Synthesis and characterizations of N-heterocyclic compounds via transition metal free C-H functionalization for C-C bond formation and C-S bond formation using elemental sulphur
Creators: name: GEETALA, Pradeep Kumar
Publisher: name: RMIT University
Year: 2024
Subjects: classificationCode: 340503
subject: Organic chemical synthesis

description: The content of this thesis entitled "Synthesis and characterizations of N-heterocyclic compounds via transition metal free C-H functionalization for C-C bond formation and C-S bond formation using elemental sulphur" is divided into five chapters based on the results of experimental work performed during the complete course of the research period.  

Cross-coupling reactions are useful for the construction of carbon-carbon, carbon-heteroatom and hetero-heteroatom bonds. In recent days these reactions are applied for the synthesis of natural and non-natural products, pharmaceutically important molecules, agrochemicals and functional materials. Traditionally, cross-coupling reactions involve electrophilic aryl halide and nucleophilic organometallic reagents including Grignard (RMgX) and organolithium (RLi) reagents. These reactions produce a large amount of metal waste. Generally, these coupling reactions are carried out by using a range of transition metals including Ru, Rh, Pd, Pt, Au, Ni etc. They need pre-functionalized substrates, expensive metal catalysts and ligands, which are in one form or other do not obey the green chemistry principles. These disadvantages can be partly overcome by applying oxidative cross-coupling strategy using cheaper metal catalysts or metal-free catalysts under oxidative conditions. In this aspect many efforts have been made in the development of new and versatile methods for various bond constructions The aim for this research is figuring out the `key' to the development of new and versatile transition metal-free methods for C-C and C-S bond constructions.                

Chapter 1 mainly discusses the importance of C-H bond transformation by comparison with classical approaches for the synthesis of C-C and C-S bond containing compounds. Further it covers the recent developments on direct transformation of C-H bond using metal free mediated systems for the construction of various C-C via oxidative CDC and C-S bond via domino reactions. 

Chapter 2 illustrates molecular oxygen mediated oxidative coupling strategy for synthesis of a wide range of E-disubstituted olefins from benzylamines with methyl substituted 2-methyl quinolines in DMSO. The olefination proceeds under mild metal-free conditions through direct deamination and benzylic C-H bond activation and provides easy access to biologically active 2-styrylquinolines with (E)-configuration. Diversely substituted 2-styrylquinolines were obtained in moderate to good yields under mild reaction conditions. Compared with other available methods for the synthesis of 2-styrylquinolines, the present method is highly efficient and easy to operate with high atom-economy. Moreover, inexpensive and environmentally benign molecular oxygen was used as the oxidant instead of toxic, harsh peroxides. 

Chapter 3 describes a novel base mediated three-component annulation reaction of simple oxindoles involving elemental sulphur and 1,2-dichloroethane (DCE), affording a streamlined pathway to diverse biologically active spiro 1,3-dithiolaneindolones. The reaction proceeds through the cleavage of C-H and C-X (Cl, Br) bonds and the formation of four C-S bonds in one pot. The developed protocol was simple, mild and afforded products in moderate to good yields. In addition, inexpensive, nontoxic, odourless, stable, and easily handled elemental sulphur was used as the sulphur source instead of odourous, toxic thiols. 

Chapter 4 consists of new approach for the synthesis of novel 4,5-thiazole-NMIs from 4-substituted arylamine napthalic monoimides and elemental sulphur has been developed under metal-free conditions. In continuation of Chapter 3, industrial waste elemental sulphur was used in the synthesis of 4,5-thiazole-NMIs. The reaction underwent the process of double C-S bond formation through C-H bond functionalization. Additionally, the photophysical and electrochemical studies exploited to understand the HOMO-LUMO nature of the derivatives. 

Overall, the developed protocols were successfully utilized for the synthesis of diverse aza-heterocycles such as 2-styrylquinolines, spiro-1,3-dithiolane-indolines and 4,5- fused thiazo-NMIs via transition metal-free C-H bond functionalisation and elemental sulphur as the sulphur source. Chapter 5 concludes the thesis and mentions the future directions of this body of work.