Fluorinations by Means of BrF3
285 Hz, CF2), 67.6, 39.1, 37.0, 35.3, 29.3, 27.9, 24.5, 22.6, 22.5,
Chlorodifluoromethyl (2-Methoxyethoxy)ethyl Ether (3h): This com-
pound was prepared from 2h (2.9 g) as described above with
19.2 . 19F NMR (188.1 MHz, CDCl3): δ
= –27.6 (s) ppm.
C11H21ClF2O (242.73): calcd. C 54.43, H 8.72; found C 54.06, H 1.7 molar equiv. of BrF3 in 60% (2.0 g), colorless oil. 1H NMR
8.98.
(200 MHz, CDCl3): δ = 4.16 (t, J = 5 Hz, 2 H, CH2), 3.77 (t, J =
5 Hz, 2 H, CH2), 3.69–3.66 (m, 2 H, CH2), 3.59–3.56 (m, 2 H,
CH2), 3.39 (s, 3 H, CH3) ppm. 13C NMR (50.3 MHz, CDCl3): δ =
125.7 (t, J = 286 Hz, CF2), 71.6, 70.5, 68.1, 67.9, 58.6 ppm. 19F
NMR (188.1 MHz, CDCl3): δ = –28.4 (s) ppm. HRMS (ESI-Qq
TOF) m/z calcd. for C6H11ClF2NaO3 227.0256 (MNa)+, found
227.0259 (MNa)+. C6H11ClF2O3 (204.60): calcd. C 35.22, H 5.42;
found C 34.98, H 4.97.
Chlorodifluoromethyl 2-Cyclohexylethyl Ether (3c): This compound
was prepared from 2c (2.9 g) as described above with 1.9 molar
equiv. of BrF3 in 65% yield (2.3 g), colorless oil. 1H NMR
(200 MHz, CDCl3): δ = 4.03 (t, J = 7 Hz, 2 H, CH2), 1.75–0.95 [m,
13 H, (CH2)5(CH)CH2] ppm. 13C NMR (50.3 MHz, CDCl3): δ =
NMR 125.9 (t, J = 287 Hz, CF2), 67.4, 35.9, 34.1, 33.1, 26.6,
26.2 ppm. 19F NMR (188.1 MHz, CDCl3): δ = –27.5 (s) ppm. MS
(ESI-Qq TOF): m/z = 213.1548 [MH]+.
Chlorodifluoromethyl N-Phthalimidoethyl Ether (3i): This com-
pound was prepared from 2i (3.6 g) as described above with 1.8 mo-
lar equiv. of BrF3 in 85% yield (3.1 g); white crystals; m.p. 54.2–
Chlorodifluoromethyl 3-Cyclohexylpropyl Ether (3d): This com-
pound was prepared from 2d (3.3 g) as described above with
1.7 molar equiv. of BrF3 in 80% yield (3.0 g), colorless oil. 1H
NMR (200 MHz, CDCl3): δ = 3.93 (t, J = 7 Hz, 2 H, CH2), 1.78–
1.69 [m, 7 H, CH2CH2(CH)CH2], 1.27–1.23 [m, 6 H, (CH2)3], 0.98–
0.93 (m, 2 H, CH2) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 125.5
(t, J = 285 Hz, CF2), 68.9, 36.7, 33.1, 26.6, 26.2, 25.8 ppm. 19F
NMR (188.1 MHz, CDCl3): δ = –27.7 (s) ppm. For MS, the usual
methods fail to show any molecular peak. However, using Amirav’s
method provided the solution and indeed a strong molecular ion
peak of m/z 226 (M)+ was observed. C10H17ClF2O (226.69): calcd.
C 52.98, H 7.56, F 16.76; found C 52.92, H 7.60, F 16.34.
1
55.1 °C. H NMR (400 MHz, CDCl3): δ = 7.91 [t, J = 5 Hz, 2 H,
(CH)2], 7.78 [t, J = 5 Hz, 2 H, (CH)2], 4.29 (t, J = 7 Hz, 2 H, CH2),
4.06 (t, J = 7 Hz, 2 H, CH2) ppm. 13C NMR (100.6 MHz, CDCl3):
δ = 125.7 (t, J = 285 Hz, CF2), 167.8, 134.2, 131.7, 123.7, 65.3,
40.7 . 19F NMR (188.1 MHz, CDCl3): δ = –28.5 (s) ppm. HRMS
(CI) m/z calcd. for C11H9ClF2NO3 276.023903 [MH]+, found
276.022870 [MH]+. C11H8ClF2NO3 (275.64): calcd. C 47.93, H
2.93, F 13.79; found C 48.16, H 2.67, F 13.96.
Chlorodifluoromethyl N-Phthalimidoundecyl Ether (3j): This com-
pound was prepared from 2j (900 mg) as described above with
1.5 mol equiv. of BrF3 in 85% yield (810 mg); white crystals; m.p.
33 °C. 1H NMR (400 MHz, CDCl3): δ = 7.83 [t, J = 5 Hz, 2 H,
(CH)2], 7.71 [t, J = 5 Hz, 2 H, (CH)2], 3.98 (t, J = 7 Hz, 2 H, CH2),
3.67 (t, J = 7 Hz, 2 H, CH2), 1.69–1.63 [m, 4 H, (CH2)2], 1.27 [s,
14 H, (CH2)7] ppm. 13C NMR (100.6 MHz, CDCl3): δ = 125.7 (t,
J = 285 Hz, CF2), 168.2, 134.1, 133.7, 123.8, 69.2, 37.9, 29.0, 28.7,
28.6, 28.4, 26.7, 25.4 ppm. 19F NMR (188.1 MHz, CDCl3): δ =
–27.5 (s) ppm. HRMS (CI) m/z calcd. for C20H26ClF2NO3
401.156928 [M]+, found 401.156860 [M]+. C20H26ClF2NO3
(401.88): calcd. C 59.77, H 6.52, N 3.49; found C 60.07, H 6.60, N
3.48.
Chlorodifluoromethyl 2-Norbornylethyl Ether (3e): This compound
was prepared from 2e (3.3 g) as described above with 1.9 molar
equiv. of BrF3 in 70% yield (2.6 g), colorless oil. 1H NMR
(400 MHz, CDCl3): δ = 3.99 (t, J = 7 Hz, 2 H, CH2), 2.23 (s, 1 H,
CH), 1.98 (s, 1 H, CH), 1.74 (s, 1 H, CH), 1.54–1.49 [m, 4 H,
(CH2)2], 1.31–1.29 (m, 2 H, CH2), 1.19–1.10 [m, 4 H, (CH2)2] ppm.
13C NMR (100.6 MHz, CDCl3): δ = 125.8 (t, J = 285 Hz, CF2),
69.7, 40.9, 38.1, 37.9, 36.6, 35.5, 31.6, 29.7, 28.6 ppm. 19F NMR
(188.1 MHz, CDCl3): δ = –27.5 (s) ppm. For MS, the usual meth-
ods fail to show any molecular peak. However, using Amirav’s
method provided the solution and indeed a strong molecular ion
peak of m/z 224 [M]+ was observed. C10H15ClF2O (224.68): calcd.
C 53.46, H 6.73, F 16.91; found C 53.56, H 6.91, F 16.55.
Preparation of Chlorodifluoromethyl 11-Aminoundecyl Ether 4j:
Compound 3j (400 mg, 0.96 mmol) was dissolved in 15 mL of etha-
nol, hydrazine hydrate (0.5 mL) was added, and the mixture was
heated at reflux for 1.5 h. The reaction mixture was cooled and
0.2 mL of concentrated hydrochloric acid was added. The white
precipitate formed was filtered, the filtrate neutralized with 30%
sodium hydroxide, extracted with chloroform and dried with
MgSO4. The solvent removed under reduced pressure to yield the
chlorodifluoromethyl 11-aminoundecyl ether (4j) in 80% yield
(208 mg), yellow oil. 1H NMR (200 MHz, CDCl3): δ = 3.91 (t, J =
7 Hz, 2 H, CH2), 2.55 (t, J = 7 Hz, 2 H, CH2), 1.73–1.64 (m, 2 H,
CH2), 1.47–1.25 [m, 16 H, 2 H br, (CH2)8, NH2] ppm. 13C NMR
(50.3 MHz, CDCl3): δ = 125.6 (t, J = 284 Hz, CF2), 69.0, 41.6,
33.2, 29.3, 28.8, 28.2, 27.2, 26.6, 25.3 ppm. 19F NMR (188.1 MHz,
CDCl3): δ = –27.6 (s) ppm. For MS, the usual methods fail to show
any molecular peak. However, using Amirav’s method provided the
solution and indeed a strong molecular ion peak of m/z 271 [M]+
was observed.
4-Chloro-1-(chlorodifluoromethoxy)benzene (3k):[9] This compound
was prepared from 2k (621 mg) as described above with 1.9 molar
equiv. of BrF3 in 40% yield (256 mg), colorless oil. 1H NMR
(200 MHz, CDCl3): δ = 7.40 [d, J = 8 Hz, 2 H, (CH)2], 7.22 [d, J
= 8 Hz, 2 H, (CH)2] ppm. 13C NMR (50.3 MHz, CDCl3): δ = 124.9
(t, J = 289 Hz, CF2), 148.5, 141.9, 132.5, 129.7, 122.7 ppm. 19F
NMR (188.1 MHz, CDCl3): δ = –26.4 (s) ppm.
Chlorodifluoromethyl 1-Adamantylethyl Ether (3f): This compound
was prepared from 2f (3.8 g) as described above with 1.9 molar
equiv. of BrF3 in 70% yield (3.1 g), colorless oil. 1H NMR
(200 MHz, CDCl3): δ = 4.05 (t, J = 7 Hz, 2 H, CH2), 1.96 [s, 3 H,
(CH)3], 1.69–1.47 [m, 14 H, (CH2)7] ppm. 13C NMR (50.3 MHz,
CDCl3): δ = 125.7 (t, J = 285 Hz, CF2), 65.6, 42.3, 42.0, 36.8,
28.4 ppm. 19F NMR (188.1 MHz, CDCl3): δ = –27.4 (s) ppm. For
MS, the usual methods fail to show any molecular peak. However,
using Amirav’s method provided the solution and indeed a strong
molecular ion peak of m/z 264 [M]+ was observed. C13H19ClF2O
(264.74): calcd. C 58.98, H 7.23, F 14.35, Cl 13.39; found C 59.10,
H 7.30, F 14.62, Cl 13.64.
Chlorodifluoromethyl 11-Bromoundecyl Ether 3g: This compound
was prepared from 2g (3.1 g) as described above with 1.5 molar
equiv. of BrF3 in 70% yield (2.6 g), colorless oil. 1H NMR
(200 MHz, CDCl3): δ = 3.98 (t, J = 7 Hz, 2 H, CH2), 3.39 (t, J =
7 Hz, 2 H, CH2), 1.88–1.67 [m, 4 H, (CH2)2], 1.30 [s, 14 H,
(CH2)7] ppm. 13C NMR (50.3 MHz, CDCl3): δ = 125.7 (t, J =
285 Hz, CF2), 69.1, 33.7, 32.7, 29.3, 28.9, 28.6, 28.3, 28.1,
25.4 ppm. 19F NMR (188.1 MHz, CDCl3): δ = –27.5 (s) ppm. For
MS, the usual methods fail to show any molecular peak. However,
using Amirav’s method provided the solution and indeed a strong
molecular ion peak of m/z 336 [M]+ was observed. C12H22BrClF2O
(335.66): calcd. C 42.94, H 6.61, F 11.32; found C 43.02, H 6.69,
F 11.70.
2,4,6-Tribromo-1-(chlorodifluoromethoxy)benzene (3l): This com-
pound was prepared from 2l (1.1 g) as described above with 1 mo-
Eur. J. Org. Chem. 2008, 2875–2880
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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