Component Condensation Reaction Research Articles

Solvent-free one-pot two component synthesis. Tuning of optoelectronic properties of fluorescent phloroglucinol-aryl Schiff base compounds

A series of new aryl-Schiff base derivatives were synthetized from the one-pot approach: two component condensation reaction in absence of solvent, in quantitative yields with a high atom economy under green conditions. All of the derivatives were fully characterized by NMR, vibrational absorption analysis, UV/vis absorption and fluorescence spectroscopy, and high-resolution mass spectrometry. The aryl-Schiff bases predominantly present the enol-imine tautomer in acetone-d6, while both enol-imine and keto-imine tautomer readily concur in dimethyl sulphoxide-d6. The emission of the series could be tailored by substituting electron donor or electron acceptor groups in the aryl-Schiff bases from fluorescent to not fluorescent molecules, respectively. Fluorescent molecules emit blue, cyan and yellow color with quantum yields in the 2.4–6.2 % range and average lifetime of ∼0.2 ns. The large Stokes’ shift for the molecule bearing a methylalcoxy (3248 cm−1) and diethyl amine (5017 cm−1) suggests a possible intramolecular charge transfer process as also corroborated by cyclic voltammetry, and explaining their low fluorescence quantum yield. The aryl-Schiff base substituted with the methylalcoxy (2b) was used as an electron donor material in photovoltaic devices in configuration: ITO/PEDOT:PSS/2b:PC61BM/Fields metal. The device built under atmospheric conditions displayed an intrinsic power conversion efficiency of PCE ∼0.4 %, with a Voc of 420 mV and Jsc 4.28 mA/cm2.

Ag nanoparticle promoted synthesis of 1,8-dioxo-decahydroacridines at room temperature

The three component condensation reaction of aldehydes with dimedone and ammonium acetate or anilines happened in the presence of Ag nanoparticles as a heterogeneous catalyst at room temperature in ethanol.Ag nanoparticles can suitably be handled and removed from the reaction mixture, generating the experimental process simple and green.The significant features of this method are suitable conversions, cleaner reaction profiles and short reaction time. The catalyst is recycled and reused for five successive times without loss of structure and significant activity.

Unexpected synthesis of 4-(4,5-dihydro-1H-imidazol-2-ylsulfanyl)butyl-H-sulfite as a catalyst for the synthesis of pyrazolophthalazines.

Several attempts for preparation of 4,4'-(2-thioxoimidazolidine-1,3-diyl)bis(butane-1-sulfonic acid) were not successful despite taking 2mmol of 1,4-butane sultone in reaction with 1mmol of imidazolidine-2-thione. Instead, 4-(4,5-dihydro-1H-imidazol-2-ylsulfanyl)butyl hydrogen sulfite (DISBHS) was prepared unexpectedly, characterized and used for the synthesis of diverse pyrazolophthalazines from the one-pot three component condensation reaction of phthalhydrazide, malononitrile and aldehydes under mild conditions.

An Efficient and Green Synthesis of Tetrahydrobenzo[b]Pyran Derivatives Using [(EMIM)Ac] at Room Temperature

AbstractAn efficient, expedient, clean and environmental being synthesis of tetrahydrobenzo[b]pyran's twenty derivatives (4 a–t) has been reported via one‐pot three component condensation reaction of various benzaldehydes, dimedone and malononitrile in presence of ionic liquid [(EMIM)Ac] as a catalyst at ambient temperature in ethanol. Advantages of these reaction follow the principle of green chemistry, which are operational simplicity, shorter reaction time, and mild reaction conditions with high yield (78–98 %) products.

Synthesis of substituted benzo[e][1,3]oxazino analogs

A synthesis of substituted benzo[e][1,3]oxazin-4-one analogs has been carried out by two methods. One of the common procedures involves refluxing in situ generated imine with salicylic acid while other method involves one-pot three component condensation reaction between aldehyde, amine and salicylic acid using DCC. The synthesized compounds have been characterized by IR, 1H and 13C NMR spectroscopy. Melting points reported are uncorrected.

P-TSA Catalyzed Synthesis of Tetrahydrobenzo[g]quinolines via Multicomponent Reaction using Pyrazole Aldehyde, Lawsone, β-Ketoesters and Ammonium Acetate

An efficient protocol has been developed for the multicomponent synthesis of tetrahydrobenzo[g]quinoline-3-carboxylate derivatives using p-toluenesulfonic acid (p-TSA) as catalyst through one-pot four component condensation reaction of pyrazole aldehyde, Lawsone, β-ketoesters and ammonium acetate in ethanol. The synthesized compounds were characterized by spectroscopic techniques.

Green Synthesis and Biological Study of Pyrimidone derivatives employing Cetyltrimethyl ammonium bromide under solvent free condition

In this study, we are reporting a solvent free Biginelli reaction using aromatic aldehydes, ethyl acetoacetate and urea in presence of cetyl tri-methyl ammonium bromide as a catalyst. The reaction is green and environmentally benign. The yield of three component condensation reaction is excellent. The products were screened for anti-bacterial and anti-fungal activity. The method is simple and convenient. The catalyst is novel and easily available, non-expensive and nontoxic.

Nickel Ferrite (NiFe₂O₄) Nanoparticles as Magnetically Recyclable Nanocatalyst for Highly Efficient Synthesis of 4H-Chromene Derivatives.

An adapted one-pot route to nanocatalyst-assisted synthesis of 4H-chromenes via three component condensation reaction between dimedone, malononitrile, and a broad range of aryl aldehydes by the use of magnetic nickel ferrite nanoparticles is described. By this achievement, not only a novel route to highly efficient synthesis of these series of heterocycles was introduced but also the scope of these medicinally important products was developed via preparation of some novel products. Above all, a new application of nickel ferrite nanoparticles (NiFe₂O₄ NPs) as highly efficient, green and magnetically recyclable catalyst has been introduced. Overall, obtaining good to excellent yields of products, environmentally and economic benign procedure, easy handling, availability of starting materials, use of non-toxic solvents, and high recyclability of nano-catalyst could be countered as most important advantages of this methodology.

Synthesis, characterization, and in vivo pharmacological evaluation of novel mannich bases derived from 1,2,4-triazole containing a naproxen moiety.

A new series of 1,2,4-triazole-5-thione Mannich derivatives containing a naproxen moiety (1a-o) was designed and synthesized to create naproxen analogs, with the aim of developing novel anti-inflammatory/analgesic agents with improved safety profiles. Target compounds were synthesized using classical Mannich reaction (i.e. one-pot three component condensation reaction), by reacting triazole molecule (1), formaldehyde, and diverse secondary amines in ethanol. The synthesized compounds were investigated using FT-IR, 1H NMR, 13C NMR and mass spectroscopies, as well as elemental analysis. Compounds were then evaluated for their potential antinociceptive and anti-inflammatory activities using some validated invivo methods. Data obtained from acetic acid induced-writhing and carrageenan-induced paw edema tests revealed that all compounds induced peripherally-mediated antinociceptive activities, as well as notable anti-inflammatory effects. The results of hot-plate and tail-clip tests indicated that compounds 1a, 1b, 1c, 1d, 1g, and 1j have also centrally-mediated antinociceptive activities in addition to their peripherally-mediated effects. Molecular docking studies were performed to investigate the putative binding modes of the interactions between all compounds and COX-1/COX-2 enzymes using AutoDock Vina software. Docking of the compounds into the COX-2 active site produced binding interactions that are essential for COX-2 inhibitory activity. None of the compounds in the serial, except for 1m and 1j, induced significant gastrointestinal irritation. Overall, the results indicated that triazol Mannich bases bearing a naproxen moiety potentially represent a novel class of antinociceptive and anti-inflammatory agent with an improved gastric safety profile.

In vitro anticancer activity of pyrano[3, 2-c]chromene derivatives with both cell cycle arrest and apoptosis induction

A series of 2-amino-4-aryl-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (4a–m) were synthesized via a one-pot three component condensation reaction between 4-hydroxy-2H-chromen-2-one, various aryl aldehydes and malononitrile in the presence of piperidine as a catalyst in ethanol under microwave irradiation conditions, with good to excellent yields. The structure elucidations of all the synthesized compounds were accomplished by spectral data, IR, 1H NMR, 13C NMR, MS, and elemental analyses. The targeted compounds were assessed for their in vitro anticancer activity against mammary gland breast cancer cell line (MCF-7), human colon cancer (HCT-116), and liver cancer (HepG-2) by using sulphorhodamine B assay (SRB) method, while doxorubicin, was utilized as standard reference drug. The cancer cells were treated with the synthesized compounds at differentiable dosages, and cell viability was determined. Compounds 4e, 4f, and 4m exhibited excellent antitumor activity versus all cancer cell lines with IC50 values ranging from 0.2 to 1.7 μM. The cell cycle arrest behavior of compounds 4e, 4f, and 4m was investigated. The results illustrated that the potent cytotoxic compounds 4e, 4f, and 4m induce cell cycle arrest at the G2/M phases and trigger apoptosis in the different tested cancer cells. Finally, the structure activity relationship (SAR) survey highlighted the antitumor activity of the new molecules that was remarkably influenced by the hydrophilicity of certain substituents at certain positions.

SYNTHESIS AND ANTIMICROBIAL EVALUATION OF 3,4-DIHYDROPYRIMIDIN- 2(1H)-ONE ANALOGS

This paper reports synthesis of functionalized 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) via a three component condensation reaction. The synthesized molecules were tested against bacterial strains Bacillus subtilis and Escherechia coli and against fungal strains Candida albicans and Aspergillus niger.Compounds 4d, 4h, 4l, 4p were found to exhibit very moderate antibacterial activity while compounds 4d, 4l showed very moderate antifungal activity as compared to standards ciprofloxacin and fluconazole.

SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF PYRIMIDO [4,5-d] [1,3,4] THIADIAZOLO[3,2-a]PYRIMIDINEDIONE

A simple, most efficient and green procedure has been developed for the synthesis of pyrimido [4,5-d] [1,3,4] thiadiazolo [3,2-a] pyrimidinedione derivatives from one-pot three component condensation reactions of barbituric acid, substituted aromatic aldehydes, and 2-amino 5-(4-chlorophenyl)-1,3,4-thiadiazole using 1-Butyl-3-methyl Imidazolium Chloride [BMIM]Cl as a green catalyst in ethanol-water. The newly synthesized compounds evaluated by their spectral techniques and screened for their Antimicrobial activity.

Sulfamic acid well dispersed in the micropores of Al-pillared α-ZrP as efficient heterogeneous catalyst for synthesis of structurally diverse 1,4-dihydropyridines under mild conditions

In this study, α-zirconium phosphate (α-ZrP) has been prepared via reflux method. The α-ZrP material was pillared with [Al13O4(OH)24(H2O)12]7+ polycations to improve its surface area and thermal stability. The aluminum oxyhydroxy clusters were synthesized by in situ partial base hydrolysis of the aluminum salt precursor using sodium hydroxide as base. The microporous inorganic matrix of Al-pillared α-ZrP (AZP) was used for molecular dispersion of sulfamic acid to prepare novel composite materials. The sulfamic acid modified AZP materials were characterized by using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Field emission scanning electron microscopy (FESEM), Transmission electron microscopy (TEM) and Brunauer–Emmett–Teller (BET) specific surface area analysis. XRD study indicated an expansion in the interlayer space as a result of bilayer intercalation of Al137+ pillaring species. The pillared interlayer space is retained in the composite material. FTIR study indicated the structural integrity of the sulfamic acid. The composite materials exhibited enhanced microporosity with surface area and pore volume in the range 80–120 m2/g and 0.1–0.2 cc/g. FESEM and HRTEM studies indicated morphological reorganization of α-ZrP particles as a result of pillaring and subsequent dispersion of sulfamic acid. Elemental mapping study suggested well dispersion of the sulfamic acid in the composite material without any sign of local agglomeration. The catalytic activity of sulfamic acid loaded AZP materials has been evaluated for the synthesis of 1,4-dihydropyridines by multi component condensation reaction of ethyl acetoacetate, arylaldehydes/chalones and ammonium acetate. The composite materials were highly active for synthesis of structurally diverse 1,4-dihydropyridines in high yield and purity under mild conditions.

Functionalized furo[3,2-c]coumarins as anti-proliferative, anti-lipolytic, and anti-inflammatory compounds: Synthesis and molecular docking studies

A simple and facile synthesis of a series of functionalized furo [3,2-c]coumarins 3a-j was successfully accomplished. A one-pot three component condensation reaction of substituted benzaldehydes with 2 equiv. of 4-hydroxycoumarin in DMSO solvent and in the presence of iodine at 80 °C lead to the preparation of the target compounds 3a-j. Moderate reaction conditions were used, the work-up method was smooth and simple and the desired target compounds were obtained in excellent yields. The in vitro antiproliferative activity of the novel synthesized target compounds was evaluated against five colorectal cancer cell lines; HT29, HCT116, SW620, SW480 and CACO2 using Sulforhodamine B (SRB) colorimetric assay. Murine RAW264.7 cells were used in anti-inflammatory and antiglycation in vitro bioassays. Compounds 3g and 3h showed outstanding antiproliferative activity in 3 out of 5 colorectal cancer cells. The non-selective cytotoxicity of the 3b compound in PDL fibroblasts was comparable to that of cisplatin. Moreover, the target compounds were also evaluated for antilipolytic activity alongside the pancreatic lipase (PL) inhibitor orlistat as a standard drug. Compounds 3f, 3h, and 3j displayed good PL inhibition. With appreciable safety profile, the remarkable anti-inflammatory activities of all tested furocoumarins were Incomparably exceeding indomethacin efficacy (IC50 value of 212 ± 8 μM) using Griess assay. Like aminoguanidine (IC50 value of 3.1 ± 0.35 μM); Furocoumarin compound 3g; among the rest, could impressively exert a moderate protection against methylglyoxal-induced carbonyl toxicity (IC50 value of 364.6 ± 32.8 μM). Molecular docking studies were performed on pancreatic lipase enzyme. The most potent inhibitor 3h showed a good fitting within the binding site of PL.

Synthesis and application of a novel nanomagnetic catalyst with Cl[DABCO-NO2]C(NO2)3 tags in the preparation of pyrazolo[3,4-b]pyridines via anomeric based oxidation

A novel nanomagnetic catalyst with Cl[DABCO-NO2]C(NO2)3 tags was designed, synthesized and fully characterized by several techniques such as Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, elemental mapping analysis, thermogravimetric analysis, derivative thermal gravimetric, powder X-ray diffraction patterns, field scanning electron microscopy, high resolution transmission electron microscopy, physical adsorption and desorption of N2 isotherms (BET) and vibrating sample magnetometer. The synthesized nanomagnetic particles were used as an efficient and recyclable catalyst for the one-pot three component condensation reaction of 3-methyl-1-phenyl-1H-pyrazol-5-amine or 3-methyl-1H-pyrazol-5-amine, aryl aldehydes and malononitrile for the synthesis of pyrazolo[3,4-b]-pyridine derivatives under neat conditions.

Fe3O4@SiO2@(C3H6)2-(Imidazolium)2-Butyl][MnCl42-] as a novel nanomagnetic catalyst for the one-pot synthesis of tetrahydrobenzo[b]pyran derivatives

In this article a convenient method for the synthesis of tetrahydrobenzo[b]pyran derivatives using imidazolium-based ionic liquid-stabilized on magnetic nanoparticles [Fe 3 O 4 @SiO 2 @(C 3 H 6 ) 2 -(Imidazolium) 2 -Butyl][MnCl 4 2- ] as a new heterogeneous catalyst has been described. These compounds were synthesized via one-pot three component condensation reaction between several aromatic aldehydes, malononitrile, and dimedone in water under reflux condition. The magnetic nanoparticle catalyst was fully characterized by Fourier transform infrared, scanning electron microscopy, energy dispersive X-ray spectroscopy, and vibrating sample magnetometer. Furthermore, the solid catalyst could be recovered and reused conveniently several times with satisfactory yields. KEY WORDS : Chromene derivatives, Magnetic nanoparticles, Dicationic ionic liquid, Reusability, One-pot synthesis Bull. Chem. Soc. Ethiop. 2018 , 32(2), 309-321. DOI: https://dx.doi.org/10.4314/bcse.v32i2.10

Synthesis of conjoined 1,5-dithiaspiro derivatives through catalyst free double reaction of carbon disulfide with dialkyl acetylenedicarboxylates and isocyanide derivatives

ABSTRACTSyntheses of symmetric 1,5-dithiaspiro derivatives through three component condensation reactions of isocyanides, dialkyl acetylendicarboxylates, and carbon disulfide at 70°C under neat conditions are reported.

Synthesis of 3-(Cyclohexylamino)-2-arylimidazo[1,2-a]pyridine-8- carboxylic Acids Via an Efficient Three-component Condensation Reaction between Cyclohexylisocyanide and 2-Aminopyridine-3-carboxylic Acid in the Presence of Aromatic Aldehyde.

The reaction of cyclohexylisocyanide and 2-aminopyridine-3- carboxylic acid in the presence of benzaldehyde derivatives in ethanol led to 3-(cyclohexylamino)-2- arylimidazo[1,2-a]pyridine-8-carboxylic acids in high yields. In a three component condensation reaction, isocyanide reacts with 2-aminopyridine-3-carboxylic acid and aromatic aldehydes without any prior activation. The synthesized products have stable structures which have been characterized by IR, 1H, 13C and Mass spectroscopy as well as CHN-O analysis. In continuation of our attempts to develop simple one-pot routes for the synthesis of 3- (cyclohexylamino)-2-arylimidazo[1,2-a]pyridine-8-carboxylic acids, aromatic aldehydes with divers substituted show a high performance. In conclusion, this study introduces the art of combinatorial chemistry using a simple one-pot procedure for the synthesis of new materials which are interesting compounds in medicinal and biological sciences.

Tandem Four Component Condensation Reaction of Aryl Aldehydes with Ethyl Acetoacetate, Malononitrile, and Hydrazine Hydrate using Boric Acid in Water as an Efficient and Green Catalytic System

ABSTRACTAqueous solution of boric acid, as an efficient and green catalytic system, was efficiently utilized tandem four-component condensation reaction of aryl aldehydes with ethyl acetoacetate, malononitrile, and hydrazine hydrate to give pyranopyrazole derivatives. By the reaction of boric acid with water, H+ was prepared and efficiently catalyzed the reaction under mild and green condition.

Synthesis of Aminofuran-Linked Benzimidazoles and Cyanopyrrole-Fused Benzimidazoles by Condition-Based Skeletal Divergence

A condition-based skeletal divergent synthesis was explored to achieve skeletal diversity in two component condensation reaction. Cyanomethyl benzimidazole was reacted with α-bromoketone under thermal conditions to furnish 2-aminofuranyl-benzimidazoles, while the same reaction afforded 3-cyano-benzopyrrolo-imidazoles under microwave irradiation. Two nonequivalent nucleophilic centers on benzimidazole moiety were manipulated elegantly by different reaction conditions to achieve the skeletal diversity.