Oxygen-containing Heterocycles Research Articles

Visible light-induced cascade sulfonylation/annulation of ortho-allyloxy chalcones with sodium sulfinates for the synthesis of sulfonated chromane derivatives.

A visible-light-induced radical cascade reaction for the synthesis of structurally diverse sulfonated chromanes is described. The protocol involves the addition of sulfonyl radicals to ortho-allyloxy chalcones and intramolecular Michael addition reactions in the presence of eosin Y as a photocatalyst. Additionally, this protocol shows that it is also an effective method to construct seven-membered oxygen-containing heterocycles. The method features a wide substrate scope, the use of easily accessible materials and excellent functional group tolerance with high to excellent yields. Control experiments and mechanistic studies indicate that a visible light-induced radical cascade process is involved in the transformation.

Photoenzymatic Enantioselective Synthesis of Oxygen-Containing Benzo-Fused Heterocycles.

New-to-nature biocatalysis in organic synthesis has recently emerged as a green and powerful strategy for the preparation of valuable chiral products, among which chiral oxygen-containing benzo-fused heterocycles are important structural motifs in pharmaceutical industry. However, the asymmetric synthesis of these compounds through radical-mediated methods is challenging. Herein, a novel asymmetric radical-mediated photoenzymatic synthesis strategy is developed to realize the efficient enantioselective synthesis of oxygen-containing benzo-fused heterocycles through structure-guided engineering of a flavin-dependent 'ene'-reductase GluER. It shows that variant GluER-W100H could efficiently produce various benzoxepinones, chromanone and indanone with different benzo-fused rings in high yields with great stereoselectivities under visible light. Moreover, these results are well supported by mechanistic experiments, revealing that this photoenzymatic process involves electron donor-acceptor complex formation, single electron transfer and hydrogen atom transfer. Therefore, we provide an alternative green approach for efficient chemoenzymatic synthesis of important chiral skeletons of bioactive pharmaceuticals.

A Review on Green Synthesis and Biological Activities of Medicinally Important Nitrogen and Oxygen Containing Heterocycles

Abstract: Recently, the application of green chemistry for the formation of potential bioactive heterocyclic moieties has turned out to be the key area of research for organic chemists due to the growing concern over environmental issues. Therefore, the development of nonhazardous synthetic protocols gained the particular attention of synthetic chemists as a frontier task in the present scenario. Nowadays, microbial infections have been haunting human civilization since prehistoric times, resulting in many deaths worldwide. Cancer is a fatal and dreadful disease without any appropriate cure, thus threatening humanity in both the developing and developed worlds. Therefore, there is a critical requirement for the design and synthesis of new classes of compounds to circumvent these diseases. Heterocycles are unique precursors for the synthesis of various pharmaceuticals and agrochemicals, particularly those possessing N- or O- moieties. The methods to prepare heterocycles are of great importance in synthesizing organic compounds, especially the heterocycles found in natural products. The synthesis of nitrogen and oxygen-containing heterocycles viz. Coumarins, dihydropyrimidinones, imidazoles, isoxazoles, and benzimidazoles represent attractive and demanding work for chemists as these molecules have found extensive applications in several fields, such as materials science, analytical chemistry and most importantly in, medicinal chemistry. In this review paper, we focus on the synthetic strategy to prepare these types of heterocyclic compounds by green methods and discuss their various biological applications.

Microwave-assisted Synthesis of Bioactive Six-membered O-heterocycles

Abstract: Microwave radiation has been utilised since the late 1970s as an alternative thermal energy source for chemical reactions. Initially used in inorganic chemistry, its potential for organic chemistry was revealed in 1986. Convertion of electromagnetic energy into heat, with frequencies ranging from 0.3-300 GHz using microwave irradi-ation, is an efficient heating method. The microwave heating method has significant potential for industrial processes, reducing reaction times and enhancing yields and se-lectivity. It finds applications in peptide and organic synthesis, materials science, pol-ymer chemistry, biochemical processes, and nanotechnology. Microwave-assisted or-ganic synthesis is environmentally friendly and beneficial for producing bioactive het-erocyclic compounds. Oxygen-containing heterocycles are abundant and possess vari-ous biological functions, making them essential for developing new drugs. Microwave technology facilitates the synthesis of these compounds, including bioactive six-mem-bered o-heterocycles such as pyrones, oxazolones, furanones, oxetanes, oxazoli-dinones, and dioxetanes. By utilizing modern organic transformations, microwave-as-sisted chemistry enhances the efficiency of synthetic processes, leading to the discovery of more beneficial molecules. The review provides an up-to-date analysis of the syn-thesis and medicinal properties of O-heterocycles, emphasizing the strengths and needs of this field. It guides researchers, facilitating microwave-assisted green synthesis re-actions and offering a flexible platform for forming bioactive heterocyclic rings.

Synthesis of Tetrahydrobenzo[b]pyrans Catalyzed by 1,3-Dibenzyl-1H-benzo[d] imidazole-3-ium Chloride

Abstract: Tetrahydrobenzo[b]pyrans are fused oxygen-containing heterocycles that are found in many biologically active compounds. Therefore, researchers in organic synthesis are searching for suitable, efficient, and useful methods for their synthesis. In this contribution, a series of tetrahydrobenzo[b]pyran derivatives was synthesized using aryl aldehydes, malononitrile, and cyclohexane-1,3-dione or dimedone as the available starting materials. The three-component reactions were catalyzed by 1,3-dibenzyl-1H-benzo[d]imidazol-3-ium chloride as the N-heterocyclic carbene precursor. The heterocyclic oxygen-containing products were obtained in good to excellent isolated yields within relatively shorter reaction times. Optimizing the reaction conditions was performed from the point of view of various parameters of the reaction. The results of these experiments showed that the best solvent system includes water-ethanol, the most suitable reaction temperature is 60ºC, and the optimal amount of the imidazolium catalyst loading is 5 mol%. Operational simplicity, no need for chromatographic methods for purification, simple work-up for pure products, and avoiding hazardous solvents are remarkable features of this three-component reaction. Moreover, in these multicomponent cyclo-condensations, no by-products were observed.

Brønsted-acidic ionic liquid supported nanomagnetic: a novel and reusable catalyst for synthesis of oxygen-containing heterocyclic compounds

Brønsted-acidic ionic liquid supported nanomagnetic: a novel and reusable catalyst for synthesis of oxygen-containing heterocyclic compounds

Catalytic asymmetric oxa-Diels–Alder reaction of acroleins with simple alkenes

The catalytic asymmetric inverse-electron-demand oxa-Diels–Alder (IODA) reaction is a highly effective synthetic method for creating enantioenriched six-membered oxygen-containing heterocycles. Despite significant effort in this area, simple α,β-unsaturated aldehydes/ketones and nonpolarized alkenes are seldom utilized as substrates due to their low reactivity and difficulties in achieving enantiocontrol. This report describes an intermolecular asymmetric IODA reaction between α-bromoacroleins and neutral alkenes that is catalyzed by oxazaborolidinium cation 1f. The resulting dihydropyrans are produced in high yields and excellent enantioselectivities over a broad range of substrates. The use of acrolein in the IODA reaction produces 3,4-dihydropyran with an unoccupied C6 position in the ring structure. This unique feature is utilized in the efficient synthesis of (+)-Centrolobine, demonstrating the practical synthetic utility of this reaction. Additionally, the study found that 2,6-trans-tetrahydropyran can undergo efficient epimerization into 2,6-cis-tetrahydropyran under Lewis acidic conditions. This structural core is widespread in natural products.

Preparation of Primary Explosive by Self-assembly of Combustible and Oxidizing Agents under Acid.

In order to further explore the effect of ligands on the performance of primary explosives and gain a deeper understanding of the coordination mechanism, we designed furan-2-carbohydrazide (FRCA), a ligand, by using oxygen-containing heterocycles and carbohydrazide. Then, FRCA and Cu(ClO4)2 were used to synthesize coordination compounds [Cu(FRCA)2(H2O)(ClO4)2]·CH3OH (ECCs-1·CH3OH) and Cu(FRCA)2(H2O)(ClO4)2 (ECCs-1). The structure of the ECCs-1 was confirmed by single-crystal X-ray diffraction, IR and EA characterization. Further experiments on ECCs-1 show that ECCs-1 has good thermal stability, but is sensitive to mechanical stimuli (impact sensitivity = IS = 8 J, friction sensitivity = FS = 20 N). The predicted value of the detonation parameter is DEXPLO5 = 6.6 km s-1, PEXPLO5 = 18.8 GPa, but the ignition test, laser test, and lead plate detonation experiment show that ECCs-1 has excellent detonation performance, which is very worthy of attention.

Anti-tumor effects of novel alkannin derivatives with potent selectivity on comprehensive analysis

BackgroundTherapeutic approaches based on glycolysis and energy metabolism of tumor cells are new promising strategies for the treatment of cancer. Currently, researches on the inhibition of pyruvate kinase M2, a key rate limiting enzyme in glycolysis, have been corroborated as an effective cancer therapy. Alkannin is a potent pyruvate kinase M2 inhibitor. However, its non-selective cytotoxicity has affected its subsequent clinical application. Thus, it needs to be structurally modified to develop novel derivatives with high selectivity. PurposeOur study aimed to ameliorate the toxicity of alkannin through structural modification and elucidate the mechanism of the superior derivative 23 in lung cancer therapy. MethodsOn the basis of the principle of collocation, different amino acids and oxygen-containing heterocycles were introduced into the hydroxyl group of the alkannin side chain. We examined the cell viability of all derivatives on three tumor cells (HepG2, A549 and HCT116) and two normal cells (L02 and MDCK) by MTT assay. Besides, the effect of derivative 23 on the morphology of A549 cells as observed by Giemsa and DAPI staining, respectively. Flow cytometry was performed to assess the effects of derivative 23 on apoptosis and cell cycle arrest. To further assess the effect of derivative 23 on the Pyruvate kinase M2 in glycolysis, an enzyme activity assay and western blot assay were performed. Finally, in vivo the antitumor activity and safety of the derivative 23 were evaluated by using Lewis mouse lung cancer xenograft model. ResultsTwenty-three novel alkannin derivatives were designed and synthesized to improve the cytotoxicity selectivity. Among these derivatives, derivative 23 showed the highest cytotoxicity selectivity between cancer and normal cells. The anti-proliferative activity of derivative 23 on A549 cells (IC50 = 1.67 ± 0.34 μM) was 10-fold higher than L02 cells (IC50 = 16.77 ± 1.44 μM) and 5-fold higher than MDCK cells (IC50 = 9.23 ± 0.29 μM) respectively. Subsequently, fluorescent staining and flow cytometric analysis showed that derivative 23 was able to induce apoptosis of A549 cells and arrest the cell cycle in the G0/G1 phase. In addition, the mechanistic studies suggested derivative 23 was an inhibitor of pyruvate kinase; it could regulate glycolysis by inhibiting the activation of the phosphorylation of PKM2/STAT3 signaling pathway. Furthermore, studies in vivo demonstrated derivative 23 significantly inhibited the growth of xenograft tumor. ConclusionIn this study, alkannin selectivity is reported to be significantly improved following structural modification, and derivative 23 is first shown to be able to inhibit lung cancer growth via the PKM2/STAT3 phosphorylation signaling pathway in vitro, indicating the potential value of derivative 23 in treating lung cancer.

Theoretical studies on the mechanisms and origins of substituent effects in CuBr-catalyzed three-component tandem reactions of terminal propargyl alcohols, aldehydes and amines

The CuBr-catalyzed A3-coupling-based tandem reactions of terminal propargyl alcohols, aldehydes and amines to synthesize five-membered dihydrofuran P1, disubstituted furan P2 and six-membered pyrone P3 have been developed. In this work, density functional theory (DFT) calculations have been performed to uncover the detailed reaction mechanisms and the substituent effects on the transformation of dihydrofuran P1 to pyrone P3. Computational results suggest that the catalytic cycle of dihydrofuran P1 is divided into three main processes: A3-coupling, isomerization and intramolecular cyclization. The generation of disubstituted furan P2 from dihydrofuran P1 proceeds via N-methylation and deprotonation steps. The transformation of five-membered dihydrofuran P1 to six-membered pyrone P3 is affected by the substituents R on substrate aldehyde 2. When R = OEt this transformation proceeds smoothly, undergoing the favorable OEt departure pathway. In contrast, the departure pathway is unworkable for Ph- and Me-substituted aldehydes due to the lack of hydrogen-bonding stabilization. They could only follow 1,2-R migration pathways. However, the high activation barriers in the migration pathways for the two aldehydes render the transformation infeasible. The results also reveal that silica gel acts as a significantly important hydrogen bond partner to stabilize the complexes in the transformation process. The theoretical research contributes to deeper insights into the mechanisms and the origins of substituent effects on the transformation between different heterocycles of the title reaction, which would promote the further development and design of the five- and six-membered oxygen-containing heterocycles.

Design, synthesis, and cytotoxic activity of some novel N-(substituted) benzamide derivatives bearing coumarin and 1-azocoumarin compounds

ABSTRACT. Among oxygen-containing heterocyclic compounds such as coumarin and azacoumarin derivatives, the scaffold has become an important construction motif for developing new drugs. Coumarin and its derivatives possess many types of biological activities and have been reported to show significant cytotoxic activity. N-(6,8-disubstituted coumarin-3-yl)benzamides (8a-c) namely (3-N-(benzoyl) aminocoumarin-6-ylmethyl acetate (8a); N-[6-(1-acetylpyrazol-3-yldiazineyl) coumarin-3-yl] benzamide (8b); N-(8-methoxy-6-bromo-coumarin-3-yl) benzamide (8c), were synthesized via a cyclocondensation reaction of 5-(chloromethyl)-2-hydroxybenzaldehyde (3), 5-(pyrazol-3-yl-diazineyl)-2-hydroxybenzaldehyde (4), and 5-bromo-3-methoxy- 2-hydroxybenzaldehyde (5) with N-benzoylglycine (7), in good yield. Treatment of compound 8c with ammonia in the presence of anhydrous potassium carbonate to yield N-(5-bromo-8-methoxy-1-azocoumarin-3-yl) benzamide (9). Compound (9) was acetylated with acetic anhydride to give N-(2-acetoxy-5-bromo-8-methoxyquinolin-3-yl) benzamide (10). N-(substituted coumarin and azacoumarin-3-yl) benzamides (8-10) were tested for their in vitro cytotoxic activity against (HepG2) cell line. Furthermore, DNA flow cytometry investigation over HepG2 cells indicated that compound 8a demonstrated arrest at G1/S stages of the cell cycle and induction of apoptosis by rising pre-G1 stage. Compound 8a displayed a significant tubulin polymerization inhibition.
 
 KEY WORDS: Synthesis, Coumarin, Azacoumarin, Drugs, Cytotoxicity
 Bull. Chem. Soc. Ethiop. 2023, 37(4), 1003-1019. 
 DOI: https://dx.doi.org/10.4314/bcse.v37i4.16

Anticancer Activities of Some Heterocyclic Compounds Containing an Oxygen Atom: A Review

The purpose of this study is to underline the progression and development of research regarding oxygen-containing heterocycles as well as the contribution that some oxygen-containing heterocycles have made as anticancer medicines. A series of publications about the antitumor effects of derivatives of heterocyclic compounds containing an oxygen atom, such as furan, benzofuran, oxazole, benzoxazole, and oxadiazole, were evaluated, and their anticancer activities showed encouraging results when compared to those of established standard treatments.

Progress on the Cu-Catalyzed 1,4-Conjugate Addition to Thiochromones.

Carbon-carbon bond formation is one of the most important tools in synthetic organic chemists' toolbox. It is a fundamental transformation that allows synthetic chemists to synthesize the carbon framework of complex molecules from inexpensive simple starting materials. Among the many synthetic methodologies developed for the construction of carbon-carbon bonds, organocopper reagents are one of the most reliable organometallic reagents for this purpose. The versatility of organocuprate reagents or the reactions catalyzed by organocopper reagents were demonstrated by their applications in a variety of synthetic transformations including the 1,4-conjugate addition reactions. Sulfur-containing heterocyclic compounds are a much less studied area compared to oxygen-containing heterocycles but have gained more and more attention in recent years due to their rich biological activities and widespread applications in pharmaceuticals, agrochemicals, and material science. This paper will provide a brief review on recent progress on the synthesis of an important class of sulfur-heterocycles-2-alkylthiochroman-4-ones and thioflavanones via the conjugate additions of Grignard reagents to thiochromones catalyzed by copper catalysts. Recent progress on the synthesis of 2-substituted thiochroman-4-ones via alkynylation and alkenylation of thiochromones will also be covered in this review.

Design, synthesis and characterization of a novel oxygen-containing heterocycle crystal with NLO properties

A new NLO chalcone crystal 1-(2-furyl)-3-(4-methylthio phenyl)-2-propen-1-one (FTMS) was successfully designed and the crystal was grown by slow evaporation solution growth technique. The cell data and structure refinement were determined from the single crystal X-ray diffraction. It was found that the SHG efficiency intensity of FTMS was 18 times that of KDP. The thermal decomposition temperature of FTMS was observed at 235 ℃. The crystal has a high transmittance (95%) in 500–2000 nm with a cutoff wavelength of 405 nm.

Release and evolution mechanism of oxygen-containing compounds and aromatics during the co-pyrolysis of waste tire and bamboo sawdust/rice husk by Py-GC/MS

Using the measurement technique pyrolysis gas-chromatography/mass spectrometry, the release characteristics of oxygen-containing compounds and aromatics during the pyrolysis of waste tire (WT) and the co-pyrolysis of WT and bamboo sawdust (BS)/rice hull (RH) were analyzed at low temperature (350 °C), medium temperature (550 °C) and high temperature (750 °C). The oxygen-containing compounds from the WT pyrolysis contained acids, phenols, alcohols, esters, peroxides and oxygen-containing heterocycles. Especially, the acids such as palmitic acid and stearic acid presented the highest proportion of 8.68% at 350 °C. The oxygen-containing compounds proportion showed a sharply decreasing trend with the increase of temperature. The aromatics proportion was extremely low at 350 °C and 550 °C, while aromatics proportion was as high as 44.64%, including benzene, alkyl substituted benzene, indene, naphthalene and alkyl substituted naphthalene at 750 °C. The proportion of benzene, toluene and xylene was 17.05%, and that of naphthalene and its derivatives was 7.86%. After adding BS or RH, the aromatics proportion increased at 550 °C. The aromatics proportion decreased by more than 16% with the addition of BS, while the aromatics proportion increased with the addition of RH, such as benzene, indene and naphthalene derivatives. It was also found that the relative oxygen-containing components and aromatics proportion showed an opposite trend along the temperature. At 750 °C, oxygen-containing compounds could be converted into aromatics through a series of free radical reactions. For the WT pyrolysis, N-containing organic compounds proportion in gas product as the temperature increased. While the S-containing organic compounds were released into gas phase only at 550 °C. Adding BS could reduce the formation of N- and S- containing organic compounds. However, adding RH inhabited the N-containing organic compounds formation only at 350 °C. Adding RH also inhabited the formation of S-containing organic compounds formation, while this while this positive effect was weaker than that of adding BS. Finally, according to the obtained results from Py-GC/MS at different temperatures, it was found that the active oxygen-containing free radicals released from BS could promote the chain breaking of rubber components and release hydrogen free radicals. With the aggravation of hydrogen transfer reaction, the oxygen-containing organic compounds were continuously transformed into hydrocarbon products. Co-pyrolysis promoted decarboxylation and decarbonylation reaction, resulting in the formation of H2 and free radicals, thus promoting the generation of alicyclic hydrocarbons, aliphatic chain hydrocarbons and benzene. This work provided the in-depth comparison and investigation the waste tire pyrolysis and products evolution.

Formation of Five- and Six-membered Oxygen-containing Heterocycles on the Basis of 1-halo-1-nitroalkenes

Formation of Five- and Six-membered Oxygen-containing Heterocycles on the Basis of 1-halo-1-nitroalkenes

Roasting treatments affect oil extraction rate, fatty acids, oxidative stability, antioxidant activity, and flavor of walnut oil.

The quality of pressed walnut oil can be improved by moderate roasting treatment. This study compared physicochemical characteristics and antioxidant ability of walnut oils pressed from differently roasted pretreated walnuts, analyzed the correlation among these indicators by using Pearson correlation coefficient and correlation coefficient heatmap, and evaluated the volatile organic compounds (VOCs) of walnut oil under optimal pretreatment roasting conditions using headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS). Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were able to remarkably distinguish walnut oil produced by different roasting processes. In addition, correlation analysis showed that there was a significant impact among indicators. There were 73 VOCs were identified in the optimum roasted treated walnut oil, consisting of 30 aldehydes, 13 alcohols, 11 ketones, 10 esters, 5 acids, 2 oxygen-containing heterocycles, 1 nitrogen-containing heterocycle and 1 other compound. GC-IMS results showed that aldehydes contributed significantly to the volatile flavor profile of walnut oil, especially (E)-2-heptenal, (E)-2-pentenal and hexenal. The properties of walnut oil based on varying roasting pretreatment of walnut kernels were significantly differentiated. Roasting at 120°C for 20 min is a suitable pretreatment roasting condition for pressing walnut oil. Roasting at 120°C for 20 min is a suitable pretreatment roasting condition for pressing walnut oil.

Reactivity of quinone methides with carbenes generated from α-diazocarbonyl compounds and related compounds.

Over the years, quinone methides have broadly been applied in synthesis and biological systems for synthesizing heterocyclic compounds and biologically active molecules. In this feature article, we have discussed the novel and uncovered reactivity of o-quinone methides, p-quinone methides, aza-o-quinone methides, and indolyl-2-methides with carbenes generated from α-diazocarbonyl compounds and related compounds. Two in situ-generated transient intermediates undergo cycloannulation reactions, metathesis-type reactions, 1,6-conjugate addition reactions, cyclopropanation reactions, and many other transformations to access nitrogen- and oxygen-containing heterocyclic compounds and beyond. The reactivity of quinone methides and carbenes is observed in various metal catalysts, Brønsted-acids, Lewis acids, phase transfer catalysts, additives, and visible-light-induced transformations.

A decade update on the application of β-oxodithioesters in heterocyclic synthesis.

The diverse synthesis of heterocyclic compounds has always been one of the popular subjects of organic chemistry. To this end, great efforts have been devoted to developing new reagents and establishing new strategies and methods concerning efficiency, selectivity and sustainability. β-Oxodithioesters and their enol tautomers (i.e., α-enolic dithioesters), as a class of simple and readily accessible sulfur-containing synthons, have been widely applied in the construction of various five- and six-membered heterocycles (e.g., thiophenes, thiopyrans, thiazoles, pyridines and quinolines) and other useful open-chain frameworks. Due to their unique chemical structures, β-oxodithioesters bear multiple reaction sites, which enable them to participate in two-component or multicomponent reactions to construct various heterocyclic compounds. In the past decade, the application of β-oxodithioesters in the synthesis of heterocycles has made remarkable progress. Herein, an update on the recent advances in the application of β-oxodithioesters in the synthesis of heterocycles during the period from 2013 to 2023/06 is provided. According to the different types of rings concerning heteroatoms in products, this review is divided into five sections under discussion including (i) synthesis of sulfur-containing heterocycles, (ii) synthesis of sulfur and nitrogen-containing heterocycles, (iii) synthesis of nitrogen-containing heterocycles, (iv) synthesis of nitrogen and oxygen-containing heterocycles, and (v) modification to other open-chain frameworks.

Quantitative evaluation of H-donating abilities of C(sp3)-H bonds of nitrogen-containing heterocycles in hydrogen atom transfer reaction.

Nitrogen-containing heterocycles are an important class of antioxidants, and their reactivity and selectivity in hydrogen atom reactions have attracted significant interest from chemists. In this work, the kinetics of hydrogen atom transfer reactions from C(sp3)-H bonds of 28 nitrogen-containing heterocycles, oxygen-containing heterocycles, alicyclic amines and cycloalkanes, which were denoted as XH, to the CumO˙ radical, were investigated. The characteristic physical parameter of the substrate, i.e., the thermo-kinetic parameter ΔG≠o(XH), was determined using the kinetic equation [ΔG≠XH/Y = ΔG≠o(XH) + ΔG≠o(Y)] to quantitatively evaluate the H-donating ability of XH. The effects of the substrate structure, substituent attached to the nitrogen atom, and ring size on the H-donating ability were discussed carefully. By comparing the H-donating abilities of cycloalkanes, alicyclic amines and nitrogen/oxygen-containing heterocycles, the influence of the introduction of N, O, or carbonyl groups in the carbon ring on the H-donating ability of C(sp3)-H bond was determined. The electronic, steric and stereo-electronic effects of the groups were also discussed. Herein, we not only quantitatively determined the H-donating ability of the substrate, but also provided ideas for the synthesis of new antioxidants.