Abstract
Amide functional groups are present in a vast array of useful molecules including numerous industrially important compounds. The synthesis of this functional group in a short period of time and at a low cost is still in high demand. The direct thermal condensation of carboxylic acids and amines in the absence of reagents or catalysts is an unviable approach, due to the presumed formation of ammonium carboxylate salts, and elevated reaction conditions. Research in this area has also focused on the use of alternative functional groups such as carboxylic acid and amine surrogates for amide synthesis. Recently, nitroarenes have been shown to be efficient substitutes for the more traditional aryl amines and they are relatively more stable than their amine analogs.
Herein, we developed a method for the generation of H2 from polysiloxane “Pd” colloids to synthesize amides using carboxylic acids and nitroarenes under reductive reaction conditions. The proposed reductive amide coupling protocol was further used in optimizing different parameters to establish the optimal method to synthesize the amide product with a yield of 78%. Further investigations indicated that the catalyst was heterogeneous in nature. (Chapter 2).
An array of substrates containing the nitrobenzene and carboxylic acid group were used to study the scope of the reaction, and most of the functional group substituents were found to be compatible with the method. (Chapter 3 and 4). The protocol favoured more of the electron-donating groups with the yields ranging from 39%-97%. The application of the protocol in the synthesis of commercially available products such as Benodanil proved to be fruitful. The products were confirmed using characterization techniques such as Nuclear Magnetic Resonance Spectroscopy (NMR, 1H and 13C) and Fourier-Transform Infrared Spectroscopy (FT-IR).