The Journal of Organic Chemistry
Page 6 of 13
24.65 g (0.099 mol, 74% yield), yellow oil, b.p. 81-82 °C (7 mm
Hg). H NMR (500 MHz, CDCl3, rotamers ~1:1): δ 3.95 – 3.85
-73.4 (s). HRMS (ESI-TOF) m/z: [M + H]+ calcd for C10H14F6NO,
278.0980; found 278.0987.
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(m, 1H), 3.82 (t, J = 8.9 Hz, 1H), 3.73 (t, J = 10.4 Hz, 1H), 3.56
(dd, J = 17.2, 8.3 Hz, 1H), 3.46 (dd, J = 18.5, 9.2 Hz, 1H), 3.23 (t,
J = 9.7 Hz, 1H), 3.13 (t, J = 10.6 Hz, 1H), 2.61 – 2.51 (m, 1H),
2.50 – 2.41 (m, 1H), 2.32 – 2.14 (m, 3H), 1.81 – 1.65 (m, 1H),
1.70 – 1.56 (m, 1H). 13C {1H} NMR (126 MHz, CDCl3): δ 156.0
(m), 126.7 (q, J = 276 Hz), 126.3 (q, J = 276 Hz), 116.3 (q, J =
287 Hz), 116.3 (q, J = 287 Hz), 52.1, 51.2, 46.8, 46.0 (d, J = 3
Hz), 36.9 (m), 33.7, 32.1, 31.0 (m), 29.5. 19F NMR (376 MHz,
CDCl3): δ -65.7 (s), -65.8 (s), -73.2 (s), -73.3 (s). HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C8H10F6NO, 250.0667; found
250.0669.
1-Bromo-4-(2,2,2-trifluoroethyl)benzene (12a)
1.5 g (6.3 mmol, 64% yield), colorless oil. H NMR (400 MHz,
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CDCl3): δ 7.50 (d, J = 8.3 Hz, 2H), 7.17 (d, J = 8.1 Hz, 2H), 3.33
(q, J = 10.7 Hz, 2H). 13C {1H} NMR (126 MHz, CDCl3): δ 132.0,
132.0, 129.24 (q, J = 3.0 Hz), 125.6 (q, J = 276.8 Hz), 122.5, 39.9
(q, J = 30.0 Hz). 19F NMR (376 MHz, CDCl3): δ -66.5 (s).
GCMS: m/z = 239 (M+). HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C8H7BrF3, 238.9683; found 238.9685.
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1-Bromo-3-(2,2,2-trifluoroethyl)benzene (13a)
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0.7 g (2.93 mmol, 60% yield), colorless oil. H NMR (400 MHz,
CDCl3): δ 7.53 – 7.43 (m, 2H), 7.26 – 7.18 (m, 2H), 3.34 (q, J =
10.6 Hz, 2H). 13C {1H} NMR (126 MHz, CDCl3): δ 133.3, 132.4
(q, J = 3.0 Hz), 131.5, 130.4, 128.9 (d, J = 8.7 Hz), 125.6 (q, J =
276.9 Hz), 122.8, 40.0 (q, J = 30.1 Hz). 19F NMR (376 MHz,
CDCl3): δ -66.3 (s). GCMS: m/z = 239 (M+). HRMS (ESI-TOF)
m/z: [M + H]+ calcd for C8H7BrF3, 238.9683; found 238.9687.
1-Bromo-2-(2,2,2-trifluoroethyl)benzene (14a)
20.1 g (84.1 mmol, 66% yield), colorless oil. 1H NMR (400 MHz,
CDCl3): δ 7.62 (d, J = 8.0 Hz, 1H), 7.39 (d, J = 7.5 Hz, 1H), 7.32
(t, J = 7.5 Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H), 3.64 (q, J = 10.5 Hz,
2H). 13C {1H} NMR (126 MHz, CDCl3): δ 133.4, 132.1, 130.4 (q,
J = 2.9 Hz), 129.9, 127.8, 125.7, 123.5 (q, J = 277.6 Hz), 39.7 (q,
J = 30.2 Hz). 19F NMR (376 MHz, CDCl3): δ -65.6 (s). GCMS:
m/z = 239 (M+). HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C8H7BrF3, 238.9683; found 238.9684.
2,2,2-Trifluoro-1-(3-(2,2,2-trifluoroethyl)piperidin-1-yl)ethan-
1-one (8a)
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18.41 g (0.07 mol, 56% yield), b.p. 52-53 °C (0.1 mm Hg). H
NMR (500 MHz, CDCl3, rotamers ~1:1): δ 4.37 (d, J = 13.2 Hz,
1H), 3.95 (dd, J = 68.2, 13.4 Hz, 1H), 3.21 – 2.63 (m, 2H), 2.16 –
1.89 (m, 4H), 1.84 – 1.71 (m, 1H), 1.64 – 1.52 (m, 1H), 1.43 –
1.28 (m, 1H). 13C {1H} NMR (126 MHz, CDCl3, rotamers ~1:1):
δ 155.7 (q, J = 36 Hz), 155.5 (q, J = 36 Hz), 126.6 (q, J = 277
Hz), 126.5 (q, J = 277 Hz), 116.6 (q, J = 288 Hz), 50.8, 48.5, 46.3
(q, J = 3 Hz), 44.1, 37.4 (q, J = 28 Hz), 31.6 (d, J = 2 Hz), 30.9,
30.6 (d, J = 2 Hz), 30.4, 25.2, 24.3. 19F NMR (376 MHz, CDCl3,
rotamers ~1:1): δ -64.0 (s), -64.3 (s), -69.5 (s), -69.6 (s). HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C9H12F6NO, 264.0823; found
264.0827.
2,2,2-Trifluoro-1-(3-(3,3,3-trifluoropropyl)azetidin-1-yl)ethan-
1-one (9a)
1-Nitro-2-(3,3,3-trifluoropropyl)benzene (15a)
10.28 g (0.043 mol, 70% yield), yellow oil; b.p. 80-81 °C / 0.1
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18.92 g (0.076 mol, 61% yield), yellow oil, b.p. 83-84 °C (10 mm
Hg). 1H NMR (500 MHz, CDCl3): δ 4.48 (t, J = 8.7 Hz, 1H), 4.22
(t, J = 9.5 Hz, 1H), 4.02 – 3.92 (m, 1H), 3.74 (dd, J = 10.4, 5.7
Hz, 1H), 2.85 – 2.70 (m, 1H), 2.12 – 1.99 (m, 2H), 1.90 (dd, J =
15.0, 7.6 Hz, 2H). 13C {1H} NMR (126 MHz, CDCl3): δ 156.4 (q,
J = 37 Hz), 126.7 (q, J = 276 Hz), 116.2 (q, J = 288 Hz), 56.8,
53.8, 31.3 (q, J = 29.3 Hz), 28.9, 26.5 (d, J = 2.8 Hz). 19F NMR
(376 MHz, CDCl3): δ -66.8, -73.4. HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C8H10F6NO, 250.0667; found 250.0666.
mm Hg. H NMR (500 MHz, CDCl3): δ 2.46-2.56 (m, 2H), 3.15
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(t, JHH = 8.1 Hz, 2H), 7.4 (d, JHH = 7.5 Hz, 1H), 7.44 (t, JHH
=
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7.9 Hz, 1H), 7.6 (t, JHH = 7.5 Hz, 1H), 7.99 (d, JHH = 7.9 Hz,
1H). 13C {1H} NMR (125 MHz, CDCl3): δ 26.1 (q, 3JCF = 3.3 Hz),
34.5 (q, 2JCF = 28.7 Hz), 125.0, 126.4 (q, 1JCF = 276.7 Hz), 128.0,
132.1, 133.4, 134.0, 148.9. 19F NMR (188 MHz, CDCl3): δ - 67.0
(s). GCMS: m/z = 219 (M+). HRMS (ESI-TOF) m/z: [M + H]+
calcd for C9H9F3NO2, 220.0585; found 220.0587.
1-Nitro-3-(3,3,3-trifluoropropyl)benzene (16a)
2,2,2-Trifluoro-1-(4-(2,2,2-trifluoroethyl)piperidin-1-yl)ethan-
1-one (10a)
1.36 g (6.2 mmol, 71% yield), yellow oil; b.p. 95-97 °C /0.15 mm
Hg. 1H NMR (500 MHz, CDCl3): δ 8.13 – 8.05 (m, 2H), 7.56 (d, J
= 7.4 Hz, 1H), 7.50 (t, J = 7.8 Hz, 1H), 3.01 (t, J = 7.9 Hz, 2H),
2.53 – 2.38 (m, 2H). 13C {1H} NMR (126 MHz, CDCl3): δ 148.6,
141.0, 134.7, 129.8, 126.5 (q, J = 276.8 Hz), 123.2, 122.0, 35.2
(q, J = 28.9 Hz), 28.0 (q, J = 3.2 Hz). 19F NMR (188 MHz,
CDCl3): δ - 67.0 (s). GCMS: m/z = 219 (M+). HRMS (ESI-TOF)
m/z: [M + H]+ calcd for C9H9F3NO2, 220.0585; found 220.0586.
1-Nitro-4-(3,3,3-trifluoropropyl)benzene (17a)
5.78 g (0.022 mol, 49% yield), yellow oil, b.p. 67-68 °C (0.15 mm
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Hg). H NMR (500 MHz, CDCl3): δ 4.53 (d, J = 13.4, 1H), 4.01
(d, J = 13.9 Hz, 1H), 3.13 (t, J =13.3 Hz, 1H), 2.77 (t, J = 13.0
Hz, 1H), 2.14 – 1.96 (m, 3H), 1.96 – 1.87 (m, 2H), 1.39 – 1.24
(m, 2H). 13C {1H} NMR (101 MHz, CDCl3): δ 126.7 (q, J = 277
Hz), 116.6 (q, J = 288 Hz), 45.7 (q, J = 3 Hz), 43.5, 39.8 (q, J =
28 Hz), 32.4, 31.5, 30.5 (q, J = 2 Hz). 19F NMR (376 MHz,
CDCl3): δ -64.0 (s), -69.5 (s). HRMS (ESI-TOF) m/z: [M + H]+
calcd for C9H12F6NO, 264.0823; found 264.0824.
0.56 g (2.56 mmol, 72% yield), white solid, m.p. 32-33 °C; b.p.
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101-103 °C /0.15 mm Hg. H NMR (500 MHz, CDCl3): δ 2.42-
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2,2,2-Trifluoro-1-(2-(3,3,3-trifluoropropyl)piperidin-1-
yl)ethan-1-one (11a)
2.51 (m, 2H), 3.01 (t, JHH = 8.3 Hz, 2H), 7.40 (d, JHH = 8.7 Hz,
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2H), 8.19 (d, JHH = 8.7 Hz, 2H). 13C {1H} NMR (125 MHz,
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4.7 g (0.017 mol, 62% yield), yellow oil, b.p. 73-74 °C (0.3 mm
Hg). 1H NMR (500 MHz, CDCl3): δ 4.48 (t, J = 8.7 Hz, 1H), 4.22
(t, J = 9.5 Hz, 1H), 4.08 – 3.95 (m, 1H), 3.82 – 3.70 (m, 1H), 2.83
– 2.72 (m, 1H), 2.12 – 2.00 (m, 2H), 1.96 – 1.87 (m, 2H). 13C
{1H} NMR (126 MHz, CDCl3): δ 156.4 (q, J = 37 Hz), 126.7 (q, J
= 276 Hz), 116.2 (q, J = 288 Hz), 56.8, 53.8, 31.3 (q, J = 29 Hz),
28.9, 26.5 (d, J = 3 Hz). 19F NMR (376 MHz, CDCl3): δ -66.8 (s),
CDCl3): δ 28.0 (q, JCF = 3.3 Hz), 34.8 (q, JCF = 29 Hz), 123.8,
126.2 (q, JCF = 276.7 Hz), 129.0, 146.3, 146.8. 19F NMR (188
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MHz, CDCl3): δ -67.0 (s). GCMS: m/z = 219 (M+). HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C9H9F3NO2, 220.0585; found
220.0587.
2-Bromo-1,1,1-trifluoroethane (18a)
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