10.1002/ejoc.202000284
European Journal of Organic Chemistry
FULL PAPER
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Instrumentales (LTI, UVa). Chemical shifts (in δ units, ppm) were
referenced to SiMe4 (1H and 13C) and CFCl3 (19F). The spectral data were
recorded at 293 K unless otherwise noted. The GC-MS analyses were
performed in a Thermo-Scientific Focus DSQ II GC/MS apparatus. The
intensities are reported as percentages relative to the base peak after the
corresponding m/z value. Deuteration reactions were carried out in
Schlenk flasks with constant stirring. To avoid metal contamination, both
the magnetic bar and the Schlenk flasks were cleaned twice with aqua
regia prior to use. Cesium carbonate, Potassium phosphate, sodium
hydroxide, tetrabutylammonium chloride, all the fluoroarenes, thiophene
and furane are commercially available and were purchased from Aldrich,
Alfa Aesar or Fluorochem. Deuterated solvents (DMSO-d6, acetone-d6,
D2O) were provided by Eurisotop. All commercial reagents and solvents
were used as received unless otherwise indicated. Tetrabutylammonium
carbonate was prepared according to the procedure in the literature.[26]
13C{1H} NMR (125.67 MHz, δ, CDCl3): 145.8 (dm, JC-F
=
250 Hz, C1, C2,C4, C5), 105.9 (m, C3, C6). 19F NMR
(470.17 MHz, δ, CDCl3): -140.19 (s, 4F). MS (EI, 70 eV):
m/z (%) 152 (100) [M+], 83 (40).
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13C{1H} NMR (125.67 MHz, δ, CDCl3): 156.9 (dm, JC-F
=
249.2 Hz, C5), 151.1 (dddd, 1JC-F = 251.3 Hz, 2JC-F = 15 Hz,
3
1
3JC-F = 11 Hz, JC-F = 5.3 Hz, C1, C3), 137.3 (dtd, JC-F
=
247.4 Hz, JC-F = 15.4 Hz, JC-F = 5.1 Hz, C2), 100.9 (m,
2
4
1JC-D
=
2JC-F = 25.5 Hz, C4, C6). 19F NMR (470.17 MHz, δ,
CDCl3): -114.37 (d, 5JF-F = 10.5 Hz, 1F, F5), -131.90 (d, 3JF-
F = 20.4 Hz 2F, F1, F3), -165.99 (td, 3JF-F = 20.4, 5JF-F = 10.5
6
Hz, 1F, F2). MS (EI, 70 eV): m/z (%) 152 (65) [M+], 121 (45), 83 (100).
Deuteration of fluorobenzene, 1,2-difluorobenzene and 1-fluoro-4-
bromobenzene.
Deuteration of pentafluorobenzene
Potassium phosphate (1.06 g, 5 mmol) was introduced in Schlenk flask
with a screw cap in a nitrogen atmosphere. Then, DMSO-d6 (5.6 mL, 80
mmol) and the corresponding fluoroarene (5 mmol) were added. The
mixture was kept in a pre-heated bath at 130 ºC during 24 h for
fluorobenzene and 1,2-difluorobenzene and during 72 h for 1-fluoro-4-
bromobenzene. After that time, total conversion was observed, as
checked by 19F NMR of the crude mixture. The deuterated fluoroarenes
were purified by flash distillation under vacuum, collecting the product by
freezing in liquid nitrogen. The total purification of 1-bromo-4-fluoro-
3,5(d2)-benzene was carried out by column chromatography in silica
using dichloromethane as eluent. All products were obtained as colorless
liquids and with good yields (see Table 2).
Cesium carbonate (78.0 mg, 0.24 mmol) was introduced in Schlenk flask
with a screw cap in a nitrogen atmosphere. Then, acetone-d6 (2.5 mL,
31.2 mmol) and pentafluorobenzene (870 µL, 7.8 mmol) were added.
The mixture was kept in a pre-heated bath at 90 ºC during 4 h. After that
time, total conversion was observed, as checked by 19F NMR of the
crude mixture. The deuterated pentafluorobenzene, was purified by an
extraction of the acetone-d6 with water in a liquid-liquid extraction. Yield:
0.95 g (75 %). NOTE: The reaction works in shorter times at the expense
of using
a higher amount of acetone-d6. In the same conditions
described above, using 62 mmol of acetone-d6 (4.7 mL) the reaction is
complete in 1 h.
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13C{1H} NMR (125.67 MHz, δ, CDCl3): 146.1 (dm, JC-F
=
1H NMR (499.73 MHz, δ, CDCl3): 7.34 (m, 2H, H3, H5),
248.3 Hz, C2, C6), 141.7 (dm, 1JC-F = 253.1 Hz, C4), 137.5
(dm, JC-F = 252.3 Hz, C3, C5), 100.5 (m, C1). 19F NMR
(470.17 MHz, δ, CDCl3): -139.02 (m, 2F, Fortho), -153.80
(t, JF-F = 20.8 Hz, 1F, Fpara), -162.19 (m, 2F, Fmeta). MS
(EI, 70 eV): m/z (%) 169 (100) [M+], 138 (15), 100 (70).
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7.14 (t, JH-H = 7.4 Hz, 1H, H4). 13C{1H} NMR (125.67
1
MHz, δ, CDCl3): 162.8 (d, 1JC-F = 248.7 Hz, C1), 129.8 (d,
1
3JC-F = 7.8 Hz, C3, C5), 123.9 (C4), 115 (m, JC-D= 25 Hz,
3
2JC-F = 20 Hz, C2, C6). 19F NMR (470.17 MHz, δ, CDCl3):
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-113.67 (t, JF-H = 5.8 Hz, 1F). MS (EI, 70 eV): m/z (%)
98 (100) [M+], 71 (74).
Deuteration of 1,3-difluorobenzene, tri- , and tetrafluorobenzenes.
1H NMR (499.73 MHz, δ, CDCl3): 7.07 (m, H4, H5).
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Cesium carbonate (162.9 mg, 0.5 mmol) was introduced in Schlenk flask
with a screw cap in a nitrogen atmosphere. Then, DMSO-d6 (5.6 mL, 80
mmol) and the corresponding fluoroarene (5 mmol) were added. The
mixture was kept in a pre-heated bath at 90 ºC during 1 h. After that time,
total conversion was observed, as checked by 19F NMR of the crude
mixture. The deuterated fluoroarenes were purified by flash distillation
under vacuum, collecting the product by freezing in liquid nitrogen. All of
them were obtained as colorless liquids and with good yields (see Table
2).
13C{1H} NMR (125.67 MHz, δ, CDCl3): 150.5 (dd, JC-F
=
=
=
2
3
4
250 Hz, JC-F = 13.6 Hz, C1, C2), 124.4 (m, JC-F = JC-F
5.2 Hz, 2JC-D = 1.5 Hz, C4), 117.1 (m, 1JC-D = 24.9, 2JC-F
12 Hz, JC-F = 5.3 Hz, C3, C6). 19F NMR (470.17 MHz, δ,
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CDCl3): -138.73 (bs). MS (EI, 70 eV): m/z (%) 116 (100)
[M+], 100 (18), 71 (60), 57 (78).
1H NMR (499.73 MHz, δ, CDCl3): 7.44 (d, 4JH-F = 5.1 Hz,
2H, H2, H6). 13C{1H} NMR (125.67 MHz, δ, CDCl3): 161.8
(d, JC-F = 248.4 Hz, C4), 132.8 (d, JC-F = 8 Hz, C2, C6),
117 (m, C3, C5), 116.4 (C1). 9F NMR (470.17 MHz, δ,
CDCl3): -115.9.(bs).
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1H NMR (499.73 MHz, δ, CDCl3): 7.29 (m, 1H, H5), 6.87
(m, 2H, H4, H6). 13C{1H} NMR (125.67 MHz, δ, CDCl3):
163.1 (dd, 1JC-F = 249.6 Hz, 3JC-F = 10 Hz, C1, C3), 130.6 (t,
3JC-F = 10 Hz, C5), 111.2 (m, C4, C6), 103.8 (m, 1JC-D= 2JC-F
= 25.5 Hz, C2). 19F NMR (470.17 MHz, δ, CDCl3): -110.28
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F
The minor isomer monoD, could not be completely
characterized (8 %). 1H NMR (499.73 MHz, δ, CDCl3):
7.44, 6.95. 13C{1H} NMR (125.67 MHz, δ, CDCl3): 132.5 (d,
3JC-F = 8 Hz, C2), 132.3 (d, 3JC-F = 8 Hz, C6), 116.3 (d, 2JC-F
= 13 Hz, C5). 9F NMR (470.17 MHz, δ, CDCl3): -115.64.
4
D
3
5
6
(m, 2F). MS (EI, 70 eV): m/z (%) 115 (100) [M+], 64 (65).
2
2
1
Br
1
13C{1H} NMR (125.67 MHz, δ, CDCl3): 163.2 (dt, JC-F
=
10
249.6 Hz, 3JC-F = 15 Hz, C1, C3, C5), 99.9 (m, C2, C4, C6).
19F NMR (470.17 MHz, δ, CDCl3): -108.10 (s, 3F). MS (EI,
70 eV): m/z (%) 135 (80) [M+], 83 (90), 66 (100).
Deuteration of ethyl 3,5-difluorobenzoate
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Cesium carbonate (213.7 mg, 0.66 mmol) was introduced in a Schlenk
flask with a screw cap in a nitrogen atmosphere. Then, DMSO-d6 (3.7
mL, 52.5 mmol) and ethyl 3,5-difluorobenzoate (0.5 mL, 3.28 mmol) were
added. The mixture was kept in a pre-heated bath at 130 ºC during 72 h.
After that time, the following mixture of compounds given below was
observed in the crude of the reaction by 19F NMR: ethyl 3,5-difluoro-4(d)-
benzoate (59 %), 3,5-difluoro-4(d)-benzoic acid (28 %), ethyl 3,5-difluoro-
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13C{1H} NMR (125.67 MHz, δ, CDCl3): 147.4 (dm, JC-F
=
251.9 Hz, C1, C4), 140.8 (dm, JC-F = 254.9 Hz, C2, C3),
110.8 (m, C5, C6). 19F NMR (470.17 MHz, δ, CDCl3): -
139.75 (m, 2F, F1, F4), -156.06 (m, 2F, F2, F3). MS (EI, 70
eV): m/z (%) 152 (100) [M+], 83 (40).
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