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PAPER
g (88%) of a yellowish solid. According to NMR spectroscopy and
gas chromatography the two isomers, 3-fluoro-2-naphthoic acid
(1b) and 2-fluoro-1-naphthoic acid (1a), were present in a in a 3:7
ratio; yield: 4.0 g (84%). Crystallization of the crude product from
H2O (1.0 L) gave 0.62 g (22%) of acid 1b as colorless platelets (mp
197–199 °C; see below). Evaporation of the mother liquor to dry-
ness and crystallization of the residue from H2O (25 mL) gave acid
1a; yield: 1.0 g (35%); mp 145 – 150 °C (Lit.10 mp 151–153 °C).
1H NMR: d = 8.41 (dd, J = 8.6, 0.8 Hz, 1 H), 8.01 (dd, J = 9.0, 5.5
Hz, 1 H), 7.89 (d, J = 8.1 Hz,1 H), 7.66 (t, J = 7.8 Hz, 1 H), 7.54 (td,
J = 7.5, 1.0 Hz, 1 H), 7.34 (dd, J = 9.9, 9.0 Hz, 1 H).
2-Methoxynaphthalene
Methyl 2-Methoxy-1-naphthoate (4a-E) and Methyl 3-Meth-
oxy-2-naphthoate (4b-E)
n-BuLi (5.0 mmol) in hexanes (3.1 mL) was combined with 2-meth-
oxynaphthalene (0.79 g, 5.0 mmol) in THF (15 mL) at 0 °C. Imme-
diately afterwards the mixture was brought to +25 °C and was
stored for 150 min at +25 °C before being poured onto an excess of
freshly crushed dry ice. The volatiles were evaporated and the resi-
due was dissolved in aq 1.0 M NaOH (20 mL), washed with Et2O
(10 mL), acidified to pH 1 and extracted with Et2O (20 mL). The
combined organic layers were concentrated and treated with ethere-
al diazomethane until persistence of the yellow color. An aliquot of
isobutylbenzene (approx. 0.1 g) was added as a calibrated ‘internal
standard’ before the gas chromatographic analysis was performed
[using two 30 m capillary columns of different polarity, DB-5MS
(methyl phenyl polysiloxane) and DB-23 (cyanopropyl phenyl si-
loxane)]. By retention time comparison with authentic samples, the
two product peaks present in a 11:89 ratio were assigned as methyl
2-methoxy-1-naphthoate (4a-E; mp 48–49 °C)28 and methyl 3-
methoxy-2-naphthoate (4b-E; mp 52–53 °C).29
3-Fluoro-2-naphthoic Acid (1b)
2-Fluoronaphthalene (3.7 g, 25 mmol) and PMDTA (5.2 mL, 4.3 g,
25 mmol) were added to a solution of s-BuLi in cyclohexane (20
mL) and THF (50 mL) kept in a dry ice/MeOH bath. After 2 h at
–75 °C, the mixture was poured on an excess of freshly crushed dry
ice. When it had reached +25 °C, it was taken up in H2O (0.10 L),
washed with Et2O (50 mL), acidified with concd HCl to pH 1 and
extracted with Et2O (3 × 50 mL). The combined organic layers were
dried and evaporated. NMR Spectroscopy and gas chromatography
(after esterification of a small sample with etheral diazomethane)
revealed the presence of two isomers in a 4:1 ratio; yield: 4.0 g
(84%). The main component was purified by repetitive trituration
with warm CHCl3; yield: 2.6 g (55%); colorless needles; mp 197–
198 °C (Lit.10 mp 196.5–198.0 °C).
Methyl 3-Methoxy-2-naphthoate (4b-E)
To carry out a similar reaction at dry ice temperature, t-BuOK (0.56
g, 5.0 mmol) was added under vigorous stirring to n-BuLi (5.0
mmol) and 2-methoxynaphthalene (0.79 g, 5.0 mmol) in hexanes
(3.1 mL) and THF (10 mL). After 45 min at –75 °C, the reaction
mixture was carboxylated and worked up as described in the pre-
ceding paragraph. The gas chromatograms showed methyl 3-meth-
oxy-2 naphthoate as the sole product, formed in 92% yield, while no
trace of the isomeric methyl 2-methoxy-1-naphthoate was detected.
1H NMR: d = 8.66 (d, J = 7.3 Hz, 1 H), 7.97 (d, J = 8.2 Hz, 1 H),
7.83 (d, J = 8.2 Hz, 1 H), 7.64 (t, J = 7.5 Hz, 1 H), 7.57 (d, J = 12
Hz, 1 H), 7.53 (t, J = 7.5 Hz, 1 H).
2-(Trifluoromethyl)naphthalene
For the preparation, isolation, and characterization of the acids 2a–
c, see ref.4
3-Methoxy-2-naphthoic Acid (4b-A)
A solution of n-BuLi (42 mmol) and 2-methoxynaphthalene (6.7 g,
42 mmol) in hexanes (20 mL) and THF (60 mL) was placed in a dry
ice/MeOH bath. t-BuOK (4.7 g, 42 mmol) was added, in the course
of 5 min, under stirring. After 45 min at –75 °C, the mixture was
poured onto an excess of freshly crushed dry ice. At +25 °C, all vol-
atiles were evaporated under reduced pressure. The crude residue
was crystallized from AcOH (40 mL) to give 6.9 g (81%) of 3-meth-
oxy-2-naphthoic acid (4b-A); mp 135–136 °C; Lit.11 mp 135–136
°C; for comparison 2-methoxy-1-naphthoic acid (4a-A; Lit.28,30 mp
176–177 °C).
2-(Trifluoromethoxy)naphthalene
a) 3-Trifluoromethoxy-2-naphthoic Acid (3b)
At –75 °C, s-BuLi (25 mmol) in cyclohexane (15 mL) was added to
2-(trifluoromethoxy)naphthalene27 (5.3 g, 25 mmol) and PMDTA
(5.2 mL, 4.3 g, 25 mmol) in THF (50 mL). The mixture was kept in
a dry ice/MeOH bath for 2 h before being poured onto an excess of
freshly crushed dry ice. At +25 °C, the volatiles were evaporated
and the residue was dissolved in aq 1.0 M NaOH (50 mL). The
aqueous phase was washed with Et2O (2 × 15 mL), acidified to pH
1, and extracted with Et2O (3 × 25 mL). The combined organic lay-
ers were dried and evaporated. Crystallization of the residue from
EtOAc gave 5.6 g (87%) of colorless needles; mp 140–142 °C.
Acknowledgment
This work was supported by the Ministero dell’Università e Ricerca
(MUR PRIN 2004 contract 2004033322) and the Schweizerische
Nationalfonds zur Förderung der wissenschaftlichen Forschung,
Bern (grant 20-100336-02).
1H NMR: d = 8.71 (s, 1 H), 7.98 (d, J = 8.1 Hz, 1 H), 7.88 (d, J = 8.0
Hz, 1 H), 7.79 (s, 1 H), 7.68 (td, J = 7.5, 1.0 Hz, 1 H), 7.60 (t, J = 7.3
Hz, 1 H).
Anal. Calcd for C12H7F3O3 (256.18): C, 56.26; H, 2.75. Found: C,
56.26; H, 2.77.
References
(1) Gschwend, H. W.; Rodriguez, H. R. Org. React. 1979, 26, 1.
(2) See also: Schlosser, M. Organometallics in Synthesis: A
Manual, 2nd ed.; Schlosser, M., Ed.; Wiley: Chichester,
2002, 1-352, espec. 85–284.
(3) Clayden, J. Organolithiums: Selectivity for Synthesis;
Pergamon: Amsterdam, 2002.
b) 1-Trifluoromethoxy-2-naphthoic Acid
An analogous reaction starting from 1-(trifluoromethoxy)naph-
thalene27 (5.3 g, 25 mmol) afforded 5.1 g (80%) of colorless cubes;
mp 160–161 °C (from EtOAc).
1H NMR: d = 8.3 (m, 1 H), 8.04 (d, J = 8.5 Hz, 1 H), 7.9 (m, 2 H),
7.8 (m, 2 H).
(4) Cottet, F.; Castagnetti, E.; Schlosser, M. Synthesis 2005,
798.
Anal. Calcd for C12H7F3O3 (256.18): C, 56.26; H, 2.75. Found: C,
56.27; H, 2.99.
(5) Schlosser, M. Eur. J. Org. Chem. 2001, 3975.
(6) Shirley, D. A.; Cheng, C. F. J. Organomet. Chem. 1969, 20,
251.
(7) (a) Javor, S.; Schlosser, M. 2004, unpublished results.
(b) See also: Javor, S. Diploma Thesis; Ecole Polytechnique
Fédérale Lausanne: Switzerland, 2004.
Synthesis 2010, No. 9, 1531–1535 © Thieme Stuttgart · New York