Download PDF
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;
Further Information

Publication History

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

    Permissions and Reprints All articles of this category

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

  • 1a Serra S. Fuganti C. Moro A. J. Org. Chem.  2001,  66:  7883 
    CrossrefGoogle Scholar
  • 1b Brenna E. Fuganti C. Serra S. J. Chem. Soc., Perkin Trans. 1  1998,  901 
    CrossrefGoogle Scholar
  • 1c Brenna E. Fuganti C. Perozzo V. Serra S. Tetrahedron  1997,  53:  15029 
    CrossrefGoogle Scholar
  • 2 Fuganti C. Serra S. J. Chem. Res., Synop.  1998,  638 
    CrossrefGoogle Scholar
  • 3 Brenna E. Fuganti C. Serra S. Synlett  1998,  365 
    Article in Thieme ConnectGoogle Scholar
  • 4a Fuganti C. Serra S. Tetrahedron Lett.  1998,  39:  5609 
    CrossrefGoogle Scholar
  • 4b Brenna E. Fuganti C. Serra S. Tetrahedron  1998,  54:  1585 
    CrossrefGoogle Scholar
  • 5a Brenna E. Fuganti C. Grasselli P. Serra S. Zambotti S. Chem.-Eur. J.  2002,  8:  1872 
    Article in Thieme ConnectGoogle Scholar
  • 5b Fuganti C. Serra S. Synlett  1999,  1241 
    Article in Thieme ConnectGoogle Scholar
  • 6a Serra S. Synlett  2000,  890 
    Article in Thieme ConnectGoogle Scholar
  • 6b Fuganti C. Serra S. J. Org. Chem.  1999,  64:  8728 
    Article in Thieme ConnectGoogle Scholar
  • 6c Fuganti C. Serra S. Synlett  1998,  1252 
    Article in Thieme ConnectGoogle Scholar
  • 7a Propargyl alcohol 3a was oxidised with chromium trioxide and sulfuric acid as described in the following reference: Veliev MG. Guseinov MM. Synthesis  1980,  461 
    Google Scholar
  • 7b

    Propargylic alcohols 3b-i were oxidised with MnO2 in CH2Cl2 at r.t.
  • 8a Propargylic alcohols 3a and 3b are commercially available. Alcohol 3c was prepared from phenylacetylene by treatment with butyllithium followed by addition of formaldehyde. Alcohol 3h was prepared by palladium mediated coupling of (E)-β-bromostyrene with propargyl alcohol accordingly to the following reference: Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett.  1975,  4467 
    CrossrefGoogle Scholar
  • 8b Alcohols 3d-g and 3i were prepared by palladium mediated coupling of propargyl alcohol with 1-bromo-4-fluorobenzene, 1-bromo-2-chlorobenzene, 4-bromoveratrole, 4-nitro-1-iodobenzene and 3-bromothiophene, respectively; this method of preparation has been performed by a small modification of the method described in the following reference: Bleicher LS. Cosford NDP. Herbaut A. McCallum JS. McDonald IA. J. Org. Chem.  1998,  63:  1109 
    CrossrefGoogle Scholar
  • 9 For the preparation of this ylide see: Hudson RF. Chopard PA. Helv. Chim. Acta  1963,  46:  2178 
    CrossrefGoogle Scholar
  • The Wittig reaction of ylide 5 with the aldehydes affords the 3-(E)-alkylidene-succinic acid monoalkyl esters in a highly stereoselective way; for previous studies on this reaction see:
  • 10a Paquette LA. Schulze MM. Bolin D. J. Org. Chem.  1994,  59:  2043 
    Google Scholar
  • 10b Röder E. Krauss H. Liebigs Ann. Chem.  1992,  177 
    Google Scholar
  • 13a Glüsenkamp KH. Büchi G. J. Org. Chem.  1986,  51:  4481 
    Google Scholar
  • 13b For the preparation of the 3,5-dihydroxybenzoic acid (R = H) see: Weston AW. Suter CM. Org. Synth.  1941,  21:  27 
    Google Scholar
  • 14a Kojima T. Ohishi T. Yamamoto I. Matsuoka T. Kotsuki H. Tetrahedron Lett.  2001,  42:  1709 
    CrossrefGoogle Scholar
  • 14b Hattori T. Takeda A. Suzuki K. Koike N. Koshiishi E. Miyano S. J. Chem. Soc., Perkin Trans. 1  1998,  3661 
    CrossrefGoogle Scholar
  • 14c Johnson MG. Foglesong RJ. Tetrahedron Lett.  1997,  38:  7001 
    CrossrefGoogle Scholar
  • 15a Occelli E. DePaoli A. Nathansohn G. Gazz. Chim. Ital.  1981,  111:  383 
    Google Scholar
  • 15b Budzikiewicz H. Metlesics W. J. Org. Chem.  1959,  24:  1125 
    Google Scholar
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.