One-pot Multicomponent Reaction Research Articles

One-Pot Multicomponent Synthesis of 3-Methyl-4-(Hetero)Arylmethylene Isoxazole-5(4H)-Ones Using Guanidine Hydrochloride as the Catalyst under Aqueous Conditions

Here, we have developed an expeditious and efficient protocol for the synthesis of isoxazole-5(4H)-ones derivatives using guanidine hydrochloride as a catalyst using water as a solvent. The one-pot multicomponent reaction of aldehydes, ethyl acetoacetate, and hydroxylamine hydrochloride at room temperature to give a 3-methyl-4-(hetero)arylmethylene isoxazole-5(4H)-ones derivatives in an excellent yield. The key advantages of the reported method are shorter reaction time, energy-efficient, easy work-up procedure, wide substrate scope tolerance, economical, etc. further the catalyst was recycled up to 5 times along with high product yield without significant loss of its catalytic activity.

Triethylammonium Hydrogen Sulfate [Et3NH][HSO4]-Catalyzed Rapid and Efficient Multicomponent Synthesis of Pyrido[2,3-d]pyrimidine and Pyrazolo[3,4-b]pyridine Hybrids.

An operationally simple, one-pot multicomponent reaction has been developed for the assembly of pyrido[2,3-d]pyrimidine and pyrazolo[3,4-b]pyridine derivatives (4a–4am) in excellent yields (92–94%) with high purity. The reactions were easy to perform simply by mixing of electron-rich amino heterocycles (including aminouracils and aminopyrazoles), aldehyde, and acyl acetonitrile in the presence of [Et3NH][HSO4] under solvent-free conditions. The remarkable feature of the present approach is that the ionic liquid possesses dual solvent-catalytic engineering capability. Results of this study revealed that 1 mmol of the ionic liquid catalyst under solvent-free conditions at 60 °C is the best reaction parameter for the construction of fused pyridine and pyrimidine derivatives in excellent yields. The present methodology showed good results under gram-scale conditions, thereby indicating its applicability in industrial as well as academic settings in the near future.

Indium-Organic Framework with soc Topology as a Versatile Catalyst for Highly Efficient One-Pot Strecker Synthesis of α-aminonitriles.

An In(III) based metal-organic framework (MOF), In-pbpta, with soc topology was constructed from the trigonal prismatic [In3(μ3-O)(H2O)3(O2C-)6] secondary building unit (SBU) and a custom-designed tetratopic linker H4pbpta (pbpta = 4,4',4″,4‴-(1,4-phenylenbis(pyridine-4,2,6-triyl))-tetrabenzoic acid)). The obtained MOF shows a Brunauer-Emmett-Teller surface area of 1341 m2/g with a pore volume of 0.64 cm3/g, which is the highest among the scarcely reported In-soc-MOFs. The constructed MOF demonstrates excellent performance as a heterogeneous Lewis acid catalyst for highly efficient conversion in a one-pot multicomponent Strecker reaction for the preparation of α-aminonitriles under solvent-free conditions, which can be easy to separate and recycle without significant loss of activity for up to seven cycles. The computational modeling studies suggest the presence of the three substrates in close vicinity to the In-oxo cluster. The strong interactions of the aldehyde/ketone and the amine with the In-oxo cluster together with the readily available cyanide ion around the In-oxo cluster lead to high catalytic conversion within a short period of time for the MOF catalyst. Our work therefore lays a foundation to develop MOF as a new class of efficient heterogeneous catalyst for one-pot Strecker reaction.

A Facile Synthesis and Biological Screening of Pyrimidine Derivatives under Ultrasonic Irradiations by ZnCr2O4 Nano-Particles Catalyst

Using a recyclable catalyst, facile synthesis of pyrimidine derivatives (4a-e) is attributed through the one-pot multi-component reaction of 2-amino benzimidazole (1) substituted aromatic aldehydes (2a-e) with malononitrile (3) under ultrasonic irradiations. Synthesized derivatives might help society in getting more active pharmaceutical constituents. In this present work, series of substituted pyrimidine (4a-e) were synthesized and confirmed with different spectra characterization methods. The ZnCr2O4 nano-particles play a vital role in eco-friendly, highly efficient, recyclable heterogeneous nanocatalyst. Furthermore, synthesized pyrimidine derivatives showed significant biological activities. Advantages of this handy route are less reaction time, simple isolation, and highly yielded products.

Eco-Friendly Synthesis, Biological Evaluation, and In Silico Molecular Docking Approach of Some New Quinoline Derivatives as Potential Antioxidant and Antibacterial Agents.

A new series of quinoline derivatives 5–12 were efficiently synthesized via one-pot multicomponent reaction (MCR) of resorcinol, aromatic aldehydes, β-ketoesters, and aliphatic/aromatic amines under solvent-free conditions. All products were obtained in excellent yields, pure at low-cost processing, and short time. The structures of all compounds were characterized by means of spectral and elemental analyses. In addition, all the synthesized compounds 5–12 were in vitro screened for their antioxidant and antibacterial activity. Moreover, in silico molecular docking studies of the new quinoline derivatives with the target enzymes, human NAD (P)H dehydrogenase (quinone 1) and DNA gyrase, were achieved to endorse their binding affinities and to understand ligand–enzyme possible intermolecular interactions. Compound 9 displayed promising antioxidant and antibacterial activity, as well as it was found to have the highest negative binding energy of -9.1 and -9.3 kcal/mol for human NAD (P)H dehydrogenase (quinone 1) and DNA gyrase, respectively. Further, it complied with the Lipinski’s rule of five, Veber, and Ghose. Therefore, the quinoline analogue 9 could be promising chemical scaffold for the development of future drug candidates as antioxidant and antibacterial agents.

An efficient and green synthesis of 1,4-dihydropyridine derivatives through multi-component reaction in subcritical EtOH

A simple, environmentally friendly and highly efficient method has been developed for the synthesis of 1,4-dihydropyridine compounds. A number of aromatic aldehydes, ethylaceto acetate and urea converted into corresponding in l,4-Dihydropyridine derivatives via one-pot multicomponent reaction in sub-critical ethanol. This study shown that 1,4-dihyropyridines can be synthesized in sub-critical ethanol and has the advantage of excellent yields, short reaction time, and simple work-up conditions.

Synthesis and characterization of CuO/ZnO/Al2O3 particles and its utilization as a catalyst for acrylamide derivatives

During the study, a novel CuO/ZnO/Al2O3 glass-ceramic was prepared via an ordinary melt annealing route. Synthesized catalyst was then characterized via Fourier Transform Spectroscopy (FT-IR), X-Ray Diffractometer (XRD), Scanning Electronic Microscopy (SEM) supported with Energy Dispersive Spectroscopy (EDAX) and X-ray mapping. The synthesized catalyst was then applied for Knoevenagel-type reaction via efficient one-pot multicomponent reaction of 2-cyano-p-methoxyacetanilide and p-nitrobenzaldehyde in the presence of CuO/ZnO/Al2O3 catalyst under solvent-free condition. The produced acetanilide derivative was found to be suitably synthesized with excellent yields in the presence of CuO/ZnO/Al2O3 catalyst compared with that previously synthesized using piperidine. The final product was also confirmed using an energy gap calculated from HUMO-LUMO via density functional theory (DFT).

One-Pot Synthesis of Pentafluorophenyl Sulfonic Esters via Copper-Catalyzed Reaction of Aryl Diazonium Salts, DABSO, and Pentafluorophenol.

Pentafluorophenyl (PFP) sulfonic esters were synthesized via a copper-catalyzed one-pot multicomponent reaction of aryl diazonium tetrafluoroborate, DABSO (DABCO·(SO2)2), and pentafluorophenol. The reaction system provided the desired pentafluorophenyl sulfonic esters in good yields and exhibited excellent functional group tolerance. In addition, the generated PFP sulfonic esters were successfully applied in Sonogashira, Suzuki, Chan-Evans-Lam, and decarboxylative coupling reactions.

A Model for Late-Stage Modification of Polyurethane Dendrimers Using Thiol-Ene Click Chemistry.

Dendritic materials possessing urethane linkage are surprisingly more stable than similar structures having functional groups such as ether, ester, amide, or carbosilane. This generates profound interest in dendritic polyurethanes. Construction of a well-defined polyurethane dendrimer is, however, challenging because of isocyanates’ high reactivity. As a model of our ongoing dendrimer-research, herein, we report a protecting group-free one-pot multicomponent Curtius reaction to furnish a robust and versatile AB2-type dendron, which ensures late-stage modification of both the dendron and dendritic macromolecule yielding a surface functionalized polyurethane dendrimer. While 5-hydroxyisophthalic acid, 11-bromoundecanol, and 4-penten-1-ol were utilized in the construction of the dendron, thiol–ene click chemistry was employed for the late-stage modification. Novel dendrons and dendrimers synthesized were characterized by NMR (1D and 2D) and high-resolution MALDI-TOF analysis. This strategy allows an easy late-stage modification of dendritic macromolecules and is highly useful in the synthesis of both symmetrical and unsymmetrical dendrimers (Janus dendrimers).

Ferrocene-Functionalized Dithiocarbamate Zinc(II) Complexes as Efficient Bifunctional Catalysts for the One-Pot Synthesis of Chromene and Imidazopyrimidine Derivatives via Knoevenagel Condensation Reaction.

Four new mononuclear/coordination polymeric (CP) zinc(II) complexes (1-4) of ferrocenyl/pyridyl-functionalized dithiocarbamate ligands, N-ferrocenylmethyl-N-butyl dithiocarbamate (L1), N-ferrocenylmethyl-N-ethylmorpholine dithiocarbamate (L2), N-ferrocenylmethyl-N-2-(diethylamino)ethylamine dithiocarbamate (L3), and N-4-methoxybenzyl-N-3-methylpyridyl dithiocarbamate (L4), have been synthesized and characterized by elemental analyses, IR, UV-vis, and 1H and 13C{1H} NMR spectroscopic techniques. The solid-state structures of complexes 1, 3, and 4 have been determined by single-crystal X-ray crystallography as well as powder X-ray diffraction. Single-crystal X-ray crystallography revealed a monomeric structure for complex 1 but 1D polymeric structures for complexes 3 and 4. In all complexes, dithiocarbamate ligands are bonded to the Zn(II) metal ion in a S^S chelating mode, and in the CPs, N atoms on the 2-(diethylamino)ethylamine and 3-pyridyl functionalities in the ligands on the neighboring molecules are also bonded to metal centers, leading to the formation of either a discrete tetrahedral molecule in 1 or 1D CP structures in 3 and 4. The Zn(II) metal centers in the polymeric structures exhibited either square-pyramidal or octahedral geometries. The supramolecular structures in these complexes are sustained via C-H···π (ZnCS2, chelate; 3 and 4), C-H···π, and H···H interactions. The catalytic performances of complexes have also been assessed in the Knoevenagel condensation and one-pot multicomponent reactions. Catalysis results showed that the CP 3 acts as a heterogeneous bifunctional catalyst with excellent transformation efficiency at low catalyst loading.

Synthesis of some heterocyclic of expected bioactivity via reactions of thiazine derivatives: Thesis Abstract

Thesis Abstract: 2-acetylphenothiazine plays an important role in organic chemistry. The behavior of 2-acetylphenothiazine towards various reagents was carried out. Thus, the aim of the present work is to design and synthesize some of heterocyclic nuclei through the reaction of phenothiazine derivatives as scaffold moiety with different reagents. α,β-Unsaturated ketones containing phenothiazine moiety 4, 5, 7 were synthesized by condensation of 2-acetylphenothiazine with different aryl aldehydes 2, 3, and (DMFDMA). Pyrazole skeletons were also synthesized by 1,3-dipolar cycloaddition reactions of α,β-unsaturated ketones with different nucleophilic reagents. Formylpyrazole derivative 36 was synthesized through the Vilsmeier-Haack reaction of phenylhydrazone 35b. Azines derivatives of phenothiazines were synthetically constructed from one-pot multicomponent reactions of 1-(4a, 10a-dihydro-10H-phenothiazine-2-yl) ethan-1-one with various reagents. Newly synthesized compounds were screened as antioxidant agents. The sequence of these reactions that adopted for the synthesis of the designed compounds in this thesis is summarized into two sections. Furthermore, studying of the biological activity of the newly synthesized compounds as antioxidants properties were performed.

Novel aggregation induced emission based 7-(diethylamino)-3-(4-nitrophenyl)-2H-chromen-2-one for forensic and OLEDs applications

In this report, a novel solvatochromism, aggregation induced emission (AIE) based 7-(diethylamino)-3-(4-nitrophenyl)-2H-chromen-2-one fluorescent probe (CFP) was synthesizes via one-pot multi-component reaction system under ultrasonication method. The synthesized CFP was characterized using different instrumental techniques namely, Fourier transform infrared spectroscopy (FTIR), Proton nuclear magnetic resonance spectroscopy (1H NMR), Mass spectrometer, Scanning electron microscope (SEM), Energy dispersive X-ray analysis (EDAX), Thermal gravimetric analysis (TGA), Transmission electron microscopy (TEM), UV−Vis spectrometry and Fluorescence spectrophotometer. The synthesized CFP produces red emission in solid as well as in liquid state. The synthesized CFP was investigated as a new labeling mediator for the visualization of latent fingerprints (LFPs) on the different non-porous materials surface. The obtained CIE result proves that the organic moiety was extremely helpful for the fabrication of red-light emitting diodes in the display device. The synthesized CFP will play a crucial role in visualizing the LFPs on various materials surface, organic light emitting diodes (OLEDs) and anti-counterfeiting applications.

Microwave assisted, sequential two-step, one-pot synthesis of novel imidazo[1,2-a]pyrimidine containing tri/tetrasubstituted imidazole derivatives.

A series of novel imidazo[1,2- a ]pyrimidine containing tri/tetrasubstituted imidazole derivatives (1-10) has been synthesized via sequential two-step, one-pot, multicomponent reaction using imidazo[1,2- a ]pyrimidine-2-carbaldehyde, benzil, primary amines, and ammonium acetate catalyzed by p -toluenesulfonic acid under microwave-assisted conditions. The results showed that target compounds can be obtained from a wide range of primary amines bearing different functional groups with moderate to good yields (46%-80%) under optimum reaction conditions. This method provides a green protocol for imidazo[1,2- a ]pyrimidine containing tri/tetrasubstituted imidazole derivatives due to ethyl alcohol as a green solvent, microwave irradiation as a greener heating method and one-pot multicomponent reaction as a green technique. The synthesized compounds have been elucidated using various spectroscopic tools such as FT-IR, 1H NMR, 13 C NMR, and MS.

DTP/SiO2:An Efficient And Reusable Heterogeneous Catalyst For synthesis of dihydropyrano[3,2-c]chromene-3-carbonitrile derivatives

An efficient and convenient method has been developed for the synthesis of 2-amino-5-oxo-4-phenyl-4, 5-dihydropyrano[3,2-c]chromene-3-carbonitrile derivatives from one-pot multicomponent reaction between 4-hydroxy-2H-chromen-2-one, aromatic aldehydes and malononitrile catalyzed by DTP/SiO2 as an efficient and reusable heterogeneous catalyst. The current method provides adavtages over reported method viz simple operational procedure, easy isolation and recyclability of the catalyst, environmental benign, reduced reaction time and superior yield.

Dendrons containing boric acid and 1,3,5-tris(2-hydroxyethyl)isocyanurate covalently attached to silica-coated magnetite for the expeditious synthesis of Hantzsch esters

A new multifunctional dendritic nanocatalyst containing boric acid and 1,3,5-tris(2-hydroxyethyl)isocyanurate covalently attached to core–shell silica-coated magnetite (Fe3O4@SiO2@PTS-THEIC-(CH2)3OB(OH)2) was designed and properly characterized by different spectroscopic or microscopic methods as well as analytical techniques used for mesoporous materials. It was found that the combination of both aromatic π–π stacking and boron–oxygen ligand interactions affords supramolecular arrays of dendrons. Furthermore, the use of boric acid makes this dendritic catalyst a good choice, from corrosion, recyclability and cost points of view. The catalytic activity of Fe3O4@SiO2@PTS-THEIC-(CH2)3OB(OH)2, as an efficient magnetically recoverable catalyst, was investigated for the synthesis of polyhydroacridines (PHAs) as well as polyhydroquinolines (PHQs) via one-pot multicomponent reactions of dimedone and/or ethyl acetoacetate, different aldehydes and ammonium acetate in EtOH under reflux conditions. Very low loading of the catalyst, high to quantitative yields of the desired PHAs or PHQs products, short reaction times, wide scope of the substrates, eliminating any toxic heavy metals or corrosive reagents for the modification of the catalyst, and simple work-up procedure are remarkable advantages of this green protocol. An additional advantage of this magnetic nanoparticles catalyst is its ability to be separated and recycled easily from the reaction mixture with minimal efforts in six subsequent runs without significant loss of its catalytic activity. This magnetic and dendritic catalyst can be extended to new two- and three-dimensional covalent organic frameworks with different applications.

Hexamethylenetetramine-based ionic liquid anchored onto the metal–organic framework MIL-101(Cr) as a superior and reusable heterogeneous catalyst for the preparation of hexahydroquinolines

Regarding the significance of medicinal and pharmacological sciences, we explored one-pot multicomponent reaction of aromatic aldehydes, aryl amines, malononitrile and dimedone in the presence of HMTA-BAIL@MIL-101 (Cr) as a novel, stable and strong catalyst. The remarkable features of this approach are good to excellent yields (92–98%), short reaction times (10–20 min), low catalyst loading, reusability and stability of the catalyst. The prepared hexamethylenetetramine-based ionic liquid/MIL-101(Cr) composite was identified via FE-SEM, XRD, EDS, TGA, BET and FT-IR techniques.

A highly efficient and green approach for the synthesis of pyrimido[4,5-b]quinolines using N,N-diethyl-N-sulfoethanaminium chloride

Abstract A highly efficient and green protocol for the synthesis of pyrimido[4,5-b]quinolines has been described. The one-pot multicomponent reaction of dimedone with arylaldehydes and 6-amino-1,3-dimethyluracil in the presence of N,N-diethyl-N-sulfoethanaminium chloride ([Et3N–SO3H][Cl]) as an ionic liquid (IL) catalyst under solvent-free conditions afforded the mentioned compounds in high yields and short reaction times. Our protocol is superior to many of the reported protocols in terms of two or more of these factors: the reaction times, yields, conditions (solvent-free versus usage of organic solvents), temperature and catalyst amount.

A new class of fluorogenic thiazolo[2,3-b]quinazolinone receptor: selective detection towards mercury and hydrogen bisulfate ions in aqueous medium.

A series of fluorophoric and structurally diverse thiazoloquinazoline derivatives were synthesized in a one-pot multicomponent cascade reaction using a microwave irradiation technique. The unique structural arrangement of the synthesized compounds encouraged us to design a new type of bioactive molecular receptor. This receptor interacts with HSO4− in 1 : 1 and Hg2+ in 1 : 2 binding stoichiometric ratios resulting in a change in fluorescence as well as absorption spectra in aqueous medium. The ion bonded receptor complex possibly enhances the fluorescence signal of the receptor via H-bonded complex formation with HSO4− ions and co-ordinate complex formation with Hg2+ ions.

A metal-free Petasis reaction towards the synthesis of N-(α-substituted)alkyl sulfoximines/sulfonimidamides.

Herein, we disclose a metal-free novel approach for the synthesis of N-(α-substituted)alkyl sulfoximines/sulfonimidamides via one-pot multicomponent Petasis reactions of aryl boronic acids, ortho-hydroxyarylaldehydes and sulfoximines/sulfonimidamides in moderate to very good yields. The presence of two chiral centres provides a mixture of diastereomers almost in a 1 : 1 ratio, which are separated successfully in most of the cases. The -OH functionality of Petasis products is further utilized to derive heterocycles via O-allylation, followed by intramolecular Heck cyclization, proving the synthetic utility of the products.

Bifunctional C2-symmetric ionic liquid-supported (S)-proline as a recyclable organocatalyst for Mannich reactions in neat condition

A bi-functional C2-symmetric ionic liquid-supported (S)-Proline organocatalyst [BHEDIMP][CF3CO2] has been designed and synthesized for the first time. The novel C2-symmetric organocatalyst [BHEDIMP][CF3CO2] (4 mol%) was employed for the one-pot multi-component Mannich reactions comprising of substituted acetophenones, arylamines, and aryl aldehydes to yield racemic β-amino ketones derivatives in neat conditions. This present synthetic method is highlighted by numerous advantages such as low catalyst loading percentage, solvent-free synthesis, short reaction times, easily accessible substrates, and devoid of chromatography purification. The supported C2-symmetric organocatalyst was recycled and reused six times without substantial damage to its catalytic efficiency.