Synthesis Studies of N-Acetyl Glyoxylamide Derivatives Using Unreactive Amines

Abstract

This research was performed to synthesize the glyoxylamide made from N-acetylisatin and anthranilic acid derivatives. The synthesis was conducted in two steps, starting from the formation of glyoxylamide using N-acetylisatin and methyl anthranilate as the starting material. The reaction was performed under reflux and inert nitrogen gaseous atmosphere for 48 h in the presence of DIPEA in acetonitrile (ACN) solvent. However, that reaction has proven to be unsuccessful. Several strategies were performed to increase the ease of glyoxylamide syntheses, such as increasing the electrophilicity of the isatin ring and increasing the nucleophilicity of the amine. The methyl anthranilate derivatives, methyl-2-amino-5-methoxybenzoate, and methyl-2-amino-4-methoxybenzoate has already been used and proven to be success to ring open the N-acetylisatin and produced glyoxylamide 5 and 6 with a yield of 12% and 11%, respectively. Thus, the desired benzoic acid functional group obtained from the hydrolysis of 5 and 6 successfully produced glyoxylamide 7 and 8 with a yield of 52% and 42%, respectively.