Rapid conversion of phenols to p-benzoquinones under acidic conditions with lead dioxide

Article abstract of DOI:10.1055/s-1998-2118

Treatment of 4-unsubstituted and 4-halogenated phenols with PbO₂ and 70% HClO₄ in AcOH afforded the corresponding p-benzoquinones in fair to high yields. The oxidation of 4-substituted 2,6-di-tertbutylphenols 6 with PbO₂ and 70% HClO₄ in acetone gave 2,6-di-tert-butyl-p-benzoquinone (2).

Full text of DOI:10.1055/s-1998-2118

SYNTHESIS
August 1998
1145
Rapid Conversion of Phenols to p-Benzoquinones under Acidic Conditions with Lead
Dioxide
Kanji Omura
College of Nutrition, Koshien University, Momijigaoka, Takarazuka, Hyogo 665, Japan
Fax +81(797)875666
Received 12 December 1997; revised 9 February 1998
Table 1. Oxidation of Phenol 1 with PbO2 and 70% HClO4 in Differ-
Abstract: Treatment of 4-unsubstituted and 4-halogenated phe-
nols with PbO2 and 70% HClO4 in AcOH afforded the corre-
sponding p-benzoquinones in fair to high yields. The oxidation of
4-substituted 2,6-di-tert-butylphenols 6 with PbO2 and 70%
HClO4 in acetone gave 2,6-di-tert-butyl-p-benzoquinone (2).
ent Solventsa
Entry
Solvent
70% HClO4
(mL)
Yield (%)
2
3
Key words: p-benzoquinones, phenols, lead dioxide, 70% HClO4
1
2
3
4
5
6
7
8
9
MeOH
MeOH
MeOH
DME
acetone
acetone
MeCN
AcOH
AcOH
none
0
39
61
71
73
85
83
95
97
99
52
28
26
21
6
trace
0
0
3
5
3
3
5
3
3
5
Benzoquinones are versatile starting materials for the
preparation of a variety of compounds. Hence, the synthe-
sis of benzoquinones from phenols is of great importance.
Up to now, various oxidation methods including Fremy’s
salt,1 Jones reagent2 and thallium(III) nitrate3 have been
used for this purpose. These oxidation methods have their
own advantages and disadvantages. Thus, development of
new oxidants is still desirable for the synthesis of benzo-
quinones from phenols.
a
Carried out with 1 (4 mmol), PbO2 (10 mmol), 70% HClO4 and a
solvent (30 mL). One mL of 70% HClO4 consists of HClO4
(11.6 mmol) and H2O (0.5 mL).
Although lead dioxide (PbO2), like alkaline potassium fer-
ricyanide, is one of the oxidants which dehydrogenates
phenols and provides C–C and/or C–O coupling products
via unstable phenoxy radicals,4 it alone is not quite suit-
able for the formation of benzoquinones from phenols.5–7
We now report the efficient formation of benzoquinones
from phenols upon oxidation with PbO2 in the presence of
a strong acid. This oxidation method may be a general and
useful synthesis of p-benzoquinones from phenols.
generated in MeOH, DME, acetone or MeCN were less
than that of 2 generated in AcOH. The oxidative reaction
in MeCN yielded only a trace amount of 3 but provided a
significant amount of unknown materials as byproducts.
On the other hand, when a large amount of 70% HClO4
(15 equiv) was used for the reaction in MeOH (Entry 3,
Table 1), acetone (Entry 6, Table 1) and AcOH (Entry 9,
Table 1), improved yields of 2 were observed. These re-
sults suggest that AcOH is the best solvent for conversion
of 1 to 2 with PbO2 and 70% HClO4.9
An AcOH solution of 2,6-di-tert-butylphenol (1) was add-
ed dropwise to a heterogeneous mixture of excess8 PbO2
(2.5 equiv), 70% HClO4 (9 equiv) and AcOH at 25°C. Af-
ter the reaction was completed, 2,6-di-tert-butyl-p-benzo-
quinone (2) was obtained in 95% yield (Scheme). No oth-
er products were identified (Entry 8, Table 1). The same
reaction as described above was performed in different
solvents such as AcOH, MeOH (Entry 2, Table 1), DME
(Entry 4, Table 1), acetone (Entry 5, Table 1) or MeCN
(Entry 7, Table 1) to give not only 2 but also 3,5,3',5'-tet-
ra-tert-butyl-4,4'-diphenoquinone (3). The yields of 2
In the absence of 70% HClO4, the reaction of 1 with
PbO2 in AcOH provided 3,5,3',5'-tetra-tert-butyl-bis(cy-
clohexa-2,5-diene)-4,4'-dione (4) (60%), the tautomer
of 3,5,3',5'-tetra-tert-butyl-4,4'-dihydroxybiphenyl (5),
along with unreacted 1 (35%). Interestingly, this result is
not consistent with literatutre,5 only 3 was obtained in
high yield (90–92%) from the same reaction as described
above. It was observed that MeOH is the best solvent to
obtain 3 from the oxidation of 1 with PbO2 (Entry 1, Table
1).
Table 2 shows the oxidation of 4-unsubstituted phenols
with PbO2 (2.5 equiv) and 70% HClO4 (15 equiv) in
AcOH. All reactions were accomplished very rapidly. The
Scheme
corresponding p-benzoquinones were formed in fair to

SYNTHESIS
Papers
1146
Table 2. Conversion of 4-Unsubstituted and 4-Halogenated Phenols
into p-Benzoquinones with PbO2 and 70% HClO4 in AcOH
Products generated from the reactions of various 4-sub-
stituted 2,6-di-tert-butylphenols 6 with PbO2 (1.3–4
equiv) and 70% HClO4 (15 equiv) were also investigat-
ed. These reactions were conducted in acetone due to the
lack of solubility of some of 6 in AcOH. The results are
shown in Table 3. All the reactions were completed rap-
idly, except the reaction of 6i, from which a significant
amount of 6i was recovered. From every reaction, p-ben-
zoquinone 2 was obtained in fair to high yield as the only
isolable product, although the reaction of 6b gave 4-hy-
droxy-4-methyl-2,6-di-tert-butylcyclohexa-2,5-dienone
(7) additionally. It is novel that any substituents at C-4
on 6 are eliminated readily by the oxidation with PbO2
and HClO4. The amount of PbO2 used was dependent on
the chemical properties of the 4-substituents in 6. In or-
der to examine the role of acid in oxidative reaction,
some reactions were conducted by replacing 70% HClO4
with H2O. The rate of the reactions of 6c, 6d, 6e, 6h and
6i in H2O was relatively slower than in 70% HClO4. The
reactions of 6d and 6i were particularly slow and they
were recovered almost quantitatively. All of the reac-
tions of these 6 with PbO2 and H2O in acetone provided
no or little 2, instead, 3 was obtained. Compound 5 was
also formed occasionally.
Phenol
Product
Yield
(%)
82
61
60
45
44
73
82
74
78
87
Table 3. Conversion of Phenols 6 into p-Benzoquinone 2 with PbO2
and 70% HClO4 in Acetone
Phenol
PbO2
(equiv)
Yield
(%)
high yields. The oxidation of 2,4,6-trichlorophenol with
PbO2 (1.3 equiv) and of 2,4,6-tribromophenol with PbO2
(2.0 equiv) also led to the p-benzoquinone derivatives, 2,6-
dichloro-p-benzoquinone and 2,6-dibromo-p-benzoquin-
one, respectively. The remainder of every p-benzoquinone
product listed in Table 2 consisted principally of polar, un-
identifiable materials: no indication for the formation of a
simple coupling product(s) such as a 4,4'-diphenoquinone
was obtained. Therefore, these p-benzoquinones were eas-
ily purified by using a silica gel column with CH2Cl2. Alter-
natively, many of the p-benzoquinones could be isolated
more simply by recrystallization of the crude products. De
Jong et al. reported oxidation of 1 with PbO2 in AcOH (see
above), 2,6-dimethylphenol, 2,6-diisopropylphenol and
6a
6ba
6c
6d
6e
6f
6g
6h
6ib
2.5
4
4
97
50
79
53
49
100
73
84
4
2.5
1.3
2
2
1.3
34
a
In addition, 7 (31%) was obtained.
In addition, 6i (37%) was recovered.
b
2,6-dimethoxyphenol. From these phenols they obtained In summary, PbO2 in combination with 70% HClO4 is a
none or some of the p-benzoquinones, the exclusive or prin- fairly strong oxidant for phenols and can convert them in-
cipal products being the 4,4'-diphenoquinones.5 Reaction of cluding 4-substituted ones to p-benzoquinones rapidly un-
2,4,6-trichlorophenol with PbO2 in AcOH was reported to der mild conditions. This inexpensive oxidant can be used
afford only a chlorinated phenoxybenzoquinone.7
in large-scale preparation of p-benzoquinones.

SYNTHESIS
August 1998
1147
1H (90 MHz) NMR spectra were taken in CDCl3 with a Hitachi R-
1900 spectrometer. Column chromatography was performed using
Merck Silica gel 60. TLC was carried out on thin silica gel plates.
Commercially available PbO2 (Aldrich) was used as received. Phe-
nols 6g,10 6h11 and 6i12 were prepared according to the reported meth-
ods. Reactions with PbO2 were carried out at 25°C. Compounds 2,13
3,14 415 and 515 obtained in our previous studies were used as authen-
tic samples.
graphed on silica gel with CH2Cl2 as eluent yielding the respective p-
benzoquinones (Table 2).
2,6-Diisopropyl-p-benzoquinone: from 2,6-diisopropylphenol; yield:
632 mg (82%); deep yellow oil; Lit.16 oil.
1H NMR δ = 6.47 (s, 2 H), 3.08 (hept, J = 6.8 Hz, 2 H), 1.14 (d, J =
6.8 Hz, 12 H).
2,6-Dimethyl-p-benzoquinone: from 2,6-dimethylphenol; yield: 333 mg
(61%); yellow crystals from petroleum ether; mp 70–72°C (Lit.17 mp
72–73°C).
Oxidation of 2,6-Di-tert-butylphenol (1) with PbO2 in AcOH:
A solution of 1 (825 mg, 4 mmol) in AcOH (15 mL) was added drop-
wise over a period of 5 min to a magnetically stirred, heterogeneous
mixture of PbO2 (2.39 g, 10 mmol) and AcOH (15 mL). The resulting
mixture was stirred for 5 min and filtered into a flask containing H2O
(ca. 150 mL). The filter cake was washed with CH2Cl2 into the same
flask. Black powder collected on the filter paper consisted of unreact-
ed PbO2. The contents of the flask were extracted with CH2Cl2. The
organic extract was washed with H2O, dried (Na2SO4), and evaporat-
ed to dryness. The 1H NMR spectrum of the semicrystalline residue
indicated that it contained bis(cyclohexadienone) 4, but neither 4,4'-
diphenoquinone 3 nor 4,4'-biphenol 5 was detectable. Recrystalliza-
tion of the residue from petroleum ether afforded 4 (134 mg) as col-
orless crystals, identical with the authentic sample (1H NMR and
TLC); mp 140–150°C (Lit.15 mp 140–150°C). The filtrate was con-
centrated and chromatographed on silica gel by gradient elution (pe-
troleum ether to 90:10 petroleum ether/benzene) to afford successive-
ly 1 (285 mg, 35% recovery), 5 (344 mg) and 3 (13 mg). Since 3 and
5 obtained can be assumed to be artifacts formed from 4 during the
chromatography,15 the content of 4 in the original residue was esti-
mated to be 491 mg (60%).
2-Isopropyl-5-methyl-p-benzoquinone: from 2-isopropyl-5-meth-
ylphenol; yield: 391 mg (60%); yellow crystals from petroleum ether;
mp 43–44°C (Lit.17 mp 46–48°C).
2,5-Dimethyl-p-benzoquinone: from 2,5-dimethylphenol; yield:
246 mg (45%); yellow crystals from diisopropyl ether; mp 123–
125.5°C (Lit.17 mp 125°C).
2,3-Dimethyl-p-benzoquinone: from 2,3-dimethylphenol; yield:
240 mg (44%); yellow crystals from petroleum ether; mp 55–57°C
(Lit.17 mp 55°C).
2,6-Dimethoxy-p-benzoquinone: from 2,6-dimethoxyphenol; yield:
493 mg (73%); yellow crystals by washing the residue with Et2O; mp
256–257°C (Lit.17 mp 251.5°C).
2-Phenyl-p-benzoquinone: from 2-phenylphenol; yield: 604 mg
(82%); deep yellow crystals from MeOH ; mp 111–113°C (Lit.17 mp
113–114 °C).
Compound 5:
Light yellow crystals, identical with the authentic sample (1H NMR
and TLC); mp 186–188°C (Lit.15 mp 184.5–185.5°C).
The reaction of 1 with PbO2 (2 equiv) in AcOH carried out following
the procedure described by de Jong et al.5 gave 1 (27% recovery) and
4 (70%).
2,6-Dichloro-p-benzoquinone: from 2,6-dichlorophenol; yield:
525 mg (74%); yellow crystals from MeOH ; mp 122°C (Lit.18 mp
119–120°C). The same benzoquinone (549 mg, 78%) was also ob-
tained from the reaction of 2,4,6-trichlorophenol.
2,6-Dibromo-p-benzoquinone: from 2,4,6-tribromophenol; yield: 929
mg (87%); yellow crystals from MeOH; mp 130.5–132°C (Lit.18 mp
131–132°C).
Oxidation of 2,6-Di-tert-butylphenol (1) with PbO2 and 70%
HClO4 in Various Solvents:
A solution of 1 (4 mmol) in the appropriate solvent (Table 1, 15 mL)
was added dropwise over a period of 3 min to a stirred mixture of
PbO2 (10 mmol), 70% HClO4 (3, or 5 mL; 35 or 58 mmol, respective-
ly) in the solvent (15 mL). The resulting mixture was stirred for 1 min
and worked up in the manner described above for the oxidation of 1
with PbO2 in AcOH. The residue was chromatographed on silica gel
with petroleum ether/benzene (85:15) as eluent to afford p-benzo-
quinone 2 and/or 3 (Table 1).
Conversion of Phenols 6 into 2,6-Di-tert-butyl-p-Benzoquinone
(2) with PbO2 and 70% HClO4 in Acetone:
A solution of 6 (4 mmol) in acetone (20 mL) was added dropwise over
a period of 3 min to a stirred mixture of PbO2 (5, 8, 10 or 16 mmol),
70% HClO4 (5 mL) and acetone (15 mL), and the resulting mixture
was stirred for 2 min. Due to the limited solubility, 6d required more
amount of acetone (35 mL) for dissolution. The reaction mixture was
worked up in the manner described above for the reaction of 1 with
PbO2 in AcOH. The residue was chromatographed on silica gel with
petroleum ether/benzene (85:15) as eluent to give 2. The reaction of
6b gave additionally dienone 7 (289 mg, 31%). From 6i, unreacted
starting material was recovered to an extent of 37% (Table 3).
Compound 7: Colorless crystals from hexane; mp 112–114°C (Lit.19
mp 112–113°C).
Compound 2:
Orange crystals from hexane, identical with the authentic sample (1H
NMR and TLC); mp 66–68°C (Lit.13 mp 65–68°C).
Compound 3:
Reddish brown crystals from benzene, identical with the authentic
sample (1H NMR and TLC); mp 244–246°C (Lit.14 mp 240–241°C).
Conversion of 4-Unsubstituted and 4-Halogenated Phenols into p-
Benzoquinones with PbO2 and 70% HClO4 in AcOH; General
Procedure:
Similar reactions of 6c, 6d, 6e, 6h and 6i were conducted by using
H2O (5 mL) in place of 70% HClO4. The results were as follows. The
reaction of 6c gave 3 (64%) and 5 (5%) and recovered 6c (28%). The
reaction of 6d gave only traces of 2 and 3, unreacted 6d was recovered
to an extent of 99%. The reaction of 6e gave 3 (33%) and 5 (13%)
together with unreacted 6e (53%). The reaction of 6h gave 2 (0.6%),
3 (16%), 5 (0.6%) and unreacted 6h (83%). The reaction of 6i gave
only a trace of 3, most of 6i (99%) remained unreacted.
A solution of the appropriate phenol (Table 2, 4 mmol) in AcOH (15
mL) was added dropwise over a period of 3 min to a stirred mixture
of PbO2 (10 mmol), 70% HClO4 (5 mL) and AcOH (15 mL), and the
resulting mixture was stirred for 2 min. In the reactions of 2,4,6-
trichlorophenol and 2,4,6-tribromophenol, 5 mmol and 8 mmol of
PbO2, respectively, were employed. The reaction mixture was
worked up in the manner described above for the oxidation of 1 with
PbO2 in AcOH, except that Et2O was used in place of CH2Cl2 for the
washing and the extractive workup. The residue was chromato-
The author is thankful to Kaori Kojima (student) for experimental
contributions.

SYNTHESIS
Papers
1148
(1) Thomson, R. H. In The Chemistry of the Quinonoid Com-
pounds; Patai, S., Ed.; Wiley: London, 1974; Part 1, p 111.
Naruta, Y.; Maruyama, K. In The Chemistry of the Quinonoid
Compounds, Vol.2; Patai, S.; Rappoport, Z., Eds.; Wiley, Lon-
don, 1988; Part 1, p 241.
Zimmer, H.; Lankin, D. C.; Horgan, S. W. Chem Rev. 1971, 71,
229.
Maruyama, K.; Otsuki, T. Bull. Chem. Soc. Jpn. 1971, 44, 2873.
(2) Liotta, D.; Arbiser, J.; Short, J. W.; Saindane, M. J. Org. Chem.
1983, 48, 2932.
(3) McKillop, A.; Perry, D. H.; Edwards, M.; Antus, S.; Farkas, L.;
Nógrádi, M.; Taylor, E. C. J. Org. Chem. 1976, 41, 282.
(4) Musso, H. In Oxidative Coupling of Phenols, Taylor, W. I.; Bat-
tersby, A. R. Eds.; Marcel Dekker: New York, 1967; p 1.
Mihailovic, M. Lj.; Cekovic, Z. In The Chemistry of the Hydro-
xyl Group; Patai, S., Ed.; Wiley: London, 1971; Part 1, p 537.
(5) de Jong, C. R. H. I.; van Dort, H. M.; Vollbracht, L. Tetrahe-
dron Lett. 1970, 1881.
tive coupling [3 (53%) + 5 (7%)] took place principally and
oxygenation [4-acetoxy-2,6-di-tert-butylphenol (28%) + 2
(5%)] took only a minor course. Trifluoromethanesulfonic acid,
another very strong acid, was almost as effective as 70%
HClO4: 2 (94%) and a trace of 3 were obtained. The results were
not essentially altered even if the reactions with these acids were
performed in the presence of added H2O (1.5 mL). From the re-
action with 97% H2SO4, ca. 80% of 1 was recovered. The acid
appeared to deactivate PbO2. The oxidation of 1 with 61%
HNO3 was complicated since it was accompanied by nitration
of 1. Reaction with 35% HCl was given up because PbO2 react-
ed with the acid.
(10) Starnes, Jr., W. H. J. Org. Chem. 1966, 31, 3164.
(11) Omura, K. J. Org. Chem. 1996, 61, 2006.
(12) Meek, J. S.; Fowler, J. S.; Monroe, P. A.; Clark, T. J. J. Org.
Chem. 1968, 33, 223.
(13) Omura, K. J. Org. Chem. 1989, 54, 1987.
(14) Omura, K. J. Org. Chem. 1984, 49, 3046.
(6) Cook, C. D.; English, E. S.; Wilson, B. J. J. Org. Chem. 1958,
23, 755.
(7) Hunter, W. H.; Morse, M. J. Am. Chem. Soc. 1926, 48, 1615.
(8) Two equivalents of PbO2 were assumed to be required for con-
verting one equivalent of a 4-unsubstituted phenol to the corre-
sponding p-benzoquinone.
(15) Omura, K. J. Org. Chem. 1991, 56, 921.
(16) Weyler, Jr., W.; Duncan, W. G.; Moore, H. W. J. Am. Chem.
Soc. 1975, 97, 6187.
(17) Teuber, H.-J.; Rau, W. Chem. Ber. 1953, 86, 1036.
(18) McKillop, A.; Swann, B. P.; Taylor, E. C. Tetrahedron 1970,
26, 4031.
(9) The reaction of 1 with PbO2 in AcOH was conducted in the
presence of an acid (9 equiv) other than 70% HClO4. In the re-
action with CF3CO2H, a weaker acid than HClO4, dehydrogena-
(19) Barton, D. H. R.; Magnus, P. D.; Quinney, J. C. J. Chem. Soc.,
Perkin Trans. 1 1975, 1610.