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Synlett 2002(10): 1661-1664
DOI: 10.1055/s-2002-34212
LETTER
© Georg Thieme Verlag Stuttgart · New York

Benzannulation of Substituted 3-Alkoxycarbonylhex-3-en-5-ynoic Acids: A New Route to 4-Substituted 3,5-Dihydroxybenzoic Acids Derivatives

Stefano Serra*, Claudio Fuganti
C.N.R. Istituto di Chimica del Riconoscimento Molecolare, Sezione ‘Adolfo Quilico’ presso Dipatimento di Chimica, Materiali ed Ingegneria Chimica ‘Giulio Natta’ del Politecnico, Via Mancinelli 7, 20133 Milano, Italy
Fax: +39(2)23993080; e-Mail: stefano.serra@polimi.it;
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Publication History

Received 1 August 2002
Publication Date:
23 September 2002 (online)

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Abstract

A new regioselective pathway to 4-substituted 3,5-dihydroxybenzoic acids derivatives is described here. According to this procedure substituted propargylic aldehydes are converted into substituted 3-alkoxycarbonylhex-3-en-5-ynoic acids, which are in turn, treated with acetic anhydride in the presence of sodium acetate to give the substituted benzoic acids derivatives. The aromatic moiety constructed using the latter benzannulation reaction is formed in regioselective fashion and a range of substituents are tolerated.

Key words

annulations - cyclizations - phenols - regioselectivity - biaryls

    References

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11

General procedure for the benzannulation of acids 6a-i to give phenols 7a-i:
Acids 6a-i (50 mmoles)were dissolved in acetic anhydride (48 mL, 0.5 mol). To this solution, anhyd sodium acetate (8.2 g, 0.1 mol) and hydroquinone (275 mg, 2.5 mmol) were added in one portion. The obtained heterogeneous mixture was heated at reflux for 2 h under a nitrogen atmosphere. After cooling to r.t., the acetic anhydride was removed in vacuo and the residue was treated with ethyl acetate (200 mL) and water (100 mL). The organic phase was separated, dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by chromatography and crystallisation to give phenols derivatives 7a-i.

12

All new compounds were fully characterised. Selected analytical data:
6f: Anal. Calcd for C17H18O6: C, 64.14; H, 5.70. Found: C, 63.98; H, 5.72. Mp 135-136 °C (ethyl acetate); 1H NMR (250 MHz, CDCl3) δ 1.30 (3 H, t, J = 7.2 Hz), 3.70 (2 H, s), 3.88 (3 H, s), 3.90 (3 H, s), 4.25 (2 H, q, J = 7.2 Hz), 6.82 (1 H, d, J = 8.5 Hz), 6.95 (1 H, d, J = 1.7 Hz), 7.04 (1 H, s), 7.10 (1 H, dd, J = 8.5, 1.7 Hz); EI-MS m/z 319 (M+ + 1), 318 (M+), 289, 273, 259, 245, 229, 217, 214, 201, 185, 151, 128, 88; FT-IR(nujol): (cm-1) 766, 807, 860, 1036, 1054, 1212, 1247, 1281, 1515, 1594, 1618, 1702, 2187.
6i: Anal. Calcd for C13H12O4S: C, 59.08; H, 4.58; S, 12.13. Found: C, 59.15; H, 4.60; S, 12.20. Mp 92 °C (hexane-ethyl acetate); 1H NMR (250 MHz, CDCl3) δ 1.30 (3 H, t, J = 7.1 Hz), 3.68 (2 H, s), 4.25 (2 H, q, J = 7.1 Hz), 7.02 (1 H, s), 7.14 (1 H, dd, J = 5, 1 Hz), 7.30 (1 H, dd, J = 5, 3 Hz), 7.56 (1 H, dd, J = 3, 1 Hz); EI-MS m/z 264 (M+), 220, 205, 191, 163, 147, 135, 111, 83; FT-IR(nujol): (cm-1) 763, 811, 1041, 1203, 1288, 1421, 1619, 1709, 2195.
7f: Anal. Calcd for C21H22O8: C, 62.68; H 5.51. Found: C, 62.90; H, 5.55. Mp 109-110 °C (hexane-ethyl acetate);
1H NMR (250 MHz, CDCl3) δ 1.39 (3 H, t, J = 7.1 Hz), 2.02 (6 H, s), 3.85 (3 H, s), 3.92 (3 H, s), 4.39 (2 H, q, J = 7.1 Hz), 6.77-6.93 (3 H, m), 7.72 (2 H, s); EI-MS m/z 402 (M+), 360, 343, 318, 303, 273, 244, 214, 199, 183, 157, 131, 115, 95; FT-IR(nujol): (cm-1) 758, 862, 911, 1030, 1200, 1227, 1258, 1309, 1523, 1586, 1605, 1719, 1770.
7i: Anal. Calcd for C17H16O6S: C, 58.61; H 4.63; S, 9.20. Found: C, 58.50; H, 4.65; S, 9.25. Mp 100-101 °C (hexane-ethyl acetate); 1H NMR (250 MHz, CDCl3) δ 1.38 (3 H, t, J = 7.1 Hz), 2.08 (6 H, s), 4.38 (2 H, q, J = 7.1 Hz), 7.11 (1 H, dd, J = 4.3, 2 Hz), 7.34-7.39 (2 H, m), 7.72 (2 H, s); EI-MS m/z 348 (M+), 306, 289, 264, 250, 236, 219, 192, 163, 134, 111, 91; FT-IR(nujol): (cm-1) 756, 868, 1043, 1198, 1208, 1307, 1562, 1719, 1768.