Pechmann Condensation Research Articles

A study on the acidity of sulfated CuO layers grown by surface reconstruction of Cu2O with specific exposed facets

Surface reconstruction and sulfation improve the acidity of Cu2O, and moderate Lewis acid sites are the active sites in Pechmann condensation.

Synthesis, computational studies and assessment of in vitro inhibitory activity of umbelliferon-based compounds against tumour-associated carbonic anhydrase isoforms IX and XII

Coumarins are widely diffused secondary metabolites possessing a plethora of biological activities. It has been established that coumarins represent a peculiar class of human carbonic anhydrase (hCA) inhibitors having a distinct mechanism of action involving a non-classical binding with amino acid residues paving the entrance of hCA catalytic site. Herein, we report the synthesis of a small series of new coumarin derivatives 7-11, 15, 17 prepared via classical Pechmann condensation starting from resorcinol derivatives and suitable β-ketoesters. The evaluation of inhibitory activity revealed that these compounds possessed nanomolar affinity and high selectivity towards tumour-associated hCA IX and XII over cytosolic hCA I and hCA II isoforms. To investigate the binding mode of these new coumarin-inspired inhibitors, the most active compounds 10 and 17 were docked within hCA XII catalytic cleft.

Synthesis of 2-substituted benzimidazole, coumarin, benzo[b][1,4]oxazin and dihydropyrimidinone derivatives using core-shell structured Fe3O4@SiO2-ZnCl2 nanoparticles as an effective catalyst

In this paper, a magnetic nanocatalyst of Fe3O4@SiO2-ZnCl2 has been used which enhances the synthesis of benzimidazoles, coumarins, benzoxazines and dihydropyrimidinones. To begin with, 2-substituted benzimidazoles have been synthesized in proper to high yields from 1,2-phenylenediamine with extensive diversity of aromatic aldehydes in the presence of magnetic nanocatalyst. Then, this magnetic nanocatalyst has been used for the synthesis of coumarin derivatives via Pechmann condensation reaction of phenols with ethyl acetoacetate in good yield under solvent-free conditions. Next, the synthesis of benzo[b][1,4]oxazines has been accomplished efficiently by the multi-component condensation of 2-aminophenol, aromatic aldehyde and isocyanide using magnetic nanocatalyst. Lastly, dihydropyrimidinones were synthesized by a one-pot three-component cyclocondensation using β-keto ester, substituted aromatic aldehyde and urea. The benefits of this method are facile, easy work-up, catalyst reusability and leading to good yields. Theoretical assessments allow us to corroborate the reactions mechanism.

Kinetics and mechanism of Pechmann condensation reaction over sulphated zirconia-supported zinc oxide

An investigation of the kinetics of the Pechmann condensation reaction over ZnO supported on sulphated zirconia (ZnO/SZ) catalyst has been performed. The ZnO/SZ catalyst contains both Lewis (L) and Brønsted (B) acid sites. The maximum B/L ratio was obtained with a ZnO content of 6%. The reaction is first-order half in both acetoacetate and resorcinol, which supports the proposed reaction mechanism. The reaction temperature was found to have a great effect on the kinetics of coumarin synthesis, and the activation energy was determined to be 42.29 kJ mol−1. The experimental activation parameters for the reaction were calculated to be ΔH≠ = 39.20 kJ mol−1, ΔS≠ = −152.62 J mol−1 K−1 and ΔG≠ = 99.18 kJ mol−1 at 393 K. The negative value of the activation entropy (ΔS≠) indicates that the entropy decreases upon forming the transition state, which proves that the transition state is more highly ordered than the reactants.

MnSb2O6‐chitosan nanocomposite: An efficient catalyst for the synthesis of coumarins via Pechmann reaction

AbstractIn this work, MnSb2O6‐chitosan nanocomposites were synthesized and have been employed in Pechmann condensation for the synthesis of coumarin derivatives. MnSb2O6‐chitosan nanocomposites were characterized by Fourier transform infrared (FTIR), X‐ray powder diffraction (XRD), scanning electron microscope (SEM), and energy‐dispersive X‐ray spectroscopy (EDX) techniques. The particles of MnSb2O6‐chitosan have uniform spheres with sizes that are less than 100 nm. Simplicity, easy work‐up, and short reaction times are advantages of this reaction. Also, we evaluated the antibacterial activity for some of the products, and the result showed significant pharmaceutical activities as antibacterial reagents against Staphylococcus aureus and Escherichia coli.

The Effects of Exposed Specific Facets and Sulfation on the Surface Acidity of Cu2 O Solids.

Cuprous oxide microcrystals with {111}, {111}/{100}, and {100} exposed facets were synthesized. 31 P MAS NMR using trimethylphosphine as the probe molecule was employed to study the acidic properties of samples. It was found that the total acidic density of samples increases evidently after sulfation compared with the pristine cuprous oxide microcrystals. During sulfation, new {100} facets are formed at the expense of {111} facets and lead to the generation of two Lewis acid sites due to the different binding states of SO4 2- on {111} and {100} facets. Moreover, DFT calculation was used to illustrate the binding models of SO4 2- on {111} and {100} facets. Also, a Pechmann condensation reaction was applied to study the acidic catalytic activity of these samples. It was found that the sulfated {111} facet has better activity due to its higher Lewis acid density compared with the sulfated {100} facet.

Zeolites in Pechmann condensation: Impact of the framework topology and type of acid sites

Abstract In this contribution, zeolites with different pore sizes and connectivity (MFI 10-10-10R, MTW 12R, Beta 12-12-12R) were prepared in bulk and hierarchical “nanosponge” form and with different composition (aluminosilicate, gallosilicate). Properties of the samples were characterized by X-ray diffraction, argon adsorption, transmission electron microscopy and adsorption of pyridine followed by FTIR spectroscopy. Catalytic performance (conversion of reactants, yields of products and turn-over frequencies) of prepared materials was investigated in the Pechmann condensation of resorcinol with ethyl acetoacetate. The lowest conversion (less than 15%) over the MFI samples suggests that its 10R channels are too narrow for the products to escape from the framework and thus the reaction proceeds mainly on the crystal surface. Conversion of reactants over MTW and Beta zeolites is higher (10%, 35%, 71% and 69% for bulk MTW, nanosponge MTW, bulk Beta and nanosponge Beta, respectively), however, undesired side-products are formed. The hierarchical form of MFI and MTW gives higher conversions and yields of products than their bulk counterparts. Interestingly, the difference between bulk and hierarchical Beta is negligible. The overall performance of aluminosilicates and gallosilicates in the reaction is comparable. Catalytic activity of the samples was determined mainly by their textural properties.

Microwave-Assisted Solvent-Free Rapid Synthesis of 4-Methyl Coumarin Derivatives by Using Silica functionalized-SO3H as an Effective Heterogeneous Catalyst

A novel silica gel functionalized-SO3H as a heterogeneous catalyst was prepared and characterized by FT-IR, XRD, TGA and elemental analysis. It has been studied for microwave-assisted solvent-free Pechmann condensation. The result revealed that 20% w/w silica bonded 3-mercapto propyl diethylene diamine N-sulfamic acid (SMPDDSA) was found to be effective. 4-methyl coumarin derivatives were the only product obtained in good to excellent yield (75–94%). The present protocol accomplishes the reaction in much lesser time as compared to the conventional method.

Theoretical and Experimental Study on the 7‐Hydroxy‐4‐Methylcoumarin Synthesis with H‐Beta Zeolite

AbstractCoumarin is an important chemical in agricultural and pharmaceutical industries. This work studied the synthesis of 7‐hydroxy‐4‐methylcoumarin via the Pechmann condensation reaction catalyzed by H‐Beta zeolite catalyst using a combination of experimental and theoretical means. Adsorptions and reactions taking place inside the 34T cluster (T=Si or Al atoms) of H‐Beta zeolite were examined by using density functional theory with the M06‐2X functional. The coumarin synthesis reaction was proposed to be a three‐step mechanism: the transesterification, the intramolecular hydroxyalkylation and the dehydration. The total activation energies for each step were calculated to be 17.8, 3.5 and 13.5 kcal⋅mol−1, respectively. The zeolite framework stabilized the adsorption complexes and decreased the activation barriers for the Pechmann condensation reaction. The synthesis of 7‐hydroxy‐4‐methylcoumarin from resorcinol and ethyl acetoacetate on H‐Beta zeolite was experimentally examined without solvent at various conditions. The adsorption of 7‐hydroxy‐4‐methylcoumarin on H‐Beta zeolite was detected by the FT‐IR spectroscopy technique. The experimental activation energy of 6.7 kcal⋅mol−1 agreed very well with the calculated apparent value of 10.6 kcal⋅mol−1. The H‐Beta zeolite can be reused at least four times with persistently high percent yield.

Synthesis, characterization and ethanol sensing properties of peripheral and non-peripheral tetrakis-(3,6-dihexyl-7-oxy-4-methylcoumarin)substituted zinc(II), cobalt(II), and copper(II) phthalocyanines

Phthalocyanines bearing coumarin moiety may exhibit interesting properties and also can soluble in organic solvents, easily. In this work, the phthalocyanine compounds bearing tetra-(3,6-dihexyl-7-oxy-4-methylcoumarin) units were synthesized and characterized. Firstly, the starting coumarin compound was synthesized by Pechmann condensation and then phthalonitrile compounds were synthesized by nucleofilic aromatic substitution. Phthalocyanine compounds were synthesized by cyclotetramerization of phthalonitriles. These compounds were characterized by spectroscopic methods such as FT-IR, 1H NMR, 13C NMR, electronic absorption spectra, MALDI-TOF mass and elemental analyses as well. The effect of the structure (position of substitution, central metal atom, etc.) of phthalocyanines on electronic absorption spectra and aggregation behavior was also investigated in this paper. In another set of experiments, the effects of the position of methylcoumarin substituent on ethanol vapor sensing performance of the synthesized compounds were investigated and discussed. The observed sensitivities of peripheral and non-peripheral substituted phthalcyanine films are different in spite of their similar bond numbers, indicating significant role of position of the substituent in interaction mechanism. According to the results, the peripheral substituted Pc based sensor not only had high sensitivity towards ethanol vapor, but exhibited very short response time and recovery times. When the concentration of ethanol reached 250 ppm, sensitivity and the response time of peripheral substituted CoPc reached 1.1 × 10−2 ppm−1 which was two-fold that than of non-peripheral substitueted CoPc. While peripheral substituted CoPc based sensor shows a response time of 70 s towards 250 ppm concentration of ethanol vapor, the response time of the non-peripheral substitueted CoPc based sensor was about 270 s. As a result, the presented peripheral methyl coumarin substituted compounds are good candidates for ethanol sensing applications.

Heterogeneously Catalyzed Pechmann Condensation Employing the Tailored Zn0.925Ti0.075O NPs: Synthesis of Coumarin

A novel heterogeneous catalytic method was developed for the synthesis of coumarin and its derivatives using the Ti(IV)-doped ZnO matrix forming catalyst Zn0.925Ti0.075O having a high surface area and good Lewis acidity. The catalyst shows high activity toward a broad spectrum of the substituted phenols with β-ketoesters such as ethyl acetoacetate, ethyl butyryl acetate, ethyl benzoyl acetate, and so forth in good yields over short reaction times during the synthesis of coumarins. The methodology was further extended for the synthesis of ayapin molecules. The catalyst also shows recycle activity up to seven cycles with very good stability.

Synthesis and Biological Evaluation of Novel Coumarins with tert-Butyl and Terpene Substituents.

Coumarins with terpene and tert-butyl substituents were synthesized via Pechmann condensation reaction. New derivatives were investigated in different model system for the exhibition of antioxidant, radical scavenging and membrane-protective activities. It has been found that 4-methylcoumarin derivatives with monoterpene moieties exhibit high antioxidant activities. The most active and promising for further investigations is 5-hydroxy-6,8-diisobornyl-4-methylcoumarin, containing two isobornyl substituents on the benzopyran ring.

Fe3O4@Boehmite-NH2-CoII NPs: An Environment Friendly Nanocatalyst for Solvent Free Synthesis of Coumarin Derivatives Through Pechmann Condensation Reaction

We report herein the synthesis of coumarin derivatives via the Pechmann condensation reaction in the presence of magnetic core–shell-like Fe3O4@Boehmite-NH2-CoII NPs. The aforesaid nanocatalyst which previously reported by our group, was found to be an efficient heterogeneous nanocatalyst in this reaction. Initially, the reaction conditions were optimized with different solvents, catalyst amounts and temperatures. Subsequently, the scope of the reaction was extended and the coumarin derivatives were obtained in reasonable yields. Interestingly, Fe3O4@Boehmite-NH2-CoII NPs was stable under reaction conditions and can be reused at least six times without a significant decrease in its catalytic activity. More importantly, using cobalt as a non-toxic, inexpensive, widely available and high-activity catalyst is great of interest than the most previously reported protocols.

Microwave assisted synthesis, characterization and investigation of antibacterial activity of 3-(5-(substituted-phenyl)-4,5-dihydro-1H-pyrazol-3-yl)-2H-chromen-2-one derivatives

A variety of 3-(5-(substituted-phenyl)-4,5-dihydro-1H-pyrazol-3-yl)-2H-chromen-2-one derivatives 3a–j were synthesized through microwave assisted thermal annulation of corresponding α,β-unsaturated ketones (chalcones) 2a–j via hydrazinolysis. Chalcones 2a–j were prepared from 3-acetyl-coumarin 1 which was previously accessed by Pechmann condensation reaction of salicylaldehyde. The series of pyrazoline-based coumarin motifs 3a–j synthesized, were structurally confirmed by analytical and spectral data. They were then evaluated for their antimicrobial activities using agar diffusion method. The result showed that microwave assisted method (MAM) for the reaction was remarkably successful and gave the targeted products 3a–j in higher yields at shorter reaction times compared to conventional synthetic method (CSM). The results showed that these skeletal frameworks exhibited marked potency as antibacterial agents. The most active antibacterial agent was 3-(5-(4-(diethylamino) phenyl)-4,5-dihydro-1H-pyrazol-3-yl)-2H-chromen-2-one 3j with MIC and MBC values of 3.92 ± 0.22 µg/mL and 7.82 ± 0.43 µg/mL respectively.

Recyclable cellulose nanocrystal supported Palladium nanoparticles as an efficient heterogeneous catalyst for the solvent‐free synthesis of coumarin derivatives via von Pechmann condensation

2‐Amino pyrimidine nanocellulose‐supported Palladium nanoparticles (CNC‐AMPD‐Pd) as a novel bio supported nanocatalyst was prepared and characterized by ICP‐AES, FT‐IR, XRD, SEM, TEM, TGA and EDX techniques. The nanocatalyst demonstrated outstanding performance in Pechmann condensation between different substituted phenols and ethyl acetoacetate to obtain coumarin derivatives in good to excellent yields. The catalyst is easily recycled and reused without loss of the catalytic activity. The combined merits of reusable catalyst and solvent‐free reaction conditions make the condensation with safe operation, no leaching of pd into environment, low pollution, rapid access to products and simple workup.

Synthesis of Novel Anti‐inflammatory Psoralen Derivatives ‐ Structures with Distinct Anti‐Inflammatory Activities

As a continuum to our work with coumarins, 12 psoralens were synthesized and evaluated for their anti‐inflammatory activity. Psoralens were prepared in three steps; at first, 7‐hydroxycoumarins were synthesized by von Pechmann condensation and then converted to 7‐(2‐oxopropoxy)coumarins. In the final step, a fused furan ring was introduced in an intramolecular ring‐formation reaction. Based on a SciFinder search, two out of the 12 synthesized psoralen derivatives (compounds 9 and 12) were found to be novel. The derivatives displayed anti‐inflammatory activity by suppressing iNOS and IL‐6 expression, but their mechanism of action seemed to be dependent on the substitution. Compound 6 with propyl side chain inhibited NF‐κB mediated transcription, while compound 10 with a phenyl substituent down‐regulated iNOS expression in a posttranscriptional manner. The results introduce psoralen derivatives as promising anti‐inflammatory compounds with potential for treatment of conditions involving iNOS and/or IL‐6‐mediated adverse responses.

Recent Advances in Synthesis of 4-Arylcoumarins.

4-Arylcoumarins (4-aryl-2H-1-benzopyran-2-one), also known as neoflavones, comprise a minor subclass of naturally occurring flavonoids. Because of their broad-spectrum biological activities, arylcoumarins have been attracting the attention of the organic and medicinal chemistry communities, and are considered as an important privileged scaffold. Since the development of Pechmann condensation, a classical acid-catalyzed condensation between phenol and β-keto-carboxylic acid, several versatile and efficient synthetic approaches for 4-arylcoumarins have been reported. This review summarizes recent advances in the synthesis of the 4-arylcoumarin scaffold by classifying them based on the final bond-formation type. In particular, synthetic methods executed under mild and highly efficient conditions, such as solvent-free reactions and transition metal catalysis, are highlighted.

Synthesis and in vitro Evaluation of 1,2,3-triazole-4-chloromethylcoumarins with Antioxidant Activity

Background: Coumarins are secondary plant metabolites typically found in the species of Asteraceae, Rutaceae and Umbeliferae families which demonstrate several pharmacological properties, including antioxidant activity. As antioxidants, coumarins are known to influence the formation and uptake of Reactive Oxygen Species (ROS), to reduce the oxidative damage caused by free radicals and to prevent eicosanoid formation, being of interest for drug design. In this context, we designed the synthesis of 4-chloromethylcoumarins via Pechmann condensation with different substituents at the position 6 of the coumarin ring through Click chemistry reactions, aiming to improve their antioxidant activities. Methods: The synthesis of the envisioned compounds started with Pechmann condensation using hydroquinone and ethyl 4-chloroaceacetate followed by functionalization of the phenolic hydroxyl with propargyl bromide via Williamsom ether synthesis. Subsequently, Click chemistry reactions were performed under microwave irradiation using previously synthesized organic azides, then yielding five 6-substituted-4-chloromethylcoumarin analogues. These compounds had their intrinsic toxicities estimated via cell viability assays using the NIH 3T3 Cell Line (mouse embryonic fibroblasts) by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. The antioxidant activities were then assayed using the DCFH-DA (2’,7’-diihydrochlorofluorescin diacetate) assay. Result and Conclusion: Five novel coumarins were synthesized with low to moderate yields (11-61%), while four of these compounds displayed some degree of toxicity in the cell viability assay. However, the remaining coumarin, LaSOM 322, was nearly atoxic in all the assayed conditions and displayed the most relevant antioxidant properties, being a promising lead for subsequent optimization. Keywords: Coumarins, antioxidants, reactive oxygen species, free radical scavenging, Click chemistry, Pechmann condensation.

Simple and Effective Integration of Green Chemistry and Sustainability Education into an Existing Organic Chemistry Course

Green chemistry and sustainable development have become increasingly important topics for the education of future chemists. The cross-disciplinary nature of green chemistry and sustainable development often means these subjects are taught in conjunction with other subjects, such as organic chemistry and chemical engineering. Herein, a straightforward and efficient approach for vertical integration of green chemistry concepts within existing undergraduate organic chemistry courses is shown. The gradual self-evaluation, “greenification”, and reassessment of an organic chemistry course at KTH Royal Institute of Technology from 2013 to 2017 is described, with particular focus on the laboratory course and a novel green chemistry project designed to promote sustainability thinking and reasoning. The laboratory project, which can also be conducted as an independent organic chemistry laboratory exercise, required students to critically evaluate variations of the same Pechmann condensation experiment according to ...

Preparation, characterization of highly active recyclable zirconium and tin tungstate catalysts and their application in Pechmann condensation reaction

In this contribution, a facile and efficient one-step method for the preparation of mesoporous zirconium and tin tungstate with different Zr or Sn:W molar ratios. The prepared catalysts were characterized by different textural and spectroscopic techniques such as XRD, Raman spectra, SEM, EDX, TEM and N2 adsorption–desorption at − 196 °C. The surface acidity was measured by nonaqueous potentiometric titration of n-butylamine and FTIR spectra of chemisorbed pyridine. XRD results showed that all the prepared samples calcined at 400 °C are amorphous, no evidence for formation of big aggregates of WOx species on the catalyst surfaces, but all WOx species are homogeneously dispersed as small particles on the surfaces. At higher ratio of W (ZrW3 and SnW3) the excess WOx species are distributed inside the pores or block the pores by covering the necks of the pores, which leads to decrease in the specific area as evident from N2 adsorption- desorption study. Raman spectra showed that the tungstate species has WO4 distorted tetrahedral structure. The surface acidity measurement showed that the catalysts contain mixture of Lewis and Bronsted acid sites with different ratios, the maximum B/L ratio reach maximum value at molar ratio 1:2 (ZrW2 and SnW2). The results showed that zirconium tungstate samples have higher surface acidities than tin tungstate samples. The prepared catalysts showed high catalytic activities for the synthesis of 7-hydroxy-4-methyl coumarin via the Pechmann condensation reaction of resorcinol with ethyl acetoacetate. High yield (~ 94%) with 100% selectivity of 7-hydroxy-4-methyl coumarin was obtained under solvent free conditions.