Deprotection of Alkyl Aryl Ethers
J . Org. Chem., Vol. 62, No. 12, 1997 4103
55.3, 92.0, 101.4, 106.7, 117.3, 133.9, 161.6, 164.2; IR (neat)
3267 (br s), 2942 (s), 2218 (s), 1607 (m) cm-1; MS m/ z (relative
intensity) 149 (M+, 100), 134 (10), 119 (16), 106 (57), 91 (38),
79 (14), 69 (12), 63 (19), 51 (20).
The reaction mixture was worked up, and the residue was
purified by chromatography (50% EtOAc in hexanes as eluant)
to give pure 24 (61.9 mg, 0.458 mmol) as a yellow solid in 96%
yield.
3-Meth ylca tech ol (28). The standard procedure was fol-
lowed by use of 1,2-dimethoxy-3-methylbenzene (25; 102 mg,
0.671 mmol, 1.0 equiv), LDA (2.0 M, 1.7 mL, 3.4 mmol, 5.0
equiv), and DMEU (0.50 mL). The reaction mixture was
worked up, and the residue was purified by chromatography
(30% EtOAc in hexanes as eluant) to give pure 28 (78.0 mg,
0.628 mmol) as a light yellow solid36a in 94% yield: mp 66-
67 °C (lit.36b mp 65-68 °C).
4-Eth ylca tech ol (29). The standard procedure was fol-
lowed by use of 4-ethyl-1,2-dimethoxybenzene (26; 103 mg,
0.617 mmol, 1.0 equiv), LDA (2.0 M, 1.6 mL, 3.1 mmol, 5.0
equiv), and DMEU (0.50 mL). The reaction mixture was
worked up, and the residue was purified by chromatography
(30% EtOAc in hexanes as eluant) to give pure 29 (81.2 mg,
0.588 mmol) as a light yellow solid in 95% yield.
4-ter t-Bu tylca tech ol (30). Meth od 1. The standard
procedure was followed by use of 4-tert-butyl-1,2-dimethoxy-
benzene (27; 99.5 mg, 0.512 mmol, 1.0 equiv), LDA (2.0 M,
1.3 mL, 2.6 mmol, 5.0 equiv), and DMEU (0.50 mL). The
reaction mixture was worked up, and the residue was purified
by chromatography (30% EtOAc in hexanes as eluant) to give
pure 30 (79.0 mg, 0.475 mmol) as a yellow solid36a in 93%
yield: mp 55-56 °C (lit.36b mp 52-55 °C).
Meth od 2. The standard procedure was followed by use of
4-tert-butyl-1,2-(methylenedioxy)benzene (54; 115 mg, 0.646
mmol, 1.0 equiv), NaN(SiMe3)2 (1.0 M, 1.6 mL, 1.6 mmol, 2.5
equiv), and DMEU (0.50 mL). The reaction mixture was
worked up, and the residue was purified by chromatography
(30% EtOAc in hexanes as eluant) to give pure 30 (100 mg,
0.602 mmol) as a yellow solid in 93% yield.
Meth od 2. The standard procedure was followed by use of
2,4-dimethoxybenzonitrile (9; 154 mg, 0.942 mmol, 1.0 equiv),
LDA (2.0 M, 1.2 mL, 2.4 mmol, 2.5 equiv), and DMEU (0.50
mL). The reaction mixture was worked up, and the residue
was purified by chromatography (50% EtOAc in hexanes as
eluant) to give pure 21 (128 mg, 0.858 mmol) as a yellow solid
in 91% yield.
2-H yd r oxy-6-m et h oxyb en zon it r ile (22).38 Met h od 1.
The standard procedure was followed by use of 2,6-dimethoxy-
benzonitrile (10; 106 mg, 0.648 mmol, 1.0 equiv), NaN(SiMe3)2
(1.0 M, 1.6 mL, 1.6 mmol, 2.5 equiv), and DMEU (0.50 mL).
The reaction mixture was worked up, and the residue was
purified by chromatography (50% EtOAc in hexanes as eluant)
to give pure 22 (85.9 mg, 0.576 mmol) as a white solid in 89%
yield: mp 164-165 °C (lit.38 mp 163-166 °C); GC tR 11.94 min;
1
TLC Rf 0.30 (50% EtOAc in hexanes); H NMR (DMSO-d6
+
CDCl3, 400 MHz) δ 3.88 (s, 3 H), 6.39 (d, J ) 8.4 Hz, 1 H),
6.57 (d, J ) 8.4 Hz, 1 H), 7.28 (dd, J ) 8.4, 8.4 Hz, 1 H); IR
(neat) 3245 (br s), 2231 (s), 1525 (m), 1478 (m) cm-1; MS m/ z
(relative intensity) 149 (M+, 100), 134 (1), 122 (15), 106 (53),
93 (14), 91 (12), 78 (16), 63 (12), 51 (12).
Meth od 2. The standard procedure was followed by use of
2,6-dimethoxybenzonitrile (10; 154 mg, 0.946 mmol, 1.0 equiv),
LDA (2.0 M, 1.2 mL, 2.4 mmol, 2.5 equiv), and DMEU (0.50
mL). The reaction mixture was worked up, and the residue
was purified by chromatography (50% EtOAc in hexanes as
eluant) to give pure 22 (131 mg, 0.878 mmol) as a white solid
in 93% yield.
4-Hydr oxy-3-m eth oxyben zon itr ile (23). Meth od 1. The
standard procedure was followed by use of 3,4-dimethoxyben-
zonitrile (11; 154 mg, 0.941 mmol, 1.0 equiv), NaN(SiMe3)2 (1.0
M, 2.4 mL, 2.4 mmol, 2.5 equiv), and DMEU (0.50 mL). The
reaction mixture was worked up, and the residue was purified
by chromatography (50% EtOAc in hexanes as eluant) to give
pure 23 (39.5 mg, 0.265 mmol) as a yellow solid36a in 28% yield
and 24 (66.8 mg, 0.494 mmol) as a yellow solid in 53% yield.
For 23: mp 87-88 °C (lit.36b mp 85-87 °C).
Meth od 3. The standard procedure was followed by use of
4-tert-butyl-1,2-(methylenedioxy)benzene (54; 105 mg, 0.587
mmol, 1.0 equiv), LDA (2.0 M, 0.75 mL, 1.5 mmol, 2.5 equiv),
and DMEU (0.50 mL). The reaction mixture was worked up,
and the residue was purified by chromatography (50% EtOAc
in hexanes as eluant) to give pure 30 (91.9 mg, 0.553 mmol)
as a yellow solid in 94% yield.
2-Meth oxy-6-m eth ylp h en ol (31) a n d 2-Meth oxy-3-m e-
th ylp h en ol (34).40 The standard procedure was followed by
use of 1,2-dimethoxy-3-methylbenzene (25; 155 mg, 1.02 mmol,
1.0 equiv), NaN(SiMe3)2 (1.0 M, 2.6 mL, 2.6 mmol, 2.5 equiv),
and DMEU (0.50 mL). The reaction mixture was worked up,
and the residue was purified by chromatography (10% EtOAc
in hexanes as eluant) to give pure 31 (34.8 mg, 0.252 mmol)
as a light yellow solid in 25% yield and 34 (81.6 mg, 0.591
mmol) as a light yellow liquid in 58% yield. For 31: mp 40-
41 °C (lit.40 mp 41-42 °C); GC tR 6.91 min; TLC Rf 0.28 (10%
EtOAc in hexanes); 1H NMR (CDCl3, 300 MHz) δ 2.32 (s, 3
H), 3.81 (s, 3 H), 5.87 (br s, 1 H), 6.71 (d, J ) 7.5 Hz, 1 H),
6.82 (d, J ) 7.5 Hz, 1 H), 6.93 (dd, J ) 7.5, 7.5 Hz, 1 H); 13C
NMR (CDCl3, 100 MHz) δ 15.8, 60.5, 113.2, 122.5, 124.6, 130.8,
145.5, 148.9; IR (neat) 3427 (br s), 2946 (s), 1597 (m), 1467
(m), 1279 (m) cm-1; MS m/ z (relative intensity) 138 (M+, 57),
123 (100), 95 (18), 77 (27), 67 (16), 65 (11), 51 (10).
Meth od 2. The standard procedure was followed by use of
3,4-dimethoxybenzonitrile (11; 247 mg, 1.49 mmol, 1.0 equiv),
LDA (2.0 M, 1.8 mL, 3.7 mmol, 2.5 equiv), and DMEU (0.50
mL). The reaction mixture was worked up, and the residue
was purified by chromatography (50% EtOAc in hexanes as
eluant) to give pure 23 (44.9 mg, 0.301 mmol) as a yellow solid
in 20% yield and 24 (125 mg, 0.925 mmol) as a yellow solid in
62% yield.
3,4-Dih yd r oxyben zon itr ile (24).39 Meth od 1. The stan-
dard procedure was followed by use of 3,4-dimethoxybenzoni-
trile (11; 87.8 mg, 0.538 mmol, 1.0 equiv), LDA (2.0 M, 1.4
mL, 2.7 mmol, 5.0 equiv), and DMEU (0.50 mL). The reaction
mixture was worked up, and the residue was purified by
chromatography (50% EtOAc in hexanes as eluant) to give
pure 24 (68.3 mg, 0.505 mmol) as a yellow solid in 94% yield:
mp 127-129 °C (lit.39 mp 128-130 °C); TLC Rf 0.30 (50%
EtOAc in hexanes); 1H NMR (CDCl3, 400 MHz) δ 6.89 (d, J )
8.8 Hz, 1 H), 7.05 (d, J ) 8.8 Hz, 1 H), 7.13 (s, 1 H); IR (neat)
3291 (br s), 2233 (s), 1605 (m) cm-1; MS m/ z (relative
intensity) 135 (M+, 100), 117 (12), 106 (11), 89 (38), 79 (10),
62 (28), 52 (25), 51 (22).
Meth od 2. The standard procedure was followed by use of
piperonylonitrile (55; 141 mg, 0.955 mmol, 1.0 equiv), NaN-
(SiMe3)2 (1.0 M, 2.4 mL, 2.4 mmol, 2.5 equiv), and DMEU (0.50
mL). The reaction mixture was worked up, and the residue
was purified by chromatography (50% EtOAc in hexanes as
eluant) to give pure 24 (122 mg, 0.903 mmol) as a yellow solid
in 95% yield.
Meth od 3. The standard procedure was followed by use of
piperonylonitrile (55; 70.6 mg, 0.479 mmol, 1.0 equiv), LDA
(2.0 M, 0.60 mL, 1.2 mmol, 2.5 equiv), and DMEU (0.50 mL).
For 34:41 GC tR 7.62 min; TLC Rf 0.45 (10% EtOAc in
1
hexanes); H NMR (CDCl3, 400 MHz) δ 2.26 (s, 3 H), 3.87 (s,
3 H), 5.70 (br s, 1 H), 6.71-6.75 (m, 3 H); 13C NMR (CDCl3,
100 MHz) δ 15.3, 55.9, 108.2, 119.1, 123.1, 123.9, 143.7, 146.2;
IR (neat) 3499 (br s), 2942 (s), 1619 (m), 1473 (m), 1355 (w),
1273 (m) cm-1; MS m/ z (relative intensity) 138 (M+, 65), 123
(100), 105 (4), 95 (25), 77 (31), 67 (17), 65 (13), 51 (11).
5-Eth yl-2-m eth oxyp h en ol (32)42 a n d 4-Eth yl-2-m eth -
oxyp h en ol (35). The standard procedure was followed by use
of 4-ethyl-1,2-dimethoxybenzene (26; 123 mg, 0.739 mmol, 1.0
equiv), NaN(SiMe3)2 (1.0 M, 1.8 mL, 1.8 mmol, 2.5 equiv), and
DMEU (0.50 mL). The reaction mixture was worked up, and
the residue was purified by chromatography (10% EtOAc in
(40) Carvalho, C. F.; Sargent, M. V. J . Chem. Soc., Chem. Commun.
1984, 227.
(38) Loic, R.; Simone, R.; Pierre, D.; Rene, R.; Raymond, C. Eur. J .
Med. Chem. Chim. Ther. 1979, 14, 281.
(41) Maissant, J . M.; Bouchoule, C.; Blanchard, M. J . Mol. Catal.
1982, 14, 333.
(39) Pelizzetti, E.; Mentasti, E.; Pramauro, E. J . Chem. Soc., Perkin
Trans. 2 1978, 620.
(42) Nolte, D. J . J . Insect. Physiol. 1976, 22, 833; Chem. Abstr. 1976,
85, 156902m.