Peculiarites of interaction between 3-(2-aminophenyl)-6-R-1,2,4-triazin-5(2H)-ones and cyclic anhydrides of non-symmetric dicarboxylic acids

O. Yu. Voskoboynik, D. Yu. Skorina, S. V. Shishkina, O. V. Shishkin, S. I. Kovalenko, V. V. Ivchuk

Abstract


The peculiarities of the reaction between 3-(2-aminophenyl)-6-R-1,2,4-triazin-5(2H)-ones and cyclic anhydrides of non-symmetric (2-methylsuccinic, 2-phenylsuccinic and camphoric) acids have been described in the present article. The influence of electronic and steric effects of substituents in the anhydride molecule on cyclisation processes has been discussed. The results have shown that the interaction of 3-(2-aminophenyl)-6-R-1,2,4-triazin- 5(2H)-ones mentioned above with 2-methylsuccinic and 2-phenylsuccinic acid anhydrides proceeded non-selectively and yielded the mixtures of 2-R1-3-(2-oxo-3-R-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)propanoic acids and 1-(2-(5-oxo-6-R-2,5-dihydro-1,2,4-triazin-3-yl)phenyl)-3-R1-pyrrolidine-2,5-diones. It has been found that low regioselectivity of the acylation process may be explained by insignificant electronic effects of substituents (of the methyl and phenyl fragment) in position 2 of the anhydride molecule on the electrophilic reaction centre. It has been also determined that the reaction between 3-(2-aminophenyl)-6-R-1,2,4-triazin-5(2H)-ones and camphoric anhydride proceeds regioselectively and yielded 1,2,2-trimethyl-3-(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin- 6-yl)cyclopentan-1-carboxylic acids. Regioselectivity of the interaction mentioned above may be explained by the steric effect of the methyl group. Identity of compounds has been proven by LC-MS, the structure has been determined via a set of characteristic signals in 1H NMR, 13C NMR spectra and position of cross peaks in the correlation HSQC-experiment. Mass spectra of the compounds synthesized have been also studied, the principal directions of the molecule fragmentation have been described. The structure of 1,2,2-trimethyl-3-(3-methyl- 2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)cyclopentane-1-carboxylic acid has been proven by X-ray analysis.


Keywords


anhydrides of non-symmetric dicarboxylic acids; cyclisation; X-ray experiment

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References


Sergeieva T. Yu., Voskoboynik O. Yu., Okovytyy S. I., Kovalenko S. I., Shishkina S. V., Shishkin O. V., Leszczynski J. J. Phys. Chem. A., 2014, 118, pp.1895-1905. doi: 10.1021/jp4052616.

Kovalenko S. I., Nosulenko I. S., Voskoboynik A. Yu., Berest G. G., Antipenko L. M., Antipenko A. N., Katsev A. M. Med. Chem. Res., 2013, 22(6), pp.2610-2632. doi: 10.1007/s00044-012-0257-x.

Kovalenko S. I., Nosulenko I. S., Voskoboynik A. Yu., Berest G. G., Antipenko L. M., Antipenko A. N., Katsev A. M. Sci. Pharm., 2012, 80, pp.837-865.10.3797/scipharm.1208-07.

Berest G. G., Voskoboynik O. Yu., Kovalenko S. I., Nosulenko I. S., Antipenko L. M., Antipenko O. M., Shvets V. M., Katsev A. M. Sci. Pharm., 2012, 80 (1), pp.37-65. doi:10.3797/scipharm.1111-15.

Berest G. G., Voskoboynik A. Yu., Kovalenko S. I., Antipenko A. M., Nosulenko I. S., Katsev A. M., Shandrovskaya A. S. Eur. J. Med. Chem., 2011, 46 (12), pp.6066-6074. doi: 10.1016/j.ejmech.2011.10.022.

Voskoboynik A. Yu., Scorina D. Yu., Sergeieva T. Yu., Kovalenko S. I., Okovytyy S. I., Omelchenko I. V., Shishkin O. V. J. Het. Chem. (in press) doi: 10.1002/jhet.2120.

UA Utility Model Patent №U201214626 Salts of (3-R-8-R1-9-R2-10-R3-11-R4-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl) alkylcarboxylic acids improving physical endurance of body Stepaniuk H. I., Pochelova O. V., Chornoivan N. H., Voskoboinik O. Y., Skoryna D. Y., Kovalenko S. I. Published 20.12.2012.

UA Utility Model Patent №U201306088 Use of sodium salt of 4-(2-oxo-3-methyl-2H-[1,2,4]triazino[2,3-c]-quinazolin-6-yl) butanoic acid as cerebroprotective agents Semenenko N. O., Stepaniuk H. I., Semenenko A. I., Kovalenko S. I., Voskoboinik O. Yu., Skoryna D. Yu. Published 17.05.2013.

UA Utility Model Patent №U 2001064232 Antidiabetic agent “Diakamf”, which reveals the hypoglycemic, antidiabetogenic and antioxidant action Merzlikin S. I., Chernykh V. P., Hladkykh O. I., Chueshov V. I., Pashnev P. D. Published 15.04.2002.

Karpenko O. V., Kovalenko S. I., Chekotylo O. O., Shishkina S. V. Heterocycles, 2007, 71 (3), pp.619-626. doi: 10.3987/COM-06-10971.

Zefirov Yu. V. Crystallography, 1997, 42 (5), pp.936-958.

Burgi H.-B., Dunitz J. D. Structure correlation. Vol. 2. VCH. Weinheim. 1994, pp.741-784.

Sheldrick G. M. Acta Crystallogr., Sect. A, 2008, A64, pp.112-122.


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DOI: https://doi.org/10.24959/ophcj.15.817

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