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Current Organic Synthesis

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ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

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Research Article

Synthesis and Structure of Hetaryl Substituted 2,5-dioxo-1,2,3,4,5,6,7,8- Octahydroquinolines

Author(s): Kadri Gokhan Ozokan* and Seniz Kaban*

Volume 19, Issue 5, 2022

Published on: 19 April, 2022

Page: [664 - 672] Pages: 9

DOI: 10.2174/1570179419666220406233307

Price: $65

Abstract

Aims and Objective: Condensation of 5-hetarylidene-2,2-dimethyl-1,3-dioxane-4,6- diones with 5,5-dimethyl-3-arylamino-2-cyclohexanones yields 1-aryl-4-hetaryl-7,7-dimethyl-2,5- dioxo-l,2,3,4,5,5,7,8-octahydro-quinolines. The structures of all the synthesized compounds have been verified by IR, 1H-NMR, 13C-NMR, and mass spectral methods. The 13C-NMR assignments were supported by HSQC and HMBC experiments. Moreover, spin decoupling and NOE experiments have been carried out in order to elucidate stereoisomeric configurations of the compounds. It has been established that the N-phenyl ring, which projects from the plane of the octahydroquinolinedione ring, has a shielding effect on the magnetic field of the protons at 7- and 8-positions of the ring in the molecules of the compounds synthesized.

Materials and Methods: The NMR spectra were recorded on a Varian Gemini spectrometer [400 MHz (1H) and 100 MHz (13C)]. EI mass spectra were obtained with a Hewlett Packard GC/MS 6890/5973 machine. MALDI-TOF mass measurements were recorded on a Bruker auto-flex III smart beam.

Results: Various reaction conditions were applied in order to find an optimum and convenient procedure for the formation of octahydroquinoline derivates having hetaryl group. The highest yields (40-50 %) were achieved using acetic acid as solvent, p-toluenesulphonic acid as acidic catalyst, and excess enaminone (1.5 equiv).

Conclusion: We synthesized eight new 1-aryl-7,7-dimethyl-4-hetaryl-1,2,3,4,5,6,7,8-octahydroquinoline- 2,5-dione compounds containing thienyl core as a result of Michael addition reaction of Knoevenagel products of Meldrum’s acid with dimedone enaminone compounds. Optimum circumstances were established using various reaction conditions and catalyzers throughout the research. The structures of all the synthesized compounds were analyzed by IR, 1H-NMR, 13CNMR, and mass spectral methods. Furthermore, the structures were verified with the help of 2D (HSQC and HMBC), spin decoupling, and NOE NMR techniques.

Keywords: Octahydroquinoline, knoevenagel, enaminone, spin decoupling, NOE, HSQC, HMBC, stereoisomeric configuration.

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[1]
Enders, D.; Demir, A.S. Asymmetric michael addition/lactamization via SAMP-/RAMP-hydrazones enantioselective synthesis of substituted tetrahydro-2,5(1H,3H)-quinolinediones. Tetrahedron Lett., 1987, 28, 3795-3798.
[http://dx.doi.org/10.1016/S0040-4039(00)96386-X]
[2]
Muller, E.; Nickl, J.; Heckel, A.; Engelhardt, G. Pharmaceutical compositions containing quinolin-2,5-diones, new ouinolin-2,5- diones and processes for the preparation thereof. U.S. Patent 5,068,334, 1991.
[3]
Strozhev, M.F.; Lielbriedis, I.E. Condensation of arylideneisopropylidenemalonates with 3-carboxyphenylamino-cyclohexen-2-ones. Chem. Heterocycl. Compd., 1990, 26, 790-792.
[http://dx.doi.org/10.1007/BF00509709]
[4]
Strozhev, M.F.; Lielbriedis, I.E.; Neiland, O.Y. Condensation of dimedone N-methylimine with isopropylidene arylidenemalonates. Chem. Heterocycl. Compd., 1990, 26, 655-657.
[http://dx.doi.org/10.1007/BF00756417]
[5]
Strozhev, M.F.; Lielbriedis, I.E. Synthesis and structure of 1,4-diaryl-7,7-dimethyl-1,2,3,4,5,6,7,8-octahydroquinoline-2,5-diones. Chem. Heterocycl. Compd., 1993, 29, 1048-1053.
[http://dx.doi.org/10.1007/BF00534391]
[6]
Anil, B.; Ozokan, K.G.; Kaban, S.; Sahin, E.; Kazaz, C. Synthesis and spectral investigation of some new hetaryl-substituted hydroquinolinone derivatives. Magn. Reson. Chem., 2016, 54(2), 184-189.
[http://dx.doi.org/10.1002/mrc.4361] [PMID: 26418336]
[7]
Wang, X.S.; Zhang, M.M.; Jiang, H.; Yao, C.S.; Tu, S.J. Three-component green synthesis of N-arylquinoline derivatives in ionic liquid [Bmim+][BF4-]: reactions of arylaldehyde, 3-arylamino-5,5-dimethylcyclohex-2-enone, and active methylene compounds. Tetrahedron, 2007, 63, 4439-4449.
[http://dx.doi.org/10.1016/j.tet.2007.03.068]
[8]
Wang, X.S.; Zhang, M.M.; Zeng, Z.S.; Shi, D.Q.; Tu, S.J.; Wei, X.Y.; Zong, Z.M. A simple and clean procedure for the synthesis of polyhydroacridine and quinoline derivatives: reaction of Schiff base with 1,3-dicarbonyl compounds in aqueous medium. Tetrahedron Lett., 2005, 46, 7169-7173.
[http://dx.doi.org/10.1016/j.tetlet.2005.08.091]
[9]
Jiang, H.; Wang, X.S.; Zhang, M.M.; Li, Y.L.; Shi, D.Q. 2-Amino-4-(2-chlorophenyl)-7,7-dimethyl-1-(4-methylphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile. Acta Crystallogr. Sect. E Struct. Rep. Online, 2006, 62, o1184-o1186.
[http://dx.doi.org/10.1107/S1600536806006465]
[10]
Suarez, M.; Ochoa, E.; Verdecia, Y.; Pita, B.; Moran, L.; Martin, N.; Quinteiro, M.; Seoane, C.; Soto, J.L.; Novoa, H.; Blaton, N.; Peters, O.M. A joint experimental and theoretical structural study of novel substituted 2,5-dioxo-l,2,3,4,5,6,7,8-octahydroquinolines. Tetrahedron, 1999, 55, 875-884.
[http://dx.doi.org/10.1016/S0040-4020(98)01078-3]
[11]
Tu, S.J.; Wei, Q.; Ma, H.; Shi, D.; Gao, Y.; Cui, G. The synthesis of novel substituted 2,5-Dioxo-1,2,3,4,5,6,7,8-octahydro-quinolines without solvent under microwave irradiation. Synth. Commun., 2001, 31, 2657-2661.
[http://dx.doi.org/10.1081/SCC-100105393]
[12]
Tu, S.J.; Zhu, X.; Zhang, J.; Xu, J.; Wang, Q. 4-(4-Chlorophenyl)-1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinoline-2,5-dione. Acta Crystallogr. Sect. E Struct. Rep. Online, 2005, 61, o3536-o3537.
[http://dx.doi.org/10.1107/S1600536805008573]
[13]
Tu, S.J.; Zhu, X.; Zhang, J.; Xu, J.; Wang, Q. 1-Cyclopentyl-4-(4-fluorophenyl)-7,7-dimethyl-4,6,7,8-tetrahydroquinoline-2,5-dione. Acta Crystallogr. Sect. E Struct. Rep. Online, 2005, 61, o4372-o4373.
[http://dx.doi.org/10.1107/S1600536805038936]
[14]
Rodriguez, H.; Suarez, M.; Perez, R.; Petit, A.; Loupy, A. Solvent-free synthesis of 4-aryl substituted 5-alkoxycarbonyl-6-methyl-3,4-dihydropyridones under microwave irradiation. Tetrahedron Lett., 2003, 44, 3709-3712.
[http://dx.doi.org/10.1016/S0040-4039(03)00625-7]
[15]
Ziarani, G.M.; Asadi, S.; Badiei, A.; Mousavi, S.; Gholamzadeh, P. One-pot four-component synthesis of 2,5-dioxo-1,2,3,4,5,6,7,8-octahydroquinolines catalyzed by silica based sulfonic acid. Res. Chem. Intermed., 2015, 41, 637-645.
[http://dx.doi.org/10.1007/s11164-013-1217-x]
[16]
Wang, S.X.; Guo, S.B.; Gao, M.Z.; Li, J.T.; Duan, Y.F. Infrared irradiation synthesis of substituted 5-Oxo-1, 2, 3, 4, 5, 6, 7, 8-octahydroquinoline derivatives under solvent-free conditions. J. Chem., 2006, 3, 159-163.
[17]
Maheswara, M.; Siddaiah, V.; Damu, G.L.V.; Rao, C.V. An efficient one-pot synthesis of polyhydroquinoline derivatives via hantzsch condensation using heterogeneous catalyst under solvent-free conditions. ARKIVOC, 2006, ii, 201-206.
[http://dx.doi.org/10.3998/ark.5550190.0007.223]
[18]
Jiang, T.S.; Feng, Z.J.; Yuan, G.; Hong, L.X. Crystal structure of 4-(4-chlorophenyl)-7,7-dimethyl-2,5-dioxo-1,2,3,4,5,6,7,8-octa-hydroquinoline. Chinese J. Struct. Chem., 2001, 20, 459-461.
[19]
Wang, X.S.; Shi, D.Q.; Tu, S.J. A convenient synthesis of 2,4-diarylpolyhydroquinoline derivations in the presence of ammonium acetate. Synth. Commun., 2002, 32, 3449-3454.
[http://dx.doi.org/10.1081/SCC-120014775]
[20]
Novoa, D.; Armes, H. Blaton, N.; Peeters, O.M.; De Ranter, C.; Suarez Navarro, M.; Verdecia Reyes, Y.; Ochoa Rodriguez, E.; Moran del Prado, L.; Martin Leon, N.; Quinteiro Fernandez, M.; Seoane Prado, C.; Soto Camara, J.L. Synthesis, structural studies and pharmacological activity of novel bicyclic compounds derived from 3,4-dihydropyridones: 4-Aryl-7,7-dimethyl-2,5-dioxo-1,2,3,4,5,6,7,8-octahydroquinolines. J. Pharm. Belg., 1999, 54, 48-50.
[21]
Krapivin, G.D.; Kulnevich, V.G.; Valter, N. 2,2-Dimethyl-5-(5-R-2-furfurylidene)-1,3-dioxan-4,6-diones. 1. Synthesis, properties, and structure. Chem. Heterocycl. Compd., 1986, 22, 1072-1075.
[http://dx.doi.org/10.1007/BF00473480]
[22]
Krapivin, G.D.; Zavodnik, V.E.; Belskii, V.K.; Valter, N.I.; Kulnevich, V.G. 2,2-Dimethyl-5-(5-R-2-furfurylidene)-1,3-dioxane-4,6-diones 2. Crystal and molecular structure of 2,2-dimethyl-5-(5-methyl-2-furfurylidene)-1,3-dioxane-4,6-dione. Chem. Heterocycl. Compd., 1988, 24, 1200-1203.
[http://dx.doi.org/10.1007/BF00633494]
[23]
Krapivin, G.D.; Valter, N.I.; Zavodnik, V.E.; Vegkh, D.; Fishera, L.; Kulnevich, V.G. 2,2-dimethyl-5-(5-R-furfurylidene)-1,3-dioxane4,6 diones 7. Synthesis, structure, and properties of 2,2dimethyl-5-(3-furfuryldiene and 3-thienylidene)-1,3dioxane-4,6-diones. Chem. Heterocycl. Compd., 1995, 31, 782-787.
[http://dx.doi.org/10.1007/BF01170736]
[24]
Scott, K.R.; Edafiogho, I.O.; Richardson, E.L.; Farrar, V.A.; Moore, J.A.; Tietz, E.I.; Hinko, C.N.; Chang, H.; el-Assadi, A.; Nicholson, J.M. Synthesis and anticonvulsant activity of enaminones. 2. Further structure-activity correlations. J. Med. Chem., 1993, 36(14), 1947-1955.
[http://dx.doi.org/10.1021/jm00066a003] [PMID: 8336334]
[25]
Scott, K.R.; Nicholson, J.M.; Edafiogho, I.O. Enanimone Esters. U.S. Patent 5,616,615, 1997.

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