T. Wang, C. Wang, J. Zhang, and H. He
Vol 000
Ocean Chemical Company, China) and visualized with ultraviolet
light (Shanghai, China). The products were purified by recrystal-
lization or flash chromatography. Column chromatography was
carried out on silica gel (300–400 mesh, Qindao Ocean Chemical
Company, China).
silica gel TLC in CH2Cl2). The mixture was then cooled to
40° C and poured into ice water (300 mL). The mixture was
extracted with CH2Cl2 (7 × 100 mL). The organic phase was
washed with water (2 × 100 mL) and brine solution
(2 × 100 mL), dried over anhydrous Na2SO4, then the solvent
was concentrated in vacuum. The residue was purified by flash
chromatography (silica gel; CH2Cl2) to give 4 as a yellow solid,
7.38 g (74%), mp 164–166°C; Rf = 0.20 (CH2Cl2); IR (KBr):
3414(OH), 3109, 2945, 2928, 2852, 1603, 1525 and 1342
Acetic acid 4-formyl-2-methoxy-phenyl ester (1). Vanillin
(10.00 g, 65.72 mmol) was dissolved in 6% aqueous sodium
hydroxide solution (50 mL), and acetic anhydride (10.60 mL,
112.34 mmol) in dry THF (60 mL) was added dropwise. The
mixture was vigorously stirred at RT for 4 h. THF was
removed under reduced pressure. The residue was extracted
with ethyl acetate (2 × 50 mL). The organic phase was
washed with brine solution and dried over anhydrous
Na2SO4. After removal of the solvent, the residue was
washed with ice ethanol (3 × 10 mL) and dried to give 1 as
white needles, 11.10 g (87%), mp 76–77°C (lit. [6a] mp 77°
C, no range given); Rf = 0.64 (petroleum ether–EtOAc, 2:1);
IR (KBr): 2960, 2847, 1750 (C═O), 1680 (C═O), 1279,
(NO2), 1298, 1220, 1064 cmÀ1 1H-NMR (DMSO-d6): δ 3.97
;
(s, 3 H, OCH3), 7.44 (s, 1 H, CHCHNO2), 7.58 (s, 1 H,
CHCHNO2), 8.25 (d, J = 13.2 Hz, 1 H, ArH), 8.44
(d, J = 13.2 Hz, 1 H, ArH), 10.88 (s, 1 H, OH); 13C-NMR
(CDCl3): δ 61.53 (OCH3), 112.59, 119.34, 124.67 (C-aryl),
130.94 (CHCHNO2), 138.86 (CHCHNO2), 139.34, 146.42,
154.98 (C-aryl); MS (EI, m/z): 240 [M]+; HR-ESI-MS: m/z
calcd for C9H8N2O6 [M + Na]+ 263.0280; found, 263.0223.
6-Hydroxy-7-methoxyindole (5).
Under nitrogen, to a
1209 cmÀ1 1H-NMR (CDCl3): δ 2.35 (s, 3 H, COCH3), 3.91
;
solution of 4 (0.50 g, 2.08 mmol) in dry methanol (10 mL), 10%
Pd/C (0.05 g) and acetic acid (0.10 mL) were added and stirred
at RT for 20 min. Then, ammonium acetate (1.21 g,
19.19 mmol) was added and stirred at RT for 15 h. The Pd/C
was filtered and washed with methanol. The combined solvents
were evaporated, and the crude residue was subjected to column
chromatography (silica gel; petroleum ether–acetone, 3:1) to
obtain 5 as a white crystal, 0.13 g (38%), mp 85°C (lit. [11] mp
85°C); Rf = 0.53 (petroleum ether–acetone, 2:1); IR (KBr): 3495
(OH), 3420 (NH), 3105, 2947, 2843, 1620, 1506, 1411,
(s, 3 H, OCH3), 7.23 (d, J = 7.6 Hz, 1 H, ArH), 7.52–7.46
(m, 2 H, ArH), 9.95 (s, 1 H, CHO); 13C-NMR (CDCl3): δ
20.75 (COCH3), 56.18 (OCH3), 110.89, 123.51, 124.84,
135.31, 145.00, 152.04 (C-aryl), 168.46 (COCH3), 191.16
(CHO); MS (EI, m/z): 194 [M]+. The spectral data are in
agreement with literature values.
Acetic acid 4-formyl-2-methoxy-3-nitro-phenyl ester
(2).
To a solution of fuming nitric acid (40mL) was slowly
added 1 (10.00g, 51.50 mmol) over 20min at À20°C. The
resulting mixture was stirred at this temperature for 0.5 h. Then,
the reaction mixture was poured into ice water (200 mL). The
precipitate was filtered, washed with ice water:ethanol (5:1,v/v)
and dried to give 2 as a white solid, 10.30g (84%), mp 84–85°C
(lit. [6c] mp 87°C, no range given); Rf = 0.40 (petroleum ether–
EtOAc, 2:1); IR (KBr): 2960, 2870, 1776 (C═O), 1709 (C═O),
1333, 1236, 1202, 1047, 725 cmÀ1 1H-NMR (CDCl3): δ 3.98
;
(s, 3 H, OCH3), 5.27 (s, 1 H, OH), 6.50 (s, 1 H, H-pyrrol),
6.81 (d, J = 8.4 Hz, 1 H, ArH), 7.11 (s, 1 H, H-pyrrol), 7.25
(s, 1 H, ArH), 8.09 (s, 1 H, NH); 13C-NMR (CDCl3): δ 60.82
(OCH3), 103.40 (C-pyrrol), 110.30, 116.61, 123.30 (C-aryl),
124.14 (C-pyrrol), 129.20, 131.78, 143.42 (C-aryl); MS
1550 and 1373 (NO2), 1277, 1182cmÀ1 1H-NMR (CDCl3): δ
;
(EI, m/z): 163.1 [M]+.
2.42 (s, 3 H, COCH3), 3.96 (s, 3 H, OCH3), 7.45 (d, J = 8.4 Hz,
1 H, ArH), 7.72 (d, J = 8.4 Hz, 1 H, ArH), 9.91 (s, 1 H, CHO);
13C-NMR (CDCl3): δ 20.94 (COCH3), 63.10 (OCH3), 125.66,
126.17, 126.25, 144.55, 145.71, 149.23 (C-aryl), 167.63
(COCH3), 185.81 (CHO); MS (EI, m/z): 239 [M]+. The spectral
data are in agreement with literature values.
7-Methoxy-1H-indol-6-yl propiolate (6). Under nitrogen,
a solution of propiolic acid (0.67 mL, 10.90 mmol) in dry
CH2Cl2 (50 mL) was stirred at 0°C for 10 min. Then,
dicyclohexylcarbodiimide (2.25 g, 10.90 mmol) in dry CH2Cl2
(5 mL) was added. A white precipitate formed after stirred 15 s.
A solution of 5 (1.18 g, 7.23 mmol) in anhydrous CH2Cl2
(2 mL) was added to the reaction mixture. Lastly, 4-
dimethylamiopryidine (0.12 g, 0.98 mmol) was dissolved in dry
CH2Cl2 and added dropwise to the stirring solution. The
reaction was stirred under nitrogen at 0°C until complete
consumption of 5 was monitored by TLC (2 h), and then the
mixture was concentrated in vacuum. The solid residue was
suspended in EtOAc, filtered, and the filtrate was washed with
brine. The collected organic layers were dried over anhydrous
MgSO4 and evaporated under reduced pressure. The solid
residue was purified by chromatography (silica gel; petroleum
ether–acetone, 3:1) to obtain 6 as a white solid, 0.74 g (48%),
mp 112–113°C; Rf = 0.60 (petroleum ether–acetone, 2:1); IR
(KBr): 3392 (NH), 3259 (C≡CH), 2941, 2810, 2123 (C≡C),
4-Hydroxy-3-methoxy-2-nitro-benzaldehyde (3).
To a
stirred solution of 7% aqueous sodium hydroxide solution
(60 mL) was slowly added 2 (10.30 g, 43.06 mmol), and the
mixture was stirred at RT for 0.5 h. The reaction mixture was
acidified with 2 M HCl at 0°C. The precipitate was filtered,
washed with ice water, and dried to give 3 in dark as a yellow
solid, 8.23 g (97%), mp 135–136°C (lit. [6a] mp 137°C, no
range given); Rf = 0.16 (petroleum ether–EtOAc, 2:1); IR (KBr):
3276 (OH), 2959, 2928, 1670 (C═O), 1575, 1540 and 1373
(NO2), 1317, 1275, 1202 cmÀ1 1H-NMR (CDCl3): δ 3.98 (s,
;
3 H, OCH3), 6.40 (s, 1 H, OH), 7.22 (d, J = 8.4 Hz, 1 H, ArH),
7.66 (d, J = 8.4 Hz, 1 H, ArH), 9.81 (s, 1 H, CHO); 13C-NMR
(CDCl3): δ 63.11 (OCH3), 117.71, 120.96, 128.42, 139.12,
144.53, 155.25 (C-aryl), 185.80 (CHO); MS (EI, m/z): 197
[M]+. The spectral data are in agreement with literature values.
1732 (C═O), 1600, 1500, 1338, 1242, 1200, 1057, 750 cmÀ1
;
1H-NMR (CDCl3): δ 3.09 (s, 1 H, C≡CH), 4.00 (s, 3 H, OCH3),
6.55 (s, 1 H, H-pyrrol), 6.85 (d, J = 8.8 Hz, 1 H, ArH), 7.23
(s, 1 H, H-pyrrol), 7.34 (d, J = 8.8 Hz, 1 H, ArH), 8.40 (s, 1 H,
NH); 13C-NMR (CDCl3): δ 61.08 (OCH3), 74.24(C≡CH),
103.41 (C-pyrrol), 115.00 (C≡CH), 115.98 (C-aryl), 125.16
(C-pyrrol), 128.59, 129.37, 136.05, 136.89 (C-aryl), 151.35
4-Hydroxy-3-methoxy-2,β-dinitrostyrene (4).
To
a
solution of 3 (8.23 g, 41.75 mmol) in acetic acid (100 mL),
ammonium acetate (8.00 g, 103.79 mmol) and nitromethane
(7.64 g, 125.16 mmol) were added under nitrogen and stirred at
120°C for 2 h (or until the reaction was complete as judged by
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet