4
Tetrahedron
chromatography on silica gel to furnish the corresponding
DCM-MeOH (v/v = 70:1), brown solid, 676 mg, 59% yield; IR
ACCEPTED MANUSCRIPT
product (1a, 1e, 1g, 1h or 1j).
(thin film): 2986, 2776, 1585, 1562, 1477, 1362, 1331, 1192,
1129, 1057, 903, 865, 820, 784, 751 cm-1; H NMR (400 MHz,
1
4.2.1. N-hydroxy-N-methyl-2-naphthamide (1a)
CDCl3) δ 8.02 (s, 1H), 7.92 - 7.87 (m, 3H), 7.60 - 7.54 (m, 3H),
4.29 (dt, J = 12.8, 6.4 Hz, 1H), 1.34 (s, 3H), 1.32 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 167.0, 134.4, 132.7, 130.1, 128.8,
128.7, 128.0, 127.8, 127.1, 124.3, 52.8, 19.9; HRMS (ESI): m/z
calcd for C14H15NO2Na [M+Na]+ 252.0995 found 252.0996.
DCM-MeOH (v/v = 40:1), white solid, 2.29 g, 88% yield; IR
(thin film): 3165, 2923, 1607, 1496, 1430, 1388, 1273, 1250,
1196, 1170, 1125, 1067, 963, 906, 865, 822, 756, 577, 477 cm-1;
1H NMR (400 MHz, CDCl3) δ 8.87 (br s, 1H), 8.04 (s, 1H), 7.90
- 7.87 (m, 3H), 7.61 - 7.53 (m, 3H), 3.46 (s, 3H); 13C NMR (100
MHz, (CD3)2SO) δ 168.8, 133.5, 132.3, 132.0, 128.6, 128.3,
127.6, 127.3, 127.1, 126.6, 125.6, 37.4; HRMS (ESI): m/z calcd
for C12H11NO2Na [M+Na]+ 224.0682 found 224.0678.
4.3.2. O-(2-naphthoyl)-N-(tert-butyl)hydroxylamine (1c') and N-
(tert-butyl)-N-hydroxy-2-naphthamide (1c)
1c': petroleum ether-EtOAc (v/v = 20:1), colourless oil, 916
mg, 75% yield; IR (thin film): 3223, 3061, 2974, 1716, 1630,
1599, 1508, 1471, 1431, 1389, 1365, 1282, 1222, 1194, 1130,
4.2.2. N-hydroxy-N-methylbenzamide (1e)
1
Petroleum ether-EtOAc (v/v = 1:1), orange oil, 1.30 g, 67%
yield; IR (thin film): 3438, 2925, 1607, 1570, 1430, 1388, 1218,
1083, 989, 955, 914, 865, 765, 593, 474 cm-1; H NMR (400
MHz, CDCl3) δ 8.61 (s, 1H), 8.05 (d, J = 8.8 Hz, 1H), 7.97 (d, J
= 8.0 Hz, 1H), 7.91 - 7.88 (m, 2H), 7.69 (br s, 1H), 7.63 - 7.54 (m,
2H), 1.28 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 167.1, 135.7,
132.6, 131.0, 129.5, 128.6, 128.5, 127.9, 127.0, 125.8, 124.8,
56.3, 26.8; HRMS (ESI): m/z calcd for C15H17NO2Na [M+Na]+
266.1151 found 266.1153.
1182, 1071, 935, 909, 786, 708, 646, 556 cm-1; H NMR (400
1
MHz, CDCl3) δ 8.74 (s, 1H), 7.54 - 7.41 (m, 5H), 3.40 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 167.5, 132.8, 130.7, 128.3, 127.9,
38.4; HRMS (ESI): m/z calcd for C8H9NO2Na [M+Na]+
174.0525 found 174.0523.
4.2.3. N-hydroxy-4-methoxy-N-methylbenzamide (1g)
1c: petroleum ether-EtOAc (v/v = 2:1), white solid, 174 mg,
14% yield; IR (thin film): 3126, 2967, 2847, 1715, 1587, 1470,
1418, 1361, 1275, 1205, 1151, 1122, 1089, 1029, 953, 905, 863,
DCM-MeOH (v/v = 40:1), white solid, 2.06 g, 88% yield; IR
(thin film): 3155, 2928, 2845, 1605, 1568, 1464, 1433, 1384,
1
820, 755, 476 cm-1; H NMR (400 MHz, CDCl3) δ 8.22 (s, 1H),
1304, 1254, 1221, 1178, 1117, 1027, 842, 757, 596 cm-1; H
1
7.92 (s, 1H), 7.86 - 7.83 (m, 3H), 7.57 - 7.49 (m, 3H), 1.35 (s,
9H); 13C NMR (100 MHz, CDCl3) δ 169.7, 134.0, 133.7, 132.5,
128.6, 128.1, 128.0, 127.6, 127.4, 126.9, 124.7, 62.1, 29.0;
HRMS (ESI): m/z calcd for C15H17NO2Na [M+Na]+ 266.1151
found 266.1150.
NMR (400 MHz, CDCl3) δ 8.99 (s, 1H), 7.49 (d, J = 8.8 Hz, 2H),
6.88 (d, J = 8.8 Hz, 2H), 3.81 (s, 3H), 3.36 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 167.6, 161.7, 130.1, 124.5, 113.8, 55.5, 38.8;
HRMS (ESI): m/z calcd for C9H10NO3 [M]- 180.0666 found
180.0666.
4.3.3. N-hydroxy-N,4-dimethylbenzamide (1f)
4.2.4. 4-bromo-N-hydroxy-N-methylbenzamide (1h)
Petroleum ether-EtOAc (v/v = 1:1), white solid, 761 mg, 92%
yield; IR (thin film): 3099, 2876, 1598, 1560, 1495, 1464, 1433,
1390, 1219, 1180, 1119, 1073, 836, 785, 744, 684 cm-1; 1H NMR
(400 MHz, CDCl3) δ 8.81 (s, 1H), 7.42 (d, J = 8.0 Hz, 2H), 7.23
(d, J = 8.0 Hz, 2H), 3.39 (s, 3H), 2.39 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 167.7, 141.3, 129.5, 129.1, 128.1, 38.6, 21.5;
HRMS (ESI): m/z calcd for C9H11NO2Na [M+Na]+ 188.0682
found 188.0680.
DCM-MeOH (v/v = 40:1), white solid, 2.10 g, 71% yield; IR
(thin film): 3165, 2923, 1597, 1560, 1473, 1431, 1391, 1264,
1
1218, 1181, 1074, 1012, 933, 836, 744, 553 cm-1; H NMR (400
MHz, CDCl3) δ 8.74 (s, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.40 (d, J
= 8.4 Hz, 2H), 3.38 (s, 3H); 13C NMR (100 MHz, (CD3)2SO) δ
167.7, 134.0, 130.8, 130.5, 123.6, 37.2; HRMS (ESI): m/z calcd
for C8H7BrNO2 [M]- 227.9666 found 227.9667.
4.2.5. N-hydroxy-N-methyl-4-nitrobenzamide (1j)
4.3.4. 4-chloro-N-hydroxy-N-methylbenzamide (1i)
DCM-MeOH (v/v = 40:1), brown solid, 2.14 g, 84% yield; IR
(thin film): 3738, 3437, 3109, 2875, 1630, 1591, 1512, 1468,
1389, 1219, 1182, 1107, 1069, 860, 720, 677, 559 cm-1; 1H NMR
(400 MHz, (CD3)2SO) δ 10.27 (s, 1H), 8.27 - 8.25 (m, 2H), 7.82
(d, J = 8.8 Hz, 2H), 3.28 (s, 3H); 13C NMR (100 MHz, (CD3)2SO)
δ 167.0, 148.0, 141.2, 129.5, 123.1, 36.8; HRMS (ESI): m/z
calcd for C8H7N2O4 [M]- 195.0411 found 195.0409.
Petroleum ether-EtOAc (v/v = 1:1), white solid, 862 mg, 93%
yield; IR (thin film): 3150, 2925, 1600, 1562, 1514, 1475, 1431,
1390, 1309, 1262, 1218, 1179, 1092, 1016, 841, 797, 749, 684,
553, 507, 469 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.66 (br s, 1H),
7.48 (d, J = 8.4 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 3.39 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 166.2, 137.2, 130.8, 129.6, 128.9,
38.5; HRMS (ESI): m/z calcd for C8H8ClNO2Na [M+Na]+
208.0136 found 208.0134.
4.3. General procedure for preparation of compounds 1b, 1c,
1f, 1i, 1k, 1l and 1m7c
4.3.5. N-hydroxy-N-methyl-3-phenylpropanamide (1k)
To a solution of MeNHOH•HCl (459.0 mg, 5.50 mmol, 1.1
Petroleum ether-EtOAc (v/v = 1:1), brown gum, 672 mg, 75%
yield; IR (thin film): 3173, 2928, 1615, 1496, 1449, 1391, 1199,
equiv; for 1f, 1i, 1k, 1l and 1m) or iPrNHOH•HCl (614 mg, 5.50
t
mmol, 1.1 equiv; for 1b) or BuNHOH•HCl (691 mg, 5.5 mmol,
1
1112, 1075, 1030, 964, 750, 700, 558, 486 cm-1; H NMR (400
1.1 equiv; for 1c) in DCM (70 mL) was added NaHCO3 (1.05 g,
12.5 mmol, 2.5 equiv) at room temperature. Then the mixture
was cooled to 0 °C and a solution of the corresponding acyl
chloride (5.00 mmol, 1.0 equiv) in DCM (30 mL) was added.
After stirring overnight at rt, the insoluble precipitate was filtered
off and the solvent was concentrated under reduced pressure. The
residue was purified by flash column chromatography on silica
gel to provide the corresponding hydroxamic acid (1b, 1c, 1f, 1i,
1k, 1l or 1m).
MHz, (CD3)2SO) δ 9.84 (s, 1H), 7.28 - 7.15 (m, 5H), 3.09 (s, 3H),
2.80 (t, J = 8.0 Hz, 2H), 2.64 (t, J = 8.0 Hz, 2H); 13C NMR (100
MHz, (CD3)2SO) δ 172.1, 141.6, 128.3, 125.8, 35.8, 33.4, 30.1;
HRMS (ESI): m/z calcd for C10H14NO2 [M+H]+ 180.1019 found
180.1027.
4.3.6. (3r,5r,7r)-N-hydroxy-N-methyladamantane-1-carboxamide
(1l)
Petroleum ether-EtOAc (v/v = 4:1), white solid, 805 mg, 77%
yield; IR (thin film): 3179, 2906, 2853, 1590, 1451, 1414, 1383,
4.3.1. N-hydroxy-N-isopropyl-2-naphthamide (1b)