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J. Liu et al. / Tetrahedron Letters 47 (2006) 6753–6756
10. We also tried the Ritter reaction between 1-(40-N,N-
dimethylamino)phenyl-2,2,2-trifluoroethanol and aceto-
nitrile under the catalysis of concentrated sulfuric acid.
The reaction was messy and we obtained only 35% yield of
trifluoromethylated amide product.
calcd for C12H13F2NO: C, 63.99; H, 5.82; N, 6.22. Found
C, 63.98; H, 5.87; N, 6.01; EI (m/z, %) 226 (M++1, 0.75),
204 (30.50), 115 (58.51), 43 (100.00). Compound 3d: White
solid, mp 138 °C. 1H NMR: d 7.22 (d, J = 8.6 Hz, 2H),
6.71 (d, J = 8.6 Hz, 2H), 5.99 (t, J = 55.2 Hz, 1H), 5.99–
6.09 (m, 1H), 5.20–5.38 (m, 1H), 2.96 (s, 6H), 2.05 (s, 3H);
19F NMR: d ꢀ126.11 (ddd, J = 332.8, 58.6, 16.9 Hz, 1F),
ꢀ127.28 (ddd, J = 332.8, 55.6, 15.8 Hz, 1F); IR (KBr):
11. Typical procedures for the Ritter reaction: into a round-
bottom flask, was added difluoromethyl alcohol 2a
(188 mg, 1 mmol) and 10 mL of CH3CN, then 1 mL of
98% concentrated H2SO4 was added. The mixture was
refluxed for 3 h. After cooling to room temperature, the
reaction mixture was diluted with saturated NaCl solu-
tion, and then carefully neutralized with cold saturated
aqueous NaHCO3 solution. The solution was extracted
with Et2O three times, and the combined Et2O phase was
dried over MgSO4. After filtration, the solvent
was evaporated under vacuum, and the crude product
was further purified by silica gel column chromatography
to give product 3a (222 mg, 97% yield) as white solid. Mp
135 °C; 1H NMR: d 7.28 (d, J = 8.7 Hz, 2H), 6.91 (d,
J = 8.7 Hz, 2H), 6.11–6.14 (m, 1H), 5.99 (t, J = 55.3 Hz,
1H), 5.28–5.40 (m, 1H), 3.81 (s, 1H), 2.06 (s, 1H). 19F
NMR: d ꢀ126.24 (ddd, J = 281.8, 56.7, 16.6 Hz, 1F),
ꢀ127.28 (ddd, J = 281.8, 55.3, 13.8 Hz, 1F). IR (KBr):
3311, 1656, 1620, 1549, 1528, 1373, 1109, 1060 cmꢀ1
.
Elemental analysis: calcd for C12H16F2N2O: C, 59.49;
H,6.66; N, 11.56. Found C, 59.33; H, 6.68; N, 11.37; EI
(m/z, %) 242 (11.57), 222 (72.89), 180 (22.24), 149 (100.00).
1
Compound 3e: White solid, mp 125–127 °C. H NMR: d
7.21–7.41 (m, 2H), 6.89–7.04 (m, 2H), 6.55 (d, J = 8.6 Hz,
1H), 6.02 (td, J = 56.5, 3.7 Hz, 1H), 5.56–5.72 (m,1H),
3.89 (s, 3H), 2.07 (s, 3H); 19F NMR: d ꢀ122.57 (ddd,
J = 277.8, 55.8, 10.7 Hz, 1F), ꢀ127.38 (ddd, J = 277.8,
56.8, 16.1 Hz, 1F); IR (KBr): 3320, 1660, 1549, 1494, 1250,
1122, 1050 cmꢀ1
.
Elemental analysis: calcd for
C11H13F2NO2: C, 57.64; H, 5.72; N, 6.11. Found: C,
57.64; H, 5.78; N, 6.06; EI (m/z, %) 229 (0.32), 209 (35.84),
136 (100.00), 121 (21.43). Compound 3f: White solid, mp
119 °C. 1H NMR: d 7.42 (d, J = 8.3 Hz, 2H), 7.27 (d,
J = 8.3 Hz, 2H), 6.22–6.10 (m, 1H), 6.01 (td, J = 55.8,
2.1 Hz, 1H), 5.31–5.46 (m, 1H), 2.06 (s, 3H), 1.31 (s, 9H);
19F NMR: d ꢀ125.46 (ddd, J = 281.2, 56.3, 16.1 Hz, 1F),
ꢀ127.01 (ddd, J = 281.2, 55.1, 15.5 Hz, 1F); IR (KBr):
3265, 2964, 1659, 1556, 1394, 1082 cmꢀ1. Elemental
analysis: calcd for C14H19F2NO: C, 65.86; H, 7.50; N,
5.49. Found: C, 65.92; H, 7.63; N, 5.47; EI (m/z, %) 235
(M+ꢀHF, 69.78), 193 (100.00), 162 (85.99), 91 (27.93).
Compound 3g: White solid, 1H NMR: d 7.38 (m, 5H), 6.29
(m, 1H), 6.03 (t, J = 55.5 Hz, 1H), 5.35–5.48 (m, 1H), 2.08
(s, 3H); 19F NMR: d ꢀ125.65 (ddd, J = 282.7, 56.5,
16.4 Hz, 1F), ꢀ127.35 (ddd, J = 282.7, 55.1, 14.4 Hz, 1F);
3311, 1660, 1615, 1548, 1515, 1440, 1255, 1056 cmꢀ1
.
Elemental analysis: calcd for C11H13F2NO2: C, 57.64; H,
5.72; N, 6.11. Found: C, 57.68; H, 5.72; N, 5.96. EI (m/z,
%): 230 (M++1, 1.01), 209 (50.97), 167 (82.69), 136
(100.00).
12. Spaggiari, A.; Blaszczak, L. C.; Prati, F. Org. Lett. 2004,
6, 3885–3888.
13. The data for other compounds. Compound 3b: White
solid, mp 160–161 °C. 1H NMR: d 7.83–7.88 (m, 4H),
7.42–7.52 (m, 3H), 6.11 (t, J = 54.6 Hz, 1H), 6.17–6.34 (m,
1H), 5.51–5.65 (m, 1H), 2.10 (s, 1H); 19F NMR: d ꢀ125.08
(ddd, J = 279.5, 56.1, 15.3 Hz, 1F), ꢀ126.72 (ddd,
J = 279.5, 55.0, 15.2 Hz, 1F); IR(KBr): 3219, 3058, 1656,
1562, 1510, 1372, 1297, 1060 cmꢀ1. Elemental analysis:
calcd for C14H13F2NO: C, 67.46; H, 5.26; N, 5.62. Found:
C, 67.57; H, 4.96; N, 5.47; EI (m/z, %) 229 (MꢀHF,
73.98), 187 (82.07), 156 (73.98), 43 (100.00). Compound
3c: White solid, mp 77 °C. 1H NMR: d 7.25–7.41 (m, 5H),
6.22–6.34 (m, 1H), 6.15 (td, J = 56.1, 5.4 Hz, 1H), 5.68–
5.94 (m, 3H), 2.04 (s, 1H); 19F NMR: d ꢀ111.65 (m, 1F),
ꢀ111.85 (m, 1F); IR(KBr): 3317, 1683, 1541, 1498, 1374,
1142, 1014, 971 cmꢀ1. Elemental analysis: calcd for
C12H13F2NO: C, 63.99; H, 5.82; N, 6.22. Found: C,
63.91; H, 5.85; N, 6.07; EI (m/z, %) 225 (0.64), 205 (10.20),
183 (9.36), 132 (76.64), 43 (100.00). Compound 3c0: White
solid, 1H NMR: d 7.26–7.41 (m, 5H), 6.72 (d, J = 16.7 Hz,
1H), 6.09–6.19 (m, 1H), 5.91 (t, J = 57.5 Hz, 1H), 5.75–
5.87 (m, 1H), 4.97–5.12 (m, 1H), 2.08 (s, 1H); 19F NMR: d
ꢀ126.32 (ddd, J = 283.2, 55.9, 12.4 Hz, 1F), ꢀ129.21
(ddd, J = 283.2, 54.7, 18.3 Hz, 1F); IR (KBr): 3315, 1648,
1542, 1374, 1141, 1014, 969 cmꢀ1. Elemental analysis:
IR (KBr): 3325, 1660, 1547, 1499, 1372, 1115 cmꢀ1
.
Elemental analysis: calcd for C10H11F2NO: C, 60.30; H,
5.57; N, 7.03. Found: C, 60.25; H, 5.61; N, 6.97; EI (m/z,
%) 200 (M++1, 0.92), 179 (25.25), 106 (100.00). Com-
1
pound 3h: White solid, mp 116 °C. H NMR: d 7.22–7.52
(m, 5H), 6.38 (t, J = 56.4 Hz, 1H), 6.02 (s, 1H), 2.02 (s,
3H), 1.77 (s, 3H); 19F NMR: d ꢀ128.35 (dd, J = 277.2,
55.9 Hz, 1F), ꢀ129.79 (dd, J = 277.2, 55.9 Hz, 1F);
IR(KBr): 3281, 3080, 1654, 1553, 1498, 1372, 1208,
1108 cmꢀ1. Elemental analysis: calcd for C11H13F2NO:
C, 61.96; H, 6.15; N, 6.57. Found: C, 61.96; H, 6.33; N,
6.54; EI (m/z, %) 213 (4.62), 162 (44.74), 120 (100.00).
Compound 3i: White solid. 1H NMR: d 7.31–7.39 (m,
10H), 7.14 (t, J = 56.7 Hz, 1H), 6.46 (s, 1H), 2.01 (s, 3H);
19F NMR: d ꢀ123.32 (d, J = 56.2 Hz, 2F); IR (KBr):
3256, 3060, 1654, 1546, 1498, 1069 cmꢀ1. Elemental
analysis: calcd for C16H15F2NO: C, 69.81; H, 5.49; N,
5.09. Found: C, 69.74; H,5.53; N, 4.91; EI (m/z, %) 275
(1.32), 182 (100.00), 104 (30.06).