Multicomponent Cyclocondensation Reaction Research Articles

Synthesis of Hetaryl Substituted Pyrazolo[3,4-b]Quinolinone Systems by Multicomponent Cyclocondensation Reaction

In this study, the synthesis of pyrazolo[3,4-b]quinolinone compounds was carried out via one-pot three-component reactions. These reactions proceed as domino processes, making them easier to occur than the conventional multistep organic reactions. By employing this method, new organic molecules can be synthesized in a single step, using minimal time and number of trials. In the first phase of this two-step study, heteroaromatic carbaldehydes (quinoline-8-carboxaldehyde and quinoline-4-carboxaldehyde) were prepared to be used as substrates in subsequent reactions by oxidation of 8-methylquinoline and 4-methylquinoline with selenium dioxide, a mild oxidant. In the second step, heteroaromatic carbaldehyde reacted with aminopyrazole and dimedone in anhydrous ethanol by one-pot multicomponent condensation method to synthesize six new compounds with heteryl-substituted pyrazolo[3,4-b]quinolinone ring system. The crude products were obtained in excellent yields and further purified by crystallization. The structures of the compounds, which were found to be completely pure as a result of chromatographic studies, were elucidated by spectroscopic methods and elemental analysis.

An effective and eco‐friendly sonochemical multicomponent synthesis of trisubstituted imidazoles via modified silica‐coated cobalt ferrite nanoparticles by tungstic acid

This research is providing a method for the synthesis of 2,4,5‐trisubstituted imidazole derivatives based on pursuing the green chemistry principles. Therefore, a one‐pot multicomponent cyclocondensation reaction through aldehyde interaction with ammonium acetate and 1,2‐diketone was carried out in EtOH:H2O solvent under ultrasound irradiation. This protocol was utilized as an eco‐effective synthetic route by applying CoFe2O4@SiO2@(‐CH2)3OWO3H nanocomposite as a nanocatalyst. The stabilized tungstic acid on 3‐chloropropyl anchored to SiO2‐coated CoFe2O4 magnetic nanoparticles was designed, prepared, and applied as a recyclable heterogeneous acid catalyst to attain high product yields and short reaction times. The structure of nanocatalyst was confirmed by using Fourier transform infrared spectroscopy (FT‐IR), X‐ray diffraction (XRD), field emission scanning electron microscopy (FE‐SEM), energy dispersive spectroscopy (EDS), vibrating sample magnetometer (VSM), thermogravimetric analysis (TGA), and Brunauer–Emmett–Teller (BET) techniques, and the obtained organic derivatives were examined through melting point, FT‐IR, and 1H NMR analyses.

Synthesis, Electrochemical Studies, Molecular Docking, and Biological Evaluation as an Antimicrobial Agent of 5-Amino-6-cyano-3-hydroxybenzo[c]coumarin Using Ni-Cu-Al-CO3 Hydrotalcite as a Catalyst.

New insights via a multicomponent cyclocondensation reaction of 2-hydroxy benzaldehyde acetoacetic ester and malononitrile were attained under efficient conditions. A detailed mechanistic study exhibits that the reaction via multicomponent, one-pot, two-step incooperating three-components’ reactants under nominal conditions efficiently synthesizes the intermediates in shorter than reported time along with the formation of a novel compound [5-amino-6-cyano-3-hydroxybenzo[c]coumarin] in the presence of Ni–Cu–Al–CO3 hydrotalcite as a heterogeneous catalyst. Hydrotalcite functions as an efficient and versatile catalyst as it is safe, easy to work up, and recyclable many times under ambient conditions, and the reaction time is shorter. The aforementioned conditions make these solid basic heterogeneous catalysts environmentally friendly. The product yield obtained was 89%. The product was characterized using FTIR, LCMS, and NMR. Electrochemical studies were also carried out to check the reduction and oxidation behavior. The synthesized product showed antimicrobial activity. Antimicrobial activity against human pathogens, viz, S. Aureus, P. Aeruginosa, and P. Bulgaria, was studied by using the agar well diffusion method. The molecular docking studies of 5-amino-6-cyano-3-hydroxybenzo[c]coumarin exhibit its suitable attachment at the active center of the type IIA topoisomerases and gyrase enzymes which suggest its potential antibacterial activity when compared using ciprofloxacin drug as the control.

Optimizing the Iodide/Iodonium/O2 Oxidation Cycle Enhances the Scope, Selectivity, and Yields of Hydroiodic Acid‐Catalyzed Multicomponent Cyclocondensation Reactions

AbstractCatalytic iodine in the presence of water acts indirectly as a source of Brønsted acid and, concurrently, generates iodonium ion and hydrogen peroxide, which mediate the final oxidative aromatization step in the multicomponent cyclocondensation of an aromatic amine and two aliphatic aldehyde compounds. The oxidative cycle in this and related iodine‐catalyzed reactions is seldom discussed, generally unoptimized, and rarely investigated in detail. This work establishes that two independent catalytic cycles (H+ and I−/I+) drive such multicomponent cyclocondensation/ oxidation reactions, provided that the oxidant is generated in sufficient concentration to inhibit oxidation of the dihydroquinoline by the intermediate iminium cation. The complementary dual catalytic cycles, when optimized, act in concert to suppress side product formation, which simplifies isolation and purification of the self‐aggregating products, and increases the efficiency and scope of the Wang‐Kozlov multicomponent reaction.magnified image

Synthesis, characterization, quantum chemical studies and electrochemical performance of new 4,7-dihydrotetrazolo[1,5-a]pyrimidine derivatives

In this study, 4,7- $$\hbox {dihydrotetrazolo}[1,5\hbox {-}a]\hbox {pyrimidine}$$ derivatives (1–5) were prepared via Multicomponent Cyclocondensation Reactions (MCRs). All structures were determined by using FT-IR, $$^{1}\hbox {H/}^{13}\hbox {C}$$ NMR and elemental analyses. The compounds were investigated as corrosion inhibitors using density functional theory (DFT) at the level of B3LYP/6-31G (d, p). According to the calculations, compound 1 appears to be a good inhibitor for corrosion. In addition, the electrochemical properties of the novel systems were investigated by CV. The synthesis, characterization, quantum chemical studies and electrochemical performance of new 4,7- $$\hbox {dihydrotetrazolo}[1,5\hbox {-}a]\hbox {pyrimidine}$$ derivatives are reported.

A Green Protocol for Simple One‐pot Synthesis of New Pyrimidine Derivatives Both Microwave Irradiation and Conventional Heating: Reactions, Characterization, and Theoretical Calculations

In this research, 5‐benzoyl‐6‐phenyl‐4‐(4‐trifluoromethylphenyl)‐2‐{oxo and thioxo}‐3,4‐dihydro‐1H‐pyrimidines (1, 2) were synthesized by using multicomponent cyclocondensation reaction under microwave irradiation and classical heating. Compounds 3, 4, 6, 7, and 8 obtained reactions of 5‐benzoyl‐6‐phenyl‐4‐(4‐trifluoromethylphenyl)‐2‐thioxo‐3,4‐dihydro‐1H‐pyrimidine (1) and acetic anhydride, diethyl 2‐bromomalonate, bromoacetic acid, 3‐bromopropionic acid, methyl iodide, respectively. Compound 4 was both acetylated and hydrolyzed in acetic acid to give compound 5. The structures of all compounds were determined by using spectroscopic techniques like FT‐IR, 1H/13C NMR, and elemental analyses, and the structures of compounds 1 and 3 were analyzed by X‐ray crystal analysis. In addition, the quantum chemical parameters and full geometry optimizations for all compounds were computed using density functional theory based on B3LYP and the 6‐31G (d, p) basis set.

Efficient catalyst-free tricomponent synthesis of new spiro[cyclohexane-1,4′-pyrazolo[3,4-e][1, 4]thiazepin]-7′(6′H)-ones

A series of spirocyclohexane-1,4′-pyrazolothiazepinones were synthesized by one-pot multicomponent cyclocondensation reactions between 5-amino-1-arylpyrazoles, cyclohexanone and mercaptoacetic acid with good yields and easy purification protocols. Some control experiments involving isolation of reaction intermediates were performed leading to the proposal of three alternative mechanistic pathways conducting to the named spiroheterocycles. All target molecules were fully characterized by IR, NMR, melting point and HRMS.

Synthesis, characterization, antioxidant properties and DFT calculation of some new pyrimidine derivatives

In this study, 5-benzoyl-4-(4-(methylthio)phenyl)-6-phenyl-1,2,3,4-tetrahydro-2-thioxo (1), oxo (2) and imino (3) pyrimidine derivatives were prepared via Multicomponent Cyclocondensation Reactions (MCRs). The compounds thiazolo[3,2-a]pyrimidin-3(5H)-one (4) and thiazin-4(6H)-one (5) were obtained via the reaction of compound 1 with bromoacetic acid and 3-bromopropionic acid, respectively. Structures were determined by using FT-IR, 1H/13C NMR and elemental analyses. Also the compounds 4 and 5 were analyzed by X-ray single crystal analysis. All compounds were investigated as corrosion inhibitors using density functional theory (DFT) at the level of B3LYP/6-31G (d, p). According to the calculations, the compound 3 appears to be a good inhibitor for corrosion. On the other hand, total antioxidant properties were measured in vitro by DPPH•, ABTS•+ test, hemolysis of phenylhydrazine erythrocytes and metal chelating effect. The results were compared with standard antioxidants such as trolox and α-tocopherol. These data revealed that compounds 1, 2 and 5 are more active with respect to 3 and 4 in scavenging the radicals.

Polybenzimidazole-Triphenylphosphene-Catalyzed One-Pot Synthesis and Evaluation of Dihydropyridine Derivative as Antibiotics and Antifungals

Dihydropyridines derivative have been synthesized by one-pot multicomponent cyclocondensation reaction using PBI-PPh3 catalyst. This catalyst is characterized by the solid state of 13C-NMR, 15N-NMR, and 31P-NMR spectrum, FT-IR, cyclic voltammetry, and XRD analysis. The selection of catalyst is quite interesting because of its affordability, toxic free nature and high stability. Functional groups of all dihydropyridines confirms by H1-NMR and FTIR spectra. Synthesized compounds show exceptional yields of 96–99 %. Synthesized compounds has evaluated for their invitro antibacterial activity against B. subtilis, and P. vulgaris (ATCC 49565) and C. albicans (ATCC 90028). Synthesized dihydropyridines showed promising antibacterial and antifungal activities, in particularly, ethyl-4-(4-methylphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexadihydropyridine-3-carboxylate are exhibiting a higher inhibition zone of 66.7 % against bacteria. Our method may help to drug chemists for design more interesting, useful, and sustainable reactions in the near future.

Synthesis, characterization, in silico molecular docking study and biological evaluation of a 5-(phenylthio) pyrazole based polyhydroquinoline core moiety

A combinatorial library of polyhydroquinoline scaffolds is successfully attempted by multicomponent cyclocondensation reaction.

Synthesis of silyl-protected terminal thioalkyne-substituted tetraaryl imidazoles: utilization of Ag–Fe/ZSM-5 bimetallic nanooxides for cyclocondensation of polysubstituted imidazoles

An improved one-pot and ecofriendly approach to tri- and tetraaryl imidazoles through three- and four-component coupling reactions under neutral and solvent-less solid-phase conditions is presented. A series of nanosized Ag/metal oxide species on H–ZSM-5 support were tested in this procedure, with Ag–Fe/ZSM-5 bimetallic oxide nanoparticles exhibiting excellent catalytic activity for improved efficiency of the one-pot, multicomponent cyclocondensation reaction. The obtained bromoimidazole derivatives were converted into silyl-protected terminal alkynyl thiolate-substituted tetraaryl imidazoles by treatment with lithium 2,2,2-tris(trimethylsilyl)ethanedithioate, produced by reaction of organolithium reagent (Me3Si)3CLi with CS2 at 0 °C. These novel and stable synthetic intermediates are potential compounds for functionalization of imidazoles.

Steroid-Derived Naphthoquinoline Asphaltene Model Compounds: Hydriodic Acid Is the Active Catalyst in I2-Promoted Multicomponent Cyclocondensation Reactions

A multicomponent cyclocondensation reaction between 2-aminoanthracene, aromatic aldehydes, and 5-α-cholestan-3-one has been used to synthesize model asphaltene compounds. The active catalyst for this reaction has been identified as hydriodic acid, which is formed in situ from the reaction of iodine with water, while iodine is not a catalyst under anhydrous conditions. The products, which contain a tetrahydro[4]helicene moiety, are optically active, and the stereochemical characteristics have been examined by VT-NMR and VT-CD spectroscopies, as well as X-ray crystallography.

Synthesis and characterization of hybrid chloroquinoline–xanthene derivatives

AbstractA novel series of chloroquinoline-xanthene hybrids were prepared by one-pot multicomponent cyclo-condensation reaction of 2,7-dihydroxynaphthalene, aromatic aldehydes, and cyclic 1,3-dicarbonyl compounds followed by condensation reaction with 4,7-dichloroquinoline. The synthesized compounds were characterized by various spectroscopic techniques and single crystal X-ray analysis.

Synthesis of 2-amino-4H-1,3-oxazines and 2-amino-4H-1,3-thiazines through a Yb(OTf)3-assisted, acid-catalyzed one-pot cyclocondensation reaction

An efficient synthesis of 2-amino-4,6-diaryl-4 H -1,3-oxazine and 2-amino-4,6-diaryl-4 H -1,3-thiazine derivatives has been demonstrated through a one-pot multicomponent cyclocondensation reaction. Ytterbium triflate and concentrated HCl has been utilized as the catalyst system for this reaction. The method produced good to excellent product yields and allowed a wide variation of the substituents in both aryl moieties. How to Cite Putatunda, S.; Chakraborty, A. Chem. Heterocycl. Compd. 201 5 , 51 , 763. [ Khim. Geterotsikl. Soedin. 2015 , 51 , 763.] For this article in the English edition see DOI 10.1007/s10593-015-1770-x

Using magnetic nanoparticles Fe3O4 as a reusable catalyst for the synthesis of pyran and pyridine derivatives via one-pot multicomponent reaction

An atom-economical, efficient and mild protocol is described for the synthesis of 2-amino-3-cyanopyridine and 2-amino-3-cyano-4H-pyran derivatives in the presence of high surface area Fe3O4 as a highly effective heterogeneous catalyst via one-pot multicomponent cyclo-condensation reaction.

Synthesis and biological evaluation of some novel pyrazole, isoxazole, benzoxazepine, benzothiazepine and benzodiazepine derivatives bearing an aryl sulfonate moiety as antimicrobial and anti-inflammatory agents

A new series of pyrazole, isoxazole, benzoxazepine, benzothiazepine and benzodiazepine derivatives were prepared by the multi-component cyclo-condensation reaction of 1-phenyl-3-(2-(tosyloxy)phenyl)propane-1,3-dione, N,N-dimethylformamide dimethyl acetal and hydrazine or hydroxylamine hydrochloride or 2-aminothiophenol or 2-aminophenol or benzene-1,2-diamine using μwave technique in aqueous media. All the synthesized compounds were evaluated for their anti-bacterial and antifungal activities. Some of the selected compounds were also screened for their anti-inflammatory activity.

ChemInform Abstract: Potassium Phthalimide: An Efficient and Green Organocatalyst for the Synthesis of 4‐Aryl‐7‐(arylmethylene)‐3,4,6,7‐tetrahydro‐1H‐cyclopenta [d]pyrimidin‐2(5H)‐ones/thiones under Solvent‐Free Conditions.

Abstract An efficient synthesis of Biginelli-type compounds using potassium phthalimide as a green, mild, and commercially available organocatalyst in a one-pot, multi-component cyclocondensation reaction of cyclopentanone, aldehydes, and urea/thiourea is reported. The present methodology is a green approach to access 4-aryl-7-(arylmethylene)-3,4,6,7-tetrahydro-1 H -cyclopenta[ d ]pyrimidin-2(5 H )-ones/thiones. It offers several merits such as simple operational procedures, no use of hazardous organic solvents, and cheap and environmentally friendly solid basic catalyst.

Potassium phthalimide: An efficient and green organocatalyst for the synthesis of 4-aryl-7-(arylmethylene)-3,4,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-2(5H)-ones/thiones under solvent-free conditions

Abstract An efficient synthesis of Biginelli-type compounds using potassium phthalimide as a green, mild, and commercially available organocatalyst in a one-pot, multi-component cyclocondensation reaction of cyclopentanone, aldehydes, and urea/thiourea is reported. The present methodology is a green approach to access 4-aryl-7-(arylmethylene)-3,4,6,7-tetrahydro-1 H -cyclopenta[ d ]pyrimidin-2(5 H )-ones/thiones. It offers several merits such as simple operational procedures, no use of hazardous organic solvents, and cheap and environmentally friendly solid basic catalyst.

Microwave-assisted synthesis of pyrido[1,2-a]benzimidazole derivatives of β-aryloxyquinoline and their antimicrobial and antituberculosis activities

A new series containing pyrido[1,2-a]benzimidazole derivatives of β-aryloxyquinoline has been synthesized via base catalyzed microwave-assisted multi-component cyclocondensation reaction. This methodology allowed us to achieve the desired products in good yields in very short time with the use of 10 mol% NaOH as a non-hazardous organic base. The chemical structures of compounds 6a–x were elucidated by 1H NMR, 13C NMR, FT-IR, elemental analysis, and mass spectral data. The titled derivatives were tested against a panel of pathogenic strains of bacteria and fungi for antimicrobial activity and against Mycobacterium tuberculosis H37Rv for their antitubercular activity. The structural activity relationship study revealed that antimicrobial and antitubercular potency of the title compounds depends not only on the bicyclic heteroaromatic pharmacophore appended through ether linked aryl ring but also on the nature of the peripheral substituents and may also upon their spatial relationship and positional changes.

ChemInform Abstract: Silica Gel‐Mediated Microwave‐Assisted Efficient Synthesis of Highly Substituted Imidazoles and Exploration of Naked Eye/Colorimetric Sensor for Anions.

AbstractAn improved and very rapid one‐pot synthesis of tri‐ and tetrasubstituted imidazoles via multicomponent cyclocondensation reactions is developed.