JOURNAL OF CHEMICAL RESEARCH 2013 759
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1320, 1295, 1260, 1172, 1000, 858, 761, 694 cm–1; H NMR δ 7.20 (m,
of the water and dried at 150°C. The recovered Fe(OTf)3 was
reused directly for at least three consecutive cycles and the
results are listed in Table 3.
2H), 7.16 (m, 2H), 4.88 (s, 1H), 4.30 (m, 2H), 2.36 (s, 3H), 1.50 (s, 9H); 13C
NMR δ 21.1, 28.3, 44.5, 79.4, 127.5, 129.3, 135.8, 136.9, 155.8.
t‑Butyl cyclohexylcarbamate (8): White solid, m.p. 63–65 °C (MeOH)
(lit.6 65–67 °C); IR:3364, 2973, 2934, 2854, 1681, 1520 1448, 1366, 1315,
1251, 1233, 1168 cm–1; 1H NMR δ 4.42 (s, 1H), 3.44 (s, 1H), 1.90–1.93 (m,
2H), 1.57–1.71(m, 3H), 1.44 (s, 9H), 1.26–1.34 (m, 2H), 1.04–1.15 (m,
3H); 13C NMR δ 22.0, 27.2, 28.3, 32.7, 48.2, 80.1, 155.7.
t‑Butyl diethylcarbamate (9): Colourless oil, (lit.26 colourless oil); IR:
2900, 2860, 1678, 1520, 1448, 1362, 1317, 1272 1160, 1020, 900 cm–1; 1H
NMR δ 3.24 (m, 4H), 1.48 (s, 9H), 1.12 (m, 6H); 13C NMR δ 13.8, 28.4,
41.3, 78.9, 155.3.
In summary, we have described a simple, efficient and
environmentally benign method for chemoselective N-Boc
protection for amines using a novel Lewis acid and an easily
recoverable catalyst Fe(OTf)3 under solvent-free conditions. Our
protocol gave the products in high yields in a reduced reaction
time and reduced amount of catalyst. Further investigations on
the application of this catalyst are underway in our laboratory.
Experimental
t‑Butyl tert‑butylcarbamate (10) Yellow oil, (lit.10 yellow oil); IR: 3420,
2950, 1799, 1762, 1680, 1451, 1367, 1207, 1113, 1066 cm–1; 1H NMR δ 3.48
(s, 1H), 2.17 (s, 9H), 1.56 (s, 9H); 13C NMR δ 27.3, 30.0, 49.9, 85.1, 147.1.
t‑Butyl 1‑hydroxy‑2‑methylpropan‑2‑ylcarbamate (11) White solid,
m.p. 48–50 °C (MeOH) (lit.26 50–52 °C); IR: 3490, 3300, 2994, 2930,
All reagents were purchased from commercial sources and used
without further purification. Melting points were determined
on a RY-1 hot stage microscope and are uncorrected. IR spectra
were determined as KBr pellets on
a Thermo Nicolet 6700
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1696, 1680, 1540, 1520, 1362, 1300, 1250, 1170, 1080, 1040 cm–1; H
spectrophotometer. NMR spectra were obtained on a Bruker Avance
DPX-300 MHz spectrometer (1H NMR at 300 MHz, 13C NMR at
75 MHz) in CDCl3, chemical shifts (δ) were given in part per million
(ppm) relative to TMS as an internal standard. The HRMS spectra
were obtained on a Thermo Finnigan spectrometer, model MAT 95XP.
All reactions were monitored by TLC on silica gel GF-254 glass plates
(E.Merck) and viewed under UV light at 254 nm.
NMR δ 6.12 (s, 1H), 4.68 (s, 1H), 3.24 (s, 2H), 1.32(s, 9H), 1.02 (s, 6H). 13C
NMR δ 24.0, 29.1, 54.4, 67.8, 76.6, 152.7.
t‑Butyl phenylcarbamate (12): Yellow oil, (lit.6 yellow oil); IR: 3308,
1686, 1526, 1438, 1366, 1313, 1240, 1148, 1053, 908, 824, 745, 691 cm–1;
1H NMR δ 7.25–7.37(m, 4H), 7.01(m, 1H), 6.55(s, 1H), 1.51(s, 9H); 13
NMR δ 28.3, 118.5, 123.0, 128.9, 138.3, 152.8.
C
t‑Butyl p‑tolylcarbamate (13): White solid, m.p. 84–86°C (MeOH)
(lit.6 86–87°C); IR: 3333, 1696, 1596, 1523, 1365, 1314, 1233, 1153, 1049,
815, 771, 668 cm–1; 1H NMR δ 7.07–7.25(m, 4H), 6.43(s, 1H), 2.29(s, 3H),
1.51(s, 9H); 13C NMR δ 20.7, 28.3, 118.7, 129.4, 132.5, 135.7, 152.9.
t‑Butyl 4‑methoxyphenylcarbamate (14): White solid, m.p. 92–93 °C
(MeOH) (lit.6 94–95 °C); IR: 3364, 2987, 1692, 1519, 1368, 1234, 1157,
Synthesis of Fe(OTf)3
Triflic acid (4.52 g, 30 mmol) was gradually added to cool water, and
then Fe2O3 powder (2.4 g, 15 mmol) was added. The mixture was heated
at 95°C until the pH of the water became neutral. After completion, the
reaction mixture was filtered and the filtrate was evaporated and the
pale white powder obtained was dried.
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1025, 823, 771, 724, 624 cm–1; H NMR δ 7.27(m, 2H), 6.83(m, 2H),
6.45(s, 1H), 3.77(s, 3H), 1.50(s, 9H); 13C NMR δ 28.3, 55.5, 80.3, 114.3,
120.8, 131.4, 153.3, 155.8.
t‑Butyl 4‑nitrophenylcarbamate (15): White solid, m.p. 110–112 °C
(MeOH) (lit.6 112–113 °C). IR: 3372, 2988, 2965, 1720, 1586, 1521, 1496,
1462, 1365, 1305, 1281, 1106, 840, 763, 721, 621 cm–1; 1H NMR δ 8.02(m,
2H), 6.64(m, 2H), 4.28(s, 1H), 1.54(s, 9H); 13C NMR δ 29.1, 51.6, 113.0,
125.3, 126.3, 137.7, 152.8.
t‑Butyl 4‑chlorophenylcarbamate (16): White solid, m.p. 101–102°C
(MeOH) (lit.15 102–104°C); IR: 3352, 2982, 1804, 1728, 1596, 1525,
1368, 1156, 1067, 844, 773, 682 cm–1; 1H NMR δ: 7.31(m, 2H), 7.22(m,
2H), 6.73(s, 1H), 1.50(s, 9H); 13C NMR δ: 28.3, 80.8, 119.8, 127.9, 128.9,
137.1, 152.8.
N‑Boc protection of amines; typical procedure
Fe(OTf)3 (1 mol%) was added to a magnetically stirred mixture of an
amine (1 mmol) and Boc2O (1 mmol) at room temperature. The mixture
was stirred until completion of the reaction (TLC), then diluted with
EtOAc and washed with water. The organic layer was dried over
anhydrous MgSO4, then the solvent was distillated off under vacuum to
yield the highly pure N-Boc derivatives.
Most of the products are known, except for entries 22 and 23 in Table 2.
All compounds were characterised by IR, 1H NMR, 13C NMR, the new
ones also by HRMS.
t‑Butyl piperidine‑1‑carboxylate (1): Colourless oil, (lit.6 colourless
oil); IR: 2990, 2840, 1678, 1520, 1450, 1360, 1272, 1238, 1170, 1050,
898 cm–1; 1H NMR δ 3.26–3.32 (m, 4H), 1.42 (s, 9H), 1.36–1.56 (m, 6H);
13C NMR δ 24.3, 25.5, 28.2, 46.6, 76.7, 157.4.
t‑Butyl 4‑methylpiperidine‑1‑carboxylate (2): Colourless oil, (lit.6
colourless oil); IR: 2990, 2984, 1680, 1451, 1407, 1358, 1266, 1245, 1164,
1119, 1079, 857 cm–1; 1H NMR δ 3.38 (m, 4H), 2.32 (m, 4H), 2.18 (s, 3H),
1.43 (s, 9H); 13C NMR δ 28.3, 43.4, 45.9, 54.7, 79.5, 154.6.
t‑Butyl 2‑hydroxyethylcarbamate (3): Colourless oil, (lit.6 colourless
oil); IR: 3357, 2976, 2933, 1690, 1525, 1366, 1279, 1251, 1171, 1068,
864 cm–1; 1H NMR δ 5.16 (s, 1H), 3.64 (m, 2H), 3.25 (m, 2H), 1.44 (s, 9H);
13C NMR δ 27.9, 42.8, 62.0, 79.5, 156.4.
t‑Butyl 1H‑imidazole‑1‑carboxylate (4): White solid, m.p. 45–46 °C
(MeOH) (lit.8 42–45°C); IR: 3125, 2975, 1747, 1464, 1379, 1315, 1291,
1241, 1150, 1089, 995, 833, 765, 644 cm–1; 1H NMR δ 8.02(s, 1H), 7.32 (s,
1H), 7.02 (s, 1H), 1.64 (s, 9H); 13C NMR δ 27.7, 84.9, 117.2, 129.8, 136.4,
147.5.
t‑Butyl benzylcarbamate (5): Colourless oil, (lit.6 colourless oil); IR:
3338, 2978, 2925, 1691, 1440, 1230, 1158, 876 cm–1; 1H NMR δ 1.50 (s,
9H), 4.24 (d, J=5.84 Hz, 2H), 4.85 (br s, 1H), 7.17–7.26 (m, 5H); 13C
NMR δ 28.3, 44.6, 127.2, 127.3, 128.5, 138.9, 155.8.
t‑Butyl morpholine‑4‑carboxylate (6): Yellow oil, (lit.10 yellow oil); IR:
2995, 1683, 1448, 1413, 1360, 1277, 1246, 1166, 1123, 1083, 860 cm–1; 1H
NMR δ 3.52 (m, 4H), 3.36 (m, 4H), 1.51 (s, 9H); 13C NMR δ 28.2, 43.7,
67.2, 79.5, 154.7.
t‑Butyl 4‑bromophenylcarbamate (17): White solid, m.p. 100–102°C
(MeOH) (lit.15 100–103 °C); IR: 33370, 2983, 1695, 1588, 1513, 1392,
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1233, 1154, 814, 767, 634 cm–1; H NMR δ: 7.39(m, 2H), 7.27(m, 2H),
6.51(s, 1H), 1.51(s, 9H); 13C NMR δ: 28.1, 79.4, 120.6, 129.3, 130.8, 139.5,
153.8.
t‑Butyl 2‑hydroxyphenylcarbamate (18): Brown solid, m.p. 140–141°C
(MeOH) (lit.15 140–143 °C); IR: 3423, 3286, 3300, 2982, 2926, 1689,
1622, 1612, 1523, 1455, 1444, 1325, 1151, 1054, 749 cm–1; 1H NMR δ 8.16
(s, 1H), 7.05–7.12 (m, 2H), 7.02 (m, 1H), 6.87 (m, 1H), 6.70 (s, 1H), 1.56 (s,
9H); 13C NMR δ 28.7, 81.4, 117.8, 121.2, 121.7, 125.8, 126.1, 147.7, 154.4.
t‑Butyl 3‑chlorophenylcarbamate (19): Brown solid, m.p. 63–64°C
(MeOH)(lit.27 m.p. 66–68°C); IR: 3368, 3306, 2987, 2938, 1695, 1592,
1519, 1400, 1268, 1237, 1178 cm–1; 1H NMR δ 7.47 (s, 1H), 7.11–7.19 (m,
2H), 7.01 (m, 1H), 6.53 (s, 1H), 1.52 (s, 9H); 13C NMR δ 28.2, 85.1, 116.4,
122.7, 128.7, 134.5, 138.8, 146.7, 152.6.
t‑Butyl 3‑methoxyphenylcarbamate (20): Brown solid, m.p. 49–52 °C
(MeOH) (lit.14 52–54 °C); IR: 3320, 2990, 2920, 1690, 1600, 1530, 1450,
1420, 1362, 1285, 1240, 1160, 1045, 1032, 960, 870, 842 cm–1; 1H NMR
δ 7.21 (m, 1H), 7.12 (s, 1H), 6.86 (m, 1H), 6.67 (s, 1H), 6.61 (m, 1H), 3.86
(s, 3H), 1.53 (s, 9H); 13C NMR δ 28.3, 55.3, 80.7, 104.1, 108.9, 110.7, 130.0,
139.8, 152.7, 160.3.
t‑Butyl 4‑hydroxyphenylcarbamate (21): White solid, m.p. 144–145°C
(MeOH) (lit.15 146 °C); IR: 3360, 2982, 1697, 1519, 1437, 1369, 1228,
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1056, 904, 830, 627 cm–1; H NMR δ 7.17(m, 2H), 6.76(m, 2H), 6.51(s,
t‑Butyl‑4‑methylbenzylcarbamate (7): White solid, m.p. 69–71°C
(MeOH) (lit.27 72–73°C); IR: 3395, 2980, 2920, 1680, 1600, 1508, 1360,
1H), 4.95(s, 1H), 1.55(s, 9H); 13C NMR δ 28.4, 84.2, 116.5, 122.3, 136.5,
147.1, 154.2.
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