The Journal of Organic Chemistry
Article
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-Acetylbenzoyl Fluoride (1s). The title compound was prepared
Isonicotinoyl Fluoride (1z). The title compound was prepared in
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9
19
in 68% yield as determined by F NMR following the general
preparation method. The title compound was also isolated from a 1
mmol scale reaction under atmosphere condition described in the
general procedure by filtration through a silica plug, washing the silica
68% yield as determined by F NMR following the general
preparation method. H NMR (400 MHz, CDCl ) δ 8.92−8.88 (m,
2H), 7.88−7.83 (m, 2H). F NMR (376 MHz, CDCl ) δ 20.93 (s,
1
3
19
3
1F).
plug with anhydrous hexane as the eluent. Obtained as a white solid in
4-(2,3-Dicyano-4,5,6-trifluorophenoxy)benzoyl Fluoride (2a).
1
3
6% isolated yield (60 mg). H NMR (400 MHz, CDCl ) δ 8.18 (d, J
The title compound was prepared in 72% yield in the form of
3
19
19
=
8.43 Hz, 2H), 8.11 (d, J = 8.38 Hz, 2H), 2.70 (s, 3H). F NMR
TFPN-substituted product as determined by F NMR following the
+
(
376 MHz, CDCl ) δ 20.23 (s, 1F). MS (EI) m/z [M] calculated for
general preparation method, using sodium 4-hydroxybenzoate (1
mmol, 160 mg), KF (3.5 mmol, 203 mg), and TFPN (2.2 mmol, 440
mg). The final product showed mixed results in NMR as GC
3
C H FO = 166, found = 166.
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7
2
4
9
4
-(Trifluoromethyl)benzoyl Fluoride (1t). The title compound
19
was prepared in 81% yield as determined by F NMR following the
indicated the product as a reaction intermediate. The main product is
1
general preparation method. After reaction was finished, 50 μL of
identified by GC with 72% yield. H NMR (400 MHz, CDCl ) δ 8.10
3
(d, J = 8.80 Hz, 2H), 7.13 (d, J = 8.78 Hz, 2H). 19F NMR (376 MHz,
0
.333 M TBAFP /CH CN standard solution was added into the vial.
6 3
1
H NMR (400 MHz, CD CN) δ 8.24 (d, J = 8.32 Hz, 2H), 7.93 (d, J
CDCl ) δ 18.18 (s, 1F), −117.29 (dd, J = 11.27, 8.25 Hz, 1F),
3
3
19
=
8.29 Hz, 2H). F NMR (376 MHz, CD CN) δ 18.52 (s, 1F), 64.05
−125.80 (dd, J = 20.54, 10.94 Hz, 1F), −132.66 (dd, J = 20.45, 8.77
3
+
+
(s, 3F). MS (EI) m/z [M] calculated for C H F O = 192, found =
Hz, 1F). HRMS (EI-TOF) m/z [M + Na] calculated for
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4 4
1
92.
C H F N O Na 343.01066; found 343.01042. The constitutional
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4
4
2
2
5
0
Methyl-4-(fluorocarbonyl)benzoate (1u). The title compound
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was prepared in 78% yield as determined by F NMR following the
general preparation method, using monomethyl terephthalate (1
mmol, 180 mg), KF (2.5 mmol, 145 mg), and TFPN (1.05 mmol, 210
mg). The title compound was also isolated from a 1 mmol scale
reaction under atmosphere condition described in the general
procedure by filtration through a silica plug, washing the silica plug
2-(6-Methoxynaphthalen-2-yl)propanoyl Fluoride (Naproxen
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Fluoride) (3a). The title compound was prepared on the benchtop
with 42% yield (40% with PC high temperature experiment) following
the general preparation method with Naproxen (1 mmol, 230 mg),
KF (2.5 mmol, 145 mg), and TFPN (1.05 mmol, 210 mg). The
reaction was quenched with 10 mL of a 1:1 hexane and DCM
mixture. The resulting mixture was then passed through a short pad of
silica using hexane as the eluent. The collected filtrate was then
concentrated under reduced pressure to saturation at about room
temperature. Then the concentrated filtrate was cooled down to −18
°C for 15 min, followed by suction filtration, to collect the final solid
with anhydrous hexane as the eluent. Obtained as a white solid in 59%
isolated yield (107 mg). H NMR (400 MHz, CDCl ) δ 8.21 (d, J =
1
3
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8.28 Hz, 2H), 8.14 (d, J = 8.42 Hz, 2H), 4.00 (s, 3H). F NMR (376
+
MHz, CDCl ) δ 20.08 (s, 1F). MS (EI) m/z [M] calculated for
C H FO = 182, found = 182.
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7
3
1
7
2
-Methoxybenzoyl Fluoride (1v). The title compound was
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prepared in 73% yield as determined by F NMR following the
general preparation method. The title compound was also isolated
from a 1 mmol scale reaction under atmosphere condition described
in the general procedure by filtration through a silica plug, washing
the silica plug with anhydrous hexane as the eluent. Obtained as a
product. Yield, 98 mg for reaction done in CH CN, and 93 mg for
3
reaction done in PC. Because of the higher polarity of the PC than
acetonitrile, we use a mixture of 42 mL of hexane and 7 mL of DCM
to quench the reaction while other steps remained the same as for the
1
reaction done in acetonitrile. H NMR (400 MHz, CDCl ) δ 7.76 (d,
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1
colorless oil in 77% isolated yield (118 mg). H NMR (400 MHz,
J = 21.1 Hz, 1H), 7.76 (d, J = 3.4 Hz, 1H), 7.70 (d, J = 1.7 Hz, 1H),
7.39 (dd, J = 8.5, 1.9 Hz, 1H), 7.20 (dd, J = 8.9, 2.5 Hz, 1H), 7.16 (d,
CDCl ) δ 7.91 (dd, J = 8.07, 1.35 Hz, 1H), 7.67−7.60 (m, 1H),
3
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3
.07−7.01 (m, 2H), 3.96 (s, 3H). F NMR (376 MHz, CDCl ) δ
J = 2.5 Hz, 1H), 4.03 (q, J = 7.1 Hz, 1H), 3.95 (s, 3H), 1.69 (dd, J =
3
+
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1.67 (s, 1F). MS (EI) m/z [M] calculated for C H FO = 154,
7.2, 0.8 Hz, 3H). F NMR (376 MHz, CDCl ) δ 39.63 (s, 1F).
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1
found = 154.
C{ H} NMR (100 MHz, CDCl ) δ 164.4 (d, C-F, 1J = 367.7
3 C‑F
2
,6-Dichlorobenzoyl Fluoride (1w). The title compound was
Hz), 158.1, 134.1, 132.4, 129.3, 128.9, 127.8, 126.4, 125.7, 119.5,
105.6, 55.4, 44.2 (d, C-F, 2JC‑F = 49.1 Hz), 18.1. MS (EI) m/z [M]+
calculated for C H FO = 232, found = 232.
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prepared in 60% yield as determined by F NMR following the
general preparation method. The title compound was also isolated
from a 1 mmol scale reaction under atmosphere condition described
in the general procedure by filtration through a silica plug, washing
the silica plug with anhydrous hexane as the eluent. Obtained as a
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2
4-(Dipropylsulfamoyl)benzoyl Fluoride (Probenecid Fluoride)
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(3b). The title compound was prepared on the benchtop with
34% yield following the general preparation method with Probenecid
(4 mmol, 1.14 g), KF (10 mmol, 0.58 g), TFPN (4.2 mmol, 0.84 g),
1
white solid in 78% isolated yield (152 mg). H NMR (400 MHz,
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CDCl ) δ 7.44−7.42 (m, 3H). F NMR (376 MHz, CDCl ) δ 53.33
and 8 mL of CH CN. The reaction mixture was first concentrated to
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1
(
3
s, 1F). C{ H} NMR (100 MHz, CDCl ) δ 153.7 (d, C-F, 1J
54.0 Hz), 132.8 (d, C-F, 3J = 1.5 Hz), 132.8, 129.0, 128.4. MS
=
2 mL of total volume and then quenched with a mixture of 40 mL of
hexane and 10 mL of DCM. Then the resulting mixture was passed
through a short silica plug, and the silica plug was washed with a 1:1
hexanes/DCM mixture. The filtrate was then concentrated under
reduced pressure to reach saturation at about room temperature.
Then the concentrated filtrate was cooled down to −18 °C for 15
3
C‑F
C‑F
+
•
35
(
(
[
EI) calculated for [M] :C H Cl FO = 192 (for Cl), found = 192
for Cl), 194 (for Cl, Cl), 196 (for Cl). HRMS (EI-TOF) m/z
M] calculated for C H Cl FO 191.9545; found 191.9543.
7 3 2
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+
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2
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2
-Naphthoyl Fluoride (1x). The title compound was prepared in
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77% yield as determined by F NMR following the general
min, followed by suction filtration, to collect the final solid product.
1
preparation method. The title compound was also isolated from a 1
mmol scale reaction under atmosphere condition described in the
general procedure by filtration through a silica plug, washing the silica
Yield, 390 mg. H NMR (400 MHz, CDCl ) δ 8.22−8.17(m, 2H),
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8.0−7.95 (m, 2H), 3.14 (t, J = 7.65 Hz, 4H), 1.58 (h, J = 7.74 Hz,
19
4H), 0.89 (t, J = 7.4 Hz, 6H). F NMR (376 MHz, CDCl ) δ 20.2 (s,
3
1F). 13C{ H} NMR (100 MHz, CDCl ) δ 156.0 (d, C-F, 1J
1
=
plug with anhydrous hexane as the eluent. Obtained as a white solid in
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C‑F
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1
3% isolated yield (126 mg). H NMR (400 MHz, CDCl ) δ 8.67 (s,
346.1 Hz), 146.7, 132.1 (d, C-F, 3JC‑F = 3.7 Hz), 128.1 (d, C-F, 2J
= 62.1 Hz), 127.5, 50.0, 22.0, 11.1. MS (EI) m/z [M] calculated for
3
C‑F
+
H), 8.06−7.92 (m, 4H), 7.75−7.68 (m, 1H), 7.68−7.60 (m, 1H).
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+
F NMR (376 MHz, CDCl ) δ 18.07 (s, 1F). MS (EI) m/z [M]
C H NO FS = 287, found = 287.
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13 18
3
calculated for C H FO = 174, found = 174.
(1-Benzoyl-5-methoxy-2-methyl-1H-indol-3-yl)acetyl Fluoride
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7
3
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38
3
-Pyridinecarbonyl Fluoride (Nicotinoyl Fluoride) (1y). The
(Indomethacin Fluoride) (3c). The title compound was prepared
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title compound was prepared in 77% yield as determined by F NMR
on the benchtop with 47% yield following the general preparation
method with Indomethacin (1 mmol, 358 mg), KF (2.5 mmol, 145
mg), and TFPN (1.05 mmol, 210 mg). Upon the completion of the
reaction, the reaction mixture was quenched with 10 mL of a 1:1
hexane and DCM mixture. Then the resulting mixture was filtrated
following the general preparation method. 1H NMR (400 MHz,
CDCl ) δ 9.23 (d, J = 2.00 Hz, 1H), 8.91 (dd, J = 4.95, 1.69 Hz, 1H),
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.34−8.29 (m, 1H), 7.51 (dd, J = 8.08, 4.90 Hz, 1H). F NMR (376
MHz, CDCl ) δ 20.60 (s, 1F).
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072
J. Org. Chem. 2021, 86, 6066−6074