A novel catalytic hypervalent iodine oxidation of p-alkoxyphenols to p-quinones using 4-iodophenoxyacetic acid and Oxone

Article abstract of DOI:10.1055/s-2007-970758

A novel catalytic hypervalent iodine oxidation of phenol derivatives using 4-iodophenoxyacetic acid and Oxone was developed. Reaction of p-alkoxyphenols with a catalytic amount of 4-iodophenoxyacetic acid in the presence of Oxone as a co-oxidant in acetonitrile-water (2:1) gave the corresponding p-quinones in excellent yields without purification. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-970758

LETTER
765
A Novel Catalytic Hypervalent Iodine Oxidation of p-Alkoxyphenols to
p-Quinones Using 4-Iodophenoxyacetic Acid and Oxone®
H
ypervalent Iod
a
ine Oxida
t
k
ion of
p
-Alk
a
oxyphenols
y
to
p
-Quinon
ues ki Yakura,* Tatsuya Konishi
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194, Japan
E-mail: yakura@pha.u-toyama.ac.jp
Received 26 December 2006
I
Abstract: A novel catalytic hypervalent iodine oxidation of phenol
OH
O
O
derivatives using 4-iodophenoxyacetic acid and Oxone® was devel-
1
X
OCOtBu
OCOtBu
®
oped. Reaction of p-alkoxyphenols with a catalytic amount of
4-iodophenoxyacetic acid in the presence of Oxone® as a co-oxidant
in acetonitrile–water (2:1) gave the corresponding p-quinones in
excellent yields without purification.
Oxone (1 equiv)
MeCN–H2O (2:1)
r.t.
2a
3a
OMe
Key words: p-alkoxyphenol, p-quinone, catalysis, hypervalent
Scheme 1
iodine oxidation, 4-iodophenoxyacetic acid, Oxone®
using a catalytic amount of 4-iodophenoxyacetic acid
(1a)14 and an equimolar amount of Oxone® as a co-oxi-
dant.
Development of efficient methods for synthesis of p-
quinone and p-quinone derivatives is one of the most im-
portant subjects in synthetic organic chemistry, since they
are structural components of a large number of natural
products and useful synthetic intermediates.1 As one of
the most convenient procedures to p-quinones, hyperval-
ent iodine oxidation of p-alkoxyphenols using phenyl-
iodine(III) trifluoroacetate (PIFA) was reported in 1989.2
After this report, several groups investigated similar
oxidations of phenol derivatives by phenyliodine(III) di-
acetate (PIDA) and other hypervalent iodine reagents.3
Moreover, an efficient p-quinone synthesis via oxidative
demethylation of phenyl ethers was reported using PIFA.4
We chose Oxone® as an environmentally safe co-oxidant
for the preparation of p-quinones, since Oxone® is an
inorganic and water-soluble oxidant with a low order of
toxicity, and moreover it is commercially available and
inexpensive.15 As alkoxyphenols have relatively high re-
activity under oxidation conditions, we first investigated
the oxidative ability of Oxone® alone.16 Thus, a mixture of
2-pivaloyloxymethyl-4-methoxyphenol (2a) and an
equimolar amount of Oxone® in acetonitrile–water (2:1)
at room temperature gave the corresponding p-benzo-
quinone (3a), but the reaction was quite sluggish, and the
yield of 3a was only 13% along with 78% of recovered
starting 2a after 24 hours. Next, we examined reactions of
2a with a catalytic amount of several iodoarenes in the
presence of Oxone® (Scheme 1). The results are summa-
rized in Table 1. According to the procedure reported by
Vinod,12 a mixture of 2a, 0.2 equivalent of 2-iodobenzoic
acid, and 1 equivalent of Oxone® in acetonitrile–water
was heated at 70 °C for 19 hours to give a complicated
mixture (entry 2). The oxidation at room temperature gave
better results (entry 3). Iodobenzene showed moderate
catalytic activity (entry 4). Methyl and methoxy groups on
the benzene ring showed to enhance the reactivity of
iodoarene (entries 5–8). Especially, when 0.2 equivalent
of 4-iodoanisole were used as catalyst, the reaction was
completed within 17 hours to give 2a in 90% yield (entry
8). Acetoxy group, however, decreased reactivity of
iodoarene (entry 9). Other iodobenzenes with a p-alkoxy
group, such as p-OMOM, p-OCH2CO2Me, p-
O(CH2)3CO2Me, are also effective to catalyze the oxida-
tion of 2a to 3a (entries 10–12). These results indicated
that electron-donating alkoxy group at the para position
on the benzene ring would increase catalytic efficiency
of iodoarene, in contrast to the reported results using
MCPBA as a co-oxidant.9–11 Slower reaction was ob-
served using 0.1 equivalent of 4-iodoanisole (entry 13),
Both PIFA and PIDA have been extensively used in re-
cent organic syntheses owing to their low toxicity, ready
availability and ease of handling.5 Pentavalent iodine
reagents such as Dess–Martin periodinane (DMP) and
o-iodoxybenzoic acid (IBX) have also attracted consider-
able attention as mild and selective oxidizing agents.6
However, these reagents are highly expensive and sto-
ichiometric amounts of iodine reagents are required in the
oxidation to produce equimolar amount of iodine waste.
Moreover, pentavalent iodine reagents are potentially
explosive. To overcome these disadvantages of these re-
agents, recyclable polymer-supported hypervalent iodine
reagents have been developed.7 Very recently, catalytic
trivalent iodine oxidations8 using m-chloroperbenzoic
acid (MCPBA) as a co-oxidant were reported by Kita,9
Ochiai,10 and Togo11 groups, respectively. Vinod12 and
Giannis13 groups independently found a catalytic use of
IBX generated from 2-iodobenzoic acid and Oxone®
(2KHSO5·KHSO4·K2SO4). We report herein an efficient
and practical oxidation of p-alkoxyphenols to p-quinones
SYNLETT 2007, No. 5, pp 0765–0768
1
6.
0
3.
2
0
0
7
Advanced online publication: 08.03.2007
DOI: 10.1055/s-2007-970758; Art ID: U15706ST
© Georg Thieme Verlag Stuttgart · New York

766
T. Yakura, T. Konishi
LETTER
however, larger amounts (0.5–1 equiv) led to decreased er 48 hours to give 92% yield of 3a (entry 2). On the other
reaction times with similar yields of 3a (entries 14 and hand, a similar reaction using 0.5 equivalent of Oxone®
15).
was not finished after several days (entry 3). These results
suggested that the most efficient amount of Oxone® for
this oxidation would be an equimolar amount. So, the use
of 0.2 equivalent of 1a and 1 equivalent of Oxone® was
selected as standard condition. Reaction of simple p-
methoxy-, p-ethoxy-, and p-butoxyphenols (2b–d) gave
p-benzoquinone (3b) in good yields, respectively (entries
4–6). This oxidation system was also effective to phenols
bearing a bulky substituent at the ortho position (entries 7
and 8). tert-Butyldiphenylsilyloxy (TBDPS) and azide
groups were tolerable under the reaction conditions (en-
tries 9 and 10). Oxidation of phenol having succinimide
group (2i) proceeded in high yield using 0.4 equivalent of
1a (entry 11). Reaction of 4-methoxy-1-naphthol (4) with
catalytic amount of 1a in the presence of Oxone® gave rise
to low yield of 1,4-naphthoquinone (5) with a complex
mixture. This result should be caused by decomposition of
4 by Oxone®, because 4 would be sensitive under oxida-
tion conditions. However, stoichiometric use of 1a pro-
duced 5 within 10 minutes in 86% yield (Scheme 2). In all
cases, 1a was recovered in good yield (75–85%) and it can
be used for the oxidation again after recrystallization.
Although p-alkoxyiodobenzenes gave satisfactory results,
unfortunately, the reactions required careful purification
by column chromatography in order to separate the prod-
uct and the recovered catalyst. Thus, we selected 4-io-
dophenoxyacetic acid (1a),14 which was easily prepared
from 4-iodophenol, in the hope of becoming a more prac-
tical catalyst because 1a has an electron-donating group at
the para position and is soluble in alkaline solution. A
similar reaction of 2a with 0.2 equivalent of 1a in the pres-
ence of 1 equivalent of Oxone® proceeded smoothly to af-
ford pure 3a in 99% yield and 75% of recovered 1a
without column chromatography (entry 16).
Table 1 Oxidation of 2a with 1 and Oxone®a
Entry
1
Time
(h)
Yield of 3a
X
(equiv)
(%)
1
2c
3
None
24
19
24
24
24
24
24
17
24
22
21
40
24
9
13 (78)b
6 (4)b
39 (6)b
64 (24)b
77 (14)b
71 (14)b
77 (4)b
90
o-CO2H
o-CO2H
H
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.1
0.5
1.0
0.2
OH
O
4
1.0 equiv 1a
®
1.0 equiv Oxone
5
p-Me
r.t., 10 min
(86%)
6
o-OMe
4
OMe
5
O
7
m-OMe
p-OMe
Scheme 2
8
9
p-OCOMe
p-OMOM
p-OCH2CO2Me
p-O(CH2)3CO2Me
p-OMe
54 (40)b
92
A possible catalytic cycle for this oxidation is shown in
Scheme 3. Iodoarene would be oxidized by Oxone® to io-
dine(V) species12,13,17 which reacts with p-alkoxyphenol18
to give p-quinone and iodine(III) species. The trivalent io-
dine species should be reduced further to monovalent de-
rivative to result in the oxidation of another phenol2 to
quinone.19 Iodoarenes with electron-donating substituents
such as methoxy and methyl groups may be more easily
oxidized by Oxone® to cause rapid reactions, whereas an
electron-withdrawing substituent such as a carboxyl
group may decrease the reactivity of iodoarene against the
oxidant.
10
11
12
13
14
15
16
94
86
73 (18)b
92
p-OMe
p-OMe
5
94
p-OCH2CO2H
1a
19
99
In summary, a novel and practical catalytic hypervalent
iodine oxidation of phenol derivatives using 1a was devel-
oped. Reaction of p-alkoxyphenols 2 with a catalytic
amount of 1a in the presence of Oxone® as a co-oxidant in
acetonitrile–water (2:1) gave the corresponding p-quino-
nes 3 in excellent yields without purification. The substit-
uent effect on iodobenzene ring in the oxidation was
observed; p-alkoxy is the most effective, with the series
following the approximate order p-RO > p-Me, o-MeO,
m-MeO > H > o-CO2H.
a Reactions were carried out in the presence of 1 equiv of Oxone® in
MeCN–H2O (2:1) at r.t.
b Parentheses are recovery of 2a.
c Reaction was carried out at 70 °C.
A variety of p-alkoxyphenols (2a–i) were oxidized with a
catalytic amount of 1a and Oxone® to the corresponding
p-quinones (Table 2). When 0.7 equivalent of Oxone®
were used in the reaction of 2a in the presence of 0.2
equivalent of 1a, the reaction was completed within long-
Synlett 2007, No. 5, 765–768 © Thieme Stuttgart · New York

LETTER
Hypervalent Iodine Oxidation of p-Alkoxyphenols to p-Quinones
767
Table 2 Catalytic Hypervalent Iodine Oxidation of 2 with 1a and Oxone®a,20
Entry
Phenol
Quinone
Time (h)
Yield (%)
1b
2c
3d
4
2a
2a
2a
OH
3a
3a
3a
O
19
48
8 d
16
99
92
incomplete
80
OMe
2b
O
3b
3b
5
6
17
17
24
23
24
22
40
79
77
53
80
96
92
89
OH
OEt
2c
3b
OH
OBu
2d
7
O
OH
O
OMe
3e
2e
8
OH
O
OMe
O
2f
3f
9
OH
O
OTBDPS
OTBDPS
OMe
2g
O
3g
10
OH
O
N3
N3
OMe
O
3h
O
2h
11e
O
N
O
N
OH
O
O
O
OMe
3i
2i
a Reactions were carried out using 0.2 equiv of 1a and 1 equiv of Oxone® in MeCN–H2O (2:1) at r.t.
b Same as entry 16, Table 1.
c 0.7 Equiv of Oxone® were used.
d 0.5 Equiv of Oxone® were used.
e 0.4 Equiv of 1a were used.
Synlett 2007, No. 5, 765–768 © Thieme Stuttgart · New York

768
T. Yakura, T. Konishi
LETTER
W.; Finch, H. J. Chem. Soc., Perkin Trans. 1 1999, 669.
(d) Ley, S. V.; Schucht, O.; Thomas, A. W.; Murray, P. J. J.
Chem. Soc., Perkin Trans. 1 1999, 1251. (e) Tohma, H.;
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2000, 39, 1306. (f) Tohma, H.; Maegawa, T.; Takizawa, S.;
Kita, Y. Adv. Synth. Catal. 2002, 328.
O
O
OH
R
R
OR'
(8) (a) Dohi, T.; Kita, Y. Kagaku 2006, 61, 68. (b) Richardson,
R. D.; Wirth, T. Angew. Chem. Int. Ed. 2006, 45, 4402.
(9) Dohi, T.; Maruyama, A.; Yoshimura, M.; Morimoto, K.;
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(10) Ochiai, M.; Takeuchi, Y.; Katayama, T.; Sueda, T.;
Miyamoto, K. J. Am. Chem. Soc. 2005, 127, 12244.
(11) Yamamoto, Y.; Togo, H. Synlett 2006, 798.
(12) Thottumkara, A. P.; Bowsher, M. S.; Vinod, T. K. Org. Lett.
2005, 7, 2933.
OH
Ar I ( V)
Ar I (III)
R
OR'
(13) Schulze, A.; Giannis, A. Synthesis 2006, 257.
(14) Compound 1a is commercially available. For preparation,
see: Abraham, D. J.; Kennedy, P. E.; Mehanna, A. S.; Patwa,
D. C.; Williums, F. L. J. Med. Chem. 1984, 27, 967.
(15) Marcotullio, M. C.; Epifano, F.; Curini, M. Trends Org.
Chem. 2003, 10, 21.
(16) Very recently, oxidation of p-alkylphenols by the
combination of Oxone® and NaHCO3 has been reported, see:
Carreño, M. C.; González-López, M.; Urbano, A. Angew.
Chem. Int. Ed. 2006, 45, 2737.
(17) It is not clear whether iodine(V) species was formed during
the reaction. However, many reports for the formation of
iodine(V) species by the oxidation of iodoarene with
oxidizing reagent have been reported, see: (a) Kennedy, R.
J.; Stock, A. M. J. Org. Chem. 1960, 25, 1901.
O
Oxone®
Ar I (I)
R
O
Scheme 3
Acknowledgment
The authors wish to thank Professor Yasuyuki Kita (Osaka Uni-
versity, Japan) for helpful discussion.
(b) Sharefkin, J. G.; Saltzman, H. Org. Synth. 1963, 43, 65.
(c) Barton, D. H. R.; Godfrey, C. R. A.; Morzycki, J. W.;
Motherwell, W. B.; Ley, S. V. J. Chem. Soc., Perkin Trans.
1 1982, 1947. (d) Kazmierczak, P.; Skulski, L.;
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V. Curr. Org. Synth. 2005, 2, 121. (g) Ladziata, U.;
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Y.; Karimov, R. R.; Geraskin, I. M.; Nemykin, V. N.;
Zhdankin, V. V. J. Org. Chem. 2006, 71, 8452.
References and Notes
(1) (a) The Chemistry of the Quinonoid Compounds, Part 1 and
2, Vol. 2; Patai, S.; Rappoport, Z., Eds.; John Wiley & Sons:
Chichester, 1988. (b) Naturally Occurring Quinones IV,
Recent Advances; Thomson, R. H., Ed.; Blackie Academic
and Professional: London, 1997.
(2) Tamura, Y.; Yakura, T.; Tohma, H.; Kikuchi, K.; Kita, Y.
Synthesis 1989, 126.
(3) (a) Barret, R.; Daudon, M. Tetrahedron Lett. 1990, 31,
4871. (b) Barret, R.; Daudon, M. Synth. Commun. 1990, 20,
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(d) Pelter, A.; Elgendy, S. M. A. J. Chem. Soc., Perkin
Trans. 1 1993, 1891.
(i) Koposov, A. Y.; Karimov, R. R.; Pronin, A. A.;
Skrupskaya, T.; Yusubov, M. S.; Zhdankin, V. V. J. Org.
Chem. 2006, 71, 9912.
(18) For the oxidation of phenol derivatives with iodine(V)
species, see ref. 3b and: Barton, D. H. R.; Godfrey, C. R. A.;
Morzycki, J. W.; Motherwell, W. B.; Stobie, A. Tetrahedron
Lett. 1982, 23, 957.
(4) Tohma, H.; Morioka, H.; Harayama, Y.; Hashizume, M.;
Kita, Y. Tetrahedron Lett. 2001, 42, 6899.
(5) For recent reviews, see: (a) Stang, P. J.; Zhdankin, V. V.
Chem. Rev. 1996, 96, 1123. (b) Kita, Y.; Takada, T.;
Tohma, H. Pure Appl. Chem. 1996, 68, 627. (c) Kitamura,
T.; Fujiwara, Y. Org. Prep. Proced. Int. 1997, 29, 409.
(d) Hypervalent Iodine in Organic Synthesis; Varvoglis, A.,
Ed.; Academic Press: San Diego, 1997. (e) Varvoglis, A.
Tetrahedron 1997, 53, 1179. (f) Zhdankin, V. V. Rev.
Heteroatom Chem. 1997, 17, 133. (g) Muraki, T.; Togo, H.;
Yokoyama, M. Rev. Heteroatom Chem. 1997, 17, 213.
(h) Varvoglis, A.; Spyroudis, S. Synlett 1998, 221.
(i) Wirth, T.; Hirt, U. H. Synthesis 1999, 1271.
(6) For reviews, see: (a) Wirth, T. Angew. Chem. Int. Ed. 2001,
40, 2812. (b) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002,
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(7) (a) Togo, H.; Nogami, G.; Yokoyama, M. Synlett 1998, 534.
(b) Togo, H.; Abe, S.; Nogami, G.; Yokoyama, M. Bull.
Chem. Soc. Jpn. 1999, 72, 2351. (c) Ley, S. V.; Thomas, A.
(19) It is possible that iodine(III) species may be oxidized by
Oxone® to regenerate iodine(V) species before the reaction
of iodine(III) with phenol.
(20) Typical Reaction Procedure: To a solution of 2 (1 mmol)
in MeCN–H2O (2:1, 6 mL) was added 1a (0.2 mmol)
followed by Oxone® (1 mmol) at r.t. and the resulting
mixture was stirred at the same temperature. After 2 was
completely consumed indicated by TLC, the mixture was
diluted with EtOAc and washed with H2O. The organic layer
was then washed with aq sat. NaHCO3 solution and dried,
concentrated to give pure 3. If necessary, the product was
purified by column chromatography on silica gel to give
pure quinone.
The alkaline solution was acidified by 10% HCl solution and
extracted with EtOAc. The organic layer was washed with
aq Na2S2O3 solution and dried, then concentrated to give
recovered 1a which was purified by recrystallization from
Et2O–hexane.
All new compounds gave satisfactory spectroscopic data.
Synlett 2007, No. 5, 765–768 © Thieme Stuttgart · New York

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