Francisco Méndez

The synthesis of nitrogen-containing heterocycles remains a subject of significant interest due to their applications in medicinal chemistry and materials science. This paper describes the preparation of imidazo[1,2-a]pyridine using a catalytic system consisting of the deep eutectic solvent (DES) choline chloride (ChCl)–tartaric acid (1:2) and I₂ by reaction between 2-aminopyridines and chalcones (1,3-diphenylprop-2-en-1-ones). The proposed mechanism suggests the activation of the chalcone carbonyl by the DES, enhancing the polarization of the conjugated system which suffers electrophilic addition by I₂ to the C=C bond. The resulting intermediate undergoes a nucleophilic attack by 2-aminopyridine followed by cyclization and iodine-promoted oxidation and aromatization to yield the corresponding imidazo[1,2-a]pyridine products. The role of the DES is crucial, as it facilitates carbonyl activation through hydrogen bond interactions, stabilizes reactive intermediates, and promotes protonation–deprotonation steps, thereby eliminating the need for metal catalysts or toxic organic solvents. Theoretical calculations at the PM6 level of theory suggest that the DES acts as a catalyst in this reaction, due to the nature of its components enabling the development of more sustainable synthetic strategies.

Una mirada al mundo del biocarbón, desde una perspectiva de aplicación en la gestión de residuos agroindustriales, para hacer conciencia del impacto que generamos con nuestro consumo habitual y como la ciencia aprovecha esos desechos para una economía circular.

Large polycyclic aromatic hydrocarbon (PAH) imides are promising candidates for optoelectronic applications in view of their narrow optical gaps and/or excited state charge transfer character. Diels–Alder (D–A) reactions of PAHs at bay regions can enable simultaneous extension of the aromatic structure and introduction of the imide moieties, but the actual use of this strategy has been limited. Herein, we demonstrate the D–A cycloaddition of dibenzo[ hi , st ]ovalene, one of the largest PAHs functioning as bisdiene, with maleimides to afford circumpyrene tetracarboxydiimides. Notably, efforts to optimize the yield of di-adduct revealed that the fully aromatized mono-adduct is inert toward further D–A reaction, and density functional theory (DFT) calculations instead indicated a partially dehydrogenated mono-adduct as the key intermediate enabling the second cycloaddition. The resulting product represents a rare example of PAH diimide featuring an acceptor-donor-acceptor type structure. Detailed spectroscopic and theoretical studies, including transient absorption and two-dimensional electronic spectroscopy, revealed the emergence of a bright intramolecular charge transfer state that could be directly excited to demonstrate distinct photophysical dynamics. These findings provide deep mechanistic insights into the D–A reactivity of large PAHs and underscores the potential of such PAH imides for advanced optoelectronic and photonic applications.

Pyridines are a crucial class of heterocycles with widespread applications in natural products, pharmaceuticals, and fluorescent organic materials. In this manuscript, we report the results from a kinetic and mechanistic investigation of an inverse‐electron‐demand Diels–Alder (IEDDA) cycloaddition involving an oxazole‐type diene synthesized via an Ugi–Zhu multicomponent reaction (UZ‐3CR). This heterodiene reacts efficiently with various dienophiles such as E ‐4‐oxopentenoic acid, fumaric acid, and monoethyl maleate, yielding highly substituted pyridines in good to excellent yields. Reaction conditions were optimized, and the influence of solvent polarity on regioselectivity was evaluated. The necessity of protonation for successful cycloadditions was probed using structurally diverse dienophiles, revealing the essential role of the carboxylic acid group in triggering the reactions. Mechanistic insights were supported by a comprehensive NMR study ( ¹ H, ¹³ C, and ¹⁵ N), which provided indirect evidence of in situ protonation of the oxazole ring. Notably, ¹⁵ N NMR revealed significant downfield shifts of the oxazole nitrogen, consistent with its protonation, and the emergence of new nitrogen signals corresponding to pyridine products. This study demonstrates the synthetic utility of Ugi–Zhu‐derived 5‐aminooxazoles in IEDDA cycloadditions and highlights the critical role of acid‐promoted activation in enabling efficient pyridine synthesis. We report the results from a kinetic and mechanistic investigation of an IEDDA cycloaddition involving an oxazole‐type diene synthesized via an UZ‐3CR.

A general, mild, and environmentally friendly method for synthesizing sulfonamides in sustainable solvents was developed. Sodium dichloroisocyanurate dihydrate (NaDCC·2H₂O) served as an efficient oxidant for converting thiols to sulfonyl chlorides, which then reacted in situ with various amines to afford sulfonamides in good to excellent yields in water, EtOH, glycerol and the DES ChCl/glycerol: 1/2. The process features simple conditions and a solvent-free workup involving only filtration, highlighting its potential as a green and practical approach to sulfonamide synthesis.

The use of deep eutectic solvents (DESs) as catalysts presents indisputable advantages, for example, their simplicity of preparation, high biodegradability, and recyclability, as well as zero toxicity and their effectiveness as environmentally friendly reaction media. However, aspects related to their reactivity and catalytic activity are still unclear. In this work, we explore the versatility of ChCl/ZnCl₂ DES in the formation of C-C bonds through the Michael-type addition of pyrrole to maleimide, where ChCl/ZnCl₂ DES leads to catalysis and chelation of the substrates, thus describing a recommended method for the construction of C-C bonds with high atomic economy. We describe experimental and theoretical aspects that explain the ability of ChCl/ZnCl₂ DES in the presence of water to act as a catalyst in the formation of C-C bonds between pyrrole and maleimide. The potential energy surface showed that the ChCl and the zinc-zincate species 2ZnCl₂·3H₂O, formed by the interaction between zinc chloride and water, decrease the relative free Gibbs energy values for all the species involved in the reaction mechanism (TSs, intermediates, product), favoring the kinetics and thermodynamics of the Michael addition.

The assertion made by Wu et al. that aromaticity may have considerable implications for molecular design motivated us to use nucleus-independent chemical shifts (NICS) as an aromaticity criterion to evaluate the antifungal activity of two series of indol-4-ones. A linear regression analysis of NICS and antifungal activity showed that both tested variables were significantly related (p < 0.05); when aromaticity increased, the antifungal activity decreased for series I and increased for series II. To verify the validity of the obtained equations, a new set of 44 benzofuran-4-ones was designed by replacing the nitrogen atom of the five-membered ring with oxygen in indol-4-ones. The NICS(0) and NICS(1) of benzofuran-4-ones were calculated and used to predict their biological activities using the previous equations. A set of 10 benzofuran-4-ones was synthesized and tested in eight human pathogenic fungi, showing the validity of the equations. The minimum inhibitory concentration (MIC) in yeasts was 31.25 µg·mL^–1 for Candida glabrata, Candida krusei and Candida guilliermondii with compounds 15-32, 15-15 and 15-1. The MIC for filamentous fungi was 1.95 µg·mL^–1 for Aspergillus niger for compounds 15-1, 15-33 and 15-34 . The results obtained support the use of NICS in the molecular design of compounds with antifungal activity.

Three Cu(II) coordination compounds with 4-methyl imidazole were obtained, such as [Cu(C₄H₆N₂)₄(NO₃)₂], [Cu(C₄H₆N₂)₄Br₂], and [Cu(C₄H₆N₂)₄Cl₂]. Crystallographic studies confirmed their structural similarity with Cu(II) in the active site of endogenous copper–zinc superoxide dismutase (CuZn-SOD). The superoxide anion radical (O₂^•–) scavenging activity was evaluated by the non-enzymatic experimental assay and followed the trend [Cu(C₄H₆N₂)₄(NO₃)₂] > [Cu(C₄H₆N₂)₄Br₂] > [Cu(C₄H₆N₂)₄Cl₂]. The density functional theory and the hard and soft acids and bases principle showed the importance of the electron-deficient character of Cu(II) in the chemical reactivity of the coordination compounds; Cu(II) is the softest site in the molecule and it is preferred for the nucleophilic and radical attacks of the soft O₂^•–. A simple rule was obtained: “the electron-deficient character of Cu(II) is the key index for the O₂^•– scavenging activity and is modulated by the electron-releasing counteranion effect on the coordination compound”.

Deep eutectic solvents (DESs) have been considered “the organic reaction medium of the century” because they can be used as solvents and active catalysts in chemical reactions. However, experimental and theoretical studies are still needed to provide information on the structures of DESs, the kinetics and thermodynamics properties, the interactions between the DESs and the substrates, the effect of water on the DES supramolecular network and its physicochemical properties, and so forth. This information is very useful to understand the essence of the processes that take place in the catalysis of chemical reactions and, therefore, to help in the design of a DES for a specific reaction and sample. This article shows a systematic study of the impact of DES choline chloride/p-toluenesulfonic acid and DES choline chloride/p-toluenesulfonic acid–water in the aza-Michael addition of arylamines to maleimide to obtain aminopyrrolidine-2,5-dione derivatives. The derivatives are obtained under very mild reaction conditions with good yield. The global reaction is exothermic, spontaneous, permitted by enthalpy, and prohibited for entropy. The calculated potential energy surface shows a reaction mechanism of six steps controlled by enthalpy (except the last step that is controlled by entropy). The water incorporated in the supramolecular DES complex stabilizes the transition states and favors the enthalpy-driven binding. A set of H/D exchange NMR experiments validates the transition state existing in the fourth stage of the mechanism.