Reaction Of Chalcones Research Articles

Synthesis of 2‐Trifluoromethyl Pyridines through Multicomponent Kröhnke Reaction

AbstractA multicomponent Kröhnke reaction route toward 2‐trifluoromethyl pyridines from reaction of chalcones with easily available and stable 1‐(3,3,3‐trifluoro‐2‐oxopropyl)pyridin‐1‐ium bromide and ammonium acetate is reported. The reaction is found to be general with a range of substituted chalcones, and the applicability of the methodology in gram scale is demonstrated. Preliminary results suggest that this transformation is initiated by 1,4‐Michael addition, followed by inter‐ and intramolecular nucleophilic addition, and elimination.

Synthesis of substituted cyclohexenones by reaction of chalcones with acetoacetic acid amides

New 4-aryl-2-oxo-6-phenyl-3-cyclohexene-1-carboxamides were obtained by the reaction of N -substituted acetoacetic acid amides with benzalacetophenone and 4-methoxybenzalacetophenone in alcohol in the presence of potassium hydroxide. Structure of the prepared compounds was proved using IR, 1H and 13C NMR spectroscopy, mass spectrometry and X-rays analysis data.

Discovery of a new dihydroeugenol-chalcone hybrid with cytotoxic and anti-migratory potential: A dual-action hit for cancer therapeutics

Cancer still represents a serious public health problem and one of the main problems related to the worsening of this disease is the ability of some tumors to develop metastasis. In this work, we synthesized a new series of chalcones and isoxazoles derived from eugenol and analogues as molecular hybrids and these compounds were evaluated against different tumor cell lines. This structural pattern was designed considering the cytotoxic potential already known for eugenol, chalcones and isoxazoles. Notably, chalcones 7, 9, 10, and 11 displayed significant activity (4.2–14.5 µM) against two cancer cell lines, surpassing the potency of the control drug doxorubicin. The reaction of chalcones with hydroxylamine hydrochloride provided the corresponding isoxazoles that were inactive against these cancer cells. The dihydroeugenol chalcone 7 showed the most promising results, demonstrating higher potency against HepG2 (CC50: 4.2 µM) and TOV-21G (CC50: 7.2 µM). Chalcone 7 was also three times less toxic than doxorubicin considering HepG2 cells, with a selectivity index greater than 11. Further investigations including clonogenic survival, cell cycle progression and cell migration assays confirmed the compelling antitumoral potential of chalcone 7, as it reduced long-term survival due to DNA fragmentation, inducing cell death and inhibiting HepG2 cells migration. Moreover, in silico studies involving docking and molecular dynamics revealed a consistent binding mode of chalcone 7 with metalloproteinases, particularly MMP-9, shedding light on its potential mechanism of action related to anti-migratory effects. These significant findings suggest the inclusion of compound 7 as a promising candidate for future studies in the field of cancer therapeutics.

Synthesis of Substituted Cyclohexenones by Reaction of Chalcones with Acetoacetic Acid Amides

Synthesis of Substituted Cyclohexenones by Reaction of Chalcones with Acetoacetic Acid Amides

Elucidating the Mechanism and Chemoselectivity in the PBu3‐Catalyzed Rauhut‐Currier Reaction of Chalcone with Ethyl Acrylate

AbstractDisclosing the chemoselectivity and regioselectivity of phosphine‐catalyzed Rauhut‐Currier (R−C) reaction remains a challenge. Here, a comprehensive study on the possible mechanisms and origins of the chemoselectivity and regioselectivity of PBu3‐catalyzed R−C reactions between ethyl acrylate and chalcone is performed by DFT. Both cross and homo R−C reactions are investigated and compared. The computational results show that the cross R−C reaction is energetically favorable than the homo R−C reaction, with head‐to‐tail product being generated preferentially. Moreover, the C−C bond formation process is identified to be the regioselectivity‐ and chemoselectivity‐determining step. The CDFT and Parr function analyses are successfully used to predict the origins of chemoselectivity and regioselectivity, respectively. This work would provide a valuable case for exploring the origins of the chemoselectivity and regioselectivity of the phosphine catalyzed reactions, which should be helpful to understand and control the selectivities by rational design.

Microwave-assisted synthesis, antioxidant activity, docking simulation, and DFT analysis of different heterocyclic compounds

In this investigation, pressure microwave irradiation was used to clarify the activity of 1-(2-hydroxyphenyl)-3-(4-methylphenyl)prop-2-en-1-one (3) towards several active methylene derivatives utilized the pressurized microwave irradiation as green energy resource . Chalcone 3 was allowed to react with ethyl cyanoacetate, acetylacetone, and thioglycolic acid; respectively, at 70 °C with pressure under microwave reaction condition to afford the corresponding 2-hydroxyphenylcyanopyridone, 2-hydroxyphenyl acetylcyclohexanone, and thieno[2,3-c]chromen-4-one derivatives respectively. Moreover, the reaction of chalcone 3 with hydrogen peroxide with stirring affords the corresponding chromen-4-one derivative. All the synthesized compounds were confirmed through spectral tools such as FT-IR, 1HNMR, 13CNMR, and mass spectrum. Furthermore, the synthesized heterocycles were exhibited excellent antioxidant activity and comparable with vitamin C, where the presence of the OH group increases the scavenger radical inhibition. Furthermore, the biological activity of compound 12 was demonstrated through molecular docking stimulation using two proteins, PDBID: 1DH2 and PDBID: 3RP8, which showed that compound 12 possesses greater binding energy and a shorter bond length comparable with ascorbic acid. Also, the compounds were optimized through DFT/B3LYP/6-31G (d,p) basis set and identification of their physical descriptors, whereas the compound 12 was confirmed through X-Ray single structure with Hirsh field analysis of the compound to know the hydrogen electrostatic bond interaction, and correlated with the optimized structure by comparing their bond length, bond angle, FT-IR, and NMR, which gave excellent correlation.

Synthesis A New Bis Oxazine and Thiazine Derivatives and Study Their Biological Activities

Oxazine and thiazine are heterocyclic organic compounds that have a wide range of pharmacological applications. In this study, some chalcone derivatives (1–5) were synthesized based on the reaction of an equal amount of p-substituted acetophenone and terephthalaldehyde in a basic medium. Oxazine derivatives (6-10) and thiazine derivatives (11–15) are synthesized from the reactions of chalcones (1-5) with urea and thiourea, respectively, in a basic medium. The newly synthesized compounds were identified using various physical techniques like 1H-NMR and FT-IR spectra, in addition to docking analysis for some of these derivatives. Finally, these compounds were tested for their biological activity, IC50, and % of PC3 cell line viability as markers of anticancer activity.

Synthesis, characterization, crystal structure, and fluorescence behavior of new 4-aryl-6-(2,5-dichlorothiophen-3-yl)-2-methylpyridine-3-carbonitrile derivatives

A series of new 4-aryl-6-(2,5-dichlorothiophen-3-yl)-2-methylpyridine-3-carbonitrile derivatives 4(a-u) were synthesized starting with Friedel-Crafts acylation of 2,5-dichlorothiophene to form compound (1), which undergoes Claisen-Schmidt condensation with the corresponding aryl aldehyde 2(a-u) to produce chalcones 3(a-u) as intermediate compounds. The reaction of chalcones 3(a-u) and 3-aminocrotononitrile furnished the new title compounds 4(a-u). The pyridines 4(a-u) were characterized by elemental analysis, ATR-FTIR, 1H NMR, 13C NMR, DEPT 135, ESIMS, and HRESIMS. The proposed structures agree with the expected physical as well as spectral data. Single crystal x-ray structure for some derivatives were determined and confirmed unambiguously the proposed structures. Compounds 4(a-u) exhibit distinct fluorescent properties in solution. The steady state fluorescence spectra of the compounds studied showed that all the compounds are blue emitters. Quantum chemical calculations have been performed to study the geometry of all compounds based on DFT/TDDFT calculations at B3LYP/6-311G (d,p) level of theory. The calculated geometries are in good agreement with determined single crystal structures. In order to get more shed into the red shifted emission of compounds 4(d-i) with respect to relevant absorption behavior, TD-DFT study was performed. The red shifted emission is found to be controlled by the conformational relaxation in the excited state on the emission spectra.

Prepare several substituted pyridines derived from Chalcone and evaluate their bioactivity

In this research, Chalcone (M1-10) was prepared by reaction of aromatic aldehydes with substituted acetophenone, through reaction of Chalcone with Malononitrile in an acidic medium, where pyridine compounds (M19-26) were obtained. The bioactivity of the prepared compounds was tested against Gram-negative and Gram-positive bacteria (Klebsellia pneumonia, Pseudomnas putida, Staph aureus, Enterococcus faecalis). the lowest inhibitory concentration compared to (Ciprofloxacin) and the prepared compounds were diagnosed by physical spectrophotometric methods using spectrophotometers. I.R, 1H-NMR, 13C-NMR.

Cs2CO3-Promoted [3 + 2] Cyclization of Chalcone and N-Tosylhydrazone

Cs2CO3-promoted [3 + 2] cyclization of chalcone and N-tosylhydrazones has been developed, a series of novel (4,5-diaryl-1H-pyrazol-3-yl)(aryl)methanone derivatives were synthesized with a wide range of substrates, good tolerance of functional groups and by a one-pot three-component reaction of chalcone, aryl formaldehyde, and TsNHNH2. In addition, the gram-scale synthesis of the product and further transformations were also investigated.

Biosynthesis of ZrO2for ZrO2@Ag‐S‐CH2COOH as the retrievable catalyst for the one‐pot green synthesis of pyrazoline derivatives and their anticancer evaluation

AbstractIn the present work,Ficus benghalensisleaf extract was used for the synthesis of ZrO2nanoparticles. Further, ZrO2@Ag‐S‐CH2‐COOH was synthesized using biosynthesized ZrO2, and its catalytic potential was examined in the synthesis of pyrazoline from reaction of chalcone and hydrazine hydrate at room temperature. The structural conformation of ZrO2@Ag‐S‐CH2‐COOH has been done using FT‐IR, SEM, EDX, XRD, TGA‐TDA, XPS, and DLS techniques, high turnover number (TON), and high turnover frequency. The ZrO2@Ag‐S‐CH2‐COOH demonstrated outstanding catalytic activity for the synthesis of pyrazolines. The structures of the pyrazoline derivatives were confirmed by FT‐IR,1H and13C NMR, and mass spectrometry techniques. Synthesized pyrazoline were tested for anticancer activity against human lung cancer cell line A549 study and confirmed by molecular docking investigations.

Green synthesis, spectroscopic and quantum chemical calculations of some pyrimidine derivatives

A series of 4-aryl-3,4,6,7,8,9-hexahydro-1H-cyclohepta[d]pyrimidine-2(5H)-thiones were synthesized via the reaction of chalcone with thiourea using various processes such as heat, ultrasonic, and grinding approach. Because of its response simplicity, shortest reaction time, fewer contamination, and excellent product yields, the potential use of pyrimidine subsidiaries in natural combination is rapidly growing. The designs of the molecules were resolved using FT-IR, 1H NMR, and 13C NMR spectroscopy. The DFT B3LYP/6-31G (d,p) principle set was used to investigate the blended compound's sub-atomic structure. The NLO property of the synthesized compound was determined using hyperpolarizability values.

Green synthesis, characterization, biological evaluation and docking study of some pyrazoline and pyrimidine derivatives

Green and classical techniques have been utilized for preparing of a variety of aryl - substituted pyrazoline and pyrimidine derivatives (2-8). Reactions of chalcones 1 with semicarbazide and thiosemicarbazide, nicotinic acid hydrazide and amino guanidine hydrochloride afforded the corresponding N-substituted pyrazoline derivatives 2-5. Pyrimidine derivatives 6-8 were achieved via reaction of chalcone derivatives 1 with several reagents namely: guanidine nitrate, thiourea and 6-amino-2-thioxo-2,3- dihydropyrimidin-4(1H)-one under conventional and ultrasonic conditions. Ultrasonic method was found to be an easy work-up procedure and it gave high yield in comparison with conventional method. The structures of new synthesis compounds were characterized by elemental and spectral analyses. Some of newly compounds were tested in vitro antibacterial activity against some gram–positive and gram–negative. The antimicrobial results displayed favorable antimicrobial activity. Molecular docking has been perfomed for compound 5b using MOE 2008.10, The data results obtained are quite promising.

Synthesis, characterization and antimicrobial activity of novel tetrazoles clubbed with pyrimidine

An attempt was made to synthesize pyrimidine tetrazole derivatives of pharmaceutical interest by oxidative cyclization of chalcones with adequate yield and purity, prompted by the diversity of their wider usage and the fact that they are an integral part of genetic content. The present work involves the reaction of 5-(2,6-dimethylphenyl)-1H-tetrazole with acetic anhydride to yield 1-[5-(2,6-dimethylphenyl)-1H-tetrazol-1-yl] ethanone (1) and which then treated with different aromatic aldehydes in presence of alkaline medium to chalcones (2a-f). Reaction of chalcones (2a-f) with urea and thiourea to produce 5-[5-(2,6-dimethylphenyl)-1H-tetrazol-1-yl]-4-(substituted aryl ) pyrimidin-2-ol (3a-f) and 5-[5-(2,6-dimethylphenyl)-1H-tetrazol-1-yl]-4-(substituted aryl) pyrimidin-2-thiol (4a-f) respectively. All compounds were characterized by infrared spectroscopy (IR), H nuclear magnetic resonance (NMR), and mass spectrometry (MS) to prove the structure and assessed in vitro for their efficacy as antibacterial and antifungal activity against four bacteria. The compounds 3c, 3d and 3f and compounds 4c, 4d and 4f possess very good activity against and E. coli and the compounds 3e, 3c and 3a and compounds 4e,4b and 4c possess very good activity against fungi and .

Synthesis and characterization of thiazolidine-4-one compounds derived from chalcone and evaluation of the biological activity of some of them

In this paper, chalcone [T1-T10] was synthesized from the reaction of (N-phenylacetamide or N-(4-chlorophenyl)acetamide) with benzaldehyde and its aromatic substitutes using ethanol as a solvent and in the presence of KOH as a basic intermediate. Schiff bases [T11-T20] were synthesized from the reaction of chalcone [T1-T10] with 4-chloroaniline using droplets of glacial acetic acid and in the presence of ethanol as a solvent. Thiazolidines-4-one compounds were synthesized from the reaction of Schiff bases [T11-T20] prepared in the second step with thioglycolic acid using heat and anhydrous ZnCl2 as a catalyst and using 10% sodium bicarbonate to neutralize the reaction. The synthetic compounds were diagnosed with some spectral methods such as [UV], [FTIR], [1H NMR] and [13C-{1H}NMR] , in addition to determining the melting and purity levels of the prepared compounds and monitoring the progress of the reactions using TLC thin layer chromatography. The effect of some prepared compounds on the growth of two types of bacterial isolates, known to be resistant to antibiotics, one negative for Gram stain [Gr-ve], which is Pseudomonas aeruginosa, and the second positive for Gram stain [Gr + ve], which is Staphylococcus aurous, were used antibiotics Amoxicillin and Ampicillin. Some of the prepared compounds showed high inhibitory efficacy against the used bacteria in addition, the conformation of prepared compounds at the lower energy level were studied.

Diastereoselective Synthesis of Polysubstituted Pyrrolidines/Dihydropyrroles: Photochemical Properties of Polysubstituted Pyrroles

AbstractPolysubstituted pyrrolidines/dihydropyrroles and the corresponding pyrrole derivatives were synthesized via three‐component/pseudo four‐component reaction of chalcone, benzylamine and benzaldehyde, and followed by DDQ oxidation. When exposed to UV light under aerobic conditions, the prepared pyrrole derivatives were found to be light‐sensitive and undergo oxidative ring‐opening reaction to yield the corresponding enamides.

Reaction of Chalcones with Cellular Thiols. The Effect of the 4-Substitution of Chalcones and Protonation State of the Thiols on the Addition Process. Diastereoselective Thiol Addition.

Several biological effects of chalcones have been reported to be associated with their thiol reactivity. In vivo, the reactions can result in the formation of small-molecule or protein thiol adducts. Both types of reactions can play a role in the biological effects of this class of compounds. Progress of the reaction of 4-methyl- and 4-methoxychalcone with glutathione and N-acetylcysteine was studied by the HPLC-UV-VIS method. The reactions were conducted under three different pH conditions. HPLC-MS measurements confirmed the structure of the formed adducts. The chalcones reacted with both thiols under all incubation conditions. The initial rate and composition of the equilibrium mixtures depended on the ratio of the deprotonated form of the thiols. In the reaction of 4-methoxychalcone with N-acetylcysteine under strongly basic conditions, transformation of the kinetic adduct into the thermodynamically more stable one was observed. Addition of S-protonated N-acetylcysteine onto the polar double bonds of the chalcones showed different degrees of diastereoselectivity. Both chalcones showed a Michael-type addition reaction with the ionized and non-ionized forms of the investigated thiols. The initial reactivity of the chalcones and the equilibrium composition of the incubates showed a positive correlation with the degree of ionization of the thiols. Conversions showed systematic differences under each set of conditions. The observed differences can hint at the difference in reported biological actions of 4-methyl- and 4-methoxy-substituted chalcones.

Synthesis and Antimicrobial Activity of New 4-Methyl-2-(3-pyridyl)thiazolyl Chalcones and Pyrazolines

In an attempt to develop active antimicrobial agents, a set of new thiazolyl chalcones has been synthesized by the Claisen–Schmidt reaction of 5-acetyl-4-methyl-2-(3-pyridyl)thiazole with various heterocyclic aldehydes in alkali media. Reaction of chalcones with hydrazine hydrate has resulted in pyrazolines that have been assessed for in vitro antimicrobial activity against ten bacterial and five fungal human pathogenic strains using the disk diffusion assay. The synthesized pyrazolines demonstrate antimicrobial activity higher than that of synthesized chalcones. 2-Thienylchalcone has been determined as the most active against P. aeruginosa. Three pyrazolines are characterized by distinctive activity towards Gram-negative bacteria S. flexneri and P. aeruginosa. Two pyrazolines demonstrate equipotent antifungal activity with amphotricin B against A. clavatus.

A Facile synthesis of some novel 1,3,4-thiadiazoles and pyridines linked to benzofuran as antimicrobial agents.

In the present study, a new series of benzofuran-integrated 1,3,4-thiadiazoles were prepared starting from pyrazol-4-carboxaldehyde derivatives 3a,b. Thus, reaction of compound 3a,b with benzyl hydrazine carbodithioate afforded hydrazine carbodithioate derivatives 4a,b. Treatment of compound 4a with hydrazonoyl halides 5e,f afforded 1,3,4-thiadiazoles 6a, b while the reaction of 4b with hydrazonoyl halides 5a-d yielded 1,3,4-thiadiazoles 7a,b. on the other hand, new pyridine derivatives can be synthesized via the reaction from the reaction of chalcone 8 with different C-nucleophile such as ethyl acetoacetate, benzoyl acetonitrile or acetyl acetone. All the new derivatives were characterized by spectral data. Some of the newly prepared compounds were investigated against different pathogenic microbes. The results of the antimicrobial activity revealed that all the tested compounds showed no activity except compound 6a which showed weak activity against all tested microorganisms. Compound 6b was weak active against B. subtilis and compound 7c was intermediate active against E. coli.

Multistep Synthesis and Photophysical Investigation of Novel Pyrazoline, a Heterocyclic D-π-a Chromophore (PTPB) as a Fluorescent Chemosensor for the Detection of Fe3+ Metal Ion

A pyridine-pyrazoline (2-(3-(pyridin-2-yl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)benzo[d]thiazole) (PTPB) has been designed and synthesized by the reaction of chalcone with 2-hydrazinylbenzo[d]thiazole. PTPB was further conformed by the FT-IR, 1H-NMR and 13 N-NMR spectroscopic techniques. The solvatochromic behavior of PTPB with electron donating and accepting group was investigated in nonpolar, polar aprotic and protic solvents experimentally. The photophysical behavior of the PTPB in different solvent was attributed to the intramolecular charge transfer (ICT) of the compound along with specific and nonspecific interaction with different solvents. On view of the effect of different type of interaction on the photophysical parameters such as stokes shift, dipole moment oscillator strength and fluorescence quantum yields have been calculated with respect to polarity of the solvent. In addition, pyridine-pyrazoline (PTPB) can use as fluorescent chemosensor to determine the Fe3+ metal ion with high selectivity among the series of cations in aqueous dimethylformamide (DMF). The recognition mechanism of PTPB toward Fe3+ has been investigated in detail by Benesi–Hildebrand, Stern–Volmer and job’s plot measurements and PTBP forms 1:1 complex with Fe3+ metal ion and displays fluorescent quenching behavior.