Inorganic Chemistry
Article
compound. All chemical shifts are reported relative to residual solvent
CDCl3): δ 3.89 (s, 2H; CH2), 3.91 (s, 2H; CH2), 3.99 (s, 2H; CH2),
6.80−6.97 (m, 3H; ArH), 7.07−7.22 (m, 3H; ArH), 7.35 (t, J = 6.5,
1H; ArH), 7.79 (dt, J = 1.6, 7.7, 1H; ArH), 8.06 (d, J = 2.8, 1H; ArH),
8.12 (dd, J = 2.8, 8.9, 1H; ArH), 8.68 (d, J = 4.9, 1H; ArH) 9.97 (brs,
2H; OH). 13C NMR (125 MHz, CDCl3): δ 56.0 (d), 56.3 (d), 56.8
(d), 117.0 (s), 117.6 (s), 119.5 (s), 120.8 (q), 122.0 (q), 123.0 (s),
123.4 (s), 126.0 (s), 126.6 (s), 129.8 (s), 130.3 (s), 138.2 (s), 140.0
(q), 148.0 (s), 155.5 (q), 157.0 (q), 163.9 (q). IR: ν (cm−1) 1585,
1478, 1453, 1436, 1330, 1271, 1151, 1088, 750. LRMS for
C20H19N3O4(MH+): 366.72. Anal. Calcd for C20H19N3O4 (379.41):
C, 65.74; H, 5.24; N, 11.50. Found: C, 65.79; H, 5.20; N, 11.49. MP =
102−104 °C.
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(1H, 13C). Be NMR spectra were recorded at a concentration of 28
mmol L−1 and a temperature of 298 K on a Bruker Avance 300 at
2+
42.17 MHz and referenced to an internal standard of Be(H2O)4 (as
the sulfate salt). All NMR samples containing beryllium were
contained within Teflon sleeves in addition to the standard NMR
glass tube. Microanalyses were performed at the Campbell Micro-
analytical Laboratory at the University of Otago. Electrospray mass
spectra were recorded on a Micromass ZMD spectrometer run in
positive-ion mode. High-resolution mass spectra were recorded on a
microTOF-Q mass spectrometer at the University of Auckland
operating at a nominal voltage of 3500 V. IR spectra were recorded
on a Bruker Alpha-P diamond anvil system. UV−vis spectra were
recorded on a Shimadzu UV-3101PC spectrophotometer using UV
Probe v1.1. Fluorescence measurements were made on a Perkin-Elmer
LS50B luminescence spectrometer using FL Winlab v4.00.02.
Reactions were followed by TLC on aluminum-backed silica gel 60
F254 sheets from E-Merck, visualized by UV light. Flash column
chromatography was performed using Scharlau silica gel 60, 0.04−0.06
mm, 230−400 mesh. The length of silica was typically 20 cm, and the
diameter was varied according to reaction scale. The silica gel slurry
was compacted with the specified solvent system of hexanes/EtOAc or
CH2Cl2/MeOH. The compound was then loaded onto the column
and eluted with the specified solvent under positive pressure.
Synthesis. General Procedure for Secondary Amines 1a−f. The
appropriate starting primary amine (4.10 mmol) and 2-hydroxyben-
zaldehyde (4.10 mmol) in MeOH (10 mL) were stirred for 30 min at
RT. NaBH4 (6.48 mmol) and NaOH (0.82 mmol) in H2O (2 mL)
were added to the reaction mixture, and the resulting solution was
stirred for 1 h. The reaction was diluted with CH2Cl2 (200 mL) and
washed with water (200 mL). The organic layer was filtered and dried
over MgSO4, and the solvent was removed. The secondary amine was
purified by silica gel column chromatography using 95:5 CH2Cl2/
MeOH. Characterization data for all new compounds are presented
below.
2-(((2-Hydroxybenzyl)(pyridin-2-ylethyl)amino)methyl)-4-nitro-
1
phenol (2b). Rf = 0.29 (95:5 CH2Cl2/MeOH). H NMR (500 MHz,
CDCl3): δ 2.94 (t, J = 6.7, 2H; CH2), 3.14 (t, J = 6.7, 2H; CH2), 3.49
(brs, 2H; OH), 3.85 (s, 4H; CH2), 6.69−6.82 (m, 3H; ArH), 7.05−
7.24 (m, 4H; ArH), 7.64 (dt, J = 1.7, 7.8, 1H; ArH), 7.94 (d, J = 2.2,
1H; ArH), 8.00 (dd, J = 2.8, 8.9, 1H; ArH), 8.54 (d, J = 5.0, 1H; ArH).
13C NMR (125 MHz, CDCl3): δ 33.9 (d), 53.7 (d), 55.2 (d), 55.7 (d),
116.5 (s), 116.6 (s), 119.7 (s), 121.6 (q), 122.1 (s), 122.4 (s), 123.7
(s), 125.5 (s), 126.2 (q), 129.6 (s), 130.9 (s), 137.6 (s), 139.7 (q),
148.8 (s), 156.1 (q), 158.6 (q), 163.9 (q). IR: ν (cm−1) 1589, 1478,
1456, 1438, 1332, 1272, 1150, 1086, 751. LRMS for C21H21N3O4
(MH+): 380.84. Anal. Calcd for C21H21N3O4·0.35H2O (385.72): C,
65.39; H, 5.67; N, 10.89. Found: C, 65.40; H, 5.48; N, 10.84. MP =
108−110 °C.
2-(((2-Hydroxybenzyl)(quinolin-8-yl)amino)methyl)-4-nitrophe-
nol (2c). Rf = 0.82 (95:5 CH2Cl2/MeOH). 1H NMR (500 MHz,
CDCl3): δ 4.48 (s, 4H; CH2), 6.80−6.85 (m, 2H; ArH), 6.90 (d, J =
9.1, 1H; ArH), 7.12−7.22 (m, 2H; ArH), 7.47 (d, J = 5.0, 2H; ArH),
7.59 (q, J = 4.1, 2H; ArH), 8.05 (dd, J = 3.2, 8.6, 1H; ArH), 8.17 (d, J
= 2.7, 1H; ArH), 8.31 (dd, J = 1.4, 8.6, 1H; ArH), 9.01 (dd, J = 1.4, 4.6,
1H; ArH), 10.46 (brs, 1H; OH), 12.59 (brs, 1H; OH). 13C NMR (125
MHz, CDCl3) δ 56.6 (d), 56.7 (d), 117.1 (s), 117.7 (s), 119.5 (s),
120.9 (q), 121.4 (s), 121.8 (s), 122.2 (q), 124.4 (s), 125.9 (s), 126.8
(s), 127.0 (s), 129.7 (s), 130.1 (q), 130.6 (s), 138.9 (s), 140.0 (q),
141.8 (q), 143.6 (q), 148.3 (s), 156.9 (q), 163.7 (q). IR: ν (cm−1)
1580, 1514, 1486, 1390, 1340, 1281, 1262, 1250, 1233, 1088, 792, 759.
LRMS for C23H19N3O4 (MH+): 402.82. Anal. Calcd for C23H19N3O4
(401.41): C, 68.82; H, 4.77; N, 10.47. Found: C, 69.03; H, 4.69; N,
10.50. MP = 184−185 °C.
2-((2-Phenylquinolin-8-ylamino)methyl)phenol (1d). Rf = 0.80
1
(95:5 CH2Cl2/MeOH). H NMR (500 MHz, CDCl3): δ 4.66 (d, J =
3.8, 2H; CH2), 6.67 (brs, 1H; NH), 6.90−6.98 (m, 3H; ArH), 7.21−
7.26 (m, 2H; ArH), 7.34 (t, J = 7.8, 1H; ArH), 7.42−7.52 (m, 3H;
ArH), 7.88 (d, J = 8.5, 1H; ArH), 7.11−7.16 (m, 3H; ArH), 8.31 (brs,
1H; OH). 13C NMR (125 MHz, CDCl3): δ 48.2 (d), 109.7 (s), 116.6
(s), 117.4 (s), 119.3 (s), 120.1 (s), 123.4 (q), 127.1 (s), 127.2 (q),
127.4 (s), 128.5 (s), 128.8 (s), 128.9 (s), 129.3 (s), 137.0 (s), 138.8
(q), 139.3 (q), 144.6 (q), 154.7 (q), 156.7 (q). IR: ν (cm−1) 1585,
1515, 1490, 1460, 1346, 1329, 1292, 1249, 1215, 767, 752, 740. HRMS
calcd for C29H23N3O4 (MH+): 478.1761. Found: 478.1756 (ESI+).
MP = 136−137 °C.
2-(((2-Hydroxybenzyl)(2-phenylquinolin-8-yl)amino)methyl)-4-ni-
trophenol (2d). Rf = 0.82 (95:5 CH2Cl2/MeOH). 1H NMR (500
MHz, CDCl3): δ 4.48 (s, 2H; CH2), 4.51 (s, 2H; CH2), 6.77−6.85 (m,
3H; ArH), 7.12−7.22 (m, 2H; ArH), 7.46−7.64 (m, 6H; ArH), 7.80
(d, J = 8.7, 1H; ArH), 7.86 (m, 2H; ArH), 8.03 (dd, J = 2.4, 9.0, 1H;
ArH), 8.17 (d, J = 2.4, 1H; ArH), 8.32 (d, J = 8.7, 1H; ArH), 10.59
(brs, 2H, OH). 13C NMR (125 MHz, CDCl3): δ 56.6 (d), 57.4 (d),
117.2 (s), 117.7 (s), 119.6 (s), 121.2 (s), 121.7 (s), 122.4 (s), 124.5
(s), 125.7 (s), 126.4 (s), 126.5 (s), 128.5 (s), 128.5 (s), 128.9 (q),
129.2 (s), 129.2 (s), 129.6 (s), 129.7 (s), 130.5 (s), 138.8 (q), 138.9
(q), 140.2 (q), 142.6 (q), 144.1 (q), 156.5 (q), 156.8 (q), 159.8 (q),
163.1 (q). IR: ν (cm−1) 1584, 1515, 1490, 1459, 1342, 1327, 1290,
1246, 1217, 765, 752, 740. LRMS for C29H23N3O4 (MH+): 478.88.
Anal. Calcd for C29H23N3O4 (477.52): C, 72.94; H, 4.85; N, 8.80.
Found: C, 71.76; H, 4.55; N, 8.67. MP = 175−176 °C.
Methyl 3-(2-Hydroxybenzylamino)propanoate (1f). Rf = 0.29
1
(95:5 CH2Cl2/MeOH). H NMR (500 MHz, CDCl3): δ 2.59 (t, J =
6.1, 2H; CH2), 2.96 (t, J = 6.1, 2H; CH2), 3.72 (s, 3H; CH3), 4.02 (s,
2H; CH2), 6.80 (td, J = 1.0, 7.3, 1H; ArH), 6.85 (dd, J = 1.0, 8.1, 1H;
ArH), 7.01 (d, J = 6.7, 1H; ArH), 7.18 (td, J = 1.0, 7.4, 1H; ArH). 13C
NMR (125 MHz, CDCl3): δ 33.6 (d), 43.6 (d), 51.8 (t), 52.4 (d),
116.3 (s), 119.0 (s), 122.2 (q), 128.4 (s), 128.8 (s), 158.1 (q), 172.8
(q). IR: ν (cm−1) 1593, 1492, 1460, 1335, 1091, 751. LRMS for
C11H15NO3 (MH+): 210.61. Anal. Calcd for C11H15NO3·0.4H2O
(216.45): C, 61.04; H, 7.36; N, 6.47. Found: C, 60.96; H, 7.10; N,
6.69.
2-(((2-Hydroxybenzyl)(2-hydroxyphenyl)amino)methyl)-4-nitro-
1
phenol (2e). Rf = 0.54 (95:5 CH2Cl2/MeOH). H NMR (500 MHz,
General Procedure for Tertiary Amines 2a−f. The appropriate
secondary amine 1a−g (2.95 mmol), 2-(chloromethyl)-4-nitrophenol
(2.95 mmol), and triethylamine (23.6 mmol) were refluxed together in
CHCl3 (20 mL) for 2 h. The reaction was diluted with CH2Cl2 (200
mL) and washed with water (200 mL). The organic layer was filtered
and dried over MgSO4. The product was purified by silica gel column
chromatography using 98:2 CH2Cl2/MeOH. The sticky residue was
isolated as a powder by dissolution in a minimum volume of CH2Cl2,
precipitating with hexane addition, decanting, and drying in vacuo.
Characterization data for all new compounds are presented below.
2-(((2-Hydroxybenzyl)(pyridin-2-ylmethyl)amino)methyl)-4-nitro-
CDCl3): δ 4.22 (s, 2H; CH2), 4.36 (s, 2H; CH2), 6.77 (d, J = 9.0, 1H;
ArH), 6.87−6.95 (m, 4H; ArH), 7.03−7.08 (m, 1H; ArH), 7.11 (brs,
3H; OH) 7.20−7.26 (m, 3H; ArH), 8.00 (dd, J = 2.8, 9.0, 1H; ArH),
8.05 (d, J = 2.8, 1H; ArH). 13C NMR (125 MHz, CDCl3): δ 54.0 (d),
57.9 (d), 116.1 (s), 116.5 (s), 116.9 (s), 120.9 (s), 121.2 (s), 121.6
(q), 121.6 (s), 122.4 (q), 125.7 (s), 126.2 (s), 127.1 (s), 130.3 (s),
131.6 (s), 133.8 (q), 140.5 (q), 151.0 (q), 154.5 (q), 163.4 (q). IR: ν
(cm−1) 1587, 1490, 1458, 1334, 1271, 1227, 1173, 1086, 747. LRMS
for C20H18N2O5 (MH+): 367.72. Anal. Calcd for C20H18N2O5
(366.37): C, 65.57; H, 4.95; N, 7.65. Found: C, 65.61; H, 4.97; N,
7.50. MP = 158−159 °C.
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phenol (2a). Rf = 0.29 (95:5 CH2Cl2/MeOH). H NMR (500 MHz,
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dx.doi.org/10.1021/ic302770t | Inorg. Chem. 2013, 52, 3969−3975