Ultrasonically Assisted N-Cyanoacylation and Synthesis of Alkyl(4-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2 H)-yl)benzoyl)amino Acid Ester Derivatives

Zainab Almarhoon; Hessa H Al Rasheed; Ayman El-Faham

doi:10.1021/acsomega.0c04730

Ultrasonically Assisted N-Cyanoacylation and Synthesis of Alkyl(4-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2 H)-yl)benzoyl)amino Acid Ester Derivatives

ACS Omega. 2020 Nov 19;5(47):30671-30678. doi: 10.1021/acsomega.0c04730. eCollection 2020 Dec 1.

Authors

Zainab Almarhoon¹, Hessa H Al Rasheed¹, Ayman El-Faham^{1

2}

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
² Chemistry Department, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia 12321, Alexandria, Egypt.

Abstract

This work represents the use of N-3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrile as a cyanoacetylating agent for the synthesis of cyanoacetamide benzoic acid and benzophenone derivatives by two different methods, namely, conventional heating and ultrasonication. The cyanoacetamide derivatives were subjected to cyclization to produce N-substituted 2-pyridone derivatives under conventional heating and by an ultrasonic method as well. The ultrasonic method afforded the products in less reaction time with high yields and purities compared to the conventional method, as observed from their spectral data. N-(4-Carboxy phenyl)-4,6-dimethyl-3-cyano-2-pyridone was coupled with different amino acid esters by the OxymaPure/DIC methodology under traditional and ultrasonic conditions. Again, ultrasonication assisted the coupling step and afforded the products with higher yields and purities compared to the traditional method. Fourier transform infrared spectroscopy, NMR (¹H and ¹³C), elemental analysis, and LC-MS were used to determine the structures of all compounds. Finally, a feature of this protocol is exploring the utilization of ultrasonication as an eco-friendly alternative conventional heating method for N-cyanoacylation and synthesis of N-substituted pyridinone derivatives and as a coupling method for the formation of an amide bond, which might be of interest for many researchers.