Green approach for drug design and discovery of paracetamol analogues as potential analgesic and antipyretic agents

摘要

Environmental friendly syntheses of potential analgesic and antipyretic compounds, 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-N-(4-hydroxyphenyl)acetamide derivatives 6a–6g and N-[(4-hydroxy-phenylcarbamoyl)-methyl]-phthalamic acid derivatives 10a–10g have been developed. Two synthetic routes (A and B) have been established for the preparation of 6a–6g. In route A, 4-aminophenol 2 was reacted with chloroacetyl chloride 3 in a solution of potassium acetate and acetic acid to yield N-(4-hydroxyphenyl)-2-chloroacetamide 4. The latter was reacted with imide compounds 5a–5g either in triethanolamine as a green solvent or in solid phase in the presence of triethylbenzylammonium chloride and potassium iodide (KI) to yield 6a–6g. Alternatively, in route B, the reaction of anhydrides 7a–7g with glycine 8 yielded the (1,3-dioxo-1,3-dihydroisoindol-2-yl)acetic acid derivatives 9a–9g which on reaction with 2 either in triethnolamine and dicyclohexylcarbodiimide (DCC) as a dehydrating agent or in solid phase in the prese...