2548
QI JinPing, et al. Sci China Chem December (2010) Vol.53 No.12
1
the ref. [16], mp 81–83 °C (ref. [16] 82–84 °C); H NMR
(400 MHz, CDCl3) 3.52 (s, 3H, OCH3), 3.83 (s, 3H,
(400 MHz, CDCl3) 3.86 (s, 3H, OCH3), 5.27 (brs, 2H,
OH), 6.48 (d, J = 8.0 Hz, 2H, Ar-H), 6.86 (t, J = 8.0 Hz,
OCH3), 3.85 (s, 3H, OCH3), 5.17 (s, 2H, CH2), 6.80 (d, 1H,
3
3
3
3J = 8.8 Hz, Ar-H), 6.85 (d, 1H, J = 8.8 Hz, Ar-H). 13C
1H, Ar-H).
NMR (CDCl3, 100 MHz): 56.4, 56.5, 60.3, 87.3, 95.7,
110.6, 113.1, 148.1, 150.0, 150.9. MS (APCI): m/z 324.1
(M+). Anal. calcd for C10H13O4I: C, 37.06 ; H, 4.04. Found:
C, 37.13; H, 4.48.
Synthesis of 4-iodo-2-methoxyresorcinol (4)
To a stirred solution of 3 (700 mg, 5 mmol) and I2 (305 mg,
6 mmol) in 10 mL of CH3CN, ammonium ceric nitrate
(CAN) (10 mol%) was added. After 10 h, the reaction was
completed. The mixture was diluted with saturated aqueous
sodium bisulfite (5 mL), followed by extraction with ethyl
acetate (3 ×20 mL). The combined organic layer was washed
with saturated brine, and then dried with anhydrous MgSO4.
The solvent was removed under vacuum and the residue
was purified by column chromatography (petroleum ether:
ethyl acetate, 5:1) to give 4 (1.197 g, 90%) as white solid,
mp 111–113 °C. 1H NMR (400 MHz, CDCl3): 3.89 (s, 3H,
OCH3), 5.49 (s, 1H, OH), 5.55 (s, 1H, OH), 6.38 (d, 1H,
3J=8.8 Hz, Ar-H), 7.25 (d, 1H, 3J=8.8 Hz, Ar-H). 13C NMR
(100 MHz, CDCl3): 151.9, 151.5, 133.5, 110.8, 108.1,
71.3, 60.7. MS (APCI): m/z 264.1 (M+-2H). Anal. calcd for
C7H7O3I: C, 31.60; H, 2.65. Found: C, 32.58; H, 2.63.
Synthesis of 4-(2,3-dimethoxy-6-(methoxymethoxy)phenyl)-
2-methylbut-3-yn-2-ol (9)
8 (1.1 g, 3.4 mmol) and 3-methyl-3-hydroxy-1-butyne (350
mg, 1.2 equiv) were dissolved in 30 mL of N,N-diisopro-
pylamine. A gentle stream of nitrogen was bubbled into the
mixture for 20 min. After addition of Pd(PPh3)2Cl2 (119.2
mg, 5 mol%) and CuI (32.5 mg, 5 mol%), the mixture was
heated to 50 °C. The mixture immediately turned dark and a
white solid precipitated. After 4 h, the reaction was com-
pleted, and then the mixture was cooled to room tempera-
ture. The solvent was removed by filtration under a reduced
pressure to yield a residue as a yellow oil. The residue was
diluted with ethyl acetate and washed with saturated brine
twice. The organic phase was dried over anhydrous Na2SO4
and the residue was purified by column chromatography
(petroleum ether:ethyl acetate, 5:1) to give 9 (799 mg, 84%)
as a pale yellow oil. 1H NMR (400 MHz, CDCl3) 1.59 (s,
3H, CH3), 1.60 (s, 3H, CH3), 2.93 (s, 1H, OH), 3.48 (s, 3H,
OCH3), 3.77 (s, 3H, OCH3), 3.87 (s, 3H, OCH3), 5.12 (s, 2H,
Synthesis of 1,2-dimethoxy-4-(methoxymethoxy)benzene (6)
Bromomethyl methyl ether (MOMBr) (0.11 mL, 1.5 mmol)
was added dropwise to a stirred solution of 3, 4-dimeth-
oxyphenol 5 (155 mg, 1 mmol) and N,N-diisopropylethyl-
amine (0.35 ml, 2 mmol) in dry CH2Cl2 (3 mL) at 0 °C under
argon. After stirring at room temperature for 17 h, the reac-
tion was quenched with 1% aqueous HCl (0.20 mL), and the
organic layer was washed with saturated NaHCO3 aqueous
solution and brine, and then dried over anhydrous Na2SO4.
The solvent was removed in vacuum, and the residue was
purified by column chromatography (petroleum ether:ethyl
acetate, 5:1) to give 6 (148 mg, 75%) as a colorless liquid.
1H NMR (400 MHz, CDCl3) 3.46 (s, 3H, OCH3), 3.81 (s,
3H, OCH3), 3.83 (s, 3H, OCH3), 5.09 (s, 2H, CH2), 6.56 (dd,
3
3
CH2), 6.73 (d, 1H, J = 8.8 Hz, Ar-H), 6.76 (d, 1H, J = 8.8
Hz, Ar-H). 13C NMR (CDCl3, 100 MHz): 31.3, 56.2, 56.5,
60.8, 65.5, 74.1, 95.8, 102.4, 109.6, 111.4, 113.2, 148.0,
151.1, 152.0. MS (APCI): m/z 280.2 (M+).
Synthesis of 2-ethynyl-3,4-dimethoxy-1-(methoxymethoxy)
benzene (10)
A mixture of 9 (448 mg, 1.6 mmol) and pulverized KOH
(448 mg, 5.0 eq) in 20 mL of iso-propanol was refluxed
under N2 with vigorous stirring for 2 h. The solution was
washed with water (2 × 20 mL) and brine, dried over anhy-
drous Na2SO4. The solvent was removed in vacuum, and the
residue was purified by column chromatography (petroleum
ether:ethyl acetate, 10:1) to give 10 (301 mg, 85%) as a pale
yellow oil. 1H NMR (CDCl3, 400 MHz): 3.46 (s, 1H, ace-
tylenic H), 3.48 (s, 3H, CH3), 3.79 (s, 3H, OCH3), 3.91 (s,
3H, OCH3), 5.16 (s, 2H, CH2), 6.78 (d, 1H, 3J = 8.8 Hz,
3
4
4
1H, J = 8.8 Hz, J = 2.4 Hz, Ar-H), 6.62 (d, J = 2.4 Hz,
Ar-H), 6.75 (d, 1H, 3J = 8.8 Hz, Ar-H).
Synthesis of 2-iodo-3,4-dimethoxy-1-(methoxy-methoxy)
benzene (8)
n-BuLi in n-hexane (2.5 M, 0.6 mL, 1.5 mmol) was added
dropwise to a stirred solution of 6 (198 mg, 1 mmol) and
5 mL dry ether at room temperature under argon. After 1 h,
I2 (0.307 g, 1.2 mmol) dissolved in 3 mL of dry ether was
added dropwise to the solution during 20 min. In the end a
distinct orange color due to excess I2 was noted and the
white, insoluble organolithium compound disappeared, re-
sulting in a clear solution. The ether solution was washed
with sodium thiosulfate aqueous solution (5 mL, 20%) to
remove I2 and LiI. After drying over anhydrous CaCl2, the
ether was evaporated in vacuum and the residue was puri-
fied by column chromatography (petroleum ether:ethyl ace-
tate, 10:1) to give 8 (233 mg, 72%) as a yellow oil. 1H NMR
3
Ar-H), 6.81 (d, 1H, J = 8.8 Hz, Ar-H). 13C NMR (CDCl3,
100 MHz): 56.1, 56.4, 60.9, 75.8, 85.2, 95.5, 108.5, 110.6,
113.8, 147.7, 151.9, 152.8. MS (APCI): m/z 222.3 (M+).
Synthesis of benzo[b] furan (11)
10 was added to a stirred mixture of 4 (266 mg, 1 mmol),
Pd(Ph3P)2Cl2 (35 mg, 5 mol%), CuI (19 mg, 10 mol%) in
Et3N/DMF (1:5, 10 mL) under N2. The mixture was stirred
at 80 °C for 18 h. The solution was washed with water (2 ×
20 mL) and brine, dried over anhydrous Na2SO4. Then the
mixture was filtered and evaporated under vacuum, The