Claisen-Schmidt Condensation Reaction Research Articles

Tailoring and exploring the basicity of magnesium oxide nanostructures in ionic liquids for Claisen-Schmidt condensation reaction

Solid basic catalysts are extremely useful for green catalytic processes because of their high activity, easy separation, and minimal corrosion. Herein, we report the development and effect of the basicity of five various MgO nanostructures developed by microwave (MW) irradiation in different ionic liquids (ILs) on the Claisen-Schmidt Condensation Reaction. The growth of the shape-controlled MgO nanostructures in the presence of the synergetic effect of the ILs with the MW irradiation developed various basic sites on the surface of the MgO nanocrystals. Due to the synergetic effect (formation of hydrogen bonding and π-π interactions between the ILs and the MgO precursor in the presence of MW irradiation) produced active basic sites in the final nanostructure. The TPD & XPS results show that the synergetic effect strongly altered the percentages of high, low, and moderate basic sites of the catalysts. To determine their catalytic activity based on the obtained different basicity in the MgO nanostructures, prepared all nano structures were tested in the reaction. The altered basicity of the MgO catalysts strongly affected on reaction results and demonstrated better activity than pure MgO. Particularly, hexagonal MgO nanostructures with exposed crystal facets (110) and (111) having high surface area and basicity showed an outstanding activity. In addition, effect or reaction parameters such as temperature, catalyst amount, solvent effect, and reaction time were determine and obtained optimized reaction condition for outstanding results. To determine the diversity of prepared MgO nanostructures, various substituted chalcones were prepared in optimized reaction condition in good to efficient yield. Recyclability of prepared catalyst was also determined up-to 6 cycles and physicochemical changes before and after recyclability test was determined. The proper correlation of obtained basicity & basic sites with the catalytic activity was established with this protocol.

(E)-3-[3-(2-Butoxyquinolin-3-yl)acryloyl]-2-hydroxy-4H-chromen-4-one

The coumarinyl-quinolinylchalcone hybrid (E)-3-[3-(2-butoxyquinolin-3-yl)acryloyl]-2-hydroxy-4H-chromen-4-one 3b was prepared in good yield from a Claisen-Schmidt condensation reaction between 3-acetyl-4-hydroxy-2H-chromen-2-one 1 and 2-butoxyquinoline-3-carbaldehyde 2 in methanol at reflux and catalyzed by KOH pellets. The structure of the synthesized compound 3b was fully confirmed by FTIR-ATR, (1D and 2D) NMR experiments, EIMS and elemental analysis.

Exploring Promising Immunomodulatory Potential of Natural and Synthetic 1,3-Diphenyl-2-propen-1-one Analogs: A Review of Mechanistic Insight.

The immune system is an intricate and coordinated nexus serving as a natural defense to preclude internal and external pathogenic insults. The deregulation in the natural balance of immunological functions as a consequence of either over expression or under expression of immune cells tends to cause disruption of homeostasis in the body and may lead to development of numerous immune system disorders. Chalcone moieties (1,3-diphenyl-2-propen-1-one) have been well-documented as ideal lead compounds or precursors to design a wide range of pharmacologically active agents to down-regulate various immune disorders. Owing to their unique structural and molecular framework, these α, β-unsaturated carbonyl-based moieties have also gained remarkable recognition due to their other multifarious pharmacological properties including antifungal, anti-inflammatory, anti-malarial, antibacterial, anti-tuberculosis, and anticancer potential. Though a great number of methodologies are currently being employed for their synthesis, this review mainly focuses on the natural and synthetic chalcone derivatives that are exclusively synthesized via Claisen-Schmidt condensation reaction and their immunomodulatory prospects. We have critically reviewed the literature and provided convincing evidence for the promising efficacy of chalcone derivatives to modulate functioning of various innate and adaptive immune players including granulocytes, mast cells, monocytes, macrophages, platelets, dendritic cells, natural killer cells, and T-lymphocytes.

Chemical Synthesis of Chalcones by Claisen-Schmidt Condensation Reaction and its Characterization

Chemical Synthesis of Chalcones by Claisen-Schmidt Condensation Reaction and its Characterization

Synthesis of N-methyl-4-piperidone Curcumin Analogues and Their Cytotoxicity Activity against T47D Cell Lines

Three piperidone curcumin analogues (N-methyl-(3E,5E)-3,5-bis-(2-chlorobenzylidene)-4-piperidone (1), N-methyl-(3E,5E)-3,5-bis-(3-bromobenzylidene)-4-piperidone (2) and N-methyl-(3E,5E)-3,5-bis-(4-chlorobenzylidene)-4-piperidone (3)) were synthesized from N-methyl-4-piperidone with halogenbenzaldehyde, 2-chlorobenzaldehyde, 3-bromobenzaldehyde and 4-chlorobenzaldehyde. The Claisen-Schmidt condensation reaction was used in alkali condition with combinatorial. All the compounds showed light yellow needle, light yellow powder, and yellow crystal form with percentage of yield 39, 66, and 40%, respectively. All the structure compounds were confirmed by using UV, IR, 13C-NMR, 1H-NMR and MS. Apart from that, the cytotoxicity results against breast cancer cell (T47D) showed strong to moderate activity with the IC50 value 8, 4, and 45 µg/mL, respectively.

The Synthesis of Chalcones as Anticancer Prodrugs and their Bioactivation in CYP1 Expressing Breast Cancer Cells.

Although the expression levels of many P450s differ between tumour and corresponding normal tissue, CYP1B1 is one of the few CYP subfamilies which is significantly and consistently overexpressed in tumours. CYP1B1 has been shown to be active within tumours and is capable of metabolising a structurally diverse range of anticancer drugs. Because of this, and its role in the activation of procarcinogens, CYP1B1 is seen as an important target for anticancer drug development. To synthesise a series of chalcone derivatives based on the chemopreventative agent DMU-135 and investigate their antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1. A series of chalcones were synthesised in yields of 43-94% using the Claisen-Schmidt condensation reaction. These were screened using a MTT assay against a panel of breast cancer cell lines which have been characterised for CYP1 expression. A number of derivatives showed promising antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1, while showing significantly lower toxicity towards a non-tumour breast cell line with no CYP expression. Experiments using the CYP1 inhibitors acacetin and α-naphthoflavone provided supporting evidence for the involvement of CYP1 enzymes in the bioactivation of these compounds. Chalcones show promise as anticancer agents with evidence suggesting that CYP1 activation of these compounds may be involved.

Synthesis, crystal structures and Hirshfeld surface studies of chalcone derivatives: (2 E )-1-(4-2, 4-Dichlorophenyl)-3-[4-(propan-2-yl)phenyl]prop-2-en-1-one and (2 E )-1-(4-Fluorophenyl)-3-[4-(propan-2-yl) phenyl] prop-2-en-1-one

Abstract The title compounds (2E)-1-(4-2,4-dichlorophenyl)-3-[4-(propan-2-yl)phenyl]prop-2-en-1-one (I) and 2E)-1-(4-fluorophenyl)-3-[4-(propan-2-yl) phenyl]prop-2-en-1-one (II), have been synthesized by the base catalyzed Claisen-Schmidt condensation reaction of 4-(propan-2-yl)benzaldehyde with substituted acetophenones. The synthesized compounds were characterized by FT-IR, elemental analysis and single crystal X-ray diffraction. In I and II, the dihedral angle between the terminal rings are 54.68 (19)° and 53.42 (8)°, respectively. The intra molecular hydrogen bond of the type C H⋯O is observed in both the title compounds. The crystal structure is stabilized through C O⋯π (I) and C F⋯π (II) weak intermolecular interactions. Hirshfeld surfaces analysis computational method was carried to quantify the intermolecular interactions. The 2D finger print plots and electrostatic potential were plotted to evidence the intermolecular interactions.

Synthesis and antibacterial evaluation of nitrogen containing novel heterocyclic chalcones

ABSTRACTThirteen different novel heterocyclic chalcones were synthesized using cycloaddition and Claisen–Schmidt condensation reactions. These newly synthesized compounds were characterized by their spectral studies and structure of (E)-3-(4-methoxyphenyl)-1-(5-methyl-1-(pyridin-3-yl)-1H-1,2,3-triazol-4-yl)prop-2-en-1-one (4h) was also evidenced by single crystal X-ray studies. These compounds were evaluated for antibacterial activities against seven bacterial strains in vitro. Compounds 4b and 4c containing 4-fluoro and 4-chloro groups have shown remarkable inhibition as showed by the standard drug ciprofloxacin against Escherichia coli and Staphylococcus aureus, respectively. Another compound 4k containing 3,4,5-trimethoxy group also showed similar activity against both these strains. Beside these three potential compounds 4b, 4c, 4k, one more compound 4g containing 4-methyl group showed equivalent inhibition as that of standard drug against E. coli. These categories of compounds are therefore good candidates for developing new effective antibacterial in future.

Synthesis, molecular docking, and evaluation of novel bivalent pyrazolinyl-1,2,3-triazoles as potential VEGFR TK inhibitors and anti-cancer agents

Investigations in the discovery of tyrosinase enzyme inhibitors have the potential to design novel anti-cancer drugs. A variety of novel bivalent pyrazolinyl triazoles 5–7 were synthesized and identified. The bis-acetyl triazole 3 was accomplished via two-step process first by preparation of diazide 2 followed its coupling reaction with acetylacetone in basic medium. The Claisen–Schmidt condensation reaction of 3 with two moles equivalent of benzaldehyde produces the corresponding bis-α, β-unsaturated ketone 4. Treatment of Schiff base 4 with excess hydrazine hydrate in either acetic acid or ethanol/DMF afforded the bis-N-acetylpyrazline 5 or bis-pyrazoline 6, respectively. Finally, treatment of 6 with two derivatives of isothiocyanate analog gives the bis-N-thioamide pyrazolines 7a and 7b. The synthesized compounds were evaluated as anti-tumor candidates against three human cancer cell lines (MCF-7, HepG2, and HCT-116). The bioscreening evaluation showed that compounds 7a and 6 had a significant antineoplastic potencies (IC50: 32.26 and 57.06 µg/mL) against breast MCF-7 and hepatic HepG2 cancerous cell lines, respectively, in relative to the standard drug, 5-fluorouracil. Molecular docking studies of the synthesized compounds were investigated as VEGFR2 TK inhibitors.

Synthesis, crystal structure, spectroscopic characterization, docking simulation and density functional studies of 1-(3,4-dimethoxyphenyl) -3-(4-flurophenyl)-propan-1-one

The compound 1-(3,4-dimethoxyphenyl)-3-(4-flurophenyl)-propan-1-one (DFPO) was synthesized by Claisen-Schmidt condensation reaction and the single crystals were obtained by slow evaporation method. Three-dimensional structure was confirmed by single crystal X-ray diffraction method and exhibiting the triclinic crystal system with space group P-1. The crystal structure is stabilized by CH⋯O intermolecular and weak interactions. Computed molecular geometry has been obtained by density functional theory (DFT) and compared with experimental results. The spectra of both FT-IR in the range (4000–400 cm-1) and FT- Raman (3500–50 cm-1) of DFPO were recorded experimentally and computed by (DFT) using B3LYP/6-311G (d,p) as basis sets. Intramolecular charge transfer has been scanned using natural bond orbital (NBO) analysis and revealed the various contribution of bonding and lone pair to the stabilization of molecule. Nonlinear optical activity (NLO) of the title compound has been determined by second harmonic generation (SHG) and computed using DFT method. Hyperpolarizability, HOMO–LUMO energy gap, hardness, softness electronegativity and others Global reactivity descriptors of DFPO has been calculated and revealed complete picture of chemical reactivity of DFPO. Hirshfeld surface analyses were applied to investigate the intermolecular interactions and revealed that more than two-thirds of the inter contacts are associated with O⋯H, C⋯H and H⋯H interactions. Docking studies of DFPO showed inhibition of Vascular endothelial growth Factor human receptor (VEGFR-2) signalling pathway, which indicates DFPO as anti-angiogenesis, that play pivotal role in cancer, so we suggest it for clinical studies to evaluate its potential to treat human cancers.

Synthesis, in vitro Acetylcholinesterase Inhibitory Activity Evaluation and Docking Investigation of Some Aromatic Chalcones

In this study, a total of twenty chalcones were synthesized via Claisen-Schmidt condensation reaction and evaluated for their in vitro acetylcholinesterase inhibitory activities using Ellman’s method. Molecular docking studies on acetylcholinesterase were performed to elucidate the interactions between these chalcone derivatives and acetylcholinesterase active site at the molecular level. From the series, six compounds (S1-5 and S17) exhibited strong acetylcholinesterase inhibitory activities with IC50 values below 100 μM compared to the parent unsubstituted chalcone. Compound S17 (4’-amino-2-chlorochalcone) showed the strongest acetylcholinesterase inhibitory activity in the investigated group with IC50 value of 36.10 μM. Molecular modeling studies were consistent with the results of in vitro acetylcholinesterase inhibitory activities, and chalcone S17 could be considered as a potential lead compound for the development of new acetylcholinesterase inhibitors.

Synthesis and Structure-activity Relationships of Chalcone Derivatives as Inhibitors of Ovarian Cancer Cell Growth

Background: Ovarian cancer remains a disease with a poor five year survival rate. As such, novel therapies are needed. Natural chalcones as well as their synthetic derivatives have shown biological activity in a number of areas including the inhibition of cancer cell growth. Objective: To synthesize a library of chalcone derivatives, including novel structures, and determiner the inhibition of ovarian cancer cell growth and Structure-activity-relationships. Methods: The Claisen-Schmidt condensation reaction between substituted acetophenones and aromatic aldehydes was used to produce a series of novel chalcones in moderate to excellent yields and good purity. Cellular proliferation of CA-OV3 cells was measured with a MTS assay. Results: Out of the thirty-four synthesized compounds, eight are new derivatives. The synthesized compounds were characterized by 1H NMR, 13C NMR, and HRMS. Biological evaluation of these β-phenylacrylophenone derivatives in CA-OV3 cells showed interesting antiproliferative activities providing initial structure – activity information. Conclusion: Fourteen of the thirty-four tested compounds showed significant activity, with several showing near complete inhibition of growth at 100 µM. The structure-activity relationships suggest that modification to the A ring is widely tolerated and that electron-donating modifications to the B ring are beneficial to activity. Electron-withdrawing modifications to the B ring did not show inhibition of cell growth. Keywords: Synthesis, chalcones, claisen-schmidt condensation, structure-activity, ovarian cancer, growth inhibition.

Graphene-supported ZnO nanoparticles: An efficient heterogeneous catalyst for the Claisen-Schmidt condensation reaction without additional base

ZnO nanoparticles supported on reduced graphene oxide (ZnO/RGO) were prepared by the hydrothermal method and characterized by TEM, XPS, XRD, and Raman spectroscopy. As a green catalyst, ZnO/RGO was applied to the Claisen-Schmidt condensation reaction of aryl aldehydes and aryl ketones under microwave irradiation. Therein, chalcone products could be efficiently synthesized and easily separated from the heterogeneous catalysis system. The catalyst could be recycled four times without significant loss of catalytic activity.

Anti-oxidant behavior of functionalized chalcone-a combined quantum chemical and crystallographic structural investigation

Compound (2E)-3-(methoxyphenyl)-1-(4-methylphenyl) prop-2-en-1-one (Ch) was synthesized by the Claisen-Schmidt condensation reaction between para-methylacetophenone and para-methoxybenzaldehyde under basic condition. The structure of the molecule was elucidated using X-ray diffraction. Compound (Ch) demonstrated higher antioxidant activities in the DPPH test and H2O2 assay (IC50 = 12.23 ± 0.53 and 15.62 ± 0.98) than with the standard ascorbic acid (IC50 = 17.32 ± 0.44 and 19.07 ± 0.35). An evaluation of the atomic and molecular properties of ascorbic acid and Ch were computed based on their antioxidant activities. The molecular properties give insight into possible reasons for the enhanced antioxidant properties of Ch compared to ascorbic acid. The atomic properties provide further insight into chemical changes of the atoms of the compounds. Such changes include electronic shifting of the compounds electrophilic and/or nucleophilic states which highlight chemical moieties which characterize the antioxidant activity but do not directly relate to a variation in their antioxidant activities. The results obtained reflect oxygen atoms having significant nucleophilic interactions of each of the compounds. This was characterized by higher Fukui indices, isotropic and anisotropic hyperfine and orbital coupling stability energy.

Design, synthesis and biological evaluation of 3,4-dihydronaphthalen-1(2H)-one derivatives as Bcl-2 inhibitors

A series of new 3,4-dihydronaphthalen-1(2H)-one derivatives (6a–f) were designed, and synthesized by the Claisen–Schmidt condensation reaction. Their structures were characterized by NMR, FTIR, and MS spectroscopy. Their antitumor activities against human neoplastic cell lines Hela, Hepg2, K562, THP-1, SW1990, MIA PaCa-2, NCI-H460 and SK-BR-3 by the MTT method exhibited obvious anticancer activities and their cytotoxicities for LO2 cell lines were lower than DOX, especially for 6b and 6d. The inhibition activities against the Bcl-2 protein for 6b was evaluated and the result shows that lipophilic 3,4-dimethoxybenzylidene and 3,4-dihydronaphthalen-1(2H)-one could bind slightly to the active pockets of the Bcl-2 protein.

Synthesis, Antimicrobial Studies, and Docking Simulations of New Bis(4,5‐dihydropyrazole) Derivatives

A novel series of bis(3‐thienyl‐4,5‐dihydropyrazoles) has been synthesized by the cyclization reactions of bischalcones with phenyl hydrazine in basic medium. The O‐alkylation reactions of chalcones with suitable 1,ω‐dibromoalkanes in the presence of anhydrous K2CO3, dry acetone, and Bu4N+I− as PTC lead to the formation of bischalcones in good yields. The chalcone required was obtained from the Claisen–Schmidt condensation reaction of 2‐acetylthiophene with 3‐hydroxybenzaldehyde. Structures of prepared compounds were elucidated from their IR, 1H‐NMR, 13C‐NMR, and ESI‐MS spectral data. Newly synthesized compounds were screened for their antimicrobial potencies against Gram‐positive, Gram‐negative bacterial strains, and fungal strains using serial tube dilution method. Docking simulations have also been carried out to visualize the possible interaction of synthesized scaffold 2(a–g) and 3(a–g) at the active sites of Escherichia coli.

Inhibition of LPS-stimulated ROS production by fluorinated and hydroxylated chalcones in RAW 264.7 macrophages with structure-activity relationship study

Based on the importance of the previous fluorinated and/or hydroxylated chalcones studies, thirty-six compounds were designed as phenyl or hydroxyphenyl bearing fluoro, trifluoromethyl or trifluoromethoxy phenyl propenones and synthesized by applying modified Claisen-Schmidt condensation reaction as a single step. Inhibitory effects of the synthesized compounds on ROS production stimulated by LPS in RAW 264.7 macrophage were evaluated. Structure-activity relationship (SAR) study revealed that the compounds possessing para-hydroxyphenyl group combined with meta-fluoro or meta-trifluoromethyl phenyl group, and meta/para-hydroxyphenyl group combined with ortho-trifluoromethoxyphenyl group have an essential role in inhibiting the LPS-stimulated ROS production in RAW 264.7 macrophages. The most significant inhibitory effect on LPS-stimulated ROS production in RAW 264.7 macrophages was observed in compound 30 that possessed para-hydroxyphenyl group along with ortho-trifluoromethoxyphenyl group.

Structural, third-order optical nonlinearities and figures of merit of (E)-1-(3-substituted phenyl)-3-(4-fluorophenyl) prop-2-en-1-one under CW regime: New chalcone derivatives for optical limiting applications

In the present work, the crystal structures and third-order nonlinear optical (NLO) properties of two novel chalcone derivatives, (E)-1-(3-bromophenyl)-3-(4-fluorophenyl) prop-2-en-1-one (F3BC) and (E)-1-(3-nitrophenyl)-3-(4-fluorophenyl) prop-2-en-1-one (F3NC) have been experimentally investigated. Both chalcones were synthesized by Claisen–Schmidt condensation reaction. The single-crystals were obtained from slow evaporation solution growth method and were structurally characterized by single-crystal X-ray diffraction. Both studied crystals are crystallized in centrosymmetric space groups. The existence of CH⋯π interactions in F3BC and CH⋯O and CH⋯F hydrogen interactions in F3NC play important roles in creating supramolecular structures. The linear optical absorption coefficient (α) of F3BC and F3NC were analyzed by UV–Vis–NIR spectral analysis and the optical band gaps (Eg) were estimated. TG-DTA analysis revealed that the F3NC crystal has higher thermal stability than F3BC crystal. The third-order nonlinear optical properties of these crystals were studied in solution using Z-scan technique with a continuous wave (CW) DPSS laser operating at 532 nm wavelength. The molecules reveal a strong third-order nonlinear absorption (NLA) and negative nonlinear refraction (NLR). The calculated values of nonlinear absorption coefficient β, nonlinear refraction coefficient n2 and third-order nonlinear susceptibility χ(3) were found to be of the order of 10−5 cm/W, 10−8 cm2/W and 10−6 esu, respectively. The value of the two-photon absorption (2 PA) cross section at 532 nm for both chalcones is of the order of 108 GM. These crystals also exhibited optical limiting (OL) properties under CW laser excitation.

(E)-1-(2-Aminophenyl)-3-(benzo[d][1,3]dioxol-5-yl)prop-2-en-1-one

The title chalcone (E)-1-(2-aminophenyl)-3-(benzo[d][1,3]dioxol-5-yl)prop-2-en-1-one was obtained in 76% yield from a NaOH catalyzed Claisen–Schmidt condensation reaction between o-aminoacetophenone and piperonal. This product will be used as a key precursor for the development of an alternative route for the total synthesis of the alkaloid Graveoline. Single crystals of the title compound suitable for X-ray diffraction were grown via slow evaporation in ethanol at room temperature. A complete crystallographic study was performed in depth to unequivocally confirm its structure. The crystal structure of the title o-aminochalcone, C16H13NO3, shows two molecules per asymmetric unit (Z = 4) and adopts an E configuration about the C=C double bond. In the title compound, the mean plane of the non-H atoms of the central chalcone fragment C—C(O)—C—C—C is as follow: [root-mean-square (r.m.s.) deviation = 0.0210 A for A–B and 0.0493 for C–D molecules]. In the crystal, molecules are linked by N–H...O and C–H...O, hydrogen bonds forming S(6), R22(6) and edge-fused R44(24)rings along with C(18) chains running parallel to (110).

Preparation, characterisation, and crystal structure analysis of (2E,2′E)-3,3′-(1,4-phenylene)bis(1-(2-aminophenyl)prop-2-en-1-one

A novel bis-chalcone, (2E,2′E)-3,3′-(1,4-phenylene)bis(1-(2-aminophenyl)prop-2-en-1-one) is synthesized through a base catalyzed Claisen-Schmidt condensation reaction of terephthalaldehyde with 2-aminoacetophenone. Its structure (sp. gr. P $$\bar 1$$ , Z = 2) is determined from single crystal X-ray diffraction data. There are two independent centrosymmetric molecules with no significant differences in bond lengths and angles between them. The NMR, IR, HRMS, and UV spectral data of the prepared bis-chalcone are presented.