Effective synthesis of difluorocyclohexadienones by electrochemical oxidation of phenols

Article abstract of DOI:10.1016/S0040-4039(02)01440-5

Electrochemical oxidation of phenols was examined using Et₃N-5HF as the electrolyte and various electrodes. Carbon fiber cloth was found to be suitable as the anode and a variety of phenols could be converted to 4,4-difluorocyclohexadienone derivatives in good yields.

Full text of DOI:10.1016/S0040-4039(02)01440-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6583–6585
Effective synthesis of difluorocyclohexadienones by
electrochemical oxidation of phenols
Tsuyoshi Fukuhara, Yuriko Akiyama, Norihiko Yoneda, Takahisa Tada and Shoji Hara*
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
Received 21 June 2002; revised 11 July 2002; accepted 12 July 2002
Abstract—Electrochemical oxidation of phenols was examined using Et3N–5HF as the electrolyte and various electrodes. Carbon
fiber cloth was found to be suitable as the anode and a variety of phenols could be converted to 4,4-difluorocyclohexadienone
derivatives in good yields. © 2002 Elsevier Science Ltd. All rights reserved.
Anodic fluorination of phenols (1) using an HF-base as
the electrolyte is a convenient method for synthesis of
4,4-difluorocyclohexadienone derivatives (2) because
toxic oxidants such as PbO2 are not required, and the
resulting 2 can be used as the precursors of various
substituted fluorophenols (Eq. (1)).1 However, under
the anodic oxidation conditions, side reactions such as
oligomerization competitively took place,2 and good
results could be obtained only when bulky substituents
were present on the benzene ring.1b We wish to report
here an electrochemical fluorination method applicable
to a wide variety of phenols.
The electrochemical fluorination of a-naphthol was
examined using Et3N–5HF as the electrolyte and
fluorine source,3 and various electrodes to find suitable
conditions (Table 1). When Pt was used as the anode,
passivation took place on the anode surface and the
desired product was scarcely obtained (entry 1). As
graphite anodes were reported to be effective for the
oxidation of phenols,4 glassy carbon,5 carbon felt,6 and
carbon fiber cloth7 were applied to the reaction. When
the glassy carbon was used, passivation took place
again and the electrolysis was prevented (entry 2). On
the other hand, the carbon felt and carbon fiber cloth
gave better results and the desired difluorocyclohexa-
dienone derivative was obtained in moderate yield
(entries 3 and 4). In order to avoid the oligomerization
on the anode surface, slow addition of the naphthol
into the cell is effective, and without the slow addition
operation, the yield decreased. Extension of the anode
O
OH
R3
R4
R1
R2
R1
R2
R3
R4
-4e
(1)
Et3N-5HF
F
F
1
2
Table 1. Electrochemical fluorination of a-naphthol using various anodea
Entry
Anodeb (number)
Charge passed (F/mol)
Yield (%)c
1
2
3
4
5
6
7
Pt
0d
0
0
Glassy carbon
Carbon felt
Carbon fiber cloth
Carbon fiber cloth (3 sheets)
Carbon fiber cloth (16 sheets)
Carbon fiber cloth (24 sheets)
0d
4.4
4.3
4.0
3.6
3.6
46
64
73
83
89
a If otherwise not mentioned, the reaction was carried out at 1.7 V versus Ag/AgClO3 in a divided cell equipped with a Nafion™ film and a
platinum cathode (2×2 cm). a-Naphthol (1 mmol) in dimethyl carbonate (4 ml) was added over 6–7 h.
b A 2×2 cm sheet was used.
c Isolation yield based on the naphthol used.
d Passivation on the anode surface took place.
Keywords: electrochemistry; halogenation; oxidation; phenols.
* Corresponding author. Fax: +81-11-706-6556; e-mail: hara@org-mc.eng.hokudai.ac.jp
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01440-5

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T. Fukuhara et al. / Tetrahedron Letters 43 (2002) 6583–6585
surface area was also found to be effective to improve
the result. As carbon fiber cloth is flexible, it is easy to
increase the number of sheets to be accommodated in
a cell (entries 5–7). Finally, the best result was obtained
by using 24 sheets of carbon cloth as the anode and
the desired product was obtained in 89% yield (entry
7).
noting that even unsubstituted phenol gave the corre-
sponding fluorinated product in 61% yield (entry 8). In
the previous report,1b the fluorinated product was
obtained only in less than 25% yield from the unsubsti-
tuted phenol. Recently, difluoromethylenephophonate
moiety is of great interest as analogs of pyro- and
triphosphates where the CF2 group is an isoelectronic
and isosteric replacement of ether oxygen.8 Therefore,
the compound 9 is interesting as an analog of
flavonoid9 which has an oxygen instead of the CF2
group.
The present method is applicable to various phenols,
and substituents at the o-positions are not necessary to
obtain the product in good yield (Table 2). It is worth
Table 2. Electrochemical fluorination of phenolsa
Yield, %b
89
Charge passed, F/mol
Product
O
Entry
1
Phenols
OH
3.6
4.0
1
2
F
F
O
OH
2
76
F
F
O
OH
OH
Ph
Ph
c
3
4
77
5.2
4.7
3
F
F
F
F
O
But
But
70
4
O
O
OH
Pr
Pr
Pr
Pr
5
6
77
68
4.1
5.8
5
F
F
F
F
OH
6
But
But
OH
O
Me
Cl
Me
Cl
7
8
62
6.9
4.1
7
F
F
OH
OH
OH
d,
e,f
8
61
F
O
68c,
g
9
9
5.1
Ph
Ph
F
F
a. If otherwise not mentioned, the reaction was carried out for 6 h at 1.7 V vs. Ag/AgClO3.
b. Isolated yield based on phenols. c. The electrolysis was carried out at 1.6 V. d. The
electrolysis was carried out at 2.0 V. e. Phenol was added over 15 h. f. As product was
volatile, it was reduced to fluorophenol by Zn. g. Phenol was added over 21 h.

T. Fukuhara et al. / Tetrahedron Letters 43 (2002) 6583–6585
6585
A typical procedure is as follows: Et3N–5HF (2×24 ml)
was introduced into divided cells, made of Teflon™
PFA, equipped with a Nafion™ 117 film as the
diaphragm using 24 sheets of carbon fiber cloth (20×20
mm, Nippon Carbon Co. Ltd GF-2097) for the anode
and a smooth Pt plate (20×20 mm) for the cathode
under a nitrogen atmosphere. (CAUTION: Although
Et3N–5HF is less corrosive than HF itself, it is recom-
mended to use rubber gloves.) The electrolysis was
carried out at room temperature with a constant poten-
tial (1.7 V versus Ag/AgClO3) and during the electroly-
sis, a-naphthol (144 mg, 1 mmol) in dimethylcarbonate
(4 ml) was added into the anodic cell over 6 h. The
electrolysis was continued until the a-naphthol was
consumed completely. The content of the anode cell
was then poured into water and extracted three times
with CH2Cl2. The combined organic layers were suc-
cessfully washed with aqueous Na2S2O3, aqueous
NaHCO3, and brine, and dried over MgSO4. The purifi-
cation by column chromatography (silica gel/hexane–
ether) gave 4,4-difluoro-1-naphtoquinone in 89%
yield.10
6. (a) Yoshida, J.; Suga, S.; Suzuki, S.; Kinomura, N.;
Yamamoto, A.; Fujiwara, K. J. Am. Chem. Soc. 1999,
121, 9546–9549; (b) Suga, S.; Suzuki, S.; Yamamoto, A.;
Yoshida, J. J. Am. Chem. Soc. 2000, 122, 10244–10245;
(c) Peacock, M. J.; Pletcher, D. Tetrahedron Lett. 2000,
41, 8995–8998; (d) Suga, S.; Suzuki, S.; Yoshida, J. J.
Am. Chem. Soc. 2002, 124, 30–31.
7. Calas, P.; Moreau, P.; Commeyras, A. Chem. Commun.
1982, 433–434.
8. (a) Blackburn, G. M.; Kent, D. E.; Kolkmann, F. J.
Chem. Soc., Perkin Trans. 1 1984, 1119–1125; (b) Cham-
bers, R. D.; Jaouhari, R.; O’Hagan, D. Tetrahedron 1989,
45, 5101–5108.
9. Bohm, B. A. Introduction to Flavonoids; Harwood Aca-
demic: Amsterdam, 1998.
10. Compound 1: mp 60–61°C; IR (KBr) 1685, 1642, 1602
cm−1; lH (CDCl3) 6.56 (1H, d, J=10.4 Hz), 6.95–7.00
(1H, m), 7.64–7.75 (2H, m), 7.84 (1H, d, J=7.8 Hz), 8.09
(1H, d, J=7.8 Hz); lF (CDCl3) −90.66 (2F, d, J=5.5
Hz); HRMS calcd for C10H6F2O: 180.0387. Found:
180.0395. Compound 2: IR (neat) 1686, 1658, 1634 cm−1
;
lH (CDCl3) 1.66–1.77 (4H, m) 2.31–2.44 (4H, m), 6.29–
6.33 (1H, m), 6.76–6.81 (1H, m); lF (CDCl3) −103.69 to
−103.65 (2F, m); HRMS calcd for C10H10F2O: 184.0700.
Found: 184.0702. Compound 3: mp 70–71°C; IR (KBr)
1652 cm−1; lH (CDCl3) 6.44 (1H, d, J=10.3 Hz), 6.83–
6.92 (2H, m), 7.40–7.44 (5H, m); lF (CDCl3) −97.33 (2F,
t, J=5.5 Hz); HRMS calcd for C12H8F2O: 206.0543.
Found: 206.0537. Compound 4: IR (neat) 1654 cm−1; lH
(CDCl3) 1.25 (9H, s), 6.23 (1H, d, J=10.3 Hz), 6.55–6.59
(1H, m), 6.70–6.75 (1H, m); lF (CDCl3) −97.97 (2F, t,
J=5.5 Hz); HRMS calcd for C10H12F2O: 186.0856.
Found: 186.0854. Compound 5: IR (neat) 1661 cm−1; lH
(CDCl3) 0.96 (6H, t, J=7.3 Hz), 1.45–1.54 (4H, m),
2.28–2.33 (4H, m), 6.50 (2H, t, J=5.3 Hz); lF (CDCl3)
−99.30 to −98.36 (2F, m); HRMS calcd for C12H16F2O:
214.1169. Found: 214.1175. Compound 6: IR (neat) 1689,
1649 cm−1; lH (CDCl3) 1.32 (9H, s), 6.26–6.29 (2H, m),
6.73–6.79 (1H, m); lF (CDCl3) −97.34 (2F, d, J=6.7 Hz);
HRMS calcd for C10H12F2O: 186.0856. Found: 186.0845.
Compound 7: IR (neat): 1697, 1675, 1632 cm−1; lH
(CDCl3) 2.01–2.03 (3H, m), 6.62–6.66 (1H, m), 6.96–6.99
(1H, m); lF (CDCl3) −97.97 to −97.91 (2F, m); HRMS
calcd for C7H5ClF2O: 177.9997. Found: 177.9979. Com-
pound 8: mp 45–46°C (lit.3 45–45.5°C); IR (KBr) 3229
cm−1; lH (CDCl3) 4.63 (1H, s), 6.80–6.75 (2H, m), 6.96–
6.90 (2H, m); lF (CDCl3) −124.80 to −124.87 (1F, m).
Compound 9: IR (neat) 1668 cm−1; lH (CDCl3) 6.78 (1H,
s), 7.47–7.52 (3H, m), 7.64–7.68 (1H, m), 7.76–7.81 (3H,
m), 7.91 (1H, d, J=7.5 Hz), 8.13 (1H, d, J=7.8 Hz); lF
(CDCl3) −88.74 (2F, s); HRMS calcd for C16H10F2O:
256.0700. Found: 256.0706.
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