Letters in Organic Chemistry - Online First

In the era of renewable energy, to avoid conventional energy sources, the present work was planned and executed. This report contains a novel approach for the synthesis of anthropinacol derivative using sunlight. Isopropyl alcohol emerged as an optimized solvent (green solvent / class-3 according to IQ3AC guidelines) because it has generated high yield (84.5%) of the product along with higher atom economy (88.5%) under milder reaction conditions such as (i) inert atmosphere free, (ii) room temperature, (iii) atmospheric pressure, and (iv) metal free. DFT studies of the product show that the energy gap between HOMO and LUMO in the product (5.56 eV) is higher than reactant (4.86 eV), which suggests higher stability of the product. Further ADME and Toxicological studies reveal that the compounds have impressive bioavailability properties, potential for BBB-penetration, skin permeability, and enzyme inhibitory properties.

Ugi-Smiles reactions play an important role in the field of organic synthesis and pharmaceutical chemistry. However, due to their low reactivity, less electrophilic aliphatic aldehydes have never been used as substrates. To expand the range of substrates for the reaction, a bis(N-(pyridin-2-ylmethyl)aminomethyl substituted Tröger's base derivative was used to promote the Ugi-Smiles reaction involving aliphatic aldehydes. With the facilitation of the catalyst, the reaction of isocyanides, malononitrile, aldehydes, and low-reactive, unfunctionalized 1H-benzo[d]imidazole-2-thiols proceeded smoothly to afford thioimidazolidinones in high yields under mild conditions. Both experimental and theoretical calculations showed that the catalyst's high catalytic activity may be due to its appropriate cavity size and alkalinity, as well as its multiple catalytic active sites.

Imines are important intermediates for the synthesis of fine chemicals, pharmaceuticals, and agricultural chemicals. The development of green and sustainable synthetic methods is always a high priority of modern synthetic chemistry. Catalysts with environmental sustainability and high catalytic performance are of great research interest for sustainable catalysis. Humic acid is a class of natural and refractory high molecular weight organic matter. The chemical structure of humic acid contains a large number of functional groups such as carboxyls, hydroxyls, and aromatic rings, indicating that it comprises quinones, phenols, sugar, polypeptides, and other compounds. Humic acid is a green, biodegradable, commercially available, inexpensive and homogeneous recyclable organocatalyst. In this article, humic acid was used to catalyze the condensation of aldehydes or ketones with primary amines to the corresponding imines. In order to optimize the reaction conditions, the condensation reaction of benzaldehyde and aniline was selected as a model reaction. The effects of catalysts, catalyst loading and solvents on the formation of imines were systematically investigated. Under the optimized conditions, the methodology was successfully applied for the synthesis of a series of imines at room temperature in high yields and can be easily scaled up to the gram scale. The results showed that the catalyst humic acid exhibited excellent activity in the synthesis of imines from carbonyl compounds and primary amines. Importantly, the catalyst humic acid is effectively recycled and reused eight times with no significant decrease in the yield of the product. Our strategy provides a sustainable, efficient route for the green synthesis and large-scale production of imines at room temperature.

The fabrication process in this study was designed to be both simple and environmentally sustainable. As a result, advanced Gd2NiMnO6 nanofibers (NFs) featuring a unique interface and a highly distinctive external surface were successfully synthesized. This was achieved through a straightforward method that produced a large external surface, constructed via a 3D hierarchical architecture composed of 2D ultrathin nanosheets. By leveraging the potential of dendritic fibrous nanocatalysts, this innovative approach offers promising advancements in the field of green chemistry. Gd2NiMnO6 nanofibers (NFs) were utilized for both static and dynamic CO2 adsorption processes. In this context, Gd2NiMnO6 NFs demonstrated exceptional CO2 adsorption capacity accompanied by remarkably rapid kinetics. The nanofiber morphology of Gd2NiMnO6 provides an optimal outer surface, ensuring efficient CO2 adsorption at each metal site. The nanofiber structure of Gd2NiMnO6 enabled controlled CO2 release, ensuring interaction across the entire surface and facilitating rapid CO2 adsorption kinetics.

Pyrazole and phthalazine moieties receive special attention in the pharmaceutical and medical industries as essential ingredients in certain drugs. It is known that these substances exhibit a wide range of biological functions. A new method has been developed for the synthesis of pyridine-fused pyrazolo[1,2-b]phthalazine derivatives via a three-component reaction of phthalhydrazide, aromatic aldehydes, and 2-aminopropene-1,1,3-tricarbonitrile. This transformation presumably occurs via Knoevenagel condensation, Michael addition, cyclization and isomerization sequence of reactions. Noteworthy features of this protocol include easy isolation, a broad substrate range, non-column chromatographic separation and high product yields. Benzaldehydes containing electron-withdrawing groups, such as Br, Cl, F, CN and NO2, were found to be very reactive in the process and to provide good yields of the appropriate pyridine-fused pyrazolo[1,2-b]phthalazine derivatives. In addition, the electron-donating groups such as hydroxyl, methoxy, ethoxy and isopropyl were also favourable for the transformation. In conclusion, the current study describes a straightforward new one-pot, three-component method for the synthesis of pyridine-fused pyrazolo[1,2-b]phthalazine derivatives. The transformation requires the use of an inexpensive and readily available catalyst and does not require column chromatographic purification for isolation of products. The devised protocol's primary advantages are its straightforward experimental process, wide range of substrates, and high yields.

An efficient CuFe2O4 nanocatalyst was created using the simple and cost-effective assisted sol gel method, which has been effectively worked with as an efficient catalyst for one-pot multicomponent synthesis of pyrano[2,3-c] pyrazoles starting from aromatic aldehydes, malononitrile, ethyl acetoacetate, and hydrazine hydrate. The synthesized catalyst was characterized by using Fourier transform infrared (FT-IR), X-ray diffraction (XRD), energy dispersive X-ray (EDX), scanning electron microscopy (SEM), and transmission electron microscope (TEM) techniques. The synthesized organic compounds were examined using IR, 1H NMR, and 13C NMR spectroscopy. The yield of pyrano[2,3-c] pyrazoles was studied using various reaction parameters such as the amount of catalyst, type of solvent, reaction conditions, and time. The present work's significant advantages such as simple setup, mild reaction conditions, non-toxic solvents, high yields, simple purification, efficiency, and utilization of recovered materials after four cycles.

A straightforward and facile method for the synthesis of imidazo[1,2-a]pyridine derivatives by one-pot, three-component reaction of phenyl glyoxals, 2-aminopyridines, and barbituric acids has been developed. The synthesis was performed in a microwave reactor and under solvent-free conditions without using any catalyst. The synthesis displayed many other attractive features such as high efficiency, short reaction time, simple product purification, and environmentally benign reaction conditions. Moreover, the synthesis could be applied on a gram scale without any significant decrease in reaction yield. Eleven imidazo[1,2-a]pyridine adducts were provided in high yields (82-96%), and their structures were confirmed by NMR data. A comparison between this method and the literature report was also included. A plausible reaction mechanism involving a Knoevenagel condensation and aza-Michael addition was also suggested.

A series of 4-(((8-hydroxyquinolin-7-yl)(phenyl)methyl)amino)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one derivatives (4a–j) were synthesized via a one-pot, three-component reaction. The reaction employed benzaldehyde derivatives (1a–j), 4-aminoantipyrine (2), and 8-hydroxyquinoline (3), using titanium dioxide nanoparticles (TiO2 NPs) as a catalyst. The TiO2 NPs, synthesized through a sol–gel method, efficiently catalyzed the transformation under mild conditions, delivering high yields in just 9 minutes at room temperature. Optimization revealed that 0.010 g of catalyst in methanol was optimal, with protic solvents outperforming aprotic and non-polar ones. The reaction progress was monitored using thin-layer chromatography (TLC), and the final products were isolated via recrystallization. A systematic study of reaction parameters confirmed TiO2 NPs as an efficient, reusable, and environmentally friendly catalyst for multicomponent organic synthesis.

Autocatalytic reaction represents an appealing approach in organic chemistry and life sciences. The development of a novel autocatalytic mode for aza-6π electrocyclization reactions represents a promising protocol for the efficient construction of aromatic N-heterocycles. Drawing inspiration from natural biosynthetic pathways for aromatic heterocycles, a wide variety of bioactive natural products can be synthesized efficiently using a biomimetic aza-6π electrocyclization strategy. However, conventional thermal catalysis inevitably suffers from a limited substrate scope and diversity. The photochemical protocol is considered a promising approach in elegant organic synthesis, but the application of photocatalysis in 6π electrocyclization has been rarely explored. In this context, we hypothesized that the aza-hexatriene system of phenanthridine precursor might cyclize with the intermediate imine, which could be formed in situ from the reaction of 2-arylaniline and aldehyde source, respectively. Subsequently, the aza-hexatriene is excited by the corresponding phenanthridine via energy transfer under visible light. The final intramolecular cyclization could generate the substituted phenanthridines. Herein, a novel visible light-induced autocatalytic aza-6π electrocyclization method was reported for the synthesis of diverse phenanthridines. A broad spectrum of 2-arylaniline and (hetero)aryl aldehydes could be well tolerated under metal- and oxidant-free conditions, affording the corresponding phenanthridines in moderate to good yields. This newly developed method represents a highly efficient and cost-effective synthetic protocol. The late-stage functionalization of celecoxib and bromopride derivatives also demonstrated the practical value of this method.