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

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  1 , Hessa H Al Rasheed  1 , Ayman El-Faham  1   2
Affiliations

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 et al. ACS Omega. .

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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Synthetic Pathways for Pyridinone Derivatives
Figure 1
Figure 1
1H NMR spectrum of compound 3. (A) Product obtained from conventional heating (S = starting material) and (B) product obtained from the ultrasonic method.
Figure 2
Figure 2
Structure of compound 3.
Figure 3
Figure 3
Structure of 10.
Scheme 2
Scheme 2. Coupling of 10 with Amino Acid Ester Derivatives
Figure 4
Figure 4
Structure of compound 11a.
See this image and copyright information in PMC

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