420 J . Org. Chem., Vol. 62, No. 2, 1997
Alonso et al.
) 6.1, 3H), 2.61 (dd, J ) 13.2, 8.2, 1H), 2.74 (dd, J ) 13.2, 4.6,
1H), 3.78 (s, 6H), 3.96-4.05 (m, 1H), 6.34-6.37 (m, 3H); 13C
NMR δ 22.75, 46.1, 55.25, 68.7, 98.45, 107.3, 140.8, 160.9; MS
m/ z 196 (M+, 41%), 152 (100); HRMS calcd for C11H16O3
196.1099, found 196.1095.
1,3-Dim et h oxy-5-(2′-h yd r oxy-2′-p h en ylet h yl)b en zen e
(4d ): oil, Rf ) 0.29 (hexane/ethyl acetate 2/1); tR )15.88 min;
IR (film) 3439, 3085, 3061, 3028, 1597, 1461, 1205, 1151, 1067
cm-1; 1H NMR δ 2.18 (s, 1H), 2.89 (dd, J ) 13.6, 8.2, 1H), 2.97
(dd, J ) 13.6, 4.9, 1H), 3.72 (s, 6H), 4.86 (dd, J ) 8.2, 4.9, 1H),
6.33, 7.33-7.39 (s and m respectively, 3H and 5H, respec-
tively); 13C NMR δ 46.35, 55.2, 75.0, 98.7, 107.4, 125.85, 127.55,
128.35, 140.25 143.7, 160.8; MS m/ z 258 (M+, 10%), 152 (100);
HRMS calcd for C16H18O3 258.1256, found 258.1260.
Solvents were evaporated (15 Torr), and the resulting residue
1
contained the title compounds 5 (>90% pure by 300 MHz H-
NMR) which were submitted to the next step. Yields are
included in Scheme 1; analytical and spectroscopic data follow.
1,3-Dim eth oxy-5-[2′-(m eth a n esu lfon yloxy)p en tyl]ben -
zen e (5a ): oil, Rf ) 0.34 (hexane/ethyl acetate 2/1); IR (film)
1596, 1463, 1350, 1206, 1172, 1152, 1059 cm-1; 1H NMR δ 0.95
(t, J ) 7.2, 3H), 1.39-1.75 (m, 4H), 2.60 (s, 3H), 2.91 (d, J )
6.4, 2H), 3.78 (s, 6H), 4.80-4.89 (m, 1H), 6.35 (t, J ) 2.1, 1H),
6.39 (d, J ) 2.1, 2H); 13C NMR δ 13.75, 18.45, 36.95, 38.0,
41.45, 55.35, 84.7, 98.85, 107.65, 139.1, 160.95; MS m/ z 302
(M+, 55%), 152 (100).
1,3-Dim eth oxy-5-[2′-(m eth an esu lfon yloxy)tr idecyl]ben -
zen e (5b): oil, Rf ) 0.68 (hexane/ethyl acetate 2/1); IR (film)
1597, 1465, 1351, 1206, 1174, 1064 cm-1; 1H NMR δ 0.88 (t, J
) 6.7, 3H), 1.25-1.49, 1.63-1.88 (2m, 20H and 2H, respec-
tively), 2.59 (s, 3H), 2.91 (d, J ) 6.7, 2H), 3.78 (s, 6H), 4.78-
4.87 (m, 1H), 6.33-6.40 (m, 3H); 13C NMR δ 14.1, 22.65, 25.05,
29.3, 29.4, 29.5, 29.55, 31.85, 34.85, 37.95, 41.3, 45.75, 55.25,
55.3, 85.0, 98.8, 107.6, 139.1, 160.9; MS m/ z 414 (M+, 12%),
152 (100); HRMS calcd for C22H38O5S 414.2440, found 414.2454.
1,3-Dim eth oxy-5-[2′-(m eth a n esu lfon yloxy)p r op yl]ben -
zen e (5c): white solid, Rf ) 0.31 (hexane/ethyl acetate 2/1);
mp 44-45 °C (hexane/ether); IR (KBr) 3016, 1597, 1469, 1345,
1204, 1174, 1155, 1063 cm-1; 1H NMR δ 1.45 (d, J ) 6.1, 3H),
2.62 (s, 3H), 2.82 (dd, J ) 14.0, 5.5, 1H), 2.94 (dd, J ) 14.0,
7.8, 1H), 3.77 (s, 6H), 4.85-4.96 (m, 1H), 6.35 (t, J ) 2.2, 1H),
6.38 (d, J ) 2.2, 2H); 13C NMR δ 21.35, 37.75, 43.1, 55.2, 81.0,
98.75, 107.45, 138.85, 160.85; MS m/ z (M+, 66%), 178 (100),
151 (100). Anal. Calcd for C12H18O5S: C, 52.54; H, 6.62; S,
11.66. Found: C, 53.20; H, 6.73; S, 10.69.
Gen er a l P r oced u r e for th e P r ep a r a tion of Com p ou n d s
6a -c. A mixture of mesylate 5 (1 mmol), sodium iodide (5
mmol), zinc powder (10 mmol), and glyme (10 mL) under argon
atmosphere was refluxed for 8 h. The reaction mixture was
filtered to remove excess sodium iodide and zinc powder.
Then, the filtrate was poured into water (10 mL) and extracted
with ether (2 × 20 mL). The organic layer was washed with
brine, dried over sodium sulfate, and concentrated under
reduced pressure (15 Torr). The residual oil was chromato-
graphed (silica gel, hexane/ethyl acetate) to afford pure title
compounds 6a -c. Yields are included in Scheme 1.
1,3-Dim eth oxy-5-(2′,2′-d im eth yl-3′-h yd r oxybu tyl)ben -
zen e (12b): oil, Rf ) 0.29 (hexane/ethyl acetate 4/1); tR ) 13.46
min; IR (film) 3551, 1607, 1463, 1206, 1153, 1069 cm-1 1H
;
NMR δ 0.99 (s, 9 H), 2.40 (dd, J ) 13.4, 10.8, 1H), 2.85 (dd, J
) 13.4, 1.5, 1H), 3.43 (m, 1H), 3.77 (s, 6 H), 6.33 (t, J ) 2.2,
1H), 6.39 (d, J ) 2.2, 1H); 13C NMR δ 25.8, 34.7, 38.75, 55.2,
80.3, 98.35, 107.15, 142.2, 160.9; MS m/ z 238 (M+, 40%), 152
(100); HRMS calcd for C14H22O3 238.1569, found 238.1570.
1,3-Dim eth oxy-5-(2′-h yd r oxyh ep tyl)ben zen e (12c): oil,
Rf ) 0.17 (hexane/ethyl acetate 6/1); tR ) 14.66 min; IR (film)
3420, 1596, 1463, 1206, 1151, 1069 cm-1; 1H NMR δ 0.89 (t, J
) 6.7, 3H), 1.26-1.66 (m, 9H), 2.56 (dd, J ) 13.4, 8.5, 1H),
2.77 (dd, J ) 13.4, 4.0, 1H), 3.78 (m, 7H), 6.34 (t, J ) 2.1, 1H),
6.37 (d, J ) 2.1, 2H); 13C NMR δ 13.95, 22.55, 25.35, 31.75,
36.7, 44.3, 55.1, 72.4, 98.25, 107.25, 140.95, 160.75; MS m/ z
252 (M+, 33%), 152 (100); HRMS calcd for C15H24O3 252.1725,
found 252.1735.
2-(3,5-Dim e t h oxyp h e n yl)-1-(4-h yd r oxyp h e n yl)e t h a -
n ol (12d ): white solid, Rf ) 0.32 (hexane/ethyl acetate 1/1);
mp 148-149 °C (hexane/MeOH); tR ) 18.44 min; IR (KBr)
3416, 3198, 1606, 1517, 1202, 1143, 1067 cm-1 1H NMR δ
;
(CD3COCD3) 2.81-2.95 (m, 2H), 3.71 (s, 6H), 4.04 (d, J ) 3.7,
1H), 4.77-4.82 (m, 1H), 6.28, 6.35 (t and d respectively, J )
2.0 Hz, 1H and 2H, respectively), 6.76, 7.18 (2d, J ) 8.5, 4H),
8.18 (br s, 1H); 13C NMR δ (CD3COCD3) 47.35, 55.35, 75.15,
98.7, 108.35, 115.5, 128.1, 137.3, 142.35, 157.2, 161.45; MS
m/ z 256 (M+ -18, 100%). Anal. Calcd for C16H18O4: C, 70.04;
H, 6.62. Found: C, 69.59; H, 6.68.
1-(3,5-Dim eth oxyben zyl)cycloh exa n ol (12e): oil, Rf
)
P r ep a r a tion of 1,3-Dim eth oxy-5-(2′-p h en yleth yl)ben -
zen e (6d ). A mixture of alcohol 4d (1 mmol) and palladium
on activated charcoal (60 mg) in a mixture of methanol-water
(5 mL/3 mL) was stirred under atmospheric pressure of
hydrogen during 36 h. The mixture was filtered through a
plug of Celite with ether to remove the catalyst. Then the
filtrate was poured into water (5 mL) and extracted with ether
(2 × 20 mL). The organic layer was washed with brine, dried
over sodium sulfate, and concentrated under reduced pressure
(15 Torr). The residual oil was chromatographed (silica gel,
hexane/ethyl acetate) to afford pure 6d . Yield is included in
Scheme 1.
0.29 (hexane/ethyl acetate 4/1); tR ) 14.97 min; IR (film) 3504,
1
1596, 1462, 1205, 1150, 1062 cm-1; H NMR δ 1.21-1.75 (m,
11H), 2.68 (s, 2H), 3.78 (s, 6H), 6.37 (s, 3H); 13C NMR δ 22.1,
25.75, 37.35, 48.95, 55.2, 71.0, 98.3, 108.6, 139.35, 160.5; MS
m/ z 250 (M+, 12%), 152 (100); HRMS calcd for C15H22O3
250.1569, found 250.1570.
(3,5-Dim eth oxyp h en yl)-N-p h en yla ceta m id e (12f): oil, Rf
) 0.39 (hexane/ethyl acetate 1/1); tR ) 17.31 min; IR (film)
1
3303, 1662, 1597, 1205, 1154, 1066 cm-1; H NMR δ 3.67 (s,
2H), 3.80 (s, 6H), 6.43, 6.47 (2m, 1H and 2H, respectively),
7.28-7.53 (m, 5H); 13C NMR δ 45.2, 55.4, 99.6, 107.5, 119.8,
124.45, 128.95, 136.5, 137.55, 161.45, 168.75; MS m/ z 271 (M+,
68%), 152 (100); HRMS calcd for C16H17NO3 271.1208, found
271.1205.
Gen er a l P r oced u r e for th e P r ep a r a tion of Ca th ecols
7a -d . A solution of methyl ether 6 (1 mmol) in 3 mL of 45%
hydrobromic acid and 3 mL of glacial acetic acid was refluxed
for 3 h. The reaction mixture was hydrolyzed with water (15
mL) and extracted with ether (2 × 20 mL). The organic layer
2-(3,5-Dim eth oxyph en yl)-N,1-diph en yleth ylam in e (12g):
oil, Rf ) 0.56 (hexane/ethyl acetate 2/1); tR ) 19.91 min; IR
(film) 3404, 3052, 3023, 1601, 1505, 1204, 1151, 1067 cm-1
;
1H RMN δ 2.93 (dd, J ) 13.8, 8.2, 1H), 3.08 (dd, J ) 13.8, 5.8,
1H), 3.71 (s, 6H), 4.16 (br s, 1H), 4.56 (dd, J ) 8.2, 5.8, 1H),
6.25 (d, J ) 2.1, 2H), 6.32 (t, J ) 2.1, 1H), 6.46 (d, J ) 7.6,
2H), 6.60 (t, J ) 7.6, 1H), 7.05 (t, J ) 7.6, 2H), 7.23-7.36 (m,
5H); 13C NMR δ 45.35, 55.15, 58.95, 98.7, 107.2, 113.6, 117.4,
126.45, 127.0, 128.5, 128.95, 139.8, 143.35, 147.2, 160.75; MS
m/ z 333 (M+, 1%), 182 (100); HRMS calcd for C22H23NO2
333.1729, found 333.1722.
was washed with brine, dried over Na2
SO4, and concentrated
under reduced pressure (15 Torr). The residual oil was
chromatographed (silica gel, hexane/ethyl acetate) to afford
pure title 7. Yields are included in Scheme 1.
P r ep a r a tion of 1,3-Dim eth oxy-5-(2′-p h en yleth en yl)-
ben zen e (8d ). A mixture of compound 4d (1 mmol) and 85%
phosphoric acid 0.5 mL in toluene (5 mL) was refluxed for 2
h. The resulting mixture was extracted with diethyl ether (2
× 20 mL) and the organic layer dried over anhyd Na2SO4 and
evaporated (15 Torr). The obtained residue was purified by
column chromatography (silica gel, hexane/ethyl acetate),
yielding the pure title compound 8d . Yield is included in
Scheme 2.
Gen er a l P r oced u r e for th e P r ep a r a tion of Mesyla tes
5. To a solution of the corresponding alcohol 4 (1 mmol) and
triethylamine (1.25 mmol) in THF (5 mL) at 0 °C was dropwise
added methanesulfonyl chloride (1.2 mmol) over a period of 5
min. Stirring for additional 60 min completed reaction. The
reaction mixture was hydrolyzed with water (10 mL) and
extracted with ether (2 × 20 mL). The organic layer was
washed with water (1 × 10 mL) and dried over anhyd Na2SO4.
P r ep a r a t ion of (E)-1-(1,3-Dih yd r oxyp h en yl)-2-p h en -
yleth en e (P in osylvin e, 9d ). To a 100 mL flask under an
atmosphere of argon was added approximately 30 mL of 1,2-