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Synlett 2007(7): 1158-1162  
DOI: 10.1055/s-2007-977423
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© Georg Thieme Verlag Stuttgart · New York

Friedel-Crafts Alkylations of Arenes with Mono- and Bis(trifluoro­methyl)oxiranes in Superacid Medium: Facile Synthesis of α-(Trifluoro­methyl)- and α,α-Bis(Trifluoromethyl)-β-Arylethanols

G. K. Surya Prakash*, Pablo J. Linares-Palomino, Kevin Glinton, Sujith Chacko, Golam Rasul, Thomas Mathew, George A. Olah*
Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California, University Park, Los Angeles 90089-1661, USA
Fax: +1(213)7406270; e-Mail: gprakash@usc.edu;
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Publication History

Received 22 December 2006
Publication Date:
13 April 2007 (online)

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Abstract

Triflic acid catalyzed Friedel-Crafts alkylation of aromatics with mono- and bis(trifluoromethyl)oxiranes through ring opening afforded α-(trifluoromethyl) and α,α-bis(trifluoromethyl)-β-phenylethanols in excellent yields. The regioselectivity of the ­oxirane ring opening and subsequent Friedel-Crafts alkylation have been found to depend on the electronic and steric effects of the ­substituents in the oxirane ring. DFT studies show that C2-O bond is longer than C1-O bond due to high electron-withdrawing effect of CF3 groups effecting C2-O cleavage resulting in a C2 electrophilic center promoting electrophilic substitution with the C2 center on aromatics.

Key words

electrophilic aromatic substitutions - alkylation - ring opening - epoxides - catalysis

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1

Visiting scientist from Dpto. Química Inorgánica y Orgánica, Facultad de Ciencias Experimentales, Universidad de Jaén, 23071 Jaén, Spain.

19

Typical Procedure for the Alkylation
To a solution of benzene (1.2 mL, 13.5 mmol) and triflic acid (1.05 mL, 11.3 mmol) in 0.75 mL of CH2Cl2, cooled to 0 °C, a solution of 2-(trifluoromethyl)oxirane (2a, 0.126 g, 1.13 mmol) in CH2Cl2 (0.75 mL) was added dropwise using a syringe over a period of 4 min with stirring. When the reaction mixture turned dark, the cooling bath was removed and the reaction mixture was allowed to come to r.t. The reaction mixture was then poured onto 10 g of crushed ice, made slightly basic with NaHCO3 and extracted with Et2O. The organic phase was washed with brine and H2O, and dried over anhyd MgSO4. The residue obtained after concentration in vacuum was purified by flash column chromatography using a mixture of n-hexane and Et2O (3:1) to obtain α-trifluoromethyl-β-phenylethanol [(1,1,1-trifluoro-3-phenylpropan-2-ol(3a)] in 78% yield. In the case of mixture of isomers where separation is difficult spectral data of the mixture are reported.
1,1,1-Trifluoro-3-phenylpropan-2-ol ( 3a) 1H NMR (400 MHz, CDCl3): δ = 2.26 (br s, 1 H) 2.71 (dd, 1 H, J 1 = 10.22 Hz, J 2 = 14.19 Hz,), 2.94 (dd, 1 H, J 1 = 2.90, J 2 = 14.19 Hz,), 3.98 (m, 1 H), 7.20 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 36.10, 71.44 (sept, J = 30.67 Hz), 124.87 (q, J = 282.17 Hz), 127.24, 128.79, 129.46, 135.76. 19F NMR (376.1 MHz, CDCl3): δ = -80.06 (d, J = 7.63 Hz, 3 F). HRMS (EI): m/z calcd for C10H10F3O: 190.0605; found: 190.0610.
1,1,1-Trifluoro-3-tolylpropan-2-ol ( 3b) Ratio of o:m:p = 24:36:40. 1H NMR (400 MHz, CDCl3): δ = 2.26 (s, 3 H), 2.52 (m, 1 H), 2.73 (m, 1 H), 2.96 (m, 1 H), 4.00 (m, 1 H), 7.07 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ = 30.05, 35.59, 36.44, 42.26, 71.76 (q, J = 30.87 Hz), 125.076 (q, J = 281.956 Hz), 126.39, 127.57, 127.94, 128.79, 129.13, 129.23, 129.27, 129.38, 129.58, 129.76, 136.02, 141.46. 19F NMR (376.1 MHz, CDCl3): δ = -80.33 (d, J = 7.63 Hz), -80.09 (d, J = 6.10 Hz), -80.04 (d, J = 6.10 Hz). HRMS (EI): m/z calcd for C10H10F3O: 204.0762; found: 204.0752.
3-Ethylphenyl-1,1,1-trifluoropropan-2-ol ( 3c) Ratio of o:m:p = 30:23:47. 1H NMR (400 MHz, CDCl3): δ = 1.23 (m, 3 H), 2.16 (br s, 1 H), 2.71 (m, 2 H), 2.83 (m, 1 H), 3.03 (m, 1 H), 4.15 (m appear as br s, 1 H), 7.16 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ = 15.19, 15.57, 25.52, 28.48, 28.78, 32.56, 35.71, 36.13, 71.46 (q, J = 30.67 Hz), 124.90 (q, J = 281.41 Hz), 126.14, 126.67, 126.81, 127.58, 128.32, 128.52, 128.78, 128.89, 129.04, 129.39, 130.35, 132.77, 143.31, 144.93. 19F NMR (376.1 MHz, CDCl3): δ = -80.30 (d, J = 6.10 Hz), -80.08 (d, J = 6.10 Hz), -80.06 (d, J = 6.10 Hz). HRMS (EI): m/z calcd for C10H10F3O: 218.0918; found: 218.0909.
1,1,1-Trifluoro-3-( n -propylphenyl)propan-2-ol ( 3d) Ratio of o:m:p = 31:28:41. 1H NMR (400 MHz, CDCl3): δ = 0.94 (m, 3 H), 1.65 (m, 2 H), 2.23 (br s, 1 H), 2.59 (m, 2 H), 2.76 (m, 1 H), 3.02 (m, 1 H), 4.06 (m, 1 H), 7.14 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ 13.85, 14.13, 24.28, 24.58, 24.62, 32.60, 34.72, 35.76, 35.73, 36.14, 37.67, 37.97, 71.65 (q, J = 26.07 Hz), 124.90 (q, J = 281.41 Hz), 125.61, 126.17, 126.67, 127.38, 127.42, 128.23, 128.49, 128.69, 128.91, 129.12, 129.29, 129.662, 129.76, 130.36, 132.76, 133.49, 135.49, 141.36, 141.76, 143.40. 19F NMR (376.1 MHz, CDCl3): δ = -80.32 (d, J = 6.10 Hz), -80.08 (d, J = 7.63 Hz), -80.06 (d, J = 6.10 Hz). HRMS (EI): m/z calcd for C10H10F3O: 232.1075; found: 232.1077.
3-(2,5-Dimethylphenyl)-1,1,1-trifluoropropan-2-ol ( 3e) 1H NMR (400 MHz, CDCl3): δ = 2.25 (s, 3 H), 2.29 (s, 3 H), 2.78 (dd, J 1 = 10.18 Hz, J 2 = 14.34 Hz, 1 H), 2.99 (dd, J 1 = 2.82 Hz, J 2 = 14.27 Hz, 1 H), 4.00 (m, 1 H), 6.97 (s, 1 H), 6.98 (s, 1 H), 7.05 (d, J 1 = 8.24 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 18.99, 20.92, 33.33, 70.72 (q, J = 30.50 Hz), 125.08 (q, J = 282.17 Hz), 128.141, 130.67, 131.10, 133.66, 133.96, 135.85. 19F NMR (376.1 MHz, CDCl3): δ = 80.33 (d, J = 6.10 Hz). HRMS (EI): m/z calcd for C11H13F3O: 218.0918; found: 218.0918.
3-(Dimethylphenyl)-1,1,1-trifluoropropan-2-ol ( 3f) Ratio of o:m:p = 11:12:77. 1H NMR (400 MHz, CDCl3): δ = 2.10 (br s, 1 H), 2.24 (m, 6 H), 2.75 (dd, J 1 = 10.3760 Hz, J 2 = 14.3400 Hz, 1 H), 2.98 (dd, J 1 = 2.8240 Hz, J 2 = 14.4195 Hz, 1 H), 3.97 (m, 1 H), 6.83-7.00 (m, 3 H). 13C NMR (100 MHz, CDCl3): δ = 19.35, 20.27, 20.93, 21.23, 32.89, 70.73 (q, J = 30.500 Hz), 125.07 (q, J = 282.29 Hz), 126.98, 127.07, 127.26, 128.59, 128.93, 130.29, 131.09, 131.54, 136.63, 137.07, 138.49. 19F NMR (376.1 MHz, CDCl3): δ = -80.61 (d, J = 7.63 Hz), -80.30 (d, J = 6.10 Hz), -80.13 (d, J = 6.10 Hz). HRMS (EI): m/z calcd for C11H13F3O: 218.0918; found: 218.0920.
2-Benzyl-1,1,1,3,3,3-hexafluoropropan-2-ol ( 4a)
1H NMR (400 MHz, CDCl3): δ = 2.82 (s, 1 H), 3.26 (s, 2 H), 7.26-7.36 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ =
-35.55, 75.84 (sept, J = 26.84 Hz), 123.07 (q, J = 287.54 Hz), 128.43, 129.013, 130.775, 131.157. 19F NMR (376.1 MHz, CDCl3): δ = -76.77 (s). HRMS (EI): m/z calcd. for C10H8OF6: 258.0479; found: 258.0477.
1,1,1,3,3,3-Hexafluoro-2-(methylbenzyl)propan-2-ol ( 4b) Ratio of o:m:p = 30:30:40. 1H (400 MHz, CDCl3): δ = 2.35, 2.36, 2.37 (3 H), 2.78, 2.79, 2.80 (1 H), 3.24, 3.34 (4 H), 7.20 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ = 19.79, 21.11, 21.34, 31.81, 35.11, 35.41, 75.64 (sept, J = 28.37 Hz), 123.20 (q, J = 286.77 Hz), 126.47, 127.42, 128.18, 128.67, 129.02, 129.32, 129.84, 130.51, 131.07, 131.43, 131.88, 132.26, 138.47, 139.00. 19F NMR (376.1 MHz, CDCl3): δ = -77.14 (s), -76.82 (s), -76.78 (s). HRMS (EI): m/z calcd for C11H10F6O: 272.0636; found: 272.0649.
2-(Ethylbenzyl)-1,1,1,3,3,3-hexafluoropropan-2-ol ( 4c) Ratio of o:m:p = 16:21:63. 1H NMR (400 MHz, CDCl3): δ = 1.24 (t, J = 7.61 Hz, 3 H), 2.66 (q, J = 7.619 Hz, 2 H), 2.82, 2.85, 2.86 (m, 1 H), 3.25, 3.26, 3.36 (s, 2 H), 7.20 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ = 15.28, 15.41, 15.56, 25.42, 28.49, 28.74, 31.06, 35.02, 35.40, 75.63 (sept, J = 28.37 Hz), 122.99 (q, J = 288.31 Hz), 126.24, 127.51, 128.03, 128.31, 128.54, 128.83, 129.00, 129.46, 130.40, 130.67, 131.04, 132.30, 144.61, 145.22. 19F NMR (376.1 MHz, CDCl3): δ = -77.05 (s), -76.84 (s), -76.83 (s). HRMS (EI): m/z calcd. for C12H12OF6: 286.0792; found: 286.0786.
1,1,1,3,3,3-Hexafluoro-2-( n -propylbenzyl)propan-2-ol ( 4d) Ratio of o:m:p = 33:21:46. 1H NMR (400 MHz, CDCl3): δ = 0.94 (t, J = 7.33 Hz, 3 H), 1.64 (hept, J = 7.60 Hz, 2 H), 2.58 (t, J = 7.26 Hz, 2 H), 2.78, 2.81, 2.83 (1 H), 3.23, 3.24, 3.35 (2 H), 6.99-7.28 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ = 13.85, 14.13, 24.28, 24.56, 24.59, 24.62, 32.60, 34.72, 35.74, 36.14, 37.67, 37.97, 38.10, 71.33 (sept, J = 30.67 Hz), 124.89 (q, J = 281.41 Hz), 125.61, 126.17, 126.67, 127.38, 127.42, 128.23, 128.49, 128.69, 128.91, 129.12, 129.29, 129.662, 129.76, 130.36, 132.76, 133.49, 135.49, 141.36, 141.76,142.73, 143.40. 19F NMR (376.1 MHz, CDCl3): δ = -80.32 (d, J = 6.10 Hz), -80.08 (d, J = 7.63 Hz), -80.06 (d, J = 6.10 Hz). HRMS (EI): m/z calcd. for C13H14OF6: 300.0949; found: 300.0957.
2-(2,5-Dimethylbenzyl)-1,1,1,3,3,3-hexafluoropropan-2-ol ( 4e)
1H NMR (400 MHz, CDCl3): δ = 2.30 (s, 3 H), 2.82 (s, 1 H), 3.29 (s, 2 H), 7.03-7.10 (m, 3 H). 13C NMR (100 MHz, CDCl3): δ = 19.26, 20.85, 31.76, 75.58 (sept, J = 29.14 Hz), 123.29 (q, J = 287.54 Hz), 128.72, 129.46, 131.36, 132.82, 135.71, 136.11. 19F NMR (376.1 MHz, CDCl3): δ = -77.20 (s). HRMS (EI): m/z calcd for C12H12F6O: 286.0792; found: 286.0780.
2-(Dimethylbenzyl)-1,1,1,3,3,3-hexafluoropropan-2-ol ( 4f)
Ratio of o:m:p = 14:6:80. 1H NMR (400 MHz, CDCl3): δ = 2.30, 2.31, 2.36 (s, 6 H), 2.72, 2.74, 2.78 (s, 1 H), 3.18, 3.29, 3.44 (s, 2 H), 6.86-7.18 (m, 3 H). 13C NMR (100 MHz, CDCl3): δ = 19.70, 20.99, 21.22, 31.50, 35.31, 75.64 (sept, J = 29.14 Hz), 123.34 (q, J = 288.31 Hz), 125.79, 127.27, 128.27, 128.94, 129.29, 130.26, 130.35, 132.20, 132.23, 138.56, 138.76, 138.94. 19F NMR (376.1 MHz, CDCl3): δ = -77.38 (s), -77.18 (s), -76.92 (s). HRMS (EI): m/z calcd for C12H12F6O: 286.0792; found: 286.0786.