Quantitative Yield Research Articles

Synthesis and single crystal X-ray studies of bis-(trimethylsilylmethyl) tellurium diiodide through an insertion route

The synthesis and single crystal X-ray studies of bis(trimethylsilylmethyl) telluriumdiiodide was studied through an insertion route with quantitative yield. This molecule was characterized with the help of 1H NMR, elemental analysis and single-crystal X-ray studies. The new crystalline molecule provides a supramolecular synthon in crystal lattices of tellurium(IV) diiodide showing 2d synthons associated with the help of C-H - - - I interactions.

L-proline-based deep eutectic solvents as green and enantioselective organocatalyst/media for aldol reaction

The use of chiral deep eutectic solvents (DESs) based on the natural amino acid L-proline and various glycols presents an environmentally friendly approach for important CC bond formation reactions. These DESs serve as both organocatalysts and reaction media in the aldol reaction, reducing the need for additional toxic or hazardous chemicals. By employing these DESs, we were able to activate the desired reaction through the condensation of ketones and L-proline via enamine activation. This approach eliminates the requirement for traditional, often environmentally harmful, organic solvents. Notably, diethylene glycol played a crucial role in modulating the reaction performance, including conversion and enantioselectivity. Diethylene glycol is a relatively safer alternative compared to other commonly used solvents or additives with potential environmental and health risks. Moreover, reducing the L-proline content in the DESs led to a slight increase in the enantiomeric excess of the predominant diastereomeric product. This finding suggests the possibility of minimizing the use of L-proline, which can be advantageous from both cost and environmental perspectives.The results of these reactions demonstrate promising green outcomes, with a diastereomeric ratio up to 25:1 for the major anti-isomer, showcasing excellent selectivity (>90 % ee). In addition to these high enantiomeric excess values, quantitative yields in the aldol reaction highlight the potential for high efficiency and reduced waste production.Overall, the utilization of chiral DESs based on L-proline and glycols offers a greener alternative for enantioselective organocatalytic reactions. This approach minimizes the use of hazardous catalysts, reduces waste generation, and demonstrates impressive selectivity, paving the way for more sustainable synthetic methodologies.

Synthesis of Selenium-Containing N-Quinazolinyl Acroleins via a 3,3-Radical Rearrangement Cascade Reaction.

An effective approach for the construction of 2-aryl-3-(3-oxo-1-aryl-2-(organoselanyl)prop-1-en-1-yl)quinazolin-4(3H)-ones was developed. Excellent to almost quantitative yields were obtained by the cascade reaction of propargyl quinazoline-4-yl ethers, diselenides, and 70% tert-butyl hydrogen peroxide aqueous solution under metal-free and mild conditions. The synthesized hybrids, with conglomeration of quinazolinone, organoselenium, aldehyde, and fully substituted alkene moieties in one molecule, will have the potential for applications in development of new drugs or drug candidates.

Sustainable methods for the carboxymethylation and methylation of ursolic acid with dimethyl carbonate under mild and acidic conditions.

Ursolic acid is a triterpene plant extract that exhibits significant potential as an anti-cancer, anti-tumour, and anti-inflammatory agent. Its direct use in the pharmaceutical industry is hampered by poor uptake of ursolic acid in the human body coupled with rapid metabolism causing a decrease in bioactivity. Modification of ursolic acid can overcome such issues, however, use of toxic reagents, unsustainable synthetic routes and poor reaction metrics have limited its potential. Herein, we demonstrate the first reported carboxymethylation and/or methylation of ursolic acid with dimethyl carbonate (DMC) as a green solvent and sustainable reagent under acidic conditions. The reaction of DMC with ursolic acid, in the presence of PTSA, ZnCl2, or H2SO4-SiO2 yielded the carboxymethylation product 3β-[[methoxy]carbonyl]oxyurs-12-en-28-oic acid, the methylation product 3β-methoxyurs-12-en-28-oic acid and the dehydration product urs-2,12-dien-28-oic acid. PTSA demonstrated high conversion and selectivity towards the previously unreported carboxymethylation of ursolic acid, while the application of formic acid in the system led to formylation of ursolic acid (3β-formylurs-12-en-28-oic acid) in quantitative yields via esterification, with DMC acting solely as a solvent. Meanwhile, the methylation product of ursolic acid, 3β-methoxyurs-12-en-28-oic acid, was successfully synthesised with FeCl3, demonstrating exceptional conversion and selectivity, >99% and 99%, respectively. Confirmed with the use of qualitative and quantitative green metrics, this result represents a significant improvement in conversion, selectivity, safety, and sustainability over previously reported methods of ursolic acid modification. It was demonstrated that these methods could be applied to other triterpenoids, including corosolic acid. The study also explored the potential pharmaceutical applications of ursolic acid, corosolic acid, and their derivatives, particularly in anti-inflammatory, anti-cancer, and anti-tumour treatments, using molecular ADMET and docking methods. The methods developed in this work have led to the synthesis of novel molecules, thus creating opportunities for the future investigation of biological activity and the modification of a wide range of triterpenoids applying acidic DMC systems to deliver novel active pharmaceutical intermediates.

Deville rebooted - practical N2O5 synthesis.

Dinitrogen pentoxide (N2O5), the anhydride of nitric acid, was synthesised by Henri Étienne Sainte-Claire Deville in Paris in 1849 using silver nitrate and chlorine gas. Herein, we revisit, optimise, and modify Deville's method using photocatalysis to enable a safe, clean, practical, and reproducible alternative for N2O5 synthesis in quantitative yields. Moreover, it is predicted that the modifications can accommodate an industrial scale-up, but the silver chloride generated must be recycled.

Synthesis and characterization of divalent metal-betaine-bistriflimide complexes: a property comparison with metal bistriflimide salts.

A panel of metal-betaine-bistriflimide complexes (with minimum formula M[Bet]2[Tf2N]2, where M = Mg, Ca, Zn, Cu and Ni) has been prepared in high purity and a quantitative yield. In parallel, a series of metal bistriflimide salts (sharing the same metal cations) has been synthesized and characterized though the same set of techniques. The current work presents a first comprehensive investigation of the physical-chemical properties of these two classes of metal systems, whose importance in a variety of applicative fields was not yet matched, to the best of our knowledge, by an adequate study of their characteristics. All the considered compounds have been spectroscopically, thermally and electrochemically characterized, and their solubility characteristics assessed, gaining insights into the role of metal cations in the definition of their properties. On the other hand, the evident effect of the betaine coordination on the prepared complexes' solubility, thermal stability, melting point, glass and solid-solid transitions, redox behaviour and electrochemical window was ascertained, providing results which would allow a more informed use and application of these classes of divalent metal complexes.

Activity against Mycobacterium tuberculosis of a new class of spirooxindolopyrrolidine embedded chromanone hybrid heterocycles.

A new class of structurally intriguing heterocycles embedded with spiropyrrolidine, oxindole and chromanones was prepared by regio- and stereoselectively in quantitative yields using an intermolecular tandem cycloaddition protocol. The compounds synthesized were assayed for their anti-mycobacterial activity against Mycobacterium tuberculosis (Mtb) H37Rv and isoniazid-resistant (katG and inhA promoter mutations) clinical Mtb isolates. Four compounds exhibited significant antimycobacterial activity against Mtb strains tested. In particular, a compound possessing a fluorine substituted derivative displayed potent activity at 0.39 μg mL-1 against H37Rv, while it showed 0.09 μg mL-1 and 0.19 μg mL-1 activity against inhA promoter and katG mutation isolates, respectively. A molecular docking study was conducted with the potent compound, which showed results that were consistent with the in vitro experiments.

Exploring 7β-amino-6-nitrocholestens as COVID-19 antivirals: in silico, synthesis, evaluation, and integration of artificial intelligence (AI) in drug design: assessing the cytotoxicity and antioxidant activity of 3β-acetoxynitrocholestane.

In light of the ongoing pandemic caused by SARS-CoV-2, effective and clinically translatable treatments are desperately needed for COVID-19 and its emerging variants. In this study, some derivatives, including 7β-aminocholestene compounds, and 3β-acetoxy-6-nitrocholesta-4,6-diene were synthesized, in quantitative yields from 7β-bromo-6-nitrocholest-5-enes (1-3) with a small library of amines. The synthesized steroidal products were then thoroughly characterized using a range of physicochemical techniques, including IR, NMR, UV, MS, and elemental analysis. Next, a virtual screening based on structures using docking studies was conducted to investigate the potential of these synthesized compounds as therapeutic candidates against SARS-CoV-2. Specifically, we evaluated the compounds' binding energy of the reactants and their products with three SARS-CoV-2 functional proteins: the papain-like protease, 3C-like protease or main protease, and RNA-dependent RNA polymerase. Our results indicate that the 7β-aminocholestene derivatives (4-8) display intermediate to excellent binding energy, suggesting that they interact strongly with the receptor's active amino acids and may be promising drug candidates for inhibiting SARS-CoV-2. Although the starting steroid derivatives; 7β-bromo-6-nitrocholest-5-enes (1-3) and one steroid product; 3β-acetoxy-6-nitrocholesta-4,6-diene (9) exhibited strong binding energies with various SARS-CoV-2 receptors, they did not meet the Lipinski Rule and ADMET properties required for drug development. These compounds showed either mutagenic or reproductive/developmental toxicity when assessed using toxicity prediction software. The findings based on structure-based virtual screening, suggest that 7β-aminocholestaines (4-8) may be useful for reducing the susceptibility to SARS-CoV-2 infection. The docking pose of compound 4, which has a high score of -7.4 kcal mol-1, was subjected to AI-assisted deep learning to generate 60 AI-designed molecules for drug design. Molecular docking of these AI molecules was performed to select optimal candidates for further analysis and visualization. The cytotoxicity and antioxidant effects of 3β-acetoxy-6-nitrocholesta-4,6-diene were tested in vitro, showing marked cytotoxicity and antioxidant activity. To elucidate the molecular basis for these effects, steroidal compound 9 was subjected to molecular docking analysis to identify potential binding interactions. The stability of the top-ranked docking pose was subsequently assessed using molecular dynamics simulations.

Trifluoroacetic acid-mediated synthesis of xanthene constructs and their extensive anti-tuberculosis evaluation.

A diverse range of 9-substituted 1,8-dioxohexahydroxanthenes was conceptualized and synthesized through a TFA-mediated approach in near quantitative yields without the use of column chromatography. From a series of 25 compounds, we found that compounds 14c and 14r exhibited promising anti-tuberculosis potential against avirulent and virulent strains of Mycobacterium tuberculosis with a Minimal Inhibitory Concentration (MIC) of 8 μg ml-1, achieving 99% bactericidal activity at the same concentration. This series of compounds was found to be inactive against common Gram-positive and Gram-negative pathogens, indicating that the activity is mycobacteria-specific. Since the strategies for treating tuberculosis employ a combinatorial therapy, we tested and observed that the two lead compounds displayed synergistic behavior with known anti-TB drugs (ATDs) and a significant (16-32 fold) decrease in MIC values of both leads was observed in combination with either RIF or INH. Interestingly the lead molecule 14c displayed only time-dependent kill kinetics and sterilized the whole culture of Mycobacterium tuberculosis H37Rv in just 48 hours.

Catalytically transforming legacy phthalate esters from plastic waste into benzoic acid and benzoate plasticizers.

This study demonstrates the catalytic conversion of real plastic waste-extracted phthalate plasticizers into benzoic acid (BA), via a one-pot hydrolysis-decarboxylation process based on inexpensive Cu2O and H-beta zeolite, in water as a safe and environmentally benign solvent. As a result of the excellent product selectivity in both reactions, BA was obtained in quantitative yields (>99%). Esterification of the purified carboxylic acid resulted in the production of an alternative benzoate plasticizer, with a total process yield up to 94%.

Intramolecular trapping of an iminium salt: rapid construction of quindoline derivatives.

Construction of the pyridine ring is a practical and streamline way to construct a variety of quindoline derivatives. We have developed a novel method for synthesis of quindoline derivatives by means of intramolecular ring-closure reactions of 3-N-methylphenylindoles via an iminium salt intermediate. This practical method has the advantages of a short reaction time, operational simplicity, and nearly quantitative yields; and it can be used for the rapid synthesis of a variety of valuable quindoline derivatives.

(TeCl)4(TiCl4) with isolated Te4Cl16 and TiCl4 molecules and second-harmonic-generation.

(TeCl4)4(TiCl4) is obtained by reaction of TeCl4 and TiCl4 at 50 °C with quantitative yield. The compound is composed of isolated, molecular (TeCl4)4 heterocubane-type units as well as isolated, molecular TiCl4 tetrahedra. The (TeCl4)4 heterocubane is arranged like a body-centred cubic cell with TiCl4 tetrahedra occupying 4 of 6 octahedral sites. (TeCl4)4(TiCl4) crystallizes in the space group I4̄ with an unidirectional alignment of the tetrahedral building units. The structure of the compound is obtained from single crystal X-ray diffraction and confirmed by Rietveld refinement of powder diffraction data. Thermogravimetry, optical spectroscopy, infrared and Raman spectroscopy are employed to further characterize the title compound. Second harmonic generation (SHG) is observed with a strong intensity (1.6-times higher than potassium dihydrogen phosphate/KDP). The SHG effect is observed in the visible spectral regime as the band gap, derived from a Tauc plot, is 2.8 eV.

1,4:3,6-Dianhydrohexites

It is known that derivatives of isosorbide and isomannide can impart a sweet taste, for example, dimethyl ether of isosorbide is used as an ingredient in the production of chewing gums, hard sweets [1], isosorbide dipropanoate is widely used in the production of bakery products [1]. Mixed isohexite esters and esters (especially isosorbide) are used as flavor enhancers. Currently, isosorbide is proposed to be used as a component of the mixture used for the water-base ink pigment. This component has excellent dispersion stability, which is necessary for printing [1]. All production methods leading to isohexites use the corresponding hexitol as the starting material. To obtain isohexites with a quantitative yield, and in order to avoid adverse reactions, a number of techniques have been developed. The rate of the dehydration sequence in reactions using as the starting compound: 1,4-anhydro derivatives of D-iditol, D-gulitol, D-glucitol, and D-mannitol (from which 1,4:3,6-dianhydro compounds of isoidide (5) and isomannide (4) are obtained) depends on the location of the hydroxyl group (with5 endo as in D-mannitol and D-glucitol, or exo as in D-iditol and D-glucitol). All three isohexites (3-5) were studied by mass spectrometry, especially D-isomannide and their O-deuterated isomers, and 5-nitroisosorbide [1]. The isomannide cation formed as a result of dehydration reactions was also detected in the mass spectra of some isomannide derivatives [1]. Mass spectrometric analysis is used to determine isosorbide and its 5-nitro derivative in human urine and blood plasma.

Polydentate chalcogen bonding: anion trapping with a water-stable host compound carrying Se-CF3 functions.

Bidentate and tetradentate chalcogen bonding host systems with SeCF3 functions as σ-hole donors in close proximity at the alkyne functions of 1,8-diethynylanthracene and its syn-dimer were prepared in quantitative yield by tin-selenium exchange reactions of the corresponding trimethylstannyl precursors with ClSeCF3. The bidentate system shows chalcogen bonding interactions with THF, but does not bind halide ions. The tetradentate system cooperatively chelates chloride, bromide and iodide ions with its four CC-SeCF3 units by rotating the four σ-holes towards the halide ion. The structures of these halide ion adducts were determined by X-ray diffraction. The hydrobromide and -iodide salts of the ethyl derivative of Schwesinger's phosphazene superbase served as halide salts with very weakly coordinating cations.

An organic-organometallic CO-releasing material comprising 4,4'-bipyridine and molybdenum subcarbonyl building blocks.

Over the past two decades, following the discovery of the important biological roles of carbon monoxide (CO), metal carbonyl complexes have been intensively studied as CO-releasing molecules (CORMs) for therapeutic applications. To improve the properties of "bare" low molecular weight CORMs, attention has been drawn to conjugating CORMs with macromolecular and inorganic scaffolds to produce CO-releasing materials (CORMAs) capable of storing and delivering large payloads of the gasotransmitter. A significant obstacle is to obtain CORMAs that retain the beneficial features of the parent CORMs. In the present work, a crystalline metal-organic framework (MOF) formulated as Mo(CO)3(4,4'-bipyridine)3/2 (Mobpy), with a structure based on Mo(CO)3 metallic nodes and bipyridine linkers, has been prepared in near quantitative yield by a straightforward reflux method, and found to exhibit CO-release properties that mimic those typically observed for molybdenum carbonyl CORMs. Mobpy was characterized by powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), FT-IR, FT-Raman and diffuse reflectance (DR) UV-vis spectroscopies, and 13C{1H} cross-polarization (CP) magic-angle spinning (MAS) NMR. The release of CO from Mobpy was studied by the deoxy-myoglobin (deoxy-Mb)/carbonmonoxy-myoglobin (MbCO) UV-vis assay. Mobpy liberates CO upon contact with a physiological buffer in the dark, leading to a maximum released amount of 1.3-1.5 mmol g-1, after 1.5 h at 37 °C, with half-lives of 0.5-1.0 h (time to transfer 0.5 equiv. of CO to Mb). In the solid-state and under open air, Mobpy undergoes complete decarbonylation over a period of 42 days, corresponding to a theoretical CO-release of 7.25 mmol g-1.

Agro-Physiologic Traits of Soybean in Response to Biological Fertilizers

Plant nutrition is one of the most important environmental factors affecting the quantitative and qualitative yield of crops. This study investigated the effect of rhizobium and azospirillum inoculum and foliar application of humic acid and nutrients of molybdenum, cobalt, and boron on node formation, yield, yield components, and morpho-phenological traits of soybean (Saman cultivar). The experiment was carried out in a factorial randomized complete block design at Golestan Agricultural and Natural Resources Research Center in 2018 and 2019 in three replications. The results showed that experimental treatments had a significant effect on the measured traits. Most of the measured traits, including yield, under the influence of seed treatment with bacteria azospirillum and cobalt, molybdenum, boron showed more increase than the control. It was found that under humic treatment, application of bacteria and nutrients can be effective on improvement of seed yield, so the highest seed yield mean (3268 kg/ha) was obtained by humic acid + Rhizobium+Azospirillum + Co+Mo+B treatments. Also, the highest protein yield mean was obtained by humic acid + Rhizobium + Co+Mo+B treatments (1103 kg/ha) and highest mean of oil yield was obtained by humic acid + Rhizobium+Azospirillum + Co+Mo treatments (577 kg/ha). Overall, the results of this study confirmed the efficiency of nitrogen-fixing bacteria as well as foliar application of micronutrients in increasing soybean yield per unit area.

A solvent-free and catalyst-free reaction of o-aminobenzophenone with aryl isothiocyanates: expedient access to congested 4-phenyl-4-hydroxyquinazolin-2-thione derivatives.

An efficient method to construct 4-phenyl-4-hydroxyquinazolin-2-thiones 3via solvent-free and catalyst-free addition of o-aminobenzophenone 1 with aryl isothiocyanates 2 under thermal conditions has been developed, providing new congested 4-phenyl-4-hydroxyquinazolin-2-thiones 3 in practically quantitative yields via simple purification by filtration/recrystallization. Extension of these conditions to o-aminoacetophenone 4 in place of o-aminobenzophenone 1 led to 4-methylenequinazoline-thione 5 as a result of a subsequent dehydration reaction.

Lewis acid catalyzed [4+2] annulation of bicyclobutanes with dienol ethers for the synthesis of bicyclo[4.1.1]octanes.

Bicyclic carbocycles containing a high fraction of Csp3 have become highly attractive synthetic targets because of the multiple applications they have found in medicinal chemistry. The formal cycloaddition of bicyclobutanes (BCBs) with two- or three-atom partners has recently been extensively explored for the construction of bicyclohexanes and bicycloheptanes, but applications to the synthesis of medium-sized bridged carbocycles remained more limited. We report herein the formal [4+2] cycloaddition of BCB ketones with silyl dienol ethers. The reaction occurred in the presence of 5 mol% aluminium triflate as a Lewis acid catalyst. Upon acidic hydrolysis of the enol ether intermediates, rigid bicyclo[4.1.1]octane (BCO) diketones could be accessed in up to quantitative yields. This procedure tolerated a range of both aromatic and aliphatic substituents on both the BCB substrates and the dienes. The obtained BCO products could be functionalized through reduction and cross-coupling reactions.

Visible-light-mediated Diels-Alder reactions under single-chain polymer confinement: investigating the role of the crosslinking moiety on catalyst activity.

Macromolecular scaffolds are rapidly emerging in catalysis owing to the ability to control catalyst placement at precise locations. This spatial proximity allows for enhanced catalyst activity that may not be observed using small molecules. Herein, we describe a triphenylpyrylium (TPT)-based visible-light active single-chain polymer nanoparticle (SCNP) that facilitates the radical cation [4 + 2]-cycloaddition. We find that the catalytic activity is highly dependent on the styrylarene comonomer used, wherein it can act as a redox mediator under confinement, increasing the catalytic turnover (TON) by up to 30 times in comparison to free TPT in solution. Mechanistic studies indicate that TPT excited states are quenched by the acene, with the resultant radical cation formed from naphthalene-based SCNPs able to proceed in oxidizing the dienophile in the elementary step of the reaction, while leading to near quantitative yields of the cycloadduct. The TPT-SCNP demonstrates enhanced photocatalyst efficiency compared to molecular TPT, and is able to be recycled and reused in three iterations of the reaction prior to decreased performance from photobleaching. Our results overall suggest that the confined nature of the SCNP and spatial proximity of acene-based pendants enforces their participation as cocatalytic redox mediators that impart enhanced photoredox catalysis under confinement.

Catalyst-free synthesis of substituted benzimidazoles and benzothiazoles in a sustainable solvent

A catalyst-free synthesis of various 2-alkyl or aryl-substituted benzothiazoles and benzimidazoles has been developed at room temperature by simply combining alkyl or arylaldehydes with ortho-phenylenediamines and 2-aminothiophenols, respectively. The synthesis of these widely applicable fused heterocycles is often challenging and requires additives. The advantages of this new benign procedure include: products with nearly quantitative yields, high atom economy and no toxic waste formation, catalyst-free process with no need for catalyst separation and/or recycling, the use of a green and sustainable solvent, ethanol, and mostly room temperature reactions with moderate reaction times to ensure that the protocol is energetically favorable.