Synthesis and using of 10-hydroxy-3,3,6,6-tetramethyl-9-(4-hydroxy-3-methoxyphenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridin-1,8-dion as acid base titration indicator

The aim of this work is the synthesis of new 10-hydroxydecahydroacridine-1,8-dione derivative, determination of the structure and to study the possibility of using this compound as an indicator of acid-base titration. Environmentally friendly synthesis of 10-hydroxy-3,3,6,6-tetramethyl-9-(4-hydroxy-3-methoxyphe-nyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridin-1,8-dion has been developed by one pot interaction of dimedone, hydroxylamine and 4-hydroxy-3-methoxybenzoic aldehyde in water-alcohol or water solution using citric acid or sodium dodecyl sulfate as catalysts, respectively. Purification of the synthesized compound was carried out by crystallization from ethanol. The obtained compound was characterised by ¹H NMR ,¹³C NMR and UV-Vis spectroscopies. This substance in water-alcohol solution shows intense violet light absorption. Addition alkali induces red shift of absorption maximum to the blue region. UV irradiation of solution of this substance in alcohol induces two-band fluorescence in the visible region. One band disappears upon addition of a base in solution. The structure of the obtained compound was confirmed by high resolution massspectrometry analysis. In the mass-spectrum of 10-hydroxy-3,3,6,6-tetramethyl-9-(4-hydroxy-3-methoxyphe-nyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridin-1,8-dion observed [M+1]⁺ ion peak. The base peak corresponds to tricyclic fragment due to the elimination aromatic cycle from molecular ion. This substance is colorless in acidic and neutral and pink in base solutions. The acid dissociation constant of this compound in a water-alcohol solution was determined by the UV-Vis spectroscopic technique. It was shown that the obtained compound can be used as an indicator for the titration of strong acids and bases.

1. Ozols YaYa, Pyrko AN, Lakhvich FA, Vigante VA, Dubure RR, Dubur GYa, et al. Synthesis of decahydrophenanthridine-1,7-dione and hexahy-droisoquinol-8-one derivatives in the reaction of 2-acetyl-2-cyclohexene-1-ones with conjugated en-aminocarbonyl compounds. Chemistry of Heterocyclic Compounds. 1990;26(1):58-62. https://di.org/10.1007/BF00506849

2. Ozols YaYa, Pyrko AN, Vigante BA, Dubure RR, Dubur GYa. Synthesis of phenyl-substituted derivatives of decahydro-1,7-phenanthridinedione and hexahydro-8-isoquinolone. Chemistry of Heterocyclic Compounds. 1992;28(5):530-534. https://doi.org/10.1007/BF00475250

3. Milkovic L, Vukovic T, Zarkovic N, Tatzber F, Bisenieks E, Kalme Z, et al. Antioxidative 1,4-dihy-dropyridine derivatives modulate oxidative stress and growth of human osteoblast-like cells in vitro. Antioxidants. 2018;7(9):1-23. https://doi.org/10.3390/antiox7090123

4. Mishnev A, Bisenieks E, Mandrika I, Pe-trovska R, Kalme Z, Bruverea I, et al. Crystal structure and metabolic activity of 4-(thien-2-yl)-2-me-thyl-5-oxo-1,4,5,6,7,8-hexahydrouinoline-3-carboxy-lic acid ethoxycarbonylphenyl-methylester. Acta Cry-stallographica. Section E. 2018;E74:1577-1579. https://doi.org/10.1107/S2056989018014251

5. Shekari F, Sadeghpour H, Javidnia K, Saso L, Nazari F, Firuzi O, et al. Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells. European Journal of Pharmacology. 2015;746:233-244. https://doi.org/10.1016/j.ejphar.2014.10.058

6. Velena A, Zarkovic N, Troselj KG, Bisenieks E, Krauze A, Poikans J, et al. 1,4-Dihydropyridine derivatives: dihydronicotinamide analogues - model compounds targeting oxidative stress. Oxidative Medicine Celluar Longevity. 2016;216. Article ID 1892412. https://doi.org/10.1155/2016/1892412

7. Marjani AP, Khalafy J, Chitan M, Mahmoodi S. Microwave-assisted synthesis of acridine-1,8(2H,5H)-diones via a one-pot, three component reaction. Iranian Journal of Chemistry and Chemical Engineerig. 2017;36(2):1-6.

8. Nalini V, Girija R. Synthesis, characterization and biological studies of 9-aryl substituted acridinedione derivatives by Hantzsh condensation. International Journal of Current Reserch. 2013;5 (10):3076-3081.

9. Safaei-Ghomi J, Ghasemzadeh MA, Zahe-di S. ZnO nanoparticles: a highly efective and readily recyclable catalyst for the one-pot synthesis of 1,8-dioxo-decahydroacridine and dioxooctahydro-xanthene derivatives. Journal of the Mexican Chemical Society. 2013;57(1):1-7.

10. Xia J-J, Zhang K-H. Synthesis of N-substituted acridinediones and polyhydroquinoline derivatives in refluxing water. Molecules. 2012;17(5):5339-5345. https://doi.org/10.3390/molecules17055339

11. Kalalawe VG, Munde RD, Kagne RP, Ni-wadange SN, Gutte RD. Synthesis of acridine derivatives using ionic liquid as promoter. International Journal of Green and Herbal Chemistry. Section B. 2018;7(2):188-193. https://doi.org/10.24214/IJGHC/GC/7/2/18893

12. Nakhi A, Srinivas PV, Rahman MS, Kisho-re R, Seerapu GPK, Kumar KL, et al. Amberlite IR-120H catalyzed MCR: design, synthesis and crystal structure analysis of 1,8-dioxo-decahydroacridines as potential inhibitors of sirtuins. Bioorganic and Medicinal Chemistry Letters. 2013;23(6):1828-1833. https://doi.org/10.1016/j.bmcl.2013.01.026

13. Shchekotikhin YuM, Nikolaeva TG, Shub GM, Kriven’ko AP. Synthesis and antibacterial activity of substituted 1,8-dioxodecahydroacridines. Pharmaceutical Chemistry Journal. 2001 ;35(4):206-211.

14. Jezek J, Sebestic J, Hlavacek J. Biomedical applications of acridines: derivatives, syntheses, properties and biological activities a focus on neuro-degenerative diseases. Springer International Publishing AG; 2017. 236 p. https://doi.org/10.1007/978-3-319-63953-6

15. Pesyan NN, Akhteh N, Batmani H, Anil B, §ahin E. A facile and catalyst-free synthesis of hexahydroacridine-1,8(2H,5H )-dione and octahy-droacridin-10(1H )-yl)thiourea derivatives: Inter- and Intramolecular Aza-Michael addition. Heterocyclic Communications. 2020;26(1):26-32. https://doi.org/10.1515/hc-2020-0005

16. Pyrko AN. Synthesis and biological testing for pesticidal activity of 9-aryl-n-aryl, alkyl-sub-stituted 1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione derivatives. Izvestiya Vuzov. Prikladnaya Khimiya i Biotekhnologiya = Proceedings of Universities. Applied Chemistry and Biotechnology. 2017;7(2):16-20. (In Russian) https://doi.org/10.21285/2227-2925-2017-7-1-16-20

17. Gutsulyak KV, Manzhara VS, Mel'nik MV, Kalin TI. Relationship between the structure and photostability of decahydroacridine derivatives. Journal of Applied Spectroscopy. 2005;72(4):488-494. https://doi.org/10.1007/s10812-005-0102-9

18. Pyrko AN. Synthesis and transformations of new 1,2,3,4,5,6,7,8,9,10- decahydroacridine-1,8-dione derivatives. Russian Journal of Organic Chemistry. 2008;44(8):1215-1224. https://doi.org/10.1134/S1070428008080198

19. Beletskaya IP, Kustov LM. Catalysis as an important tool of green chemistry. Russian Chemical Reviews. 2010;79(6):493-515. https://doi.org/10.1070/RC2010v079n06ABEH004137

20. Christian GD, Dasgupta PK, Schug KA. Analytical chemistry. 7th revised ed. Washington: Wiley; 2013. 848 p.

21. Shchekotikhin YuM, Nickolaeva TG. Characteristics of the dissociative ionization of 9-aryl-(hetaryl)-3,3,6,6-tetra- methyldecahydroacridine-1,8-diones under the influence of electron impact. Chemistry of Heterocyclic Compounds. 2004;40(8): 1031-1035. https://doi.org/10.1023/B:COHC.0000046693.85136.ac