustainable two-step protocol was developed for the synthesis of the antihistamine drug Thenfadil by combining a reductive amination process with a Cu-catalyzed Ullmann-type C–N coupling reaction run in environmentally responsible deep eutectic solvents (DESs), constructed from biobased compounds. Under optimized conditions, both reactions proceed smoothly under aerobic conditions and in the absence of any additional ligand, with the desired active pharmaceutical ingredient isolated in an overall reaction yield of 39% with an effective suppression of the side products arising from competitive Cu-catalyzed C–O coupling reactions. A novel and simplified workup procedure has also been set up, which avoids the need for chromatographic purification, while allowing the recovery and the recycling of the unreacted intermediate secondary amine. The potential application and the robustness of the proposed methodology has been demonstrated (a) in scale-up studies up to 50 g of substrate in 0.5 kg of DES, taking place with no decrease in the reaction yield, and (b) in the synthesis of three other ethylenediamine derivatives (Thenfadil’s analogs) like tripelennamine, methaphenilene, and thonzylamine in 39%–44% overall yield. Typical metrics applied at First and Second Pass, according to the CHEM21 Metrics Toolkit, have been calculated as well for the whole synthetic procedure of Thenfadil and results compared with those of the classical procedure.

Dearomative Periphery Modification of Quinolinium Salts to Assemble Ring-Encumbered Pyrrolidine-Tetrahydroquinoline Polycycles.

We report an unexpected dearomative periphery modification strategy for transforming quinolinium salts into structurally crowded pyrrolidine-tetrahydroquinoline polycyclic systems with complete regio- and diastereoselectivity. Importantly, the reaction pathway was regulated by simply tuning the substituents, achieving substituent-directed divergent synthesis. The notable features of this transformation include readily available starting materials, green conditions, a simple workup procedure, high bond- and ring-forming efficiency, and substituent-directed diverse synthesis.

Ionic Liquid-Assisted Fabrication of Bioactive Heterogeneous Magnetic Nanocatalyst with Antioxidant and Antibacterial Activities for the Synthesis of Polyhydroquinoline Derivatives.

Antibacterial materials have obtained much attention in recent years due to the presence of hazardous agents causing oxidative stress and observation of pathogens. However, materials with antioxidant and antibacterial activities can cause toxicity due to their low biocompatibility and safety profile, urging scientists to follow new ways in the synthesis of such materials. Ionic liquids have been employed as a green and environmentally solvent for the fabrication of electrically conductive polymers. In the present study, an antibacterial poly(p-phenylenediamine)@Fe3O4 (PpPDA@Fe3O4) nanocomposite was fabricated using [HPy][HSO4] ionic liquid. The chemical preparation of PpPDA@Fe3O4 nanocomposite was initiated through the oxidative polymerization of p-phenylenediamine by ammonium persulfate in the presence of [HPy][HSO4]. The PpPDA@Fe3O4 nanocomposite exhibited antibacterial properties against Gram-negative (Escherichia coli) and Gram-positive (Bacillus subtilis) bacteria. The PpPDA@Fe3O4 nanocomposite was employed as a heterogeneous nanocatalysis for one-pot synthesis of polyhydroquinoline derivatives using aromatic aldehyde, dimedone, benzyl acetoacetate, and ammonium acetate. Polyhydroquinoline derivatives were synthesized in significant yields (90–97%) without a difficult work-up procedure in short reaction times. Additionally, PpPDA@Fe3O4 nanocatalyst was recycled for at least five consecutive catalytic runs with a minor decrease in the catalytic activity. In this case, 11 derivatives of polyhydroquinoline showed in vitro antioxidant activity between 70–98%.

The multicomponent synthesis of urea substituted 2-arylfurans

For the first time, we elaborated a one-step approach for the synthesis of 2-arylfurans containing urea moiety. The proposed method is based on multicomponent condensation of various carbo- and heterocyclic enols, arylglyoxals and cyanamide. The considered approach is general and allows one to use the various enol derivatives as starting compounds. The advantages of the studied method are the use of readily available starting compounds, atom economy, easy work-up procedure without chromatographic purification. The structure of one of synthesized products was determined by X-Ray diffraction.

5‐Sulfosalicylicacid an organocatalyst for the synthesis of highly functionalized piperidines through the multicomponent reaction

AbstractThe synthetic protocol was developed for the synthesis of highly derivatized piperidines molecules in high yield with 5‐sulfosalicylic acid as an organocatalyst via a multicomponent reaction between the aromatic aldehydes, the aromatic anilines, and the β‐ketoesters at room temperature. The method has numerous advantages over other reported methods, such as the use of an inexpensive, reusable, nontoxic, and metal‐free catalyst along with readily available precursors, mild reaction conditions, and simple workup procedures. Instrumental techniques like high‐resolution mass spectroscopy (HRMS), proton nuclear magnetic resonance (1H NMR), 13‐carbon nuclear magnetic resonance (13C NMR), and Fourier transform infrared (FTIR) spectroscopy were used to confirm the structure and relative stereochemistry of the compounds. In this protocol, an anti‐isomer has been obtained as a major product at room temperature. Syn: Anti diastereomeric ratio has been confirmed by1H NMR.

Simple grinding for the synthesis of monomeric, dimeric, and trimeric pyridinium salts and its photophysical studies

AbstractSynthesis of water‐soluble‐substituted pyridinium cation which is attached with base sensitive fluorophore peripheral units with different inorganic counter anions under conventional/silica‐supported Muffle furnace methods. Solvent‐free synthetic approach has more merits than the conventional method, such as non‐toxic, shorter reaction time, easy workup procedure without purification process, and higher yields. Ultraviolet–visible spectra were recorded in neutral, acidic, and alkaline medium; it showed greater red shift in alkaline medium compared with neutral and acidic pH medium.

Synthesis, molecular docking, and in silico ADME studies of dihydropyrimidine derivatives using tetrabutylphosphonium methanesulphonate ionic liquid as a catalyst under solvent-free conditions

This paper describes the synthesis and characterization of tetrabutylphosphonium methanesulphonate ionic liquid and its use for the first time as a catalyst in a multicomponent reaction for one-pot synthesis of dihydropyrimidine derivatives from various aromatic aldehydes, methyl or ethyl acetoacetate, and urea or thio-urea under solvent-free conditions at 120 °C. About 21 different dihydropyrimidine derivatives have been synthesized in excellent yields. The advantages of this method are the following: solvent-free conditions, a small amount of catalyst required, shorter reaction time, easy workup procedure, and no hazardous organic solvents or toxic catalysts. This catalyst was easily prepared and showed an excellent level of reusability. The molecular docking study was performed to evaluate interactions between the active compounds with Leishmania pteridine reductase 1 (PTR1). Using theoretical evaluation, ADME properties in silico were investigated for their oral bioavailability to predict the safer efficacy of the synthesized compounds.

Facile Multicomponent Synthesis, Computational, and Docking Studies of Spiroindoloquinazoline Compounds.

Synthesis of spiroindoloquinazolines via one-pot three-component condensation reactions of tryptanthrin, malononitrile or ethylcyanoacetate, and nucleophiles was carried out in MeOH using triethylamine as the base catalyst under reflux conditions. This method has the advantages of short reaction time, excellent yields, and an easy work-up procedure. The structural properties of the compound 4c {2-amino-6-methyl-spiro-[12H]Indolo(2,1-b)quinazoline-12-one]12′,4-pyrano(2,3-c)pyrazole]-3-carbonitrile} and the obtained crystal were analyzed by the DFT theoretical calculation method, using the B3LYP 6-311G(d,p) basis set and were found to be in agreement with the experimental results. The importance of biological application and drug design of the same compound was verified by molecular docking studies.

Hybrid Synthetic and Computational Study of an Optimized, Solvent-Free Approach to Curcuminoids

A green and optimized protocol has been developed for the preparation of symmetric 1,7-bis(aryl)-1,6-heptadiene-3,5-diones and asymmetric 2-aryl-6-arylidenecyclohexanones with modified substrate scope and good functional group tolerance. Syntheses proceed smoothly under solvent-free conditions, providing moderate to excellent product yields with a minimal workup procedure. Control experiments, spectroscopic, and computational studies support a mechanism involving the boron-assisted in situ generation of imine intermediates. Crystal structures of three curcuminoids and isolated mechanistic intermediates are reported. The data provide insight for the further development of solvent-free protocols toward diverse curcumin derivatives in the fields of pharmaceutical and synthetic chemistries.

Green and eco-friendly synthesis of α-hydroxyphosphonates as antioxidant and antimicrobial agents

An efficient, fast and eco-friendly synthesis of α-hydroxyphosphonates are synthesized via neat reaction of various structurally diverse aldehydes and diethyl phosphite under ambient temperature and solvent free conditions using nano NiO as catalyst. Use of nano NiO as an inexpensive catalyst makes the protocol more economical. Mild reaction conditions and simple work-up procedure are the added advantages of the present protocol. The bio-assay revealed that the title compounds exhibited good antioxidant and antimicrobial activities. Especially compounds 3a, 3e, 3h and 3i showed high activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) and hydrogen peroxide (H2O2) methods whereas the compounds 3b, 3c and 3f showed good antimicrobial results compared than that of the standard drugs.

Glycine: An Efficient Catalyst for the Synthesis of Tetra-Substituted Imidazole Derivatives in Aqueous Medium

A single-pot, tandem reaction in which cyclization through condensation of 1, 2-diphenylethane-1, 2-dione, benzaldehyde, aniline, and ammonium acetate has been accomplished by orthodox condition. The reaction has been conducting in an aqueous medium with help of glycine. This compact purveys corresponding tetra-substituted imidazole derivatives in high yields, shorter duration of reaction, and simple work-up procedures with the green facets by eschewing harmful reagents.

Methyltrimethoxysilane (MTM) as a Reagent for Direct Amidation of Carboxylic Acids.

Methyltrimethoxysilane [MTM, CH3Si(OMe)3] has been demonstrated to be an effective, inexpensive, and safe reagent for the direct amidation of carboxylic acids with amines. Two simple workup procedures that provide the pure amide product without the need for further purification have been developed. The first employs an aqueous base-mediated annihilation of MTM. The second involves simple product crystallization from the reaction mixture providing a low process mass intensity direct amidation protocol.

One-Pot Synthesis of Dihydroxyindeno[1,2-d]Imidazoles and Naphthoquinone Substituted Indandione and Oxindole Derivatives

A series of potentially bioactive compounds having either indole or indene frameworks such as dihydroindenone and indolinone derivatives were synthesized in good to high yields by one-pot, multi-component reaction of various amines, trichloroacetonitrile, ninhydrin or isatin, and 2-hydroxy-1,4-naphthoquinone. The present method offers desirable advantages including mild conditions, absence of catalyst, simple workup procedure, and easy purification process with no chromatographic technique.