DIFFERENT ROUTES FOR THE SYNTHESIS OF BENZALDEHYDE-BASED DIHYDROPYIMIDINONES VIA BIGINELLI REACTION
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Multicomponent reactions involving three or more reactants are commonly used to prepare dihydropyrimidinone with various bioactivities. This study reports the different routes for the synthesis of benzaldehyde-based dihydropyrimidinone via the Biginelli reaction and investigates the yield of the obtained products. The synthesis was performed via routes A, B, C, D, and E based on the formation of iminium, enamine, and Knoevenagel intermediates between urea, benzaldehyde, and ethyl acetoacetate. Route A, through a one-pot reaction via iminium, produced dihydropyrimidinone with a yield of 58%. The product from route B via iminium was obtained in 62% yield. Route C and D occurred via enamine at room temperature, and reflux gave the product 31% and 40% yield, respectively. Route E involving Knoevenagel intermediate provided the product in a 38% yield. 1H NMR, FTIR, and MS spectroscopic techniques were used for structure elucidation.
Chiang, A.N., Valderramos, J.C., Balachandran, R., Chovatiya, R.J., Mead, B.P., Schneider, C., Bell, S.L., Klein, M.G., Huryn, D.M., Chen, X.S., Day, B.W., Fidock, D.A., Wipf, P. and Brodsky, J.L., 2009. Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum. Bioorganic and Medicinal Chemistry, 17(4), pp.1527–1533.
CO., K., 1997. A reexamination of the mechanism of the Biginelli dihydropyrimidine synthesis . Support for an N - Acyliminium ion intermediate1 Recent advances in the Biginelli dihydropyrimidine synthesis . New tricks from an old dog A solid phase protocol of the Bigine. Journal of Organic Chemistry, 62(21)(6), pp.7201–4.
Freitas, E.F., Souza, R.Y., Passos, S.T.A., Dias, J.A., Dias, S.C.L. and Neto, B.A.D., 2019. Tuning the Biginelli reaction mechanism by the ionic liquid effect: The combined role of supported heteropolyacid derivatives and acidic strength. RSC Advances, 9(46), pp.27125–27135.
Kaur, R., Chaudhary, S., Kumar, K., Gupta, M.K. and Rawal, R.K., 2017. Recent synthetic and medicinal perspectives of dihydropyrimidinones: A review. European Journal of Medicinal Chemistry, 132, pp.108–134.
Manzoor, S., Prajapati, S.K., Majumdar, S., Raza, K., Gabr, M.T., Kumar, Shivani, Pal, K., Rashid, H., Kumar, Suresh, Krishnamurthy, S. and Hoda, N., 2021. Discovery of new phenyl sulfonyl-pyrimidine carboxylate derivatives as the potential multi-target drugs with effective anti-Alzheimer's action: Design, synthesis, crystal structure and in-vitro biological evaluation. European Journal of Medicinal Chemistry, 215, p.113224.
Nagarajaiah, H., Mukhopadhyay, A. and Moorthy, J.N., 2016. Biginelli reaction: an overview. Tetrahedron Letters, 57(47), pp.5135–5149.
Puripat, M., Ramozzi, R., Hatanaka, M., Parasuk, W., Parasuk, V. and Morokuma, K., 2015. The Biginelli Reaction Is a Urea-Catalyzed Organocatalytic Multicomponent Reaction. Journal of Organic Chemistry, 80(14), pp.6959–6967.
Russowsky, D., Canto, R.F.S., Sanches, S.A.A., D'Oca, M.G.M., de Fátima, í‚., Pilli, R.A., Kohn, L.K., Antí´nio, M.A. and de Carvalho, J.E., 2006. Synthesis and differential antiproliferative activity of Biginelli compounds against cancer cell lines: Monastrol, oxo-monastrol and oxygenated analogues. Bioorganic Chemistry, 34(4), pp.173–182.
Sahota, N., Abusalim, D.I., Wang, M.L., Brown, C.J., Zhang, Z., El-Baba, T.J., Cook, S.P. and Clemmer, D.E., 2019. A microdroplet-accelerated Biginelli reaction: Mechanisms and separation of isomers using IMS-MS. Chemical Science, 10(18), pp.4822–4827.
De Souza, R.O.M.A., Da Penha, E.T., Milagre, H.M.S., Garden, S.J., Esteves, P.M., Eberlin, M.N. and Antunes, O.A.C., 2009. The three-component biginelli reaction: A combined experimental and theoretical mechanistic investigation. Chemistry - A European Journal, 15(38), pp.9799–9804.
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