One-pot Multicomponent Reaction Research Articles

Vegetable oil as a highly effective 100% bio-based alternative solvent for the one-pot multicomponent Biginelli reaction

Multicomponent one-pot Biginelli reactions have been successfully performed using vegetable oil as bio-based, non-toxic, and environmentally friendly solvents.

Multi-component cascade reaction of 3-formylchromones: highly selective synthesis of 4,5-dihydro-[4,5'-bipyrimidin]-6(1H)-one derivatives.

A novel protocol for the construction of highly functionalized bipyrimidine derivatives 4 and 5 from 3-formyl-chromones, ethyl 2-(pyridine-2-yl)acetate derivatives, and amidine hydrochlorides via an interesting and considerably complex multi-component cascade reaction was developed. The cascade reaction was manifested by refluxing a mixture of the three substrates in acetonitrile or DMF along with Cs2CO3. A series of 4,5-dihydro-[4,5'-bipyrimidin]-6(1H)-ones (DBPMOs) 4 was constructed regioselectively in suitable to excellent yields. Moreover, intermediates 4 then underwent a novel, metal- and oxidant-free cascade reaction to produce a series of [4,5'-bipyrimidin]-6(1H)-ones (BPMOs) 5. The formation of the bipyrimidine derivatives 4-5 was enabled by the formation of five bonds and the cleavage of one bond in one pot. This protocol can be used in the synthesis of functionalized bipyrimidine derivatives via a multi-component one-pot cascade reaction rather than multi-step reactions, which is suitable for both combinatorial and parallel syntheses of bipyrimidine derivatives.

ZnO nanoparticles supported on dendritic fibrous nanosilica as efficient catalysts for the one-pot synthesis of quinazoline-2,4(1H,3H)-diones.

The transmutation of waste into valuable materials has a special place in green chemistry. Herein, we report the preparation of quinazoline-2,4(1H,3H)-diones from 2-iodoaniline, isocyanides, and carbon dioxide in the presence of ZnO NPs stably placed on the surface of dendritic fibrous nanosilica by cellulose (DFNS/cellulose-ZnO) as a catalyst. This is a great economic strategy to create three bonds in a one-pot multicomponent reaction step employing functional groups. To prepare the catalyst, the dendritic fibrous nanosilica surface was first activated using cellulose as a substrate to support ZnO NPs. Cellulose acts as a stabilizing and reducing agent for the ZnO nanocatalyst and eliminates the need for a reducing agent. The structure of the prepared DFNS/cellulose-ZnO was examined by various methods, including thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma (ICP). The largest amount of quinazoline-2,4(1H,3H)-diones was obtained under ideal situations in the presence of 5 mg of DFNS/cellulose-ZnO under carbon dioxide (1 atm) utilizing a balloon set at 70 °C for 3 hours. The substance was reused for ten consecutive runs and the quinazoline-2,4(1H,3H)-dione content was more than 92% each time. This indicates the potential for application in the green and economic production of quinazoline-2,4(1H,3H)-diones, especially from low-cost feedstocks.

Multicomponent Synthesis of Luminescent Iminoboronates.

A family of iminoboronates was prepared through a one-pot multicomponent reaction, starting from boronic acid, anthranilic acid, and different salicylaldehydes. Their synthesis was straightforward and the complexes were obtained in good to excellent yields. Their photophysical properties were assessed in a diluted solution, and the complexes proved to be faintly luminescent. These chelates demonstrated remarkable Aggregation-Induced Emission Enhancement, which was rationalized using crystal structures.

Cu(OAc)2 Catalyzed Synthesis of Novel Chromeno [4,3-b]Pyrano[3,4-e]Pyridine-6,8-Dione Derivatives via a One-Pot Multicomponent Reaction in Water under Mild Reaction Conditions

An efficient method is introduced based on the copper(II) acetate catalyzed one-pot multicomponent synthesis of novel chromeno[4,3-b]pyrano[3,4-e]pyridine-6,8-dione derivatives under mild reaction conditions in water as a “green” solvent. The synthesis involves the multicomponent reaction of 4-aminocoumarin, 6-methyl-2H-pyran-2,4(3H)-dione, and aldehydes in the presence of 10 mol% of copper(II) acetate as catalyst under mild reaction conditions. Eight different derivatives are synthesized using various benzaldehydes with different functional groups. All the produced chromeno[4,3-b]pyrano[3,4-e]pyridine-6,8-diones were synthesized successfully in very good isolated yields. A possible mechanism was proposed and presented. In general, the method is simple and is based on commercially available reagents and catalyst.

Amide-Linked Monocarbonyl Curcumin Analogues: Efficient Synthesis, Antitubercular Activity and Molecular Docking Study

An approach toward the synthesis of novel conjugates of 3,5-bis (arylidene)-4-piperidones (DAP) pharmacophore with amide-linkage has been developed via one-pot multicomponent reaction of aryl aldehydes, piperidinone and 2-chloro-N-phenylacetamide using [Et3NH][HSO4] as a catalyst/medium. Both substitutions on arylidene rings and piperidinone nitrogen (substituted 2-chloro-N-phenylacetamide) were varied. The synthesized conjugates were evaluated for their in vitro antitubercular activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. Among the series, compounds 4f, 4g, 4i and 4j showed remarkable broad spectrum antitubercular activity with low IC50 values. Furthermore, computer docking simulations, for the most active conjugates were performed with the active site of mycobacterial enoyl-acyl carrier protein reductase (InhA) support the antitubercular activity. Lower cytotoxicity, high potency and promising activity against MTB and M. Bovis BCG suggest that amide linked DAP could serve as good leads for further modifications and development.

Cu(II)-Containing Nano-Silica Triazine Based Dendrimer: A Green and Proficient Catalyst for the Synthesis of Propargylamines

One-pot multicomponent reactions are an attractive synthetic strategy to generate multiple molecular scaffolds. Activation of a terminal alkyne C–H bond by transition metal catalysts is a reaction of fundamental interest in organic synthesis. One of the best examples of such a process is three components coupling of aldehydes, alkynes, and amines (A3-coupling). Herein, Cu(II)-containing nano-silica triazine based dendrimer was prepared, characterized and utilized as a retrievable catalytic system (Cu(II)-TrDen@nSiO2) for green formation of propargylamines under solvent-free conditions. The various aldehydes/ketones, amines, and phenylacetylene were reacted at 100 °C in the presence of the 1.34 mol% of the catalyst to synthesize propargylamines in high yields (87%–98%). The prepared catalyst can be isolated assisted by a simple filtration and recovered for five courses without significant reduction in its efficiency. The as-prepared nano-catalyst was characterized by FT-IR, TEM, SEM, EDX, TGA and ICP. Performing the reactions in environmentally friendly and affordable conditions, the low catalyst percentage, high yield of products, short reaction times and easy workup are the merits of this protocol.

Mesoporous Carbon of Carbonized Human Urine Waste: A Valuable Heterogeneous Catalyst for Chromene and Xanthene Derivative Synthesis

Human urine is universal unused waste material that is regularly disposed of by the human body. We, for the first time, presented an economically beneficial, sustainable, and novel route to synthesize mesoporous human urine carbon (HUC)-containing heteroatoms, i.e., C, Na, Cl, N, S, and P, using a human urine waste. The as-synthesized HUC were envisaged for their structural elucidation, morphology evolution, crystal structure, functional bonding, and elemental composition analyses through various sophisticated technologies. The HUC catalyst had a moderately crystalline nature due to the graphitic phase of carbon with a particle size of 20–50 nm, which was successfully used to synthesizing chromenes, 1,8-di-oxo-octahydroxanthenes, and benzypyrazolylcoumarin and biscoumarin derivatives through a one-pot multicomponent reaction with 20 mg of catalyst in EtOH/H2O solvent. This eco-friendly and simple method offers numerous advantages such as easy purification, clean reaction, and excellent yield for organic synthesis. The HUC catalyst can be recycled ten times and reused multiple times after activation without affecting catalytic performance.

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity.

A rapid route for obtaining unsymmetrical 1,2-dihydropyridines (1,2-DHPs) as opposed to 1,4-dihydropyridines (1,4-DHPs) has been achieved via a one-pot multicomponent Hantzsch reaction. A benign protocol has been developed for the preparation of various 1,2-dihydropyridine derivatives using heterogenized phosphotungstic acid on alumina support (40 wt %). High yields of over 75% have been accomplished in just 2–3.5 h after screening several heterogeneous catalysts and investigating the optimal reaction conditions. The catalyst chosen has passed the heterogeneity test and was shown to have the potential of being reused for up to 8 consecutive cycles before having a significant loss in activity. In addition, aromatic aldehydes gave the aforementioned regioisomer while the classical 1,4-DHPs were obtained when carrying out the reaction using aliphatic aldehydes. The preliminary study of the antiproliferative activity against human solid tumor cells demonstrated that 1,2-DHPs could inhibit cancer cell growth in the low micromolar range.

Nano-cerium Oxide/Aluminum Oxide: An Efficient and Useful Catalyst for the Synthesis of Tetrahydro[a]xanthenes-11-one Derivatives

Tetrahydro[a]xanthenes-11-one derivatives have been widely used industrially as agrochemicals, cosmetics and pigments are reported to exert broad spectrum biological and pharmacological activities. Herein, we reported an efficient and environmentally benign one-pot multi–component reaction for the synthesis of tetrahydro[a]xanthenes-11-one derivatives from the reaction of dimedone, aromatic aldehydes, and 2-naphthols in the presence of a catalytic amount of nano-nano-CeO2/Al2O3. The advantages of the effective method included good yields (91-98%), short reaction times, simple work-up and reusable catalyst. The catalyst could be recycled and reused for five times without much loss in its activity.

Synthesis of Substituted Phthalimides via Ultrasound-Promoted One-Pot Multicomponent Reaction.

In this work, a novel strategy for the straightforward synthesis of substituted phthalimides is described, which includes base-mediated Michael addition/intramolecular cyclization/[1,5]-H shift/cleavage of CS2/aromatization/nucleophilic acyl substitution reaction of 2-(4-oxo-2-thioxothiazolidin-5-ylidene)acetates and α,α-dicyanoolefines under ultrasound (US) irradiation. Some advantages of this method are as follows: having simple operation, easily accessible starting materials, chemoselective cascade process, synthetically useful yields, and green conditions by utilizing US irradiation as a source of energy and using ethanol as solvent.

Stereoselective Synthesis of Spirooxindole Derivatives Using One-Pot Multicomponent Cycloaddition Reaction and Evaluation of Their Antiproliferative Efficacy.

A highly stereoselective, one-pot, multicomponent method has been developed to synthesize pyrrolizidine- and N-methyl pyrrolidine-substituted spirooxindole derivatives. The [3 + 2] cycloaddition reaction involves the reaction between the dipole azomethine ylides, generated in situ from the reaction between isatin and secondary amino acids such as L-proline or sarcosine, and α,β-unsaturated carbonyl compounds as the dipolarophile. The reaction condition was optimized to achieve excellent regio- and stereoselectivity. Products were obtained in good yield using ethanol as a solvent at the reflux temperature. The newly synthesized spirooxindole derivatives were evaluated for their antiproliferative efficacy against National Cancer Institute (NCI)-60 cancer cell lines and DNA G-quadruplex (G4) interaction capacity. Compound 14b produced selective cytotoxicity against leukemia, renal, colon, and prostate cancer cell lines at a 10 μM concentration. The G4 interaction studies further suggested that these spirooxindole derivatives were devoid of any activity as DNA G4 ligands.

Green Bio‐organic and Recoverable Catalyst Taurine (2‐aminoethanesulfonic acid) for Synthesis of Bio‐active Compounds 3,4‐Dihydropyrimidin Derivatives in Aqueous Medium.

AbstractA highly green bio‐organic catalyst known as Taurine (2‐aminoethanesulfonic acid) is plentifully in the tissues of humans and animals and is an efficient and environmentally benign catalyst for the one‐pot multicomponent reaction synthesis of bio‐active 3,4‐dihydropyrimidin‐2(1H)‐ones/thiones (Biginelli Reaction) in aqueous medium. The advantages of this protocol by way of the Taurine catalyst are that it is eco‐friendly, commercially available, low cost, has high reusability, short reaction times, high yields and the products obtained high purities without using any organic solvents.

Facile and green synthesis of a series of dihydro-[1,2,4]triazolo[1,5-a]pyrimidine scaffolds

This work presents a new catalytic application of 4,4′-trimethylenedipiperidine for the efficient synthesis of a series of dihydro-[1,2,4] triazolo[1,5-a]pyrimidines. According to the principles of green chemistry, the reaction was performed (a) in a solvent mixture comprised of water and ethanol (1:1 v/v) at reflux temperature and (b) solvent-free grinding in a mortar by a pestle. The organocatalyst could be reused up to 10 runs, and no reduction of catalytic activity was detected. A variety of substituted dihydro-[1,2,4] triazolo[1,5-a]pyrimidines were obtained in good to excellent yields under eco-friendly conditions. 4,4′-Trimethylenedipiperidine is commercially available and easy to handle, and it also shows high thermal stability and good solubility in water. This work revealed that this organocatalyst, a hydrogen bond donor to active carbonyl groups and simultaneously a Lewis base through the nitrogen atom of second piperidine moiety, could play a vital role in the promotion of the one-pot multi-component reactions. The main merits of the current methodology include short reaction time, wide substrate scope, use of a metal-free catalyst and green solvents, and simple work-up process. Furthermore, this organocatalyst can be an alternative to piperidine for organic transformations.

Preparation and application of a novel supported 3-(3-sulfamic acid imidazolium trifluoroacetate)propyl triethoxysilane on magnetic nanoparticles as a new magnetic ionic liquid for the synthesis of triazole quinazolinones and fused pyrimidines

Supported 3-(3-sulfamic acid imidazolium trifluoroacetate)propyl triethoxysilane on magnetic nanoparticles as a novel nanocatalyst was synthesized and characterized by FT-IR, XRD, TGA, SEM, TEM and VSM techniques. The catalytic activity of the magnetic catalyst was studied through one-pot synthesis of triazole quinazolinones and fused pyrimidine derivatives via one-pot multi-component reactions under thermal conditions. This catalyst demonstrated excellent catalytic properties with high percentage in short reaction times, low cost and easily separated using an external magnet and reusable without significant loss of its catalytic efficiency.

Highly effective synthesis of 1-thioamidoalkyl-2-naphthols and tetrahydropyridines using a nanostructured silica-based catalyst under mild conditions

Nano-2-[N',N'-dimethyl-N'-(silica-n-propyl)ethanaminium chloride]- N,N-dimethylaminium bisulfate (nano-[DSPECDA][HSO4]) was used as a highly effective and heterogeneous silica-based nanostructured catalyst for the synthesis of 1-thioamidoalkyl-2-- naphthols and substituted tetrahydropyridines. The expected products were prepared in mild conditions. In this work, three novel 1-thioamidoalkyl-2-naphthols and two new tetrahydropyridine derivatives were synthesized and characterized by IR, 1H and 13C NMR and Mass spectroscopy. One-pot multi-component condensation of 2-naphthol with arylaldehydes and thioacetamide catalyzed by nano-[DSPECDA][HSO4] under green, mild and solvent-free conditions led to 1-thioamidoalkyl-2-naphthols in high yields. The nanocatalyst was also used for the preparation of functionalized tetrahydropyridines by the one-pot multi-component reaction of anilines, arylaldehydes and ethylacetoacetate under solvent-free and mild conditions. The reaction results were found to be better compared to the literature in terms of one or more of these factors: yield, time, and the reaction media. All the products were purified by recrystallization from EtOH, and without column chromatography, being in good agreement with the green chemistry protocols.

Facile Synthesis of 1,8-dioxooctahydro Xanthenes by Reusable Zinc Sulfide based Ternary Nanocomposite via Hydrothermal Route

Background: Metal oxide or metal oxide composite nanoparticles are attaining tremendous importance due to their catalytic activities for various organic transformations. Objective: To report the one-pot synthesis of xanthene derivatives prepared by ZnS-Fe2O3-Ag composite under solvent-free conditions. Method: To prepare nanocomposite by a facile and simple hydrothermal approach. Results: The prepared composite is smaller (17.56 nm) in size and can be easily separable, recycled and reused six times without any significant loss of catalytic activity with excellent yields. In short reaction time, great catalytic activity was perceived with no co-catalyst and any other activator. Conclusion: In conclusion, ZnS-Fe2O3-Ag composite provides a simple, economical, efficient and greener method for the synthesis of one-pot multicomponent reaction of aldehyde with 1,3-diketones under solvent free conditions for the synthesis of 1,8-dioxooctahydro xanthenes. In short reaction time, great catalytic activity was perceived with no co-catalyst and any other activator.

Solvent free and green synthesis of efficient solvochromism based coumarin moieties for quick visualization of LFPs and OLEDs applications

We report a novel solvochromism based coumarin thiophene fluorescent tags (CTFTs) namely, 3-(thiophen-2-yl)-2H-chromen-2-one (3a) and 6, 8-dichloro-3-(thiophen-2-yl)-2H-chromen-2-one (3b) via solvent free, eco-friendly, low-cost and one-pot multicomponent reaction system under microwave irradiation protocol. The synthesized CTFTs derivatives were characterized by different analytical techniques namely, Fourier transform infrared spectroscopy (FTIR), Proton nuclear magnetic resonance spectroscopy (1H NMR), Mass spectrometer, Powder X-ray diffraction (PXRD), Scanning electron microscope (SEM), Energy dispersive X-ray analysis (EDAX), Ultraviolet-visible (UV−vis) and Photoluminescence spectrometer (PL). The CTFTs show strong excitation peaks at 407 nm (3a) and 431 nm (3b) due to π-π* and n-π* transitions in the aromatic core and CTFTs show strong emission peaks at 456 nm (3a) and 501 nm (3b) due to σ-π* and π-π* transitions. The CTFTs derivatives exhibit cyan blue (3a) and greenish blue (3b) luminescence in liquid and solid-state. The CTFTs are investigated as an innovative category for the visualization of latent fingerprints on various non-porous material surfaces. The obtained results prove that the CTFTs can be served as promising small organic fluorescent tags for flat-panel display and latent fingerprint applications.

A new approach for the synthesis of fluorescent pyrido[1,2-a]benzimidazoles

A facile synthesis of new pyrido[1,2-a]benzimidazoles through a one-pot multicomponent reaction of malononitrile, electron-deficient aryl aldehydes and heterocyclic enamines followed by a nitrous acid release under mild condition, is reported. Depending on the substituents on heterocyclic enamine, newly synthesized products have been obtained either as an inseparable mixture of regioisomers or as a single regioisomer. A plausible mechanism can be proposed for the formation of pyrido[1,2-a]benzimidazoles via this unfamiliar transformation with the HNO2 extrusion. The structures of all title compounds were elucidated using spectroscopic methods and physical characteristics involving single crystal X-ray diffraction and TOF-MS measurements. In addition, among all the products, CN- and CF3-substituted ones showed promising absorption and fluorescent properties.

Ionic liquid mediated one-pot multicomponent synthesis of methyl 1,2-diaryl-4-hydroxy-5-oxo-2,5-dihydro-1h-pyrrole-3-carboxylates

Abstract A simple, efficient, eco-friendly and a green synthetic method has been developed for the synthesis of polysubstituted pyrrolidinone derivatives via one-pot multi component reaction of aromatic aldehydes, aromatic amines with dimethyl but-2-ynedioate by using inexpensive nontoxic ionic liquid [bmim]BF4 under PEG-400 medium. The present methodology offers more environmental acceptability, higher yields with very shorter reaction time and recyclability of the ionic liquid.