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. New series. Series: Chemistry. Biology. Ecology, 2019, vol. 19, iss. 2, pp. 128-132. DOI: https://doi.org/10.18500/1816-9775-2019-19-2-128-132


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547.856.1
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Russian

Synthesis and Ways of Formation of Hydroxyphenyl Substituted Triazolohexahydroquinazolines

Abstract

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.

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