PAPER
Metalation of 1- and 2-(Trifluoromethyl)naphthalenes
801
ish platelets; yield: 13.1 g (79%); mp 98–100 °C (Lit.52 mp 98–
mL) for 2 h at 0 °C, before gaseous CO was bubbled into the reac-
2
1
00 °C);.
tion mixture for 20 min. The solvent was evaporated and the residue
partitioned between 6.0 M HCl (20 mL) and Et O (20 mL). The or-
2
1
-Bromo-8-(trifluoromethyl)naphthalene (2)
ganic layer was dried and evaporated. Crystallization of the residue
from a 3:1 mixture of heptanes and EtOAc afforded colorless nee-
dles; yield: 1.72 g (72%): mp 159–161 °C (Lit. mp 167–168 °C).
‘Spray-dried’ KF (2.9 g, 50 mmol) and CuI (9.5 g, 50 mol) were
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3
thoroughly mixed and heated under vacuum (1 mmHg) with the
flame of a Bunsen burner under gentle shaking until an homoge-
neous greenish color was obtained. N-Methylpyrrolidinone (0.10 L)
and trimethyl(trifluoromethyl)silane (7.4 mL, 7.1 g, 50 mmol) were
added.The slurry was heated to 75 °C in the course of 45 min before
1
H NMR: d = 8.1 (m, 2 H), 8.0 (m, 1 H), 7.7 (m, 3 H).
1
3
C NMR:* d = 168.5, 135.5, 133.0 (q, J = 3 Hz), 131.2, 129.7,
30.1, 129.3 (2 C), 126.7, 125.0 (q, J = 274 Hz), 124.1 (q, J = 32
1
Hz), 122.2 (q, J = 4 Hz).
1
-bromo-8-iodonaphthalene (17 g, 50 mmol) was added. After 20 h,
the cold reaction mixture was poured into 12% ammonia and ex-
Anal. Calcd for C H F O (240.18): C, 60.01; H, 2.94. Found: C,
59.77; H, 2.86.
1
2
7
3
2
tracted with Et O (3 × 0.10 L). The combined organic layers were
2
washed consecutively with 12% ammonia (2 × 0.10 L), 2.0 M HCl
(
0.10 L), a sat. aq solution of NaHCO (0.10 L) and brine (0.10 L).
3
2,3-Dibromonaphthalene
After drying and evaporation, crystallization of the residue from
hexanes afforded slightly brownish platelets; yield: 12.6 g (92%);
mp 77–79 °C.
Chlorotrimethylsilane (28 mL, 24 g, 0.22 mol) was added all at once
50
to a slurry of 6,7-dibromo-1,4-dihydronaphthalene-1,4-epoxide
(
23 g, 75 mmol) and NaI (34 g, 0.22 mol) in MeCN (0.25 L). In the
course of 2 min, the temperature spontaneously rose to 60 °C. After
5 min, the reaction mixture was poured into a sat. solution of
1
H NMR: d = 8.11 (d, J = 7.4 Hz, 1 H), 8.07 (dd, J = 7.7, 1.3 Hz, 1
1
H), 8.04 (d, J = 8.3 Hz, 1 H), 7.89 (dd, J = 8.0, 1.3 Hz, 1 H), 7.53
NaHCO (0.10 L) and extracted with Et O (2 × 0.30 L). The com-
(
ddq, J = 8.3, 7.4, 0.8 Hz, 1 H), 7.37 (t, J = 7.8 Hz, 1 H).
3
2
bined organic layers were washed consecutively with a 2.0 M aq so-
lution of Na S O (0.10 L) and brine (0.10 L), dried and evaporated.
1
3
C NMR: d = 136.7, 136.5, 134.7 (q, J = 1 Hz), 129.6, 128.9, 128.7
2
2
3
(
q, J = 8 Hz), 126.6, 125.3 (q, J = 31 Hz), 124.5, 124.2 (q, J = 273
Crystallization of the residue from heptanes afforded slightly yel-
Hz), 117.0.
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lowish needles; yield: 15.9 g (74%); mp 138–139 °C (Lit. mp
Anal. Calcd for C H BrClF (275.07): C, 48.03; H, 2.20. Found: C,
137–139 °C).
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5
3
4
7.80; H, 2.15.
2
-Bromo-3-iodonaphthalene (8)
8
-Trifluoromethyl-1-naphthoic Acid (3)
At –10 °C, isopropylmagnesium chloride (60 mmol) was added to a
solution of 2,3-dibromonaphthalene (17 g, 60 mmol) in THF (0.10
L). After 45 min at this temperature, the reaction mixture was
cooled to –75 °C and then treated with I (15 g, 60 mmol) dissolved
in THF (60 mL). The mixture was partitioned between aq 2.0 M so-
lution of Na S O (50 mL) and Et O (0.10 L). The organic layers
BuLi (15 mmol) in hexanes (9 mL) was added dropwise in the
course of 10 min to a solution of 1-bromo-8-(trifluoromethyl)naph-
thalene (2; 4.1 g, 15 mmol) in THF (30 mL) kept in a dry ice/MeOH
bath. After 5 min at –75 °C, the reaction mixture was poured onto
an excess of freshly crushed dry ice covered with THF (20 mL). The
2
2
2
3
2
volatiles were evaporated and the residue partitioned between Et O
were filtered through a pad of basic alumina (0.20 L), which was
2
(50 mL) and 6.0 M HCl (20 mL). After drying and evaporation, the
rinsed with a 2:1 mixture of petroleum ether and Et O. Evaporation
2
residue crystallized from a 3:1 mixture of heptanes and EtOAc as
tiny colorless needles; yield: 2.75 g (76%); mp 169–171 °C.
afforded slightly yellowish needles which were used as such for the
next step; yield: 18.2 g (91%); mp 117–119 °C (Lit. mp 120 °C).
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5
1
H NMR:* d = 8.30 (d, J = 8.0 Hz, 1 H), 8.22 (dd, J = 8.3, 1.6 Hz,
2
-Bromo-3-(trifluoromethyl)naphthalene (9)
1
H), 8.12 (d, J = 7.4 Hz, 1 H), 8.03 (dd, J = 7.0, 1.3 Hz, 1 H), 7.77
Prepared from 2-bromo-3-iodonaphthalene (8; 17 g, 50 mmol) anal-
ogously as described above for 1-bromo-8-(trifluoromethyl)naph-
thalene (2) for 20 h at 50 °C. When the residue obtained after
extraction and evaporation was triturated with MeOH (50 mL), un-
consumed starting material (5.2 g) remained undissolved. Filtration,
evaporation and crystallization from pentanes afforded tiny color-
less needles; yield: 6.91 g (48%); mp 46–48 °C.
(
ddq, J = 8.0, 7.4, 0.9 Hz, 1 H), 7.69 (dd, J = 8.3, 7.0 Hz, 1 H).
1
3
C NMR:* d = 170.0, 135.7, 134.8, 133.4, 131.8, 130.9, 129.9 (q,
J = 7 Hz), 126.8 (q, J = 31 Hz), 126.4, 126.2, 126.0 (q, J = 273 Hz),
1
25.3 (q, J = 1 Hz).
Anal. Calcd for C H F O (240.18): C, 60.01; H, 2.94. Found: C,
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3
2
5
9.91; H, 2.82.
1
H NMR: d = 8.22 (s, 1 H), 8.20 (s, 1 H), 7.91 (d, J = 8.3 Hz, 1 H),
1
-Bromo-2-(trifluoromethyl)naphthalene (7)
7
.81 (d, J = 8.3 Hz, 1 H), 7.64 (ddd, J = 8.6, 6.7, 1.3 Hz, 1 H), 7.60
3
8
Prepared from 1-bromo-2-iodonaphthalene (33 g, 0.10 mol) anal-
ogously as described above for 1-bromo-8-(trifluoromethyl)naph-
thalene (2) but heating the reaction mixture for 20 h only to 50 °C.
Upon distillation a colorless liquid was collected which solidified;
yield: 16.9 g (61%); mp 58–60 °C; bp 114–116 °C/5 mmHg.
(
ddd, J = 8.3, 6.7, 1.3 Hz, 1 H).
1
3
C NMR: d = 135.2, 133.8, 130.6, 129.2, 128.8, 128.6 (q, J = 6
Hz), 127.6, 127.0 (q, J = 35 Hz), 123.1 (q, J = 273 Hz), 114.8 (q,
J = 1 Hz).
1
Anal. Calcd for C11H BrF (275.06): C, 48.03; H, 2.20. Found: C,
6 3
H NMR: d = 8.50 (d, J = 8.6 Hz, 1 H), 7.90 (d, J = 8.6 Hz, 1 H),
4
7.93; H, 2.22.
7
.88 (dd, J = 8.3, 1.6 Hz, 1 H), 7.73 (d, J = 8.6 Hz, 1 H), 7.69 (ddd,
J = 8.3, 7.0, 1.6 Hz, 1 H), 7.65 (ddd, J = 8.0, 6.7, 1.3 Hz, 1 H).
3
-Trifluoromethyl-2-naphthoic Acid (5)
1
3
C NMR: d = 135.4, 132.5, 128.6, 128.4, 128.3, 128.3 (q, J = 28
Hz), 128.2, 128.1, 123.5 (q, J = 274 Hz), 122.8 (q, J = 6 Hz), 122.6
q, J = 2 Hz).
Prepared from 2-bromo-3-(trifluoromethyl)naphthalene (9; 2.8 g,
0 mmol) exactly as described for 2-trifluoromethyl-1-naphthoic
acid (4); colorless needles (from a 3:1 mixture of pentanes and
1
(
5
3
EtOAc); yield: 1.94 g (81%); mp 198–200 °C (Lit. mp 201–203).
Anal. Calcd for C H BrClF (275.07): C, 48.03; H, 2.20. Found: C,
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3
4
8.15; H, 2.19.
1
H NMR:* d = 8.59 (s, 1 H), 8.49 (s, 1 H), 8.20 (sym. m, 2 H), 7.80
sym. m, 2 H).
(
2
-Trifluoromethyl-1-naphthoic Acid (4)
1
-Bromo-2-(trifluoromethyl)naphthalene (7; 2.7 g, 10 mmol) was
treated with isopropylmagnesium chloride (10 mmol) in THF (20
Synthesis 2005, No. 5, 798–803 © Thieme Stuttgart · New York