J. Wang, S. Jin, S. Akay, B. Wang
FULL PAPER
hydride (110 mg, 2.8 mmol, 1.5 equiv.), dry DMF (40 mL) was
added at room temperature. The result solution was stirred for
10 min at room temperature, then methyl iodide (0.18 mL,
2.8 mmol, 1.5 equiv.) was added. The mixture was stirred for 5 h
at room temperature. The solvent was evaporated under vacuum.
Compound 6 (700 mg, 1.6 mmol, 88%) was obtained as yellow
powder after chromatography (hexane/ethyl acetate, 3:1). TLC
(hexane/ethyl acetate, 2:1, Rf = 0.45), m.p. 161–163 °C. 1H NMR
(CDCl3, 400 MHz, 25 °C): δ = 8.62 (dd, J = 6.4, 2.4 Hz, 1 H, 7-
H), 8.51 (dt, J = 8.4, 1.6 Hz, 2 H, 5-H, 2-H), 7.64 (t, J = 7.2 Hz,
1 H, 6-H), 7.27–7.41 (m, 4 H, phenyl-H), 7.19 (dd, J = 8.0, 1.6 Hz,
1 H, 3-H), 5.66 (d, J = 1.2 Hz, 2 H, 11-H), 4.56 (s, 2 H, 12-H),
3.51 (s, 3 H, OCH3), 2.99 (s, 3 H, NCH3) ppm. 13C NMR (CDCl3,
100 MHz, 25 °C): δ = 164.7 (C=O), 164.1 (C=O), 156.5 (C-4), 137.0
(C-2), 132.8 (C-7), 131.4 (C-5), 130.8 (C-9), 128.7, 127.6, 127.5 (6
C, phenyl-C), 125.6 (C-6), 125.3 (C-8), 122.8 (C-10), 115.0, 114.8
(C-1, C-3), 70.8 (C-11), 61.3 (C-12), 57.6 (OCH3), 41.0 (NCH3)
ppm. C22H19BrN2O3 (439.30): calcd. C 60.15, H 4.36, N 6.38;
found C 60.28, H 4.30, N 6.18.
Experimental Section
4-Amino-N-(methoxymethyl)naphthalimide (3): 4-Aminonaphthal-
imide (2) (3 g, 14.1 mmol, 1.0 equiv.) in dry DMF (120 mL) was
treated at room temperature with 2 sodium methoxide in meth-
anol (7.8 mL, 15.5 mmol, 1.1 equiv.) for 10 min followed by me-
thoxydichloromethane (1.2 mL, 15.5 mmol, 1.1 equiv.) addition in
a dropwise fashion. The mixture was stirred at room temperature
for 5 h. Then the solvent was evaporated under vacuum. Com-
pound 3 (2.2 g, 8.6 mmol, 61%) was obtained as a yellow powder
after column chromatography (ethyl acetate). TLC (hexane/ethyl
acetate, 1:1, Rf = 0.45). M.p. 214–216 °C. 1H NMR (DMSO,
400 MHz, 25 °C): δ = 8.64 (d, J = 8.4 Hz, 1 H, 7-H), 8.44 (d, J =
7.2 Hz, 1 H, 5-H), 8.22 (d, J = 8.4 Hz, 1 H, 2-H), 7.65 (t, J =
8.0 Hz, 1 H, 6-H), 7.51 (s, 2 H, -NH2), 6.87 (d, J = 8.4 Hz, 1 H, 3-
H), 5.41 (s, 2 H, 11-H), 3.32 (s, 3 H, -OCH3) ppm. 13C NMR
(DMSO, 100 MHz, 25 °C): δ = 164.5 (C=O), 163.4 (C=O), 153.4
(C-4), 134.6, 131.7 (C-2, C-7), 130.6, 130.1 (C-5, C-9), 124.4, 121.9
(C-6, C-8), 119.8 (C-10), 108.7, 107.4 (C-1, C-3), 70.5 (C-11), 57.1
(OCH3) ppm. MS (ESI+): m/z (%) = 257 (100) [M+ + H], 225.
C14H12N2O3 (256.25): calcd. C 65.62, H 4.72, N 10.93; found C
65.42, H 4.65, N 10.68.
4-Amino-N-benzylnaphthalimide (4): 4-Aminonaphthalimide (2)
(3 g, 14.1 mmol, 1.0 equiv.) in dry DMF (120 mL) was treated at
room temperature with 2 sodium methoxide in methanol
(7.8 mL, 15.5 mmol, 1.1 equiv.) for 10 min, and then benzyl bro-
mide (1.85 mL, 15.5 mmol, 1.1 equiv.) was added dropwise. The
mixture was stirred at room temperature for 5 h. Then solvent was
evaporated under vacuum. Column chromatography (ethyl acetate)
of the residue gave 4 (2.5 g, 8.3 mmol, 59%) as a yellow powder.
TLC (hexane/ethyl acetate, 1:1, Rf = 0.45), m.p. 238–240 °C. 1H
NMR (DMSO, 400 MHz, 25 °C): δ = 8.65 (d, J = 8.4 Hz, 1 H, 7-
H), 8.45 (d, J = 7.6 Hz, 1 H, 5-H), 8.23 (d, J = 8.4 Hz, 1 H, 2-H),
7.64 (t, J = 8.4 Hz, 1 H, 6-H), 7.50 (s, 2 H, -NH2), 7.22–7.34 (m,
5 H, H-phenyl), 6.87 (d, J = 8.4 Hz, 1 H, 3-H), 5.22 (s, 2 H, 11-H)
ppm. 13C NMR (DMSO, 100 MHz, 25 °C): δ = 164.3 (C=O), 163.3
(C=O), 153.4 (C-4), 138.4 (C-2), 134.7 (C-7), 131.7, 130.29 (C-5,
C-9), 130.0, 128.7, 127.9, 127.3 (6 C, phenyl), 124.5, 122.1, 119.8
(C-6, C-8, C-10), 108.7, 107.7 (C-1, C-3) ppm. MS (ESI+): m/z (%)
= 303 (100) [M+ + H], 225, 157, 140. C19H14N2O2 (302.32): calcd.
C 75.48, H 4.67, N 9.27; found C 75.21, H 4.51, N 9.08.
4-[(2-Bromobenzyl)amino]-N-(methoxymethyl)naphthalimide (5) and
4-[Bis(2-bromobenzyl)amino]-N-(methoxymethyl)naphthalimide (5a):
Dry DMF (50 mL) was added to a mixture of 3 (1 g, 3.9 mmol,
1.0 equiv.) and sodium hydride (150 mg, 3.9 mmol, 1.0 equiv.) at
room temperature. The resulting solution was stirred at room tem-
perature for 10 min, followed by 2-bromobenzyl bromide (975 mg,
3.9 mmol, 1.0 equiv.) addition. The mixture was stirred at room
temperature for 5 h before solvent evaporation under vacuum.
Compounds 5 (1.2 g, 2.8 mmol, 72%) and 5a (0.5 g, 0.8 mmol,
21%) were obtained as yellow powders after column chromatog-
raphy (hexane/ethyl acetate, 1:1).
1
5: TLC (hexane/ethyl acetate, 1:1, Rf = 0.55), m.p. 148–150 °C. H
NMR (DMSO, 400 MHz, 25 °C): δ = 8.81 (d, J = 8.4 Hz, 1 H, 7-
H), 8.48 (t, J = 7.6 Hz, 2 H, 5-H, 17-H), 8.23 (d, J = 8.4 Hz, 1 H,
2-H), 7.62 (t, J = 8.4 Hz,1 H, 6-H), 7.70 (d, J = 7.6 Hz, 1 H, 14-
H), 7.32 (s, 1 H, -NH), 7.25 (br. s, 2 H, 15-H, 16-H), 6.57 (d, J =
8.4 Hz, 1 H, 3-H), 5.40 (s, 2 H, 11-H), 4.67 (d, J = 4.4 Hz, 2 H,
12-H), 3.31 (s, 3 H, OCH3) ppm. 13C NMR (DMSO, 100 MHz,
25 °C): δ = 164.4 (C=O), 163.4 (C=O), 150.7 (C-4), 136.8 (C-2),
134.8 (C-7), 133.2 (C-5), 131.5 (C-9), 130.2, 129.7, 129.3, 128.8,
128.4, 125.2 (6 C, phenyl), 123.0 (C-6), 122.2 (C-8), 120.7 (C-10),
108.6, 105.0 (C-1, C-3), 70.5 (C-11), 57.1 (OCH3), 47.0 (C-12) ppm.
MS (ESI+): m/z (%) = 425, 427 (100) [M+ + H], 393, 395, 214.
C21H17BrN2O3 (425.27): calcd. C 59.31, H 4.03, N 6.59; found C
59.48, H 4.00, N 6.40.
N-Benzyl-4-[(2-bromobenzyl)amino]naphthalimide (7): Dry DMF
(50 mL) was added at room temperature to a mixture of 4 (1 g,
3.3 mmol, 1.0 equiv.) and sodium hydride (132 mg, 3.3 mmol,
1.0 equiv.). The resulting solution was stirred at room temperature
for 10 min before 2-bromobenzyl bromide (825 mg, 3.3 mmol,
1.0 equiv.) was added. The mixture was stirred at room temperature
for 5 h. Then the solvent was evaporated under vacuum. Column
chromatography (hexane/ethyl acetate, 1:1) gave
7 (880 mg,
5a: TLC (hexane/ethyl acetate, 1:1, Rf = 0.65), m.p. 156–158 °C. 1H
NMR (CDCl3, 400 MHz, 25 °C): δ = 8.61 (d, J = 7.2 Hz, 1 H, 7-
H), 8.53 (d, J = 8.0 Hz, 1 H, 5-H), 8.45 (d, J = 7.2 Hz, 1 H, 2-H),
7.65 (t, J = 7.2 Hz, 1 H, 6-H), 7.58 (d, J = 7.2 Hz, 2 H, 17-H), 7.45
(d, J = 8.8 Hz, 2 H, 15-H), 7.26 (d, J = 7.6 Hz, 2 H, 16-H), 7.15
(m, 3 H, 3-H, 14-H), 5.61 (s, 2 H, 11-H), 4.69 (s, 4 H, 12-H), 3.49
(s, 2 H, OCH3) ppm. 13C NMR (CDCl3, 100 MHz, 25 °C): δ =
164.5 (C=O), 163.9 (C=O), 154.0 (C-4), 135.8 (2 C, C-13), 133.2 (2
C, C-17), 132.3 (C-2), 131.5 (C-7), 130.5 (C-5), 130.2 (C-9), 129.0
(2 C, C-14), 128.8 (2 C, C-16), 127.6 (2 C, C-15), 126.6 (C-6), 125.9
(2 C, C-18), 123.6 (C-8), 122.9 (C-10), 117.2, 116.0 (C-1, C-3), 70.8
(C-11), 57.9 (OCH3), 57.6 (C-12) ppm. MS (ESI+): m/z (%) = 594.8
(100) [M+ + H], 562, 387, 225, 157, 89. C28H22Br2N2O3 (594.29):
calcd. C 56.59, H 3.73, N 4.71; found C 56.45, H 3.70, N 4.57.
1.9 mmol, 57%) and recovered 4 (250 mg, 0.8 mmol, 25%) as yel-
low powders. 7: TLC (hexane/ethyl acetate, 1:1, Rf = 0.55), m.p.
185–186 °C. H NMR (CDCl3, 400 MHz, 25 °C): δ = 8.57 (d, J =
1
7.2 Hz, 1 H, 7-H), 8.43 (d, J = 8.4 Hz, 1 H, 5-H), 8.10 (d, J =
8.4 Hz, 1 H, 2-H), 7.56–7.63 (m, 2 H, 6-H, 17-H), 7.53 (d, J =
7.6 Hz, 2 H, phenyl-H), 7.37 (d, J = 7.6 Hz, 3 H, phenyl-H), 7.19
(t, J = 6.8 Hz, 2 H, phenyl-H), 6.67 (d, J = 8.4 Hz, 1 H, 3-H), 5.76
(d, J = 4.8 Hz, 1 H, –NH), 5.35 (s, 2 H, 11-H), 4.68 (d, J = 4.2 Hz,
2 H, 12-H) ppm. 13C NMR (CDCl3, 100 MHz, 25 °C): δ = 164.5
(C=O), 164.0 (C=O), 148.7 (C-4), 137.7 (C-2), 135.8 (C-7), 134.4
(C-5), 133.2 (C-9), 131.3, 129.7, 129.5, 129.2 (4 C, phenyl-C), 128.8
(2 C, phenyl-C), 128.3 (2 C, phenyl-C), 127.8, 127.2, 125.9, 124.9
(4 C, phenyl-C), 123.5 (C-6), 123.1 (C-8), 120.3 (C-10), 111.0, 105.0
(C-1, C-3), 48.0 (C-11), 43.3 (C-12) ppm. MS (ESI+): m/z (%) =
471, 473 (80) [M+ + H], 358 (100), 162. C26H19BrN2O2 (471.34):
calcd. C 66.25, H 4.06, N 5.94; found C 65.99, H 4.03, N 5.64.
4-[(2-Bromobenzyl)methylamino]-N-(methoxymethyl)naphthalimide
(6): To a mixture of 5 (780 mg, 1.8 mmol, 1.0 equiv.) and sodium
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Eur. J. Org. Chem. 2007, 2091–2099