Selective oxidation of phenol and anisole derivatives to quinones with hydrogen peroxide and polymer-supported methylrhenium trioxide systems

Article abstract of DOI:10.1016/S0040-4020(02)01025-6

A convenient and efficient application of heterogeneous poly(4-vinylpyridine)/methyl rhenium trioxide (PVP/MTO) systems for the selective oxidation of substituted phenol and anisole derivatives to benzoquinones is described. Environment friendly, easily available, and low cost H₂O₂ was used as the oxygen atom donor. All catalysts were stable systems for at least five recycling experiments. In the oxidation of some natural phenols such as cardanol derivatives higher conversion and yields of benzoquinones were observed with respect to MTO in homogeneous phase suggesting a support-mediated molecular recognition process based on hydrogen-bonding interactions.

Full text of DOI:10.1016/S0040-4020(02)01025-6

Tetrahedron 58 (2002) 8493–8500
Selective oxidation of phenol and anisole derivatives to quinones
with hydrogen peroxide and polymer-supported methylrhenium
trioxide systems
a
a
b
Raffaele Saladino,a Veronica Neri, Enrico Mincione and Paolino Filippone
,
*
a
`
Dipartimento di Agrobiologia ed Agrochimica, Universita della Tuscia, Via S. Camillo de Lellis s.n.c., 01100 Viterbo, Italy
`
Centro per lo studio delle Sostanze Organiche di Origine Naturale, Universita di Urbino, piazza della Repubblica 13, Urbino, Italy
b
Received 7 June 2002; revised 24 July 2002; accepted 15 August 2002
Abstract—A convenient and efficient application of heterogeneous poly(4-vinylpyridine)/methyl rhenium trioxide (PVP/MTO) systems for
the selective oxidation of substituted phenol and anisole derivatives to benzoquinones is described. Environment friendly, easily available,
and low cost H2O2 was used as the oxygen atom donor. All catalysts were stable systems for at least five recycling experiments. In the
oxidation of some natural phenols such as cardanol derivatives higher conversion and yields of benzoquinones were observed with respect to
MTO in homogeneous phase suggesting a support-mediated molecular recognition process based on hydrogen-bonding interactions. q 2002
Elsevier Science Ltd. All rights reserved.
1. Introduction
their homogeneous counterparts. In the past few years
methylrhenium trioxide (CH3ReO3, MTO)23 has been
shown to possess interesting catalytic properties in oxi-
dation reactions with environment friendly hydrogen
peroxide (H2O2) as an oxygen atom donor.24 Among
them, the oxidation of phenol and methoxybenzene
derivatives has been studied. Methoxy-substituted benzenes
are oxidized with the MTO/H2O2 system in acetic acid to
yield the corresponding alkoxy-substituted para-benzo-
quinones,25 some of which show important biological
activities.26 In a similar way, the oxidation of para-
unsubstituted alkylphenols, characterized by small alkyl
side-chains, afforded 1,4-benzoquinones in acceptable
yields.27 Noteworthy, a fine-tuned substituent effect on the
regioselectivity of the oxidation (ortho-benzoquinones
versus para-benzoquinones) was observed in the case of
natural phenols, such as cardanol derivatives, depending on
the steric hindrance and position of the alkyl substituents on
the aromatic ring.28 Recently, we have described the
preparation of novel heterogeneous rhenium compounds
of general formula (polymer)f/(MTO)g (the f/g quotient
expresses the ratio by weight of the two components) by
heterogenation of MTO on poly(4-vinylpyridine) and
polystyrene as low cost and easily available polymeric
supports.29 These novel MTO compounds were efficient and
selective heterogeneous catalysts for the epoxidation of
olefins even in the case of sensitive epoxides. Poly(4-
vinylpyridine)/MTO systems were prepared starting from
poly(4-vinylpyridine) 25% cross-linked (with divinyl-
benzene) (PVP-25%), and poly(4-vinylpyridine-N-oxide)
2% cross-linked (PVPN-2%), as supports. Poly(4-vinyl-
pyridine) 2% cross-linked (PVP-2%)30 was also used as a
Natural products having a benzoquinone structure show
biologically important properties such as cardiovascular,
antitumour, antibacterial, antigerminative and anti-
protozoan activities.1 Furthermore, benzoquinones are
important fine-chemicals in industry and are useful
dienophiles in chemical transformations.2 Benzoquinones
are usually prepared by direct oxidation of phenol and
methoxy benzene derivatives. The most commonly
employed stoichiometric oxidants for these syntheses are
Fremy’s salt,3 Weitz’s salt (BAHA),4 ceric ammonium
nitrate (CAN),5 ortho-chloranil (tetrachlorobenzo-1,2-
quinone),6 chromium(VI) salts,7 hypervalent iodine(III),8
N-bromosuccinimide (NBS),9 and silver(I) oxide–HNO3
system.10 However, the different reagents used show
varying degree of success as well as limitations due to
low reproducibility,11 the possibility of explosion,12 high
reaction temperatures,13 and strongly basic or acidic
conditions that may be incompatible with substituents on
the aromatic ring.14 To avoid these problems, catalytic
systems including heteropolyacids,15 ruthenium deriva-
tives,16 metalloporphyrins,17 transition metal compounds,18
supported vanadium,19 cobalt,20 and copper21 salts, and
titanium and chromium silicalites22 have been used. Most of
these systems perform in homogeneous phase reactions, and
the process may be improved by using stable heterogeneous
catalysts which usually have advantages with respect to
Keywords: oxidation; phenols; catalysis; natural products.
*
Corresponding author. Tel.: þ39-761-357284; fax: þ39-761-357242;
e-mail: saladino@unitus.it
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01025-6

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R. Saladino et al. / Tetrahedron 58 (2002) 8493–8500
Table 1. Poly(4-vinylpyridine)/MTO catalysed oxidation of phenols 1–4
entry
Catalyst
Substrate Conversion Product Yield(s)a
(%)
(s)
(%)
1
2
3
4
5
6
7
8
MTOb
MTO
1
1
1
1
1
2
2
2
3
4
53
73
79
58
71
69
48
65
83
23
5
5
5
5
5
6
6
6
7
8(9)
58
86
83
92
79
85
73
81
PVP-2%/MTO
PVP-25%/MTO
PVPN-2%/MTO
PVP-2%/MTO
PVP-25%/MTO
PVPN-2%/MTO
PVP-2%/MTO
PVP-2%/MTO
9
10
.98
37(11)
Under otherwise specified all the reactions were performed in ethanol
(5 mL) at 458C, with H2O2 (35% aqueous solution), using a value of the
catalyst loading factor of 1.0.
a
Refers to isolated materials. Yields normalized to 100% conversion.
Reaction performed at room temperature.
b
Figure 1.
with the use of MTO heterogeneous compounds for the
synthesis of quinone derivatives.
reference system. Microencapsulated polystyrene/MTO
compounds were obtained by the use of polystyrene 2%
cross-linked (with divinylbenzene) (PS-2%) or a mixture of
PS-2% and PVP-2% (optimal ratio 5:1). All new MTO
compounds were characterized by FT-IR, scanning electron
microscopy (SEM), and wide-angle X-ray diffraction
(WAXS). The reticulation grade of the polymer was found
to be an important factor for the catalysts based on poly(4-
vinylpyridine), either for the morphology of the surface of
particles or for the reaction selectivity. The WAXS analysis
showed that in these systems the rhenium atom is bonded to
two nitrogen atoms of two pyridinyl moieties (probably on
different polymeric chains) in a octahedral-like structure.
The structure of PVP-2%/MTO, PVP-25%/MTO, and
PVPN-2%/MTO catalysts is represented in the schematic
drawing in Fig. 1.
2. Results and discussion
Initially, the oxidation of phenol derivatives with poly(4-
vinylpyridine)/MTO systems were investigated using
3-methyl phenol 1, 2,6-dimethyl phenol 2, 2,3,6-trimethyl
phenol 3, and 4-ethyl phenol 4 as simple representative
model compounds. As a general procedure, the phenol
(1 mmol) to be oxidized was added to a suspension of the
catalyst (PVP-2%/MTO, PVP-25%/MTO, and PVPN-
2%/MTO) using a value of the loading factor of 1.0 (that
is mmol of MTO for 1 g of support) in ethanol (EtOH,
5 mL). The use of acetic acid (AcOH) as solvent in the
homogeneous MTO oxidation of alkyl phenols has been
previously reported.27 In our procedure we selected ethanol
as reaction solvent to avoid the formation of peroxyacetic
acid,25 the presence of which in the medium can influence
the efficiency and the selectivity of the transformation. H2O2
(2.0 mmol, 30% aqueous solution) was added to the
suspension and the mixture was stirred at room temperature
or at 458C. The oxidation results are summarized in Table 1
and Scheme 1. In the absence of the catalyst, less than 2%
conversion of substrates took place under otherwise
We report here that these polymer-supported MTO systems
may be used for the efficient and selective oxidation of
natural phenol and anisole derivatives to the corresponding
benzoquinones with H2O2 (35% water solution) as environ-
ment friendly primary oxi0dant. Even if silica-supported
MTO complex of g-(2,2 -dipiridyl) aminopropylpoly-
siloxane,31 and a NaY zeolite/MTO super cage system32
have been used for the epoxidation of olefins, to the best of
our knowledge this is the first report in the literature dealing
Scheme 1.

R. Saladino et al. / Tetrahedron 58 (2002) 8493–8500
8495
identical conditions. The oxidations with the MTO/H2O2
catalyst system were performed as references. Catalysts
were recovered by filtration at the end of the reaction after
washing with EtOH and were used in successive oxidations
under identical conditions (vide infra).
MTO-catalysed oxidation of 2,6-di-tert-butyl-4-methyl
phenol in acetic acid to give 2,6-di-tert-butyl-4-methyl-
2,5-cyclohexadien-1-one-4-ol in 30% yield.34 Based on
these data it is reasonable to suggest that the unisolable
reactive 4-ethyl-2,5-cyclohexadien-1-one-4-ol intermediate
occurs in the initial step of the oxidation of 4. Acid-
catalysed elimination of water due to the strong Lewis acid
character of MTO, may afford quinone methide 9. Table 2
shows that poly(4-vinylpyridine)/MTO systems are stable
enough to perform at least five recycling experiments with
similar conversion and selectivity.
Irrespective of the experimental conditions, all para-
unsubstituted alkyl phenols, compounds 1–3, afforded
selectively the corresponding alkyl para-benzoquinones.
The oxidation of 1 with the MTO/H2O2 system at room
temperature gave 2-methyl-1,4-benzoquinone 5 in moderate
yield (Table 1, entry 1). The reaction temperature has a
remarkable effect on the transformation since at 458C better
conversion of phenol and higher yield of quinone (73 and
86%, respectively) were obtained (Table 1, entry 2).
Oxidations with poly(4-vinylpyridine)/supported MTO
systems were successively performed at 458C. Treatment
of 1 with the PVP-2%/MTO catalyst under similar
experimental conditions afforded 5 in 79% conversion and
83% yield (Table 1, entry 3). In a similar way, the oxidation
performed with PVP-25%/MTO gave 5 as the only
recovered product. In this case low conversion but higher
yield were obtained (Table 1, entry 4). PVPN-2%/MTO
showed a behaviour similar to PVP-2%/MTO (Table 1,
entry 5). It is worthy of note that all poly(4-vinylpyridine)/
MTO systems retain their selectivity and catalytic activity in
the oxidation of 1. Probably, in accord with the mechanism
previously proposed for the MTO catalytic oxidation of
phenols in AcOH,27 the reaction involves the initial
formation of arene oxide intermediates (not shown).
Under similar experimental conditions at least the same
extent of conversions of 2,6-dimethyl phenol 2 and yields of
2,6-dimethyl-1,4-benzoquinone 6 were achieved, with the
PVP-2%/MTO or PVPN-2%/MTO systems being the most
active catalysts (Table 1, entries 6–8). These results suggest
that the oxidation of 2,6-dialkyl-substituted phenols is
independent of the steric effect of the substituents even in
the case of heterogeneous systems. As expected for catalysts
with electrophilic properties, the more electron-rich phenol
3 with PVP-2%/MTO gave higher substrate conversion and
yield of the corresponding 2,3,6-trimethyl-1,4-benzo-
quinone 7 (TMBQ) than phenols 1 and 2 (Table 1, entry
9). TMBQ is a key intermediate in the manufacture of
vitamin E.33 The oxidation of para-substituted 4-ethyl-
phenol 4 with PVP-2%/MTO was very slow, and less than
30% of conversion of the substrate was obtained. Moreover,
the oxidation showed a different selectivity and the
4-methyl-1,2-benzoquinone 8 and the quinone methide
derivative 9 were isolated in low yields as the only
recovered products (Table 1, entry 10). We have not
investigated in detail the mechanism of formation of the
quinone methide 9. Adam and co-workers25 described the
In view of the synthetic utility of poly(4-vinylpyridine)/
MTO catalysts to prepare biologically active benzoquinone
derivatives, we studied the oxidation of some natural
phenols obtained from cardanol, 3-n-pentadecylphenol
10,35 and 2-tert-butyl-5-n-pentadecylphenol 11.36 Cardanol
is the main component of the roasted cashew nut shell liquid
(CNSL) that is a side-product from the mechanical
processing of the nut of Anacardium occidentale L., a
process of considerable industrial importance in view of the
edibility of the kernel.37 Benzoquinones of cardanol
derivatives show several biological activities and have
been recently used as starting materials to prepare the
corresponding hydroquinone and catechol derivatives.38
These latter compounds show antioxidant activity higher
than similar commercial products, such as 2,6-di-tert-butyl-
4-phenol (BHT) and 2,6-di-tert-buty-4-methoxy phenol
(DBHA).39 In spite of the high number of chemical
transformations reported for cardanol derivatives, to the
best of our knowledge, there are no heterogeneous catalytic
procedures for the selective synthesis of cardanol ortho- and
para-benzoquinones. Oxidation of compounds 10 and 11
were performed under the experimental conditions pre-
viously described (Scheme 2). We started to study the
oxidation of compound 10 using the reference system MTO/
H2O2 in EtOH at 458C. The 4-n-pentadecyl-1,2-benzo-
quinone 12 was obtained in low conversion and yield as
the only recovered product (Table 3, entry 1). Probably, the
poor mass balance observed, even at partial consumption
of the starting substrate, may be due to formation of
water-soluble ring-opened products, as a consequence of
over-oxidation side-processes. When the oxidation was
performed with the PVP-2%/MTO/H2O2 system, the ortho-
benzoquinone 12 was again obtained as the only recovered
product in moderate yield (Table 3, entry 2). On the other
hand, the reported oxidation was very selective and other
possible benzoquinone isomers or products of benzylic
oxifunctionalization were not detected in the reaction
mixture.40 It is reasonable to suggest that this high
selectivity may be due to the presence of the bulky 3-n-
pentadecyl side-chain. This hypothesis is in accordance with
Table 2. Stability of poly(4-vinylpyridine)/MTO catalyst in the oxidation of 3-methylphenol 1
Catalyst
Conversion (%)
Run no. 1
Run no. 2
Run no. 3
Run no. 4
Run no. 5
PVP-2%/MTO
PVP-25%/MTO
PVPN-2%/MTO
79 (83)a
58 (92)
71 (79)
74 (78)
57 (86)
67 (73)
79 (83)
50 (90)
72 (80)
71 (85)
56 (87)
71 (73)
75 (83)
56 (87)
63 (80)
The reactions were performed in ethanol (5 mL) at 458C with H2O2 (35% aqueous solution) using a value of the catalyst loading factor of 1.0.
Values of the benzoquinone yields are given in parentheses and are normalized to 100% of conversion.
a

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R. Saladino et al. / Tetrahedron 58 (2002) 8493–8500
Scheme 2.
Table 3. Poly (4-vinylpyridine)/MTO catalysed oxidation of cardanol
dertivatives 10,11
of the oxidation toward the formation of para-benzo-
quinone. Moreover, the best results were obtained in the
oxidation of 11 with PVP-25%/MTO and PVPN-2%/MTO
catalysts. In fact 13 was recovered in high yield (Table 3,
entries 7 and 8). Table 4 shows that in these oxidations,
PVP-2%/MTO, and PVPN-2%/MTO catalysts, are stable
enough to perform at least five recycling experiments with
similar conversions and selectivities.
entry
Catalyst
Substrate Conversion Product(s) Yield(s)a
(%)
(%)
1
2
3
4
5
6
7
8
MTO
10
10
10
10
11
11
11
11
38
43
56
41
41
58
75
62
12
12
12
12
13
13
13
13
46
53
61
50
38
71
98
96
PVP-2%/MTO
PVP-25%/MTO
PVPN-2%/MTO
MTO
PVP-2%/MTO
PVP-25%/MTO
PVPN-2%/MTO
It is noteworthy that in the oxidation of cardanol derivatives
10 and 11, poly(4-vinylpyridine)-supported MTO systems
are more reactive than their homogeneous counterparts,
even if usually a catalytic species loses part of its catalyst
efficiency after the heterogenation process (see for example
Table 3, entry 5 versus entries 6–8). This apparent anomaly
may be in part explained on the basis of data reported by ten
Brinke and co-workers, on the order–disorder transition of
the system poly(4-vinylpyridine)/3-n-pentadecyl phenol
10.41 The poly(4-vinylpyridine)-supported MTO oxidations
of anisoles 14–16 were carried out in ethanol in analogy to
reported transformations of phenol derivatives to quinones.
The results in Table 5 show that the benzoquinones 17, 19,
and 22 (Scheme 3) can be obtained from moderate to good
yields (30–90% based on converted starting material)
depending on the nature of substrate and catalyst. In the
absence of the catalyst, less than 2% conversion of substrate
took place under otherwise identical conditions. The
oxidation of 1,2-dimethoxy-4-methylbenzene with MTO
in ethanol was observed to slowly afford benzoquinone 17 in
fair yield (Table 5, entry 1). A side-product, that after
spectroscopic characterization was assigned to be a dienone
derivative, 2-methoxy-4-methyl-2,5-cyclohexadien-1-one-
4-olo 18, was also recovered. According to data reported
by Adam and co-workers,25 the formation of 18 may be
explained with the presence of a reactive arene oxide
intermediate further involved in a catalysed demethylation
Under otherwise specified all the reactions were performed in ethanol
(5 mL) at 458C, with H2O2 (35% aqueous solution) using a value of the
catalyst loading factor of 1.0.
a
Refers to isolated materials. Yields normalized to 100% conversion.
our previous findings on the oxidation of cardanol
derivatives with the MTO/H2O2 system in AcOH,28 and
further supported by previously described oxidation of
cresol 1 for which para-benzoquinone was the only
recovered product likely due to the absence of steric
hindrance by methyl group. Better results were obtained
with the PVP-25%/MTO catalyst (Table 3, entry 3), while
PVPN-2%/MTO showed a reaction pathway similar to
PVP-2%/MTO (Table 3, entry 4).
With the more electron-rich 2-tert-butyl-5-n-pentadecyl
phenol 11, highest conversion of substrate and yield of
benzoquinone were generally observed. Thus, while the
control experiment for 11 exhibits only moderate substrate
conversion and product yield (Table 3, entry 5), 58%
conversion of substrate and 71% yield of 13 were recovered
in the presence of PVP-2%/MTO (Table 3, entry 6). These
data indicate that the presence of a bulky tert-butyl
substituent in the C-2 position of 11 switches the selectivity
Table 4. Stability of poly(4-vinylpyridine)/MTO catalysts in the oxidation of 2-tert-butyl-5-n-pentadecyil phenol 11
Catalyst
Conversion (%)
Run no. 3
Run no. 1
Run no. 2
Run no. 4
Run no. 5
PVP-25%/MTO
PVPN-2%/MTO
75 (98)a
62 (96)
76 (93)
65 (91)
71 (97)
63 (93)
75 (96)
60 (98)
76 (97)
61 (96)
Under otherwise specified all the reactions were performed in ethanol (5 mL) at 458C, with H2O2 (35% aqueous solution) using a value of the catalyst loading
factor of 1.0.
a
Values of the benzoquinone yields are given in parentheses and are normalized to 100% of convertion.

R. Saladino et al. / Tetrahedron 58 (2002) 8493–8500
Table 5. Poly(4-vinylpyridine)/MTO catalysed oxidation of anisole derivatives
8497
Entry
Catalyst
Subtrate
Conversion (%)
Product(s)
Yield(s)a (%)
1
2
3
4
5
6
7
8
9
10
MTO
14
14
14
14
15
15
15
15
16
16
35
45
41
47
61
65
63
73
30
25
17 (18)
17 (18)
17 (18)
17 (18)
19 (20) [21]
19 (20) [21]
19 (20) [21]
19 (20) [21]
22
21 (25)
45 (15)
42 (12)
48 (6)
24 (34) [18]
22 (36) [7]
17 (47) [10]
37 (25) [8]
32
PVP-2%/MTO
PVP-25%/MTO
PVPN-2%/MTO
MTO
PVP-2%/MTO
PVP-25%/MTO
PVPN-2%/MTO
MTO
PVP-2%/MTO
22
96
Under otherwise specified the reactions were performed in ethanol (5 mL) at 458C, with H2O2 (35% aqueous solution) using a value of the catalyst loading
factor of 1.0.
a
Refers to isolated materials. Yields normalized to 100% conversion.
Scheme 3.
process. Noteworthy, while fair conversions were again
obtained with the poly(4-vinylpyridine)/MTO catalysts
(Table 5, entries 2–4), a better selectivity was observed
and benzoquinone 17 began the major product by using the
best catalyst system PVP-2%/MTO (Table 5, entry 2).
Irrespective of the experimental conditions only a poor
selectivity was obtained in the oxidation of 1-methoxy-3-
methylbenzene 15, for which along with benzoquinone
19, phenols 20 and 21 were recovered in appreciable
yield (Table 5, entries 5–8). With the exception of the
PVPN-2%/MTO catalytic system, 2-methyl-4-methoxy
phenol 20 was recovered as the most abundant
reaction product. This compound may be further oxidized
with MTO in AcOH to give benzoquinone 19 in quantitative
yield.
friendly, easily available, and low cost H2O2 as the oxygen
atom donor. Independently from the catalyst used in the
transformation, values of the loading factor of the catalyst
higher than 1.0 did not give an appreciable increase in the
conversion of substrate. All catalysts were stable systems
for at least five recycling experiments. In the case of para-
unsubstituted phenols with small alkyl side-chains 1–3, the
corresponding para-benzoquinones were selectively
obtained in high yields (70–90% based on converted
starting material), by using PVP-2%/MTO system as the
most active catalyst. With the para-substituted phenol 4 a
different selectivity was observed, and the ortho-benzo-
quinone 8 became the main reaction product, along with
the quinone methide derivative 9. When the poly(4-
vinylpyridine)/MTO catalysts were applied for the oxi-
dation of natural para-unsubstituted phenols with a longer
alkyl side-chain, cardanols 10 and 11, the regioselectivity of
the reaction was found to be dependent on the nature and the
position of the substituents. In particular, the presence of an
alkyl substituent on the C-2 position of the phenolic ring
appears to direct the selectivity of the oxidation from ortho-
benzoquinone to para-benzoquinone. The suggestion that
PVP/MTO catalysts may organize the cardanol substrates
on the surface of their particles by means of specific and
selective molecular recognition processes is at least in part
confirmed by the higher conversions and yields to
corresponding benzoquinones than MTO in homogeneous
phase. Under similar experimental conditions, poly(4-
vinylpyridine)/MTO systems are able to oxidize anisole
derivatives to the corresponding para-benzoquinones even
if moderate conversions and yields, as well as and poor mass
balances, were generally observed.
Finally, we studied the oxidation of the anisole derivative 16
that is an easily available methyl ether derivative of tyrosol,
one of the main components of the vegetation water of Olea
europea (Scheme 3).42 The oxidation was studied with the
PVP-2%/MTO catalyst as a representative poly(4-vinyl-
pyridine)/MTO system (Table 5, entries 9 and 10). In this
case, the benzoquinone 22 was obtained as the only
recovered product in high yield, showing again an high
selectivity for the oxidation.
3. Conclusions
Poly(4-vinylpyridine)/MTO systems are efficient and selec-
tive catalysts for the conversion of alkyl-substituted phenols
to the corresponding benzoquinones, using environment

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R. Saladino et al. / Tetrahedron 58 (2002) 8493–8500
4. Experimental
spectrometry, and comparison with authentic commercial
samples.
NMR spectra were recorded on a Bruker (200 MHz)
spectrometer and are reported in d values. Mass spectra
were recorded on a VG 70/250S spectrometer with an
electron beam of 70 eV. Elemental analyses were performed
by a Carlo Erba 1106 analyser. Infrared spectra were
recorded on a Perkin–Elmer 298 spectrophotometer using
NaCl plates. For the SEM photographs, samples were
spitter-coated with gold (20 nm). All solvents are ACS
reagent grade and were redistilled and dried according to
standard procedures. Chromatographic purifications were
performed on columns packed with Merck silica gel 60,
230–400 mesh for flash technique. Thin layer chromato-
graphy was carried out using Merck platen Kieselgel 60
F254.
4.2.1. 2-Methyl-1,4-benzoquinone (5). 92%; solid; mp
68–708C (from EtOAc) (lit.,46 67–708C).
4.2.2. 2,6-Dimethylbenzoquinone (6). 85%; solid; mp
72–738C (from EtOAc) (lit.,47 71–738C).
4.2.3. 2,3,5-Trimethylbenzoquinone (7). 98%; solid; mp
28–298C (from EtOAc) (lit.,48 298C).
4.2.4. 4-Ethyl-1,2-benzoquinone (8). 37%; oil; nmax (KBr)
750, 975, 1250, 1545, 1660, 2855, 2920; dH [CDCl3,
200 MHz] 1.55 (3H, m, CH3), 2.60 (2H, m, CH2), 6.70 (1H,
m, CH), 6.80 (1H, m, CH), 7.13 (1H, m, CH); dC [CDCl3,
20 MHz] 14.96 (CH3), 32.58 (CH2), 126.66 (CH), 129.92
(CH), 143.54 (CH), 152.03 (C), 179.71 (C), 180.68 (C); m/z
136 (Mþ, 31%). Anal. calcd for C8H8O2: C (68.85%), H
(4.95%), O (26.20); Found C (68.71%), H (5.00%), O
(26.29%).
4.1. Starting materials
Poly(4-vinylpyridine)/MTO catalysts were prepared as
previously reported.29 In summary, PVP-2%, PVP-25%,
and PVPN-2%43 were suspended in ethanol at room
temperature and the appropriate amount of powdered
MTO was added at room temperature. After 1 h the mixture
was cooled at 08C and the catalyst recovered by filtration.
Under otherwise specified, poly(4-vinylpyridine) catalysts
were prepared with a loading factor (that is mmol of MTO
for 1 g of support) equal to 1.0. Catalysts were used after
washing with ethyl acetate. Phenol derivatives 1–4 were
obtained from a commercial source (Aldrich). 3-n-Penta-
decyl phenol 10 was prepared by hydrogenation of distilled
cardanol.44 2-tert-Butyl-5-n-pentadecylphenol 11 was pre-
pared starting from 3-n-pentadecyl phenol as previously
reported.45 Anisole derivatives were prepared starting from
the corresponding phenols under usual experimental
conditions by reaction with K2CO3 and MeI in dry DMF
at room temperature.
4.2.5. Quinone methide derivative (9). 11%; oil; nmax
(KBr) 750, 980, 1250, 1541, 1659, 2855, 2920; dH [CDCl3,
200 MHz] 1.56 (3H, m, CH3), 6.60 (1H, m, CH), 6.63–6.80
(4H, m, CH); dC [CDCl3, 200 MHz] 12.49 (CH3), 122.85
(CH), 138.91 (CH), 139.41 (CH), 141.69 (C), 143.06 (CH),
186.34 (C); m/z 120 (Mþ, 28%). Anal. calcd for C8H8O: C
(79.97%), H (6.71%), O (13.32); Found C (80.03%), H
(6.68%), O (13.29%).
4.2.6. 4-n-Pentadecyl-1,2-benzoquinone (12). 61%; oil;
nmax (KBr) 750, 975, 1000, 1250, 1655, 2850, 2920; dH
[CDCl3, 200 MHz] 0.82 (3H, t, J¼6.0 Hz, CH3), 1.20 (24H,
m, CH2), 1.45 (2H, m, CH2), 2.5 (2H, m, CH2), 6.51 (1H, m,
CH), 6.68 (2H, m, CH); dC [CDCl3, 200 MHz] 14.04 (CH3),
22.62 (CH2), 27.73 (CH2), 28.96 (CH2), 29.26 (CH2), 29.30
(CH2), 29.43 (CH2), 29.62 (CH2), 31.87 (CH2), 132.29
(CH), 136.16 (CH), 136.73 (CH), 149.66 (C), 187.44 (C),
187.75 (C); m/z (EI) 318 (Mþ, 79%). Anal. calcd for
C21H34O2: C (79.19%), H (10.76%), O (10.05); Found C
(79.05%), H (10.83%), O (10.12%).
4.2. Oxidation of phenol and anisole derivatives: general
procedure
To the suspension of 146 mg of the appropriate catalyst
(loading 1.0) in 5.0 mL of ethanol was added the phenol
(1.0 mmol) to be oxidized and H2O2 (2.0 mmol, 35% water
solution). The reaction mixture was stirred at 408C under a
nitrogen gas atmosphere for 10–14 h and monitored by gas
chromatography(GC), using dodecane as an internal
standard. The GC analysis was performed using a OV-1
column (25 m£0.30 mm and 0.25 mm film thickness) and
an isothermal temperature profile of 1008C for the first
5 min, followed by a 158C/min temperature gradient to
2808C for 10 min. The injector temperature was 2808C. The
suspension was filtered and the recovered catalyst was
washed five times with 10 mL of ethyl acetate each time.
After drying under high vacuum, the catalyst was used for
further reaction to evaluate its stability. The filtrate was
treated with a low amount of manganese dioxide (MnO2) at
258C to decompose the excess of H2O2 and filtered. The
organic solvent was dried under Na2SO4 and removed under
reduced pressure. The crude was purified by flash-
chromatography (n-hexane/EtOAc) and the reaction
products were identified by spectroscopic analyses, mass
4.2.7. 2-tert-Butyl-5-n-pentadecyl-1,4-benzoquinone
(13). 98%; solid; mp 51–538C (from EtOAc) (lit.,rifn 51–
538C].
4.2.8. 2-Methoxy-5-methyl-1,4-benzoquinone (17). 48%;
oil; nmax (KBr) 735, 971, 1020, 1251, 1665, 2850, 2920; dH
[CDCl3, 200 MHz] 1.97 (3H, s, CH3), 3.73 (3H, s, CH3),
5.54 (1H, s, CH), 6.46 (1H, s, CH); dC [CDCl3, 200 MHz]
15.57 (CH3), 56.09 (CH3), 107.39 (CH), 131.08 (CH),
146.69 (C), 158.56 (C), 181.95 (C), 187.75 (C); m/z (EI) 152
(Mþ, 39%). Anal. calcd for C8H8O3: C (63.15%), H
(5.30%), O (31.55); Found C (63.21%), H (5.19%), O
(31.60%).
4.2.9. 2-Methoxy-4-methyl-2,5-cyclohexadien-1-one-4-
olo (18). 25%; oil; nmax (KBr) 755, 977, 1000, 1253,
1658, 2860, 2920; dH [CDCl3, 200 MHz] 1.45 (3H, s, CH3),
3.66 (3H, s, CH3), 5.72 (1H, J¼2.7 Hz, CH), 6.26 (1H, m,
CH), 6.89 (1H, m, CH); dC [CDCl3, 200 MHz] 23.82 (CH3),
55.01 (CH3), 80.29 (CH), 115.60 (CH), 129.11 (CH), 150.19

R. Saladino et al. / Tetrahedron 58 (2002) 8493–8500
8499
(C), 151.86 (C), 180.88 (C); m/z (EI) 154 (Mþ, 39%). Anal.
calcd for C8H10O3: C (62.33%), H (6.54%), O (31.13);
Found C (62.20%), H (6.70%), O (31.10%).
3. (a) Cherkaoni, O.; Nebois, P.; Fillion, H.; Domard, M.; Fenet,
B. Tetrahedron 1996, 52, 9499. (b) Itoh, S.; Ogino, M.;
Haranou, S.; Terasaka, T.; Ando, T.; Komatsu, M.; Ohshiro,
Y.; Fukuzumi, S.; Kano, K.; Takagi, K.; Ideka, T. J. Am.
Chem. Soc. 1995, 117, 1485.
4.2.10. 2-Methoxy-5-methyl-1,4-benzoquinone (19).
37%; oil; nmax (KBr) 740, 985, 1251, 1665, 2850, 2920;
dH [CDCl3, 200 MHz] 2.04 (3H, s, CH3), 3.77 (3H, s, CH3),
5.86 (1H, s, CH), 6.53 (1H, s, CH); dC [CDCl3, 200 MHz]
15.49 (CH3), 56.27 (CH3), 107.27 (CH), 133.82 (CH),
142.10 (C), 158.0 (C), 181.11 (C), 186.10 (C); m/z (EI) 152
(Mþ, 45%). Anal. calcd for C8H8O3: C (63.15%), H
(5.30%), O (31.55); Found C (63.21%), H (5.19%), O
(31.60%).
4. Takeya, T.; Moregi, S.; Itoh, T.; Tobinaga, S. Chem. Pharm.
Bull. 1997, 45, 613.
5. Brimble, M. A.; Duncalf, L. J.; Phythiom, S. J. J. Chem. Soc.,
Perkin Trans. 1 1997, 1399.
6. Feldman, K. S.; Quideau, S.; Appel, H. M. J. Org. Chem.
1996, 61, 6656.
7. (a) Vanderlei, J. M. L.; Coelho, F.; Almeida, W. P.
Tetrahedron: Asymmetry 1997, 8, 2781. (b) Almeida, W. P.;
Corriera, C. R. Tetrahedron Lett. 1994, 35, 1367.
8. (a) Kinugawa, M.; Masuda, Y.; Arai, H.; Nishikawa, H.;
Osaga, T.; Tomiok, S.; Kasai, M. Synthesis 1996, 633.
(b) Kato, N.; Sugaya, T.; Mimura, T.; Ikuta, M.; Kato, S.;
Kuge, Y.; Tomioka, S.; Kasai, M. Synthesis 1997, 625.
9. Boyd, V. A.; Sulikowski, G. A. J. Am. Chem. Soc. 1995, 117,
8472.
4.2.11. 2-Methyl-4-methoxyphenol (20). 47%; oil; nmax
(KBr) 750, 805, 1223, 1359, 1495, 2850, 2920, 3450; dH
[CDCl3, 200 MHz] 2.21 (3H, s, CH3), 3.73 (3H, s, CH3),
6.62 (1H, d, J¼2.4 Hz, CH), 6.66 (1H, s, CH), 6.69 (1H, d,
J¼2.4 Hz, CH); dC [CDCl3, 200 MHz] 16.09 (CH3), 55.57
(CH3), 111.79 (CH), 115.48 (CH), 116.58 (CH), 124.92 (C),
147.80 (C), 153.49 (C); m/z (EI) 138 (Mþ, 91%). Anal.
calcd for C8H10O2: C (69.54%), H (7.30%), O (23.16);
Found C (69.67%), H (7.21%), O (23.12%).
10. Brumble, M. A.; Phythian, S. J. Tetrahedron Lett. 1993, 34,
5813.
11. Tamura, Y.; Sasho, M.; Akar, S.; Wada, A.; Kita, Y.;
Tetrahedron, . 40 1984, 4539.
4.2.12. 2-Methoxy-4-methylphenol (21). 18%; oil; bp 228C
(from EtOAc) [lit.,28 228C].
12. Moser, W.; Howie, R. A. Inorg. Phys. Theor. J. Chem. Soc. A
1968, 3039.
13. Shishido, K.; Goto, K.; Meyoshi, S.; Takaishi, T.; Shibuya, M.
J. Org. Chem. 1994, 59, 406.
4.2.13. 2-Methoxy-4[10-ethanyl-20-olo]1,4-benzoquinone
(22). 96%; oil; nmax (KBr) 740, 985, 1253, 1668, 2853,
2921; dH [CDCl3, 200 MHz] 2.66 (2H, t, J¼6.0 Hz, CH2),
3.79 (3H, s, OCH3), 3.82 (2H, t, J¼6.0 Hz, CH2), 5.91 (1H,
s, CH), 6.60 (1H, s, CH); dC [CDCl3, 20 MHz] 51.94 (CH2),
75.64 (CH3), 80.24 (CH2), 127.0 (CH), 151.84 (CH), 166.52
(C), 178.0 (C), 201.0 (C), 204.50 (C); m/z (EI) 182 (Mþ,
29%). Anal. calcd for C9H10O4: C (61.22%), H (6.16%), O
(32.62); Found C (61.08%), H (6.25%), O (32.67%).
14. Watanabe, M.; Shinoda, E.; Shimizu, Y.; Furukawa, S.; Iwao,
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