Maaroof Zarei* Pages 590 - 595 ( 6 )
Background: β-Lactam antibiotics are plenty applied for the treatment of bacterial infections.Other biological activities and utilizing as a building block of 2-azetidinones is also well reported. The most useful method for the synthesis of 2-azetidinones is the Staudinger reaction. Generally ketenes were prepared from acyl halides which acyl halides shows unfavorable results such as low stability, low yield of products, and difficulties in handling and preparation.Objective: In the present study, efficient procedure for synthesis of 2-azetidinoes from imines and carboxylic acids via 1,4-dichlorophthalazine was investigated. Method: In the model reaction, a Schiff base reacts with phenoxyacetic acid in the presence of triethylamine and 1,4-dichlorophthalazine at room temperature in dry dichloromethane to form corresponding 2-azetidinone. Optimization of condition reaction was performed using this model reaction. According to optimization of condition, different Schiff bases were treated with different substituted acetic acids, 1,4-dichlorophthalazine and triethylamine, to prepare several 2-azetidinones which were purified by crystallization from EtOAc or column chromatography. Results: The optimized condition was found 1.3 mmol of 1,4-dichlorophthalazine and 1.3 mmol phenoxyacetic acid react with 1.0 mmol of Schiff base in dry dichloromethane at room temperature overnight. The 2- azetidinones were obtained in moderate to excellent yields and their structures were confirmed by spectral data and elemental analyses. Conclusion: A mild and efficient one-pot methodology to synthesize monocyclic, spirocyclic, polycyclic, N-alkyl and 3-electron-withdrawing group 2-azetidinones of from readily available Schiff bases and carboxylic acids using 1,4-dichlorophthalazine has been developed.
β-Lactam, 2-azetidinone, Staudinger reaction, 1, 4-dichlorophthalazine, ketene, imine.
Department of Chemistry, Faculty of Sciences, University of Hormozgan, Bandar Abbas 71961