Clauson-Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach.

Pyrrole is an important aromatic heterocyclic scaffold found in many natural products and predominantly used in pharmaceuticals. Continuous efforts are being made to design and synthesize various pyrrole derivatives using different synthetic procedures. Among them, the Clauson-Kaas reaction is a very old and well-known method for synthesizing a large number of N-substituted pyrroles. In recent years, due to global warming and environmental concern, research laboratories and pharmaceutical industries around the world are searching for more environmentally friendly reaction conditions for synthesizing compounds. As a result, this review describes the use of various eco-friendly greener protocols to synthesize N-substituted pyrroles. This synthesis involves the reaction of various aliphatic/aromatic primary amines, and sulfonyl primary amines with 2,5-dimethoxytetrahydrofuran in the presence of numerous acid catalysts and transition metal catalysts. The goal of this review is to summarize the synthesis of various N-substituted pyrrole derivatives using a modified Clauson-Kaas reaction under diverse conventional and greener reaction conditions.

Synthesis of novel potent cytotoxicy podophyllotoxin-naphthoquinone compounds via microwave-assited multicomponent domino reactions.

A series of novel podophyllotoxin-naphthoquinone compounds 5a-p were synthesized in good yields using microwave-assisted four-component reactions of 2-hydroxy-1,4-naphthoquinone, aromatic benzaldehydes, tetronic acid and ammonium acetate. All the synthesized compounds were fully characterized by spectral data and evaluated for their cytotoxicity activities against KB, HepG2, Lu1, MCF7, and non-cancerous Hek-293 cell lines. Among 16 new compounds screened, compounds 5a, 5d, 5h, and 5k displayed high potent inhibitory activities with IC50 < 40 nM against HepG2 and SK-Lu-1 cell lines, and showed lower toxicity for non-cancerous Hek-293 cell line, demonstrating the potential importance of these compounds in the development of potential anticancer agents.

Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki-Heck reaction.

A series of new phosphonocarboxylates containing an imidazo[1,2-a]pyridine ring has been synthesized via the microwave-assisted Mizoroki-Heck reaction. The efficient modification of the imidazo[1,2-a]pyridine ring has been achieved as late-stage functionalization, enabling and accelerating the generation of a library of compounds from a common precursor.

Ecofriendly microwave-assisted reaction and extraction of bioactive compounds from hawthorn leaf.

INTRODUCTION: The main active components in hawthorn leaves possess various biological activities such as anti-inflammatory, antioxidant, and hypolipidemic effects. Therefore, it is necessary to develop an effective and reliable extraction method to extract these active compounds from hawthorn leaves. OBJECTIVE: To establish a simple, rapid, and sensitive method for extraction and determination of polyphenolic compounds from hawthorn leaves. METHODS: In this study, a microwave-assisted reaction and extraction (MARE) combined with ultra-high-performance liquid chromatography with ultraviolet detector method was established to extract and determine the polyphenolic compounds in hawthorn leaves. The solid reagent aqueous solutions were applied as extraction solvents, preventing the use of organic solvents. The target analytes were identified by quadrupole time-of-flight tandem mass spectrometry. Several experimental parameters that can significantly affect the extraction efficiency were evaluated and optimised. RESULTS: The optimal conditions were as follows: 0.1 g of sodium carbonate was used as solid reagent, the amount of sodium borate was set at 0.01 g, extraction time was 10 min, extraction temperature was set at 50°C, pH value was adjusted to 7. The validation experiments demonstrated that the method had high sensitivity with the limits of detection in the range 26.5-37.7 ng/mL. The average recoveries ranged from 80.22% to 93.27%. CONCLUSION: In this work, the proposed MARE method was successfully applied to extract and determine polyphenolic compounds in hawthorn leaf samples. Compared with other reported methods, the present method was faster, greener, and more sensitive.

Optimizing the Synthetic Route of Chromone-2-carboxylic Acids: A Step forward to Speed-Up the Discovery of Chromone-Based Multitarget-Directed Ligands.

6-Bromochromone-2-carboxylic acid (3) was synthesized by a microwave-assisted process. The optimization of the reaction was performed varying parameters, such as type of base/number of reagent equivalents, solvent, temperature and reaction time. The yield of the reaction was improved to 87%. The new synthetic route is versatile as several chromone-2-carboxylic acids (compounds 4B-10B) were obtained with good yields (54-93%). Only in the case of the nitro substituent (compound 11B), an ester was obtained instead of the desired carboxylic acid. Following this synthetic route chromone carboxylic acids can be attained with a high degree of purity, without the need of the tedious and expensive purification processes through column chromatography. The reaction is safe, cost-effective, fast and robust, and can be used in the development of concise and diversity-oriented libraries based on chromone scaffold. The overall study can be looked as a step forward to speed-up the discovery of chromone-based multitarget-directed ligands.

Synthesis, biological activities and pharmacokinetic properties of new fluorinated derivatives of selective PDE4D inhibitors.

A new series of selective PDE4D inhibitors has been designed and synthesized by replacing 3-methoxy group with 3-difluoromethoxy isoster moiety in our previously reported cathecolic structures. All compounds showed a good PDE4D3 inhibitory activity, most of them being inactive toward other PDE4 isoforms (PDE4A4, PDE4B2 and PDE4C2). Compound 3b, chosen among the synthesized compounds as the most promising in terms of inhibitory activity, selectivity and safety, showed an improved pharmacokinetic profile compared to its non fluorinated analogue. Spontaneous locomotor activity, assessed in an open field apparatus, showed that, differently from rolipram and diazepam, selective PDE4D inhibitors, such as compounds 3b, 5b and 7b, did not affect locomotion, whereas compound 1b showed a tendency to reduce the distance traveled and to prolong the immobility period, possibly due to a poor selectivity.

Comparative life cycle cost analysis of bio-valorized magnetite nanocatalyst for biodiesel production: Modeling, optimization, kinetics and thermodynamic study.

An active, high surface area, recyclable, magnetic, basic, iron oxide-based nanocatalyst was developed from banana leaves waste and used for microwave-assisted transesterification of soybean oil to biodiesel. According to the Hammett indicator, the catalyst has a high total basicity of 15 < H < 18.4. After optimization through the response surface methodology, the reaction allows 96.5 % biodiesel yield in the presence of 24:1 methanol to soybean oil molar ratio, 6 wt% BLW@Fe3O4, 0.5 h at 65 °C. The magnetic nature of the catalyst improves reusability for up to 6 cycles. Thermodynamic analyses showed that transesterification of soybean oil to biodiesel is an endothermic reaction. Moreover, the catalyst has the potential to reduce biodiesel production costs by utilizing abundant biomass waste materials. The calculated cost for 1 kg of catalyst is $1.14, while the biodiesel's cost per kg produced in this work is merely $1.05, showing high commercial viability.

One-pot sequential synthesis of isocyanates and urea derivatives via a microwave-assisted Staudinger-aza-Wittig reaction.

A fast and efficient protocol for the synthesis of N,N'-disubstituted urea derivatives from alkyl halides and primary or secondary amines has been developed. The synthetic pathway combines nucleophilic substitutions and a Staudinger-aza-Wittig reaction in the presence of polymer-bound diphenylphosphine under 14 bar of CO2 pressure and has been performed in a one-pot two-step process. The protocol has been optimized under microwave irradiation and the scale-up experiment has been conducted under conventional conditions in a Parr reactor. The final compounds were isolated after simple filtration in almost quantitative overall yields which makes this procedure facile and rapid to execute.

Microwave accelerated transglycosylation of rutin by cyclodextrin glucanotransferase from Bacillus sp. SK13.002.

Rutin was subjected to intermolecular transglycosylation assisted with microwave irradiation using cyclodextrin glucanotransferase (CGTase) produced from Bacillus sp. SK13.002. Compared with the conventional enzymatic method for rutin transglycosylation (without microwave irradiation), microwave-assisted reaction (MAR) was much faster and thus more efficient. While the conventional reaction took dozens of hours to reach the highest conversion rate of rutin and yield of transglycosylated rutin, MAR of rutin transglycosylation completed within only 6 min providing almost the same conversion rate of rutin and yield of products consisting of mono-, di-, tri-, tetra-, penta-glucosylated rutins. The optimum transglycosylation conditions for microwave irradiation were 40 °C and 60 W with the reaction system consisting mainly of the mixture of 0.3 g rutin (0.49 mmol) pre-dissolved in 15 mL methanol, 1.8 g maltodextrin in 15 mL of 0.2 M sodium acetate buffer (pH 5.5) and CGTase (900 U). Results from this study indicated that MAR could be a potentially useful and economical technique for a faster and more efficient transglycosylation of rutin.

Microwave-Assisted, One-Pot Synthesis of Doxycycline under Heterogeneous Catalysis in Water.

The selective synthesis of active pharmaceutical molecules is a challenging issue, particularly when attempting to make the reactions even more sustainable. The present work focuses on the microwave-assisted hydrogenolysis of oxytetracycline to selectively produce α-doxycycline. Although the combination of microwave irradiation and a heterogeneous rhodium catalyst provided good conversions, the selective synthesis of active α-doxycycline was only achieved when an oxytetracycline-cyclodextrin complex was used as the starting material, giving the desired product at 34.0% yield in a one-step reaction under very mild conditions.

Polymer-Based Graphene Derivatives and Microwave-Assisted Silver Nanoparticles Decoration as a Potential Antibacterial Agent.

Nanocomposites obtained by the decoration of graphene-based materials with silver nanoparticles (AgNPs) have received increasing attention owing to their antimicrobial activity. However, the complex synthetic methods for their preparation have limited practical applications. This study aims to synthesize novel NanoHybrid Systems based on graphene, polymer, and AgNPs (namely, NanoHy-GPS) through an easy microwave irradiation approach free of reductants and surfactants. The polymer plays a crucial role, as it assures the coating layer/substrate compatibility making the platform easily adaptable for a specific substrate. AgNPs' loading (from 5% to 87%) can be tuned by the amount of Silver salt used during the microwave-assisted reaction, obtaining spherical AgNPs with average sizes of 5-12 nm homogeneously distributed on a polymer-graphene nanosystem. Interestingly, microwave irradiation partially restored the graphene sp2 network without damage of ester bonds. The structure, morphology, and chemical composition of NanoHy-GPS and its subunits were characterized by means of UV-vis spectroscopy, thermal analysis, differential light scattering (DLS), Field Emission Scanning Electron Microscopy (FE-SEM), Energy Dispersive X-ray analysis (EDX), Atomic Force Microscopy (AFM), and High-Resolution Transmission Electron Microscopy (HRTEM) techniques. A preliminary qualitative empirical assay against the typical bacterial load on common hand-contacted surfaces has been performed to assess the antibacterial properties of NanoHy-GPS, evidencing a significative reduction of bacterial colonies spreading.

Synthesis of bioactive quinazolin-4(3H)-one derivatives via microwave activation tailored by phase-transfer catalysis.

A series of nine new 2,3-disubstituted 4(3H)-quinazolin-4-one derivatives was furnished starting from the 2-propyl-4(3H)-quinazo-line-4-one (2). The reinvestigation of the key starting quinazolinone 2 was performed under microwave irradiation (MW) and solvent-free conditions. Combination of MW and phase-transfer catalysis using tetrabutylammonium benzoate (TBAB) as a novel neutral ionic catalyst was used for carrying out N-alkylation and condensation reactions of compound 2 as a simple, efficient and eco-friendly technique. The structure of the synthesized compounds was elucidated using different spectral and chemical analyses. In vitro antimicrobial activity of the compounds was investigated against four bacterial and two fungal strains; very modest activity was achieved. Some of the synthesized compounds were screened for their antitumor activity against different human tumor cell lines. The screened compounds exhibited a significant antitumor activity on some of the cancer cell lines, melanoma (SK-MEL-2), ovarian cancer (IGROV1), renal cancer (TK-10), prostate cancer (PC-3), breast cancer (MCF7) and colon cancer (HT29). The most active, even more active than the reference 5-fluorouracil, were found to be ethyl 4-[(4-oxo-2-propylquinazolin-3(4H)-yl)methyl]benzoate (3c), 3-{2-[6-(pyrrolidin-1-yl-sulfonyl)-1,2,3,4-tetrahydroquinoline]-2-oxoethyl}-2-propylquinazolin--4(3H)-one (3e), N'-[(E)-(2H-1,3-benzodioxo-5-yl)methylidene]-2-(4-oxo-2-propylquinazolin-3(4H)-yl)acetohydrazide (10a), N'-[(E)-(4-hydroxyphenyl)methylidene]-2-(4-oxo-2-propylquinazo-lin-3(4H) -yl)acetohydrazide (10b) and N'-[(E)-(4-nitrophenyl)methyl idene]-2-(4-oxo-2-propylquinazolin-3(4H)-yl)acetohydrazide (10c).

Catalyst- and solvent-free synthesis of 2-fluoro-N-(3-methylsulfanyl-1H-1,2,4-triazol-5-yl)benzamide through a microwave-assisted Fries rearrangement: X-ray structural and theoretical studies.

An efficient approach for the regioselective synthesis of (5-amino-3-methylsulfanyl-1H-1,2,4-triazol-1-yl)(2-fluorophenyl)methanone, C10H9FN4OS, (3), from the N-acylation of 3-amino-5-methylsulfanyl-1H-1,2,4-triazole, (1), with 2-fluorobenzoyl chloride has been developed. Heterocyclic amide (3) was used successfully as a strategic intermediate for the preparation of 2-fluoro-N-(3-methylsulfanyl-1H-1,2,4-triazol-5-yl)benzamide, C10H9FN4OS, (4), through a microwave-assisted Fries rearrangement under catalyst- and solvent-free conditions. Theoretical studies of the prototropy process of (1) and the Fries rearrangement of (3) to provide (4), involving the formation of an intimate ion pair as the key step, were carried out by density functional theory (DFT) calculations. The crystallographic analysis of the intermolecular interactions and the energy frameworks based on the effects of the different molecular conformations of (3) and (4) are described.

Studies via X-ray analysis on intermolecular interactions and energy frameworks based on the effects of substituents of three 4-aryl-2-methyl-1H-imidazoles of different electronic nature and their in vitro antifungal evaluation.

The crystal structures of 2-methyl-4-phenyl-1H-imidazole, C10H10N2, (3a), 4-(4-chlorophenyl)-2-methyl-1H-imidazole hemihydrate, C10H9ClN2·0.5H2O, (3b), and 4-(4-methoxyphenyl)-2-methyl-1H-imidazole, C11H12N2O, (3c), have been analyzed. It was found that the electron-donating/withdrawing tendency of the substituent groups in the aryl ring influence the acid-base properties of the 2-methylimidazole nucleus, changing the strength of the intermolecular N-H...N interactions. This behaviour not only influences the crystal structure but also seems to have an important effect on the antifungal activity. Considering the substituent groups, that is, H in (3a), Cl in (3b) and OMe in (3c), the formation of strong N-H...N connections has the probability (3a) > (3b) > (3c), while compound (3c) proves to be more active than (3a) and (3b) at all concentrations against C. neoformans.

A series of (E)-5-(arylideneamino)-1-tert-butyl-1H-pyrrole-3-carbonitriles and their reduction products to secondary amines: syntheses and X-ray structural studies.

An efficent access to a series of N-(pyrrol-2-yl)amines, namely (E)-1-tert-butyl-5-[(4-chlorobenzylidene)amino]-1H-pyrrole-3-carbonitrile, C16H16ClN3, (7a), (E)-1-tert-butyl-5-[(2,4-dichlorobenzylidene)amino]-1H-pyrrole-3-carbonitrile, C16H15Cl2N3, (7b), (E)-1-tert-butyl-5-[(pyridin-4-ylmethylene)amino]-1H-pyrrole-3-carbonitrile, C15H16N4, (7c), 1-tert-butyl-5-[(4-chlorobenzyl)amino]-1H-pyrrole-3-carbonitrile, C16H18ClN3, (8a), and 1-tert-butyl-5-[(2,4-dichlorobenzyl)amino]-1H-pyrrole-3-carbonitrile, C16H17Cl2N3, (8b), by a two-step synthesis sequence (solvent-free condensation and reduction) starting from 5-amino-1-tert-butyl-1H-pyrrole-3-carbonitrile is described. The syntheses proceed via isolated N-(pyrrol-2-yl)imines, which are also key synthetic intermediates of other valuable compounds. The crystal structures of the reduced compounds showed a reduction in the symmetry compared with the corresponding precursors, viz. Pbcm to P-1 from compound (7a) to (8a) and P21/c to P-1 from compound (7b) to (8b), probably due to a severe change in the molecular conformations, resulting in the loss of planarity observed in the nonreduced compounds. In all of the crystals, the supramolecular assembly is controlled mainly by strong (N,C)-H...N hydrogen bonds. However, in the case of (7a)-(7c), C-H...Cl interactions are strong enough to help in the three-dimensional architecture, as observed in Hirshfeld surface maps.

Solution Synthesized p-Type Copper Gallium Oxide Nanoplates as Hole Transport Layer for Organic Photovoltaic Devices.

p-Type metal-oxide hole transport layer (HTL) suppresses recombination at the anode and hence improves the organic photovoltaic (OPV) device performance. While NiOx has been shown to exhibit good HTL performance, very thin films (<10 nm) are needed due to its poor conductivity and high absorption. To overcome these limitations, we utilize CuGaO2, a p-type transparent conducting oxide, as HTL for OPV devices. Pure delafossite phase CuGaO2 nanoplates are synthesized via microwave-assisted hydrothermal reaction in a significantly shorter reaction time compared to via conventional heating. A thick CuGaO2 HTL (∼280 nm) in poly(3-hexylthiophene):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCBM) devices achieves 3.2% power conversion efficiency, on par with devices made with standard HTL materials. Such a thick CuGaO2 HTL is more compatible with large-area and high-volume printing process.

Visible light photocatalytic degradation of dyes by bismuth oxide-reduced graphene oxide composites prepared via microwave-assisted method.

Bi2O3-reduced graphene oxide (RGO) composites were successfully synthesized via microwave-assisted reduction of graphite oxide in Bi2O3 precursor solution using a microwave system. Their morphologies, structures, and photocatalytic performance in the degradation of methylene blue (MB) and methyl orange (MO) were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction spectroscopy, UV-vis absorption spectroscopy, and electrochemical impedance spectroscopy, respectively. The results show that the RGO addition can enhance the photocatalytic performance of Bi2O3-RGO composites. Bi2O3-RGO composite with 2 wt.% RGO achieves maximum MO and MB degradation rates of 93% and 96% at 240min under visible light irradiation, respectively, much higher than those for the pure Bi2O3 (78% and 76%). The enhanced photocatalytic performance is ascribed to the increased light adsorption and the reduction in electron-hole pair recombination in Bi2O3 with the introduction of RGO.