Oximes of 2-Aryl-6-methoxy-3,4-dihydronaphthalene
39
2-[3-(1-Hydroximinoethyl)phenyl]-6-methoxy-3,4-dihydronaphthalene (7a)
(2E)-[4-(2-Methyl-1,3-dioxolan-2-yl)benzylidene]-6-methoxy-1-tetralone
(10b)
.
A mixture of 0.27 g (0.97 mmol) 6a, 0.2 g (2.9 mmol) NH2OH HCl, 0.4 g
(4.9 mmol) NaOAc and 30 ml CH3OH was stirred and heated at 65 °C for
2 days. The solution was poured into 150 ml water and extracted three times
with CH2Cl2 (50 ml). The organic layer was washed with H2O and dried over
Na2SO4. After evaporation of the solvent in vacuo, the crude product 7a
(270 mg, 94.9 %) was obtained, which was purified by recrystallization from
EtOAc / petroleum ether. mp 92–93.5 °C. IR (KBr): ν = 3250 (s, OH), 3010
(w), 2840–2960 (m, CH), 1620 (s, C=C), 1575 (s, C=C) (vs) cm–1.– 1H NMR
(DMSO(d6)): δ ppm: 2.22 (s, 3H, CH3), 2.69 (t, J = 8.0 Hz, 2H, ArCH2CH2),
2.91 (t, J = 8.0 Hz, 2H, ArCH2), 3.78 (s, 3H, OCH3), 6.78 (d, J = 8.0, 1H,
Ar-H, -H7), 6.82 (s, 1H, Ar-H, -H5), 6.98 (s, 1H, =CH), 7.17 (d, J = 8.0, 1H,
Ar-H, -H8), 7.41 (m, 1H, Ar′-H, -H5′), 7.57 (m, 2H, Ar′-H, -H4′, -H6′), 7.83
(s, 1H, Ar′-H, -H2′), 11.23 (s, 1H, =NOH).– MS m/z (%) = 275 (100) (M+ –
H2O), 260 (45), 189 (30). Anal. (C19H19NO2) C,H,N.
1.3 g (7.4 mmol) of 6-methoxy-1-tetralone and 9b (1.4 g, 7.3 mmol) were
dissolved in 13 ml 4% KOH/EtOH, and stirred 12 h at room temperature to
give 1.0 g of 10b (39.1%, white crystals). mp 127–128 °C. IR (KBr): ν =
3005 (w), 2840–2980 (m, CH), 1665 (s, C=O), 1610 (s, C=C), 1595 (s, C=C),
1570 (s, C=C) (vs) cm–1.– 1H NMR (CDCl3): δ = 1.68 (s, 3H, CH3), 2.92 (t,
J = 6.4 Hz, 2H, ArCH2CH2), 3.12 (t, J = 6.4 Hz, 2H, ArCH2), 3.82 (t, J = 7.5
Hz, 2H, CH2O), 3.87 (s, 3H, OCH3), 4.06 (t, J = 7.5 Hz, 2H, CH2O), 6.71 (s,
1H, Ar-H, -H5), 6.87 (d, J = 8.4 Hz, 1H, Ar-H, -H7), 7.40 (d, J = 8.4 Hz, 2H,
Ar′-H, -H3′, -H5′), 7.52 (d, J = 8.4 Hz, 2H, Ar′-H, -H2′, -H6′), 7.82 (s, 1H,
=CH), 8.11 (d, J = 8.4 Hz, 1H, Ar-H, -H8).– MS m/z (%) = 350 (12) (M+),
349 (14) (M+ – 1), 335 (100), 87(80).
6-Methoxy-2-[3-(2-methyl-1,3-dioxolan-2-yl)benzyl]-1-tetralone (11a)
2-[4-(1-Hydroximinoethyl)phenyl]-6-methoxy-3,4-dihydronaphthalene (7b)
A mixture of 10a (400 mg, 1.14 mmol), 10% Pd/C (40 mg) and absolute
CH3OH (50 ml) was hydrogenated at normal pressure for 20 min until an
equimolar amount of H2 was absorbed. The mixture was filtered and the
filtrate was evaporated under reduced pressure to give 370 mg (92.0%) of
11a. Recrystallization from EtOH yielded a white solid. mp 89–91 °C. IR
(KBr): ν = 3040 (w), 2800–2960 (m, CH), 1670 (s, C=O), 1610 (s, C=C),
1590 (s, C=C) (vs) cm–1.– 1H NMR (CDCl3): δ = 1.67 (s, 3H, CH3),
1.76–1.81 (m, 1H, ArCH2CH2CH), 2.07 (m, 1H, ArCH2CH2CH), 2.62 (m,
2H, Ar′CH2), 2.90 (m, 2H, ArCH2), 3.50–3.53 (m, 1H, ArCOCH), 3.77–3.80
(m, 2H, CH2O), 3.85 (s, 3H, OCH3), 4.02–4.06 (m, 2H, CH2O), 6.67 (s, 1H,
Ar-H, -H5), 6.83–6.84 (d, J = 8.8 Hz, 1H, Ar-H, -H7), 7.17 (d, J = 7.5 Hz,
1H, Ar′-H, -H6′), 7.27 (d, J = 7.5 Hz, 1H, Ar′-H, -H4′), 7.34 (m, 2H, Ar′-H,
-H2′, -H5′), 8.05 (d, J = 8.8 Hz, 1H, Ar-H, -H8).
.
0.3 g (1.1 mmol) 6b, 0.25 g (3.6 mmol) NH2OH HCl, 0.45 g (5.5 mmol)
NaOAc, gave 0.3 g yellow needle crystals of 7b (95.3%). mp 192–194 °C.
IR (KBr): ν = 3240 (s, OH), 3090 (w), 2840–2960 (m, CH), 1610, 1575 (s,
C=C) (vs)cm–1.– 1H NMR (DMSO(d6)): δ ppm: 2.12 (s, 3H, CH3), 2.62 (t,
J = 8.4 Hz, 2H, ArCH2CH2), 2.82 (t, J = 8.4 Hz, 2H, ArCH2), 3.72 (s, 3H,
OCH3), 6.72 (m, 2H, Ar-H, -H5, -H7), 6.96 (s, 1H, =CH), 7.10 (d, J = 8.0,
1H, Ar-H, -H8), 7.54 (m, 2H, Ar′-H, -H2′, -H6′), 7.63 (m, 2H, Ar′-H, -H3′,
-H5′), 11.16 (s, 1H, =NOH).– MS m/z (%) = 275 (90) (M+- H2O), 260 (50),
189 (25), 18 (100). Anal. (C19H19NO2) C,H,N.
3-(2-Methyl-1,3-dioxolan-2-yl)-benzaldehyde (9a)
6-Methoxy-2-[4-(2-methyl-1,3-dioxolan-2-yl)benzyl]-1-tetralone (11b)
To a stirred solution of 3a (2.43 g, 0.01mol) in THF (30 ml) under dry
nitrogen at –30 °C was added n-BuLi (0.011 mol) and stirred for 2 h. Then
1.2 ml (0.015 mol) DMF was added at –40 °C and subsequently stirred at
room temperature for 2 h. The reaction mixture was worked up with 1N HCl
and extracted three times with CH2Cl2 (100 ml). The organic layer was
washed with H2O and dried over Na2SO4. Evaporation of the solvent in vacuo
gave the crude product 9a (1.48 g, 77%, liquid) which was used without
further purification for the next reaction.
A mixture of 10b (400 mg, 1.14 mmol), 10% Pd/C (40 mg) and absolute
CH3OH (50 ml) was hydrogenated at normal pressure for 20 min until an
equimolar amount of H2 was absorbed. The mixture was filtered and the
filtrate was evaporated under reduced pressure to give 380 mg (94.5%) of
11b. Recrystallization from EtOH yielded a white solid. mp 101–103 °C. IR
(KBr): ν = 3060 (w), 2840–2960 (m, CH), 1670 (s, C=O), 1610 (s, C=C),
1590 (s, C=C) (vs) cm–1.– 1H NMR (CDCl3): δ = 1.66 (s, 3H, CH3),
2.03–2.09 (m, 2H, ArCH2CH2CH), 2.73 (m, 2H, Ar′CH2), 2.90 (m, 2H,
ArCH2), 3.50–3.53 (m, 1H, ArCOCH), 3.77–3.80 (m, 2H, CH2O), 3.85 (s,
3H, OCH3), 4.04 (m, 2H, CH2O), 6.67 (s, 1H, Ar-H, -H5), 6.83-6.84 (d, J =
8.8 Hz, 1H, Ar-H, -H7), 7.34 (d, J = 8.4, 2H, Ar′-H, -H2′, -H6′), 7.90 (d, J =
8.4, 2H, Ar′-H, -H3′, -H5′), 8.04 (d, J = 8.8 Hz, 1H, Ar-H, -H8)
4-(2-Methyl-1,3-dioxolane-2-yl)-benzaldehyde (9b)
2.43 g of 3b, gave 1.51 g of 9b (78.6%).
(2E)-[3-(2-Methyl-1,3-dioxolan-2-yl)benzylidene]-6-methoxy-1-tetralone
(10a)
1-Hydroxy-6-methoxy-2-[3-(2-methyl-1,3-dioxolan-2-yl)benzyl]-1-tetralin
(12a)
To a stirred solution of KOH in EtOH (13 ml, 4%) were added 6-methoxy-
1-tetralone (8) (1.3 g, 7.4 mmol) and 9a (1.4 g, 7.3 mmol) successively and
stirred for 12 h at room temperature. After the end of reaction was shown by
TLC control, 100 ml of H2O was added and the mixture was extracted three
times with CH2Cl2 (100 ml). The organic layer was washed with 1N HCl,
H2O and dried over Na2SO4. After the solvent was removed in vacuo, the
crude product was purified by silica gel column chromatography using 4%
EtOAc / petroleum ether as eluent to give 0.9 g (35.2%) of 10a (colorless
crystals). mp 115–7°C. IR (KBr): δ = 3050 (w), 2820–2980 (m, CH), 1660
(s, C=O), 1610 (s, C=C), 1600 (s, C=C) (vs) cm–1.– 1H NMR (CDCl3): δ =
1.68 (s, 3H, CH3), 2.93 (t, J = 6.4 Hz, 2H, ArCH2CH2), 3.12 (t, J = 6.4 Hz,
2H, ArCH2), 3.80–3.83 (m, 2H, CH2O), 3.88 (s, 3H, OCH3), 4.05–4.08 (m,
2H, CH2O), 6.70 (s, 1H, Ar-H, -H5), 6.89 (d, J = 8.4 Hz, 1H, Ar-H, -H7),
7.35–7.41 (m, 2H, Ar′-H, -H4′, -H5′), 7.46–7.48 (d, J = 7.1 Hz, 1H, Ar′-H,
-H6′), 7.56 (s, 1H, Ar′-H, -H2′), 7.84 (s, 1H, =CH), 8.12 (d, J = 8.8 Hz, 1H,
Ar-H, -H8).– MS m/z (%) = 350 (10) (M+), 349 (15) (M+ – 1), 335 (60), 87
(100).
To a suspension of 100 mg (2.64 mmol) NaBH4 in 30 ml C2H5OH was
added 300 mg (0.85 mmol) 11a in 5 ml C2H5OH and the mixture was stirred
at 70 °C for 15 h. After the end of reaction was shown by TLC control, the
solution was poured into 150 ml water and extracted three times with CH2Cl2
(50ml). The organic layer was washed with H2O and dried over Na2SO4.
After evaporation of the solvent in vacuo, the crude product 12a (270 mg,
90%, liquid) was obtained and used without further purification for the next
reaction. IR (KBr): ν = 3450 (s, OH), 3050 (w, Ar-H), 2870-2960 (m, CH),
1610 (s, C=C), 1580 (w, C=C) (vs) cm–1.– 1H NMR (CDCl3): δ = 1.65 (s,
3H, CH3), 2.01–2.09(m, 2H, ArCH2CH2), 2.47–2.52 (m, 1H,
ArCH2CH2CH) 2.71–2.73 (m, 2H, ArCH2), 2.77–2.83 (m, 1H, Ar′CH2),
2.95–3.04 (m, 1H, Ar′CH2), 3.74–3.77 (m, 2H, CH2O), 3.77(m, 1H, OH),
3.78 (s, 3H, OCH3), 4.0–4.03 (m, 2H, CH2O), 4.44–4.48(m, 1H, ArCHOH),
6.65 (s, 1H, Ar-H, -H5), 6.79 (m, 1H, Ar-H, -H7), 7.13–7.17 (m, 1H, Ar′-H,
-H6′), 7.31–7.32 (m, 2H, Ar′-H, -H2′, -H4′), 7.34 (m, 1H, Ar′-H, -H5′), 7.40
(m, 1H, Ar-H, -H8).
Arch. Pharm. Pharm. Med. Chem. 331, 36–40 (1998)