Facile One-Pot Synthesis of Novel Hexahydro-2-quinolinecarboxylic Acids under Solvent-Free Reaction Conditions


A simple and fastthree-component synthesis of new and biologically active hexahydro-2-quinolinecarboxylic acid scaf-fold 4 was carried out using cyclocondensation reaction of arylmethylidenepyruvic acids 1, 1,3-cyclohexandiones 2 and ammonium acetate 3 under solvent-free conditions and at room temperature. This protocol has the advantages of facility, easy work-up, high yields, short reaction time and environmentally friendly character.

Share and Cite:

S. Balalaie, S. Abdolmohammadi and B. Soleimanifard, "Facile One-Pot Synthesis of Novel Hexahydro-2-quinolinecarboxylic Acids under Solvent-Free Reaction Conditions," International Journal of Organic Chemistry, Vol. 2 No. 3, 2012, pp. 276-281. doi: 10.4236/ijoc.2012.23037.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] J. A. Joule, K. Mills and G. F. Smith, “Heterocyclic Chemistry,” 3rd Edition, Chapman & Hall, London, 1995.
[2] M. Q. Zhang, A. Haemers, D. Vanden Berghe, S. R. Pattyn, W. Bollaert and I. Levshin, “Quinolone Antibacterials. 2. 6-Substituted-7-(2-thiazolyl and thiazolidinyl) Quinolones,” Journal of Heterocyclic Chemistry, Vol. 28, No. 3, 1991, pp. 1685-1695. doi:10.1002/jhet.5570280324
[3] K. Roy, R. P. Srivastava, B. L. Tekwani, V. C. Pandev and A. P. Bhaduri, “Syntheses and Exploration of New Biological Activities in Ethyl 6/7-Substituted and 6,7- Disubstituted Quinolin-4-one-3-carboxylates,” Bioorganic & Medicinal Chemistry Letters, Vol. 6, No. 2, 1996, pp. 1121-1126. doi:10.1016/0960-894X(95)00577-G
[4] M. Reuman, S. J. Daum, B. Singh, M. P. Wentland, R. B. Perni, P. Pennock, P. M. Carabateas, M. D. Gruett, M. T. Saindane, P. H. Dorff, S. A. Coughlin, D. M. Sedlock, J. B. Rake and G. Y. Lesher, “Synthesis and Antibacterial Activity of Some Novel 1-Substituted 1,4-Dihydro-4-oxo- 7-pyridinyl-3-quinolinecarboxylic Acids. Potent An- tistaphylococcal Agents,” Medicinal Chemistry, Vol. 38, No. 14, 1995, pp. 2531-2540. doi:10.1021/jm00014a005
[5] S. Bogialli, G. D’Ascenzo, A. Di Corcia, A. Laganà and S. Nicolardi, “A Simple and Rapid Assay Based on Hot Water Extraction and liquid Chromatography-Tandem Mass Spectrometry for Monitoring Quinolone Residues in Bovine Milk,” Food Chemistry, Vol. 108, No. 1, 2008, pp. 2354-2360. doi:10.1016/j.foodchem.2007.10.044
[6] W. H. Suh, K. S. Suslick and Y. H. Suh, “Therapeutic Agents for Alzheimer’s Disease,” Current Medicinal Chemistry Central Nervous System Agents, Vol. 5, No. 4, 2005, pp. 259-269. doi:10.2174/156801505774913035
[7] A. Kumar, S. Sharma, V. D. Tripathi, R. A. Maurya, S. P. Srivastava, G. Bhatia, A. K. Tamrakar and A. K. Sriva- stava, “Design and Synthesis of 2,4-Disubstituted Poly- hydroquinolines as Prospective Antihyperglycemic and Lipid Modulating Agents,” Bioorganic & Medicinal Chemistry Letters, Vol. 18, No. 11, 2010, pp. 4138-4148. doi:10.1016/j.bmc.2009.11.061
[8] N. Bergans, W. Stalmans, S. Goldmann and F. Vanstapel, “Molecular Mode of Inhibition of Glycogenolysis in Rat Liver by the dihydropyridine Derivative, BAY R3401: Inhibition and Inactivition of Glycogen Phosphorylase by an Activated Metabolite,” Diabetes, Vol. 49, No. 9, 2000, pp. 1419-1426. doi:10.2337/diabetes.49.9.1419
[9] S. Goldmann, H. J. Ahr, W. Puls, H. Bischoff, D. Petz- inna, K. Schlossmann and J. Bender, “Dihydropyridine Compounds and Their Use in Reducing Blood Sugar,” Patent No. 4786641, 1988.
[10] G. H. Ladouceur, J. H. Cook, E. M. Doherty, W. R. Schoen, M. L. MacDougall and J. N. Livingston, “Discovery of 5-Hydroxyalkyl-4-phenylpyridines as a New Class of Glucagon Receptor Antagonists,” Bioorganic & Medicinal Chemistry Letters, Vol. 12, No. 3, 2002, pp. 2461-2464. doi:10.1016/S0960-894X(01)00766-1
[11] N. G. Oikonomakos, K. E. Tsitsanou, S. E. Zographos, V. T. Skamnaki, S. Goldmann and H. Bischoff, “Allosteric Inhibition of Glycogen Phosphorylase a by the Potential Antidiabetic Drug 3-Isopropyl 4-(2-Chlorophenyl)-1,4- di-hydro-1-ethyl-2-methyl-pyridine-3,5,6-tricarboxylate,” Protein Science, Vol. 8, No. 10, 1999, pp. 1930-1945. doi:10.1110/ps.8.10.1930
[12] W. R. Schoen, G. H. Ladouceur, J. H. Cook, T. G. Lease, D. J. Wolanin, R. H. Kramss, D. L. Hertzog and M. H. Osterhout, “Substituted biphenyls,” Patent No. 6218431, 2001.
[13] G. S. Poindexter, R. T. Swann, M. A. Bruce, M. A. Morton, Y. Huang, S. Y. Sit and J. G. Breitenbucher, “Dihy- dropyridine NPY Antagonists: Cyanoguanidine Derivatives,” Patent No. 6001836, 1999.
[14] E. Q. Adams, H. L. Haller, “Kryptocyanines. A New Series of Photosensitizing Dyes,” Journal of the American Chemical Society, Vol. 42, No. 12, 1920, pp. 2661- 2663. doi:10.1021/ja01457a026
[15] J. Quiroga, D. Mej??a, B. Insuasty, R. Abon??a, M. No-gueras, A. Sánchez, J. Cobo and J. N. Low, “Regioselective Synthesis of 4,7,8,9-Tetrahydro-2H-pyrazolo[3,4-b]- quinolin-5(6H)-ones. Mechanism and Structural Analysis,” Tetrahedron, Vol. 57, No. 32, 2001, pp. 6947-6953. doi:10.1016/S0040-4020(01)00649-4
[16] X.-S. Wang, M.-M. Zhang, Z.-S. Zeng, D.-Q. Shi, S.-J. Tu, X.-Y. Wei and Z.-M. Zong, “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,” Tetrahe-dron Letters, Vol. 46, No. 42, 2005, pp. 7169-7173. doi:10.1016/j.tetlet.2005.08.091
[17] S. Gowrisankar, J. E. Na, M. J. Lee and J. N. Kim, “Synthesis of 3-Benzyl-2-hydroxy-7,8-dihydro-6H-quinolin-5 -ones from Baylis-Hillman Adducts,” Cheminform, Vol. 36, No. 26, 2005, pp. 319-322. doi:10.1002/chin.200526083
[18] S. Abdolmohammadi and S. Balalaie, “Novel and Efficient Catalysts for the One-Pot Synthesis of 3,4-Dihydro-pyrano[c]chromene Derivatives in Aqueous Media,” Tet- rahedron Letters, Vol. 48, No. 18, 2007, pp. 3299-3303. doi:10.1016/j.tetlet.2007.02.135
[19] S. Balalaie, S. Abdolmohammadi and B. Soleimanifard, “An Efficient Synthesis of Novel Hexahydropyrido[2,3- d]pyrimidine Derivatives from (Arylmethylidene)pyruvic Acids (=(3E)-4-Aryl-2-oxobut-3-enoic Acids) in Aqueous Media,” Helvetica Chimica Acta, Vol. 92, No. 5, 2009, pp. 2932-2936. doi:10.1002/hlca.200800318
[20] S. Balalaie, M. Bararjanian, S. Hosseinzadeh, F. Rominger, H. R. Bijanzadeh and E. Wolf, “Designing a Se- quential Ugi/Ullmann Type Reaction for the Synthesis of Indolo[1,2-a]quinoxalinones Catalyzed by CuI/l-Proline,” Tetrahedron, Vol. 67, No. 38, 2011, pp. 7294-7300. doi:10.1016/j.tet.2011.07.052
[21] M. Bararjanian, S. Balalaie, F. Rominger and S. Barouti, “A Novel and Efficient One-Pot Synthesis of 2-Amino-pyrimidinones and Their Self-Assembly,” Helvetica Chimica Acta, Vol. 93, No. 4, 2010, pp. 2777-2784. doi:10.1002/hlca.200900319
[22] M. Bararjanian, S. Balalaie, F. Rominger, B. Movassagh and H. R. Bijanzadeh, “Six-Component Reactions for the Stereoselective Synthesis of 3-Arylidene-2-oxindoles via Sequential One-Pot Ugi/Heck Carbocyclization/Sonogashira/Nucleophilic Addition,” The Journal of Organic Chemistry, Vol. 75, No. 9, 2010, pp. 2806-2812. doi:10.1021/jo902713x
[23] M. Bararjanian, S. Hosseinzadeh, S. Balalaie and H. R. Bijanzadeh, “Palladium Catalyzed Stereoselective Syn- thesis of 3-(Anilinoarylmethylene)-2-oxindoles as Hes-peradin Analogoues,” Tetrahedron, Vol. 67, No. 14, 2011, pp. 2644-2650. doi:10.1016/j.tet.2011.02.005
[24] M. J. Khoshkholgh, S. Balalaie, R. Gleiter and F. Rom- inger, “Intramolecular Hetero-Diels-Alder Reaction of 1-Oxa-1,3-butadienes with Terminal Acetylenes in Aque- ous Media Using CuI,” Tetrahedron, Vol. 64, No. 48, 2008, pp. 10924-10929. doi:10.1016/j.tet.2008.08.056
[25] M. J. Khoshkholgh, M. Lotfi, S. Balalaie and F. Rom- inger, “Efficient Synthesis of Pyrano[2,3-c]coumarins via In-tramolecular Domino Knoevenagel Hetero-Diels-Alder Reac-tions,” Tetrahedron, Vol. 65, No. 21, 2009, pp. 4228- 4234. doi:10.1016/j.tet.2009.03.032
[26] G. Choudhary and R. K. Peddinti, “An Expeditious, Highly Efficient, Catalyst-Free and Solvent-Free Synthe- sis of Nitroamines and Nitrosulfides by Michael Addi- tion,” Green Chemistry, Vol. 13, No. 2, 2011, pp. 2276- 2282. doi:10.1039/c0gc00830c
[27] Y. Gu, R. De Sousa, G. Frapper, C. Bachmann, J. Barrault and F. Jerome, “Catalyst-Free Aqueous Multicom- ponent Domino Reactions from Formaldehyde and 1,3- Dicarbonyl Derivatives, “Green Chemistry, Vol. 11, No. 12, 2009, pp. 1968-1972. doi:10.1039/b913846c
[28] S. Iliescu, G. Ilia, N. Plesu, A. Popa and A. Pascariu, “Solvent and Catalyst-Free Synthesis of Polyphosphates,” Green Chemistry, Vol. 8, No. 8, 2006, pp. 727-730. doi:10.1039/b602462a
[29] S. L. Jain, S. Singhal and B. Sain, “PEG-Assisted Solvent and Catalyst Free Synthesis of 3,4-Dihydropyrimidinones under Mild Reaction Conditions,” Green Chemistry, Vol. 9, No. 7, 2007, pp. 2740-2741. doi:10.1039/b702311a
[30] M. A. P. Martins, C. P. Frizzo, D. N. Moreira, L. Buriol and P. Machado, “Solvent-Free Hetero-cyclic Synthesis,” Chemical Reviews, Vol. 109, No. 9, 2009, pp. 4140-4182. doi:10.1021/cr9001098
[31] B. C. Ranu, S. S. Dey and A. Hajra, “Highly Efficient Acylation of Alcohols, Amines and Thiols under Solvent-Free and Catalyst-Free Conditions,”Green Chemistry, Vol. 5, No. 1, 2003, pp. 44-46. doi:10.1039/b211238h
[32] L. D. S. Yadav, S. Singh and V. K. Rai, “Catalyst-Free, Step and Pot Economic, Efficient Mercap-toacetylative Cyclisation in H2O: Synthesis of 3-Mercaptocoumarins,” Green Chemistry, Vol. 11, No. 6, 2009, pp. 878-882. doi:10.1039/b904655k
[33] S. Yan, Y. Chen, L. Liu, N. He and J. Lin, “Three-Component Solvent-Free Synthesis of Highly Substituted Bi- cyclic Pyridines Containing a Ring-Junction Nitrogen,” Green Chemistry, Vol. 12, No. 11, 2010, pp. 2043-2052. doi:10.1039/c0gc00373e
[34] J. Zhang, Z. Cui, F. Wang, Y. Wang, Z. Miao and R. Chen, “Mannich Type Reactions of Chlorophosphites, Phosphoramides and Aldehydes (Ketones) under Solvent-Free and Catalyst-Free Conditions-Synthesis of N- Phosphoramino [Small Alpha]-Aminophosphonates,” Green Chemistry, Vol. 9, No. 12, 2007, pp. 1341-1345. doi:10.1039/b710008f
[35] N. Annan, R. Paris and F. Jordan, “(E)-4-(.Alpha.-halo- p-tolyl)-2-oxo-3-butenoic Acids Inhibit Yeast Pyruvate Decarboxylase by a Diversity of Mechanisms: Multiple Fate for the Thiamin-Bound Enamine Intermediate,” Journal of the American Chemical Society, Vol. 111, No. 24, 1989, pp. 8895-8901. doi:10.1021/ja00206a019

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.