Current Organocatalysis - Volume 12, Issue 4, 2025

Encapsulated metal oxide nanocomposites actively engaged in heterocyclic transformations represent a potent and adaptable notion in catalysis. The facile derivatization of metal oxide nanocomposites by surface modification has popularized them as versatile catalysts for domino heterocyclization.

With the emergence of multicomponent domino reactions (MDRs) as frontier synthetic tools for medicinally relevant heterocycles, optimally satisfying one-step syntheses is the domain of current research.

The search for a suitable catalyst for the domino multiple bond-forming synthesis of medicinal heterocyclic scaffolds has become a central evolving theme. In particular, metal oxide nanocomposites have drawn considerable attention as viable catalytic alternatives to conventional materials because of their facile adaptability in stabilizing functional cores or activating surfaces.

This review discusses the catalytic potential of derivatized metal oxide nanocomposites immobilized into or supported on various materials (metals, inorganic and organic nanocomposites, etc.) for domino heterocyclization.

This review highlights how the encapsulation of moieties on the surface of metal oxide nanoparticles has improved their catalytic recovery and reusability, as well as product yield, especially in domino synthesis. Furthermore, this review summarizes the domino synthesis of heterocycles with privileged medicinal scaffolds. The present review provides new insights into designing domino protocols that utilize metal oxide nanocomposites as vital catalysts for drug discovery at the industrial level.

Novel homochiral L-bis-prolinamides 1 and 2 were synthesized from meso-1,2-diphenylethylenediamine. They were evaluated as organocatalysts in the asymmetric intermolecular aldolic reaction. The reaction was conducted between several ketones (20 equiv) and aromatic aldehydes (1 equiv), using chloroacetic acid (10 mol%), water (10 equiv), and a catalyst loading of 10 mol%, all under wet conditions at 0°C. The best results were obtained with L-bis-prolinamide 1, which yielded the aldolic product from cyclohexanone and 4-nitrobenzaldehyde in 86% yield, with a diastereomeric ratio of 95:5, and an enantioselectivity of 95%, favoring the anti-isomer as major product. Computational studies were performed to calculate the transition state (TS) structure, explaining the effects of water and the stereoselectivity of the major (R) isomer of the reaction between 4-nitrobenzaldehyde and acetone catalyzed by L-bis-prolinamide 1. All structures were optimized and characterized with the Gaussian 16 program, using the M06-2X/6-31G(d,p) method. Gibbs free energy (ΔG) corrections were performed with the M06-2X/6-311++G(2d,2p) level of theory, at 298.15 K and 1 atm.

The objective of this work is to synthesize chiral organocatalysts from meso-1,2-diphenylethylenediamine, which were evaluated as organocatalysts in the asymmetric intermolecular aldol reaction.

In this work, a synthetic route is reported where the reactions were carried out using the best conditions mentioned above (0°C, 4 h) and 10 mol% of chloroacetic acid, in the presence of 10 equiv of water, under humid conditions.

L-Bis-prolinamides 1 and 2 were synthesized by an easy and efficient two-step route, from commercially available meso-1,2-diphenylethylenediamine obtained with good to excellent performance, with overall yields of 93% and 86%, respectively.

Overall, this work demonstrates the efficiency of L-bis-prolinamide as an organocatalyst in asymmetric aldol reactions.

The ester functional group is crucial in organic chemistry as well as in other fields due to its diverse applications. Thus, its synthesis in a simple and effective manner remains an interesting task. In literature, many one-pot reactions are reported for the transformation of carboxylic acid into ester. However, many of them are inapplicable due to their limitations, such as, longer reaction time, harsh reaction conditions, usage of expensive reagents, etc. Hence, a simple as well as effective transformation of carboxylic acid to ester is still desirable.

The study intends to develop a procedure for esterification reaction in a simple and cost effective manner under a mild reaction condition.

The demonstration reflects the activation of carboxylic acid employing a combination of triphenylphosphine and N-bromosuccinimide (NBS) at low temperatures. The activated carboxylic acid reacts with alcohol to form the corresponding ester. At elevated temperatures, the reaction can be completed at a faster rate, while at room temperatures the process is relatively slower and takes quite a long time.

Carboxylic acids (containing aromatic and heteroaromatic moieties) were made to react with different alcohols, and the desired esters were obtained quickly under optimum reaction conditions. Good to excellent yields of the desired esters were obtained in most of the reactions.

An ameliorated procedure for the esterification of carboxylic acid is reported. Activation of carboxylic acid was achieved using triphenylphosphine and NBS. The activated acid thus formed, upon reaction with various alcohols, produced the corresponding ester in good yields.

Oxidation with peroxides plays an important role in dopamine catabolism, the disruption of which is responsible for the development of neurodegenerative diseases, including Parkinson's disease. However, the mechanism of dopamine oxidation with peroxides has not been studied in detail, indicating the need to develop the kinetic patterns of the model reaction between dopamine hydrochloride and potassium peroxodisulfate.

This article aims to establish the kinetic patterns of dopamine hydrochloride oxidation in the presence of potassium peroxodisulfate using the conductometry method to monitor the reaction rate.

Conversion monitoring of dopamine hydrochloride and potassium peroxodisulfate was conducted by conductometry, which demonstrated high efficiency and was in good agreement with results independently obtained by potentiometry and UV spectroscopy.

The use of conductometry to monitor the current concentration of dopamine during its oxidation in the presence of peroxodisulfate anion is described for the first time. It was found that the activation energy of dopamine hydrochloride oxidation by potassium peroxodisulfate is approximately 60 kJ mol^-1, and the reaction proceeds through a highly ordered transition state with an activation entropy of –127 J mol^-1 K^-1, under the first-order kinetic law.

It is shown that dopamine acts as an activator of peroxide breakdown and can potentially serve as a source of radicals for the development of oxidative stress, which is one of the causes of neurodegenerative diseases, such as Parkinson's disease. To explain the first order of the reaction and the small value of the pre-exponential factor, an assumption was made about the intermediate formation of charge-transfer complexes between dopamine and the peroxodisulfate anion, as well as about the pronounced hydration of the transition state formed when these reagents approach each other.