Employing acetoacetamide as a key synthon for synthesizing novel thiophene derivatives and assessing their potential as antioxidants and antimicrobial agents

Almatari, Altaf S., Saeed, Ali, Abdel-Ghani, Ghada E., Abdullah, Mahmood M. S., El-Demerdash, Amr ORCID: https://orcid.org/0000-0001-6459-2955 and Abdel-Latif, Ehab (2024) Employing acetoacetamide as a key synthon for synthesizing novel thiophene derivatives and assessing their potential as antioxidants and antimicrobial agents. Journal of Heterocyclic Chemistry, 61 (7). pp. 1075-1090. ISSN 0022-152X

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Abstract

The objective of this study is to synthesize novel heterocyclic scaffolds containing a thiophene moiety using easily accessible acetoacetamide as a key synthon. The reaction of acetoacetamide with diazonium salts resulted in the formation of the corresponding thiophene derivatives 4a–c. Additionally, the reaction of acetoacetamide derivative 3 with malononitrile, ethyl cyanoacetate, or 2-cyanoacetamide, along with elemental sulfur, under refluxing in dioxane containing triethylamine afforded thiophene-containing derivatives 5a–c. Furthermore, compound 3 reacted with phenyl isothiocyanate in dry dimethylformamide and K2CO3 to yield compound 7. In situ alkylation of the non-isolable salt 6 was achieved by the addition of methyl iodide, resulting in the formation of methylthio-thiophene-2-carboxamide 8. Compound 7 was employed with numerous alpha-halogenated reagents in ethanol, affording thiazole derivative 9 and thiophene derivatives 10a and 10b, respectively. Moreover, compound 8 was reacted with hydrazine to produce the 1H-pyrazole-4-carboxamide derivative 11. Additionally, refluxing acetoacetamide derivative 3 with malononitrile and/or ethyl cyanoacetate in dioxane, in the presence of catalytic amount of triethylamine afforded 4-imino-3,7-dimethyl-4H-pyrido[1,2-a]thieno[3,2-e]pyrimidin-9(5H)-one derivatives 12a and 12b. Furthermore, the reactivity of acetoacetamide derivative 3 with 2-cyanoacetohydrazide was investigated through refluxing the reactants in dioxane, which subsequently yielded the corresponding cyanoacetamide derivative 13. The chemical identity of the newly synthesized compounds was determined by employing infrared spectroscopy (IR), 1H NMR, and 13C NMR techniques. Newly synthesized heterocycles incorporating thiophenes were evaluated for their antioxidant and antimicrobial potentials. Notably, thiophene scaffolds 5a, 10b, 11, and 13 displayed notable antioxidant and antimicrobial activities.

Item Type:	Article
Additional Information:	Funding Information: The authors acknowledge the financial support through Researchers Supporting Project number (RSPD2024R688), King Saud University, Riyadh, Saudi Arabia. Publisher Copyright: © 2024 Wiley Periodicals LLC.
Uncontrolled Keywords:	organic chemistry ,/dk/atira/pure/subjectarea/asjc/1600/1605
Faculty \ School:	Faculty of Science > School of Pharmacy (former - to 2024)
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	12 Aug 2024 17:30
Last Modified:	25 Sep 2024 17:58
URI:	https://ueaeprints.uea.ac.uk/id/eprint/96202
DOI:	10.1002/jhet.4832

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