Search Results (50)

Heterocyclic unnatural amino acids and their biheterocyclic derivatives represent invaluable structural scaffolds in modern medicinal chemistry and peptidomimetics due to their ability to induce conformational constraints and modulate pharmacokinetic profiles. While saturated nitrogen heterocycles and monocycle heteroaromatic systems are well-established pharmacophores, research on linear biheterocyclic amino acid frameworks remains significantly underrepresented in the literature. Addressing this structural gap, this study aims to synthesize and characterize a novel series of functionalized pyrimidine (hetero)cyclic molecular hybrids acting as chiral heterocyclic amino acid derivatives. The target pyrimidine-5-carboxylates and pyrimidine-4-carboxylic acid derivatives were prepared from β-dicarbonyl compounds and their corresponding enamine analogues via cyclocondensation approaches. Particular attention was paid to reaction optimization, substrate scope exploration, and stereochemical integrity preservation, utilizing chiral HPLC analysis to evaluate enantiomeric retention. Pyrimidine-5-carboxylates prepared from β-enamino keto esters retained high enantiomeric excess (90.2–100% ee), whereas cyclization of β-diketones under strongly basic conditions at elevated temperature resulted in complete racemization (ee < 1%). Modification of the synthetic route and application of milder cyclization conditions partially suppressed racemization, affording pyrimidine derivatives with 61.8–65.5% ee. These findings suggest that substrate structure influences stereochemical integrity during pyrimidine synthesis. Full article

2-Oxazolines are five-membered heterocyclic compounds with significant biological properties. They also play an important role in organic synthesis, acting as chiral ligands and protecting groups for hydroxyamino acids and amino alcohols. Poly(2-oxazolines) are known coating materials, for example, in biomedicine. Classic synthetic methods of 2-oxazolines involve a dehydrative cyclisation reaction between amino alcohols and carboxylic acids, acid chlorides, nitriles, imidates, and aldehydes. However, the electrophilic intramolecular cyclization of unsaturated amides is becoming an increasingly important synthetic method for the preparation of 2-oxazolines. This brief review summarizes procedures for synthesizing oxazolines using the electrophilic intramolecular oxidative cyclisation of N-allyl and N-propargyl amides, as published between 2014 and 2024. It covers the synthesis of 5-halomethyl-, 5-trifluoromethyl-, 5-sulfonylmethyl-, 5-sulfenylmethyl-, 5-selenylmethyl-, 5-acetoxymethyl-, 5-hydroxymethyl-, 5-aminomethyl-, 5-alkilo-, and 5-alkylideneoxazolines. Full article

A novel synthetic methodology has been developed for the efficient preparation of Quinoxalin-2(1H)-one derivatives through a strategically designed combination of Ugi four-component reaction (4CR) followed by metal-catalyzed cross-coupling reactions. This innovative approach demonstrates exceptional versatility in generating molecular diversity by systematically modulating the reactivity profiles of the initially formed Ugi adducts, thereby enabling access to a broad library of structurally diverse quinoxalinone compounds. The synthetic protocol consistently delivered the desired final products in good to moderate yields, demonstrating the reliability and practicality of this methodology for preparative applications. Comprehensive structural characterization of all synthesized derivatives was accomplished through a combination of advanced spectroscopic techniques, including proton nuclear magnetic resonance (¹H NMR), carbon-13 nuclear magnetic resonance (¹³C NMR), and high-resolution mass spectrometry, ensuring unambiguous confirmation of product identities and purities. The methodological framework employs 2-iodoaniline and 2-chloroacetic acid as the fixed amine and carboxylic acid components, respectively, in the multicomponent Ugi reaction, providing a consistent synthetic foundation. Subsequently, the resulting Ugi adducts undergo palladium-catalyzed cross-coupling transformations under optimized reaction conditions, facilitating the crucial cyclization and functionalization steps necessary for the formation of the target Quinoxalin-2(1H)-one derivatives. This sequential approach represents a significant advancement in heterocyclic synthesis methodology. Full article

The chemical recycling process of polyethylene terephthalate (PET) was executed through aminolysis employing N, N-Diisopropylethylamine (DIPEA) as the catalytic agent, commencing with the systematic collection and comprehensive purification of discarded PET bottles to remove contaminants and additives. The depolymerization reaction utilized hydrazine as the primary amine source, facilitating the cleavage of ester bonds within the polymer matrix under controlled temperature and pressure conditions. The synthesis of the diamine compound, terephthalohydrazide, was successfully achieved through this catalytic aminolysis pathway, demonstrating high conversion efficiency and product selectivity. The resulting terephthalohydrazide served as a crucial intermediate and was subsequently utilized for the further synthesis of bis-1,3,4-Oxadiazole derivatives through a comprehensive methodology rigorously aligned with the fundamental principles of green chemistry, including atom economy, reduced waste generation, and environmentally benign reaction conditions. A diverse series of six distinct products derived from various carboxylic acids employed in the cyclization synthesis of bis-1,3,4-Oxadiazoles were systematically produced under optimized reaction parameters. These products were meticulously characterized using advanced nuclear magnetic resonance (NMR) spectroscopy techniques, including both ¹H and ¹³C NMR analyses, confirming their structural integrity and chemical composition. This sequential approach represents a significant advancement in heterocyclic synthesis methodology, using sustainable pathways to find structural diversity. Full article

The stereoselective synthesis of trisubstituted alkenes has become a key topic in modern organic chemistry. At the same time, trisubstituted alkenes also serve as valuable starting materials for a wide range of transformations. However, it remains unclear to what extent these alkenes are utilized in comparison to their mono- and disubstituted counterparts. This review aims to provide a comprehensive overview of fundamental transformations involving all-carbon-substituted trisubstituted alkenes. The first section focuses on additions of carbon, oxygen, and nitrogen nucleophiles, as well as halogenation and carboxylation reactions. The second part discusses oxidative cleavage processes, while the final section addresses the cyclization and cycloisomerization reactions of trisubstituted alkenes. Full article

CO₂, an abundant and renewable C1 source, presents significant potential for applications in organic synthesis. Hydrazones, recognized for their distinctive properties, exhibit high versatility in synthetic chemistry, facilitating numerous chemical transformations. Given their crucial roles in organic synthesis, the combination of CO₂ with hydrazones has garnered increasing research interest. This review provides a comprehensive summary of recent progress in reactions involving CO₂ and hydrazones or their derivatives. These include the coupling of amines and N-tosylhydrazones with CO₂, the umpolung-mediated carboxylation of hydrazones/N-tosylhydrazones with CO₂, the cyclization of hydrazones with CO₂, and lactamization reactions incorporating N-tosylhydrazones and CO₂. These transformations utilize the diverse reactivity of hydrazones and their derivatives to capture and convert CO₂, generating valuable organic compounds with both academic and practical relevance. Additionally, the review examines the mechanisms underlying these reactions, offering critical insights for advancing research in this area. Full article

The conversion of waste biomass into biochar through inert pyrolysis represents a promising strategy for carbon sequestration. However, biochar production is often accompanied by the release of small molecular chemical substances during pyrolysis, and the resulting biochar is susceptible to environmental degradation. To enhance the carbon retention rate of biochar during pyrolysis and its stability in the environment, this study explored the incorporation of various metal soluble salts (CaCl₂, Ca(H₂PO₄)₂, MgCl₂, FeCl₃) and clay minerals (quartz, goethite, bentonite, albite) with two types of waste biomass (phragmites and goldenrod) for pre-treatment to enhance both carbon retention and stability in the resulting biochar. Furthermore, to elucidate the regulatory mechanisms of minerals on biochar structural formation, the three primary components of raw biomass—hemicellulose, cellulose, and lignin—were individually mixed with the minerals at a ratio of 1:5 (mineral/biomass, w/w) to produce biochars for a comparative analysis. The experimental results demonstrated that metal soluble salts, particularly Ca(H₂PO₄)₂, exhibited a superior performance in enhancing biochar’s carbon retention compared to clay minerals. Specifically, Ca(H₂PO₄)₂ treatment resulted in a remarkable 15% increase in the carbon retention rate. Through K₂Cr₂O₇ oxidation simulating soil aging conditions, Ca(H₂PO₄)₂-treated biochar showed approximately 12% greater stability than the untreated samples. This enhanced stability was primarily attributed to the formation of stable chemical bonds (C–O–P and P–O), which facilitated the preservation of aromatic carbon structures and small molecular compounds including sugars, alcohols, and ethers. Mechanistic investigations revealed that Ca(H₂PO₄)₂ significantly influenced the pyrolysis process by increasing the activation energy from 85.9 kJ mol⁻¹ to 156.5 kJ mol⁻¹ and introducing greater reaction complexity. During the initial pyrolysis stage (<300 °C), Ca(H₂PO₄)₂ catalyzed depolymerization, ring-opening, and C–C bond cleavage in hemicellulose, enhanced cellulose depolymerization, and side-chain cleavage in lignin phenylpropanes. In the intermediate temperature range (300–400 °C), Ca(H₂PO₄)₂ facilitated carboxylate nucleophilic addition reactions and promoted cyclization to form aromatic carbon structures. The innovative aspect of this work is that minerals can increase both the yield and carbon retention rate of biochar. Furthermore, it reveals the mechanisms underlying the improvements in pyrolysis, providing a scientific basis and theoretical foundation for better displaying the carbon sequestration potential of biochar in future applications. Full article

The metabolic cycle of L-proline plays a crucial role in cancer cell survival, proliferation, and metastasis. A key intermediate in the biosynthesis and degradation of proline is 3,4-dihydro-2H-pyrrole-2-carboxylic acid. A direct route for synthesizing substituted derivatives of this acid involves the cyclization of 2-amino-5-oxonitriles. Michael additions of [(diphenylmethylene)amino]acetonitrile to enones in a basic medium—either with aqueous sodium hydroxide or under solid–liquid phase-transfer catalysis conditions using CaO as a base—enable the synthesis of substituted 2-amino-5-oxonitriles as single diastereoisomers or as diastereoisomeric mixtures. Selective removal of the diphenylmethylene-protecting group, followed by in situ cyclization in acidic conditions, yields trans- and cis-3,5-diaryl-3,4-dihydro-2H-pyrrole-2-carbonitriles. The reaction of nitriles with HCl/dioxane/methanol followed by treatment with water produces esters and amides as by-products. In vitro screening of the synthesized compounds against multiple human cancer cell lines revealed that some compounds exhibit a good or high selectivity index. In conclusion, the synthetic schemes presented offer simple and efficient routes for the preparation of the derivatives of substituted 3,4-dihydro-2H-pyrrole-2-carboxylic acids, with some compounds exhibiting promising antiproliferative activity. Full article

The cyclization of propargyl alcohols with CO₂ represents a highly significant method for the utilization of CO₂. The resulting cyclic carbonates possesses high chemical value and hold great potential for applications in battery electrolytes, polymer precursors, and pharmaceutical intermediates. However, most existing reports on this cyclization have been limited to simple propargyl alcohol substrates that are substituted with inert alkyl, cycloalkyl, and phenyl groups. For functionalized propargyl alcohols, such as alkyne-1,2-diols, only a single report has been documented thus far. In this study, we have developed an innovative catalytic system comprising cost-effective copper salts and environmentally friendly ionic liquids (CuCl/1-ethyl-3-methylimidazolium acetate) for the cyclization of alkyne-1,2-diols with CO₂. Compared to the previously reported AgF/bulky monophosphine ligand (BrettPhos) system, our system is free of traditional volatile solvents, phosphine ligands, and additives. Notably, this is the first reported Cu(I)-catalyzed system for this cyclization, offering significant advantages in terms of cost-effectiveness and reduced toxicity compared to silver salts. Moreover, the use of ionic liquids ensures considerable recyclability, further enhancing the sustainability and practicality of this approach. Full article

The conversion of CO₂ into 2-oxazolidinones through carboxylative cyclization with propargylic amines is considered an effective method for utilizing waste gas as a sustainable C1 resource and mitigating the greenhouse effect. In this context, a series of nano-SiO₂-supported ionic liquids have been prepared and developed as multifunctional heterogeneous catalysts in the carboxylative cyclization of propargylic amines with CO₂. The catalyst IL-SbF₆@nano-SiO₂ demonstrated a high compatibility with various propargylic amines, achieving excellent yields (90~98%) for the desired 2-oxazolidinones under mild conditions. Additionally, IL-SbF₆@nano-SiO₂ can be easily separated from the reaction mixture and reused for up to six cycles without any significant activity loss. This is important for sustainable chemistry, as it reduces waste and potentially lowers costs. This study offers novel insights into the development and design of green and efficient catalysts for the synthesis of 2-oxazolidinones from carbon dioxide. Full article

Selenium reagents are useful for selenoenzyme-mimicking reactions, as well as for organic synthesis. However, the reaction waste containing selenium frequently smells unpleasant and exhibits serious toxicity. Herein, we have developed new-type on-resin selenium reagents, H-UXX···-PAM (5) and Ac-(X)U*XX···-PAM (6), where U and U* represent selenocysteine (U) and p-methoxybenzyl (PMB)-protected U, respectively, as recyclable catalysts, in which U-containing peptide chains are linked to the polystyrene resin PAM. Synthesized on-resin selenopeptides 5a–g with a variable amino acid sequence were evaluated for their glutathione peroxidase (GPx)-like activity using the UV and ¹H NMR methods, using the reaction between dithiothreitol (DTT^red) and H₂O₂ in methanol. It was found that the intramolecular interaction between U and a basic amino acid residue, such as histidine (H) and lysine (K), enhances peroxidase activity through the formation of an NH···Se hydrogen bond. On the other hand, the catalytic activity of 6a–d was evaluated in the oxidative cyclization of β,γ-unsaturated acids (7) into α,β-unsaturated lactones (8). Although the yield of 8 was significantly decreased after second- or third-round reaction, due to detachment of the selenium moiety from the resin, the results demonstrated reusability, as well as a substrate scope of 6 as a catalyst. Since U is a natural amino acid, on-resin selenopeptides are potential targets as novel-type green redox catalysts. Full article

A new approach to 1,2,5-trisubstituted 1H-indole-3-carboxylic esters has been developed and studied. The method begins with the preparation of imines from aldehyde and primary amine derivatives. Treatment of these imines with the K₂CO₃-derived anion from methyl 2-(2-fluoro-5-nitrophenyl)acetate or methyl 2-(5-cyano-2-fluorophenyl)acetate in DMF initiates a [3+2] cyclization by addition of the anion to the imine followed by ring closure of the adduct nitrogen to the activated aromatic moiety via an S_NAr process. Twenty-one examples are reported. Temperatures required for the conversion range from 90 to 95 °C for the nitro-activated substrates to 125 to 130 °C for the cyano-activated precursors. Though efficient and atom economical, limitations arise from steric hindrance in the reacting partners. The initial indoline formed is not observed but instead undergoes spontaneous air oxidation to the give the aromatic heterocycle. Imines from nonaromatic aldehydes and amines are also possible, but these give slightly lower yields of 1H-indoles and only react with the nitro-activated substrates. The results are presented with a discussion of the mechanism and the factors important to the success of the reaction. Full article

A convenient synthesis of a novel fluoroquinolone precursor, methyl 6,7-difluoro-2-[(4-fluorobenzyl)sulfanyl]-4-hydroxyquinoline-3-carboxylate, at a 78% yield starting from 3,4-difluorophenyl isothiocyanate was developed. The structure of the product was established by ¹H, ¹³C, and ¹⁹F NMR spectroscopy, mass spectrometry, IR spectroscopy and confirmed by elemental analysis. The title compound, containing the pharmacophoric 4-fluorobenzyl group, will be used in the synthesis of novel fluoroquinolone derivatives. Full article

Reaction of [Ru(H)₂(CO)(PPh₃)₃] 1 with an equimolar amount of pyrrole-2-carboxylic acid (H₂L₁) leads to the homoleptic chelate derivative k²(O,O)-[RuH(CO)(HL₁)(PPh₃)₂] 2. Prolonged acetonitrile refluxing promotes an unusual k²(O,O)- → k²(N,O)- dynamic chelate conversion, forming a neutral, stable, air- and moisture- insensitive, solvento-species k²(N,O)-[Ru(MeCN)(CO)(L₁)(PPh₃)₂] 3. Analogously, reaction of 1 with the pyrrole-2-carboxyaldehyde (HL₂) affords k²(N,O)-[RuH(CO)(HL₂)(PPh₃)₂] 4, 5, as a couple of functional isomers. Optimized reaction conditions such as temperature and solvent polarity allow the isolation of dominant configurations. Structure 5 is a pyrrolide Ru-carbaldehyde, obtained from cyclization of the pendant CHO function, whereas species 4 can be viewed as an ethanoyl-conjugated Ru-pyrrole. Derivatives 3–5 were characterized by single crystal X-ray diffraction, ESI-Ms, IR, and NMR spectroscopy, indicating distinct features for the Ru-bonded pyrrolyl groups. DFT computational results, coplanarity, bond equalization, and electron delocalization along the fused five-membered rings support aromatic features. In accordance with the antisymbiotic trans-influence, both the isolated isomers 4 and 5 disclose CO ligands opposite to N- or O-anionic groups. The quantitative Mayer bond order evidences a stabilizing backbonding effect. Antibacterial and antifungal trials on Gram-positive (Staphylococcus aureus), Gram-negative (Escherichia coli), and Candida albicans were further carried out. Full article

In-depth insights into the oligomers of carbon dots (CDs) prepared from small-molecule precursors are important in the study of the carbonization mechanism of CDs and for our knowledge of their complex structure. Herein, citric acid (CA) and ethylenediamine (EDA) were used as small-molecule precursors to prepare CDs in an aqueous solution. The structure of oligomers acquired from CA and EDA in different molar ratios and their formation process were first studied using density functional theory, including the dispersion correction (DFT-D3) method. The results showed that the energy barrier of dimer cyclization was higher than that of its linear polymerization, but the free energy of the cyclized product was much lower than that of its reactant, and IPCA (5-oxo-1,-2,3,5-tetrahydroimidazo [1,2-a]pyridine-7-carboxylic acid) could therefore be obtained under certain conditions. The oligomers obtained from different molar ratios of EDA and CA were molecular clusters formed by short polyamide chains through intermolecular forces; with the exception of when the molar ratio of EDA to CA was 0.5, excessive CA did not undergo an amidation reaction but rather attained molecular clusters directly through intermolecular forces. These oligomers exhibited significant differences in their surface functional groups, which would affect the carbonization process and the surface structure of CDs. Full article