Acetal Formation Research Articles

Design, Synthesis, and Biological Evaluation of Novel Heterocyclic Derivatives of 2,4‐Thiazolidine Dione as Anti‐Cancer Agents

ABSTRACTThis study explores the development of novel 2,4‐thiazolidinedione derivatives as potential anticancer agents. We report the synthesis of 15 novel analogs utilizing a strategic approach focused on intermediate diversification. Key intermediates, (Z)‐5‐([1,1′‐biphenyl]‐4‐ylmethylene)thiazolidine‐2,4‐dione 5a and (Z)‐5‐(benzo[1,3]dioxol‐5‐ylmethylene)thiazolidine‐2,4‐dione 5b, were synthesized via Knoevenagel condensation and acetal formation reactions, respectively. Subsequent N‐alkylation reactions provided a platform for introducing diverse functionalities and exploring structure–activity relationships to optimize the medicinal chemistry profile of these novel compounds. The synthesized compounds were tested against various human cancer cell lines, including for breast (MCF‐7, MDA‐MB‐453), lung (A549), and prostate (PC‐3) cancers, using an MTT assay. Compounds 8c and 10g emerged as particularly promising, exhibiting activity against all tested cell lines with IC50 values between 3.41 ± 0.51 and 40 μM. These compounds also induced apoptosis, suggesting that they inhibit cell proliferation through this cell death pathway. Moreover, relative molecular docking studies provided evidence that compound 8c likely functions by intercalating with DNA.

Characterization of Composite Film Containing Polyvinyl Alcohol Cross‐Linked With Dialdehyde Cellulose Using Citric Acid as a Catalyst for Sustainable Packaging

ABSTRACTThis study is aimed at fabricating composite films by cross‐linking polyvinyl alcohol (PVA) and dialdehyde cellulose (DAC) in varying ratios using citric acid as a catalyst. The acetal formation between the two components was studied using FTIR. Characterizations of the physiochemical properties revealed that increasing the DAC ratio of the composite film improved the hydrophobicity, tensile strength and barrier properties (water vapour, UV and oxygen) of the films while reducing elongation at break (flexibility), swelling and solubility of the film in water. When the DAC ratio was elevated to 50%, the tensile strength was enhanced to 98 MPa. In comparison, flexibility diminished to 29%, the solubility of the film reduced to 10% and water vapour permeability was lower by two orders of magnitude than that of the control PVA film. The peroxide value of linoleic acid decreased from 21.2% ± 7.6 (packed with PVA film) to 9.9% ± 0.9 (packed with 50% DAC composite film) after 15 days. Furthermore, the composite films demonstrated effective absorption of UV radiation, with the order of effectiveness being UV‐C > UV‐B > UV‐A radiation. No significant difference in biodegradability was detected in the composite films with an increase in DAC ratio during indoor soil burial tests for 30 days. This study implies that the composite film could serve as an alternative sustainable packaging option, especially when transparency and high oxygen barrier properties are desired.

C-H activation under visible light using DDQ organo-photocatalyst: Practical, tunable and additive free

Here we present a practical, mild, selective, eco-friendly, metal-free, cost-effective, and tunable method for the photoactivation of C-H compounds using an organo photocatalyst without any additives. For this purpose, the organo photocatalyst DDQ was employed as a versatile and highly efficient catalyst for C-H bond functionalization under visible light irradiation in a straightforward reaction setup, free from additives and co-catalysts. Notably, under appropriate solvent conditions, the photooxidation of alkylarenes produced ketones, aldehydes, and carboxylic acids from corresponding starting materials. In CH3CN solvent, carboxylic acids were obtained. Interestingly over oxidation to carboxylic acid is avoided and aldehydes were produced from methyl arenes via acetal formation in CH3CN:MeOH. Furthermore, our results demonstrated that the photooxidation of 4-methoxytoluene was more efficient than that of 4-methoxybenzylalcohol. The proposed mechanism for this reaction involved the formation of a charge transfer complex between the starting material and DDQ, as indicated by UV–Vis and fluorescence spectra. Also, this method exhibited promising scalability, with 30 mmol of 4-methoxytoluene being converted to 4-methoxybenzoic acid with a yield of 92 % (TON: 345).

Modular Enantioselective Total Syntheses of the erythro-7,9-Dihydroxy- and 9-Hydroxy-7-Keto-8,4'-Oxyneolignans.

A modular, enantioselective approach to access the bioactive 7,9-dihydroxy- and 9-hydroxy-7-keto-8,4'-oxyneolignans is disclosed, which employs stereoselective Mitsunobu reactions of enantiopure 2-aryl-1,3-dioxan-5-ols and functionalized phenols. The enantiopure dioxanols are prepared through Sharpless asymmetric dihydroxylation of protected coniferyl or sinapyl alcohols and subsequent benzylidene acetal formation. Through a mix-and-match coupling approach, six of the eight possible erythro-7,9-dihydroxy-8,4'-oxyneolignan enantiomeric natural products (bearing a C-1' hydroxypropyl chain) were generated following sequential deprotection. Subsequent benzylic oxidation afforded the 7-keto-derivatives, resulting in enantioselective syntheses of each enantiomer of the natural products asprenol B and icariol A1.

Fourier Transform Infrared Spectroscopy and the Physicochemical Properties of Modified Plukenetia Conophora and Thevetia Peruviana Seed Oils for Lubricant Purposes

Recently, there have been diversion of attention from lubricant from fossil sources to biolubricants due to its effect on the environment and human life. Vegetable oils have found usefulness in the production of biolubricant but have some drawbacks. In other to mitigate this problems, Plukenetia conophora (PKCO) and Thevetia peruviana (TVTO) seed oils were chemically modified via epoxidation, hydroxylation, and acetylation. Epoxidation was done using glacial acetic acid (0.05mol of acid: 1 mol C=C; Amberlite IR – 120H ion exchange resin; 1.5mol H2O2: 1 mol C=C) at 65oC for both PKCO and TVTO. The hydroxylation reactions were done at room temperature (97% formic acid; 30% H2O2) for 12hr. Acetylation from epoxidation was also carried out. Reactions were monitored by FTIR spectroscopy, and the physicochemical and lubricant properties investigated. The bands at 925-820cm-1 confirms the presence of epoxy group in EPPKCO and EPTVTO. The band at 3450–3430cm-1 indicate the hydroxyl group in both PKCO-OH and TVTO-OH. It also confirms hydroxyl acetal formation. EPPKCO has proven to be the best candidate for biolubricant formulation based on the physicochemical and lubricant properties, whereas the peroxide value must be improved using appropriate additives.

Capturing Enzyme-Loaded Diblock Copolymer Vesicles Using an Aldehyde-Functionalized Hydrophilic Polymer Brush.

Compared to lipids, block copolymer vesicles are potentially robust nanocontainers for enzymes owing to their enhanced chemical stability, particularly in challenging environments. Herein we report that cis-diol-functional diblock copolymer vesicles can be chemically adsorbed onto a hydrophilic aldehyde-functional polymer brush via acetal bond formation under mild conditions (pH 5.5, 20 °C). Quartz crystal microbalance studies indicated an adsorbed amount, Γ, of 158 mg m-2 for vesicle adsorption onto such brushes, whereas negligible adsorption (Γ = 0.1 mg m-2) was observed for a control experiment conducted using a cis-diol-functionalized brush. Scanning electron microscopy and ellipsometry studies indicated a mean surface coverage of around 30% at the brush surface, which suggests reasonably efficient chemical adsorption. Importantly, such vesicles can be conveniently loaded with a model enzyme (horseradish peroxidase, HRP) using an aqueous polymerization-induced self-assembly formulation. Moreover, the immobilized vesicles remained permeable toward small molecules while retaining their enzyme payload. The enzymatic activity of such HRP-loaded vesicles was demonstrated using a well-established colorimetric assay. In principle, this efficient vesicle-on-brush strategy can be applied to a wide range of enzymes and functional proteins for the design of next-generation immobilized nanoreactors for enzyme-mediated catalysis.

Polyvinyl alcohol nanofibrous mat impregnated with ClCNTs/Fe2O3 nanocomposite for absorption of diesel oil in water

Oil contamination is one of the main sources of water pollution in the world. In this study, a sorption material that showed great promise as an absorbent for diesel oil in aqueous solution was developed. Chlorinated carbon nanotubes (CNTs) previously synthesized using a chemical vapor deposition (CVD) method were loaded with iron oxide nanoparticles via a co-precipitation method. The sorption materials were prepared by embedding ClCNTs/Fe2O3 nanocomposite into a polyvinyl alcohol (PVA) polymer matrix via electrospinning. The PVA mat containing only ClCNTs was also prepared for comparison and the maximum sorption capacity of 9.7 g g−1 was obtained. The optimum concentration of ClCNTs/Fe2O3 nanocomposite that gave uniform, and well-distributed nanofibers was 0.5 wt%. Crosslinking the PVA/ClCNTs/Fe2O3 nanofiber mat with glutaraldehyde (GA) resulted in increased absorption capacity for oil of ∼ 9.4 g g−1 in comparison with an absorption capacity of ∼ 7.6 g g−1 attained with a pure nanofiber mat. The crosslinked nanofiber mat remained stable even after 60 min of oil absorption which proves that crosslinking assisted in increasing the affinity of PVA for oil by reducing the amount of OH groups through acetal formation making PVA less soluble to water. The oil sorption capacity of the prepared materials was not maintained even after two cycles indicating poor reusability.

Beta-Irradiation of pure 1-alkyl-3-methylimidazolium-based ionic liquids

1-Alkyl-3-methylimidazolium ionic liquids are common cellulose solvents and biomass pretreatment agents, while beta-irradiation (“e-beaming”) is often used to decrease the recalcitrance of biomass towards hydrolysis or saccharification. Aiming at the general goal of elucidating the interaction between lignocellulosics, imidazolium-based ionic liquids, and beta-irradiation, we studied the effect of beta-irradiation on the pure ILs 1-ethyl-3-methylimidazolium and 1-butyl-3-methylimidazolium, both as chloride and acetate. Contrary to the expectation of inertness, irradiation caused degradation of the ILs, which was proportional to irradiation dosage, i.e., to irradiation time and intensity. At a dosage of 2400 kGy, 0.2% (2000 ppm) of the IL were chemically altered. The main degradation pathway is the formation of imidazole and N-methylimidazole with concomitant dealkylation. The cleaved-off alkyl groups, apparently in cationic form, react with the anions present, accounting for the formation of alkyl chlorides and alkyl acetates from the chloride ILs and acetate ILs, respectively. A second, minor pathway comprises the degradation of the imidazole ring under conversion of the C2-unit from the former C4-C5 moiety into ethylenediamine and reaction of the C1-unit from the former C2 with the IL anions. Because of the non-neglible byproduct formation, the degradation of the ILs upon beta-irradiation and possible side reactions of the resulting byproducts need to be kept in mind for all setups that involve beta-irradiation and imidazolium ILs simultaneously.Graphical abstract

Controlling Adsorption of Diblock Copolymer Nanoparticles onto an Aldehyde-Functionalized Hydrophilic Polymer Brush via pH Modulation.

Sterically stabilized diblock copolymer nanoparticles with a well-defined spherical morphology and tunable diameter were prepared by RAFT aqueous emulsion polymerization of benzyl methacrylate at 70 °C. The steric stabilizer precursor used for these syntheses contained pendent cis-diol groups, which means that such nanoparticles can react with a suitable aldehyde-functional surface via acetal bond formation. This principle is examined herein by growing an aldehyde-functionalized polymer brush from a planar silicon wafer and studying the extent of nanoparticle adsorption onto this model substrate from aqueous solution at 25 °C using a quartz crystal microbalance (QCM). The adsorbed amount, Γ, depends on both the nanoparticle diameter and the solution pH, with minimal adsorption observed at pH 7 or 10 and substantial adsorption achieved at pH 4. Variable-temperature QCM studies provide strong evidence for chemical adsorption, while scanning electron microscopy images recorded for the nanoparticle-coated brush surface after drying indicate mean surface coverages of up to 62%. This fundamental study extends our understanding of the chemical adsorption of nanoparticles on soft substrates.

Bifunctional heterogeneous catalyst: A sustainable route for cyclic acetals synthesis through tandem hydroformylation-acetalization reaction

A novel sustainable approach for the synthesis of 2-ethyl 1,3 dioxolane and various short to long-chain or aromatic cyclic acetals through a tandem hydroformylation-acetalization reaction using Rh oxide nanoparticle supported on zirconium phosphate has been established. The Rh oxide nanoparticle supported on zirconium phosphate was synthesized and characterized by various physicochemical methods. The SEM and TEM analysis revealed the average particle size of rhodium oxide was found to be ∼7.56 nm in 2%Rh@ZrP catalyst. Furthermore, the synthesized catalyst was employed to carry out a tandem hydroformylation reaction in a green solvent (ethylene glycol). Experimental results demonstrated that 2 wt.% of Rhodium on zirconium phosphate efficiently activated olefins, leading to the selective formation of cyclic acetals (60–99%) at 80°C for 6 h. In this cascade reaction, significant selectivity towards the desired product, linear cyclic acetals was observed for styrenes. This can be attributed to highly dispersed Rh oxide nanoparticles and plentiful acidic sites on the zirconium phosphate supports, which played a crucial role in tandem hydroformylation and acetalization reactions. The catalyst exhibited the ability to be reused three times without losing significant catalytic activity or selectivity. This is the first report on the synthesis of a fuel additive and other cyclic acetals via a tandem hydroformylation-acetalization reaction using heterogeneous catalysts.

Synthesis of the MN Ring of Caribbean Ciguatoxin C-CTX-1 via Desymmetrization by Acetal Formation.

The MN ring of Caribbean ciguatoxin C-CTX-1 was synthesized from a meso-syn-2,7-dimethyloxepane derivative corresponding to the M ring via desymmetrization by acetal formation with a camphor derivative, followed by construction of the N ring via the Horner-Wadsworth-Emmons reaction and acetal formation. The meso-syn-2,7-dimethyloxepane derivative was synthesized via photoinduced electrocyclization of a conjugated exo-diene under flow conditions, giving a cyclobutene derivative, followed by ring expansion via oxidative cleavage and diastereoselective reduction of a β-hydroxy ketone.

Mechanistic insights into the metabolic pathways of vanillin: unraveling cytochrome P450 interaction mechanisms and implications for food safety.

Vanillin, a key flavor compound found in vanilla beans, is widely used in the food and pharmaceutical industries for its aromatic properties and potential therapeutic benefits. This study presents a comprehensive quantum chemical analysis to elucidate the interaction mechanisms of vanillin with CYP450 enzymes, with a focus on mechanism-based inactivation. Three potential inactivation pathways were evaluated: aldehyde deformylation, methoxy dealkylation, and acetal formation. Aldehyde deformylation was identified as the most energy-efficient, involving the removal of the aldehyde group from vanillin and leading to the formation of benzyne intermediates that could react with the iron porphyrin moiety of CYP450, potentially resulting in enzyme inactivation. Further investigation into the interactions of vanillin with CYP2E1 and CYP1A2 was conducted using molecular docking and molecular dynamics (MD) simulation. The docking analyses supported the findings from DFT studies, wherein vanillin revealed high binding affinities with the studied isozymes. Moreover, vanillin occupied the main binding site in both isozymes, as evidenced by the inclusion of the heme moiety in their binding mechanisms. Employing a 100 ns molecular dynamics simulation, we scrutinized the interaction dynamics between vanillin and the two isozymes of CYP450. The assessment of various MD parameters along with interaction energies revealed that vanillin exhibited stable trajectories and substantial energy stabilization during its interaction with both CYP450 isozymes. These insights can guide future research and ensure the safe application of vanillin, especially in scenarios where it may interact with CYP450 enzymes.

A RuCl3 complex catalytic system for hydroesterification of ethylene, carbon monoxide, and ethanol

CO, ethylene, and CH3CH2OH can be converted to ethyl propionate by ethylene hydroesterification. The RuCl3 complex catalytic system (RuCl3‐DMF‐NaI‐NaOH) is reported for ethylene hydroesterification in this paper. The function mechanisms of each substance of the catalytic system have been analyzed. The catalytic activity of RuCl3 is increased by DMF (N,N‐dimethylformamide) as the ligand. The formation of 3‐pentanone is prevented by NaI by accelerating the termination rate at which ethyl attacks the propionyl species, while the formation of acetal is inhibited by NaOH. The formation mechanism of ethyl propionate has been analyzed. In‐depth researches have been done on the reaction temperature, catalyst concentration, and other factors influencing the performance of catalytic system. In RuCl3‐DMF‐NaI‐NaOH catalytic system, at reaction conditions (180°C, P(C2H4) = P(CO) = 1.5 MPa), after 4 h reaction, the conversion of ethylene reaches 87.1% with 92.8% selectivity of ethyl propionate. This work provides a neoteric catalytic system for the synthesis of ethyl propionate by ethylene hydroesterification.

Acetal Formation of Flavoring Agents with Propylene Glycol in E-Cigarettes: Impacts on Indoor Partitioning and Thirdhand Exposure.

The widespread use of flavored e-cigarettes has led to a significant rise in teenage nicotine use. In e-liquids, the flavor carbonyls can form acetals with unknown chemical and toxicological properties. These acetals can cause adverse health effects on both smokers and nonsmokers through thirdhand exposure. This study aims to explore the impacts of these acetals formed in e-cigarettes on indoor partitioning and thirdhand exposure. Specifically, the acetalization reactions of commonly used flavor carbonyls in laboratory-made e-liquids were monitored using proton nuclear magnetic resonance (1H NMR) spectroscopy. EAS-E Suite and polyparameter linear free energy relationships (PP-LFERs) were employed to estimate the partitioning coefficients for species. Further, a chemical two-dimensional partitioning model was applied to visualize the indoor equilibrium partitioning and estimate the distribution of flavor carbonyls and their acetals in the gas phase, aerosol phase, and surface reservoirs. Our results demonstrate that a substantial fraction of carbonyls were converted into acetals in e-liquids and their chemical partitioning was significantly influenced. This study shows that acetalization is a determinant factor in the exposure and toxicology of harmful carbonyl flavorings, with its impact extending to both direct exposure to smokers and involuntary exposure to nonsmokers.

Acetal Radicals: Synthetic Access and Applications

AbstractAldehydes and ketones are two of the most versatile functional groups in organic synthesis, and the development of new reagents and protocols to install them are always warranted. Recently, the reemergence of radical chemistry has provided new opportunities to introduce these important carbonyl motifs. As such, acetal radicals can be employed as synthetic radical equivalents for acyl radicals that can also circumvent known stability challenges. This review aims to summarize the advancements and known uses of acetal radicals, as well as explore acetal radical formation and synthetic applications.

Annulation of O-silyl N,O-ketene acetals with alkynes for the synthesis of dihydropyridinones and its application in concise total synthesis of phenanthroindolizidine alkaloids.

The formation of N-heterocycles with multiple substituents is important in organic synthesis. Herein, we report a novel method for the construction of functionalized dihydropyridinone rings through the annulation of an amide α-carbon with a tethered alkyne moiety. The reaction of the amide with the alkyne was achieved via O-silyl N,O-ketene acetal formation and silver-mediated addition. Furthermore, the developed method was applied for the total synthesis of phenanthroindolizidine and phenanthroquinolizidine alkaloids. By varying the coupling partners, a concise and collective total synthesis of these alkaloids was achieved.

Insight into the Promotion Effect of Trace Pd Doping on the Catalytic Performance of Ag/Al2O3 for C3H6-SCR of NOx.

The mechanistic cause of the enhancement of the C3H6-SCR activity of Ag/Al2O3 by trace Pd doping and the corresponding structure-property relationship were investigated. Pd doping enhanced the water resistance of Ag/Al2O3 for C3H6-SCR by changing the reaction pathway. Under wet conditions, a series of in situ DRIFT studies indicated that the production of an active acetate intermediate on Ag/Al2O3 was suppressed during the partial oxidation of C3H6, while trace Pd doping promoted the formation of another active intermediate, an enolic species. Furthermore, a pathway for the formation of enolic species by the reaction of acrylate with hydroxyl species was proposed. DFT calculations revealed that the surface of Ag clusters was easily covered by hydroxyl in the presence of water vapor, which could inhibit the formation of acetates. Doping with Pd facilitated the activation of acrylate which might further react with hydroxyl species to form enolic species. These findings can be helpful for the future design of efficient HC-SCR catalysts.

Thermodynamics of cellulose esterification

This research discusses the standard enthalpies of the combustion and formation of cellulose acetates and nitrates. In addition, the standard enthalpies of cellulose esterification were calculated. For cellulose acetates, it was shown that an increase in the degree of substitution (SD) contributes to enhancing both the exothermic enthalpy of the formation and the exothermic enthalpy of the reaction. It was concluded that the feasibility of the acetylation reaction of cellulose, especially to di- and triacetates, is determined mainly by the exothermic enthalpy. The experiments with nitrocelluloses have shown that with an increase in SD, the enthalpies of combustion and formation become less exothermic. When cellulose is nitrated with dilute nitric acid to SD < 1.5, the enthalpy of the nitration reaction is endothermic. Thus, to implement the nitration process of cellulose with a dilute reagent, the contribution of the entropy to the Gibbs potential of this reaction is necessary. On the other hand, when cellulose is nitrated with more concentrated nitric acid to SD >1.5, the reaction enthalpy becomes exothermic. In this case, the feasibility of the cellulose nitration process will be determined mainly by the exothermic reaction enthalpy. As the degree of substitution increases, the specific gravity of cellulose acetates decreases, while that of nitrocelluloses increases. From experimental values of specific gravity, the degree of substitution of cellulose derivatives was calculated.

Pre-electrolysis of LiClO4 in Acetonitrile: Electrochemically Induced Protolytic Carbon-Carbon Bond Formation of Benzylic Ethers and Acetals with Allyl Trimethylsilane and Other Carbon Nucleophiles.

The pre-electrolysis of LiClO4 in acetonitrile in an undivided cell applying only "catalytic" amounts of current (e.g., 0.05 F) led to the formation of a strong acidic medium for the activation of benzylic ethers and acetals. The activated primary and secondary benzylic ethers and acetals could be converted with a range of carbon nucleophiles, such as allyl trimethylsilane, silyl enol ethers, and enol acetates, for the formation of new carbon-carbon bonds. A chemoselective reaction was observed when electron-deficient benzylic acetals were converted with allyl trimethylsilane to the monoallylated products, whereas an electron-rich benzylic acetal led to the double allylated product under activation of both ether groups.

Moisture induced degradation in field-aged multicrystalline silicon photovoltaic modules

Moisture ingress is one of the key fault mechanisms responsible for photovoltaic (PV) devices degradation. Understanding moisture induced degradation (MID) mechanisms in field-aged PV modules is more reflective of the reality in the field. In the present work, MID products of reclaimed solar cells from 20-year-old field-aged silicon PV modules is investigated. The defective areas in the PV modules were identified using visual inspection, electroluminescence (EL), ultraviolet fluorescence (UV–F), and infrared thermal (IR-T) techniques. SEM-EDS analysis is used to elucidate the role of moisture on the observed degradation mechanisms. Degradation of the ethylene vinyl acetate (EVA) encapsulation produces acetic acid, carbon dioxide, phosphorus, sulfur, fluorine, and chlorine. Migration of metal ions under the influence of moisture ingress makes the formation of oxides, hydroxides, sulfides, phosphates, acetates, and carbonates of silver, lead, tin, copper, zinc, and aluminum feasible. Also, other competing reactions can lead to the formation of stannates of copper, silver, sodium, and zinc. Another observation is that, in the presence of MID species, Pb is preferentially corroded (to form lead acetate complexes) instead of the expected sacrificial Sn in the solder. These MID species account for different defects and fault modes that lead to parasitic resistance losses. This is witnessed by the 1.2%/year degradation in the Pmax of the PV module.