Subscribe to RSS
DOI: 10.1055/s-2002-20458
Facile Synthesis of o- and p-(1-Trifluoromethyl)-alkylated Phenols via Generation and Reaction of Quinone Methides
Publication History
Publication Date:
05 February 2007 (online)

Abstract
Several ortho- and para-(1-chloro-2,2,2-trifluoroethyl)phenols were prepared from the corresponding alcohols and thionyl chloride in the presence of pyridine. They reacted smoothly with sodium borohydride and Grignard reagents under mild conditions, forming 2,2,2-trifluoroethyl- or 1-trifluoromethylalkylphenols in high yields.
Key words
trifluoroalkyl - phenol - sodium borohydride - Grignard reagent - quinone methide
- 1
Smart BE. J. Fluorine Chem. 2001, 109: 3 -
2a
Nagata W.Okada K.Aoki T. Synthesis 1979, 365 -
2b
Bigi F.Casiraghi G.Casnati G.Sartori G.Fava GG.Belicchi MF. J. Org. Chem. 1985, 50: 5018 -
2c
Casiraghi G.Bigi F.Casnati G.Sartori G.Soncini P.Fava GG.Belicchi MF. J. Org. Chem. 1988, 53: 1779 - 3
Rhoads SJ. Org. React. 1974, 22: 1 -
4a
Snieckus V. Chem. Rev. 1990, 90: 879 -
4b
Mitchell RH.Lai Y.-H.Williams RV. J. Org. Chem. 1979, 44: 4733 -
4c
Knochel P.Majid T. Tetrahedron Lett. 1990, 31: 4413 - 5
McLoughlin BJ. J. Chem. Soc., Chem. Commun. 1969, 540 -
6a
Mitchell D.Doecke CW.Hay LA.Koenig TM.Wirth DD. Tetrahedron Lett. 1995, 36: 5335 -
6b
Van de Water RW.Magdziak DJ.Chau JN.Pettus TRR. J. Am. Chem. Soc. 2000, 122: 6502 -
6c
Jones RM.Van de Water RW.Lindsey CC.Hoarau C.Ung T.Pettus TRR. J. Org. Chem. 2001, 66: 3435 -
7a
Yoshida M.Amemiya H.Kobayashi M.Sawada H.Hagii H.Aoshima K. J. Chem. Soc., Chem. Commun. 1985, 234 -
7b
Guan H.-P.Hu C.-M. J. Fluorine Chem. 1996, 78: 101 -
8a
Gong Y.Kato K.Kimoto H. Synlett 1999, 1403 -
8b
Gong Y.Kato K.Kimoto H. Bull. Chem. Soc. Jpn. 2001, 74: 377
References
1b: A colorless oil. 1H NMR (CDCl3): δ = 7.09 (2 H, s), 4.98 (1 H, q, J = 6.8 Hz), 4.52 (1 H, br, s), 2.25 (6 H, s). 19F NMR (CDCl3): δ = 88.68 (3 F, d, J = 6.8 Hz). MS: m/z (%) = 238(32) [M+], 203(100), 169(41), 153(67). HRMS: Calcd: 238.0372; found: 238.0373. 2b: A colorless oil. 1H NMR (CDCl3): δ = 7.37 (2 H, d, J = 8.4 Hz), 6.85 (2 H, d, J = 8.4 Hz), 5.76 (1 H, br, s), 5.06 (1 H, q, J = 6.8 Hz). 19F NMR (CDCl3): δ = 88.39 (3 F, d, J = 6.8 Hz). MS: m/z (%) = 210(39) [M+], 175(100), 141(42), 125(67), 96(24). HRMS: Calcd: 210.0059; found: 210.0059. 3b: A colorless oil. 1H NMR (CDCl3): δ = 7.59 (1 H, d, J = 7.5 Hz), 7.20 (1 H, m), 7.02 (1 H, m), 6.82 (1 H, d, J = 8.1 Hz), 6.17 (1 H, br, s), 5.82 (1 H, q, J = 7.0 Hz). 19F NMR (CDCl3): δ = 88.80 (3 F, d, J = 7.0 Hz). MS: m/z (%) = 210(68) [M+], 175(60), 155(30), 145(60), 141(74), 127(100), 96(39). HRMS: Calcd: 210.0059; found: 210.0061. 1c: Colorless needles, mp 86-87 °C. 1H NMR (CDCl3): δ = 6.89 (2 H, s), 4.62 (1 H, s), 3.21 (2 H, q, J = 10.8 Hz), 2.23 (6 H, s). 19F NMR (CDCl3): δ = 95.53 (3 F, t, J = 10.8 Hz). MS. m/z (%) = 204(57) [M+], 135(100), 109(7), 91(25). Anal. Calcd for C10H11F3O: C, 58.82; H, 5.43. Found: C, 58.72; H, 5.42. 2c: Colorless needles, mp 56-58 °C. 1H NMR (CDCl3): δ = 7.15 (2 H, d, J = 8.2 Hz), 6.81 (2 H, d, J = 8.2 Hz), 5.95 (1 H, br, s), 3.27 (2 H, q, J = 11.0 Hz). 19F NMR (CDCl3): δ = 95.48 (3 F, t, J = 11.0 Hz). MS: m/z (%) = 176(40) [M+], 157(3), 107(100). Anal. Calcd for C8H7F3O: C, 54.55; H, 4.01. Found: C, 54.50; H, 4.02. 3c: A colorless oil. 1H NMR (CDCl3): δ =7.25 (1 H, d, J = 7.5 Hz), 6.92-7.22 (2 H, m), 6.79 (1 H, d, J = 7.9 Hz), 5.12 (1 H, br, s), 3.46 (2 H, q, J = 10.8 Hz). 19F NMR (CDCl3): δ = 96.33 (3 F, t, J = 10.8 Hz). MS: m/z (%) = 176(72) [M+], 156(42), 107(100). Anal. Calcd for C8H7F3O: C, 54.55; H, 4.01. Found: C, 54.47; H, 4.00. 1d: Colorless needles, mp 109-110 °C. 1H NMR (CDCl3): δ = 6.87 (2 H, s), 5.60 (1 H, m), 5.00 (1 H, d, J = 18.0 Hz), 4.96 (1 H, d, J = 9.2 Hz), 4.67 (1 H, s), 3.14 (1 H, m), 2.66 (2 H, m), 2.21 (6 H, s). 19F NMR (CDCl3): δ = 91.99 (3 F, d, J = 9.4 Hz). MS: m/z (%) = 244(10) [M+], 203(100), 153(27), 91(12). Anal. Calcd for C13H15F3O: C, 63.93; H, 6.19. Found: C, 63.73; H, 6.16. 11: Colorless plates, mp 57-58 °C. 1H NMR (CDCl3): δ = 6.51 (1 H, s), 5.97 (1 H, s), 5.20 (1 H, q, J = 8.1 Hz), 1.97 (3 H, s), 1.95 (3 H, s). 19F NMR (CDCl3): δ = 106.96 (3 F, d, J = 8.1 Hz). MS: m/z (%) = 203(100) [M+], 153(26). Anal. Calcd for C10H9F3O: C, 59.41; H, 4.49. Found: C, 59.60; H, 4.50. 2d: A colorless oil. 1H NMR (CDCl3): δ = 7.15 (2 H, d, J = 8.4 Hz), 6.81 (2 H, d, J = 8.4 Hz), 5.60 (1 H, m), 5.21 (1 H, s), 5.00 (1 H, d, J = 16.9 Hz), 4.96 (1 H, d, J = 10.3 Hz), 3.23 (1 H, m), 2.67 (2 H, m). 19F NMR (CDCl3): δ = 91.67 (3 F, d, J = 9.4 Hz). MS: m/z (%) = 216(15) [M+], 175(100), 127(6), 125(51). Anal. Calcd for C11H11F3O: C, 61.11; H, 5.13. Found: C, 61.03; H, 5.11. 3d: A colorless oil. 1H NMR (CDCl3): δ = 7.31 (1 H, d, J = 8.3 Hz), 6.94-7.18 (2 H, m), 6.87 (1 H, d, J = 7.7 Hz), 5.60 (1 H, m), 5.07 (1 H, s), 4.99 (1 H, d, J = 15.4 Hz), 4.95 (1 H, d, J = 9.01 Hz), 4.10 (1 H, m), 2.70 (2 H, m). 19F NMR (CDCl3): δ = 92.49 (3 F, d, J = 9.2 Hz). MS: m/z (%) = 216(39) [M+], 215(44), 195(17), 175(62), 155(61), 127(100), 115(28), 107(31). Anal. Calcd for C11H11F3O: C, 61.11; H, 5.13. Found: C, 61.09; H, 5.10.