The Journal of Organic Chemistry
Note
added dropwise to a solution of 1-methoxy-2-naphthoic acid (2) (606
mg, 3.0 mmol) in THF at 0 °C. Stirring was maintained this
temperature for 2 h. Standard workup followed by recrystallization (n-
hexane/ethylacetate 1:3) gave 5f as a pale yellow solid (630 mg, 84%).
1-(2-Methoxyphenyl)-2-naphthoic acid (5g). Table 2, entries
7 and 8 (1,2 + 2-MeOC6H4Li). According to the general procedure,
(2-methoxyphenyl)lithium (8.0 mmol) was added dropwise to a
solution of 1-fluoro-2-naphthoic acid (1) (380 mg, 2.0 mmol) or 1-
methoxy-2-naphthoic acid (2) (404 mg, 2.0 mmol) in THF at −30 °C.
The reaction mixture was stirred at −30 °C for 2 h. Standard workup
followed by chromatography on silica gel (cyclohexane/DCM 30:70
→ 0:1 and DCM/ethylacetate 95:5 → 0:1) afforded 5g as a white solid
hexane/ethylacetate 9:1 → 0:1) gave 5l as a pale yellow solid (40 mg,
13% from 1, 90 mg, 29% from 2): mp 242−244 °C; H NMR (200
1
MHz, CDCl3) δ 8.08 (d, J = 8.7 Hz, 1H), 7.92−7.87 (m, 2H), 7.58−
7.33 (m, 4H), 6.71 (d, J = 8.4 Hz, 2H), 3.61 (s, 6H); 13C NMR (50
MHz, DMSO-d6) δ 168.5, 157.4 (2), 134.5, 134.3, 132.1, 129.5, 129.1,
127.9, 127.1, 127.0, 126.6, 126.4, 126.0, 115.8, 104.2 (2), 55.5 (2); IR
(ATR, cm−1) 2940, 1665, 1587, 1470, 1430, 1286, 1248, 1105, 910,
759, 724; HRMS calcd for C19H16O4 ([M]+) 308.1049, found
308.1064.
[1,1′-Binaphthalene]-2-carboxylic acid (5m). Table 3, entries
1 and 2 (1,2 + 1-naphthyllithium). According to the general
procedure, naphthalen-1-yllithium (4.4 mmol) was allowed to react
with 1-fluoro-2-naphthoic acid (1) (380 mg, 2.0 mmol) or 1-methoxy-
2-naphthoic acid (2) (404 mg, 2.0 mmol) in THF at −30 °C for 2 h
for 1 and for 16 h for 2. Standard workup and chromatography on
silica gel (cyclohexane/ethylacetate 95:5 → 0:1) afforded 5m as a
white solid (516 mg, 87% from 1, 544 mg, 91% from 2): mp 180−182
1
(293 mg, 53% from 1; 109 mg, 20% from 2): mp 182−184 °C; H
NMR (400 MHz, acetone-d6) δ 8.00−7.94 (m, 3H), 7.54 (m, 1H),
7.46−7.37 (m, 3H), 7.10−7.08 (m, 2H), 7.02 (m, 1H), 3.60 (s, 3H);
13C NMR (100 MHz, acetone-d6) δ 169.0, 158.3, 139.3, 135.8, 133.6,
131.7, 129.8 (2), 129.0, 128.8, 128.3, 128.2, 128.1, 127.3, 126.8, 121.0,
111.9, 55.8; IR (ATR, cm−1) 2835, 1687, 1492, 1284, 910, 787, 756;
HRMS calcd for C18H14O3 ([M]+) 278.0943, found 278.0956.
1-(2-Methylphenyl)-2-naphthoic acid (5h). Table 2, entries 11
and 12 (1,2 + 2-MeC6H4Li). According to the general procedure, o-
tolyllithium (4.4 mmol) was added dropwise to a solution of 1-fluoro-
2-naphthoic acid (1) (380 mg, 2.0 mmol) or 1-methoxy-2-naphthoic
acid (2) (404 mg, 2.0 mmol) in THF at −30 °C. The reaction mixture
was then stirred at this temperature for 2 h. Standard workup followed
by chromatography on silica gel (cyclohexane/DCM 20:80 → 0:1 then
DCM/ethylacetate 1:0 → 1:1) afforded 5h as a white solid (446 mg,
°C (lit.34 177−184 °C); H NMR (400 MHz, CDCl3) δ 8.05 (d, J =
1
8.7 Hz, 1H), 7.95−7.89 (m, 4H), 7.54−7.49 (m, 2H), 7.43 (m, 1H),
7.30−7.20 (m, 4H), 7.12 (d, J = 8.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 172.2, 141.4, 136.6, 135.2, 133.3, 133.2, 132.9, 128.3, 128.2
(2), 128.0 (2), 127.9, 127.3, 127.0, 126.8, 126.2, 126.1, 126.0, 125.7,
125.3; IR (ATR, cm−1) 2922, 1691, 1461, 1251, 913, 795, 768; HRMS
calcd for C21H15O2 ([M + H]+) 299.1072, found 299.1077.
Table 3, entry 3 (2 + naphthalen-1-ylmagnesium bromide).
According to the general procedure, naphthalen-1-ylmagnesium
bromide (0.66 M in THF, 10.0 mL, 6.6 mmol) was added dropwise
to a solution of 1-methoxy-2-naphthoic acid (2) (606 mg, 3.0 mmol)
in THF at −30 °C. The mixture was then refluxed for 2 h. Standard
workup followed by chromatography on silica gel (cyclohexane/
ethylacetate 3:2) afforded 5m as a white solid (630 mg, 70%).
2′-Methoxy-[1,1′-binaphthalene]-2-carboxylic acid (5o).
Table 3, entry 6 (2 + (2-methoxynaphthalen-1-yl)magnesium
bromide). According to the general procedure, (2-methoxynaphtha-
len-1-yl)magnesium bromide (0.25 M in THF, 17.5 mL, 4.4 mmol)
was added dropwise to a solution of 1-methoxy-2-naphthoic acid (2)
(404 mg, 2.0 mmol) in THF at rt. The mixture was then refluxed for 2
h. Standard workup followed by chromatography on silica gel
(cyclohexane/ethylacetate 9:1 → 0:1) afforded 5o as a white solid
(265 mg, 40%): mp 258−261 °C; 1H NMR (400 MHz, CDCl3) δ 8.15
(d, J = 8.7 Hz, 1H), 7.99 (m, 2H), 7.93 (d, J = 8.2 Hz, 1H), 7.86 (d, J
= 8.2 Hz, 1H), 7.53 (ddd, J = 1.6 Hz, J = 6.4 Hz, J = 8.1 Hz, 1H), 7.39
(d, J = 9.1 Hz, 1H), 7.32−7.19 (m, 3H), 7.17 (ddd, J = 1.3 Hz, J = 6.8
Hz, J = 8.3 Hz, 1H), 6.90 (d, J = 8.5 Hz, 1H), 3.70 (s, 3H); 13C NMR
(100 MHz, DMSO-d6) δ 168.2, 153.9, 135.7, 134.5, 133.3, 132.3,
130.1, 129.3, 128.5, 128.1, 127.9, 127.7, 127.5, 126.8, 126.7, 126.3,
126.1, 124.3, 123.2, 121.2, 113.9, 56.1; IR (ATR, cm−1) 1688, 1669,
1464, 1248, 1082, 1053, 913, 797, 765, 756, 737; HRMS calcd for
C22H20NO3 ([M + NH4]+) 346.1443, found 346.1425.
2-sec-Butyl-1-naphthoic acid (6b). Table 1, entry 7 (3 + s-
BuLi). According to the general procedure, 2-methoxy-1-naphthoic
acid (3) (606 mg, 3.0 mmol) was allowed to react with s-BuLi (0.90 M
in hexane, 7.3 mL, 6.6 mmol) at −78 °C. Standard workup followed by
recrystallization (cyclohexane/ethylacetate 1:3) afforded 6b as a white
solid (650 mg, 95%): mp 168−170 °C (lit.31 166−168 °C); 1H NMR
(400 MHz, CDCl3) δ 11.93 (s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.89 (d,
J = 8.8 Hz, 1H), 7.83 (d, J = 8.5 Hz, 1H), 7.56 (m, 1H), 7.50−7.43 (m,
2H), 3.12 (m, 1H), 1.83−1.69 (m, 2H), 1.36 (d, J = 6.8 Hz, 3H), 0.88
(t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 176.1, 142.5,
131.8, 130.4, 129.5, 129.1, 128.1, 127.2, 125.8, 124.8, 123.5, 35.1, 30.7,
22.1, 12.3; IR (KBr, cm−1) 2850, 1695, 1400, 1253, 900, 780, 751;
HRMS calcd for C15H16O2 ([M]+) 228.1150, found 228.1170. Anal.
Calcd for C15H16O2: C, 78.92; H, 7.06. Found: C, 78.67; H, 7.14.
2-tert-Butyl-1-naphthoic acid (6c). Table 1, entry 8 (3 + t-
BuLi). According to the general procedure, 2-methoxy-1-naphthoic
acid (3) (606 mg, 3.0 mmol) was reacted with t-BuLi (1.70 M in
pentane, 3.9 mL, 6.6 mmol) at −78 °C. Standard workup followed by
recrystallization (cyclohexane/ethylacetate 1:3) afforded 6c as a white
solid (600 mg, 87%): mp 120−123 °C; 1H NMR (400 MHz, CDCl3)
δ 10.75 (s, 1H), 7.93 (d, J = 8.4 Hz 1H), 7.89 (d, J = 8.8 Hz, 1H), 7.83
1
85% from 1, 437 mg, 84% from 2): mp 136−138 °C; H NMR (200
MHz, CDCl3) δ 10.90 (br, 1H), 8.03 (d, J = 8.6 Hz, 1H), 7.86 (d, J =
8.9 Hz, 2H), 7.51 (m, 1H), 7.36−7.30 (m, 3H), 7.29−7.21 (m, 2H),
7.06 (d, J = 7.4 Hz, 1H), 1.92 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
173.0, 142.8, 138.4, 136.7, 135.4, 132.6, 129.7, 129.3, 128.1, 127.8,
127.7, 126.9, 126.4, 126.2, 125.6, 20.0; IR (KBr, cm−1) 2859, 1693,
1464, 1253, 942, 770, 755; HRMS calcd for C18H14O2 ([M]+)
262.0994, found 262.0997.
1-(4-Methoxyphenyl)-2-naphthoic acid (5i). Table 2, entry 14
(2 + 4-MeOC6H4MgBr). According to the general procedure, 1-
methoxy-2-naphthoic acid (2) (606 mg, 3.0 mmol) was allowed to
react with (4-methoxyphenyl)magnesium bromide (0.85 M in THF,
7.8 mL, 6.6 mmol) for 2 h at rt. Standard workup followed by
chromatography on silica gel (cyclohexane/ethylacetate 9:1 → 0:1)
1
afforded 5i as a white solid (691 mg, 83%): mp 177.5−180.0 °C; H
NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.7 Hz, 1H), 7.88 (d, J = 8.5
Hz, 2H), 7.61 (d, J = 8.5 Hz, 1H), 7.54 (m, 1H), 7.41 (m, 1H), 7.25−
7.21 (m, 2H), 7.02−6.99 (m, 2H), 3.90 (s, 3H); 13C NMR (50 MHz,
CDCl3) δ 173.5, 159.1, 142.4, 135.2, 133.1, 130.8 (2), 130.7, 128.1,
127.9, 127.8, 127.7, 127.0, 126.7, 125.9, 113.6 (2), 55.3; IR (ATR,
cm−1) 1698, 1675, 1504, 1463, 1329, 1285, 1238, 1175, 1034, 827,
769; HRMS calcd for C18H14O3 ([M]+) 278.0943, found 278.0940.
1-(2,5-Dimethylphenyl)-2-naphthoic acid (5j). Table 2, entry
15 (2 + 2,5-diMeC6H4MgBr). According to the general procedure,
(2,5-dimethylphenyl)magnesium bromide (0.50 M in THF, 13.2 mL,
6.6 mmol) was allowed to react with 1-methoxy-2-naphthoic acid (2)
(606 mg, 3.0 mmol) in THF at rt. The reaction mixture was refluxed
for 2 h. Standard workup followed by recrystallization (cyclohexane)
1
afforded 5j as a white solid (600 mg, 72%): mp 165- °C; H NMR
(400 MHz, CDCl3) δ 8.04 (d, J = 8.7 Hz, 1H), 7.88−7.86 (m, 2H),
7.53 (m, 1H), 7.37−7.36 (m, 2H), 7.22−7.13 (m, 2H), 6.89 (s, 1H),
2.32 (s, 3H), 1.88 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 172.8,
142.9, 138.1, 135.3, 134.8, 133.6, 132.5, 129.9, 129.5, 128.5, 128.0,
127.9, 127.6, 126.8, 126.3, 126.1, 21.0, 19.4; IR (KBr, cm−1) 2916,
1673, 1410, 1279, 913, 771, 758; HRMS calcd for C19H17O2 ([M +
H]+) 277.1229, found 277.1234.
1-(2,6-Dimethoxyphenyl)-2-naphthoic acid (5l). Table 2,
entries 18 and 19 (1,2 + 2,6-diMeOC6H3MgBr). According to the
general procedure, (2,6-dimethoxyphenyl)magnesium bromide (0.43
M in THF, 5.1 mL, 2.2 mmol) was added dropwise at rt to a solution
of 1-fluoro-2-naphthoic acid (1) (190 mg, 1.0 mmol) or 1-methoxy-2-
naphthoic acid (2) (202 mg, 1.0 mmol) in THF. After 2 h refluxing,
standard workup followed by chromatography on silica gel (cyclo-
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dx.doi.org/10.1021/jo202017z | J. Org. Chem. 2012, 77, 718−724