Synthesis of 2,4-Diaryl-3,4-dihydro-2H-naphth[2,1-e][1,3]oxazines
δ ϭ 51.70 (CHNH2), 118.81 (C-2), 120.26 (C-4), 121.70 (C-3Ј),
FULL PAPER
General Method for the Synthesis of 2,4-Diaryl-3,4-dihydro-2H-
121.75 (C-3), 122.54 (C-8), 125.15 (C-8a), 125.51 (C-7), 126.45 (C- naphth[2,1-e][1,3]oxazines 17Ϫ23: Et3N (0.11 g, 1.1 mmol) and an
6), 126.71 (C-6Ј), 127.86 (C-5), 130.10 (C-2Ј), 130.83 (C-5Ј), 130.93 equivalent amount of aromatic aldehyde (freshly distilled if liquid)
(C-4Ј), 133.98 (C-4a), 140.75 (C-1Ј), 149.87 (C-1) ppm.
were added to a solution of the appropriate aminonaphthol hydro-
chloride (10Ϫ16, 1 mmol) in absolute MeOH (20 mL). The mixture
was left to stand at ambient temperature for 24 h. Any crystalline
product was then filtered off, washed with MeOH and recrys-
tallized (Table 4). In the event of an oily product, the solvent was
evaporated and the residue was partitioned between H2O and
CHCl3 (10 mL each). The separated organic layer was dried with
Na2SO4 and the solvent was then evaporated. The oily product was
dried in a vacuum desiccator for 24 h. The NMR spectra proved
that the purities of these compounds were greater than 95%. All
the new compounds gave satisfactory data on elemental analysis
(C, H, N Ϯ0.3%). The physical data on compounds 17Ϫ23 are
listed in Table 4.
2-(α-Amino-4-bromobenzyl)-1-naphthol Hydrochloride (12): Yield
8.57 g (47%), m.p. 117Ϫ119 °C. 1H NMR (400.13 MHz, DMSO,
300 K): δ ϭ 6.13 (s, 1 H, CHNH2), 7.46Ϫ7.55 (m, 5 H, 4-H, 6-H,
7-H, 2Ј-H), 7.57Ϫ7.65 (m, 3 H, 3-H, 3Ј-H), 7.82Ϫ7.88 (m, 1 H, 5-
H), 8.31Ϫ8.37 (m, 1 H, 8-H), 9.24 (br. s, 2 H, NH2), 10.18 (br. s,
1 H, OH) ppm. 13C NMR (100.03 MHz, DMSO, 300 K): δ ϭ 51.49
(CHNH2), 119.12 (C-2), 120.21 (C-4), 121.17 (C-4Ј), 122.52 (C-8),
124.84 (C-3), 125.21 (C-8a), 125.48 (C-6), 126.64 (C-7), 127.81 (C-
5), 129.77 (C-2Ј), 130.60 (C-6Ј), 131.44 (C-3Ј), 132.30 (C-5Ј), 133.96
(C-4a), 137.60 (C-1Ј), 149.83 (C-1) ppm.
2-(α-Amino-4-chlorobenzyl)-1-naphthol Hydrochloride (13): Yield
8.01 g (50%), m.p. 167Ϫ169 °C. 1H NMR (400.13 MHz, DMSO,
17g: Mixture of Schiff base (80%), cis-ring form (5%) and trans-
3
1
300 K): δ ϭ 6.14 (s, 1 H, CHNH2), 7.47 (d, JH,H ϭ 8.1 Hz, 2 H,
ring form (15%). Selected signals: H NMR (CDCl3, 300 K): δ ϭ
3
2Ј-H), 7.49Ϫ7.58 (m, 5 H, 4-H, 6-H, 7-H, 3Ј-H), 7.60 (d, JH,H
ϭ
5.42 (br. s, 1 H, 4-H, trans), 5.62 (br. s, 1 H, 2-H, trans), 5.80 (br.
s, 1 H, 2-H, cis), 6.14 (br. s, 1 H, 4-H, cis), 6.34 (s, 1 H,
NphCHArNH, Schiff base), 8.66 (s, 1 H, NHϭCHAr, Schiff base)
ppm. 13C NMR (CDCl3, 300 K): δ ϭ 54.30 (C-4, trans), 84.00 (C-
2, trans), 71.70 (NphCHArNH, Schiff base), 162.70 (NHϭCHAr,
Schiff base) ppm. Assignments of the carbon atoms in the cis-ring
form could not be made owing to the low concentration.
8.6 Hz, 1 H, 3-H), 7.82Ϫ7.88 (m, 1 H, 5-H), 8.30Ϫ8.36 (m, 1 H,
8-H), 9.19 (br. s, 2 H, NH2), 10.16 (br. s, 1 H, OH) ppm. 13C NMR
(100.03 MHz, DMSO, 300 K): δ ϭ 51.33 (CHNH2), 119.10 (C-2),
120.23 (C-4), 122.55 (C-8), 124.82 (C-3), 125.17 (C-8a), 125.64 (C-
7), 126.67 (C-6), 127.90 (C-5), 128.77 (C-2Ј), 129.40 (C-5Ј), 129.41
(C-3Ј), 129.80 (C-6Ј), 132.71 (C-4a), 133.96 (C-4Ј), 137.15 (C-1Ј),
149.83 (C-1) ppm.
18a: Mixture of Schiff base (12%), cis-ring form (31%) and trans-
1
2-(α-Aminobenzyl)-1-naphthol Hydrochloride (14): Yield 8.14 g
ring form (57%). Selected signals: H NMR (CDCl3, 300 K): δ ϭ
1
5.29 (d, 3JH,H ϭ 6.0 Hz, 1 H, 4-H, trans), 5.65 (d, 3JH,H ϭ 10.3 Hz,
(57%), m.p. 171Ϫ174 °C. H NMR (400.13 MHz, DMSO, 300 K):
3
3
δ ϭ 6.14 (s, 1 H, CHNH2), 7.34 (t, JH,H ϭ 7.3 Hz, 1 H, 4Ј-H),
1 H, 4-H, cis), 5.86 (d, JH,H ϭ 12.6 Hz, 1 H, 2-H, trans), 6.33 (d,
3
3JH,H ϭ 10.0 Hz, 1 H, 2-H, cis), 6.37 (s, 1 H, NphCHArNH, Schiff
base), 8.82 (s, 1 H, NHϭCHAr, Schiff base) ppm. 13C NMR
(CDCl3, 300 K) 54.20 (C-4, trans), 82.90 (C-2, trans), 58.60 (C-4,
cis), 86.80 (C-2, cis), 70.80 (NphCHArNH, Schiff base), 161.00
(NHϭCHAr, Schiff base) ppm.
7.40 (t, JH,H ϭ 7.3 Hz, 2 H, 3Ј-H), 7.47Ϫ7.58 (m, 5 H, 4-H, 6-H,
3
7-H, 2Ј-H), 7.60 (d, JH,H ϭ 8.8 Hz, 1 H, 3-H), 7.82Ϫ7.88 (m, 1
H, 5-H), 8.30Ϫ8.37 (m, 1 H, 5-H), 9.13 (br. s, 2 H, NH2), 10.14
(br. s, 1 H, OH) ppm. 13C NMR (100.03 MHz, DMSO, 300 K):
δ ϭ 51.57 (CHNH2), 119.43 (C-2), 120.06 (C-4), 122.47 (C-8),
124.68 (C-3), 125.17 (C-8a), 125.48 (C-6), 126.63 (C-7), 126.96 (C-
5), 126.98 (C-2Ј), 128.11 (C-4Ј), 128.40 (C-6Ј), 128.60 (C-3Ј), 129.00
(C-5Ј), 133.90 (C-4a), 138.14 (C-1Ј), 149.77 (C-1) ppm.
Acknowledgments
The authors thank the Hungarian Research Foundation (OTKA
no. TS04888) for financial support.
2-(α-Amino-4-methylbenzyl)-1-naphthol Hydrochloride (15): Yield
8.24 g (55%), m.p. 165Ϫ166 °C. 1H NMR (400.13 MHz, DMSO,
300 K): δ ϭ 2.27 (s, 3 H, Ar-CH3), 6.12 (s, 1 H, CHNH2), 7.19 (d,
3
3JH,H ϭ 8.1 Hz, 2 H, 3Ј-H), 7.43 (d, JH,H ϭ 8.1 Hz, 2 H, 2Ј-H),
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7.46Ϫ7.54 (m, 3 H, 4-H, 6-H, 7-H), 7.62 (d, JH,H ϭ 8.6 Hz, 1 H,
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F. Fülöp, K. Pihlaja, J. Mattinen, G. Bernath, J. Org. Chem.
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s, 2 H, NH2), 10.12 (br. s, 1 H, OH) ppm. 13C NMR (100.03 MHz,
DMSO, 300 K): δ ϭ 20.63 (Ar-CH3), 51.52 (CHNH2), 119.76 (C-
2), 120.14 (C-4), 122.65 (C-8), 125.05 (C-3), 125.28 (C-8a), 125.40
(C-6), 126.57 (C-7), 127.38 (C-2Ј), 127.86 (C-5), 128.30 (C-6Ј),
129.33 (C-3Ј), 129.70 (C-5Ј), 133.88 (C-4a), 135.29 (C-4Ј), 137.28
(C-1Ј), 149.72 (C-1) ppm.
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2-(α-Amino-4-methoxybenzyl)-1-naphthol Hydrochloride (16): Yield
9.47 g (60%), m.p. 168Ϫ169 °C. 1H NMR (400.13 MHz, DMSO,
300 K): δ ϭ 3.73 (s, 3 H, OCH3), 6.31 (s, 1 H, CHNH2), 6.95 (d,
´
´ ´
´
A. Hetenyi, T. A. Martinek, L. Lazar, Z. Zalan, F. Fülöp,
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´
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3
3JH,H ϭ 7.6 Hz, 2 H, 3Ј-H), 7.47 (d, JH,H ϭ 8.8 Hz, 2 H, 2Ј-H),
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M. Betti, Org. Synth. Coll. Vol. 1941, 1, 381Ϫ383.
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3-H), 7.81Ϫ7.88 (m, 1 H, 5-H), 8.31Ϫ8.38 (m, 1 H, 8-H), 9.10 (br.
s, 2 H, NH2), 10.09 (br. s, 1 H, OH) ppm. 13C NMR (100.03 MHz,
DMSO, 300 K): δ ϭ 51.30 (CHNH2), 55.16 (OCH3), 113.93 (C-
3Ј), 114.60 (C-5Ј), 119.81 (C-2), 120.18 (C-4), 122.57 (C-8), 124.92
(C-3), 125.24 (C-8a), 125.36 (C-6), 126.49 (C-7), 127.84 (C-5),
128.98 (C-2Ј), 129.40 (C-6Ј), 130.13 (C-4a), 133.81 (C-1Ј), 149.58
(C-1), 158.90 (C-4Ј) ppm.
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2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 2237