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Chem Cent J. 2014 Apr 28;8(1):27. eCollection 2014 Dec.

Microwave irradiation: synthesis and characterization of α-ketoamide and bis (α-ketoamide) derivatives via the ring opening of N-acetylisatin.

Author information

1
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, 11451 Riyadh, Kingdom of Saudi Arabia ; Department of Chemistry, Faculty of Science, Alexandria University, Ibrahimia, P.O. Box 426, 21321 Alexandria, Egypt.
2
Department of Chemistry, Faculty of Science, Alexandria University, Ibrahimia, P.O. Box 426, 21321 Alexandria, Egypt.
3
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box. 2457, 11451 Riyadh, Saudi Kingdom of Arabia.
4
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, 11451 Riyadh, Kingdom of Saudi Arabia.

Abstract

BACKGROUND:

The carbonyl group at position 2 of N-acetylisatin behaves as an amide which is more susceptible to nucleophilic attack via ring-opening in the presence of nucleophiles. Because of this behavior, in the present work we describe the microwave synthesis of a series of α-ketoamide and bis-(α-ketoamide) derivatives via the facile ring-opening of N-acylisatin with different amines and diamines. The microwave irradiation afforded the product in less reaction time, higher yield and purity. Reaction of N-acylisatin with methanol under microwave irradiation afforded the α-phenylglyoxyl methyl ester derivatives with excellent yields and purities. Aminolysis of the ester derivatives with piperidine and morpholine afforded the same α-ketoamide derivatives obtained from direct aminolysis of N-acylisatin. The structures of the synthesized compounds were confirmed by FT-IR, NMR, X-ray and elemental analysis.

RESULTS:

Reaction of N-acetylisatin and N-propoionylsatin with different amines and diamines afforded a series of α-ketoamide and bis-(α-ketoamide) derivatives respectively via the ring opening of N-acylisatins. The reaction was performed under conventional condition as well as microwave irradiation. The microwave irradiation afforded the product in less reaction time, higher yield and purity. Reaction of N-acylisatin with methanol under microwave irradiation afforded the α-phenylglyoxyl methyl ester derivatives in excellent yields and purities as observed from their spectral data. A plausible mechanism involves nucleophilic attack by methanol at C2 carbonyl carbon of N-acetylisatin and subsequent ring opening to generate the α-ketoester. Aminolysis of α-ketoester with amine afforded the same α-ketoamide which is obtained by direct aminolysis of N-acylisatin. The IR, NMR spectra, microanalyses, and single crystal X-ray diffraction confirmed the structures of the synthesized compounds.

CONCLUSIONS:

In conclusion, we have demonstrated that microwave irradiation could be employed efficiently for the synthesis of biologically important α-ketoamide and bis-(α-ketoamide) derivatives. The microwave irradiation has more advantageous over the classical method with regard to reaction time, solvent quantity, and product yield. Reaction of N-acylisatin with methanol under microwave irradiation afforded the α-phenylglyoxyl methyl ester derivatives with excellent yields and purities. Aminolysis of the methyl ester derivatives with amine under microwave irradiation afford the same α-ketoamide derivatives as obtained from direct aminolysis of N-acylisatins.

KEYWORDS:

Microwave irradiation; N-acetylisatin; N-propionylisatin; X-ray crystallography; bis- α-ketoamide; α-ketoamide

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