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Current Organic Synthesis

Author(s): Nguyen D. Thanh*, Do S. Hai, Vu T.N. Bich, Pham T.T. Hien, Nguyen T.K. Duyen, Nguyen T. Mai, Tran T. Dung, Hoang T.K. Van, Vu N. Toan, Duong N. Toan and Le H. Dang

DOI: 10.2174/1570179416666190104124652

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Using Sodium Hydride and Potassium Carbonate as Bases in Synthesis of Substituted 2-Amino-4-aryl-7-propargyloxy-4H-chromene-3-carbonitriles

Page: [423 - 430] Pages: 8

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Abstract

Aims and Objective: 1-Alkynes are the important precursors for the CuAAC click chemistry. The hybrid of 1,2,3-triazole ring to the chromene ring and sugar moiety could bring some remarkable biological properties. Propargyl derivatives are usually used in the click chemistry. This article reported the synthesis of 2-amino-4-aryl-7-propargyloxy-4-aryl-4H-chromene-3-carbonitriles using propargyl bromide as alkylation agent and the use of potassium carbonate and sodium hydride as bases in the conversion of 2-amino-4-aryl-7- hydroxy-4-aryl-4H-chromene-3-carbonitriles into corresponding propargyl ethers in Williamson’s ether synthesis.

Materials and Methods: The use of CTAB for the synthesis of benzylidene malononitriles and anhydrous potassium carbonate as a catalyst in absolute ethanol in the synthesis of 2-amino-7-hydroxy-4H-chromene-3- carbonitriles is an efficient and simple synthetic method. Propargyl ether compounds of these 4H-chromene-3- carbonitriles were obtained from the alkylation reaction by propargyl bromide. Two procedures were applied: K2CO3 as a base in acetone solvent (Procedure A) and NaH as a base in DMF solvent (Procedure B). The single-crystal X-ray structure of propargyl ether 5e has been studied.

Results: The use of K2CO3 and NaH as bases in the Williamson’s ether synthesis from 2-amino-7-hydroxy-4Hchromene- 3-carbonitriles showed that Procedure B was the better route and gave ethers in the higher yields. 2- Amino-4-aryl-7-propargyloxy-4-aryl-4H-chromene-3-carbonitriles were obtained from corresponding 7- hydroxy-4H-chromene-3-carbonitriles. Yields of ethers 5a-i were 70−89% and 80−96%, respectively depending on the used procedures.

Conclusion: The described methods are simple, clean and environmentally friendly alternatives for the preparation of 2-amino-4-aryl-7-hydroxy-4H-chromene-3-carbonitriles. The conditions for the transformation of these compounds into propargyl ethers include dried DMF as a solvent, NaH as a base and reaction time of 2 h at the room temperature. A series of 2-amino-4-aryl-7-hydroxy-4-aryl-4H-chromene-3-carbonitriles were obtained based on investigated reaction condition.

Keywords: 4H-Chromene, multi-component reaction, propargyl ether, potassium carbonate, sodium hydride, Williamson’s ether synthesis.

Graphical Abstract

[1]
Bugaut, X.; Constantieux, T.; Coquerel, Y., and; Rodriguez, J. 1,3- Dicarbonyls in multicomponent reactions. In: Multicomponent Reactions in Organic Synthesis; Zhu, J.; Wang, Q.; Wang, M.-X., Eds. Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim (Germany), 2014; pp. 109-158.
[2]
Hepworth, J.D.; Heron, B.M. Chapter 6.4 Six-Membered Ring Systems: With O and/or S Atoms. In: Progress in Heterocyclic Chemistry; Gribble, G.; Joule, J.A., Eds.; Elsevier, 2011; Vol. 22, pp. 449-490.
[3]
Bingi, C.; Emmadi, N.R.; Chennapuram, M.; Poornachandra, Y.; Kumar, C.G.; Nanubolu, J.B.; Atmakur, K. One-pot catalyst-free synthesis of novel kojic acid tagged 2-aryl/alkyl substituted-4H-chromenes and evaluation of their antimicrobial and anti-biofilm activities. Bioorg. Med. Chem. Lett., 2015, 25(9), 1915-1919.
[4]
Sashidhara, K.V.; Kumar, M.; Modukuri, R.K.; Srivastava, A.; Puri, A. Discovery and synthesis of novel substituted benzocoumarins as orally active lipid modulating agents. Bioorg. Med. Chem. Lett., 2011, 21(22), 6709-6713.
[5]
Chung, S-T.; Huang, W-H.; Huang, C-K.; Liu, F-C.; Huang, R-Y.; Wu, C-C.; Lee, A-R. Synthesis and anti-inflammatory activities of 4H-chromene and chromeno[2,3-b]pyridine derivatives. Res. Chem. Intermediat., 2016, 42(2), 1195-1215.
[6]
El-Agrody, A.M.; Halawa, A.H.; Fouda, A.M.; Al-Dies, A-A.M. The anti-proliferative activity of novel 4H-benzo[h]chromenes, 7H-benzo[h]-chromeno[2,3-d]pyrimidines and the structure–activity relationships of the 2-, 3-positions and fused rings at the 2, 3-positions. J. Saudi Chem. Soc., 2017, 21(1), 82-90.
[7]
Subbareddy, C.V.; Sundarrajan, S.; Mohanapriya, A.; Subashini, R.; Shanmugam, S. Synthesis, antioxidant, antibacterial, solvatochromism and molecular docking studies of indolyl-4H-chromene-phenylprop-2-en-1-one derivatives. J. Mol. Liq., 2018, 251, 296-307.
[8]
Zghab, I.; Trimeche, B.; Mansour, M.B.; Hassine, M.; Touboul, D.; Jannet, H.B. Regiospecific synthesis, antibacterial and anticoagulant activities of novel isoxazoline chromene derivatives. Arab. J. Chem., 2017, 10, S2651-S2658.
[9]
Nancy, T.; Mary, Z.S.; Prasanna, R. 4-Aryl-4H-Chromene-3-Carbonitrile Derivates: Synthesis and Preliminary Anti-Breast Cancer Studies. J. Heterocycl. Chem., 2016, 53(6), 1778.
[10]
Koteswara Reddy, M.; Jayaprakash Rao, Y.; David Krupadanam, G.L. Synthesis and anti-microbial activity of new (1-alkyl-1H-1,2,3-triazol-4-yl)methyl-2H-chromene-3-carboxylates: A click chemistry approach. J. Saudi Chem. Soc., 2015, 19(4), 372-378.
[11]
Kolb, H.C.; Finn, M.G.; Sharpless, K.B. Click chemistry: Diverse chemical function from a few good reactions. Angew. Chem. Int. Ed., 2001, 40(11), 2004-2021.
[12]
Meldal, M.; Tornøe, C.W. Cu-catalyzed azide−alkyne cycloaddition. Chem. Rev., 2008, 108(8), 2952-3015.
[13]
Cabello, J.A.; Campelo, J.M.; Garcia, A.; Luna, D.; Marinas, J.M. Kno-evenagel condensation in the heterogeneous phase using aluminum phosphate-aluminum oxide as a new catalyst. J. Org. Chem., 1984, 49(26), 5195.
[14]
Sturz, H.G.; Noller, C.R. New compounds. some substituted benzalmalononitriles. J. Am. Chem. Soc., 1949, 71(8), 2949.
[15]
Corson, B.B.; Stoughton, R.W. Reactions of alpha, beta-unsaturated dinitriles. J. Am. Chem. Soc., 1928, 50(10), 2825-2837.
[16]
Mona, H-S.; Hashem, S.; Samane, E. Solvent-free knoevenagel condensations over TiO2. Chin. J. Chem., 2007, 25(10), 1563.
[17]
Li, G.; Xiao, J.; Zhang, W. Knoevenagel condensation catalyzed by a tertiary-amine functionalized polyacrylonitrile fiber. Green Chem., 2011, 13(7), 1828-1836.
[18]
Makarem, S.; Mohammadi, A.A.; Fakhari, A.R. A multi-component electro-organic synthesis of 2-amino-4H-chromenes. Tetrahedron Lett., 2008, 49(50), 7194.
[19]
Javanshir, S.; Safari, M.; Dekamin, M.G. A facile and green three-component synthesis of 2-amino-3-cyano-7-hydroxy-‎‎4H-chromenes on grinding. Sci. Iran., 2014, 21(3), 742-747.
[20]
Dolomanov, O.V.; Bourhis, L.J.; Gildea, R.J.; Howard, J.A.K.; Puschmann, H. OLEX2: a complete structure solution, refinement and analysis program. J. Appl. Cryst., 2009, 42(2), 339-341.
[21]
Farrugia, L. WinGX and ORTEP for Windows: an update. J. Appl. Cryst., 2012, 45(4), 849-854.