Synthesis of New 3-Substiuted Quinazolin-4(3H)-one Compounds

Abstract

Quinazolin-4(3H)-one is a well-known heterocyclic compound with a unique place in medicinal chemistry, and it has drawn much attention due to its diversified biological activity. In this research we report the synthesis of some quinazolin-4-one derivatives containing acetylenic moiety. The quinazolin-4(3H)-one (1) was synthesized from the reaction of anthranilic acid with formamide under the conventional or microwave irradiation conditions. The quinazolin-4(3H)-one was converted to the corresponding 3-propargyl derivative (2) by its reaction with propargyl bromide in presence of potassium carbonate as a base and acetone as a solvent. The 3-propargyl quinazolin-4(3H)-one (2) was used as a precursor to synthesize new three series of heterocyclic compounds containing quinazolin-4(3H)-one moiety. Compound (2) was treated with ethyl magnesium bromide, then the resulted solution treated immediately with carbon disulfide and sublimed sulfur to synthesize 1,2-dithiol-3-thione compound (3). The 1,2,3-triazole compounds (5a-d) were synthesized by the reaction of compound (2) with alkyl azides (4a-d) according to Click reaction. The Mannich bases (6a-i) were synthesized via Mannich reaction by reaction of the acetylenic compound (2) with secondary amines in presence of paraformaldehyde in1,4-dioxane as a solvent. All the synthesized compounds were characterized by physical and spectral measurements.

Keywords

• Quinazolin-4-one,2-dithiol-3-thione,1,2,3-triazole,Click reaction,Mannich reaction

References

1. Hess, H. J.; Cronin, T. H.; Scriabine, A., (1968), J. Med. Chem. 11, 140. Ghorab, M. M. (2000), Farmco. 55, 249. Bartroli, J.; Turmo, E.; Alguero, M.; Boncompte, E.; Vericant, M. L.; Conte Ramis, J.; Merlos, M.; Gracia-Rafanell, J. F., (1998), J .Med .Chem. 48, 1869. Dohle, W.; Jourdan, F.L.; Menchon, G.; Prota, A.E.; Foster, P.A.; Mannion, P.; Hamel, E.; Thomas, M.P.; Kasprzyk, P.G.; Ferrandis, E.; (2018), J. Med. Chem. 61, 1031–1044. Abdel-Hamid, S. G. (1997), J. Indian Chem. Soc. 74, 613. El-Brollosy, N. R.; Abdel-Megeed, M. F.; Genady, A. R. (2003), Alexandria J. Pharm. Sci. 17(1), 17. Shab, B. R.; Bhatt, J. J.; Patel, H. H.; Undavia, N. K.; Trivedi, P. B.; Desai, N. C. (1995), Indian. J.Chem. 34B, 201. Khili, M. A.; Soliman, R.; Furghuli, A. M.; Bekhit, A. A. (1994), Arch. Pharm. 327, 27. Shivaram, H. B.; Padmaja, M. T.; Shivnanda, M. K.; Akbarali, P. M. (1998), Indian. J. Chem. 37B, 715. Noureldin, N.A.; Kothayer, H.; Lashine, E.-S.M.; Baraka, M.M.; El-Eraky, W.; El Awdan, S.A. (2017), Arch. Pharm. Chem. Life Sci. 350, e1600332. Saravanan G., Alagarsamy V., Prakash CR; (2010), Int. J. Pharm. Pharm. Sci., 2010, 2:83–86. Sasmal S, Balaji G, Kanna R. HR, Balasubrahmanyam D, Srinivas G, Kyasa S, Sasmal PK, Khanna I, Talwar R, Suresh J, Jadhav VP, Muzeeb S, Shashikumar D, Harinder Reddy K, Sebastian VJ, Frimurer TM, Rist Ø, Elster L, Högberg T; (2012), Bioorg. Med. Chem. Lett. 22:3157–3162. Sjoqvist F and Gilette J, (1965) Life Sci. 4, 1031. Leslie G.B. and MaxwellD. R. (1904), Nature, 202, 97. Tang C, Castoldi AF, Costa LG, (1993) Biochem. Mol. Biol. Int. 29 (6): 1047–54. Disingrini T, Muth M, Dallanoce C, Barocelli E, Bertoni S, Kellershohn K, Mohr K, De Amici M, Holzgrabe U; (2006), J. Med. Chem. 491, 366-372 . Dallanoce, C.; Conti, P.; De Amici, M.; De Micheli, C.; Barocelli, E.; Chiavarini, M.; Ballabeni, V.; Bertoni, S.; Impicciatore, M., (1999), Bioorg. Med. Chem. 7, 1539-1547. Xu J M, Zhang E, Shi X J, Wang Y C, Yu B, Jiao W W, Guo Y Z, Liu H M, (2014), Eur.J. Med. Chem. 80, 593. Saqlain H, A. Sarwar A M, Hinna H, Syed S, Abhijeet D, Firasat H, Perwez A, Sadiq U, Pasha M A Q, Sameena B, Syed N, Yakub A, Chetna K, (2014), Eur. J. Med. Chem. 81, 204. Lee W. W, Bueding E, (1986), Carcinogenesis, 7(8), 1379–1381. Kensler T W, Egner P A, Dolan P M, Groopman J D, B. D. Roebuck B D, (1987), Cancer Research, 47, 4271-4277. Furniss B S; Hannaford A J; Smith P W; Tatchell A R; (1989) "Vogel's Textbook of Practical Organic Chemistry", John Wiley & Sons. Inc. New York, pp.534.