Cite this article as:
Demidova D. M., Vasilkova N. O., Krivenko A. P. Synthesis and Ways of Formation of Hydroxyphenyl Substituted Triazolohexahydroquinazolines. Izvestiya of Saratov University. Chemistry. Biology. Ecology, 2019, vol. 19, iss. 2, pp. 128-132. DOI: https://doi.org/10.18500/1816-9775-2019-19-2-128-132
Synthesis and Ways of Formation of Hydroxyphenyl Substituted Triazolohexahydroquinazolines
With three-component condensation of 1,2,4-triazol-3-amine, hydroxy-substituted aromatic aldehyde (2-hydroxybenzaldehyde, 4-hydroxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde, 2-naphthalene-carbaldehyde), cyclohexanone, the aldehyde component has a defining impact on the shaping of triazologic hydroquinazolines with different types of rings articulation and the position of the double bond in them (C4a–C5 and C4a–C8a). When salicylic aldehyde is used, the positional isomers of the triazologic hexahydroquinazolines of angular and linear structure are formed in an equimolar ratio. When the hydroxyl group in the aldehyde is moved from the ortho to the para position, the reaction proceeds similarly, but the proportion of the linear isomer increases (the ratio of the angular and linear isomers = 1:2), which can be associated with a decrease in the possibility in stabilization of the angular isomer due to electronic and steric factors in the convergence of NH- and OH-groups. Condensation of 4-hydroxy-3-methoxybenzaldehyde (2-hydroxynaphthalenecarbaldehyde), 1,2,4-triazol-3-amine and cyclohexanone proceeds selectively with the formation of 9- (4-hydroxy-3-methoxyphenyl (2-hydroxynaphthalenyl)) hexahydro-triazolo [5,1-b] quinazoline linear structure and different position of the double bond (C4a–C5). This result can be explained by the possibility of isomerization of the initially arising triazologic hexahydroquinazolines with a 1,4-dihydropyrimidine fragment, which is facilitated by the reaction conditions (acid catalysis) and the presence of bulky aryl substituents. The composition and structure of the products are confirmed by elemental analysis data, IR and 1H NMR spectra. Thus, new members of a series of triazologohydroquinazolines have been synthesized, containing pharmacophoric hydroxyaryl substituents substituents, providing the potential for further study of their biological activity.
1. Ajani O. O. Quinazoline pharmacophore in therapeutic medicine. Bangladesh J. Pharmacol., 2016, vol. 11, no. 3, pp. 716–733. DOI: https://doi.org/10.3329/bjp.v11i3.25731
2. Carmen Balo, Carmen López, José Manuel Brea, Franco Fernánde, Olga Caamaño. Synthesis and Evaluation of Adenosine Antagonist Activity of a Series of [1,2,4] Triazolo[1,5-c]quinazolines. Chem. Pharm. Bull., 2007, vol. 55, pp. 372–375. DOI: https://doi.org/10.1248/cpb.55.372
3. Rashad Al-Salahi, Kamal-Eldin El-Tahir, Ibrahim Alswaidan, Nabih Lolak, Mohammed Hamidaddin, Mohamed Marzouk. Biological effects of a new set 1,2,4-triazolo[1,5- a]quinazolines on heart rate and blood pressure. Chem. Cent. J., 2014, vol. 8, pp. 1–8. DOI: https://doi.org/10.1186/1752-153X-8-3
4. Alagarsamy V., Pathak U. S. Synthesis and antihypertensive activity of novel 3-benzyl-2-substituted 3H-[1,2,4]triazolo[5,1-b]quinazolin-9-ones. Bioorg. Med. Chem., 2007, vol. 15, pp. 3457–3462. DOI: https://doi.org/10.1016/j.bmc.2007.03.007
5. Khazhieva I. S., Glukhareva T. V., El’tsov O. S., Morzherin Yu. Yu., Minin A. A., Pozdina V. A., Ulitko M. V. Synthesis and study of cytotoxic effect of 1,2,3-triazole derivatives on glioma cells. Pharm. Chem. J., 2015, vol. 49, no. 5, pp. 12–15. DOI: https://doi.org/10.30906/0023-1134-2015-49-5-12-15
6. Boechat N., Pinheiro L. C. S., Silva T. S., Aguiar A. C. C., Carvalho A. S., Bastos M. M., Costa C. C. P., Pinheiro S., Pinto A. C., Mendonça J. S., Dutra K. D. B., Valverde A. L., Santos-Filho O. A., Ceravolo I. P., Krettli A. U. New Trifluoromethyl Triazolopyrimidines as Anti-Plasmodium falciparum Agents. Molecules, 2012, vol. 17, pp. 8285–8302. DOI: https://doi.org/10.3390/molecules17078285
7. Chebanov V. A., Desenko S. M., Gurley T. W. Azaheterocycles Based on α, β-Unsaturated Carbonyls. Berlin, Heidelberg, Springer Verlag, 2008. 210 p.
8. Ivonin M. A., Al Fahdawi A. H. A., Sorokin V. V., Kriven’ko A. P. Synthesis and Ways of Formation of Hydroxyphenyl Substituted Benz[4,5]imidazole-1,2,3,4,5,6-hexahydro[1,2-a]quinazolines. Izv. Saratov Univ. (N. S.), Ser. Chemistry. Biology. Ecology, 2018, vol. 18, iss. 1, pp. 4–8 (in Russian). DOI: https://doi.org/10.18500/1816-9775-2018-18-1-4-8
9. Vasil’kova N. O., Kriven’ko A. P. Trekhkomponentnyj sintez orto-fenilzameshchennyh tetrazologeksagidrohinazolinov. Vliyanie orto-effekta na sootnoshenie pozicionnyh izomerov. Int. Sci. publ. SWorld : collected papers. Odessa, 2015, vol. 25, iss. 1, pp. 4–7.
10. Vasil’kova N. O., Anis’kov A. A., Sorokin V. V., Kriven’ko A. P. Three-component condensation of 1,2,4-triazol-3-amine with cyclohexanone and ortho-substituted benzaldehydes. J. Org. Chem., 2018, vol. 54, no. 6, pp. 928–931. DOI: https://doi.org/10.1134/S1070428018060179
