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DOI: 10.1055/s-2004-829533
Preparation of (Phenyldifluoromethyl)- and (Phenoxydifluoromethyl)-silanes by Magnesium-Promoted Carbon-Chlorine Bond Activation
Publication History
Publication Date:
29 June 2004 (online)
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Abstract
Treatment of α-chloro-α,α-difluorotoluene and α-chloro-α,α-difluoroanisole with chlorotrimethylsilane in the presence of magnesium in DMF led to their corresponding trimethylsilyl derivatives. These compounds are able to transfer their fluorinated group to various electrophilic substrates (carbonyl compounds, disulfides, phenyl isocyanate).
Key words
fluorine - alkyl halides - silicon - magnesium - nucleophilic additions
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References
This method is reported to give an almost quantitative yield. In our hands, the yield was limited to 20%, even with carefully distilled solvents.
10DMF has already been used for the formation of fluorinated organometallic intermediates. [12]
12Transformation of 1,4-bis(trifluoromethyl)benzene into α-trimethylsilyl-α,α,α′,α′,α′-pentafluoroxylene by Gilman’s procedure in DMF has been reported.13 However, these conditions are not efficient when the aromatic ring is substituted by only one trifluoromethyl group.
14Preparation of 2: To anhyd DMF (20 mL) were added magnesium powder (0.486 g, 20 mmol) and chlorotri-methylsilane (5.07 mL, 40 mmol) under argon. Then α-chloro-α,α-difluorotoluene(4) (1.625 g, 10 mmol) was added dropwise. The reaction was very exothermic and the mixture was stirred until it turned brown. After hydrolysis, the mixture was extracted with Et2O and the organic layer washed with H2O, dried over MgSO4 and then purified by flash chromatography on silica gel using pentane as eluent to afford 1.96 g of a colourless liquid identified as 2 (98% from PhCF2Cl). 13C NMR (50 MHz, CDCl3): δ = -4.9, 124.6 (t, 3 J CF = 7 Hz), 128.2, 128.8, 131.8 (t, 1 J CF = 265 Hz), 138.2 (t, 2 J CF = 20 Hz).
15
Preparation of 3: In the same way, (phenoxydifluoro-methyl)trimethylsilane was synthesised by reaction of α-chloro-α,α-difluoroanisole(5) (1.785 g, 10 mmol), magnesium powder (0.486 g, 20 mmol) and chlorotrimethyl-silane (12.67 mL, 100 mmol). The reaction mixture was stirred and heated (55 °C) until it turned brown. Treatment and purification are the same as for compound 2. Reagent 3 was isolated as a colourless liquid (60% from PhOCF2Cl). 19F NMR (282 MHz, CDCl3): δ = -75.2 (s); 1H NMR (300 MHz, CDCl3): δ = 0.33 (s, 9 H, CH3), 7.18-7.39 (m, 5 H,
Ar-H). 13C NMR (50 MHz, CDCl3): δ = -4.7, 122.1, 125.0, 129.1, 131.1 (t, 1
J
CF = 268 Hz), 150.6 (t, 4
J
CF = 5 Hz). MS: m/z (%) = 216 (11)[M+
] 197 (2) [M+
- F] 77 (100), [ Ph] 73 (43) [SiMe3]. Degradation of 3 into olefins 6 and 7 sometimes occurs and does not allow an accurate elemental analysis.
Olefin 6: 19F NMR (188 MHz, CDCl3): δ = -128.6 (s). 1H NMR (200 MHz, CDCl3): δ = 7.16-7.43 (m, 10 H, Ar-H). Olefin 7: 19F NMR (188 MHz, CDCl3): δ = -122.5 (s). 1H NMR (200 MHz, CDCl3): δ = 7.12-7.39 (m, 5 H, Ar-H).
17Dimerisation of the analogous chlorophenoxycarbene has been reported.13
19Preparation of difluorinated compounds 8 and 9: Fluoride source [KF or (n-Bu4N+, Ph3SnF2 -), 0.5 mmol), DMF (5 mL) and the electrophile (10 mmol) were introduced, in that order, into a round bottomed flask under argon. The difluoroalkyltrimethysilylated reagent was then added in one portion. The solution was stirred. Evolution of the mixture was followed by 19F NMR. After consumption of the silylated compound, the mixture was poured onto 20 mL of HCl (0.5 M) and stirred for 20 min. The aqueous layer was extracted with Et2O and the resulting organic phase was washed with brine, an iced sat. NaHCO3 aq solution and again with brine. The organic phases were dried over MgSO4 and concentrated under vacuum. Alcohols were obtained in their O-silylated form; deprotection was achieved by an acidic treatment [HCl 35% (0.2 mL) in EtOH (10 mL)]. See Table [1] and Table [2] for 1H NMR and 19F NMR data. Compound 8b: 13C NMR (75 MHz, CDCl3): δ = 76.9 (t, 2 J CF = 31 Hz), 121.2 (t, 1 J CF = 248 Hz), 126.3 (t, 3 J CF = 6 Hz), 127.8, 127.9, 128.0, 128.6, 130.0, 133.8 (t, 2 J CF = 26 Hz), 135.8. IR: 3431, 3057, 3032 cm-1. MS: m/z (%) = 127 (26) [PhCF2], 107 (88) [PhCHOH], 77 (51) [Ph]. Anal. Calcd for C14H12F2O: C, 71.79%; H, 5.13%. Found: C, 71.69%; H, 5.03%. The spectral data agree with those reported in the literature.8,9 Compound 8f: isolated as a white solid, mp 102 °C. 13C NMR (75 MHz, CDCl3): δ = 114.8 (t, 1 J CF = 254 Hz), 120.3, 125.6 (t, 3 J CF = 6 Hz), 125.7, 128.7, 129.2, 131.1, 132.6 (t, 2 J CF = 25 Hz), 135.8, 149.3, 161.9 (t, 2 J CF = 31 Hz). IR: 3334, 3057, 1685 cm-1. MS: m/z (%) = 247 (78) [M+], 127 (76) [PhCF2], 120 (67) [PhNHC(O)], 92 (79) [PhNH], 77 (41) [Ph]. Anal. Calcd for C14H11F2ON: C, 68.00%; H, 4.45%. Found: C, 68.21%; H, 4.47%.