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R. Csutortoki et al. / Tetrahedron 67 (2011) 8564e8571
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(Na2SO4) and concentrated under reduced pressure. The residue
was crystallized from n-hexane/EtOAc (20 mL:1 mL).
129.0 (C-60), 130.0 (C-4), 132.2 (C-50), 132.9 (C-8a), 136.4 (C-10), 137.1
(PhCH2), 148.6 (C-20), 153.7 (C-2), 155.9 (NHCOO). Anal. Calcd for
C25H20N2O5 (428.44): C, 70.08; H, 4.71; N, 6.54. Found: C, 70.15; H,
4.69; N, 6.49.
Yield: 3.97 g (90%), mp: 120e122 ꢀC. 1H NMR (600 MHz, DMSO):
d
¼6.54 (s,1H, PhCHNH2), 7.09 (d, 1H, 3-H, J¼8.8 Hz), 7.20 (t,1H, 6-H,
J¼7.4 Hz), 7.30 (t,1H, 7-H, J¼7.6 Hz), 7.37 (d, 1H, 60-H, J¼7.9 Hz), 7.42
(d, 1H, 8-H, J¼8.6 Hz), 7.52 (t, 1H, 40-H, J¼7.8 Hz), 7.58 (t, 1H, 50-H,
J¼7.5 Hz), 7.76 (d, 2H, 4-H, 5-H, J¼8.5 Hz), 8.07 (d, 1H, 30-H,
4.1.5. 1-(Amino(2-aminophenyl)methyl)-2-naphthol (4); starting
from 5. The nitroderivative 5 (5.14 g, 0.012 mol) was dissolved in
MeOH (15 mL). In parallel, Pd/C (3.43 g) was suspended in MeOH
(10 mL). The mixture was hydrogenated at atmospheric pressure
for 2 h. The catalyst was then removed by filtration and washed
with MeOH (2ꢂ10 mL). The filtrate was concentrated under vac-
uum and the residue was crystallized from n-hexane (20 mL). The
product was purified by recrystallization from i-Pr2O (20 mL).
Yield: 2.19 g (69%), mp: 127e129 ꢀC. The NMR and analytical
data were identical with those of the material synthesized starting
from 3.
J¼8.1 Hz). 13C NMR (150 MHz, DMSO):
¼50.1 (PhCHNH2), 115.0 (C-
d
1),120.4 (C-3, C-8),122.2 (C-6),124.8 (C-30),126.7 (C-7),127.8(C-4a),
128.7 (C-5), 129.1 (C-40), 129.7 (C-4), 130.1 (C-60), 131.7 (C-8a), 133.8
(C-50), 136.7 (C-10), 148.5 (C-20), 158.3 (C-2). Anal. Calcd for
C17H14N2O3 (294.30): C, 69.38; H, 4.79; N, 9.52. Found: C, 69.29; H,
4.74; N, 9.49.
4.1.3. 1-(Amino(2-aminophenyl)methyl)-2-naphthol (4); starting
from 3. Compound 3 (3.53 g, 0.012 mol) was dissolved in MeOH
(15 mL). In parallel, Pd/C (1.32 g) was suspended in MeOH (10 mL).
The mixture was hydrogenated at atmospheric pressure for 1.5 h.
The catalyst was then filtered off and washed with MeOH
(2ꢂ10 mL). The filtrate was concentrated to dryness under reduced
pressure and the residue was crystallized from n-hexane (20 mL).
The product was purified by recrystallization from i-Pr2O (20 mL).
Yield: 2.15 g (68%), mp: 128e130 ꢀC. 1H NMR (600 MHz, DMSO):
4.1.6. 10,11-Dihydro-8H,15bH-naphth[1,2-e][1,3]oxazino[3,4-c]quina-
zoline (6). Aqueous formaldehyde (0.53 mL, 30%) was added to
a solution of 4 (0.53 g, 0.002 mol) in CHCl3 (15 mL). The mixture was
stirred at rt for 1.5 h. The solution was then dried (Na2SO4) and the
solvent was evaporated off. The product was isolated by column
chromatography (n-hexane/EtOAc 2:1 v/v), crystallized from Et2O
(10 mL) and recrystallized from i-Pr2O (12 mL).
d
¼5.37 (br s, 2H, PhNH2), 6.14 (s, 1H, PhCHNH2), 6.34 (t, 1H, 40-H,
J¼7.5 Hz), 6.63 (d, 1H, 30-H, J¼7.8 Hz), 6.75 (d, 1H, 60-H, J¼8.0 Hz),
6.92 (t, 1H, 50-H, J¼7.7 Hz), 7.03 (d, 1H, 3-H, J¼8.8 Hz), 7.17 (t, 1H, 6-
H, J¼7.5 Hz), 7.27 (t, 1H, 7-H, J¼7.7 Hz), 7.47 (d, 1H, 8-H, J¼8.7 Hz),
7.70 (d, 1H, 4-H, J¼8.9 Hz), 7.73 (d, 1H, 5-H, J¼8.0 Hz). 13C NMR
Yield: 0.23 g (40%), mp: 145e147 ꢀC. 1H NMR (600 MHz, CD2Cl2):
d
¼4.40 (d, 1H, 10-Hax, J¼12.2 Hz), 4.84 (d, 1H, 8-Heq, J¼7.3 Hz), 4.91
(d, 1H, 8-Hax, J¼7.3 Hz), 4.96 (d, 1H, 10-Heq, J¼12.2 Hz), 5.83 (s, 1H,
15b-H), 6.42 (t, 1H,14-H, J¼7.5 Hz), 6.50 (d,1H, 12-H, J¼8.0 Hz), 6.75
(d, 1H, 15-H, J¼7.7 Hz), 6.98 (t, 1H, 13-H, J¼7.6 Hz), 7.09 (d, 1H, 6-H,
J¼8.9 Hz), 7.38 (t, 1H, 3-H, J¼7.5 Hz), 7.51 (t, 1H, 2-H, J¼7.5 Hz), 7.74
(d, 1H, 5-H, J¼8.9 Hz), 7.82 (d, 1H, 4-H, J¼8.3 Hz), 7.87 (d, 1H, 1-H,
(150 MHz, DMSO):
d
¼50.1 (PhCHNH2), 115.7 (C-1), 115.8 (C-60),
116.4 (C-40), 120.3 (C-3), 121.7 (C-8), 121.9 (C-6), 126.1 (C-7), 127.7
(C-4a), 127.9 (C-30), 128.1 (C-50), 128.4 (C-4, C-5), 128.7 (C-10), 132.0
(C-8a), 145.6 (C-20), 158.2 (C-2). Anal. Calcd for C17H16N2O (264.32):
C, 77.25; H, 6.10; N, 10.60. Found: C, 77.32; H, 6.08; N, 10.56.
J¼7.4 Hz). 13C NMR (150 MHz, CD2Cl2):
¼54.4 (C-15b), 61.5 (C-10),
d
78.4 (C-8), 114.5(C-12), 115.8 (C-15c), 117.8 (C-14), 119.0 (C-6), 120.6
(C-15a), 123.4 (C-1), 123.7 (C-3), 127.1 (C-2), 128.4 (C-13), 128.8 (C-
4), 129.1 (C-4a), 129.5 (C-5), 129.8 (C-15), 133.2 (C-15d), 141.2 (C-
11a), 150.5 (C-6a). MS: (EI) m/z (%)¼288 (50) [M]þ, 259 (100), 230
(42), 115 (35). Anal. Calcd for C19H16N2O (288.34): C, 79.14; H, 5.59;
N, 9.72. Found: 79.21; H, 5.56; N, 9.68.
4.1.4. Benzyl
(2-hydroxynaphthalen-1-yl)(2-nitrophenyl)methyl-
carbamate (5). A mixture of 2-naphthol (1, 3.60 g, 0.025 mol), 2-
nitrobenzaldehyde (3.78 g, 0.025 mol) and benzyl carbamate
(3.77 g, 0.025 mol) was heated at 80 ꢀC for 32 h under neat con-
ditions. When TLC showed that no starting material remained, the
residue was crystallized from MeOH (30 mL) and the beige crystals
that separated out were filtered off and washed with MeOH
(2ꢂ10 mL).
4.1.7. 2-(Aryl-substituted)-4-(2-hydroxynaphthalen-1-yl)-1,2,3,4-
tetrahydroquinazolines (7aeg). The appropriate aromatic aldehyde
(0.0022 mol; freshly distilled if liquid) was added to a solution of 4
(0.53 g, 0.002 mol) in MeOH (30 mL). The mixture was left to stand
for 1 day at ambient temperature, during, which crystalline mate-
rial separated out. The crystalline product (7aeg) was filtered off,
washed with cold MeOH (2ꢂ5 mL) and recrystallized from a mix-
ture of i-Pr2O/EtOAc. All of the recrystallized new compounds
(7aeg) gave satisfactory data on elemental analysis (C, H, N). The
physical and analytical data for 7aeg are listed in Table 5.
Yield: 8.14 g (76%), mp: 204e206 ꢀC. 1H NMR (600 MHz, DMSO):
d
¼5.08 (m, 2H, PhCH2), 7.05 (d, 1H, 3-H, J¼8.9 Hz), 7.26e7.31 (m,
3H, 400-H, 6-H, PhCHNH), 7.33e7.37 (m, 4H, 300-H, 500-H, 200-H, 600-H),
7.41 (t, 1H, 7-H, J¼7.3 Hz), 7.47 (t, 1H, 40-H, J¼7.4 Hz), 7.58e7.66 (m,
2H, 50-H, 60-H), 7.73 (d, 1H, 4-H, J¼8.8 Hz), 7.76 (d, 1H, 30-H,
J¼8.0 Hz), 7.79 (d,1H, 5-H, J¼8.0 Hz), 7.91 (d,1H, 8-H, J¼8.7 Hz), 8.14
(br d, 1H, CHNH, J¼8.4 Hz), 9.81 (br s, 1H, OH). 13C NMR (150 MHz,
Table 5
Physical and analytical data on 2-(aryl-substituted)-4-(2-hydroxynaphthalen-1-yl)-1,2,3,4-tetrahydroquinazolines (7aeg)
Compd
Mp (ꢀC)
Yield (%)
Formula
MW
C% found (calculated)
H% found (calculated)
N% found (calculated)
7aa
7ba
7cb
7dc
7eb
7fb
7ga
191e194
174e176
179e182
172e174
168e171
174e176
148e151
77
52
63
88
66
90
57
C24H19N3O3
C24H19ClN2O
C24H19ClN2O
C24H20N2O
C25H22N2O
C25H22N2O2
C26H25N3O
397.43
386.87
386.87
352.43
366.45
382.45
395.5
72.49 (72.53)
74.58 (74.51)
74.62 (74.51)
81.68 (81.79)
81.97 (81.94)
78.62 (78.51)
78.85 (78.96)
4.78 (4.82)
4.91 (4.95)
4.92 (4.95)
5.79 (5.72)
6.01 (6.05)
5.75 (5.80)
6.32 (6.37)
10.52 (10.57)
7.21 (7.24)
7.28 (7.24)
7.92 (7.95)
7.61 (7.64)
7.35 (7.32)
10.59 (10.62)
a
Recrystallized from i-Pr2O/EtOAc (15 mL:5 mL).
Recrystallized from i-Pr2O/EtOAc (15 mL:2 mL).
Recrystallized from i-Pr2O/EtOAc (15 mL:1 mL).
b
c
DMSO):
d
¼47.9 (PhCHNH), 65.5 (PhCH2), 116.0 (C-1), 118.4 (C-3),
4.1.8. (2S*,4S*)-2-Phenyl-4-(2-hydroxynaphthalen-1-yl)-1,2,3,4-
122.5 (C-400), 122.6 (C-8), 124.1 (C-30), 126.6 (C-7), 127.4 (C-200, C-600),
127.7 (C-6), 127.8 (C-40), 128.1 (C-4a), 128.3 (C-300, C-500), 128.5 (C-5),
tetrahydroquinazoline (7d). Yield: 0.62 g (88%), mp: 172e174 ꢀC. 1H
NMR (600 MHz, CD2Cl2):
d¼4.33 (br s, 1H, 3-H), 5.50 (s, 1H, 2-H),