Synlett 2017; 28(16): 2126-2130
DOI: 10.1055/s-0036-1590815
letter
© Georg Thieme Verlag Stuttgart · New York

Ethynylation of Isoquinoline and Quinoline Derivatives with Calcium Carbide

Alireza Samzadeh-Kermani
Chemistry Department, Faculty of Science, University of Zabol, Zabol, Iran   Email: [email protected]
› Author Affiliations
Further Information

Publication History

Received: 23 March 2017

Accepted after revision: 31 May 2017

Publication Date:
14 July 2017 (online)


Abstract

An operatically simple method for the ethynylation of isoquinolines and quinolines is described. The ionic adduct derived from an alkynoic ester and the N-heterocycle was attacked by calcium carbide to give the ethynylation product. The procedure uses tetrabutylammonium fluoride trihydrate as a catalyst in aqueous N,N-dimethylacetamide. Steric and electronic effects of various substituents on the outcome of the reaction were examined.

Supporting Information

 
  • References and Notes

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  • 30 N-Alkynylisoquinolines 4 and N-Alkynylquinolines 6; General Procedure The N-heterocycle (1.1 mmol), acetylenic ester (1.0 mmol), carbide (2 mmol, 0.13 g), and TBAF·3 H2O (0.1–0.2 mmol; see Tables 2 and 3) were added to 1% H2O–DMA (3 mL), and the mixture was stirred at 55 °C for 6 h. When the reaction was complete, the mixture was diluted with EtOAc (5 mL) and sat. aq NH4Cl (5 mL). The mixture was stirred for an additional 30 min and then the two layers were separated. The aqueous layer was extracted with EtOAc (3 × 10 mL), and the combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by chromatography [silica gel, hexane–EtOAc (5:1)]. Dimethyl (2E)-2-(1-Ethynylisoquinolin-2(1H)-yl)but-2-enedioate (4a) Clear oil; yield: 0.27 g (91%). IR (KBr): 3055, 2981, 2229, 1731, 1723, 1546, 1320, 1126 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.56 (d, 3 J = 2.1, 1 H, CH), 3.57 (s, 3 H, MeO), 3.69 (s, 3 H, MeO), 4.63 (d, 3 J = 2.1, 1 H, CH), 5.75 (d, 3 J = 6.4, 1 H, CH), 6.46 (d, 3 J = 7.1, 1 H, CH), 6.63 (s, 1 H, CH), 7.21–7.37 (m, 4 H, 4 × CH). 13C NMR (125.7 MHz, CDCl3): δ = 53.6 (MeO), 55.9 (MeO), 62.5 (CH), 72.1 (CH), 83.5 (C), 101.6 (CH), 112.1 (CH), 124.3 (CH), 126.7 (CH), 127.1 (CH), 127.9 (CH), 128.8 (CH), 135.4 (C), 139.0 (C), 149.1 (C), 165.3 (C), 166.8 (C). EI-MS: m/z = 297 (12) [M+], 272 (25), 154 (51), 142 (67), 129 (100), 54 (38). Anal. Calcd for C17H15NO4 (297.31): C, 68.68; H, 5.09; N, 4.71. Found: C, 68.92; H, 5.43; N, 4.97. Dimethyl (2Z)-2-(2-Ethynylquinolin-1(2H)-yl)but-2-enedioate (6a) Clear oil; yield: 0.24 g (82%). IR (KBr): 3081, 2953, 2197, 1736, 1728, 1567, 1341, 1118 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.76 (d, 3 J = 2.0, 1 H, CH), 3.55 (s, 3 H, MeO), 3.91 (s, 3 H, MeO), 4.12 (dd, 3 J = 2.0, 3 J = 6.2, 1 H, CH), 5.50 (s, 1 H, CH), 5.79 (d, 3 J = 6.8, 1 H, CH), 6.42 (d, 3 J = 6.5, 1 H, CH), 6.94 (t, 3 J = 6.1, 1 H, CH), 7.20 (d, 3 J = 6.1, 1 H, CH), 7.25 (d, 3 J = 6.1, 1 H, CH), 7.36 (t, 3 J = 7.0, 1 H, CH). 13C NMR (125.7 MHz, CDCl3): δ = 54.1 (MeO), 57.2 (MeO), 63.1 (CH), 73.4 (CH), 82.9 (C), 109.1 (CH), 116.1 (CH), 119.1 (CH), 120.4 (C), 126.1 (CH), 127.0 (CH), 128.2 (CH), 129.5 (CH), 139.8 (C), 143.7 (C), 165.1 (C), 166.3 (C). EI-MS: m/z = 297 (8) [M+], 272 (41), 154 (31), 142 (72), 129 (100), 54 (67). Calcd for C17H15NO4 (297.31): C, 68.68; H, 5.09; N, 4.71. Found: C, 68.87; H, 5.34; N, 4.93. Dimethyl 11bH-Pyrido[2,1-a]isoquinoline-3,4-dicarboxylate (10) A solution of isoquinoline derivative 4a (1.0 mmol) in 1,4-dioxane (1 mL) was added to a stirred mixture of AgOTf or AgBF6 (20 mol%) and 1,4-dioxane (2 mL), and the resulting mixture was heated to 70 °C for 16 h. When the reaction was complete, the mixture was diluted with EtOAc (5 mL) and sat. aq NH4Cl (5 mL). The mixture was stirred for an additional 30 min, and the two layers were separated. The aqueous layer was extracted with EtOAc (3 × 10 mL), and the combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by chromatography [silica gel, hexane–EtOAc (3:1)] to give a yellow oil; yield: 0.15 g (51%). IR (KBr): 3046, 2967, 1731, 1718, 1647, 1470, 1345, 1227 cm–1. 1H NMR (500 MHz, CDCl3): δ = 3.71 (s, 3 H, MeO), 3.90 (s, 3 H, MeO), 4.79 (d, 3 J = 6.7, 1 H, CH), 5.79 (d, 3J = 6.5, 1 H, CH), 6.35 (d, 3 J = 6.2, 1 H, CH), 6.45 (d, 3 J = 6.2, 1 H, CH), 6.78 (d, 3 J = 6.5, 1 H, CH), 7.27–7.36 (m, 4 H, 4 CH). 13C NMR (125.7 MHz, CDCl3): δ = 52.6 (MeO), 56.1 (MeO), 69.2 (CH), 102.1 (CH), 112.2 (CH), 117.1 (C), 125.3 (CH), 126.1 (CH), 126.7 (CH), 128.1 (CH), 128.7 (CH), 130.9 (CH), 133.1 (C), 137.2 (C), 148.2 (CH), 166.8 (C), 167.8 (C). EI-MS: m/z = 297 (3) [M+], 266 (34), 235 (41), 208 (100), 180 (76). Calcd for C17H15NO4 (297.31): C, 68.68; H, 5.09; N, 4.71. Found: C, 68.82; H, 5.37; N, 4.96.