Regioselective Dealkylation of Alkyl Aryl Ethers with Niobium(v) Pentachloride
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116.0, 119.7, 120.5, 123.4, 123.5, 126.1, 126.2, 127.8, 127.9, 129.1,
1199, 1132, 1086, 1072, 883 cm–1. MS (EI): m/z = 284 (M+). HRMS
129.20, 129.22, 129.3, 134.0, 134.1, 154.3, 154.9 ppm. IR (KBr): ν
(EI): calcd. for C10H11F3O4S, 284.0330; found 284.0349.
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= 1618, 1590, 1507, 1459, 1354, 1237, 1096, 1062, 809 cm–1. LRMS
(FAB): m/z = 328 (M+). HRMS (FAB): calcd. for C23H20O2,
328.1463; found 328.1451. [α]2D4 –55.5 (c = 1.0, CHCl3).
Synthesis of 8e and 9e: To a suspension of NbCl5 (168 mg,
0.62 mmol) in dichloroethane (4.7 mL) was added a solution of 7e
in dichloroethane (88 mg, 0.56 mmol, 0.9 mL) at room tempera-
ture. After this mixture was stirred for 1.5 h under reflux condi-
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2-Methoxy-6-methylphenyl Methansulfonate (8a): Colorless oil, H
NMR (CDCl3, 400 MHz): δ = 2.32 (s, 3 H), 3.17 (s, 3 H), 3.85 (s, tions, the reaction was quenched with water (2 mL) and the re-
3 H), 7.04 (dd, J = 8.0, 8.0 Hz, 1 H), 7.12–7.20 (m, 2 H) ppm. 13C
NMR (CDCl3, 100 MHz): δ = 15.8, 37.9, 60.9, 122.1, 124.3, 130.0,
sulting mixture was extracted with CH2Cl2 (5 mL, 3 times). The
combined organic layers were washed with brine (5 mL) and dried
with Na2SO4. After the organic solvents were removed in vacuo,
the resulting crude product was dissolved in dichloromethane
(5.6 mL). To this solution were added NEt3 (157 µL, 1.13 mmol)
and AcCl (80 µL, 1.13 mmol) at room temperature, and the mixture
was stirred for 1 h. The reaction was quenched with sat. aq. NH4Cl
(2 mL) and the mixture was extracted with CH2Cl2 (5 mL, 3 times).
The combined organic layers were washed with brine (5 mL), dried
with Na2SO4, and concentrated. The resulting residue was purified
by flash column chromatography on silica gel (hexane/AcOEt,
12:1) to give 8e (79.3 mg, 76%) and 9e (2.7 mg, 3%) as colorless
oils.
2-Fluoro-6-methoxyphenyl Acetate (8e): 1H NMR (CDCl3,
400 MHz): δ = 2.35 (d, J = 0.4 Hz, 3 H), 3.83 (s, 3 H), 6.73–6.79
(m, 2 H), 7.10–7.16 (m, 1 H) ppm. 13C NMR (CDCl3, 100 MHz):
δ = 20.2, 56.3, 107.6 (d, J = 2.4 Hz), 108.5 (d, J = 19.7 Hz), 126.3
(d, J = 9.8 Hz), 127.8 (d, J = 14.8 Hz), 155.2 (d, J = 246.8 Hz),
133.4, 142.7, 150.1 ppm. IR (neat): ν = 3022, 2939, 1482, 1426,
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1367, 1267, 1240, 1213, 1175 cm–1. MS (FAB): m/z = 217 [M +
H]+. HRMS(FAB): calcd. for C9H12O4S, 216.0456; found 216.0467.
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2-Methoxy-3-methylphenyl Methansulfonate (9a): Colorless oil, H
NMR (CDCl3, 400 MHz): δ = 2.38 (s, 3 H), 3.31 (s, 3 H), 3.86 (s,
3 H), 6.81–6.85 (m, 2 H), 7.13 (dd, J = 8.0, 8.0 Hz, 1 H) ppm. 13C
NMR (CDCl3, 100 MHz): δ = 16.9, 39.6, 55.8, 110.0, 123.1, 127.2,
134.0, 137.9, 151.6 ppm. IR (neat): ν = 3022, 2941, 2836, 1611,
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1482, 1359, 1307, 1278 cm–1. MS (FAB): m/z = 217 [M + H]+.
HRMS(FAB): calcd. for C9H12O4S, 216.0456; found 216.0467.
Synthesis of 2-Methoxy-6-methylphenyl Trifluoromethanesulfonate
(10a): To a suspension of NbCl5 (391 mg, 1.46 mmol) in dichloro-
ethane (13 mL) was added 7a (200 mg, 1.31 mmol) at room tem-
perature. After this mixture was stirred for 1 h under reflux condi-
tions, the reaction was quenched with water (10 mL) and the re-
sulting mixture was extracted with CH2Cl2 (5 mL, 3 times). The
combined organic layers were washed with brine (5 mL) and dried
with Na2SO4. After the organic solvents were removed in vacuo,
the resulting crude product was dissolved in CH2Cl2 (13 mL). To
this solution were added Tf2O (0.66 mL, 3.94 mmol) and pyridine
(0.32 mL, 3.94 mmol) at room temperature, and the mixture was
stirred for 1 h. The reaction was quenched with sat. aq. NH4Cl
(5 mL) and the mixture was extracted with CH2Cl2 (5 mL, 3 times).
The combined organic layers were washed with brine (5 mL), dried
with Na2SO4, and concentrated. The resulting residue was purified
by flash column chromatography on silica gel (hexane/AcOEt,
15:1) to give 10a (262 mg, 74%) as a colorless oil. 1H NMR
(CDCl3, 400 MHz): δ = 2.36 (s, 3 H), 3.88 (s, 3 H), 6.84 (d, J =
8.4 Hz, 1 H), 6.85 (d, J = 8.4 Hz, 1 H), 7.19 (dd, J = 8.4, 8.4 Hz,
1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 16.3, 56.0, 110.4,
118.7 (q, J = 318.4 Hz), 123.1, 128.2, 132.1, 137.8, 151.3 ppm. IR
152.9 (d, J = 4.1 Hz), 168.1 ppm. IR (neat): ν = 1767, 1615, 1479,
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1288, 1251, 1176, 1083, 899 cm–1. MS (EI): m/z = 184 (M+). HRMS
(EI): calcd. for C9H9FO3, 184.0536; found 184.0526.
3-Fluoro-2-methoxyphenyl Acetate (9e): 1H NMR (CDCl3,
400 MHz): δ = 2.33 (s, 3 H), 3.93 (d, J = 1.6 Hz, 3 H), 6.81–6.86
(m, 1 H), 6.97–7.02 (m, 2 H) ppm. 13C NMR (CDCl3, 100 MHz):
δ = 20.5, 61.2, 114.6 (d, J = 19.8 Hz), 118.3 (d, J = 3.3 Hz), 122.8
(d, J = 8.2 Hz), 140.2 (d, J = 12.3 Hz), 144.2 (d, J = 5.0 Hz), 156.0
(d, J = 246.8 Hz), 168.8 ppm. IR (neat): ν = 1769, 1492, 1471, 1281,
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1194, 1024, 999, 901, 869 cm–1. MS (EI): m/z = 184 (M+). HRMS
(EI): calcd. for C9H9FO3, 184.0536; found 184.0542.
2-Ethoxy-5-methylphenol (8f) and 2-Ethoxy-4-methylphenol (9f): To
a suspension of NbCl5 (175 mg, 0.65 mmol) in dichloroethene
(4.4 mL) was added a solution of 7f (106.0 mg, 0.59 mmol) in
dichloroethane (1.5 mL). After stirring for 27 h at room tempera-
ture, the reaction mixture was quenched with water (2 mL) and the
resulting mixture was extracted with CH2Cl2 (5 mL, 3 times). The
combined organic layers were washed with brine, dried with
Na2SO4, and concentrated in vacuo. The resulting residue was puri-
fied by flash column chromatography on silica gel (hexane/AcOEt,
1:12) to give a 1:1 mixture of 8f and 9f (82.8 mg, 93%) as a colorless
(neat): ν = 1482, 1413, 1199, 1130, 1091, 1077, 880 cm–1. MS (EI):
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m/z = 270 (M+). HRMS (EI): calcd. for C9H9F3O4S, 270.0174;
found 270.0186.
Transformation of 10a to m-Cresol (11a): To a solution of 10a
(243 mg, 0.9 mmol) in DMF (3 mL) and formic acid (0.1 mL,
2.7 mmol) were added PdCl2(PPh3)2 (38 mg, 54 µmol, 5 mol-%),
dppp (56 mg, 0.13 mmol) and tributylamine (0.90 mL, 3.78 mmol)
at room temperature. After this mixture was stirred for 8 h at 80 °C,
the reaction was quenched with water (10 mL) and the resulting
mixture was extracted with Et2O (5 mL, 3 times). The combined
organic layers were washed with brine (5 mL), dried with Na2SO4
and concentrated. The resulting residue was purified by flash col-
umn chromatography (hexane/AcOEt, 50:1) on silica gel to give
11a (50.3 mg, 0.41 mmol, 46%) as a colorless oil. Compounds 10b
and 11b were also prepared from 8b[25] by a procedure similar to
that shown in Scheme 3.
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oil. H NMR (CDCl3, 400 MHz): δ = 1.39–1.44 (m, 6 H), 2.25 (s,
3 H), 2.27 (s, 3 H), 4.03–4.10 (m, 4 H), 5.54 (s, 1 H), 5.65 (s, 1 H),
6.60–6.82 (m, 6 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 14.9,
20.7, 21.0, 64.3, 64.6, 111.6, 112.5, 114.0, 115.3, 120.2, 121.4, 129.5,
131.0, 143.4, 143.6, 145.5 ppm. IR (neat): ν = 3536, 2927, 2921,
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1509, 1267, 1232, 1197, 1150, 1121, 1040, 794 cm–1. LRMS (EI):
m/z = 152 (M+). HRMS (EI): calcd. for C9H12O2, 152.0837; found
152.0842.
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra of all new compounds and NMR
2-Ethoxy-6-methylphenyl Trifluoromethanesulfonate (10b): 1H
NMR (CDCl3, 400 MHz): δ = 1.45 (t, J = 6.8 Hz, 3 H), 4.10 (q, J
= 6.8 Hz, 2 H), 6.82 (d, J = 8.4 Hz, 1 H), 6.83 (d, J = 8.4 Hz, 1
H), 7.16 (dd, J = 8.4, 8.4 Hz, 1 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 14.2, 16.3, 64.7, 110.0, 118.6 (q, J = 318.4 Hz),
study described in Scheme 3.
[1] E. J. Roskamp, S. F. Pedersen, J. Am. Chem. Soc. 1987, 109,
6551–6553.
[2] E. J. Roskamp, S. F. Pedersen, J. Am. Chem. Soc. 1987, 109,
122.8, 128.1, 132.0, 137.9, 150.6 ppm. IR (neat): ν =1473, 1414,
3152–3154.
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Eur. J. Org. Chem. 2006, 752–758
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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