1,2-Didehydro-3- and -4-(trifluoromethoxy)benzene: The "aryne" route to 1- and 2-(trifluoromethoxy)naphthalenes

Article abstract of DOI:10.1002/1099-0690(200111)2001:21<3991::AID-EJOC3991>3.0.CO;2-J

Upon treatment of 1-bromo-2-(trifluoromethoxy)benzene with lithium diisopropylamide (LIDA) at -100°C, 3-bromo-2-(trifluoromethoxy)phenyllithium is generated. It can be trapped as such, but isomerizes to afford 2-bromo-6-(trifluoromethoxy)phenyllithium whe

Full text of DOI:10.1002/1099-0690(200111)2001:21<3991::AID-EJOC3991>3.0.CO;2-J

FULL PAPER
1,2-Didehydro-3- and -4-(trifluoromethoxy)benzene:
The ‘‘Aryne’’ Route to 1- and 2-(Trifluoromethoxy)naphthalenes
Manfred Schlosser*[a] and E. Castagnetti[a]
Keywords: Dehydroarenes (‘‘arynes") / DielsϪAlder cycloadducts / FluorineϪlithium interactions / Site-selective
hydrogenϪmetal exchange / Substituent effects
Upon treatment of 1-bromo-2-(trifluoromethoxy)benzene
with lithium diisopropylamide (LIDA) at −100 °C, 3-bromo-2-
(trifluoromethoxy)phenyllithium is generated. It can be
trapped as such, but isomerizes to afford 2-bromo-6-(tri-
fluoromethoxy)phenyllithium when the temperature is raised
3-(trifluoromethoxy)benzene. Both ‘‘arynes’’ can be inter-
cepted in situ with furan. The resulting [4+2] cycloadducts
can be reduced with zinc powder, giving 1- and 2-
(trifluoromethoxy)naphthalenes, they may be submitted to
acid-catalyzed isomerization to produce trifluoromethoxy-1-
to −75 °C. The latter intermediate can be directly obtained naphthols, or they may be brominated to afford vic-dibromo
from 1-bromo-3-(trifluoromethoxy)benzene. 1-Bromo-4-(tri-
derivatives. Base-promoted dehydrobromination of the latter
fluoromethoxy)benzene gives 5-bromo-2-(trifluoromethoxy)- compounds produces 2- or 3-bromo-1,4-epoxy-1,4-dihydro-
phenyllithium at −100 °C, but at −75 °C it slowly eliminates
5- or −6-(trifluoromethoxy)naphthalenes, which undergo re-
lithium bromide, thus setting free 1,2-dehydro-4- gioselective ring-opening in acidic media and halogen/metal
(trifluoromethoxy)benzene. In the same way, 1,2-dehydro-3-
(trifluoromethoxy)benzene can be generated from 1-bromo-
exchange when treated with butyllithium.
5-Bromo-2,2-difluoro-1,3-benzodioxole has been re-
ported to undergo smooth deprotonation at the doubly ac-
tivated 4-position upon treatment with lithium 2,2,6,6-tetra-
methylpiperidide (LITMP) in tetrahydrofuran (THF) at
Ϫ75 °C and, upon carboxylation, to afford the correspond-
ing acid in 76% yield.[1] Under these circumstances, it was
reasonable to predict analogous behavior in the structurally
related 1-bromo-3-(trifluoromethoxy)benzene. When this
compound was treated consecutively with lithium diisopro-
pylamide (LIDA) and dry ice, the carboxylic acid 2 was
indeed formed, again in high yield (90%). The isomers 1-
bromo-2-(trifluoromethoxy)benzene and 1-bromo-4-(tri-
fluoromethoxy)benzene could be submitted to the same de-
protonation/carboxylation sequence (although the lithiation
had to be performed at Ϫ100 °C in these cases) to obtain
pure acids 1 (73%) and 3 (74%; at Ϫ75 °C: 86%), respec-
tively.
Obviously, the trifluoromethoxy substituent activates its
immediate vicinity more powerfully than the bromine atom,
a notoriously weak[2] neighboring group, does. When the
reaction sequence was performed at Ϫ75 °C, however, the
organometallic intermediate initially derived from 1-bromo-
2-(trifluoromethoxy)benzene was found to isomerize to the
less basic 2-bromo-6-(trifluoromethoxy)phenyllithium (71%
of acid 2 after 45 min). Apparently, amide-promoted depro-
tonations become reversible under such conditions, and
lithiation at the site adjacent to bromine begins to compete
with the otherwise exclusive attack next to the trifluoro-
methoxy group. 2-Bromo-3-(trifluoromethoxy)phenyl-
lithium, the new organometallic intermediate thus generated,
cannot be intercepted as such, since it immediately isomer-
izes by positional permutation of its bromine and lithium
substituents. The crucial step is presumably a halogen/metal
exchange between 2-bromo-3-(trifluoromethoxy)phenyl-
lithium and trace amounts of incidentally formed 1,2-di-
bromo-3-(trifluoromethoxy)benzene (4). Analogous mech-
[a]
´
ˆ
Institut de Chimie organique de l’Universite, Batiment de
Chimie (BCh),
1015 Lausanne-Dorigny, Switzerland
Fax: (internat.) ϩ 41-21/692-3965
Eur. J. Org. Chem. 2001, 3991Ϫ3997
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/1121Ϫ3991 $ 17.50ϩ.50/0
3991

M. Schlosser, E. Castagnetti
FULL PAPER
anisms have been invoked to explain similar halogen migra-
tions in the arene and pyridine series.[3,4]
sis,
At Ϫ75 °C, the para isomer also produces minute quant-
ities of a more basic species, i.e., 2-bromo-5-(trifluoro-
methoxy)phenyllithium, at the expense of the thermo-
dynamically more stable 5-bromo-2-(trifluoromethoxy)-
phenyllithium, as equilibration becomes possible. Upon
carboxylation, a 99:1 mixture of 5-bromo-2-(trifluoro-
methoxy)benzoic acid (3) and its regioisomer 2-bromo-5-
(trifluoromethoxy)benzoic acid[5] (5) were detected by gas
chromatography (after esterification of the acids with diazo-
methane).
the ions pre-10 and pre-13 should be preferentially formed
at the expense of their counterparts pre-11 and pre-12. This
expectation is fulfilled in the 1-trifluoromethoxy series, but is
at variance with the findings in the 2-trifluoromethoxy series.
A tentative explanation of the observed regiopreferences can
be developed if one restricts the area of charge delocalization
to just an allyl unit (considering only the area between the
solid dots). Then the allyl cation is attached either to an or-
tho or a meta or a para position with respect to the trifluoro-
methoxy substituent. The shorter the distance, the greater
the destabilizing effect this electronegative group exerts on
the allyl cation.
The 2-bromo-5- and -6-(trifluoromethoxy)phenyllithium
intermediates eliminate lithium halide at around Ϫ60 °C
and Ϫ30 °C, respectively. The 1,2-didehydro(trifluorome-
thoxy)benzenes thus liberated could be effectively trapped
with furan by DielsϪAlder cycloaddition.[6Ϫ14] 1-Bromo-3-
or -4-(trifluoromethoxy)benzene were added to a solution
of LIDA in tetrahydrofuran and furan (approximately equal
volumes) at Ϫ75 °C and the temperature was allowed to
come to ϩ25 °C over the course of 2 h. The 1,4-dihydro-
1,4-epoxy-5- and -6-(trifluoromethoxy)naphthalenes (6 and
7) were isolated upon distillation in 74% and 70% yields, re-
spectively.
The two 7-oxabenzobicyclo[2.2.1]heptenes 6 and 7 were
reduced with zinc dust in acetic acid to 1- and 2-(trifluoro-
methoxy)naphthalene (8 and 9). When heated in the pres-
ence of hydrogen chloride, the DielsϪAlder cycloadducts 6
and 7 isomerized to pairs of hydroxy(trifluoromethoxy)-
naphthalenes 10 and 11 or 12 and 13, in 1:8 and 1:5 ra-
tios, respectively.
When brominated under the conditions applied by Balcı
et al.[15] to benzonorbornene, each of the cycloadducts 6 and
7 provided three stereoisomers (14aϪc and 15aϪc). These
were separated by chromatography and fractional crystalliza-
tion. The potassium tert-butoxide-promoted elimination of
hydrogen bromide converted the stereoisomer 14a into the
regioisomer 16 and the stereoisomer 14c into the regioisomer
The regiochemical outcome of the acid-catalyzed opening 17. The exo-syn-elimination mode being favored for obvious
of the 1,4-epoxy bridge in adducts 6 and 7 was surprising. reasons, the cis-dibromide 14b reacted only sluggishly to af-
The cations pre-10 Ϫ pre-13 can safely be assumed to act as ford a 1:1 mixture of 16 and 17. In the same way, the di-
the crucial intermediates. If both rings were participating in bromo derivatives 15a and 15c selectively gave the bromo-
the resonance stabilization through charge delocalization, the 1,4-epoxy-1,4-dihydro-6-(trifluoromethoxy)naphthalene iso-
electron-withdrawing trifluoromethoxy substituent would be mers 18 and 19, respectively, whereas intermediate 15b pro-
better accommodated at an antinodal position. On this ba- duced a 1:1 mixture of 18 and 19.
3992
Eur. J. Org. Chem. 2001, 3991Ϫ3997

The “Aryne” Route to 1- and 2-(Trifluoromethoxy)naphthalenes
FULL PAPER
The bromo-1,4-epoxy-1,4-dihydronaphthalenes 16؊19
reacted smoothly with butyllithium at Ϫ75 °C to generate
the corresponding cycloalkenyllithium species. Carb-
oxylation of the latter afforded the 1,4-epoxy acids 20, 23,
26, and 29, which could be deoxygenated to the (trifluoro-
methoxy)naphthalenecarboxylic acids 21, 24, 27, and 30.
Treatment with acid converted the bromocycloalkenes
16؊19 into the trifluoromethoxy-substituted 2-bromo-1-
naphthols 22, 25, 28, and 31.
The strict regioselectivity obeyed in the acid-catalyzed
ring-opening of the bromocycloadducts 16؊19 implies a di-
minished thermodynamic stability of cations 32 in compar-
ison with their counterparts 33. Apparently, bromine lo-
cated at the terminus of an allyl cation exerts an electron-
donating resonance effect that outweighs its electron-with-
drawing inductive effect, whereas the halogen acts exclu-
sively in the latter fashion when attached to the nodal posi-
tion.
Experimental Section
Resonance stabilization of methyl, allyl, and benzyl cat-
ions bearing α-fluoro and α-chloro substituents is well
documented.[16Ϫ27] Data relating to α-bromoalkyl
cations[28Ϫ29] are scarce, and nonexistent as far as 1-bro-
moallyl cations are concerned.[30]
For standard laboratory practice and abbreviations, see previous
1
publications from this laboratory (e.g., refs.[31Ϫ32]). Ϫ H and 13C
NMR spectra were recorded at 400 MHz (or 600 MHz, if marked
by an asterisk) and at 101 MHz, respectively, by using samples dis-
solved in deuteriochloroform.
Eur. J. Org. Chem. 2001, 3991Ϫ3997
3993

M. Schlosser, E. Castagnetti
needles; m.p. 181Ϫ183 °C (from hexanes).
1H NMR
FULL PAPER
Bromo(trifluoromethoxy)benzoic Acids
Ϫ
(D3CCOCD3): δ ϭ 8.59 (d, J ϭ 9.1 Hz, 1 H), 7.96 (d, J ϭ 2.6 Hz,
1 H), 7.60 (dm, J ϭ 9.2 Hz, 1 H), 1.53 (s, 9 H). Ϫ 13C NMR
(D3CCOCD3): δ ϭ 168.0, 152.2, 141.7, 136.6, 127.4, 123.6, 120.3
(q, J ϭ 260.1 Hz), 119.8, 115.3, 80.4, 27.4 (3C)]. Deprotection of
the latter compound with trifluoroacetic acid in dichloromethane
at 25 °C over 2 h afforded 2-amino-5-(trifluoromethoxy)benzoic acid
[colorless needles, m.p. 137Ϫ138 °C (from water). Ϫ 1H NMR: δ ϭ
7.79 (d, J ϭ 2.4 Hz, 1 H), 7.20 (dd, J ϭ 9.0, 2.6 Hz, 1 H), 6.66 (d,
J ϭ 9.0 Hz, 1 H). Ϫ 13C NMR: δ ϭ171.6, 149.8, 138.8, 129.0,
124.4, 120.4 (q, J ϭ 262.0 Hz), 117.7, 108.9. Ϫ C8H6F3NO3
(221.14): calcd. C 43.45, H 2.73; found C 43.29, H 2.92; yield 4.3 g
(96%)]. Some of the deprotected compound (1.1 g, 5.0 mmol) was
dissolved in 48% aqueous hydrobromic acid (10 mL). Under ice
cooling, sodium nitrite (0.35 g, 5.0 mmol) was introduced por-
tionwise (spatula tip quantities) over the course of 2 min, followed
by cupric bromide (1.1 g, 5.0 mmol). The mixture was heated to 75
°C for 15 min, diluted with water (10 mL), and extracted with di-
ethyl ether (3 ϫ 15 mL). The combined organic layers were dried
and the solvents evaporated. Upon recrystallization of the residue
from hexanes, product 5 was obtained in the form of colorless
3-Bromo-2-(trifluoromethoxy)benzoic Acid (1): Butyllithium
(25 mmol) in hexanes (15 mL) and diisopropylamine (3.5 mL,
2.5 g, 25 mmol) in tetrahydrofuran (50 mL) were mixed at 0 °C.
The solution was then cooled to Ϫ100 °C, and 1-bromo-2-
(trifluoromethoxy)benzene (3.8 mL, 6.0 g, 25 mmol) was added.
After 2 h at Ϫ100 °C, the mixture was poured onto an excess of
freshly crushed dry ice. After evaporation of the volatiles, the res-
idue was dissolved in a 1  aqueous solution (50 mL) of sodium
hydroxide, washed with diethyl ether (2 ϫ 15 mL), and acidified
with concentrated hydrochloric acid (7 mL) to pH 1. Upon extrac-
tion with diethyl ether (3 ϫ 30 mL) a 95:5 mixture, according to
gas chromatographic analysis (30 m, DB-1701, 100 °C; 30 m DB-
210, 120 °C), of product 1 and its isomer 2 was obtained. Concen-
tration and recrystallization from a 1:5 (v/v) mixture of ethyl acet-
ate and hexanes afforded the pure acid 1 as colorless cubes; m.p.
123Ϫ124 °C; yield 5.2 g (73%). Ϫ 1H NMR: δ ϭ 7.99 (dd, J ϭ 7.8,
1.6 Hz, 1 H), 7.89 (dd, J ϭ 8.0, 1.7 Hz, 1 H), 7.33 (t, J ϭ 7.8 Hz,
1 H). Ϫ 13C NMR: δ ϭ 169.6, 147.5, 138.6, 131.3, 128.4, 126.9,
120.3 (q, J ϭ 259.7 Hz), 119.4. Ϫ C8H4BrF3O3 (285.02): calcd. C
33.71, H 1.42; found C 33.88, H 1.38.
1
needles; m.p. 70Ϫ71 °C; yield 1.2 g (84%). Ϫ H NMR: δ ϭ 7.87
(d, J ϭ 2.5 Hz, 1 H), 7.76 (d, J ϭ 8.7 Hz, 1 H), 7.29 (dd, J ϭ 8.8,
2.5 Hz, 1 H). Ϫ 13C NMR: δ ϭ169.3, 148.0, 136.3, 131.6, 126.0,
124.9, 120.4, 120.3 (q, J ϭ 259.6 Hz). Ϫ C8H4BrF3O3 (285.02):
calcd. C 33.71, H 1.42; found C 33.29, H 1.58.
When the lithiation reaction was carried out at Ϫ75 °C, a 4:96 ratio
of acids 1 and 2 in 71% yield resulted.
2-Bromo-6-(trifluoromethoxy)benzoic Acid (2): An analogous reac-
tion performed at Ϫ75 °C and using 1-bromo-3-(trifluoro-
methoxy)benzene (3.7 mL, 6.0 g, 25 mmol) as the substrate, gave
pure acid 2; colorless needles; m.p. 70Ϫ71 °C (from ethyl acetate/
hexanes); yield 6.4 g (90%). Ϫ 1H NMR: δ ϭ 7.57 (dd, J ϭ 7.4,
1.2 Hz, 1 H), 7.3 (m, 2 H). Ϫ 13C NMR: δ ϭ 168.5, 146.4, 131.8,
131.1, 128.8, 120.3, 120.2 (q, J ϭ 259.6 Hz), 119.2. Ϫ C8H4BrF3O3
(285.02): calcd. C 33.71, H 1.42; found C 33.86, H 1.14.
1,4-Epoxy-1,4-dihydro(trifluoromethoxy)naphthalenes, (Trifluoro-
methoxy)naphthalenes, and (Trifluoromethoxy)naphthols
1,4-Epoxy-1,4-dihydro-5-(trifluoromethoxy)naphthalene (6): At Ϫ75
°C, precooled diisopropylamine (28 mL, 20 g, 0.20 mol) in tetrahy-
drofuran (0.20 L), furan (0.20 L), and 1-bromo-3-(trifluorometh-
oxy)benzene (29 mL, 48 g, 0.20 mol) were added consecutively to
butyllithium (0.20 mol) in hexanes (0.10 L). The mixture was al-
lowed to warm up, reaching ϩ25 °C over 2 h. It was washed with
1  hydrochloric acid (2 ϫ 0.10 L) and dried. Upon distillation, a
colorless liquid was collected; b.p. 91Ϫ93 °C/2 Torr; n2D0 1.4808;
yield 33.6 g (74%). Ϫ 1H NMR: δ ϭ 7.18 (d, J ϭ 7.0 Hz, 1 H), 7.0
(m, 3 H), 6.82 (dt, J ϭ 8.3, 0.9 Hz, 1 H), 5.91 (br. s, 1 H), 5.74 (br.
s, 1 H). Ϫ 13C NMR: δ ϭ 152.3, 143.3, 142.3, 141.1, 140.0, 127.2,
120.4 (q, J ϭ 259.5 Hz), 119.2, 119.0, 82.5, 80.2. Ϫ C11H7F3O2
(288.17): calcd. C 57.90, H 3.09; found C 57.97, H 3.11.
5-Bromo-2-(trifluoromethoxy)benzoic Acid (3): When the reaction
and workup conditions described above were applied to 1-bromo-
4-(trifluoromethoxy)benzene (3.7 mL, 6.0 g, 25 mmol), the acid 3
and its isomer 5 were formed in a 99:1 ratio (gas chromatography:
30 m, DB-1701, 100 °C; 30 m, DB-210, 100 °C); colorless needles;
m.p. 92Ϫ93 °C (from hexanes); yield 6.1 g (86%). Ϫ 1H NMR: δ ϭ
8.24 (d, J ϭ 2.5 Hz, 1 H), 7.75 (dd, J ϭ 8.9, 2.4 Hz, 1 H), 7.27 (d,
J ϭ 8.7 Hz, 1 H). Ϫ 13C NMR: δ ϭ 168.1, 147.4, 137.5, 135.6,
125.1, 124.4, 120.4 (q, J ϭ 260.2 Hz), 120.3. Ϫ C8H4BrF3O3
(285.02): calcd. C 33.71, H 1.42; found C 33.71, H 1.63.
1,4-Epoxy-1,4-dihydro-6-(trifluoromethoxy)naphthalene (7): In ex-
actly the same way, 1-bromo-4-(trifluoromethoxy)benzene (29 mL,
48 g, 0.20 mol) gave the isomer 7; colorless liquid; b.p. 87Ϫ89 °C/
1 Torr; n2D0 1.4816; yield 31.8 g (70%). Ϫ 1H NMR: δ ϭ 7.18 (d,
J ϭ 7.8 Hz, 1 H), 7.09 (s, 1 H), 7.1 (m, 2 H), 6.80 (dq, J ϭ 7.7,
1.0 Hz, 1 H), 5.68 (br. s, 2 H). Ϫ 13C NMR: δ ϭ 151.6, 147.5,
146.4, 143.1, 142.7, 120.5, 120.4 (q, J ϭ 259.7 Hz), 117.1, 114.5,
82.2, 82.1. Ϫ C11H7F3O2 (228.17): calcd. C 57.90, H 3.09; found C
57.73, H 3.19.
A reduction in the lithiation temperature to Ϫ100 °C produced
acid 3 uncontaminated by any isomer.
2-Bromo-5-(trifluoromethoxy)benzoic Acid (5): A 9:1 mixture of ac-
ids 3 and 5 was isolated in 88% yield (6.3 g) after 1-bromo-4-(tri-
fluoromethoxy)benzene (25 mmol) in tetrahydrofuran (50 mL) had
been allowed to react for 2 h at Ϫ75 °C with lithium 2,2,6,6-tetra-
methylpiperidide (25 mmol, from 2,2,6,6-tetramethylpiperidine and
a 1.6  solution of butyllithium in hexanes) followed by quenching
with dry ice. The by-product was identified, after esterification with
diazomethane, by gas chromatographic comparison (30 m, DB-
1-(Trifluoromethoxy)naphthalene (8): A solution of the cycloadduct
6 (11.4 g, 50 mmol) in acetic acid (0.10 L) and in the presence of a
1701, 100 °C; 30 m, DB-210, 100 °C; 30 m, DB-WAX, 100 °C) large excess of zinc (33 g, 0.50 mol) was heated under reflux (at ഠ
with an authentic sample. The latter was prepared as follows: tert-
butyl 4-(trifluoromethoxy)phenylcarbamate [6.9 g, 25 mmol; pre-
pared from 4-(trifluoromethoxy)aniline and di-tert-butyl dicarbon-
120 °C) for 20 h. The solvents were evaporated to dryness and the
residue extracted with diethyl ether (4 ϫ 50 mL). Distillation af-
forded a colorless liquid; b.p. 55Ϫ56 °C/3 Torr; n2D0 1.5123; yield
1
ate] was added to
a
precooled solution of sec-butyllithium
7.5 g (71%). Ϫ H NMR: δ ϭ 8.18 (d, J ϭ 8.5 Hz, 1 H), 7.91 (d,
(50 mmol) in tetrahydrofuran (50 mL) and hexanes (30 mL). After
2 h at Ϫ75 °C, the mixture was poured onto an excess of freshly
crushed dry ice. Extraction and crystallization afforded 2-(tert-
butoxycarbonyl)amino-5-(trifluoromethoxy)benzoic acid [colorless
J ϭ 8.2 Hz, 1 H), 7.78 (d, J ϭ 8.0 Hz, 1 H), 7.6 (m, 2 H), 7.44 (t,
J ϭ 7.8 Hz, 1 H), 7.37 (d, J ϭ 7.8 Hz, 1 H). Ϫ 1H NMR*: δ ϭ
8.17 (d, J ϭ 8.3 Hz, 1 H), 7.90 (d, J ϭ 8.1 Hz, 1 H), 7.79 (d, J ϭ
8.1 Hz, 1 H), 7.6 (m, 2 H), 7.46 (t, J ϭ 7.8 Hz, 1 H), 7.39 (dm, J ϭ
3994
Eur. J. Org. Chem. 2001, 3991Ϫ3997

The “Aryne” Route to 1- and 2-(Trifluoromethoxy)naphthalenes
FULL PAPER
7.7 Hz, 1 H). Ϫ 13C NMR: δ ϭ 145.2, 134.7, 127.8, 126.9 (2C), methoxy)naphthalene (6; 11.4 g, 50 mmol) in tetrachloromethane
126.8, 125.1, 122.2, 121.4, 120.3 (q, J ϭ 259.8 Hz), 116.4. Ϫ (0.33 L) was heated to gentle reflux (ഠ 80 °C) while bromine
C11H7F3O (212.17): calcd. C 62.27, H 3.33; found C 62.04, H 3.21. (2.6 mL, 8.0 g, 50 mmol) in tetrachloromethane (20 mL) was added
dropwise over the course of 2 min. The heating was continued for
3 min. According to gas chromatographic analysis (30 m, DB-1701,
2-(Trifluoromethoxy)naphthalene (9): This compound was prepared
analogously, from the isomeric cycloadduct 7 (11.4 g, 50 mmol);
180 °C; 30m DB-210, 180 °C), three products had formed, in the
colorless liquid; b.p. 58Ϫ60 °C/3 Torr; n2D0 1.5085; yield 7.7 g (73%).
approximate ratio of 3:3:4. Elution with a 1:8 (v/v) mixture of ethyl
Ϫ
1H NMR: δ ϭ 7.9 (m, 3 H), 7.64 (s, 1 H), 7.5 (m, 2 H), 7.31
acetate and hexanes from silica gel (0.35 L) gave two fractions. The
first one (11.1 g, 57%) contained two compounds, one of which
(14c) crystallized from ethanol (10 mL) as colorless prisms and the
other of which (14a) subsequently crystallized from hexanes as col-
orless platelets. A third isomer (14b) was isolated from the second
fraction (5.8 g, 30%) by crystallization from hexanes in the form of
colorless needles. Ϫ Compound 14a: m.p. 86Ϫ87 °C, yield 4.0 g
1
(dd, J ϭ 9.0, 1.6 Hz, 1 H). Ϫ H NMR*: δ ϭ 7.9 (m, 2 H), 7.83
(d, J ϭ 8.0 Hz, 1 H), 7.65 (s, 1 H), 7.5 (m, 2 H), 7.32 (dd, J ϭ 9.0,
1.6 Hz, 1 H). Ϫ 13C NMR: δ ϭ 146.8, 133.5, 131.7, 130.0, 127.8
(2C), 127.0, 126.3, 120.3 (q, J ϭ 258.0 Hz), 120.1, 118.1. Ϫ
C11H7F3O (212.17): calcd. C 62.27, H 3.33; found C 62.17, H 2.96.
5-(Trifluoromethoxy)-1-naphthol (10) and 8-(Trifluoromethoxy)-1-
naphthol (11): 1,4-Epoxy-1,4-dihydro-5-(trifluoromethoxy)naph-
thalene (6; 5.7 g, 25 mmol) was dissolved in methanol (40 mL) con-
taining concentrated (32%) hydrochloric acid (10 mL). After 2 h
heating under reflux (ഠ 75 °C), the solution was evaporated to
dryness and the residue was distilled; b.p. 92Ϫ93 °C/4 Torr; yield
5.3 g (93%). The 1:8 regioisomeric mixture was separated by pre-
parative gas chromatography (3 m, 10% SE-30, 70 Ǟ 200 °C [10
°C/min]). Ϫ Compound 10: m.p. 107Ϫ108 °C. Ϫ 1H NMR: δ ϭ
8.21 (d, J ϭ 8.0 Hz, 1 H), 7.70 (d, J ϭ 8.5 Hz, 1 H), 7.48 (t, J ϭ
8.1 Hz, 1 H), 7.4 (m, 2 H), 6.89 (d, J ϭ 7.6 Hz, 1 H). Ϫ 1H NMR*
: δ ϭ 8.19 (d, J ϭ 8.2 Hz, 1 H), 7.71 (d, J ϭ 8.5 Hz, 1 H), 7.46 (t,
J ϭ 8.0 Hz, 1 H), 7.42 (t, J ϭ 8.1 Hz, 1 H), 7.40 (dm, J ϭ 8.2 Hz,
1 H), 6.90 (dd, J ϭ 7.4, 0.8 Hz, 1 H), 5.39 (br. s, 1 H). Ϫ 13C
NMR: δ ϭ 151.4, 145.1, 128.4, 127.0, 125.9, 124.4, 120.9 (q, J ϭ
259.6 Hz), 120.8, 117.1, 114.2, 109.6. Ϫ Compound 11: m.p. 48Ϫ49
1
(21%). Ϫ H NMR: δ ϭ 7.35 (dd, J ϭ 8.0, 7.4 Hz,1 H), 7.29 (d,
J ϭ 7.3 Hz, 1 H), 7.18 (d, J ϭ 8.1 Hz, 1 H), 5.69 (d, J ϭ 4.5 Hz, 1
H), 5.48 (s, 1 H), 4.52 (dd, J ϭ 4.7, 2.5 Hz, 1 H), 3.81 (d, J ϭ
2.6 Hz, 1 H). Ϫ 13C NMR: δ ϭ 144.5, 144.4, 133.7, 130.4, 119.5,
118.2, 120.4 (q, J ϭ 258.9 Hz), 87.2, 81.2, 52.3, 49.9. Ϫ Compound
1
14b: m.p. 116Ϫ117 °C, yield 5.6 g (29%). Ϫ H NMR: δ ϭ 7.3 (m,
2 H), 7.12 (d, J ϭ 7.2 Hz, 1 H), 5.68 (s, 1 H), 5.55 (s, 1 H), 4.25
(s, 1 H). Ϫ 13C NMR: δ ϭ 145.7, 142.0, 134.9, 130.7, 121.5, 120.5
(q, J ϭ 260.0 Hz), 119.2, 88.0, 85.5, 51.2, 50.7. Ϫ Compound 14c:
m.p. 74Ϫ75 °C, yield 6.3 (32%). Ϫ 1H NMR: δ ϭ 7.4 (m, 2 H),
7.18 (d, J ϭ 7.1 Hz, 1 H), 5.65 (s, 1 H), 5.50 (d, J ϭ 4.7 Hz, 1 H),
4.55 (dd, J ϭ 4.6, 2.5 Hz, 1 H), 3.83 (d, J ϭ 2.6 Hz, 1 H). Ϫ 13C
NMR: δ ϭ 144.5, 143.0, 133.8, 129.8, 122.1, 121.2, 120.5 (q, J ϭ
259.2 Hz), 84.6, 83.3, 51.7, 49.9. Ϫ C11H7Br2F3O2 (387.99): calcd.
C 34.05, H 1.82; found C 34.07, H 1.92.
1
°C. Ϫ H NMR: δ ϭ 7.75 (dd, J ϭ 8.2, 1.1 Hz, 1 H), 7.43 (d, J ϭ
4.3 Hz, 2 H), 7.4 (m, 2 H), 7.29 (d, J ϭ 7.7 Hz, 1 H), 7.03 (quint,
J ϭ 4.4 Hz, 1 H). Ϫ H NMR*: δ ϭ 7.75 (dd, J ϭ 8.2, 1.1 Hz, 1
2,3-Dibromo-1,4-epoxy-1,2,3,4-tetrahydro-6-(trifluoromethoxy)-
naphthalenes (15): Analogous bromination of compound 7 (11.4 g,
50 mmol) gave a 1:1:1 mixture of three products (30 m, DB-1701,
180 °C, 30 m, DB-Wax, 150 °C). Column chromatography (see
above) afforded a first fraction (9.4 g, 48%) from which isomer 15c
was separated as colorless prisms by fractional crystallization from
ethanol, followed on subsequent recrystallization from hexanes by
isomer 15a, again as colorless prisms, and a second fraction (5.0 g,
26%) from which isomer 15b was obtained as colorless cubes by
crystallization from hexanes. Ϫ Compound 15a: m.p. 79Ϫ81 °C. Ϫ
1H NMR: δ ϭ 7.38 (d, J ϭ 8.0 Hz, 1 H), 7.27 (s, 1 H), 7.18 (dm,
J ϭ 8.2 Hz, 1 H), 5.49 (s, 1 H), 5.45 (d, J ϭ 4.6 Hz, 1 H), 4.55 (dd,
J ϭ 4.6, 2.5 Hz, 1 H), 3.80 (d, J ϭ 2.5 Hz, 1 H). Ϫ 13C NMR: δ ϭ
149.2, 140.0, 139.1, 121.1, 120.9, 120.3 (q, J ϭ 259.9 Hz), 116.9,
86.6, 82.9, 52.4, 50.0. Ϫ Compound 15b: m.p. 103Ϫ105 °C, yield
1
H), 7.43 (d, J ϭ 4.3 Hz, 2 H), 7.38 (t, J ϭ 7.8 Hz, 1 H), 7.34 (br.
s, 1 H), 7.29 (d, J ϭ 7.6 Hz, 1 H), 7.02 (quint, J ϭ 4.4 Hz, 1 H).
Ϫ
13C NMR: δ ϭ 151.9, 145.1, 136.9, 128.1, 127.6, 125.0, 120.5 (q,
J ϭ 259.2 Hz), 120.2, 116.1, 115.2, 112.7. Ϫ C11H7F3O2 (228.17):
calcd. C 57.90, H 3.09; found C 57.77, H 3.29.
6-(Trifluoromethoxy)-1-naphthol (12) and 7-(Trifluoromethoxy)-1-
naphthol (13): These compounds were prepared analogously, from
1,4-epoxy-1,4-dihydro-6-(trifluoromethoxy)naphthalene (9; 5.7 g,
25 mmol), yield 5.0 g (88%). The 1:5 regioisomeric mixture (30 m,
DB-1701, 100 °C, 30 m DB-210, 100 °C) was again separated by
preparative gas chromatography (3 m, 10% SE-30, 70 Ǟ 200 °C
1
[10 °C/min]). Ϫ Compound 12: m.p. 80Ϫ82 °C. Ϫ H NMR: δ ϭ
8.27 (d, J ϭ 9.0 Hz, 1 H), 7.64 (s, 1 H), 7.43 (d, J ϭ 8.3 Hz, 1 H),
1
1
4.5 g (23%). Ϫ H NMR: δ ϭ 7.37 (d, J ϭ 8.2 Hz, 1 H), 7.23 (s, 1
7.4 (m, 2 H), 6.83 (dd, J ϭ 7.2, 1.0 Hz, 1 H). Ϫ H NMR*: δ ϭ
H), 7.11 (dm, J ϭ 8.2, 1.0 Hz, 1 H), 5.52 (d, J ϭ 0.9 Hz, 2 H), 4.23
(s, 2 H). Ϫ 13C NMR: δ ϭ 144.9, 142.9, 141.1, 121.7, 120.9, 120.4
(q, J ϭ 260.2 Hz), 114.0, 87.5, 87.3, 51.3, 51.2. Ϫ Compound 15c:
8.25 (d, J ϭ 9.1 Hz, 1 H), 7.63 (s, 1 H), 7.41 (d, J ϭ 8.4 Hz, 1 H),
7.35 (t, J ϭ 7.9 Hz, 1 H), 7.32 (d, J ϭ 9.3 Hz, 1 H), 6.82 (dd, J ϭ
7.3, 0.8 Hz, 1 H), 5.40 (br. s, 1 H). Ϫ 13C NMR: δ ϭ 151.6, 147.5,
135.1, 127.4, 124.3, 122.7, 120.6 (q, J ϭ 256.5 Hz), 120.3, 119.2,
117.6, 108.8. Ϫ Compound 13: m.p. 77Ϫ78 °C. Ϫ 1H NMR: δ ϭ
8.06 (s, 1 H), 7.85 (d, J ϭ 8.7 Hz, 1 H), 7.47 (d, J ϭ 8.1 Hz, 1 H),
1
m.p. 71Ϫ72 °C. Ϫ H NMR: δ ϭ 7.44 (d, J ϭ 8.1 Hz, 1 H), 7.25
(s, 1 H), 7.19 (dm, J ϭ 8.2 Hz, 1 H), 5.49 (s, 1 H), 5.45 (d, J ϭ
4.6 Hz, 1 H), 4.55 (dd, J ϭ 4.6, 2.5 Hz, 1 H), 3.82 (d, J ϭ 2.6 Hz,
1 H). Ϫ 13C NMR: δ ϭ 148.9, 143.6, 139.9, 124.5, 120.4 (q, J ϭ
260.4 Hz), 120.3, 113.4, 86.8, 82.7, 52.2, 50.2. Ϫ C11H7Br2F3O2
(387.99): calcd. C 34.05, H 1.82; found C 33.98, H 1.85.
1
7.4 (m, 2 H), 6.88 (d, J ϭ 7.3 Hz, 1 H). Ϫ H NMR*: δ ϭ 8.04 (s,
1 H), 7.83 (d, J ϭ 8.9 Hz, 1 H), 7.46 (d, J ϭ 8.3 Hz, 1 H), 7.34 (d,
J ϭ 8.9 Hz, 1 H), 7.31 (t, J ϭ 7.9 Hz, 1 H), 6.85 (d, J ϭ 7.5 Hz, 1
H), 5.55 (br. s, 1 H). Ϫ 13C NMR: δ ϭ 151.2, 146.5, 136.4, 129.7,
126.2, 124.5, 120.7, 120.5 (q, J ϭ 260.1 Hz), 120.4, 112.8, 109.4. Ϫ
C11H7F3O2 (228.17): calcd. C 57.90, H 3.09; found C 58.02, H 3.24.
3-Bromo-1,4-epoxy-1,4-dihydro-5-(trifluoromethoxy)naphthalene
(16): Compound 14a (7.8 g, 20 mmol), to which the 2-exo,3-endo
configuration was assigned on the basis of its NMR spectrum (see
above), was dissolved in tetrahydrofuran (40 mL) and treated with
potassium tert-butoxide (2.2 g, 20 mmol) over 2 h at 50 °C. Upon
distillation, a colorless liquid was collected; b.p. 99Ϫ101 °C/4 Torr;
2,3-Dibromo-1,4-epoxy-1,2,3,4-tetrahydro(trifluoromethoxy)-
naphthalenes, Bromo-1,4-epoxy-1,4-dihydro(trifluoromethoxy)naph-
thalenes, and Bromo(trifluoromethoxy)naphthols
2,3-Dibromo-1,4-epoxy-1,2,3,4-tetrahydro-5-(trifluoromethoxy)- n2D0 1.5123; yield 5.4 g (88%). Ϫ 1H NMR: δ ϭ 7.21 (d, J ϭ 7.0 Hz,
naphthalenes (14): A solution of 1,4-epoxy-1,4-dihydro-5-(trifluoro-
1 H), 7.10 (dd, J ϭ 8.3, 7.0 Hz, 1 H), 7.01 (d, J ϭ 2.1 Hz, 1 H),
Eur. J. Org. Chem. 2001, 3991Ϫ3997
3995

M. Schlosser, E. Castagnetti
FULL PAPER
1
6.92 (dq, J ϭ 8.5, 0.8 Hz, 1 H), 5.76 (m, 1 H), 5.71 (s, 1 H). Ϫ 13C
NMR: δ ϭ 151.0, 142.6, 139.9, 138.8, 136.0, 128.2, 120.4 (q, J ϭ
258.6 Hz), 119.2, 118.8, 84.6, 84.4. Ϫ C11H6BrF3O2 (307.07): calcd.
C 43.03, H 1.97; found C 43.22, H 1.98.
3.1 g (76%). Ϫ H NMR: δ ϭ 7.90 (d, J ϭ 1.9 Hz, 1 H), 7.26 (d,
J ϭ 7.6 Hz, 1 H), 7.09 (t, J ϭ 7.7 Hz, 1 H), 6.93 (d, J ϭ 7.9 Hz, 1
H), 6.12 (s, 1 H), 5.89 (br. s, 1 H). Ϫ 13C NMR: δ ϭ 166.5, 154.9,
149.7, 148.5, 148.3, 139.6, 128.0, 120.6 (q, J ϭ 259.4 Hz), 119.7,
119.5, 83.7, 79.7. Ϫ C12H7F3O4 (272.18): calcd. C 52.95, H 2.59;
found C 52.54, H 2.48.
2-Bromo-1,4-epoxy-1,4-dihydro-5-(trifluoromethoxy)naphthalene
(17): Starting with isomer 14c (7.8 g, 20 mmol), to which the 2-
endo,3-exo configuration was assigned, compound 17 was obtained
1,4-Epoxy-1,4-dihydro-5-trifluoromethoxy-2-naphthoic Acid (23):
This compound was prepared analogously, from 2-bromo-1,4-
1.5095; yield 5.8 g (94%). Ϫ H NMR: δ ϭ 7.33 (d, J ϭ 7.3 Hz, 1 epoxy-1,4-dihydro-5-(trifluoromethoxy)naphthalene (17; 4.6 g,
after distillation as a colorless liquid; b.p. 95Ϫ97 °C/4 Torr; n2D0
1
H), 7.09 (dd, J ϭ 8.3, 7.0 Hz, 1 H), 6.95 (d, J ϭ 1.9 Hz, 1 H), 6.91
(dt, J ϭ 8.2, 0.8 Hz, 1 H), 5.93 (s, 1 H), 5.51 (d, J ϭ 1.0 Hz, 1 H). yield 3.5 g (86%). Ϫ 1H NMR: δ ϭ 7.83 (d, J ϭ 1.2 Hz, 1 H), 7.36
13C NMR: δ ϭ 150.2, 141.8, 139.7, 138.9, 136.7, 127.6, 120.4 (q,
(d, J ϭ 7.0 Hz, 1 H), 7.10 (dd, J ϭ 8.3, 6.9 Hz, 1 H), 6.90 (d, J ϭ
J ϭ 257.8 Hz), 120.2, 119.6, 87.1, 82.1. Ϫ C11H6BrF3O2 (307.07): 8.4 Hz, 1 H), 6.07 (s, 1 H), 5.94 (s, 1 H). Ϫ 13C NMR: δ ϭ 167.6,
15 mmol); colorless needles; m.p. 149Ϫ150 °C (dec.; from hexanes);
Ϫ
calcd. C 43.03, H 1.97; found C 43.28, H 2.14.
154.2, 150.9, 149.1, 142.6, 138.4, 128.3, 120.6 (q, J ϭ 258.3 Hz),
119.8 (2C), 82.1, 81.5. Ϫ C12H7F3O4 (272.18): calcd. C 52.95, H
2.59; found C 52.75, H 2.36.
The reaction between isomer 14b (7.8 g, 20 mmol) and potassium
tert-butoxide required 20 h to attain completion. The elimination
products 16 and 17 were obtained as a 53:47 mixture (30 m, DB-
1701, 150 °C; 30 m, DB-210, 150 °C). The two isomers (together
1,4-Epoxy-1,4-dihydro-7-trifluoromethoxy-2-naphthoic Acid (26):
This compound was prepared analogously, from 2-bromo-1,4-
5.7 g, 97%) could be quantitatively separated by column chromato- epoxy-1,4-dihydro-7-(trifluoromethoxy)naphthalene (18; 4.6 g,
graphy, using a 1:7 mixture of ethyl acetate and hexanes.
15 mmol); colorless cubes; m.p. 108Ϫ110 °C (dec.; from hexanes);
yield 3.4 g (83%). Ϫ 1H NMR: δ ϭ 7.86 (d, J ϭ 2.0 Hz, 1 H), 7.30
(d, J ϭ 7.8 Hz, 1 H), 7.28 (s, 1 H), 6.89 (dm, J ϭ 7.8 Hz, 1 H),
5.91 (s, 1 H), 5.88 (br. s, 1 H). Ϫ 13C NMR: δ ϭ 168.0, 155.4,
150.3, 148.5, 147.1, 144.6, 121.7, 120.6 (q, J ϭ 258.5 Hz), 117.9,
115.3, 83.2, 81.8. Ϫ C12H7F3O4 (272.18): calcd. C 52.95, H 2.59;
found C 52.44, H 2.31.
3-Bromo- and 2-Bromo-1,4-epoxy-1,4-dihydro-6-(trifluoromethoxy)-
naphthalene (18 and 19): A 1:1 mixture of compound 15a and 15c
(9.7 g, 25 mmol), to which the 2-exo,3-endo and 2-endo,3-exo con-
figurations, respectively, were assigned, was allowed to react with
potassium tert-butoxide (2.8 g, 25 mmol) over 2 h at 50 °C. On elu-
tion with a 1:7 (v/v) mixture of ethyl acetate and hexanes from a
column filled with silica gel (0.25 L), a perfect separation of the 1,4-Epoxy-1,4-dihydro-6-trifluoromethoxy-2-naphthoic Acid (29):
two regioisomers (formed in a 1:1 ratio; gas chromatography: 30
This compound was prepared analogously, from 2-bromo-1,4-
m, DB-1701, 150 °C; 30 m, DB-210, 150 °C) was achieved. Ϫ Com-
epoxy-1,4-dihydro-6-(trifluoromethoxy)naphthalene (19; 4.6 g,
pound 18: b.p. 97Ϫ99 °C/4 Torr; n2D0 1.5060; yield 3.4 g (44%). Ϫ 15 mmol); colorless needles; m.p. 139Ϫ140 °C (dec.; from hexanes);
1H NMR: δ ϭ 7.26 (s, 1 H), 7.24 (d, J ϭ 7.8 Hz, 1 H), 7.00 (d,
yield 3.6 g (88%). Ϫ 1H NMR: δ ϭ 7.87 (d, J ϭ 1.9 Hz, 1 H), 7.37
J ϭ 2.2 Hz, 1 H), 6.92 (dm, J ϭ 7.8 Hz, 1 H), 5.77 (br. s, 1 H), (d, J ϭ 7.8 Hz, 1 H), 7.19 (s, 1 H), 6.89 (dq, J ϭ 7.9, 1.0 Hz, 1 H),
5.48 (s, 1 H). Ϫ 13C NMR: δ ϭ 149.6, 146.6, 146.1, 139.8, 136.4, 5.91 (s, 1 H), 5.86 (br. s, 1 H). Ϫ 13C NMR: δ ϭ 167.5, 154.5,
120.4 (q, J ϭ 256.8 Hz), 120.5, 118.1, 115.1, 86.7, 84.0. Ϫ Com-
149.0, 148.9, 146.9, 146.3, 121.6, 120.5 (q, J ϭ 260.1 Hz), 118.2,
pound 19: b.p. 97Ϫ99 °C/4 Torr; n2D0 1.5131; yield 3.2 g (42%). Ϫ 115.4, 83.4, 81.6. Ϫ C12H7F3O4 (272.18): calcd. C 52.95, H 2.59;
1H NMR: δ ϭ 7.36 (d, J ϭ 7.8 Hz, 1 H), 7.13 (s, 1 H), 6.97 (d,
J ϭ 2.0 Hz, 1 H), 6.88 (dm, J ϭ 7.8 Hz, 1 H), 5.74 (br. s, 1 H),
5.47 (s, 1 H). Ϫ 13C NMR: δ ϭ 150.5, 147.4, 145.8, 139.6, 137.3,
121.6, 120.7 (q, J ϭ 258.4 Hz), 117.8, 114.7, 86.9, 84.4. Ϫ Both
products 18 and 19 proved to be too unstable to be dispatched to
an outside analytical service.
found C 52.63, H 2.55.
8-Trifluoromethoxy-2-naphthoic Acid (21): A large excess of zinc
powder (6.6 g, 0.10 mol) was added to a solution of 1,4-epoxy-1,4-
dihydro-8-trifluoromethoxy-2-naphthoic acid (20; 2.7 g, 10 mmol).
After having been heated for 20 h under reflux (ഠ 120 °C), the
mixture was filtered under suction, diluted with water (0.10 L), and
extracted with diethyl ether (3 ϫ 50 mL). The combined organic
layers were dried and the solvents evaporated. Upon crystallization
Regioisomer 15b of the dibromo compound (7.8 g, 20 mmol) re-
quired treatment with potassium tert-butoxide (2.2 g, 20 mmol) in
tetrahydrofuran over 20 h at 50 °C to afford a 1:1 mixture of the from hexanes (10 mL), colorless prisms were obtained, m.p.
elimination products 18 and 19; total yield 4.7 g (76%).
177Ϫ179 °C, yield 1.8 g (70%). Ϫ 1H NMR: δ ϭ 9.00 (s, 1 H), 8.21
(dd, J ϭ 8.7, 1.6 Hz, 1 H), 7.97 (d, J ϭ 8.7 Hz, 1 H), 7.85 (d, J ϭ
8.1 Hz, 1 H), 7.61 (d, J ϭ 7.9 Hz, 1 H), 7.47 (d, J ϭ 7.8 Hz, 1 H).
1,4-Epoxy-1,4-dihydro(trifluoromethoxy)-2-naphthoic Acids, Tri-
fluoromethoxy-2-naphthoic Acids, and 2-Bromo(trifluoromethoxy)-
1-naphthols
Ϫ
13C NMR: δ ϭ 171.1, 146.1, 136.9, 128.3, 128.1, 127.6, 126.6,
126.5, 126.1, 125.6, 120.7 (q, J ϭ 261.1 Hz), 116.9. Ϫ C12H7F3O3
(256.18): calcd. C 56.26, H 2.75; found C 56.41, H 2.57.
1,4-Epoxy-1,4-dihydro-8-trifluoromethoxy-2-naphthoic Acid (20): 2-
Bromo-1,4-epoxy-1,4-dihydro-8-(trifluoromethoxy)naphthalene
(16; 4.6 g, 15 mmol) in tetrahydrofuran (30 mL) was treated at Ϫ75
°C with butyllithium (15 mmol) in cyclohexane (10 mL). After 15
min the reaction mixture was poured onto an excess of freshly
crushed dry ice. The solvents were evaporated and the residue was
dissolved in a 1  aqueous solution of sodium hydroxide (30 mL).
The alkaline phase was washed with diethyl ether (2 ϫ 15 mL),
acidified to pH 1, and extracted with diethyl ether (3 ϫ 20 mL).
The combined organic layers were dried and the solvents evapor-
ated. The remaining solid material was recrystallized from hexanes
5-Trifluoromethoxy-2-naphthoic Acid (24): This compound was pre-
pared analogously, from 1,4-epoxy-1,4-dihydro-5-trifluorometh-
oxy-2-naphthoic acid (23; 2.7 g, 10 mmol); colorless prisms; m.p.
186Ϫ187 °C; yield 2.0 g (78%). Ϫ 1H NMR: δ ϭ 8.78 (s, 1 H), 8.26
(m, 2 H), 7.97 (dd, J ϭ 7.8, 1.1 Hz, 1 H), 7.6 (m, 2 H). Ϫ 13C
NMR: δ ϭ 171.0, 145.1, 133.7, 131.8, 129.3, 128.8, 127.4, 126.5,
126.3, 122.1, 120.7 (q, J ϭ 260.2 Hz), 119.1. Ϫ C12H7F3O3
(256.18): calcd. C 56.26, H 2.75; found C 56.27, H 2.58.
7-Trifluoromethoxy-2-naphthoic Acid (27): This compound was pre-
(10 mL) to afford colorless prisms; m.p. 127Ϫ129 °C (dec.); yield pared analogously, from 1,4-epoxy-1,4-dihydro-2-trifluorometh-
3996 Eur. J. Org. Chem. 2001, 3991Ϫ3997

The “Aryne” Route to 1- and 2-(Trifluoromethoxy)naphthalenes
oxy-2-naphthoic acid (26; 2.7 g, 10 mmol). Colorless prisms were (grant 20-55Ј303-98) and the Bundesamt für Bildung und Wissen-
FULL PAPER
obtained; m.p. 169Ϫ170 °C (from hexanes), yield 1.8 g (70%). Ϫ
schaft, Bern (grant 97.0083 linked to the TMR project
1H NMR: δ ϭ 8.73 (s, 1 H), 8.17 (dd, J ϭ 8.6, 1.6 Hz, 1 H), 7.98 FMRXCT-970129).
(d, J ϭ 8.9 Hz, 2 H), 7.83 (s, 1 H), 7.50 (dd, J ϭ 8.9, 1.5 Hz, 1 H).
Ϫ
13C NMR: δ ϭ 170.7, 147.4, 134.1, 132.6, 131.7, 130.0, 128.2,
127.7, 125.9, 122.7, 120.5 (q, J ϭ 260.6 Hz), 119.4. Ϫ C12H7F3O3
(256.18): calcd. C 56.26, H 2.75; found C 55.92, H 2.43.
[1]
[2]
[3]
[4]
[5]
E. Castagnetti, M. Schlosser, Eur. J. Org. Chem. 2001,
691Ϫ695.
F. Mongin, M. Schlosser, Tetrahedron Lett. 1997, 37,
1559Ϫ1562.
F. Mongin, A. Tognini, F. Cottet, M. Schlosser, Tetrahedron
Lett. 1998, 39, 1749.
F. Mongin, E. Marzi, M. Schlosser, Eur. J. Org. Chem. 2001,
in press.
R. Ruzziconi, S. Leconte, M. Schlosser, unpublished work
(2001).
G. Wittig, L. Pohmer, Angew. Chem. 1955, 67, 348Ϫ348.
J. P. Brewer, H. Heaney, Tetrahedron Lett. 1965, 7, 4709Ϫ4712.
D. D. Callander, P. L. Coe, J. C. Tatlow, J. Chem. Soc., Chem.
Commun. 1966, 143Ϫ144.
H. Heaney, J. M. Jablonski, Tetrahedron Lett. 1966, 8,
4529Ϫ4531.
G. W. Gribbe, W. J. Kelly, Tetrahedron Lett. 1981, 22,
2475Ϫ2478.
6-Trifluoromethoxy-2-naphthoic Acid (30): This compound was pre-
pared analogously, from 1,4-epoxy-1,4-dihydro-6-trifluorometh-
oxy-2-naphthoic acid (29; 2.7 g, 10 mmol); colorless cubes; m.p.
210Ϫ211 °C (from hexanes); yield 2.2 g (86%). Ϫ 1H NMR
(D3CCOCD3): δ ϭ 8.69 (s, 1 H), 8.17 (dd, J ϭ 8.6, 1.6 Hz, 1 H),
8.04 (d, J ϭ 9.0 Hz, 1 H), 7.91 (d, J ϭ 8.7 Hz, 1 H), 7.72 (s, 1 H),
7.41 (dd, J ϭ 8.9, 1.6 Hz, 1 H). Ϫ 13C NMR (D3CCOCD3): δ ϭ
168.1, 148.4, 135.8, 131.5, 131.1, 130.7, 127.9 (2C), 126.7, 120.6,
120.5 (q, J ϭ 260.9 Hz), 117.5. Ϫ C12H7F3O3 (256.18): calcd. C
56.26, H 2.75; found C 56.34, H 2.60.
[6]
[7]
[8]
2-Bromo-8-trifluoromethoxy-1-naphthol (22): 3-Bromo-1,4-epoxy-
1,4-dihydro-5-(trifluoromethoxy)naphthalene (16; 3.1 g, 10 mmol)
was added to a mixture of methanol (15 mL) and concentrated
(32%) hydrochloric acid (5 mL), which was heated to 75 °C for 20 h
before being evaporated to dryness. The residue was eluted from
silica gel (0.15 L) with hexanes containing 10% of ethyl acetate,
giving colorless prisms; m.p. 39Ϫ41 °C (from hexanes); yield 2.6 g
[9]
[10]
[11]
[12]
[13]
G. Yamamoto, M. Suzuki, M. Oki, Bull. Chem. Soc. Jpn. 1983,
56, 306Ϫ313.
˜
G. Gavina, S. V. Luis, A. M. Costero, P. Gil, Tetrahedron 1986,
1
(85%). Ϫ H NMR: δ ϭ 7.73 (d, J ϭ 8.1 Hz, 1 H), 7.60 (d, J ϭ
42, 155Ϫ166.
9.0 Hz, 1 H), 7.45 (t, J ϭ 8.0 Hz, 1 H), 7.37 (d, J ϭ 7.9 Hz, 1 H),
7.32 (d, J ϭ 8.9 Hz, 1 H), 7.18 (s, 1 H). Ϫ 13C NMR: δ ϭ 147.9,
144.3, 136.0, 130.8, 127.5, 125.9, 121.0, 120.5 (q, J ϭ 262.1 Hz),
118.0, 117.4, 107.2. Ϫ C11H6BrF3O2 (307.07): calcd. C 43.03, H
1.97; found C 43.10, H 1.86.
G. W. Gribble, D. J. Keavy, E. R. Olson, I. D. Rae, A. Staffa,
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35Ϫ154; spec. pp. 74, 89 and 123.
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[14]
[15]
[16]
[17]
[18]
[19]
2-Bromo-5-trifluoromethoxy-1-naphthol (25): This compound was
prepared analogously, from 2-bromo-1,4-epoxy-1,4-dihydro-5-(tri-
fluoromethoxy)naphthalene (17; 3.1 g, 10 mmol); colorless needles
(from hexanes); m.p. 84Ϫ85 °C; yield 2.9 g (94%). Ϫ 1H NMR:
δ ϭ 8.18 (d, J ϭ 8.2 Hz, 1 H), 7.6 (m, 2 H), 7.50 (t, J ϭ 8.1 Hz, 1
H), 7.41 (d, J ϭ 7.6 Hz, 1 H), 6.09 (s, 1 H). Ϫ 13C NMR: δ ϭ
148.2, 145.0, 129.5, 127.3, 125.7, 125.6, 121.3, 120.4 (q, J ϭ
260.6 Hz), 117.4, 114.9, 105.3. Ϫ C11H6BrF3O2 (307.07): calcd. C
43.03, H 1.97; found C 43.13, H 1.88.
H. Volz, W. D. Mayer, Justus Liebigs Ann. Chem. 1975,
835Ϫ848.
J. Burdon, D. W. Davies, G. del Conde, J. Chem. Soc., Perkin
Trans. 2 1976, 1193Ϫ1195.
H. Volz, H. J. Streicher, Tetrahedron 1977, 33, 3133Ϫ3135.
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1513Ϫ1517.
R. D. Chambers, M. Salisbury, G. Asey, G. Moggi, J. Chem.
Soc., Chem. Commun. 1988, 680Ϫ681.
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839Ϫ851.
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67, 2188Ϫ2195.
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Morton, J. Am. Chem. Soc. 1990, 112, 1427Ϫ1434.
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Chem. 1996, 100, 2942Ϫ2949.
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Chem. Soc. 1997, 119, 6648Ϫ6655.
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Olah, P. V. R. Schleyer), Wiley, New York, 1976, 2135Ϫ2262
(Chapter 36).
[20]
[21]
2-Bromo-7-trifluoromethoxy-1-naphthol (28): This compound was
prepared analogously, from 2-bromo-1,4-epoxy-1,4-dihydro-7-(tri-
fluoromethoxy)naphthalene (18; 3.1 g, 10 mmol); colorless needles
(from hexanes); m.p. 69Ϫ71 °C; yield 2.9 g (94%). Ϫ 1H NMR: δ ϭ
8.05 (s, 1 H), 7.80 (d, J ϭ 9.0 Hz, 1 H), 7.51 (d, J ϭ 9.0 Hz, 1 H),
7.36 (dd, J ϭ 9.0, 2.1 Hz, 1 H), 7.32 (d, J ϭ 8.9 Hz, 1 H), 6.11 (br.
s, 1 H). Ϫ 13C NMR: δ ϭ 148.0, 147.1, 131.9, 129.7, 128.9, 124.6,
120.9 (2C), 120.5 (q, J ϭ 258.8 Hz), 113.2, 105.2. Ϫ C11H6BrF3O2
(307.07): calcd. C 43.03, H 1.97; found C 43.04, H 1.89.
[22]
[23]
[24]
[25]
[26]
[27]
2-Bromo-6-trifluoromethoxy-1-naphthol (31): This compound was
prepared analogously, from 2-bromo-1,4-epoxy-1,4-dihydro-6-(tri-
fluoromethoxy)naphthalene (19; 3.1 g, 10 mmol); colorless needles
(from hexanes); m.p. 73Ϫ74 °C; yield 2.8 g (91%). Ϫ 1H NMR:
δ ϭ 8.28 (d, J ϭ 9.2 Hz, 1 H), 7.62 (s, 1 H), 7.54 (d, J ϭ 8.9 Hz,
1 H), 7.36 (d, J ϭ 9.1 Hz, 1 H), 7.30 (d, J ϭ 8.9 Hz, 1 H), 6.02 (s,
1 H). Ϫ 13C NMR: δ ϭ 148.3, 142.9, 129.9, 124.8, 124.6, 122.6,
121.0, 120.5 (q, J ϭ 260.7 Hz), 120.1, 117.6, 104.3. Ϫ C11H6BrF3O2
(307.07): calcd. C 43.03, H 1.97; found C 43.19, H 1.78.
[28]
[29]
[30]
[31]
[32]
M. Schlosser, J. Porwisiak, F. Morgin, Tetrahedron 1998, 54,
895Ϫ900.
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3263Ϫ3268.
Acknowledgments
This work was financially supported by the Schweizerische Na-
tionalfonds zur Förderung der wissenschaftlichen Forschung, Bern
Received May 10, 2001
[O01228]
Eur. J. Org. Chem. 2001, 3991Ϫ3997
3997