A Convenient Base-Mediated Diastereoselective Synthesis of 2-Oxo-N,4,6-triarylcyclohex-3-enecarboxamides via Claisen-Schmidt Condensation

Document Type : Research Article

Author

Young Researchers and Elites Club, Science and Research Branch, Islamic Azad University, Tehran, I.R. IRAN

Abstract

Sodium acetate catalyzed the multi-component reaction of acetophenone, aromatic aldehydes, and acetoacetanilide in the water-ethanol mixture (1:1) at ambient temperature via Claisen-Schmidt condensation results in the formation of highly substituted cyclohexenones in 89–98% yields. The developed efficient catalytic approach to the substituted cyclohexenones – the promising compounds for inflammation and autoimmune diseases therapy and different biomedical applications – is beneficial from the viewpoint of diversity-oriented large-scale processes and represents facile, efficient and environmentally benign synthetic concept for multicomponent reactions strategy. This protocol offers several advantages including high yields, operational simplicity, clean reaction conditions, the minimum pollution of the environment, no need to column chromatography and simple work-up procedure.

Keywords

Main Subjects


[1] Domling A., Ugi I., Multicomponent Reactions with Isocyanides, Angew. Chem. Int. Ed., 39: 3168-3210 (2000).
[2] Brase S., Gil C., Knepper K., The Recent Impact of Solid-phase Synthesis on Medicinally Relevant Benzoannelated Nitrogen Heterocyclic, Bioorg. Med. Chem., 10: 2415-2437 (2002).
[4] Ugi I., Recent Progress in the Chemistry of Multicomponent Reactions, Pure Appl. Chem., 73: 187-191 (2001).
[5] Bonne D., Dekhane M., Zhu J., Modulating the Reactivity of α-Isocyanoacetates: Multicomponent Synthesis of 5-Methoxyoxazoles and Furopyrrolones, Angew. Chem. Int. Ed., 46: 2485-2488 (2007).
[6] Yoshida H., Fukushima H., Ohshita J., Kunai A., CO2 Incorporation Reaction Using Arynes: Straightforward Access to Benzoxazinone, J. Am. Chem. Soc., 128: 11040-11041 (2006).
[7] Duan X.H., Liu X.Y., Guo L.N., Liao M.C., Liu W.M., Liang Y.M., Palladium-catalyzed One-pot Synthesis of Highly Substituted Furans by a Three-component Annulation Reaction, J. Org. Chem., 70: 6980-6983 (2005).
[10] Tietze L.F., Brasche G., ″In Domino Reactions in Organic Synthesis″, (Ed.), Gericke K., Wiley-VCH, Weinheim, (2006).
[11] Zhu J., ″In Multicomponent Reactions″, (Ed.), Bienayme H., Wiley-VCH, Weinheim, (2005).
[12] Jiang B., Tu S.J., Parminder K., Walter W., Li G., Four-component Domino Reaction Leading to Multifunctionalized Quinazolines, J. Am. Chem. Soc., 131: 11660-11661 (2009).
[13] Jiang B., Shi F., Tu S.J., Microwave-assisted Multicomponent Reactions in the Heterocyclic Chemistry, Curr. Org. Chem., 14: 357-378 (2010).
[14] Hernandez J.G., Juaristi E., Recent Efforts Directed to the Development of More Sustainable Asymmetric Organocatalysis, Chem. Commun., 48: 5396-5409 (2012).
[16] Helene P., Recent Developments in Asymmetric Organocatalytic Domino Reactions, Adv. Synth. Catal., 354: 237-294 (2012).
[17] Mohammadi Ziarani G., Aleali F., Lashgari N., Badiei A., An Efficient Green Approach for the Synthesis of Structurally Diversified Spirooxindoles Using Sulfonic Acid Functionalized Nanoporous Silica (SBA-Pr-SO3H), Iran. J. Chem. Chem. Eng. (IJCCE), 35: 17-23 (2016).
[19] Padmavathi V., Sharmila K., Balaiah A., Reddy A.S., Reddy D.B., Cyclohexenone Carboxylates. A Versatile Source for Fused Isoxazoles and Pyrazoles, Synth. Commun., 31: 2119-2126 (2001).
[21] Padmavathi V., Sharmila K., Padmaja A., Reddy D.B., An Efficient Synthesis of 6,8-Diaryl-carbazoles via Fischer Indole Cyclizations, Heterocycl. Commun., 5: 451-456 (1999).
[22] Heathcock C.H., Ellis J.E., McMurry J.E., Coppolino A., Acid-catalyzed Robinson Annelations, Tetrahedron Lett., 12: 4995-4996 (1971).
[23] Acheson R.M., Robinson R., Experiments Bearing on the Synthesis of Cortisone. Part I. Some Cyclopentenone Derivatives, J. Chem. Soc., 1127-1133 (1952).
[24] Hiromichi F., Naoyuki K., Yoshinari S., Yasushi N., Yasuyuki K., Concise Asymmetric Synthesis of a Model Compound, (4S,5S,6S)-6-(2,2-Dimethoxy)ethyl-4,5-epoxy-6-hydroxy-2-cyclohexenone, for the Cyclohexenone Core of Scyphostatin, Tetrahedron Lett., 43: 4825-4828 (2002).
[25] Safaei-Ghomi J., Alishahi Z., The Preparation of Some Novel Indazole Derivatives by Using Chalcones, J. Fudan. Univ. Nat. Sci., 44: 789-790 (2005).
[26] Mc Bride C., Renhowe P., Heise C., Jansen J., Lapointe G., Ma S., Pineda R., Vora J., Wiesmann M., Shafer C., Design and Structure–Activity Relationship of 3-Benzimidazol-2-yl-1H-indazoles as Inhibitors of Receptor Tyrosine Kinases, Bioorg. Med. Chem. Lett., 16: 3595-3599 (2006).
[27] Yamaguchi M., Maruyama N., Koga T., Kamei K., Akima M., Kuroki T., Hamana M., Ohi N., Novel Antiasthmatic Agents with Dual Activities of Thromboxane A2 Synthetase Inhibition and Bronchodilation. VI. Indazole Derivatives, Chem. Pharm. Bull., 43: 332-334 (1995).
[29] Vyas D.H., Tala S.D., Akbari J.D., Dhaduk M.F., Joshi H.S., Synthesis, Antimicrobial and Antitubercular Activity of Some Cyclohexenone and Indazole Derivatives, Indian J. Chem., 48B: 1405-1410 (2009).
[30] Katsori A.-M., Hadjipavlou-Litina D., Recent Progress in Therapeutic Applications of Chalcones, Expert Opin. Ther. Patents, 21: 1575-1596 (2011).
[31] Padmavathi V., Sharmila K., Reddy A.S., Reddy D.B., Reactivity of 3,5-Diaryl Cyclohexanones - Synthesis of Spiro Cyclohexanes, Indian J. Chem., 40B: 11-14 (2001).
[32] Zhang X.W., Zhao D.H., Quan Y.C., Sun L.P., Yin X.M., Guan L.P., Synthesis and Evaluation of Antiinflammatory Activity of Substituted Chalcone Derivatives, Med. Chem. Res., 19: 403-412 (2010).
[33] Kaushik S., Kumar N., Drabu S., Synthesis and Anticonvulsant Activities of Phenoxychalcones, T. Ph. Res., 3: 257-262 (2010).
[34] Romagnoli R., Baraldi P.G., Carrion M.D., Cara C.L., Cruz-Lopez O., Preti D., Design, Synthesis, and Biological Evaluation of Thiophene Analogues of Chalcones, Bioorg. Med. Chem., 16: 5367-5376 (2008).
[35] Lunardi F., Guzela M., Rodrigues A.T., Corre R., Eger-Mangrich I., Steindel M., Grisard E.C., Assreuy J., Calixto J.B., Santos A.R.S., Trypanocidal and Leishmanicidal Properties of Substitution-containing Chalcones, Antimicrob. Agents. Chemother., 47: 1449-1451 (2003).
[36] Lahtchev K.L., Batovska D.I., Parushev S.P., Ubiyvovk V.M., Sibirny A.A., Antifungal Activity of Chalcones: a Mechanistic Study Using Various Yeast Strains, Eur. J. Med. Chem., 43: 2220-2228 (2008).
[37] Bag S., Ramar S., Degani M.S., Synthesis and Biological Evaluation of α,β-Unsaturated Ketone as Potential Antifungal Agents, Med. Chem. Res., 18: 309-316 (2009).
[39] Cheng M.S., Shi R., Kenyon G., A Solid Phase Synthesis of Chalcones by Claisen-Schmidt Condensations, Chin. Chem. Lett., 11: 851-854 (2000).
[40] Begum N.A., Roy N., Laskar R.A., Roy K., Mosquito Larvicidal Studies of Some Chalcone Analogues and their Derived Products: Structure-Activity Relationship Analysis, Med. Chem. Res., 19: 1-14 (2011).
[41] Najafian M., Ebrahim-Habibi A., Hezareh N., Yaghmaei P., Parivar K., Larijani B., Trans-chalcone: A Novel Small Molecule Inhibitor of Mammalian Alpha-amylase, Mol. Biol. Rep., 10: 271-274 (2010).
[42] Sivakumar P.M., Prabhakar P.K., Doble M., Synthesis, Antioxidant Evaluation and Quantitative Structure-activity Relationship Studies of Chalcones, Med. Chem. Res., 20: 482–492 (2011).
[43] Coutlangus M.L., Filla S.A., Rowland A.T., A Tandem Michael-aldol Reaction Sequence, J. Chem. Educ., 66: 520 (1989).
[44] Padmavathi V., Reddy B.J.M., Baliah A., Padmaja A., Reddy D.B., Synthesis of Some Novel Spiro Heterocycles- Part II, Arkivoc., xiv: 1-13 (2005).
[45] Voronin V.G., Polevaya O.Y., Mukhanova V.G., Landau M.A., Kolbanov V.M., Privol’neva T.P., Chugunov V.V., Lavertskaya E.F., Synthesis and Biological Activity of Spiro [cycloalkane-2-thiobarbituric] Acids, Khim.-Farm. Zh., 10: 43-46 (1976).
[46] Mousavi M.R., Maghsoodlou M.T., Habibi-Khorassani S.M., One-pot Diastreoselective Synthesis of Highly Functionalized Cyclohexenones: 2-Oxo-N,4,6-triarylcyclohex-3-enecarboxamides, Mol. Divers., 18: 821-828 (2014).
[47] Mousavi M.R., Gharari H., Maghsoodlou M.T., Hazeri N., Dastorani P., Soria-Martínez R., García-Granda S., Diastereoselective and One-pot Synthesis of Highly Substituted Cyclohexenones Using Claisen–Schmidt Condensation and Michael Addition, J. Chem. Res., 39: 509-514 (2015).
[50] Mousavi M.R., Hazeri N., Maghsoodlou M.T., Salahi S., Habibi-Khorassani S.M., Entirely Green Protocol for the Synthesis of β-Aminoketones Using Saccharose as a Homogenous Catalyst, Chin. Chem. Lett., 24: 411-414 (2013).
[51] Mousavi M.R., Maghsoodlou M.T., Nano-SiO2: A Green, Efficient and Reusable Heterogeneous Catalyst for the Synthesis of Quinazolinone Derivatives, J. Iran Chem. Soc., 12: 743-749 (2015).