Synthesis and spectrometric study of some nucleophilic reactions of the antiepileptic molecule; 5,5-diphenyl imidazolidine-2,4-dione.

Al-Nuzal, Saadi M. D.; Al-Dulaimi, Muhammad F.; Hassan, Athraa T.

doi:10.37652/juaps.2022.171509

	Synthesis and spectrometric study of some nucleophilic reactions of the antiepileptic molecule; 5,5-diphenyl imidazolidine-2,4-dione.
Journal of University of Anbar for Pure Science
Article 9, Volume 12, Issue 1, 2018, Pages 38-53 PDF (1.16 M)
Document Type: Research Paper
DOI: 10.37652/juaps.2022.171509
Authors
Saadi M. D. Al-Nuzal¹; Muhammad F. Al-Dulaimi²; Athraa T. Hassan^* ²
¹Environmental Research Center, The University of Technology, Baghdad, Iraq
²Chemistry Department, College of Science, Al-Anbar University, Al-Ramadi, Iraq
Abstract
New reaction routs were performed for the compound 5,5-diphenyl 2,4-imidazolidinedione (I) to give derivatives (II – VII). These reactions include acylation, halogenation, reduction, and nucleophilic substitutions. Most of the derivatives showed variable chemical reactivities and thermal stability, and the N1 and N3 disubstituted analogue were found much less stable, and hydrolyzes easily in the reaction medium. According to 1H and 13C NMR measurement's, 1,3-Dichloro-5,5-diphenyl imidazolidine-2,4-dione (V) was found to chlorinate the methyl group of the solvent DMSO-d6. Sodium hydroxide consumption analysis was established to reveal the molecularity against NaOH, by following acid-base volumetric method.
Keywords
Phenytoin; 5; 5-diphenyl 2; 4-imidazolidinedione; I; sodium hydroxide consumption analysis; antiepileptic drug; acylation; halogenation; reduction; and nucleophilic substitutions

References
[1] Biltz, H (1908). "Constitution of the products of the interaction of substituted carbamates of Benzil.", Chem. Abstr., 2, 2252. [2] Putnam, T.J., Merritt, H.H. (1937). Experimental determination of the anticonvulsant properties of some phenyl derivatives. Science., 85, 525-526. [3] Goldenberg, M. M., "Overview of Drugs Used For Epilepsy and Seizures, Etiology, Diagnosis, and Treatment.", Pharmacy and Theraputis., Vol. 35(7), Pp. 392-415, 2010. [4] Shorvon, S. D., "Drug treatment of epilepsy in the century of the ILEA: The first 50 years, 1909-1958.", Epilepsia, Vol. 50 (Suppl. 3), Pp. 69–92, 2009. [5] Imanzadeh G, Aliabadi A, and Zamanloo M (2016). Organic-salt-mediated highly regioselective N3-alkylation of 2-thiophenytoin via Michael reaction under solvent-free conditions. Grean Chemistry Latters and Reactions, Vol. 9(2), 106-113. [6] Lopez, A. C., Trigo, C. G. in "The Chemistry of Hydantoins. Advances in Heterocycles Chemistry, A. R Katrizky, Ed., Academic Press, New York, 1985. [7] Meusel, M, and Gutcho, M, (2004). Recent Developments in Hydantoin Chemistry. a Review. Org. Prep. Proced. Int., 36(5), 391 - 443. [8] Scholl, S.; Koch, A.; Henning, D.; Kempter, G.; Kleinpeter, E. (1999). The Influence of Structure and Lipophilicity of Hydantoin Derivatives on Anticonvulsant Activity. Struct. Chem., 10, 355-366. [9] Dunnavant, W R and James, F L. Molecular Rearrangements. I., (1956). The base-catalyzed condensation of benzil with urea. J. Am. Chem. Soc., 78, p2740–2743. [10] Giulio G. Muccioli, Jacques H. Poupaert, Johan Wouters, Bernadette Norberg, Wolfgang Poppitz, Gerhard K. E. Scribad and Didier M. Lamberta (2003). A rapid and efficient microwave-assisted synthesis of hydantoins and thiohydantoins, Tetrahedron, 59 1301-1307. [11] Botros, S., Khalil, N. A., Naguib, B. H., & El-Dash, Y. (2013). Synthesis and anticonvulsant activity of new phenytoin derivatives. European journal of medicinal chemistry, 60, 57-63.‏ [12] Saadi M. D. Al-Nuzal, (2014). New Derivatives of 3-Substituted 5,5-Diphenyl-2,4-imidazolidinedione as Anticonvulsant and Antiepileptic Candidates. Journal of Applicable Chemistry, 3(3), 1319-1326. [13] Hudkins, R. L., DeHaven-Hudkins, D. L., & Doukas, P. (1997). Design of dual acting anticonvulsant-antimuscarinic succinimide and hydantoin derivatives. Bioorganic & Medicinal Chemistry Letters, 7(8), 979-984.‏ [14] Keiko, N. A., Kuznetsova, T. A., Vchislo, N. V., Chuvashev, Y. A., Larina, L. I., & Voronkov, M. G. (2007). Synthesis of new 5-substituted hydantoins from 2-alkoxy-1-cyano-1-trimethylsiloxypropenes. Russian Journal of General Chemistry, 77(12), 2145-2149.‏ [15] Amer M. Alanazi • Adel S. El-Azab • Ibrahim A. Al-Swaidan • Azza R. Maarouf • Eman R. El-Bendary • Mohamed A. Abu El-Enin • Alaa A.-M. Abdel-Aziz (2013) Synthesis, single-crystal, in vitro antitumor evaluation and molecular docking of 3-substitued 5,5-diphenylimidazolidine2,4-dione derivatives. Med Chem Res (2013) 22:6129–6142. [16] Thirupathi RY, Narsimha RP, Koduru S, Damodaran C, Crooks PA (2010) Aplysinopsin analogs: synthesis and anti-proliferative activity of substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-diones. Bioorg Med Chem 18:3570–3574. [17] Dreyfus, J. J., 2000. The Story of a Remarkable Medicine. Lantern Books, 2^nd edition. [18] Trišović, N., Božić, B., Obradović, A., Stefanović, O., Marković, S., Čomić, L., & Ušćumlić, G. (2011). Structure-activity relationships of 3-substituted-5, 5-diphenylhydantoins as potential antiproliferative and antimicrobial agents. Journal of the Serbian Chemical Society, 76(12), 1597-1606.‏ [19] Dhanawat, M., Banerjee, A. G., and Shrivastava, S. K., (2012) Design, synthesis, and anticonvulsant screening of some substituted piperazine and aniline derivatives of 5-phenyl-oxazolidin-2,4-diones and 5,5-diphenylimidazolidin-2,4 diones. Medicinal Chemistry Research, 21, (10), Pp. 2807–2822. [20] Al-Nuzal, S. M. D., Al-Dulaymmi, M. F. M., and Hasan, R. A. (2017). One pot synthesis of new derivatives of 3-substituted 5,5-Diphenyl imidazolidine-2,4-dione with their biological activity study. Journal of applied sciences research, 13(1), 31-40. [21] Nihar, P., Shankarananth, V., Padmavathamma, M., Kalyani, Y., Rajasekhar, K. K., & Ranaganayakulu, D. (2013). • Synthesis and biological activity of some 5, 5-diphenyl N (3)-substituted imidazolidine 2, 4-dione derivatives. International Journal of Pharmaceutical Archive ISSN: 2319-7226, 2(5). [22] Asif, M. (2015). Biological Activities of Phenytoin and Related Compounds. Discovery Chemistry, 1(2), 55-63 [23] Hussin, S. S., Al-Nuzal, S. M., & Jabbar, R. A. (2013). The susceptibilities of Gardnerella vaginalis isolates from Iraqi hospitals towards various antibiotics and new mixed ligand complexes of 5.5-diphenyl-imidazolidine-2.4-dione with transition metals (II). Al-Mustansiriyah Journal of Science, 24(2), 39-54. [24] Obradovic A, Zizic J, Trisovic N, Bozic B, Uscumlic G, Bozic B, Markovic S. (2013). Evaluation of antioxidative effects of twelve 3-substituted-5,5-diphenylhydantoins on human colon cancer cell line HCT-116 Turk J Biol, 37, 741-747. [25] Kieć-Kononowicz, K., Stadnicka, K., Mitka, A., Pękala, E., Filipek, B., Sapa, J., & Zygmunt, M. (2003). Synthesis, structure and antiarrhythmic properties evaluation of new basic derivatives of 5,5-diphenylhydantoin. European journal of medicinal chemistry, 38(6), 555-566.‏ [26] Flosi W. J., DeGoey D. A., Grampovnik D. J., Chen H-J, Klein L. L., Dekhtyar T., Masse S, Marsh K., Mo H. M., Kempf D., (2006). Discovery of imidazolidine-2,4-dione-linked HIV protease inhibitors with activity against lopinavir-resistant mutant HIV. Bioorganic & Medicinal Chemistry 14(19):6695-712. [27] Whitehead, D. C., Staples, R. J., & Borhan, B. (2009). A simple and expedient method for the preparation of N-chloro-hydantoins. Tetrahedron letters, 50(6), 656-658. [28] Biltz H., Seydel K., and Hamburger-Glazer E., (1922). Ann., 428, 198. [29] Mague, J. T., Abdel-Aziz, A. M., & El-Azab, A. S. (2014). 3-Amino-5, 5-diphenylimidazolidine-2, 4-dione. Acta Crystallographica Section E: Structure Reports Online, 70(3), o262-o263.‏ [30] Lipinski, C. A., Bordner, J., Butterfield, G. C., & Marinovic, L. C. (1990). N‐chlorination of dilantin and sorbinil. Journal of heterocyclic chemistry, 27(6), 1793-1799.
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