Synlett, Table of Contents Synlett 2020; 31(13): 1298-1302DOI: 10.1055/s-0039-1690880 letter © Georg Thieme Verlag Stuttgart · New York A Convenient One-pot Synthesis of Chromenyl Acrylates and Acrylonitriles Diogo Lopes a Department of Chemistry, University of Minho, Campus de Gualtar, Braga, Portugal Email: fproenca@quimica.uminho.pt.com , Marta Costa b Life and Health Sciences Research Institute (ICVS), University of Minho, Campus de Gualtar, Braga, Portugal c ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal , João Louçano a Department of Chemistry, University of Minho, Campus de Gualtar, Braga, Portugal Email: fproenca@quimica.uminho.pt.com , Fernanda Proença∗ a Department of Chemistry, University of Minho, Campus de Gualtar, Braga, Portugal Email: fproenca@quimica.uminho.pt.com › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Abstract 2H-Oxo-chromenyl acrylates and 2H-imino-chromenyl acrylonitriles have been prepared from a salicylaldehyde and ethyl cyanoacetate or 2-amino-1,1,3-tricyanopropene, respectively. The reaction occurs in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) and the products were isolated in good to quantitative yields. Despite the simplicity of the synthesis, this is the first time that these substituted chromenes have been isolated. Key words Key wordschromenyl-acrylate - chromenyl-acrylonitrile - salicylaldehyde - ethyl cyanoacetate - malononitrile Full Text References References and Notes 1a Welsch ME, Snyder SA, Stockwell BR. Curr. Opin. Chem. Biol. 2010; 14: 347 1b Thomas N, Zachariah SM. Asian J. Pharm. Clin. Res. 2013; 6: 11 1c Medina FG, Marrero JG, Macías-Alonso M, Gonzalez MC, Córdova-Guerrero I, García AG. T, Osegueda-Robles S. Nat. Prod. Rep. 2015; 32: 1472 1d Costa M, Dias T, Brito A, Proença F. Eur. J. Med. Chem. 2016; 123: 487 2a Patil SA, Patil R, Pfeffer LM, Miller DD. Future Med. Chem. 2013; 5: 1647 2b Patil PO, Bari SB, Firke SD, Deshmukh PK, Donda ST, Patil DA. Bioorg. Med. Chem. 2013; 21: 2434 2c Pratap R, Ji-Ram V. Chem. 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Lett. 2012; 363 12b Ramani A, Chanda BM, Velu S, Sivasanker S. Green Chem. 1999; 1: 163 13a Pratap R, Ram VJ. Chem. Rev. 2014; 114: 10476 13b Borges F, Roleira F, Milhazes N, Santana L, Uriarte E. Curr. Med. Chem. 2005; 12: 887 14 Volmajer J, Toplak R, Leban I, Marechal AM. Tetrahedron 2005; 61: 7012 15 Costa M, Areias F, Abrunhosa L, Venancio A, Proenca F. J. Org. Chem. 2008; 73: 1954 16 Fujimoto A, Sakurai A. Synthesis 1977; 871 17 Yang F, Wang Z, Wang H, Wang C, Wang L. RSC Adv. 2015; 5: 57122 18 Ethyl 3-amino-2-cyano-3-(8-methoxy-2-oxo-2H-chromen-3-yl)acrylate (8b); Typical Procedure: DABCO (0.75 g, 6.68 mmol) was added to a solution of o-vanillin 6b (0.50 g, 3.29 mmol) and ethyl cyanoacetate 7a (880 μL, 8.26 mmol) in EtOH (30 mL). The mixture was heated at 80 °C in a closed vial and, after 15 min, a white solid started to precipitate. The white solid was filtered after 5 h 45 min and identified as 8b (0.96 g, 3.04 mmol, 92%). Mp 247–249 °C. 1H NMR (DMSO-d 6, 400 MHz): δ = 9.88 (s, 1 H, NH2), 9.18 (s, 1 H, NH2), 8.38 (s, 1 H, H4), 7.43 (dd, J = 2.4, 7.2 Hz, 1 H, H7), 7.34–7.40 (m, 2 H, H5 and H6), 4.18 (q, J = 7.2 Hz, 2 H, H5′), 3.94 (s, 3 H, OCH3), 1.23 (t, J = 7.2 Hz, 3 H, H6′). 13C NMR (DMSO-d 6, 100.6 MHz): δ = 166.4 (C3′), 164.2 (C1′), 156.9 (C2), 146.5 (C8), 144.6 (C4), 142.8 (C8a), 125.2 (C6), 122.7 (C3), 120.3 (C5), 118.3 (C4a), 118.1 (CN), 115.8 (C7), 71.4 (C2′), 59.9 (C5′), 56.3 (OCH3), 14.3 (C6′). Anal. Calcd for C16H19N2O5 (319): C, 60.40; H, 4.53; N, 8.81. Found: C, 60.29; H, 4.45; N, 8.89. 19 Junek H, Wibmer P, Thierrichter B. Synthesis 1977; 560 20 2-(Amino(2-imino-8-methoxy-2H-chromen-3-yl)methylene) malononitrile (11b); Typical Procedure: A solution of o-vanillin 6b (0.17 g, 1.14 mmol) and DABCO (0.12 g, 1.03 mmol) in EtOH (0.5 mL) was stirred in an ice bath. After about 1 min a suspension of 2-amino-1,1,3-tricyanopropene 12 (0.15 g, 1.14 mmol) in acetone (1.4 mL) was added. When the color of the suspension changed, the reaction mixture was connected to a vacuum system to remove the acetone. Stirring was concluded after 40 min, when a thick suspension was formed. The solid was filtered and washed sequentially with EtOH and cold acetone. Product 11b was isolated as a yellow solid (0.22 g, 0.83 mmol, 73%). Alternative Procedure: A solution of o-vanillin 6b (0.53 g, 3.48 mmol), N-methylpiperazine (772 μL, 6.96 mmol), EtOH (2 mL), 2-amino-1,1,3-tricianopropene 12 (0.46 g, 3.48 mmol), and acetone (2.5 mL) was stirred for 37 min. Product 11b was isolated as a yellow solid (0.76 g, 2.86 mmol, 82%). Mp > 300 °C (slow decomp. after 217 °C). 1H NMR (DMSO-d 6, 400 MHz): δ = 8.93 (s, 1 H, NH2), 8.91 (s, 1 H, NH2), 8.70 (s, 1 H, NH), 7.70 (s, 1 H, H4), 7.23 (dd, J = 1.6, 8.0 Hz, 1 H, H7), 7.16 (t, J = 7.6 Hz, 1 H, H6), 7.11 (dd, J = 1.6, 7.6 Hz, 1 H, H5), 3.86 (s, 3 H, OCH3). 13C NMR (DMSO-d 6, 100.6 MHz): δ = 168.3 (C2′), 151.9 (C2), 146.0 (C8), 142.6 (C8a), 137.0 (C4), 124.9 (C3), 123.9 (C6), 120.2 (C5), 118.4 (C4a), 116.6 (CN), 115.2 (C7), 115.1 (CN), 56.0 (OCH3), 49.6 (C1′). Anal. Calcd for C14H10N4O2 (266): C, 63.15; H, 3.79; N, 21.04. Found: C, 63.42; H, 3.98; N, 20.89. Supplementary Material Supplementary Material Supporting Information
