A Facile and Green Synthesis of Novel Imide and Amidic Acid Derivatives of Phenacetin as Potential Analgesic and Anti-Pyretic Agents

Facile and green syntheses of potential analgesic and antipyretic compounds, N-(4-ethoxy-phenyl)-2-(1,3- dioxo-1,3-dihydroisoindol-2-yl)acetamide derivatives 6a-g and N-[(4-ethoxy-phenylcarbamoyl)methyl]phthalamic acid derivatives 10a-g have been developed. Two synthetic routes (A and B) have been established for the preparation of 6a-g. In the route-A, 4-ethoxyaniline 2 was reacted with chloroacetyl chloride 3 in a solution of potassium acetate and acetic acid to yield N-(4-ethoxyphenyl)-2-chloroacetamide 4. The latter was reacted with imide compounds 5a-g either in triethanolamine as a green solvent or in solid phase in the presence of TEBAC and KI to yield 6a-g. Alternatively, in the route-B, reaction of anhydrides 7a-g with glycine 8 yielded the (1, 3-dioxo-1, 3-dihydroisoindol-2-yl)acetic acid derivatives 9a-g which on reaction with 2 either in triethnolamine and DCC as a dehydrating agent or in solid phase in the presence of DCC gave 6a-g. The latter were hydrolyzed in 0.5N ethanolic KOH to afford 10a-g.