Synthesis of Hetaryl Substituted Pyrazolo [3,4-b] Quinolinone Systems by Multicomponent Cyclocondensation Reaction

Year 2024, , 1204 - 1216, 15.11.2024

Mustafa Kemal Gümüş , Şeniz Kaban

https://doi.org/10.34248/bsengineering.1545551

Abstract

In this study, the synthesis of pyrazolo[3,4-b]quinolinone compounds was carried out via one-pot three-component reactions. These reactions proceed as domino processes, making them easier to occur than the conventional multistep organic reactions. By employing this method, new organic molecules can be synthesized in a single step, using minimal time and number of trials. In the first phase of this two-step study, heteroaromatic carbaldehydes (quinoline-8-carboxaldehyde and quinoline-4-carboxaldehyde) were prepared to be used as substrates in subsequent reactions by oxidation of 8-methylquinoline and 4-methylquinoline with selenium dioxide, a mild oxidant. In the second step, heteroaromatic carbaldehyde reacted with aminopyrazole and dimedone in anhydrous ethanol by one-pot multicomponent condensation method to synthesize six compounds with heteryl-substituted pyrazolo[3,4-b]quinolinone ring system. The crude products were obtained in excellent yields and further purified by crystallization. The structures of the compounds, which were found to be completely pure as a result of chromatographic studies, were elucidated by spectroscopic methods and elemental analysis.

Keywords

One-Pot reactions, Quinolinone, Selenium dioxide, Methylquinoline, Multicomponent reactions (MCRs), Biological activity

Synthesis of Hetaryl Substituted Pyrazolo[3,4-b]Quinolinone Systems by Multicomponent Cyclocondensation Reaction

Abstract

In this study, the synthesis of pyrazolo[3,4-b]quinolinone compounds was carried out via one-pot three-component reactions. These reactions proceed as domino processes, making them easier to occur than the conventional multistep organic reactions. By employing this method, new organic molecules can be synthesized in a single step, using minimal time and number of trials. In the first phase of this two-step study, heteroaromatic carbaldehydes (quinoline-8-carboxaldehyde and quinoline-4-carboxaldehyde) were prepared to be used as substrates in subsequent reactions by oxidation of 8-methylquinoline and 4-methylquinoline with selenium dioxide, a mild oxidant. In the second step, heteroaromatic carbaldehyde reacted with aminopyrazole and dimedone in anhydrous ethanol by one-pot multicomponent condensation method to synthesize six compounds with heteryl-substituted pyrazolo[3,4-b]quinolinone ring system. The crude products were obtained in excellent yields and further purified by crystallization. The structures of the compounds, which were found to be completely pure as a result of chromatographic studies, were elucidated by spectroscopic methods and elemental analysis.

Keywords

One-Pot reactions, Quinolinone, Selenium dioxide, Methylquinoline, Multicomponent reactions (MCRs), Biological activity

References

• Blatt AH. 1986. Organic syntheses. Longman Group Ltd., London, UK, Vol: 2, pp: 914.
• Chebanov VA, Gura KA, Desenko SM. 2010. Aminoazoles as key reagents in multicomponent heterocyclizations. In: Orru R, Ruijter E, editors. Synthesis of Heterocycles via Multicomponent Reactions I. Topics in Heterocyclic Chemistry. Springer, Berlin, Heidelberg, Germany, pp: 41-84. https://doi.org/10.1007/7081_2009_21
• Danel A, Gondek E, Kucharek M, Szlachcic P, Gut A. 2022. 1H-Pyrazolo[3,4-b]quinolines: Synthesis and properties over 100 years of research. Molecules, 27(9): 2775. https://doi.org/10.3390/molecules27092775
• Desenko SM, Gorobets MY, Lipson VV, Sakhno YI, Chebanov VA. 2024. Dihydroazolopyrimidines: Past, present and perspectives in synthesis, green chemistry and drug discovery. Chem Rec, 24(e202300244): 1-50. https://doi.org/10.1002/tcr.202300244
• Dogan IS, Gumus MK, Gorobets NY, Reis R, Orak D, Sipahi H, Chebanov VA. 2022. In vitro cytotoxicity of methano[1,2,4]triazolo-[1,5-c][1,3,5]benzoxadiazocine derivatives and their effects on nitrite and Prostaglandin E2 (PGE2) Levels. Pharm Chem J, 56(6): 769-776. https://doi.org/10.1007/s11094-022-02708-w
• Gumus MK. 2009. Cyclocondensation reactions of heteroaromatic systems. PhD thesis, Yıldız Tecnical University, Institute of Science, Istanbul, Türkiye, pp: 1-201.
• Gumus MK, Kansiz S, Dege N, Kalibabchuk VA. 2018. Hirshfeld surface analysis and crystal structure of 7-methoxy-5-methyl-2-phenyl-11,12-dihydro-5,11-methano-1,2,4-triazolo[1,5-c][1,3,5]benzoxadiazocine. Acta Cryst E, 74(9): 1211-1214. https://doi.org/10.1107/S2056989018010848
• Gumus MK, Gorobets MY, Uludag N. 2024. Microwave-assisted synthesis of 5-Substituted 3-Amino-1,2,4-triazoles from aminoguanidine bicarbonate and carboxylic acids. Processes, 12(3): 573. https://doi.org/10.3390/pr12030573
• Kaplan H. 1941. The use of selenium dioxide in the preparation of quinoline aldehydes. JACS, 63(10): 2654-2655.
• Lipson VV, Desenko SM, Shirobokova MG, Borodina VV. 2003a. Synthesis of 9-Aryl-6,6-dimethyl-5,6,7,9-tetrahydro-1,2,4-triazolo-[5,1-b]quinazolin-8(4H)ones. Chem Heterocycl Compd, 39: 1213–1217. https://doi.org/10.1023/B:COHC.0000008269.69460.ac
• Lipson VV, Desenko SM, Shishkina SV, Shirobokova MG, Shishkin OV, Orlov VD. 2003b. Cyclocondensation of 2-Aminobenzimidazole with dimedone and its arylidene derivatives. Chem Heterocycl Compd, 39: 1041–1047. https://doi.org/10.1023/B:COHC.0000003522.71893.77
• Quiroga J, Mejia D, Insuasty B, Abonia R, Nogueras M, Sanchez A, Cobo J, Low JN. 2001. Regioselective synthesis of 4,7,8,9-Tetrahydro-2H-pyrazolo[3,4-b]-quinolin-5(6H)-ones. Mechan Struct Analysis, Tetrahedron, 57: 6947–6953. https://doi.org/10.1016/S0040-4020(01)00649-4
• Quiroga J, Insuasty B, Hormaza A, Saitz C, Jullian C. 1998a. Synthesis of 4‐aryl‐4,7,8,9‐tetrahydro‐6H‐pyrazolo[3,4‐b]quinolin‐5‐ones. J Heterocycl Chem, 35(3): 575-578. https://doi.org/10.1002/jhet.5570350313
• Quiroga J, Hormaza A, Insuasty B, Ortíz AJ, Sánchez A, Nogueras M. 1998b. Synthesis of pyrimido [4,5‐b] quinolines in the reaction of 6‐aminopyrimidines with dimedone and benzaldehydes. J Heterocycl Chem, 35(1): 231-233. https://doi.org/10.1002/jhet.5570350142
• Seyhan M, Fernelius WC. 1957. Formazyl complexes of the quinoline series. J Org Chem, 22: 217-219.
• Wagner FF, Bishop JA, Gale JP, Shi X, Walk M, Ketterman J, Pan JQ. 2016. Inhibitors of glycogen synthase kinase 3 with exquisite kinome-wide selectivity and their functional effects. ACS Chem Biol, 11(7): 1952-1963. https://doi.org/10.1021/acschembio.6b00306
• Zhu J, Bienayme H. 2005. Multicomponent reactions. WILEY-VCH, Weinheim, Germany, pp: 95-114.