A Sustainable synthesis, eco-safe approach efficiency and DFT study of novel 5,6,7,8-Tetrahyroquinazolin-2(1H)-one derivatives as antioxidant reagents

Mohammed Abed Kadhim; Amin Farouk Mohamed Fahmy; Emad Khelil Mohammed Zangana; Aya Ibrahim Hassaballah; Sameh Ahmed Rizk

doi:10.22146/ijc.83583

A Sustainable synthesis, eco-safe approach efficiency and DFT study of novel 5,6,7,8-Tetrahyroquinazolin-2(1H)-one derivatives as antioxidant reagents

https://doi.org/10.22146/ijc.83583

Mohammed Abed Kadhim⁽¹⁾, Amin Farouk Mohamed Fahmy⁽²⁾, Emad Khelil Mohammed Zangana^(3*), Aya Ibrahim Hassaballah⁽⁴⁾, Sameh Ahmed Rizk⁽⁵⁾

(1) Department of Chemistry, College of Sciences, University of Anbar, Ramadi 55431, Iraq
(2) Department of Chemistry, Faculty of Science, Ain Shams University, Cairo 11566, Egypt
(3) Department of Chemistry, Faculty of Science and Health, Koya University, Koya KOY45, Iraq
(4) Department of Chemistry, Faculty of Science, Ain Shams University, Cairo 11566, Egypt
(5) Department of Chemistry, Faculty of Science, Ain Shams University, Cairo 11566, Egypt
(*) Corresponding Author

Abstract

5,6,7,8-Tetrahydroquinazolin-2-(thio)-ones (THQ) fits the class of N-heterocycles as a structural core in numerous bioactive compounds. They promptly extended previous decades. They were significantly recognized in combinatorial chemistry and materials science to determine the drug discovery, antioxidants, and pharmaceuticals fields. In the present work, one-pot multicomponent sustainable synthesis of THQ with easily accessible starting materials, i.e., cyclohexanone, different aromatic aldehydes and (thio)urea, has been performed to determine the proposed Biginelli mechanism that is supported by DFT. It is found that the THQs are synthesized by a mechano-chemical (grinding) tool to achieve a yield of 85.2% within 3.5 min, i.e., YE (% yield/time) 24.34 differs from the conventional method in which lower % yield (YE = 0.72) of THQ was achieved. This confirmed that in the green chemistry principle, the determination of % yield according to saving reaction time must be considered. Moreover, DFT-based antioxidant properties of the THQ were also studied in which the most potent antioxidant compounds were 7b > 6d > 2f. Softness (σ, eV⁻¹) and hardness (η, eV mol⁻¹) can approve the soft molecule that stays more reactive as a result of decreasing the energy gap along heterocyclic with values 0.1491 > 0.1300 > 0.1168 eV⁻¹ one-to-one with the efficiency of antioxidant.

Keywords

green chemistry; eco-safe approach efficiency; DFT; antioxidant reagents; 5,6,7,8-tetrahyroquinazolin-2(1H)-one

Full Text:

Full Text PDF

References

[1] Folkers, K., and Johnson, T.B., 1933, Researches on pyrimidines. CXXXVI. The mechanism of formation of tetrahydropyrimidines by the Biginelli reaction¹, J. Am. Chem. Soc., 55 (9), 3784–3791.

[2] Sweet, F., and Fissekis, J.D., 1973, Synthesis of 3,4-dihydro-2(1H)-pyrimidinones and the mechanism of the Biginelli reaction, J. Am. Chem. Soc., 95 (26), 8741–8749.

[3] Kappe, C.O., Fabian, W.M.F., and Semones, M.A., 1997, Conformational analysis of 4-aryl-dihydropyrimidine calcium channel modulators. A comparison of ab initio, semiempirical and X-ray crystallographic studies, Tetrahedron, 53 (8), 2803–2816.

[4] Chen, R., Singh, P., Su, S., Kocalar, S., Wang, X., Mandava, N., Venkatesan, S., Ferguson, A., Rao, A., Le, E., Rojas, C., and Njoo, E., 2022, Benchtop ¹⁹F nuclear magnetic resonance (NMR) spectroscopy provides mechanistic insight into the Biginelli condensation towards the chemical synthesis of novel trifluorinated dihydro- and tetrahydropyrimidines as antiproliferative agents, ACS Omega, 8 (11), 10545–10554.

[5] Balraj, G., Rammohan, K., Anilkumar, A., Sharath Babu, M., and Ayodhya, D., 2023, An improved eco-friendly and solvent-free method for the one-pot synthesis of tetrahydropyrimidine derivatives via Biginelli condensation reaction using ZrO₂/La₂O₃ catalysts, Results Chem., 5, 100691.

[6] Fu, R., Yang, Y., Lai, W., Ma, Y., Chen, Z., Zhou, J., Chai, W., Wang, Q., and Yuan, R., 2015, Efficient and green microwave-assisted multicomponent Biginelli reaction for the synthesis of dihydropyrimidinones catalyzed by heteropolyanion-based ionic liquids under solvent-free conditions, Synth. Commun., 45 (4), 467–477.

[7] Fiorito, S., Genovese, S., Curini, M., Preziuso, F., Taddeo, V.A., and Epifano, F., 2017, Ytterbium triflate promoted solvent-free synthesis of 2-amino-4H-pyranes, Tetrahedron Lett., 58 (16), 1659–1661.

[8] Bochevarov, A.D., Harder, E., Hughes, T.F., Greenwood, J.R., Braden, D.A., Philipp, D.M., Rinaldo, D., Halls, M.D., Zhang, J., and Friesner, R.A., 2013, Jaguar: A high‐performance quantum chemistry software program with strengths in life and materials sciences, Int. J. Quantum Chem., 113 (18), 2110–2142.

[9] Cao, M., Wang, S., Gao, Y., Pan, X., Wang, X., Deng, R., and Liu, P., 2020, Study on physicochemical properties and antioxidant activity of polysaccharides from Desmodesmus armatus, J. Food Biochem., 44 (7), e13243.

[10] EL-Hashash, M., Rizk, S.A., El-Bassiouny, F., Guirguis, D., Khairy, S., and Guirguis, L., 2017, Facile synthesis and structural characterization of some phthalazin-1(2H)-one derivatives as antimicrobial nucleosides and reactive dye, Egypt. J. Chem., 60 (3), 407–420.

[11] Shutalev, A.D., Kishko, E.A., Sivova, N.V., and Kuznetsov, A.Y., 1998, A new convenient synthesis of 5-acyl-1,2,3,4-tetrahydropyrimidine-2-thiones/ones, Molecules, 3 (3), 100–106.

[12] Abdalrazaq, E., Jbarah, A.A.Q., Al-Noor, T.H., Shinain, G.T., and Jawad, M.M., 2022, Synthesis, DFT calculations, DNA interaction, and antimicrobial studies of some mixed ligand complexes of oxalic acid and Schiff base trimethoprim with various metal ions, Indones. J. Chem., 22 (5), 1348–1364.

[13] Fahmy, A.F.M., El-Sayed, A.A., and Hemdan, M.M., 2016, Multicomponent synthesis of 4-arylidene-2-phenyl-5(4H)-oxazolones (azlactones) using a mechanochemical approach, Chem. Cent. J., 10 (1), 59.

[14] Al-Atbi, H.S., Al-Assadi, I.J., Al-Salami, B.K., and Badr, S.Q., 2020, Study of new azo-azomethine derivatives of sulfanilamide: Synthesis, characterization, spectroscopic, antimicrobial, antioxidant and anticancer activity, Biochem. Cell. Arch., 20 (2), 4161–4174.

[15] Al-Khazragie, Z.K., Al-Salami, B.K., and Al-Fartosy, A.J.M., 2022, Synthesis, antimicrobial, antioxidant, toxicity and anticancer activity of a new azetidinone, thiazolidinone and selenazolidinone derivatives based on sulfonamide, Indones. J. Chem., 22 (4), 979–1001.

[16] Bursavich, M.G., Parker, D.P., Willardsen, J.A., Gao, Z.H., Davis, T., Ostanin, K., Robinson, R., Peterson, A., Cimbora, D.M., Zhu, J.F., and Richards, B., 2010, 2-Anilino-4-aryl-1, 3-thiazole inhibitors of valosin-containing protein (VCP or p97), Bioorg. Med. Chem. Lett., 20 (5), 1677–1679.

[17] Imai, S., Kikui, H., Moriyama, K., and Togo, H., 2015, One-pot preparation of 2,5-disubstituted and 2,4,5-trisubstituted oxazoles from aromatic ketones with molecular iodine, oxone, and trifluoromethanesulfonic acid in nitriles, Tetrahedron, 71 (33), 5267–5274.

[18] Rizk, S.A., and Shaban, S., 2019, A Facile One‐pot Synthesis and anticancer evaluation of interesting pyrazole and pyrimidinthione via heterocyclic interconversion, J. Heterocycl. Chem., 56 (9), 2379–2388.

[19] El‐Hashash, M.A., and Rizk, S.A., 2016, Regioselective diastereomeric Michael adducts as building blocks in heterocyclic synthesis, J. Heterocycl. Chem., 53 (4), 1236–1240.

[20] Akanni, O.O., Owumi, S.E., and Adaramoye, O.A., 2014, In vitro studies to assess the antioxidative, radical scavenging and arginase inhibitory potentials of extracts from Artocarpus altilis, Ficus exasperate and Kigelia africana, Asian Pac. J. Trop. Biomed., 4, S492–S499.

[21] Yahyazadeh, A., Nafei-Kohi, M., Abbaspour-Gilandeh, E., and Aghaei-Hashjin, M., 2022, A new procedure for the preparation of 3,4-dihydropyrimidin-2(1H)-one and octahydroquinazolinone derivatives catalyzed by SCMNPs@CA-EASO₃H under solvent-free conditions, Lett. Org. Chem., 19 (10), 867–883.

[22] Puripat, M., Ramozzi, R., Hatanaka, M., Parasuk, W., Parasuk, V., and Morokuma, K., 2015, The Biginelli reaction is a urea-catalyzed organocatalytic multicomponent reaction, J. Org. Chem., 80 (14), 6959–6967.

DOI: https://doi.org/10.22146/ijc.83583