T. M. Kru¨lle et al. / Tetrahedron Letters 48 (2007) 1537–1540
1539
O
R
F
F
F
(b)
(a)
CO2H
1
6
7: R = CH3
8: R = OH
(c)
(a) quinoline, Cu powder, reflux, 48 h, 80%
(b) AcCl, AlCl3, DCM, -78 oC to rt, 12 h, quant.
(c) NaOCl, MeOH, 48 h, 73%
Scheme 3.
4. Vercouillie, J.; Abarbi, M.; Parrain, J.; Duchene, A.;
Thibonnet, J. Synth. Commun. 2004, 3751–3762.
5. Owton, M. W.; Brunavs, M. Synth. Commun. 1991, 981–
987.
6. Nussbaumer, P.; Dorfstaetter, G.; Leitner, I.; Mraz, K.;
Vyplel, H.; Stuetz, A. J. Med. Chem. 1993, 36, 2810–2816.
7. Tagat, J. R.; McCombie, S. W.; Nazareno, D. V.; Boyel,
C. D.; Kozlowski, J. A.; Chackalamannil, S.; Joisen, H.;
Wang, Y.; Zhou, G. J. Org. Chem. 2002, 67, 1171–1177.
8. Dewar, M. J. S.; Grisdale, P. J. J. Am. Chem. Soc. 1962,
84, 3541–3546.
9. Adcock, W.; Dewar, M. J. S. J. Am. Chem. Soc. 1967, 89,
386–390.
10. Price, C. C.; Chapin, E. C.; Goldman, A.; Krebs, E.;
Shafer, H. M. J. Am. Chem. Soc. 1941, 63, 1857–1861.
11. Price, C. C.; Huber, C. F. J. Am. Chem. Soc. 1942, 64,
2136–2139.
12. 6-Fluoronaphthalene-1-carboxylic acid 1: Anhydrous alu-
minium chloride (65 g, 487 mmol) was added carefully to a
suspension of furan-2-carboxylic acid (25 g, 260 mmol) in
fluorobenzene (250 mL) at 0 ꢁC. After 1 h the ice bath was
removed and the mixture was slowly heated to 75 ꢁC and
then kept at this temperature for a further 12 h. The
mixture was added to a 2 N HCl solution (1.5 L) before
extraction into ether (3 · 300 mL). The combined ether
layers were washed with water (250 mL) and then
extracted with saturated NaHCO3 solution (3 · 250 mL).
The alkaline solution was then made acidic with concd
HCl solution and re-extracted with EtOAc (3 · 250 mL).
Concentration in vacuo after drying (MgSO4) gave a solid
residue which was stirred in the presence of toluene
(50 mL) for 12 h. Filtration gave the title compound
(11.4 g, 23%) as an off-white solid, mp 234–236 ꢁC. 1H
NMR: dH (DMSO-d6, 500 MHz): 7.56 (1H, ddd, J1
2.8 Hz, J2 8.6 Hz, J3 9.5 Hz, H-7), 7.66 (1H, dd, J1 = J2
7.8 Hz, H-3), 7.84 (1H, dd, J1 2.8 Hz, J2 9.9 Hz, H-5), 8.16
(2H, m, H-2, H-4), 8.97 (1H, dd, J1 6.0 Hz, J2 9.5 Hz, H-
8), 13.27 (1H, br s); MS: ESIÀ, m/z 189.19 [MÀH]À.
13. Lowe, J. A.; Nagel, A. A.; US Patent No. 4,831,031;
Chem. Abstr. 1989, 111, 153842.
nation to form the dihydronaphthalene intermediate
that aromatises under these conditions. Aqueous
work-up hydrolyses the aluminium adduct and liberates
1-naphthoic acid 1.
The relative ease by which the naphthalene scaffold can
be assembled in this way makes the synthesis of other b-
substituted naphthalenes feasible. For example a classi-
cal copper/quinoline decarboxylation19 of 6-fluoro-1-
naphthoic acid 1 gave the 2-fluoronaphthalene 6 in a
good yield (Scheme 3). Friedel–Crafts acylation20,21 of
2-fluoronaphthalene 6 takes place regioselectively at
the 8-position to form ketone 7,22,23 we found that a
slow increase of the reaction temperature over a period
of several hours provides a quantitative conversion.
Successive oxidation with sodium hypochlorite finally
allowed the isolation of 1-naphthoic acid 8 in four
simple steps overall.
In conclusion, we have developed a very convenient
method for the preparation of gram quantities of 6-flu-
oro- and 6,7-difluoro-1-naphthoic acids (1 and 2, respec-
tively) in a one-pot process. Decarboxylation of 6-
fluoronaphthoic acid 1 followed by the regioselective
Friedel–Crafts acylation of 2-fluoronaphthalene 6 pro-
vided an easy access to a 1,7-disubstituted naphthalene
derivative 7 which could be oxidised to 7-fluoro-1-naph-
thoic acid 8 with bleach.
Acknowledgement
We would like to thank Professor George W. J. Fleetà
for his valuable suggestions with regards to a plausible
mechanism.
14. Jacobs, T. L.; Winstein, S.; Henderson, R. B.; Bond, J.;
Ralls, J. W.; Seymour, D.; Florsheim, W. H. J. Org. Chem.
1946, 11, 229–238.
References and notes
15. 1H NMR 2: dH (DMSO-d6, 500 MHz): 7.66 (1H, dd,
J1 = J2 7.7 Hz, H-3), 8.13 (1H, dd, J1 8.4 Hz, J2 8.9 Hz, H-
5), 8.21 (1H, d, J 8.4 Hz, H-4), 8.27 (1H, d, J 7.4 Hz, H-2),
8.91 (1H, dd, J1 8.4, J2 8.9 Hz, H-8), 13.70 (1H, br s).
HRMS: ESIÀ, calcd for C11H5F2O2 [MÀH]À 207.0257,
found 207.0262.
1. Boehm, H.-J.; Banner, D.; Bendels, S.; Kansy, M.; Kuhn,
B.; Mueller, K.; Obst-Sander, U.; Stahl, M. ChemBioChem
2004, 5, 637–643.
2. Martinez, G. R. Tetrahedron: Asymmetry 1995, 6, 1491–
1494.
16. N1909, Sigma–Aldrich.
3. Cui, D.; Kawamura, M.; Shimada, S.; Hayashi, T.;
Tanaka, M. Tetrahedron Lett. 2003, 44, 4007–4010.
17. 1H NMR 4: dH (DMSO-d6, 500 MHz): 7.67 (1H, dd,
J1 = J2 7.6 Hz, H-3), 8.07 (1H, d, J 10.2 Hz, H-5), 8.19
(1H, d, J 8.1 Hz, H-4), 8.22 (1H, dd, J1 1.0, J2 7.3 Hz, H-
2), 9.16 (1H, d, J 7.9 Hz, H-8); 5: 7.64 (1H, dd, J1 = J2
à Central Research Laboratories, University of Oxford.