(50 mL), H2O (50 mL) and THF (50 mL) were then added; the
organic layer was subsequently collected, and the aq. layer was
extracted with Et2O (2 × 50 mL). The organic layers were com-
bined, washed with brine (2 × 50 mL), dried over MgSO4, and
filtered. The filtrate was evaporated to give a white powder that
stirred mixture of NaOH (3.0 g, 75 mmol) and 11 (1.5 g,
3.8 mmol) in THF/H2O (50 mL/50 mL) at r.t. After 16 h, aq.
NH4Cl (100 mL) and THF (50 mL) were added; the organic
layer was collected, and the aq. layer was extracted with Et2O
(2 × 50 mL). The organic layers were combined, dried over
MgSO4, and then filtered. The filtrate was evaporated to give a
residue that was dissolved in minimum CH2Cl2 and loaded onto
a silica gel column; hexanes–EtOAc (7 : 3) was used as elutant.
The appropriate fractions were collected and evaporated to yield
a white solid that was washed with hexanes–EtOAc (7 : 3, 2 ×
20 mL), collected, and dried in vacuo. Yield = 0.43 g (39%). 1H
NMR (600 MHz, CDCl3): δ 3.45 (CHOH, s, 1H), 3.89 and 3.90
(OCH3, s, 3H each), 3.96 (CHH, t, 1H, J = 10), 4.16 (CHH, dd,
1H, J = 9.9, 3.0), 5.03 (CHOH, d, 1H, J = 9.0), 5.64 (Ar–OH, s,
1H), 6.85–7.06 (Ar–H, m, 7H); the data agree with those
reported.25 13C{1H} NMR (150 MHz, CDCl3): δ 55.98 (OCH3),
56.06 (OCH3), 72.29 (CHOH), 76.56 (CH2), 108.86, 112.07,
114.34, 116.20, 119.48, 121.22, 122.71, 131.61, 145.53, 146.76,
148.10, 150.29. ESI/MS+: 313 [M + Na]+. Anal. Calcd for
C16H18O5·0.3H2O: C, 64.99; H, 6.34. Found: C, 65.0; H 6.1.
1
was dried in vacuo. Yield = 1.9 g (77%). H NMR (600 MHz,
CDCl3): δ 1.46 (OCH2CH3, t, 3H, J = 7.2), 3.75 (OH, s, 1H),
3.87 and 3.88 (OCH3, s, 3H each), 3.97 (CHH, t, 1H, J = 10),
4.09 (OCH2CH3, q, 2H, J = 6.6), 4.15 (CHH, dd, 1H, J = 9.6,
3.0), 5.05 (CHOH, dd, 1H, J = 9.9, 3.0), 6.83–7.03 (Ar–H, m,
7H). 13C{1H} NMR (150 MHz, CDCl3): δ 14.90 (OCH2CH3),
55.91 (OCH3), 56.01 (OCH3), 64.44 (OCH2CH3), 72.18
(CHOH), 76.23 (CH2), 109.71, 112.00, 112.56, 115.67, 118.69,
121.19, 122.45, 132.21, 148.06, 148.11, 149.43, 150.00. ESI/
MS+: 341 [M + Na]+. Anal. Calcd for C18H22O5·H2O: C, 64.27;
H, 7.19. Found: C, 64.3; H, 7.2.
4-Benzoyl-3-methoxy-bromoacetylbenzene (10).25,27 Benzoyl
chloride (19 g, 0.14 mol) and pyridine (11 g, 0.14 mol) were
added drop-wise to a stirred reaction mixture of acetovanillone
(20 g, 0.12 mol) in CHCl3 (100 mL) at r.t. After 1 h, the solvent
was removed and the residue was extracted with EtOAc (2 ×
100 mL). This solvent was then removed, and the residue was
dissolved in CHCl3 (100 mL). Br2 (19 g, 0.12 mol) was then
added drop-wise, and the mixture was then stirred for 16 h at r.t.
Subsequent evaporation of the solvent gave a white solid that
was recrystallized from hexanes–EtOAc (7 : 3, 200 mL), filtered
off, washed with hexanes (2 × 40 mL), and dried in vacuo. Yield
1-(4-Hydroxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)-
ethanone (6). The procedure was identical to that used for the
synthesis of 3, the corresponding alcohol, but with omission of
the NaBH4 treatment. The fraction containing 6 from the silica
gel column was initially obtained as a colourless oil, but drying
1
in vacuo gave a white solid. Yield = 0.37 g (34%). H NMR
(600 MHz, CDCl3): δ 3.88 and 3.93 (OCH3, s, 3H each), 5.29
(CH2, s, 2H), 6.22 (OH, s, 1H), 6.81–6.87 (Ar–H, m, 2H),
6.88–6.99 (Ar–H, m, 3H), 7.58–7.64 (Ar–H, m, 2H). 13C{1H}
NMR (150 MHz, CDCl3): δ 55.98 (OCH3), 56.19 (OCH3),
71.96 (CH2), 110.24, 112.19, 114.12, 114.67, 120.89, 122.41,
123.43, 127.61, 146.92, 147.64, 149.76, 151.07, 193.24 (CvO).
ESI/MS+: 311 [M + Na]+. Anal. Calcd for C16H16O5·0.5H2O: C,
64.64; H, 5.76. Found: C, 64.5; H, 5.4.
1
= 30 g (74%). H NMR (400 MHz, CDCl3): δ 3.89 (OCH3, s,
3H), 4.46 (CH2, s, 2H), 7.28 (Ar–H, d, 1H, J = 8.4), 7.53 (Ar–
H, t, 2H, J = 7.6), 7.61–7.69 (Ar–H, m, 3H), 8.21 (Ar–H, d, 2H,
J = 6.8); the data agree with those reported.25,27 13C{1H} NMR
(100 MHz, CDCl3): δ 30.69 (CH2Br), 56.29 (OCH3), 112.52,
122.54, 123.35, 128.77, 128.95, 130.52, 132.84, 133.98, 144.95,
152.09, 164.28 (OvC–O), 190.42 (OvCCH2). ESI/MS+: 371
[M + Na]+. Anal. Calcd for C16H13O4Br: C, 55.04; H, 3.75.
Found: C, 55.0; H, 3.7.
3-Hydroxy-2-(2-methoxyphenoxy)-1-phenyl-1-propanone (7).
A 1 : 1 EtOH–acetone solution (30 mL) containing 4 (1.00 g,
4.13 mmol), K2CO3 (685 mg, 4.96 mmol), and formaldehyde
(516 mg, 6.36 mmol, purchased as a 37% by weight aq. solution
with ∼10% MeOH) was stirred for 2 h at r.t. The solvent was
evaporated off to leave a residue that was extracted with CH2Cl2.
The extracts were purified via silica gel chromatography
(2 : 1 hexanes–EtOAc), the appropriate fractions being collected,
evaporated to dryness, and re-precipitated with CH2Cl2/hexanes
to yield a white solid that was collected and dried in vacuo.
1-(4-Benzoyl-3-methoxyphenyl)-2-(2-methoxyphenoxy)-
ethanone (11).25,27 Guaiacol (2.2 g, 18 mmol) was added drop-
wise to a stirred acetone solution (150 mL) of K2CO3 (2.5 g,
18 mmol) and 10 (5.0 g, 14 mmol) at r.t. After 16 h, the solid
was filtered off, and the filtrate was evaporated to give a residue
that was loaded onto a silica gel column; hexanes–EtOAc (7 : 3)
was used as elutant. The appropriate fractions were collected and
evaporated to yield a white powder that was washed with
hexanes–EtOAc (7 : 3, 2 × 20 mL) and then dried in vacuo.
1
Yield = 290 mg (26%). H NMR (400 MHz, CDCl3): δ 3.03
1
Yield = 1.8 g (32%). H NMR (400 MHz, CDCl3): δ 3.88 and
(OH, t, 1H, J = 6.2), 3.85 (OCH3, s, 3H), 4.07 (HOCH2, m, 2H),
5.44 (CH, t, 1H, J = 5.2), 6.83 (Ar–H, t, 1H, J = 7.8), 6.92 (Ar–
H, d, 2H, J = 7.2), 7.02 (Ar–H, t, 1H, J = 7.6), 7.48 (Ar–H, t,
2H, J = 7.6), 7.60 (Ar–H, t, 1H, J = 7.4), 8.06 (Ar–H, d, 2H, J =
7.2). 13C{1H} NMR (100 MHz, CDCl3): δ 55.95 (OCH3), 63.57
(HOCH2), 85.00 (CH), 112.51, 119.05, 121.35, 123.95, 128.93,
133.92, 135.14, 147.05, 150.71, 196.75 (CvO). ESI/MS+: 295
[M + Na]+. Anal Calcd for C16H16O4·0.5H2O: C, 68.31;
H, 6.09. Found: C, 68.3; H, 6.1.
3.89 (OCH3, s, 3H each), 5.34 (CH2, s, 2H), 6.83–7.03 (Ar–H,
m, 4H), 7.27 (Ar–H, d, 1H, J = 8.4), 7.52 (Ar–H, t, 2H, J = 8.0),
7.62–7.75 (Ar–H, m, 3H), 8.21 (Ar–H, d, 2H, J = 6.8); the data
agree with those reported.23,25 13C{1H} NMR (100 MHz,
CDCl3): δ 56.01 (OCH3), 56.26 (OCH3), 72.35 (CH2), 112.05,
112.32, 115.05, 120.96, 121.53, 122.71, 123.39, 128.75, 129.01,
130.52, 133.52, 133.93, 144.73, 147.53, 149.92, 152,01, 164.33
(OvC–O), 193.76 (OvCCH2). ESI/MS+: 415 [M + Na]+. Anal.
Calcd for C23H20O6: C, 70.40; H, 5.14. Found: C, 69.9; H, 5.1
Methyl 2-(2-methoxyphenoxy)acetate (12).28 Methyl bromo-
acetate (10 g, 65 mmol) and guaiacol (7.4 g, 60 mmol) were
added drop-wise to a stirred mixture of K2CO3 (9.0 g, 65 mmol)
1-(4-Hydroxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)ethanol
(3).27 NaBH4 (0.32 g, 8.5 mmol) was added over 5 min to a
This journal is © The Royal Society of Chemistry 2012
Dalton Trans., 2012, 41, 11093–11106 | 11103