Reaction Of 4-hydroxycoumarin Research Articles

L-proline H2SO4 catalyzed synthesis of novel coumarin-based spiroindolino-3,4-dihydropyrimidin-2(1H)-ones: in vitro cytotoxic assay and molecular docking study.

Development of environmentally benign catalyst systems, especially those derived from readily available nature's pool, in multicomponent synthesis, consolidates multiple facets of green chemistry. Here, an L-proline derived green acid catalyst in the form of L-proline⋅H2SO4 was developed and employed for multicomponent synthesis of coumarin-based spiroindolino-3,4-dihydropyrimidin-2(1H)-ones from the reaction of 4-hydroxycoumarin, isatin and urea/thiourea. Preliminary cytotoxicity studies showed that a couple of compounds (M5 and M6) have good cytotoxicity (40-50%) against in Dalton's Lymphoma (DL) cells while demonstrating minimal cytotoxicity (10-12%) for normal non-cancerous cell lines. Molecular docking simulations for the least and most cytotoxic compounds, M3 and M6 respectively, against nineteen tumor target proteins were carried out, and seven of them were identified to test against all the sixteen compounds. Based on the estimated docking score and inhibition constants (Ki), the interaction of the compounds with the tumor target protein, beta-hexosaminidase B (PDB ID: 1NOW) matched closely with in vitro cytotoxicity data.

A novel magnetic FSM-16 supported ionic liquid/Pd complex as a high performance and recyclable catalyst for the synthesis of pyrano[3,2-c]chromenes.

In this work, Fe3O4@FSM-16/IL-Pd was successfully designed and synthesized via a new procedure of palladium(ii) complex immobilization onto magnetic FSM-16 using an ionic liquid, as a novel heterogeneous nanocatalyst. Multiple techniques were employed to characterize this magnetic nanocatalyst such as Fourier transform infrared spectroscopy (FT-IR), Brunauer-Emmett-Teller (BET), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), Field Emission Scanning Electron Microscopy (FE-SEM), thermogravimetric analysis (TGA), Transmission electron microscopy (TEM), and Vibrating Sample Magnetometry (VSM). After complete characterization of the catalyst, its catalytic activity was used for the synthesis of pyrano[3,2-c]chromene-3-carbonitriles via the reaction of 4-hydroxycoumarin, aldehyde, and malononitrile under solvent-free conditions. Also, it can be recovered and reused several times without a significant decrease in its catalytic activity or palladium leaching.

A facile and practical p-toluenesulfonic acid catalyzed route to dicoumarols and their biological evaluation

ABSTRACT New Dicoumarols 2a-g efficiently synthesized employing p-TSA as a catalyst from the reaction of 4-hydroxycoumarin with aryl aldehydes in water. This method offers direct access to structurally diverse Dicoumarols derivatives in a good yields (65-94%). Upon heating 3,3' -arylidenebis-4-hydroxycoumarins derivative in acetic anhydride, the epoxydicoumarins were formed. 1H, 13C{1H}-NMR, elemental analysis, and infrared spectroscopic techniques were used for the characterization of the obtained compounds. A possible relationship between such hydrogen-bonded structures and the antimicrobial and the antioxidant activities of compounds is suggested. The synthetized compounds 2a-g and 3a-g were subjected to in vitro antimicrobial and antifungal activities against DNA gyrase and Mycobacterium tuberculosis-CYP51 target proteins at the active sites. Compound 3d shows effective inhibitory effect in terms of MIC = 15 µg mL-1. against Salmonella typhimuriumATCC 14028. Compounds 2b, 2c, 3b, 3c, 3e and 3g have recorded an important scavenging activity against the radical DPPH. The EC50 of these compounds was 47.17, 46.90, 50.55,48.27 , 46.55 and 47.54 µg mL-1 respectively. Investigation of the anti-inflammatory activity of the synthesized compounds showed that compounds 2b,2c, 3f, 3b and 3c are the most potent inflammatory activities.

An efficient one pot synthesis of (2-hydroxyphenyl)-5-phenyl-6-(pyrrolidine-1-carbonyl)-1H-pyrano[2,3-d]pyrimidine-2,4(3H,5H)-dione derivatives as a potent biological agents

In this paper, we reported the synthesis of a novel series of (2-hydroxyphenyl)-5-phenyl-6-(pyrrolidine-1-carbonyl)-1H-pyrano[2,3-d]pyrimidine-2,4(3H,5H)-dione derivatives 5(a–j) by the reaction of 4-hydroxy coumarin, substituted aldehydes, barbituric acid, and pyrolidine in ethanol at ambient temperature. The titled pyranopyrimidines 5(a–j) were characterized by spectral analysis including IR, NMR (1H & 13C), and HRMS. The newly synthesized compounds were examined for in vitro anti-inflammatory activity. The results demonstrated that compound 5b displayed excellent efficacy and the remaining compounds exhibited moderate activity. Also, the potency of the new compounds toward antimicrobial and antifungal activity was investigated by a disk diffusion method. The results show that compounds 5b and 5g were more potent than the other compounds. Furthermore, the molecular docking studies were carried out using a COX-2 receptor.

Rapid and Green One-Pot Synthesis of Novel 2-(4-Hydroxy-2-oxo-2Hchromen- 3-yl)-2-(arylamino)-1H-indene-1,3(2H)-diones

Abstract:A green and efficient protocol was developed for the one-pot three-component synthesis of novel 2-(4-hydroxy-2-oxo-2H-chromen-3-yl)-2-(arylamino)-1H-indene-1,3(2H)-dione derivatives by the reaction of 4-hydroxycoumarin, ninhydrin and aromatic amines in the presence of guanidine hydrochloride as an organocatalyst under solvent-free conditions. The present approach offers several advantages such as low cost, simple work-up, short reaction times, chromatography-free purification, high yields and greener conditions.

Reactions of 4-hydroxycoumarin with heterocyclic aldehydes

Reactions of 4-hydroxycoumarin 1 with heterocyclic aldehydes 2-4 led to bis-4-hydroxycoumarin derivatives 5-7 under microwave irradiation as well as under the classical heating. The subsequent reactions of products 5-7 are described. 4,4’-Epoxydicoumarins 8, 9 were prepared by the reaction of 5-7 in acetic acid / p-toluenesulfonic acid medium. Compound 10 was prepared by the reaction of 5 in acetic anhydride in the presence sodium acetate. Dioxocine-1,15-dione 11 was prepared by the reaction of 6 with dichloromethane in sodium hydroxide-toluene.

Synthesis, characterization and application of N,N,N',N'-tetramethylethylenediaminium-N-(silica-n-propyl)-N'-sulfonic acid chloride trifluoroacetate as a novel and effective catalyst for preparation of bis-coumarins

In this research, a novel material namely N,N,N',N'-tetramethylethylenediaminium-N-(silica-n-propyl)-N'-sulfonic acid chloride trifluoroacetate ([TEDSPSCT]) was synthesized, and its structure was characterized using Fourier-transform infrared spectroscopy (FT-IR), energy-dispersive X-ray (EDS), field emission scanning electron microscopy (FE-SEM), thermal gravimetric (TG), differential thermal gravimetric (DTG) and x-ray diffraction (XRD); most of the partcles were in nano-size, and a few of them were in micro-size. Afterward, [TEDSPSCT] was used as effective and recyclable catalyst for the preparation of bis-coumarins via the reaction of 4-hydroxycoumarin (2 equivalents) with arylaldehydes (1 equivalent) under solvent-free conditions; these compounds were obtained in high yields and short reaction times. Moreover, an attractive and logical mechanism based on dual-functionality of the catalyst has been described {this catalyst has both acidic group (SO3H) and weak basic group (trifluoroacetate)}.

Selectivity control in the reaction between 2-hydroxyarylaldehydes and 4-hydroxycoumarin. Antioxidant activities and computational studies of the formed products

A series of 6H,7H-7-(4-Hydroxy-3-coumarinyl)[1]benzopyrano[4,3-b][1]benzopyran-6-ones 4a-g and 3-(2-hydroxybenzoyl)-2H-chromen-2-ones 5a-g derivatives were synthesized by reaction of 4-hydroxycoumarin with 2-hydroxyarylaldehydes 2a-f or 2-hydroxynaphtaldehyde 2g using different solvents and acid/base catalysts. The approach relies on a regioselective cascade reaction involving one/two molar equiv of the 4-hydroxy coumarin iteratively acting as active methylene substrate in a Knoevenagel condensation and in a Michael addition. The structures of all compounds were established by IR, mass spectrometry, 1H-NMR and 13C-NMR. Antioxidant activity of the synthesized compounds were determined using the DPPH scavenging assay, best results being obtained with 5b (IC50 = 236 µg/mL). Computational studies showed that the compounds bind in the ATP-binding site of p38 MAPK, in a same manner than known polyaromatic potent inhibitors. The synthesized compounds might be considered further for cancer therapy.

Another look at reactions of 4-hydroxycoumarin with hydroxyl radical in the environment: deprotonation and diffusion effects

Quantum chemistry calculations suggest that chemical fate of the anticoagulant rodenticide 4-hydroxycoumarin in the environment is crucially dependent on deprotonation in aqueous medium.

A one-pot four-component synthesis of 3-[(2-amino-4-arylthiazolium-5-yl)(aryl)methyl]-2-oxo-2H-1-benzopyran-4-olates

ABSTRACT An efficient method has been developed for the synthesis of 3-[(2-amino-4-arylthiazolium-5-yl)(aryl)methyl]-2-oxo-2H-1-benzopyran-4-olates via a tandem reaction involving 4-hydroxycoumarin, benzaldehydes, thiourea, and 2-bromo-1-arylethan-1-ones, using p-toluenesulfonic acid as catalyst in glacial acetic acid under reflux. The identity of the parent product was confirmed by X-ray analyses while the other similar derivatives were identified by NMR. The good yields of the products, regioselectivity, and lack of metal promoters are the main advantages of this protocol. Highlights The reaction of 4-hydroxycoumarin, thiourea, benzaldehydes, and 2-bromo-1-arylethan-1-ones leads to the formation of functionalized 3-[(2-amino-4-arylthiazolium-5-yl)(aryl)methyl]-2-oxo-2H-1-benzopyran-4-olates in good yields.

ZIF@ZnTiO3 Nanocomposite as a Reusable Organocatalyst for the Synthesis of 3, 4-dihydropyrano[c]chromene Derivatives

Background: Dihydropyrano [3, 2-c]chromenes and their derivatives have great attention for scientists. They have different activities such as biological properties, spasmolytic, diuretic, anticoagulant, anti-cancer, and anti-anaphylactic activity. For these vary biological activities, chromene derivatives have made significant for further progress in medicinal and organic synthesis studies. So, in view of the importance of chromenes, we aimed to synthesis of 3, 4-dihydropyrano [3, 2-c] chromene derivatives. ZIF@ZnTiO3nanocomposite as organocatalyst was used. Method: An effective and applicable technique was used for preparation of 3, 4-dihydropyrano [3, 2- c] chromene derivatives. Dihydropyrano [c] chromenederivatives were prepared by using ZIF@ZnTiO3compositeas a recyclable catalyst. One-pot three-component reaction of aromatic aldehydes, malononitrile, and 4-hydroxycoumarin was done for synthesis of dihydropyrano [c] chromenederivatives over composite catalyst with excellent yields. The as prepared dihydropyrano [c] chromenederivatives were measured by melting point, FTIR, 1H NMR, and 13C NMR. The nano catalyst could be recycled several times. Result: A novel nano catalyst of MOF containing Mn2+ ions and 2- methyl imidazole (ZIF) and zinctitanate (ZIF@ZnTiO3) composite was prepared. The synthesized organocatalyst was studied for preparation of 3, 4-dihydropyrano [3, 2-c] chromene derivatives. One-pot three-component reaction of aromatic aldehydes, malononitrile, and 4-hydroxycoumarin was done for synthesis of dihydropyrano [c] chromene derivatives over composite catalyst with excellent yields. The reaction was optimized. Conclusion: The organocatalyst composite of consist of ZIF and zinctitanate was prepared. The ZIF@ZnTiO3 was used as catalyst for synthesis of 3, 4-dihydropyrano [3, 2-c] chromene derivatives via one-pot three-component condensations of aromatic aldehydes,malononitrile, and 4 hydroxycoumarin. The results of melting point, FTIR, 1H NMR, 13C NMR also confirmed the formation of high yield of 3, 4-dihydropyrano [3, 2-c] chromene derivatives at short time. The appealing properties of this method are environmentally friendly, mild reaction conditions (low reaction time and high yields of pure products), easy work up and recyclability of reaction catalyst.

Visible Light Assisted Hantzsch Reaction: Synthesis of Polycyclic Dihydropyridines

The polycyclic dihydropyridine nucleus represents the heterocyclic system of invaluable core motifs with wide applications in chemical, biological and physical properties. Although this kind of compounds have been extensively synthesized by other groups, the synthesis of these compounds under CFL light intensity were not explored. The synthesis of polycyclic dihydropyridine derivatives were achieved through the reaction of 4-hydroxycoumarin, aromatic aldehydes and ammonium acetate under CFL light irradiation conditions. A series of polycyclic dihydropyridine derivatives were prepared under CFL light irradiation conditions with high yield, short reaction time, ambient condition and without the use of catalyst. The results displayed an efficient method for the synthesis of polycyclic dihydropyridine derivatives. Clean profile, short reaction time, low cost and use of CFL light intensity instead of catalyst making it a genuinely green protocol.

Efficient atom-economic one-pot multicomponent synthesis of benzylpyrazolyl coumarins and novel pyrano[2,3-c]pyrazoles catalysed by 2-aminoethanesulfonic acid (taurine) as a bio-organic catalyst

The present work describes eco-friendly multicomponent protocol for the synthesis in excellent yields of structurally diverse benzylpyrazolyl coumarin 5 (a–s) involving the reaction of 4-hydroxycoumarin, ethyl acetoacetate, hydrazine hydrate/phenyl hydrazine hydrate and aldehydes, also novel pyrano[2,3-c]pyrazole derivatives 8 (a–k) integrated by isonicotinic acid hydrazide from reaction of aldehyde, ethyl acetoacetate, malononitrile with isoniazid, employing water as a reaction medium and 2-aminoethanesulfonic acid (taurine) as the catalyst. This new methodology endowed the advantages such as short reaction time, recovery of catalysts after catalytic reaction and reusing them without losing their activity and alleviate of operation.

A greener and microwave-mediated synthesis and spectral studies of β-aminomethylhydroxylcoumarins

ABSTRACT A series of warfarin analogs, β-aminomethylhydroxylcoumarins, was obtained in good yields from the Mannich reaction of 4-hydroxycoumarin, aromatic aldehydes and secondary amines in water under microwave irradiation at 100 °C. The salient features of the synthesis are: catalyst-free protocol, green solvent (water), complete avoidance of organic solvents in the synthesis, facile workup and high yields.

Metal-Free Construction of Fused Pyrimidines via Consecutive C-C and C-N Bond Formation in Water.

A facile and efficient protocol has been developed for mild construction of fused pyrimidines via l-proline-catalyzed reaction of 4-hydroxy coumarins, aldehydes, and 2-aminobenzothiazoles/urea. The reaction has been carried out rapidly and efficiently in water under mild and metal-free conditions. Current etiquette has efficiently synthesized the heterocycles and avoids the use of hazardous solvents over conventional organic solvents. A plausible reaction mechanism has been established in this study. This study represents the first case in which l-proline as a homogeneous catalyst has been explored in the synthesis of fused pyrimidines in water in view of simple procedure and acceptable efficiency. This method gives the target product in excellent yield with ease of workup.

Synthesis of furo[3,2-c]coumarins via I2/TBHP-mediated reaction of 4-hydroxycoumarins with terminal alkynes

An efficient I2/TBHP-mediated process for the formation of furo[3,2-c]coumarins from readily available materials has been developed. This process for the formation of furo[3,2-c]coumarins is quite environmental friendly and atom-economical.

Multicomponent synthesis of pyrano[2,3-c]coumarins.

A base-catalyzed, pseudo-four-component reaction of 4-hydroxycoumarin, two molecules of acetone, and amine towards the synthesis of pyrano[2,3-c]coumarins is reported. The mechanism of this multicomponent reaction is proposed. The reaction is further extended to the preparation of coumarin-substituted pyrano[2,3-c]coumarins by a base-catalyzed, pseudo four-component reaction of two molecules of 4-hydroxycoumarin and two molecules of acetone.

SBA-15-SO3H-assisted preparation of 4-aza-phenanthrene-3,10-dione derivatives via a one-pot, four-component reaction

A novel four-component approach for the synthesis of 1-phenyl-1,4-dihydro-2H-9-oxa-4-aza-phenanthrene-3,10-dione derivatives has been presented via the reaction of 4-hydroxycoumarin, ammonia solution, Meldrum’s acid and aromatic aldehydes. The products were characterized by FT-IR, 1HNMR, 13CNMR, CHN elemental analysis and mass spectroscopy. According to the obtained results, SBA-15-SO3H is considered as an efficient catalyst for the preparation of novel 4-aza-phenanthrene-3,10-dione derivatives.

An efficient approach to the synthesis of coumarin-fused dihydropyridinones

Abstract 3,4-Dihydro-2H-chromeno[4,3-b]pyridine-2,5(1H)-dione derivatives were efficiently prepared by the reaction of 4-hydroxycoumarin, ammonia, aromatic aldehyde and Meldrum’s acid in refluxing 1-propanol.

Reaction of 4-Hydroxycoumarin with Salicylaldehyde: Products Formed Under Various Conditions and their Antiproliferative Activity

Reaction of 4-Hydroxycoumarin with Salicylaldehyde: Products Formed Under Various Conditions and their Antiproliferative Activity