PAPER
Catechol and 8-Hydroxyquinoline Derivatives
1109
Anal. Calcd for C18H20N2O4 3/2H2O: C, 60.83; H, 6.52; N, 7.88.
Found: C, 60.79; H, 6.00; N, 7.63.
N-Dodecanoylglycine(2,3-dihydroxybenzyl)amide (5-H2)
Yield: 80%, white solid.
Mp 126 °C
N-t-Butoxycarbonylglycine(2,3-dimethoxybenzyl)amide (3c)
Compound 3c is prepared from 2c (200 mg, 1.12 mmol) as de-
scribed for the preparation of 3a. The crude product is purified by
chromatographic work up (silica gel, hexane–EtOAc, 1:1).
IR (KBr): (cm-1) = 3411, 3344, 3299, 3090, 2921, 2851, 1751,
1676, 1669, 1646, 1596, 1560, 1540, 1481, 1286, 1265, 734.
1H NMR (CDCl3): = 8.68 (br s, 1 H), 8.47 (br s, 1 H), 8.12 (m, 3
H), 6.62 (br s, 1 H), 6.56 (br s, 1 H), 4.26 (br s, 2 H), 4.00 (br s, 2
H), 2.38 (br s, 2 H), 1.56 (br s, 2 H), 1.27 (m, 16 H), 0.86 (t, J = 6.9
Hz, 3 H).
13C NMR (CDCl3): = 178.3 (C), 170.5 (C), 145.3 (C), 142.6 (C),
123.9 (C), 121.9 (CH), 120.6 (CH), 115.6 (CH), 31.9 (CH2, double
intensity), 29.6 (CH2, double intensity), 29.5 (CH2), 29.4 (CH2, dou-
ble intensity), 29.3 (CH2), 29.2 (CH2), 25.7 (CH2), 22.7 (CH2, dou-
ble intensity), 14.1 (CH3).
Yield: 1.42 g (88%), yellow oil.
IR (KBr): 3571, 3278, 3078, 2978, 2937, 2835, 1700, 1666, 1522,
1482, 1274, 1171, 1091, 1060, 1004, 788, 750 cm–1.
1H NMR (CDCl3): = 6.99 (t, J = 7.9 Hz, 1 H), 6.85 (m, 2 H), 6.57
(br s, 1 H), 5.29 (br s, 1 H), 4.46 (d, J = 5.9 Hz, 2 H), 3.85 (s, 3 H),
3.84 (s, 3 H), 3.77 (d, J = 4.7 Hz, 2 H), 1.41 (s, 9 H).
13C NMR (CDCl3): = 169.1 (C), 156.0 (C), 152.6 (C), 147.1 (C),
131.5 (C), 124.2 (CH), 121.2 (CH), 112.0 (CH), 80.1 (C), 60.7
(CH3), 55.7 (CH3), 44.3 (CH2), 38.8 (CH2), 28.3 (CH3).
FAB-MS (Pos., DMSO/3-NBA): m/z = 379 [M + H]+, 401 [M +
Na]+.
MS (EI, 70 eV): m/z = 324 [M]+, 166.
Anal. Calcd for C21H34N2O4 2/3H2O: C, 64.59; H, 9.12; N, 7.17.
Found: C, 64.14; H, 8.77; N, 6.84.
HRMS: m/z calcd for C16H24N2O5: 324.1685, found: 324.1692.
Anal. Calcd for C16H24N2O5 1/2H2O: C, 57.64; H, 7.56; N, 8.40.
Found: C, 57.29; H, 7.31; N, 8.73.
N-Benzoylglycine(2,3-dihydroxybenzyl)amide (6-H2)
Yield: 65%, beige solid.
N-(n-Octadecylaminocarbonyl)glycine(2,3-dimethoxyben-
zyl)amide (4) via Glycine(2,3-dimethoxybenzyl)amide Hydro-
chloride
The BOC-protected derivative 3c is stirred for 3 h in a sat. soln of
HCl in Et2O at r.t. The precipitated glycine(2,3-dimethoxyben-
zyl)amide hydrochloride is used without further purification.
Mp 152 °C (decomp.).
IR (KBr): 3500, 3435, 3299, 3089, 1898, 1767, 1642, 1538, 1284,
740, 709 cm–1.
1H NMR (CD3OD): = 7.88–7.86 (m, 2 H), 7.55–7.52 (m, 1 H),
7.47–7.44 (m, 2 H), 6.71–6.68 (m, 2 H), 6.64–6.61 (m, 1 H), 4.37
(s, 2 H), 4.06 (s, 2 H).
13C NMR (CD3OD): = 170.9 (C), 169.1 (C), 145.2 (C), 143.1 (C),
133.6 (C), 131.5 (CH), 128.2 (CH, double intensity), 127.1 (CH,
double intensity), 124.8 (C), 119.9 (CH), 119.2 (CH), 114.2 (CH),
42.5 (CH2), 38.6 (CH2).
Under argon glycine(2,3-dimethoxybenzyl)amide hydrochloride
(200 mg, 0.76 mmol) is dissolved in CH3CN (40 mL) and N-meth-
ylmorpholine (NMM, 84 L, 0.76 mmol) is added. After 20 min at
r.t. n-octadecylisocyanate (224 mg, 0.76 mmol) is added and the
mixture is stirred over night. The product precipitates and is isolated
by filtration.
MS (EI, 70 eV): m/z = 300 [M]+, 105.
Yield: 329 mg (83%), white solid.
Mp: 145 °C.
HRMS: m/z calcd for C16H16N2O4: 300.1110; found: 300.1117.
Anal. Calcd for C16H16N2O4 H2O: C, 60.37; H, 5.70; N, 8.80.
Found: C, 60.65; H, 5.39; N, 8.51.
IR (KBr): 3381, 3306, 3081, 2923, 2848, 2596, 2265, 1651, 1609,
1555, 1509, 1486, 1467, 1444, 1392, 1277, 1231, 1219, 1085, 1002,
779, 750 cm–1.
1H NMR (CDCl3): = 7.01 (t, J = 8.0 Hz, 1 H), 6.81 (d, J = 8.0 Hz,
2 H), 6.53 (br t, 1 H), 4.89 (br t, 1 H), 4.46 (d, J = 5.9 Hz, 2 H), 4.42
(br t, 1 H), 3.86 (d, overlaid, 2 H), 3.86 (s, 6 H), 3.15 (q, J = 6.5 Hz,
2 H), 1.47 (m, 2 H), 1.25 (m, 30 H), 0.87 (t, J = 7.0 Hz, 3 H).
13C NMR (CDCl3): = 169.8 (C), 157.9 (C), 152.6 (C), 147.2 (C),
131.4 (C), 124.2 (CH), 121.3 (CH), 112.0 (CH), 60.7 (CH3), 55.8
(CH3), 44.3 (CH2), 40.8 (CH2), 38.9 (CH2), 31.9 (CH2), 30.1 (CH2),
29.7 (CH2, six fold intensity), 29.7 (CH2, double intensity), 29.6
(CH2), 29.6 (CH2), 29.4 (CH2), 29.3 (CH2), 26.9 (CH2), 22.7 (CH2),
14.1 (CH3).
N-(n-Octadecylaminocarbonyl)glycine(2,3-dihydroxyben-
zyl)amide (7-H2)
Yield: 79%, white solid.
Mp 135 °C.
IR (KBr): 3409, 3326, 2849, 1649, 1619, 1578, 1544, 1481, 1464,
1376, 1342, 1292 cm–1.
1H NMR (DMSO-d6): = 8.19 (br s, 1 H), 6.64 (t, J = 4.5 Hz, 1 H),
6.54 (m, 2 H), 6.10 (br s, 1 H), 6.02 (br s, 1 H), 4.17 (s, 2 H), 3.64
(d, J = 5.2 Hz, 2 H), 2.94 (m, 2 H), 1.32 (m, 2 H), 1.21 (m, 30 H),
0.83 (t, J = 6.5 Hz, 3 H).
13C NMR (DMSO-d6): = 171.2 (C), 158.4 (C), 145.6 (C), 143.4
(C), 126.3 (C), 119.5 (CH), 119.1 (CH), 114.7 (CH), 43.3 (CH2),
38.1 (CH2), 31.7 (CH2, double intensity), 30.4 (CH2), 29.5 (CH2, six
fold intensity), 29.3 (CH2), 29.2 (CH2, double intensity), 28.8
(CH2), 26.9 (CH2), 22.5 (CH2, double intensity), 19.2 (CH2), 14.4
(CH3).
FAB-MS (Pos., DMSO/3-NBA): m/z = 520 [M + H]+.
HRMS: m/z calcd for C30H54N3O4: 520.4114; found: 520.4120.
Anal. Calcd for C30H53N3O4: C, 69.32; H, 10.28; N, 8.08. Found: C,
69.13; H, 10.00; N, 8.17.
FAB-MS (Pos., DMSO/3-NBA): m/z = 492 [M + H]+, 514 [M +
Cleavage of Methyl Aryl Ethers; General Procedure
Na]+.
The dimethoxybenzene derivative (approx. 1 mmol) is dissolved in
CH2Cl2 anhyd (15 mL) under argon and BBr3 (2.5 equiv) is added.
After 3 h the mixture is cooled in an ice bath and CH3OH (10 mL)
is added. The solvent is removed and the crude product is dissolved
in CH3OH which is removed again. Water is added to the residue
and the mixture is treated with ultrasound. The product precipitates,
is collected by filtration and dried in vacuum.
HRMS: m/z calcd for C28H50N3O4: 492.3801; found: 492.3790.
Anal. Calcd for C28H49N3O4 0.25H2O: C, 67.77; H, 10.05; N, 8.47.
Found: C, 67.40; H, 9.54; N, 8.66.
Synthesis 2003, No. 7, 1105–1111 ISSN 0039-7881 © Thieme Stuttgart · New York