Current Organocatalysis - Volume 10, Issue 3, 2023

Organocatalysis is an important and rapidly growing area for the synthesis of various organic molecules. Because of the inherent non-metal properties, mild reaction conditions, and broad functional group tolerance, the use of small organic compounds encoding and converting another organic component has developed into a remarkable process. C-H activation reactions, on the other hand, have already emerged as a powerful strategy for forming C-C and C-X (X= N, O, S) bonds. Combining organocatalysis and C-H bond functionalization is highly rational as two coexisting and rapidly growing research fields in modern synthetic chemistry, and the cooperative strength along this consistent has proven to be a successful way of making C-H bond functionalization much more feasible, reliable, and specific. At the same time, the synthesis of heterocyclic compounds is an important field in organic chemistry due to the vast application of heterocycles in pharmaceuticals, polymers, and material science. This mini-review describes the recent developments in the synthesis of heterocyclic compounds through the alliance of organocatalysis and C-H bond functionalizations.

Background: Palladium metal has been extensively used in the synthesis of organic molecules for the last few decades. Heterocyclic ring synthesis being a significant part of organic synthesis, transition metal catalysis, especially catalysis by palladium, has been actively employed in heterocyclic synthesis. However, since palladium is an expensive metal, there has always been an urge to reuse or recycle the palladium catalyst to make the process economically viable. Modern synthetic chemists are also in constant search for newer sustainable strategies for molecular synthesis, which will lead to eco-friendly synthetic protocols. Thus, in the last few years, palladium catalysed green synthesis of heterocycles has gained importance as these aim to make the synthetic organic chemical world slightly more sustainable. Methods: This review comprises palladium catalysed synthetic strategies that proceed in a sustainable fashion. A few protocols included here involve either organic solvent-free or greener solvents as reaction medium, which is one of the modes adopted towards sustainability. Other modes of sustainability included in this review are recyclability of the palladium catalyst, one pot tandem reaction strategy, use of air as oxidant, etc. All these modes aim at achieving one or the other green chemistry principles like reduction of waste and by-products, increasing atom economy, reduction of cost and use of safer solvents. Results: The review aims to reflect the scope of sustainability in palladium catalysed synthesis of heterocycles so that economically and environmentally viable synthetic methodologies may be selectively identified and applied in academia and industries. Conclusion: Keeping the principles of green chemistry in mind, in this review, we aim to compile the recent advancements in palladium catalysed sustainable synthesis of heterocycles in a single platter that may serve as a piece of reliable literature for further research in this area.

The diverse field of chemistry demands various greener pathways in our quest to maintain sustainability. The utilization of energy inputs (mechanochemistry, ultrasound, or microwave irradiation), photochemistry, and greener reaction media being applied to organic synthesis are the key trends in the greener and sustainable process development in the current synthetic chemistry. These strategic methods aim to address the majority of the green chemistry principles, developing functional chemicals with less amount of waste production. In the synthesis of biologically potential heterocyclic molecules, green chemistry is a topic of great interest. It encompasses all branches of chemistry and is found in the notion of conducting chemical reactions while also conserving the environment through pollution-free chemical synthesis. Water as a solvent media is an excellent choice of solvent in organic synthesis development in the present day, as it is highly abundant, nontoxic, and non-combustible. Medicinal chemists have recently focused their attention on environmentally friendly procedures that use greener solvent media. Using water as a solvent, several studies on the process of optimization and selectivity have been reported, and the combination with microwave irradiation has emerged as a green chemistry protocol to produce high atom economy and yields. In this review, we have compiled microwave-assisted organic synthesis in aqueous media, including examples of the most cutting-edge methodologies employed for the heterocyclic scaffolds used in medicinal chemistry. It covers the most valuable advanced synthetics taking place in the area of heterocyclic molecule synthesis, between the decennary period of 2012 to 2021. The reported work discusses both synthetic and pharmacological applications.

Background: The spiro entity and heterocyclic scaffolds are decorated with a variety of biological and pharmaceutical properties. Therefore, the fusion of spiro compounds with individual moieties. Thus, the designing and expansion of the methods for the synthesis of various spiro-fused heterocyclic scaffolds are significantly important for synthetic organic chemistry. Methods: A variety of spiro-fused heterocyclic scaffolds are synthesized through different strategies and methods, such as one-pot multi-components synthesis, and multi-step methods via different organic reactions. Results: The wide range of the applications and their interesting biological and medicinal properties encouraged the interest of the researchers to design and construct advanced strategies and methodologies for synthesizing novel spiro-fused heterocyclic molecules which resulted in the publication of numerous research papers and review articles in the literature. In this review article, we have access to the various Schemes for the synthesis of different spiro-fused heterocyclic molecules and their biological importance.

In recent years, heterocycle derivatives have emerged as promising molecules, and have exhibited remarkable pharmacological applications. The statistical data analysis of the presently available drug molecules in the market has revealed that more than 70% of the drug candidates are derived from the heterocycles. Various synthetic protocols have been established employing a wide range of catalysts and reaction conditions; among them, one of the catalytic areas includes nanomaterials of metals and metal oxides. Nanocatalysts play an important role in the organic transformation under green chemistry protocol, due to their recycling nature and provision of the required catalytic amount. In this review, we have provided a comprehensive summary of the recent progress made in the catalytic heterogeneous metal oxide NPs application, exclusively for the synthesis of heterocyclic compounds reported in the period from 2012 to 2021. Also, this review provides an inherent framework for the reader to select a suitable catalytic system of interest to synthesize desired oxygen, nitrogen, and sulphur heteroatoms containing heterocyclic scaffold with potential pharmacological activities.

Heterocyclic moieties are ubiquitous in nature and the exploration of heterocyclic chemistry goes centuries back, which have coalesced into the invention of greener methodologies towards the synthesis of heterocycles of potential uses. Benzothiazine is an important class of heterocyclic molecule, in which a benzene ring is fused with a six–member N, S containing ring. Amongst the three possible isomers, 1,4–benzothiazines show a wide spectrum of pharmaceutical and biological activities like anti–inflammatory, anti–rheumatic, antihypertensive, andantipathogenic roles. In search of greener protocols,metal–free catalysts, and environmentally benign reaction conditions, a lot have been unboxed to date, and many other dimensions remain yet to be deciphered. This minireview is an attempt to classify various sustainable protocols for the synthesis of 1,4–benzothiazine scaffolds over the last decade based on the reacting components and pathways, along with the consideration of plausible mechanistic insights and critical analysis.

Thiadiazole is a paradigm of five membered heterocyclic compound that contains two nitrogens and one sulphur as heteroatoms with molecular formula C2H2N2S. Thiadiazole is mainly present in four isomeric forms such as 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,2,5-thiadiazole and 1,3,4-thiadiazole. Out of these isomers, 1,3,4-thiadiazole has attracted remarkable attention in the field of medicinal chemistry. Some of the drugs containing 1,3,4-thiadiazole moiety are used clinically and are available in the market including Sulphamethizole (Antibacterial), Acetazolamide (Diuretic), Azetepa (Antineoplastic), Cefazolin (Antibiotic), Megazol (Antiprotozoal), Atibeprone (anti-depressant). Several greener approaches are applied for the synthesis of thiadiazole scaffolds including microwave irradiation, ultrasonic irradiation, grinding, ball milling technique, etc. These methods are eco-friendly, nonhazardous, reproducible, and economical approach. Based on these Green chemistry approaches, thiadiazole derivatives are synthesized from thiosemicarbazide. The functionalization of these heterocyclic compounds generates thiadiazole derivatives with diverse chemical structures. This review covers green synthesis, biological potentials, and structure activity relationship study of thiadiazole analogs.

The synthesis of heterocyclic compounds has drawn considerable attention in the scientific community due to their existence in the majority of medicinal & pharmaceutically important compounds as well as natural products. Among them, the remarkable existence of tetrazoles has been realized in several commercially available drugs. In this regard, various synthetic protocols to access tetrazoles have been developed to address the efficiency and environmental impacts in terms of minimization of the steps, elevating yields, and conducting environmentally benign and sustainable chemistry. The management and detrimental environmental impact of waste has been recognised as a consistent concern, along with the costs associated with its disposal. Among various approaches to minimise unwanted materials from a process, one of the best alternatives is to perform a reaction in the absence of excess chemical reagents and catalysts. Other options include the reactions affected by the application of heat, light, sound, or electrolysis. The multicomponent reactions (MCR) display a unique approach establishing a step forward toward clean, step and atom-economical chemical synthesis. Most of them utilize the required substrates, eliminating the stoichiometric use of reagents, reducing the possibility of forming unwanted side products. The present review displays the concepts of MCR in the synthesis and functionalization of tetrazole, which contributes to green and sustainable chemistry.