An Efficient One-Pot Synthesis of Phenol Derivatives by Ring Opening and Rearrangement of Diels-Alder Cycloadducts of Substituted Furans Using Heterogeneous Catalysis and Microwave Irradiation

Abstract

The use of silica-supported Lewis acids as catalysts ­under microwave irradiation promotes regiospecific opening of the 7-oxa bridge of Diels-Alder cycloadducts of furan derivatives and produces polysubstituted phenols in a single step. This rapid and ­efficient procedure permits the synthesis of tri-, tetra- and penta­substituted benzene derivatives by reaction of 2,5-dimethylfuran (1), 2-ethylfuran (2) and 2-methoxyfuran (3) with dienophiles such as dimethyl acetylenedicarboxylate and methyl propiolate.

furans - Diels-Alder reactions - heterogeneous catalysis - microwaves - phenol derivatives

References

1a Fraile JM. García JI. Massam J. Mayoral JA. Pires E. J. Mol. Catal. A: Chem.  1997,  123:  43 

1b Fraile JM. García JI. Gracia D. Mayoral JA. Pires E. J. Org. Chem.  1996,  61:  9479 

2 Fraile JM. García JI. Gómez MA. de la Hoz A. Mayoral JA. Moreno A. Prieto P. Salvatella L. Vazquez E. Eur. J. Org. Chem.  2001,  2891 

3a Mingos DPM. Whittaker AG. Microwave Dielectric Heating Effects in Chemical Synthesis, In Chemistry under Extreme or non-Classical Conditions   Eldik R. Hubbard CD. Wiley; New York: 1997. 

3b Caddick S. Tetrahedron  1995,  52:  10403 

3c Lidström P. Tierney J. Wathey B. Westman J. Tetrahedron  2001,  57:  9225 

3d Microwaves in Organic Synthesis   Loupy A. Wiley-VCH; Weinheim: 2002. 

4a Loupy A. Petit A. Hamelin J. Texier-Boullet F. Jacquault P. Mathé D. Synthesis  1998,  1213 

4b Varma RS. Green Chem.  1999,  1:  43 

5 Loupy A. Bram G. Sansoulet J. New J. Chem.  1992,  16:  233 

6 de la Hoz A. Díaz-Ortiz A. Moreno A. Langa F. Eur. J. Org. Chem.  2000,  3659 

7 de la Hoz A. Díaz-Ortiz A. Fraile JM. Gómez MV. Mayoral JA. Moreno A. Saiz A. Vazquez E. Synlett  2001,  753 

8a Hart H. Nwokogu G. J. Org. Chem.  1981,  46:  1251 

8b Huang NZ. Xing YD. Xe DY. Synthesis  1982,  1041 

8c Xing YD. Huang NZ. J. Org. Chem.  1982,  47:  140 

8d Wong HNC. Ng T.-K. Wong T.-Y. Heterocycles  1983,  20:  1815 

8e Wong HNC. Xing YD. Zhou YF. Gong QQ. Zhang C. Synthesis  1984,  787 

8f Wong HNC. Ng T.-K. Wong T.-Y. Xing YD. Heterocycles  1984,  22:  875 

9a Chambers RD. Roche AJ. Rock MH. J. Chem. Soc., Perkin Trans. 1  1996,  1095 

9b Martin-Matute B. Nevado C. Cardenas DJ. Echavarren AM. J. Am. Chem. Soc.  2003,  125:  5757 

10a Padwa A. Dimitroff M. Waterson AG. Wu T. J. Org. Chem.  1997,  62:  4088 

10b Zhu G.-D. Staeger MA. Boyd SA. Org. Lett.  2000,  2:  3345 

11a Maggiani A. Tubul A. Brun P. Synthesis  1997,  631 

11b Maggiani A. Tubul A. Brun P. Tetrahedron Lett.  1998,  39:  4485 

12 Rhodes CN. Brown DR. J. Chem. Soc., Faraday Trans.  1993,  89:  1387 

13a Cativiela C. Fraile JM. García JI. Mayoral JA. Pires E. Royo AJ. Figueras F. de Mérnoval LC. Tetrahedron  1993,  49:  4073 

13b Cativiela C. Figueras F. García JI. Mayoral JA. Pires E. Royo AJ. Tetrahedron: Asymmetry  1993,  4:  621 

14

Typical Experimental Procedure: A mixture of furan (1-3, 9.0 mmol), an acetylenic dienophile (4 and 5, 1.5 mmol) and silica-supported Lewis acid (0.5 g) was charged to a commercial 25 mL Teflon PTFE vessel. The vessel was closed and irradiated in a Miele Electronic M720 microwave oven at 450 W during 30 min. In all reactions the compounds were isolated by adding 50 mL of CH₂Cl₂ to the mixture and separating the catalyst by filtration. The solvent was removed from the filtrate under reduced pressure and the crude reaction mixtures were analysed by ¹H NMR and ¹³C NMR spectroscopy in CDCl₃. The products were purified by column chromatography on silica gel (hexane-EtOAc 8:1 for compound 9 and 3:1 for product 11) [17] or by distillation under reduced pressure in a Kugelrohr apparatus (for compounds 6, [18] 7, [19] 8 and 10 [20] ). Yields were determined by ¹H NMR spectroscopy using CH₂Br₂ (δ = 4.93 ppm) as an internal standard. It should be remarked that for the reactions in entries 15 and 23 (Table [1] ) the isolated yields show differences of between 3% and 7% less than the calculated yields using CH₂Br₂ as internal standard, thus demonstrating the accuracy of this method. All compounds were characterised by analytical methods and ¹H NMR and ¹³C NMR spectroscopy, using one- and two-dimensional techniques. The new compounds exhibit NMR spectra consistent with their structures and gave satisfactory molecular weight determinations (mass spectrometry). [21] Catalysts modified with Lewis acids were obtained by treating silica gel with 1 M solutions of ZnCl₂, AlEt₂Cl or TiCl₄ following the previously described method. [12] [13] The silica contained 1.5 mmol of Zn g^-1, 1.4 mmol of Al g^-1 and 1.2 mmol of Ti g^-1, respectively, as determined by plasma emission spectroscopy. For the Si(Zn) catalyst, activation for 2 h at 150 °C under vacuum was necessary before use. Reactions carried out using thermal heating were performed in an oil bath under the same conditions of temperature and time as the microwave reactions. This temperature was determined at the end of a blank reaction using microwave irradiation.

15 The modified silicas were characterised by IR spectroscopy. Pyridine adsorption-desorption experiments were carried out in order to determine the relative proportion of Lewis and Brønsted acidic sites. Thus, Lewis/Brønsted acid area ratios were determined by the integral areas of Lewis and Brønsted IR bands of pyridine adsorbed onto modified silicas previously described by: Fraile JM. García JI. Mayoral JA. Pires E. Salvatella L. Ten M. J. Phys. Chem. B  1999,  103:  1664 

16

Program AMPAC, v. 7.0 Semichem, Inc. 2000.

17 Schmidt U. Boekens H. Lieberknecht A. Griesser H. Liebigs Ann. Chem.  1983,  9:  1459 

18 Newman MS. Chung HM. J. Org. Chem.  1974,  39:  1036 

19 Snider BB. Patricia JJ. J. Org. Chem.  1989,  54:  38 

20 Keay BA. Rodrigo R. Tetrahedron  1984,  40:  4597 

21

The physical and spectroscopic data for the new synthetic compounds. Compound 8: yellow oil, bp 225 °C (oven temperature)/0.1 mbar in a Kugelrohr apparatus. MS (EI): m/z = 238 [M⁺]. ¹H NMR (CDCl₃): δ = 1.18 (t, J = 7.6 Hz, 3 H, -CH₂CH₃), 2.50 (q, J = 7.6 Hz, 2 H, -CH₂CH₃), 3.80 (s, 3 H, 1-COOCH₃), 3.84 (s, 3 H, 2-COOCH₃), 7.0 (d, J = 8.4 Hz, 1 H, 4-H), 7.34 (d, J = 8.4 Hz, 1 H, 5-H), 10.83 (s, 1 H, -OH). ¹³C NMR (CDCl₃): δ = 17.0 (-CH₃), 27.0 (-CH₂-), 52.0 (1-OCH₃), 53.0 (2-OCH₃), 108.2 (2-C), 119.3 (4-C), 132.0 (6-C), 134.0 (1-C), 136.0 (5-C), 159.8 (3-C), 169.3, 169.4 (1-COO, 2-COO). Compound 9: yellow oil. MS (EI): m/z = 180 [M⁺], ¹H NMR (CDCl₃): δ = 1.18 (t, J = 7.6 Hz, 3 H, -CH₂CH₃), 2.88 (q, J = 7.6 Hz, 2 H, -CH₂CH₃), 3.88 (s, 3 H, 1-COOCH₃), 6.40 (s, 1 H, -OH), 6.97 (dd, J = 8.3 Hz, J = 2.7 Hz, 1 H, 3-H), 7.12 (d, J = 8.3 Hz, 1 H, 4-H), 7.38 (d, J = 2.7 Hz, 1 H, 6-H). ¹³C NMR (CDCl₃): δ = 16.0 (-CH₃), 27.8 (-CH₂-), 52.0 (1-OCH₃), 117.9 (6-C), 120.0 (3-C), 130.0 (1-C), 132.0 (4-C), 138.0 (5-C), 153.9 (2-C), 168.2 (1-COO).