Synthesis of Phthaloylglycyl Hydrazide Derivatives: Selective Protection of Phthalimide Group from Hydrazinolysis

摘要

Background: N-phthalimide amino acid hydrazide is a class of compounds that have the potentialtherapeutic use. In general, hydrazinolysis of N-substituted amino acid(s) ester removes the ester group andyields the corresponding hydrazide. However, in case if N-substitution group is phthalimide, phthalimidegroup is cleaved and not the ester group. The resulted compound, therefore, is amino acid ester rather than Nphthalimideamino acid hydrazide. The above class of compounds, because of susceptibility of phthalimidegroup to hydrazinolysis, has previously been synthesized by a lengthy three-step procedure.Objective: N-phthaloylglycyl hydrazide was synthesized by using new efficient, simplified, one step process.Hydrazone derivatives from substituted benzaldehydes, and substituted furaldehyde were also synthesized.Method: N-phthaloylglycyl hydrazide was synthesized from the corresponding carboxylic acid using 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as a coupling agent and hydroxybenzotriazole (HOBt) as anactivator. Hydrazone derivatives were synthesized by condensation of N-phthaloylglycyl hydrazide with substitutedbenzaldehyde/substituted furaldehydes. All the compounds were characterized by IR, 1H-NMR, 13CNMR,mass spectroscopy and elemental analysis.Results: The presence of EDC/HOBt resulted in hydrazinolysis of the carboxylic acid group and not thephthalimide group. N-phthaloylglycyl hydrazide was synthesized in good yield.Conclusion: We report the improved process of the synthesis of N-phthaloylglycyl hydrazide. This is the firstreport where stability of phthaloyl amino acid compound to hydrazine is demonstrated. The reaction may beexplored for the reaction schemes where stability of phthalimide group to hydrazinolysis is required.