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Synlett 2008(2): 281-285  
DOI: 10.1055/s-2007-1000867
LETTER
© Georg Thieme Verlag Stuttgart · New York

The First Synthesis of 4-Unsubstituted 3-(Trifluoroacetyl)coumarins by the Knoevenagel Condensation of Salicylaldehydes with Ethyl Trifluoroaceto­acetate Followed by Chromene-Coumarin Recyclization

Dmitrii L. Chizhov*a, Vyacheslav Ya. Sosnovskikhb, Marina V. Pryadeinaa, Yanina V. Burgarta, Victor I. Saloutina, Valery N. Charushina
a I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, 620041 Ekaterinburg, Russian Federation
Fax: +7(343)3693058; e-Mail: dlchizhov@ios.uran.ru;
b Department of Chemistry, Ural State University, 620083 Ekaterinburg, Russian Federation
Further Information

Publication History

Received 17 October 2007
Publication Date:
21 December 2007 (online)

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Abstract

A series of ethyl 6-substituted 2-hydroxy-2-(trifluoro­methyl)-2H-chromene-3-carboxylates was obtained in good yields via the Knoevenagel condensation of salicylaldehydes with ethyl trifluoroacetoacetate in the presence of piperidinium acetate. The subsequent recyclization of these chromenes proceeds smoothly in refluxing chlorobenzene in the presence of p-toluenesulfonic acid affording previously unknown 3-(trifluoroacetyl)coumarins in moderate to good yields.

Key words

ethyl trifluoroacetoacetate - salicylaldehydes - Knoevenagel condensation - 3-(trifluoroacetyl)coumarins - chromene-coumarin recyclization

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Typical Procedure for Preparation of 6 A mixture of salicylaldehyde (5.0 mmol), ethyl trifluoro­-acetoacetate (5.0 mmol) and piperidinium acetate (4 mg, 5 mol%) was refluxed in MeCN (10 mL) for 3-4 h and then diluted with H2O (30 mL). The precipitate that formed was filtered, washed with warm H2O (50 °C, 5 × 10 mL) and dried on air to give 6.
Data for Compounds 6a,d Compound 6a: colorless crystals; mp 102-103 °C (hexane). IR (mull): ν = 3294, 1686, 1635, 1607, 1576 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.40 (t, J = 7.2 Hz, 3 H, Me), 4.38 (q, J = 7.2 Hz, 2 H, OCH2), 7.01-7.06 (m, 2 H, H-6, H-8), 7.26 (dd, J = 7.9, 1.7 Hz, 1 H, H-5), 7.39 (ddd, J = 8.2, 7.5, 1.7 Hz, 1 H, H-7), 7.50 (s, 1 H, OH), 7.78 (s, 1 H, H-4). 19F NMR (376 MHz, CDCl3): δ (C6F6) = 74.50 (s, CF3). 13C NMR (100 MHz, CDCl3): δ = 14.02 (Me), 62.54 (CH2), 95.29 (q, 2 J CF = 35.3 Hz, C-2), 114.74, 116.00 (CH), 117.55, 122.66 (q, 1 J CF = 292.0 Hz, CF3), 122.68 (CH), 129.51 (CH), 133.94 (CH), 139.36 (CH), 152.62 (C-8a), 166.80 (C=O). Anal. Calcd for C13H11F3O4 (%): C, 54.18; H, 3.85; F, 19.77. Found: C, 54.20; H, 3.85; F, 19.82.
Compound 6d: light-yellow crystals; mp 120-120.5 °C (benzene). IR (mull): ν = 3230, 1686, 1619, 1578, 1527, 1345 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.43 (t, J = 7.2 Hz, 3 H, CH3), 4.42 (q, J = 7.2 Hz, 2 H,OCH2), 7.18 (br.d, J = 9.0 Hz, 1 H, H-8), 7.55 (s, 1 H, OH), 7.82 (s, 1 H, H-4), 8.23 (d, J = 2.6 Hz, 1 H, H-5), 8.29 (dd, J = 9.0, 2.6 Hz, 1 H, H-7). 19F NMR (376 MHz, CDCl3): δ (C6F6) = 74.80 (s). 13C NMR (100 MHz, CDCl3): δ = 13.82 (s, Me), 63.07 (s, OCH2), 95.96 (q, 2 J CF = 35.8 Hz, C-2), 116.79 (s, CH), 117.13, 117.63, 122.11 (q, 1 J CF = 291.5 Hz, CF3), 125.02 (CH), 128.81 (CH), 137.09 (CH), 142.79, 156.69 (s, C-8a), 165.98 (s, C=O). Anal. Cald for C13H10NF3O6 (%): C, 46.86; H, 3.03; F, 17.10; N, 4.20. Found: C, 46.73; H, 3.16; F, 16.97; N, 4.29.

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General Procedure for Preparation of 7
A mixture of chromene 6 (0.5 mmol) and TsOH·H2O (10 mg, 10 mol.%) was refluxed in chlorobenzene (5 mL) for 10-17 h and then concentrated to ca. 2 mL in volume. The resulting reaction mixture was dried in vacuo, dissolved in toluene (15 mL) and washed with H2O (3 × 5 mL). Toluene solution was refluxed with a Dean-Stark trap for 5 h, the solvent was evaporated in vacuo and the residue was sublimed affording 7.
Data for Compounds 7a,d Compound 7a: pale yellow crystals; mp 117-118 °C. IR (mull): ν = 1752, 1696, 1605, 1558 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.38-7.45 (m, 1 H, H-8, H-6), 7.70 (dd, J = 7.8, 1.6 Hz, 1 H, H-5), 7.76 (ddd, J = 8.2, 7.6, 1.6 Hz, 1 H, H-7), 8.52 (s, 1 H, H-4). 19F NMR (376 MHz, CDCl3): δ (C6F6) = 88.37 (s, CF3). 13C NMR (100 MHz, CDCl3): δ = 115. 65 (q, 1 J CF = 290.6 Hz, CF3), 116.93 (CH), 117.24, 119.03, 125.49 (CH), 130.63 (CH), 136.25 (CH), 151.07 (C-4), 155.48 (C-8a), 155.90 (C-2), 178.36 (q, 2 J CF = 37.7 Hz, COCF3). Anal. Calcd for C11H5F3O3 (%): C, 54.56; H, 2.08; F, 23.54. Found: C, 54.55; H, 2.30; F, 23.53.
Compound 7d: yellowish crystals; mp 115.5-116 °C (sublim.). IR (mull): ν = 1751, 1719, 1611, 1566, 1342 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.58 (dm, J = 9.1 Hz, 1 H, H-8), 8.58 (s, 1 H, H-4), 8.60 (dd, J = 9.1, 2.6 Hz, 1 H, H-7), 8.65 (d, J = 2.6 Hz, 1 H, H-5). 19F NMR (376 MHz, CDCl3): δ (C6F6) = 88.16 (s). 13C NMR (100 MHz, CDCl3): δ = 115.47 (q, 1 J CF = 290.1 Hz, CF3), 117.15, 118.19, 118.53 (CH), 126.08 (CH), 130.06 (CH), 144.68, 149.00 (q, 4 J CF = 1.2 Hz, C-4), 154.24 (s, C-8a), 158.55 (C-2), 177.96 (q, 2 J CF = 38.6 Hz, COCF3). Anal. Calcd for C11H4NF3O5 (%): C, 46.01; H, 1.40; N, 4.88; F, 19.85. Found: C, 46.00; H, 1.15; N, 4.72; F, 19.94.