4464 J . Org. Chem., Vol. 67, No. 13, 2002
Deffieux et al.
tive scale electrolyses. Acetonitrile (Riedel de Hae¨n, HPLC
grade) was distilled over P2O5 prior to voltammetric analyses.
Tetrabutylammonium tetrafluoroborate (Fluka) was dried at
100 °C under vacuum and stored under N2 before use. Diethyl
ether (Et2O) was purified by distillation from sodium/ben-
zophenone under Ar immediately before use. CH2Cl2 was
distilled from CaH2 prior to use. Light petroleum refers to the
fraction boiling in the 40-60 °C range. Column chromatog-
raphy was carried out under positive N2 pressure using 40-
63 µm silica gel (Merck) and the indicated solvents. Evapora-
tions were conducted under reduced pressure at temperatures
less than 45 °C unless otherwise noted. Further drying of the
residues was accomplished under high vacuum. Melting points
are uncorrected. IR spectra were recorded on a Perkin-Elmer
Targon 1000 spectrometer. NMR spectra of samples in the
indicated solvent were run at 250 MHz unless otherwise noted.
Electron impact and liquid secondary ion mass spectrometry
low and high-resolution mass spectrometric analyses (EIMS,
and LSIMS, HRMS) were obtained from the mass spectrom-
etry laboratory at the CESAMO, Bordeaux 1 University.
176.8, 152.2, 142.7, 124.9, 123.2, 120.8, 111.8, 81.6, 55.4, 24.6;
EIMS m/z (relative intensity) 210 (M+, 31), 165 (16), 124 (100).
r-(2-Meth oxyp h en oxy)p r op ion ic Acid (3b). To a stirred
solution of 2-methoxyphenol (2.0 g, 16 mmol) in acetone (40
mL) were added ethyl bromopropionate (3.6 g, 20 mmol),
potassium carbonate (2.76 g, 20 mmol), and potassium iodide
(0.13 g, 0.8 mmol). The reaction mixture was refluxed for 22
h. After being cooled to room temperature, the potassium salts
were removed by filtration. The filtrate was diluted in EtOAc-
AcOH [100 mL, (100:1)] and washed with 1 M H3PO4 (50 mL)
and brine (3 × 50 mL). After separation, the organic layer was
dried over MgSO4, filtered, and evaporated to give a residue
which was further dried under under high vacuum overnight
to give 3.8 g of crude product. To a stirring solution of this
crude ester in absolute ethanol (25 mL) was added a solution
of potassium hydroxide (1.0 g, 18.3 mmol) in absolute ethanol
(5 mL). The mixture was refluxed for 24 h. After cooling to
room temperature, the mixture was acidified with 10% aq HCl
(10 mL), extracted with Et2O (2 × 50 mL), dried over Na2SO4,
filtered, and evaporated to give crude 3b. Crystallization from
benzene-pentane yielded pure 3b (1.36 g, 43%) as white
Cyclic Volta m m etr y. Cyclic voltammetry experiments
were carried out in an acetonitrile solution containing NBu4-
BF4 or LiClO4 (0.1 M) in a 20 mL three-neck round-bottom
flask cell. The potentiostat used was an Autolab PGSTAT100.
The working electrode was a 3 mm diameter platinum disk.
The counter electrode was a platinum wire, and the reference
electrode (double-junction) was a silver (Ag) wire immersed
in a saturated potassium chloride (KCl) solution separated
from the bulk solution by a salt bridge fine glass frit. The
reference electrode was calibrated after each experiment
crystals, mp 82 °C (lit.27 mp 85 °C). IR (NaCl) 2962, 1720 cm-1
;
1H NMR (CDCl3) δ 1.65 (d, J ) 6.7 Hz, 3H), 3.84 (s, 3H), 4.72
(q, J ) 6.7 Hz, 1H), 6.83-7.04 (m, 4H), 9.41 (bs, 1H), 13C NMR
(CDCl3, 62.9 MHz) δ 176.4, 149.9, 146.5, 123.4, 120.9, 117.3,
112.2, 74.8, 55.7, 18.3.
r-(2-Meth oxyp h en oxy)a cetic Acid (3c). To a stirred
solution of 2-methoxyphenol (3.0 g, 24 mmol) in 5% aq sodium
hydroxide (20 mL) was added methyl chloroacetate (5.2 g, 48
mmol) in 8% aq sodium hydroxide (50 mL). The mixture was
heated on a steam-bath at 80 °C for 16 h. After being cooled
to room temperature, the mixture was acidified with 10% aq
HCl, extracted with Et2O (2 × 50 mL), dried over Na2SO4,
filtered, and evaporated to give crude 3c. Crystallization from
benzene-pentane yielded pure 3c (2.1 g, 48%) as white
crystals, mp 121 °C (lit.28 mp 121.5 °C). IR (NaCl) 3014, 1745,
1710 cm-1; 1H NMR (CDCl3) δ 3.88 (s, 3H), 4.70 (s, 2H), 6.90-
7.06 (m, 4H), 9.44 (bs, 1H); 13C NMR (CDCl3, 62.9 MHz) δ
173.4, 149.6, 146.9, 123.4, 121.0, 115.7, 112.1, 67.1, 55.8.
+
against the ferrocene/ferrocinium couple (E°Fc/Fc ) 0.46 V vs
the Ag/AgCl reference electrode). Feedback correction was
applied in order to minimize the ohmic drop between the
working and reference electrodes. The precision of the mea-
surements was about (5 mV.
P r ep a r a t ive E lect r och em ica l Oxid a t ion . Electrolyses
were carried in a 100 mL undivided cylindrical cell, equipped
with a platinum-coated titanium grid (50 g Pt/m2, 40 × 60 mm)
as the anode (available from Magneto-Chemie) and a 160 mm
Pt wire (0.5 mm diameter) as the cathode. LiClO4 (1.5 g, 14.0
mmol) was added as supporting electrolyte to a 100 mL
mixture of acetonitrile-methanol or acetonitrile-water (9:1
or 7:3). The starting acid and the base (e.g., 2,6-lutidine, 2
equiv) were introduced, and the electrolysis was then per-
formed at constant potential on an Autolab PGSTAT 100
potentiostat using an Ag/AgCl reference electrode until the
current decayed smoothly to background. All reactions were
vigorously stirred. After electrolysis, the solution was evapo-
rated, and the residue was diluted in Et2O (50 mL) and washed
with brine (3 × 30 mL). The layers were then separated, and
the aqueous layer was extracted three times with Et2O (3 ×
30 mL). The combined organic extracts were dried over Na2-
SO4, filtered, and evaporated to dryness.
r-(2-Met h oxyp h en oxy)-2-m et h ylp r op ion ic Acid (3a ).
To a stirred ice-cold solution of 2-methoxyphenol (2.0 g, 16
mmol) and 1,1,1-trichloro-2-methylpropan-2-ol (H2O)x (7.88 g,
44 mmol)11 in acetone (40 mL) was added powdered sodium
hydroxide (6.0 g, 150 mmol) in three equal portions at 2 h
intervals. After each addition, the reaction mixture was
allowed to warm to room temperature. Before the last addition,
an additional 40 mL of acetone was added to the thick
suspension. The mixture was then stirred for 18 h at room
temperature, and the solvent was evaporated to give a residue,
which was diluted in water and acidified to pH 1 with 10% aq
HCl. The aqueous phase was extracted three times with Et2O
(3 × 100 mL). The organic layer was dried over MgSO4,
filtered, and evaporated to give crude 3a as light brown oil.
Crystallization from benzene-hexane afforded pure 3a (2.0
g, 60%) as white crystals, mp 42 °C (lit.26 mp 45-47 °C). IR
(NaCl) 2990, 1705 cm-1; 1H NMR (CDCl3) δ 1.49 (s, 6H), 3.80
(s, 3H), 6.81-7.10 (m, 4H); 13C NMR (CDCl3, 62.9 MHz) δ
3,3-Dim eth yl-1,4-Dioxa sp ir o(4.5(d eca -7,9-d ien e-6,6-d i-
m eth oxy-2-on e (4a ). Electro-oxidation of a solution of 3a (118
mg, 0.56 mmol) in acetonitrile-methanol (9:1) was performed
in the presence of 2 equiv of 2,6-lutidine according to the
general procedure described above for preparative electro-
chemical oxidation. Electrolysis was carried out at a constant
potential of 1.8 V/Ag/0.1 M AgCl until the current decayed
smoothly to background with passage of 5.0 F/mol. The
reaction mixture was then processed as described above, and
the residue was further dried overnight to give 4a (106 mg,
78%) as a pale yellow oil. IR (NaCl) 1800 cm-1 1H NMR
;
(CDCl3) δ 1.48 (s, 3H), 1.57 (s, 3H), 3.39 (s, 3H), 3.40 (s, 3H),
5.81-6.13 (m, 4H); 13C NMR (CDCl3, 62.9 MHz) δ 175.3, 130.7,
127.8, 127.3, 126.5, 106.3, 97.6, 76.4, 51.6, 51.3, 27.2, 24.5;
EIMS m/z (relative intensity) 240 (M+, 22), 209 (7), 154 (100),
139 (30), 123 (20), 111 (84); HRMS (EIMS) calcd for C12H16O5
240.0998, found 240.0994.
r-(4-Meth oxyp h en oxy)-2-m eth ylp r op ion ic Acid (5a ).
This acid was prepared as described for 3a . Crystallization of
the resulting crude light brown oil from benzene-pentane
yielded pure 5a (2.4 g, 70%) as beige needles, mp 54 °C (lit.29
mp 57 °C). IR (NaCl) 2963, 1736 cm-1; 1H NMR (CDCl3) δ 1.55
(s, 6H), 3.76 (s, 3H), 6.77-6.94 (m, 4H); 13C NMR (CDCl3, 62.9
MHz) δ 179.5, 155.7, 147.9, 122.6, 114.2, 79.8, 55.4, 24.9; EIMS
m/z (relative intensity) 210 (M+, 31), 165 (18), 124 (100).
r-(4-Meth oxyp h en oxy)p r op ion ic Acid (5b). This acid
was prepared as described for 3b. Crystallization from benzene-
pentane yielded pure 5b (1.9 g, 60%) as colorless needles, mp
1
86 °C (lit.12 mp 90 °C). IR (NaCl) 2949, 1719 cm-1; H NMR
(CDCl3) δ 1.63 (d, J ) 6.7 Hz, 3H), 3.76 (s, 3H), 4.70 (q, J )
(27) Bischoff, L. Chem. Ber. 1900, 33, 1393.
(28) Hirota, M.; Hirano, G. Bull. Chem. Soc. J pn. 1972, 45, 1448-
1452.
(26) J ones, W. G. M.; Thorp, J . M.; Waring, W. S. 1961; p GB Patent
# 860, 303.
(29) J ulia, M. Bull. Soc. Chim. Fr. 1956, 776-783.