FUNCTIONALIZATION OF Csp2 BONDS USING TRANSITION METAL FREE STRATEGIES

Abstract

The theme of the thesis is to design, synthesize and spectral characterization of molecules, namely, α-ketoamides, benzothiazoles and benzoxazinones. All these compounds exhibit immense pharmacological properties. For instance, α-ketoamides act as calpain inhibitor, HIV protease inhibitor, orexin receptor antagonist. Also, they are regarded as synthons for different chemical transformation. Similarly, benzothiazoles exhibit anti-inflammatory, antiproliferative, anti-HIV, anti-TB properties. Moreover, their significance in materials has also been well established. Likewise, benzoxazinones have been known to showcase antitumor, anti-diabetic, anti-HCoV properties. Benzoxazione derivatives were found to treat obesity problem. Also, their role in designing fluorescent probe has also been proven. The thesis highlights the synthesis of aforementioned compounds using novel approaches with a focus on utilizing transition metal-free conditions. The use of transition metal-free strategies is of utmost importance in today’s scientific era as it directly accounts to save environmental structure in benign ways. The common strategy used in the synthesis of either of the compounds involve the functionalization of the Csp2 bonds. Broadly, the synthesis of these compounds has been achieved in two ways, the first one is conventional oxidative approach and the other is visible light mediated chemical transformations at room temperature. The central idea of the thesis is basically to demonstrate the synthesis of potent molecules in facile, mild and easy manner using contemporary methodologies. The mechanisms to synthesize these moieties were proposed in context with their respective control experiments and literature studies. Furthermore, the synthesized molecules were characterized by different spectral studies, viz; 1H, 13C, IR, HRMS, GC-MS, CHNS. The thesis is mainly divided into six chapters. Chapter 1 is an introductory portion that provides the detailed significance of the molecules, namely, α-ketoamides, benzothiazoles and benzoxazinones. This significance was supported by a number of examples. Moreover, the basic principle of visible light mediated strategies has been thoroughly explained in this chapter. Also, the role and importance of a photocatalyst has been clearly justified. The mode of action of photocatalysts has also been discussed. Different examples thereof have also been provided. Chapter 2 demonstrates an efficient method to synthesize tertiary α-ketoamides using readily available substrates, α-ketoaldehydes and amines in the presence of catalytic DABCO using aerobic oxygen as an oxidant. This transformation requires the simultaneous activation of Csp2-H and N-H bonds to afford tertiary α-ketoamides in moderate to good yields. Chapter 3 gives description of visible light mediated strategy to access both tertiary and secondary α-ketoamides using 1 mol % rose bengal as a photocatalyst. The reaction was successfully carried out at room temperature. Not only limited to secondary amines, primary aliphatic amines were also successfully employed. The reaction was sought to be driven via oxidative quenching of the rose bengal. The use of either radical scavenger or the dark conditions were found detrimental for the reaction. Chapter 4 describes the metal-free and photocatalyst-free synthesis of benzothiazoles. α-ketoacids feasibly reacted with 2-aminothiophenols under blue LED irradiation at room temperature. This transformation was driven by an EDA complex, formed between the reacting substrates. The reaction could not take place in dark condition implying that light is an essential component for this photooxidative conversion. Also, the use of radical scavenger in the reaction conditions decreased the yield of the desired product significantly. Chapter 5 provides insights into blue LED promoted synthesis of 1,4-benzoxazinones from reaction between α-ketoacids and o-aminophenols in DMSO at room temperature without using any metal or a photocatalyst. Interestingly, the reaction was found very particular with respect to the solvent, as only DMSO was found to be an ideal working solvent. Also, decreasing the wattage of blue LED from 12 W or changing the light source to green LED declined the yields of the desired 1,4-benzoxazinones. Chapter 6 corresponds to experimental section and supporting information of the synthesized molecules.