C-N and C-O Bond Formation Reactions: Synthesis of N-Aryl Amides, Benzoxazoles and 3(2H)-Furanones

Abstract

Carbon-carbon and carbon-heteroatom bond formation is the key strategy for all reaction in organic synthesis. Several methods have been developed so far to achieve C-C and C-heteroatom bonds. Among them, metal-catalysed coupling reactions are of central importance because of mild reaction condition and wide functional group tolerance profile. Most importantly, these methods produce the lesser amount or no waste during the transformation. Carbon-nitrogen and carbon-oxygen bond formation reactions are two vital reactions that produce numerous acyclic and cyclic (heterocyclic) compounds of biological significance. In this context, our effort towards the copper-catalysed synthesis of N-aryl amides and benzoxazoles is presented in this thesis. Additionally, copper-catalysed 4-hydroxy alkynone synthesis and its subsequent facile transformation to biologically potent 3(2H)-furanones is also described.
The current thesis entitled “C-N and C-O Bond Formation Reactions: Synthesis of N-aryl Amides, Benzoxazoles, and 3(2H)-Furanones” has been divided into five chapters. Chapter one, two, and three highlight the C-N bond formation reactions, while chapter four describes the synthesis of 3(2H)-furanone from the 4-hydroxy ynones through the C-O bond formation reaction. The last chapter includes the overall conclusions and future scopes of the present work. A brief summary of the chapters are as follows:
Chapter 1. Catalytic Synthesis Amides: A Brief Overview
A brief discussion on different methods of amide bond formation with the special focus on metal-catalysed amide bond formation has been presented in this chapter. Along with this, the objective of the present work is defined.
Chapter 2. Copper-catalysed synthesis of N-aryl amides from aldoximes
This chapter reveals a one-step protocol for the direct transformation of aldoximes into N-arylated amides in the presence of an inexpensive commercially abundant copper catalyst (i.e., CuSO4. 5H2O). This reaction procedure is very simple and does not require any inert atmosphere to afford good yields of the amides with the complete alleviation of the regioselectivity problem that is frequently associated with the Beckmann rearrangement. Here an alternative reaction pathway for the Cu/L catalysed oxidative/ reductive pathway has been proposed for successful transformation to an amide.
Chapter 3. Copper catalysed synthesis of 2-aryl benzoxazoles
This chapter describes Cu-mediated C-N bond formation strategy has been employed for the synthesis of 2-aryl benzoxazoles from the reaction of aldoxime and 2-iodo phenol. It has been observed that benzaldoxime reacts with 2-iodo O-silyl protected benzene in the presence of 10 mol% of CuI and KOH in DMF to produce 2-phenyl benzoxazoles in moderate yield. Following this stratergy several benzoxazoles were prepared. Additional use of copper catalyzed protocol for similar transformation to benzoxazoles from the reaction of benzaldoxime and 2-bromo iodo benzene was described.
Chapter 4. A Practical Approach to 3(2H)-Furanones
In this chapter synthesis of 4-hydroxy ynones from the reaction of acid chloride and 2-methylbut-3-yn-2-ol in the presence, triethyl amine has been demonstrated. These alkynones have been successfully transformed in to 3(2H)-furanones by KOH in methanol at room temperature. This protocol allows synthesizing functionalized 3(2H)-furanones, which can be further functionalized by cross-coupling reactions to produce biologically more potent furanone derivatives.
Chapter 5. Conclusions and future scopes the present work
A one-step protocol for the direct transformation of aldoximes into N-arylated amides in the presence of inexpensive commercially abundant copper catalyst has been reported. This Cu-mediated C-N bond formation strategy has been further employed for the synthesis of 2-arylbenzoxazoles from the reaction of aldoxime and 2-iodo phenol. Then, subsequent C-O bond formation including the base promoted cyclization of 4-hydroxy alkynones into 3(2H)-furanones is also explored. These above mentioned methodologies have been further planned to produce biologically more potent molecules as the future assignment.