One-pot Multicomponent Reaction Research Articles

Ultrasonic Assisted Three Component Synthesis of 3-Cyano-pyridine-2(1H)-ones

The requirements of sustainability and the green chemistry principles have prompted organic chemistry researchers to come up with novel methods for the synthesis of organic compounds that require minimum energy consumption and pose lesser environment harm. Ultrasonication of reaction mixtures is one such methodology. High frequency sound waves are known to emit energy that is utilized in product generation. Attempts were made to synthesize 2-pyridone derivatives using ultrasonication assisted method of synthesizing 3-cyano-pyridine-2(1H)-one starting from a three component one pot reaction. The reaction between cyanoacetamide, aromatic ketones and substituted aromatic aldehydes in the presence of NaOH as base yielded 4,6-diaryl-2-oxo-1,2-dihydropyridine-3-carbonitrile derivatives as a result of one-pot multicomponent reaction. The synthesized 4,6-diaryl-2-oxo-1,2-dihydropyridine-3-carbonitrile derivatives were characterized by 1H NMR, 13C NMR, HRMS and FTIR spectra. Ultrasonication has been found to significantly reduce reaction time, enhance reaction rate and yield compared to conventional heating methods.

Copper-based laboratory waste: Its application as a catalyst and recovery

In this study, Cu2O was isolated from laboratory waste, and its catalytic potential was explored for the synthesis of 1,4-disubstituted 1,2,3-triazole via a one-pot multicomponent click reaction in water at room temperature. Isolated Cu2O was characterized using IR spectroscopy, PXRD, XPS, SEM, and TEM. The catalytic activity of the recovered Cu2O and commercial Cu2O was compared and it was found to be the same. The catalyst was recycled and reused up to three cycles without significant loss of yield. Further, the remaining Cu2O-waste was converted to copper sulphate pentahydrate (CuSO4·5H2O) by treating it with hydrogen peroxide, (H2O2) and sulfuric acid (H2SO4) with 97 % Cu recovery.

Green preparation of new pyrimidine triazole derivatives via one-pot multicomponent reactions of guanidine.

In this research the goal was to produce novel pyrimidine triazole compounds in high yields using triethylamin as an efficient catalyst. These new compounds were synthesized by using multicomponent reaction of aldehydes, guanidine, electron deficient acetylenic compounds, tert-butyl isocyanide and hydrazonoyle chloride in aqueous media. Due to the presence of an NH group, which was assessed using two different methodologies, newly synthesized pyrimidine triazoles have antioxidant properties. Additionally, the antibacterial activity of newly created pyrimidine triazoles was assessed using the disk distribution method with two different types of Gram-positive bacteria and Gram-negative bacteria, demonstrating that the use of these compounds prevented the growth of bacteria. Applied to the preparation of pyrimidine triazole derivatives, this method has short reaction times, high product yields, and the ability to separate catalyst and product using simple procedures.

Stereoselective Synthesis of a Novel Series of Dispiro-oxindolopyrrolizidines Embodying Thiazolo[3,2-a]benzimidazole Motif: A Molecular Electron Density Theory Study of the Mechanism of the [3 + 2] Cycloaddition Reaction

A one-pot multi-component reaction was employed for the stereoselective synthesis of a novel set of dispiro-oxindolopyrrolizidines analogs incorporating a thiazolo[3,2-a]benzimidazole scaffold based on the [3 + 2] cycloaddition (32CA) reaction approach. The desired novel dispiro-oxindolopyrrolizidines 9a–d were achieved using the 32CA reaction of new ethylene derivatives based on thiazolo[3,2-a]benzimidazole moiety seven with thiazolidine derivatives eight and different substituted isatin compounds 5a–d (R = H, Cl, NO2, and Br). The final dispiro-oxindolopyrrolizidines cycloadducts were separated, purified, and fully characterized by means of a set of spectroscopic tools including IR, HNMR, CNMR, and MS. The Molecular Electron Density Theory (MEDT) was applied to explain the mechanism and stereoselectivity in the of the key 32CA reaction step. The reactive pseudo(mono)radical electronic structure of the in situ generated azomethine ylides and the high polar character of the corresponding 32CA reactions account for the low computed activation Gibbs free energies and total endo stereoselectivity of this kinetically controlled exergonic reaction. The computed relative Gibbs free activation energies of competitive reaction paths and regioisomers ratio distribution of 80:20 justify the major formation of 9a via the most favorable ortho/endo reaction path.

Fe3O4@SiO2@APTES@MPIB-Mn(II) as an eco-friendly and magnetically recyclable nano catalyst for the green synthesis of various xanthene derivatives

Due to the importance of the magnetic heterogeneous catalysts in the recent advances, especially organic synthesis, in this work, we introduced the new functionalised manganese magnetic nanoparticles as Fe3O4@SiO2@APTES@MPIB-Mn(II). The new magnetic material was studied by analyses, including Fourier-transform infrared spectroscopy (FT-IR), Field emission scanning electron microscope (FE-SEM), energy-dispersive X-ray (EDX), and vibrating sample magnetometer (VSM). The synthesized catalyst was used as a recyclable catalyst in the one-pot multi-component reactions (MCRs) for the preparation of xanthene derivatives (1,8-dioxo-octahydroxanthene, 14-substituted-14H-dibenzo[a,j]xanthene, 12-aryl-tetrahydrobenzo[a]xanthenes-11-one derivatives) under solvent-free conditions at 100 ℃. The studies revealed that this catalyst system exhibited excellent performance. The outstanding advantages in the present work include quick reaction time, high yields of products, and simple workup procedure. Also, no need to use any solvent, escape of the extra steps for separation of product from the catalyst, environmentally benign, high stability, and recovery of the catalyst for at least six repeated runs which provide reasonably-priced rewards are the other advantages of this protocol in the direction of green chemistry. This method can be an environmentally friendly protocol for other heterocyclic syntheses.

Multicomponent Synthesis of Imidazole-Linked Fully Conjugated 3D Covalent Organic Framework for Efficient Electrochemical Hydrogen Peroxide Production.

The semiconducting properties and applications of three dimensional (3D) covalent organic frameworks (COFs) are greatly hampered because of their long-ranged non-conjugated skeletons and relatively unstable linkages. Here, a robust imidazole-linked fully conjugated 3D covalent organic framework (BUCT-COF-7) is synthesized through the one-pot multicomponent Debus-Radziszewski reaction of the saddle-shaped aldehyde-substituted cyclooctatetrathiophene, pyrene-4,5,9,10-tetraone, and ammonium acetate. The semiconducting BUCT-COF-7, as a metal-free catalyst, shows excellent two electron oxygen reduction reaction (ORR) activity in alkaline medium with high hydrogen peroxide (H2 O2 ) selectivity of 83.4 %. When the BUCT-COF-7 as cathode catalyst is assembled into the electrolyzer, the devices showed high electrochemical production rate of H2 O2 up to 326.9 mmol g-1 h-1 . The accumulative amount of H2 O2 could totally degrade the dye methylene blue via Fenton reaction for wastewater treatment. This is the first report about intrinsic 3D COFs for efficient electrochemical synthesis of H2 O2 , revealing the promising applications of fully conjugated 3D COFs in the environment-related field.

Synthetic Methods of 1H-Pyrazolo[1,2-b]Phthalazine Derivatives

Abstract: This review deals with the synthetic methods of pyrazolo[1,2-b]phthalazine derivatives using one-pot multi-component reactions via modern and traditional methods. The synthetic methods are subdivided into groups according to the type of reactants e.g (1) one-pot three-component reaction of 2,3-dihydrophthalazine-1,4-dione, aldehydes and acetonitriles; (2) one-pot three-component reaction of 2,3-dihydrophthalazine-1,4-dione, aldehydes and aroyl acetonitriles; (3) one-pot three-component reaction of 2,3-dihydrophthalazine-1,4-dione, aldehydes and acetylacetone or 4-hydroxy-2H-chromen-2-one or acetylene derivatives; (4) one-pot four-component condensation reaction of phthalimide, hydrazine hydrate, aldehydes and acetonitriles; (5) one-pot four-component reaction of phthalic acid, hydrazine hydrate, indole-3- carbaldehyde and acetonitriles; and (6) one-pot three-component condensation reaction of 2,3- dihydrophthalazine-1,4-dione, aldehyde, and dimedone derivatives. Moreover, the various methods were reported.

Indole-pyridine carbonitriles: multicomponent reaction synthesis and bio-evaluation as potential hits against diabetes mellitus.

Background: Diabetes mellitus is a significant health disorder; therefore, researchers shouldfocus on discovering new drug candidates. Methods: A series of indole-pyridine carbonitrile derivatives, 1-34, were synthesized through a one-pot multicomponent reaction and evaluated for antidiabetic and antioxidant potential. Results: In this library, 12derivatives - 1, 2, 4, 5, 7, 8, 10-12, 14, 15 and 31 -exhibited potent inhibitory activities against α-glucosidase and α-amylase enzymes, in comparison to acarbose (IC50=14.50±0.11μM). Furthermore, kinetics, absorption, distribution, metabolism, excretionand toxicityand molecular docking studies were used to interpret the type of inhibition, binding energiesand interactions of ligands with target enzymes. Conclusion: These results indicate that the compounds may be promising hits for controlling diabetes mellitus and its related complications.

Green One-Pot Pseudo-Four Component Synthesis of Substituted 5-Cyano-2-imino-4-aryl/ heteroaryl-6-(phenylthio)-2H-pyran-3-carboxylic Acid Catalyzed by Montmorillonite K-10 Clay

A synthetic method of substituted 5-cyano-2-imino-4-aryl/heteroaryl-6-(phenylthio)-2H-pyran-3-carboxylic acid (4a-d) using Montmorillonite K-10 clay as catalyst was developed via one-pot pseudo-four-component reaction. Various aldehydes and thiophenols exhibit swift reactivity with cyanoacetic acid, resulting in satisfactory to exceptional yields (ranging from 70% to 90%) within an exceptionally short reaction duration of 0.75 to 1.5 h. The structural characterization of the synthesized compounds was conducted through IR, 1H, 13C NMR and elemental analysis. Safer technique, simple work-up as well as reusability of the catalyst for two runs are the characteristic features of this method. This multicomponent one-pot reaction approach demonstrates a straightforward synthetic strategy for the formation of two novel C-C bonds, one C-S bond, one C-O bond, and the formation of a new ring structure. Additionally, this reaction exhibits high efficiency as all the reactants are completely utilized.

One-pot synthesis, computational chemical study, molecular docking, biological study, and in silico prediction ADME/pharmacokinetics properties of 5-substituted 1H-tetrazole derivatives

An efficient synthesis of 5-substituted 1H-tetrazoles was successfully achieved through one-pot multi-component condensation reactions of some aromatic aldehydes or indolin-2,3-dione with malononitrile and sodium azide using diverse reaction conditions to obtain considerable product yields. Furthermore, it has been achieved for the first time to construct desired products under neat condition. Molecular docking studies with CSNK2A1 receptor disclosed the lowest binding energy displayed by the dimethoxyphenyl derivative 4c with − 6.8687 kcal/mol. The synthesized tetrazoles were screened for their in-vitro cytotoxic activity against epidermoid cancer cell line (A431) and colon cancer line (HCT116) with respect to normal skin fibroblast cell line (BJ-1) using MTT assay, and antimicrobial activity against the bacteria: K. pneumonia, S. aureus, and the fungi: Candida albicans, as well as their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl assay. In addition, the toxicity of tetrazole derivative was assessed by determination of their approximate lethal dose fifty (LD50), calculated via an oral administration to rats, through measurement of ALT and bilirubin levels in serum. The antitumor results can suggest that the potent tetrazole derivative namely, 3-(3,4-dimethoxyphenyl)-2-(1H-tetrazol-5-yl)acrylonitrile (4c) could be a potential drug against epidermoid carcinoma. The antioxidant results indicated to tetrazoles exhibited great antioxidant properties even at very low doses. A molecular dynamics simulation was performed for the synthesized compounds (ligands) to investigate their tendency for binding with the active sites of protein.

Synthesis and characterization of Co-MOF@Ag2O nanocomposite and its application as a nano-organic catalyst for one-pot synthesis of pyrazolopyranopyrimidines

In this study, a Co-MOF was synthesized via a co-precipitation procedure and then used as support for stabilizing Ag ions and producing Co-MOF@Ag2O nanocomposite by microwave irradiation. The characterization of synthesized Co-MOF@Ag2O nanocomposite was performed by using different techniques such as field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray (EDX) analyses, X-ray diffraction (XRD), Thermogravimetric analysis (TGA), Brunauer–Emmett–Teller (BET) and Fourier-transform infrared (FT-IR). The prepared Co-MOF@Ag2O nanocomposite was applied as a heterogeneous nano-catalyst in the synthesis of pyrazolopyranopyrimidines in water at 50 °C via the one-pot multicomponent reaction of ethyl acetoacetate, hydrazine hydrate, aromatic aldehydes and barbituric acid derivatives. Through this straightforward and effective protocol, different tricyclic fused pyrazolopyranopyrimidines were synthesized at high yields, and short reaction times, through an uncomplicated work-up process with no by-product. The Co-MOF@Ag2O nanocomposite has been effectively recycled for four consecutive cycles without appreciable loss in its activity. Cost-effectiveness, no need for column chromatography, mild conditions, catalyst recyclability, and eco-friendly nature make it a promising candidate compared to other methods.

Nano-γ-Al2O3/Sb(V) as an effective catalyst for the synthesis of highly substituted tetrahydropyridines under ultrasonic or thermal conditions

In this research work, nano-γ-Al2O3/Sb(V) was synthesized and characterized as a heterogeneous Lewis acid catalyst. Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FESEM), Brunauer–Emmett–Teller plot (BET), energy dispersive X-ray spectroscopy (EDS), and thermo gravimetric analysis (TG-DTG) were used to the characterization of nano-γ-Al2O3/Sb(V). Tetrahydropyridine is known as the core moiety in some natural products and drugs. Polysubstituted tetrahydropyridine-3-carboxylates are synthesized through a one-pot multicomponent reaction (MCR) of ethyl acetoacetate, aldehyde, and aniline derivative. This present study introduces the synthesis of these structures in the presence of nano-γ-Al2O3/Sb(V) under ultrasonic or thermal conditions. Compared with previously reported methods, our approach is convenient and offers several advantages such as milder reaction conditions, shorter reaction time, excellent yield, and the use of reusable catalyst.

Synthesis and Characterization of Novel 2D Ultrathin Nanoribbons Cd-Ag-MOF@ZnO Composite as Organo-Nanocatalyst for Preparation of Polyhydroquinoline Heterocycles

Novel ultrathin Cd-Ag-MOF@ZnO composite nanoribbons (Ut-Nr Cd-Ag-MOF@ZnO C) were prepared and characterized in this research to serve as organocatalyst in Hantzsch condensation for selective synthesis of asymmetric polyhydroquinolines through a one-pot multi-component condensation reaction of various substituted arylaldehyde, 5,5-dimethyl-1,3-cyclohexanedione, ammonium acetate and ethyl acetoacetate under solvent-free conventional heating in relatively short reaction times. The developed catalysts were easily recycled and reutilized at least three times under optimized reaction conditions with no noticeable decline in their initial catalytic activities. Operational simplicity and environmental compatibility, combined with the application of a reusable and affordable heterogeneous catalyst, significant efficiency, relatively short reaction time, and good yield are among the main characteristics of the proposed synthetic approach.

Visible-Light-Irradiated Multicomponent Reactions of Aliphatic Amines, Propiolate Acid Esters, and CF3 SO2 Na for Accessing β-CF3 Enamines.

A novel one-pot two-step multicomponent reaction has been achieved for the preparation of β-CF3 enamines by using different aliphatic amines, propiolates, and CF3 SO2 Na as starting material. In this protocol, various aliphatic amines including primary amines, cyclic or acyclic secondary amines were demonstrated to be good coupling partners, and different β-CF3 enamines were obtained in moderate to good yields. Among them, the primary aliphatic amines only gave pure (E)-β-CF3 enamines as products. The synthetic utility of the MCRs strategy was further demonstrated by mild conditions, gram-scale synthesis and natural sunlight-induced protocol. Preliminary mechanistic studies suggest that this trifluoromethylation of C(sp2 )-H involves radical process.

(Betaine: Citric Acid: H2O) a Natural Deep Eutectic Solvent (NaDES)-Mediated Efficient and Green Synthesis of 4-Benzylidene Isoxazol-5-one Derivatives

A biodegradable catalyst based on natural deep eutectic solvents (NaDESs) designed from Betaine and natural acids (Betaine: Citric Acid: H2O) with a molar ratio of (1:1.5:1) has been utilized in one-pot multi-component reaction for the synthesis of Isoxazol-5-ones derivatives in a mild, green and efficient manner. The reaction was carried out under different conditions that are, at 400C, ultrasonic and microwave. The developed method provided many advantages, including an excellent yield of up to 98% in a shorter reaction time, avoiding the use of toxic solvents and an easy handling process. Additionally, the use of NaDESs enabled the conservation of resources due to their simple preparation. The developed process adheres to the requirements of green chemistry by employing a bio-sourced and recyclable catalyst.

Lewis Acid Catalyzed Multicomponent Reaction of Aliphatic Aldehydes, Ynamides, Carboxylic Acids, and Amines to Access β3-Acylamino Amides

AbstractAn atom-economical strategy for the synthesis of alkylated β3-acylamino amides via Lewis acid catalyzed one-pot multicomponent reaction of ynamides, carboxylic acids, and aromatic amines with aliphatic aldehydes is described. In addition to the synthetic utility and scalability, the method exhibits excellent substrate scope and functional-group tolerance. The products can easily be transformed into valuable building blocks, such as peptide chains.

The full spectrum tuning of fluorescent molecules via a one-pot multicomponent reaction

Fluorogenic probes for imaging enable visualization and analysis of difficult-to-reach cells and organelles. However, there are limited efficient examples of tuning these fluorescent molecules to higher wavelengths. This is vital since different tissues are sensitive to varying wavelength emissions. To address this need, we report the discovery, tuning, structure-photophysical property relationships (SPPR), and time-dependent DFT (TD-DFT) computations of 400–700+ nm fluorescent pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolines and substituted imidazo[1,2-a]pyridin-3-amines. The syntheses involve the trimethylsilylcyanide (TMSCN) modified Groebke-Blackburn-Bienaymé (GBB) multicomponent reaction as well as the TMSCN modified GBB combined with subsequent condensation of an aldehyde, and Aza-Friedel-Crafts-Intramolecular Cyclization-Oxidation all in one pot. The SPPR reveals that electron-withdrawing strength in the para-position of the aminopyridine starting material has direct control over the absorption and fluorescence emission wavelengths of these molecules. The TD-DFT computations show the changes in the natural transition orbitals (NTOs) with differing substitutions to the parent molecule that dictate the observed excitations, emissions, and fluorescence intensities. These findings give insights and directions for tuning the fluorescent properties of these motifs for various uses as probes and imaging agents.

Catalytic performance of cadmium pyrophosphate in the knoevenagel condensation and one-pot multi-component reaction of chromene derivatives

Catalytic performance of cadmium pyrophosphate in the knoevenagel condensation and one-pot multi-component reaction of chromene derivatives

Triple superphosphate modified by tin (II) chloride: As a reusable and efficient catalyst for the one-pot synthesis of xanthene and xanthenone derivatives under green conditions

A simple method was developed for preparing tin (II) chloride-triple superphosphate. The material was thoroughly characterized using various techniques, including transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), and Brunauer–Emmett–Teller (BET) analysis. XRD analysis, BET, and SEM images indicated that the catalyst exhibited a crystalline structure and had particle sizes ranging from 21 to 23 nm. The catalytic performance was evaluated by conducting multicomponent one-pot condensation reactions. Specifically, the condensation of 2-naphthol with aldehydes and dimedone was conducted to produce 12-aryl(alkyl)-8,9,10,12 tetrahydrobenzo [a]xanthen-11-one derivatives, and the condensation of 2-naphthol with aldehydes was performed to synthesize 14-aryl(alkyl)-14H-dibenzo [a,j]xanthene derivatives. The acidic sites of the catalyst were determined using pyridine FTIR spectroscopy. The studies revealed that this catalyst system exhibited excellent performance, resulting in high product yields (88–96%) and reduced reaction times (12–20 min). The catalyst demonstrated high catalytic activity, good reusability, and a simple preparation method, thereby showing promise for potential industrial-scale applications.

Preparation of GO/Cys-Cu(II) as a novel, effective and recoverable catalyst for the multi component synthesis of spirooxindoles under mild conditions

Modified graphene oxide (GO/CPTES/Cys-Cu(II)) was prepared as a reusable catalyst and characterized by various analytical and spectroscopic methods, including Fourier transform spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray (EDX), scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and inductively coupled plasma (ICP) techniques. Obtained results from demonstrated the existence of cystein/Cu(II) on the MWCNTs surfaces. EDX and ICP analysis shown about 11% Cu (II) and about 8.5% of N element in the catalyst structure. Also, other characterization data confirmed the successfully preparation of synthesized catalyst. The efficiency of this novel catalyst was evaluated through the green synthesis of two variety of spirooxindole derivatives in a One-pot multi component reaction in ethanol as a green solvent. The catalyst showed high efficiency in this process and all of spirooxindoles were obtained after short time (18 min) in high to excellent yields (89–95%). The structure of all obtained products was assigned with hydrogen and carbon nuclear magnetic resonance (1H and 13C NMR) and FTIR. Furthermore, the catalyst could be easily recovered and directly reused at least five times without a notable reduction in activity. The other advantages of the presented methodology are high yields of products without the formation of by-products, simple and clean process, mild reaction conditions and agreement with green chemistry protocols.