G
L. Politanskaya, E. Tretyakov
Paper
Synthesis
IR (neat): 3489, 3388, 2958, 2899, 2150, 1626, 1603, 1564, 1502,
1431, 1308, 1252, 1228, 1190, 877, 841, 760, 698, 633 cm–1
HRMS (EI): m/z [M]+ calcd for C8H7F2NO: 171.0490; found: 171.0486.
.
1H NMR (300 MHz, acetone-d6): δ = 7.32 [d, J (H3,F5) = 7.8 Hz, 1 H, H3],
6.51 [d, J (H6,F5) = 11.5 Hz, 1 H, H6], 5.54 (s, 2 H, NH2), 0.24 (s, 9 H,
CH3), 0.21 (s, 9 H, CH3).
1-(2-Amino-3,5-difluorophenyl)ethanone (4b)
Yellowish solid; yield: 78 mg (91%); Rf = 0.56 (EtOAc/hexane, 1:5);
mp 92.3 °C (dec.).
13C NMR (126 MHz, acetone-d6): δ = 164.3 [d, 1J (C5,F5) = 251.1 Hz, C5],
152.3 [d, 3J (C1,F5) = 12.4 Hz, C1], 138.0 [d, 3J (C3,F5) = 3.8 Hz, C3], 104.0
(d, C2), 100.6 (s, C≡C), 100.6 [d, 2J (C6,F5) = 25.3 Hz, C6], 100.0 [d,
2J (C4,F5) = 17.7 Hz, C4], 99.7 (d, C≡C), 99.1 (s, C≡C), 96.7 (d, C≡C), 0.1 (s,
CH3).
19F NMR (282 MHz, acetone-d6): δ = –106.4 [dd, J (F5,H6) = 11.6 Hz,
J (F5,H3) = 7.8 Hz, 1 F, F5].
IR (KBr): 3439, 3333, 3063, 2928, 2857, 1653, 1599, 1560, 1464, 1431,
1362, 1273, 1205, 1119, 989, 966, 856, 800, 634, 594, 575, 552 cm–1
.
1H NMR (300 MHz, acetone-d6): δ = 7.45 [dm, J (H6,F5) = 9.8 Hz,
J (H6,H4) = 2.8 Hz, J (H6,F3) = 1.8 Hz, 1 H, H6], 7.20 [m, J (H4,F3) = 11.3
Hz, J (H4,F5) = 8.4 Hz, J (H4,H6) = 2.8 Hz, 1 H, H4], 6.72 (s, 2 H, NH2), 2.59
(s, 3 H, CH3).
13C NMR (126 MHz, acetone-d6): δ = 200.6 (s, C=O), 152.5 [dm,
1J (C5,F5) = 234 Hz, C5], 152.3 [dm, 1J (C3,F3) = 243 Hz, C3], 138.1 [d,
2J (C2,F3) = 12.8 Hz, C2], 119.6 [t, 3J (C1,F5) ≈ 3J (C1,F3) = 6.8 Hz, C1], 113.4
HRMS (EI): m/z [M]+ calcd for C16H22FNSi2: 303.1269; found:
303.1267.
2
2
2
[dd, J (C6,F5) = 21.9 Hz, C6], 109.4 [dd, J (C4,F5) = 27.9 Hz, J (C4,F3) =
22.7 Hz, C4], 28.7 (s, CH3).
3,6-Difluoro-2,4-bis[(trimethylsilyl)ethynyl]aniline (3k)
Brown oil; yield: 1.41 g (88%); Rf = 0.75 (EtOAc/hexane, 1:7).
IR (neat): 3502, 3396, 3302, 2960, 2901, 2158, 1633, 1595, 1491,
19F NMR (282 MHz, acetone-d6): δ = –127.7 [dd, J (F5,H6) = 9.8 Hz,
J (F5,H4) = 8.4 Hz, 1 F, F5], –131.3 [dd, J (F3,H4) = 11.3 Hz, J (F3,H6) = 1.8
Hz, 1 F, F3].
1444, 1298, 1250, 1142, 1003, 914, 847, 760, 700, 644 cm–1
.
HRMS (EI): m/z [M]+ calcd for C8H7F2NO: 171.0490; found: 171.0487.
1H NMR (300 MHz, acetone-d6): δ = 7.03 [dd, J (H5,F6) = 11.2 Hz,
J (H5,F3) = 6.2 Hz, 1 H, H5], 5.45 (s, 2 H, NH2), 0.29 (s, 9 H, CH3), 0.24 (s,
9 H, CH3).
1-(2-Amino-3,5,6-trifluorophenyl)ethanone (4c)
13C NMR (100 MHz, acetone-d6): δ = 160.8 [d, 1J (C3,F3) = 250.2 Hz, C3],
Yellowish solid; yield: 88 mg (93%); Rf = 0.67 (EtOAc/hexane, 1:10);
mp 79.6–81.0 °C.
1
2
146.3 [d, J (C6,F6) = 236.3 Hz, C6], 140.7 [dm, J (C1,F6) = 15.7 Hz, C1],
2
2
118.8 [d, J (C5,F6) = 21.3 Hz, C5], 106.9 (s, C≡C), 98.5 [dm, J (C4,F3) =
21.1 Hz, C4], 98.0 [d, 2J(C2,F3) = 14.3 Hz, C2], 93.9 (s, C≡C), 89.0 (s, C≡C),
86.1 (s, C≡C), 0.0 (s, CH3), –0.1 (s, CH3).
IR (KBr): 3433, 3323, 3080, 3009, 2928, 1649, 1599, 1564, 1471, 1390,
1369, 1327, 1271, 1171, 1113, 982, 930, 864, 723, 613, 523, 501 cm–1
.
1H NMR (300 MHz, acetone-d6): δ = 7.38 [m, J (H4,F3) = 11.0, J (H4,F5) =
10.2 Hz, J (H4,F6) = 7.5 Hz, 1 H, H4], 6.71 (s, 2 H, NH2), 2.58 (d, J = 8 Hz,
3 H, CH3).
13C NMR (100 MHz, acetone-d6): δ = 198.1 (m, C=O), 148.5 [dm,
1J (C6,F6) = 247.0 Hz, 2J (C6,F5) = 13.3 Hz, C6], 146.7 [dm, 1J (C3,F3) =
238.9 Hz, 3J (C3,F5) = 9.8 Hz, C3], 139.7 [dm, 1J (C5,F5) = 235.2 Hz,
2J (C5,F6) = 16.4 Hz, C5], 137.7 [dm, 2J (C2,F3) = 15 Hz, C2], 110.3 2 [dm,
2J (C1,F6) = 15 Hz, C1], 109.4 [tm, 2J (C4,F3) ≈ 2J (C4,F5) = 25 Hz, C4], 33.1
(d, J = 11.3 Hz, CH3).
19F NMR (282 MHz, acetone-d6): δ = –136.5 [m, J (F3,F6) = 14.6 Hz,
J (F3,H4) = 11.0 Hz, J (F3,F5) = 3.5 Hz, 1 F, F3], –138.6 [m, J (F6,F5) = 23 Hz,
J (F6,F3) = 15 Hz, J (F6,H4) = 7.5 Hz, 1 F, F6], –154.3 [ddd, J (F5,F6) = 23.0
Hz, J (F5,H4) = 10.2 Hz, J (F5,F3) = 3.5 Hz, 1 F, F5].
19F NMR (282 MHz, acetone-d6): δ = –109.5 [dd, J (F3,F6) = 14.3 Hz,
J (F3,H5) = 6.2 Hz, 1 F, F3], –137.7 [dd, J (F6,F3) = 14.3 Hz, J (F6,H5) = 11.2
Hz, 1 F, F3].
HRMS (EI): m/z [M]+ calcd for C16H21F2NSi2: 321.1175; found:
321.1171.
Methyl Aryl Ketones 4; General Procedure
To a solution of trimethylsilylarylacetylene 3 (0.50 mmol) in EtOH (10
mL) (BuOH for 3f) was added p-TSA monohydrate (95 mg, 0.50
mmol), and the mixture was heated under reflux for 10 h with stir-
ring. The mixture was allowed to cool to r.t., placed directly onto a
chromatography plate (silica gel) and air-dried. The methyl aryl ke-
tone 4 was isolated by TLC using EtOAc/hexane as an eluent.
HRMS (EI): m/z [M]+ calcd for C8H6F3NO: 189.0396; found: 189.0393.
Anal. Calcd for C8H6F3NO: C, 50.80; H, 3.20. Found: C, 50.76; H, 3.18.
1-(2-Amino-4,5-difluorophenyl)ethanone (4a)
Yellowish solid; yield: 80 mg (93%); Rf = 0.50 (EtOAc/hexane, 1:5);
mp 74.2–75.3 °C.
1-(2-Amino-3,4,5-trifluorophenyl)ethanone (4d)
Yellowish solid; yield: 92 mg (97%); Rf = 0.61 (EtOAc/hexane, 1:5);
mp 133.8–134.1 °C.
IR (KBr): 3522, 3417, 3361, 3298, 3180, 3062, 2928, 1647, 1589, 1558,
1516, 1439, 1381, 1362, 1269, 1244, 1196, 1159, 1041, 949, 893, 872,
IR (KBr): 3429, 3319, 2926, 2854, 1657, 1591, 1568, 1522, 1462, 1427,
839, 644, 598, 538, 467 cm–1
.
1387, 1362, 1284, 1209, 1016, 953, 864, 850, 681, 596, 517, 467 cm–1
.
1H NMR (300 MHz, acetone-d6): δ = 7.70 [dd, J (H6,F5) = 12.0 Hz,
J (H6,F4) = 9.0 Hz, 1 H, H6], 7.08 (s, 2 H, NH2), 6.67 [dd, J (H3,F4) = 13.0
Hz, J (H3,F5) = 7.0 Hz, 1 H, H3], 2.51 (s, 3 H, CH3).
13C NMR (126 MHz, acetone-d6): δ = 199.7 (s, C=O), 155.6 [dd, 1J (C4,F4)
= 251.6 Hz, 2J (C4,F5) = 14.4 Hz, C4], 150.8 [d, 3J (C2,F4) = 11.2 Hz, C2],
141.8 [dd, 1J (C5,F5) = 234.0 Hz, 2J (C5,F4) = 13.8 Hz, C5], 120.9 [dd,
2J (C6,F5) = 17.5 Hz, 3J (C6,F4) = 3.1 Hz, C6], 114.4 (m, C1), 105.1 [d,
2J (C3,F4) = 20.0 Hz, C3], 28.5 (s, CH3).
1H NMR (500 MHz, acetone-d6): δ = 7.64 [m, J (H6,F5) = 11.7 Hz,
J (H6,F4) = 8.3 Hz, J (H6,F3) = 2.3 Hz, 1 H, H6], 6.93 (s, 2 H, NH2), 2.55 (s,
3 H, CH3).
13C NMR (126 MHz, acetone-d6): δ = 199.6 (s, C=O), 143.8 [dm,
1J (C4,F4) = 253.5 Hz, 2J (C4,F3) = 17.0 Hz, 2J (C4,F5) = 13.0 Hz, C4], 141.2
[dm, 1J (C5,F5) = 235 Hz, 2J (C5,F4) = 10.6 Hz, C5], 140.5 [dm, 1J (C3,F3) =
242.5 Hz, 2J (C3,F4) = 11.4 Hz, C3], 139.3 [dm, 2J (C2,F3) = 10.5 Hz, C2],
114.5 [dm, 2J (C6,F5) = 13 Hz, C6], 113.8 (m, C1), 28.1 (s, CH3).
19F NMR (282 MHz, CDCl3): δ = –127.8 [ddd, J (F4,F5) = 22 Hz, J (F4,H3) =
11.3 Hz, J (F4,H6) = 9.0 Hz, 1 F, F4], –152.3 [ddd, J (F5,F4) = 22.3 Hz,
J (F5,H6) = 10.5 Hz, J (F5,H3) = 6.3 Hz, 1 F, F5].
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J