Synthesis and reactions of nitro derivatives of hydrogenated cardanol

Article abstract of DOI:10.1016/j.tet.2006.03.105

3-n-Pentadecylphenol (hydrogenated cardanol) and its derivative 5-n-pentadecyl-2-tert-butylphenol can be nitrated using nitric acid in acetonitrile or methanol to give mono, di or trinitro products. 5-n-Pentadecyl-2-nitrophenol undergoes reductive carbonylation to give a benzoxazole-2-one derivative. An efficient catalytic oxidation reaction in the presence of MeReO₃ has also been studied.

Full text of DOI:10.1016/j.tet.2006.03.105

Tetrahedron 62 (2006) 6113–6120
Synthesis and reactions of nitro derivatives
of hydrogenated cardanol
Orazio A. Attanasi,a Stefano Berretta,a Cinzia Fiani,c Paolino Filippone,a,
*
Giuseppe Meleb and Raffaele Saladinoc,
*
a
`
Centro di Sudio delle Sostanze Organiche Naturali, Facolta di Scienze Matematiche, Fisiche e Naturali,
`
Universita degli Studi di Urbino ‘Carlo Bo’, Via Sasso 75, 61029 Urbino, Italy
`
b
Dipartimento di Ingegneria dell’Innovazione, Universita di Lecce, Via Arnesano, 73100 Lecce, Italy
c
`
Dipartimento di Agrobiologia ed Agrochimica, Universita della Tuscia, Via San Camillo de Lellis, 01100 Viterbo, Italy
Received 11 November 2005; revised 16 March 2006; accepted 30 March 2006
Available online 27 April 2006
Abstract—3-n-Pentadecylphenol (hydrogenated cardanol) and its derivative 5-n-pentadecyl-2-tert-butylphenol can be nitrated using nitric
acid in acetonitrile or methanol to give mono, di or trinitro products. 5-n-Pentadecyl-2-nitrophenol undergoes reductive carbonylation to
give a benzoxazole-2-one derivative. An efficient catalytic oxidation reaction in the presence of MeReO3 has also been studied.
Ó 2006 Elsevier Ltd. All rights reserved.
OH
1. Introduction
OH
COOH
In recent years an increasing amount of work on cashew nut
shell liquid derivatives has appeared in the literature. Cashew
nut shell liquid (CNSL) is obtained as a by-product from
mechanical processing for edible use of cashew kernel (Ana-
cardium occidentale L.) and is a mixture of anacardic acid 1,
cardanol 2 and smaller amounts of cardol 3 and 2-methyl-
cardol 4.1 Due to the easy thermal decarboxylation of ana-
cardic acid 1, the main component of distilled CNSL is
cardanol 2 (yield up to 70–80% and purity up to 90%) as
a mixture of saturated (3-n-pentadecylphenol), monoolefinic
[3-(n-pentadeca-8-enyl)phenol], diolefinic [3-(n-pentadeca-
8,11-dienyl)phenol], and triolefinic [3-(n-pentadeca-8,11,14-
trienyl)phenol] long-chain phenols, with an average value of
two double bonds per molecule. Cardol 3 and methylcardol 4
are present in smaller percentages (Fig. 1).2
C15H25-31
C15H25-31
2
OH
1
OH
CH3
HO
HO
C15H25-31
C15H25-31
4
3
C15H25-31
Figure 1. Components of CNSL.
World-wide cashew nut production is presently estimated to
be 1,200,000 tons per annum and the availability of CNSL is
300,000–360,000 tons per annum. As the production of
cashew nuts is rising every year the availability of up to
600,000 tons per annum of CNSL should be reached in the
near future. Cardanol, upon catalytic hydrogenation, yields
3-n-pentadecylphenol (hydrogenated cardanol) and this
unique alkyl phenol derivative is produced commercially
in high purity.3 Owing to the difficulty of synthesizing
long-chain alkyl phenols with an aliphatic chain in the meta
position, hydrogenated cardanol represents a simple and
easily available entry to various derivatives useful for dif-
ferent purposes (e.g., antioxidants, flame-retardants, water-
proofing agents, gum inhibitors for gasoline). Recently we
have reported allylation and regioselective cyclocarbonyl-
ation4 reactions on hydrogenated cardanol and the prepa-
ration of phthalocyanines,5 porphyrins6 and fullerene7
derivatives of cardanol that possess lower melting points
and higher solubility than similar products lacking long alkyl
side-chains. Even azocrown ethers have been prepared from
cardanol derivatives.8 So these derivatives are an attractive
* Corresponding authors. Tel.: +39 0722 303443; fax: +39 0722 303441;
e-mail addresses: filippone@uniurb.it; saladino@unitus.it
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.03.105

6114
O. A. Attanasi et al. / Tetrahedron 62 (2006) 6113–6120
renewable bio-source to develop new eco-friendly func-
tional materials.
TGA/DSC on 3-n-pentadecyl-2,4,6-trinitrophenol 12 were
carried out (see Section 4). 5-n-Pentadecyl-2-tert-butylphe-
nol 13 reacted in 30 min at room temperature in acetonitrile
or methanol with an equimolar amount of nitric acid (65%)
affording a reaction mixture that after work-up procedures
and chromatographic separations furnished 2-tert-butyl-5-
n-pentadecyl-4-nitrophenol 14 (69%) and 3-n-pentadecyl-
6-tert-butyl-2-nitrophenol 15 (15%). 5-n-Pentadecyl-2-tert-
butylphenol 13 reacted with nitric acid (65%) in a molar
ratio 1:2 affording 3-n-pentadecyl-6-tert-butyl-2,4-dinitro-
phenol 16 (79%) (Scheme 2).
2. Results and discussion
2.1. Nitration of cardanol derivatives
In this paper we describe a mild and efficient protocol for
the nitration of 3-n-pentadecylphenol 5 and its derivative
5-n-pentadecyl-2-tert-butylphenol 13.2 Nitration of cardanol
derivatives has been carried out some time ago but only a few
products9 have been reported and a complete study of this
interesting reaction has not been conducted until now. Nitro
derivatives are useful materials and are very important inter-
mediates in organic synthesis, especially in the preparation
of amino derivatives. Some patents are related to preparation
of 5-n-pentadecyl-2-nitrophenol 6 and 3-n-pentadecyl-4-
nitrophenol 7 but the synthetic utility of other products
from the nitration process has not been described.10 There-
fore, we undertook the study of reactions between hydro-
genated cardanol and nitric acid.
OH
OH
OH
NO2
HNO3 65%
MEOH, rt,
30 min.
+
C15H31
C15H31
69%
C15H31
NO2
13
14
15 15%
OH
OH
NO2
2HNO3 65%
MEOH, rt,
30 min.
C15H31
C15H31
The reactions proceeded smoothly at room temperature,
under mild conditions, with a stoichiometric amount of nitric
acid with easy work-up procedures. 3-n-Pentadecylphenol 5
reacted in 30 min at room temperature in acetonitrile or
methanol with an equimolar amount of nitric acid (65%).
After work-up procedures and chromatographic separations
of the reaction mixture, 5-n-pentadecyl-2-nitrophenol 6
(38%), 3-n-pentadecyl-4-nitrophenol 7 (40%) and 3-n-penta-
decyl-2-nitrophenol 8 (15%) were obtained. Under the same
experimental conditions, 3-n-pentadecylphenol 5 reacted
with nitric acid (65%) in a molar ratio 1:2 and 5-n-penta-
decyl-2,4-dinitrophenol 9 was isolated in high yields (75%)
along with small quantities of two other isomers 3-n-penta-
decyl-2,4-dinitrophenol 10 (7%) and 3-n-pentadecyl-2,6-
dinitrophenol 11 (1%) (GC–MS), due to steric hindrance of
position 2 of 3-n-pentadecylphenol. When the ratio 3-n-
pentadecylphenol/nitric acid (65%) was increased to 1:3 the
only recovered reaction product was 3-n-pentadecyl-2,4,6-
trinitrophenol 12 in high yields (86%) (Scheme 1).
NO2
13
Scheme 2.
16
79%
2.2. MeReO3 oxidation of cardanol derivatives
In spite of the high number of synthetic transformations
reported for cardanol derivatives,11 to the best of our knowl-
edge there are few catalytic oxidative procedures. In this
context, we described a convenient and efficient application
of the catalytic system MeReO3/H2O2 for the preparation of
ortho- and para-benzoquinones from cardanol derivatives.12
The regioselectivity of these oxidations was found to be
dependent on the nature and position of substituents on the
aromatic ring, ortho-benzoquinones being obtained only in
the absence of an alkyl substituent on the C-2 position of
the aromatic ring.
OH
OH
OH
OH
O2N
NO2
HNO3 65%
+
+
MEOH, rt,
C15H31
30 min.
C15H31
40%
C15H31
C15H31
15%
NO2
7
5
6
38%
8
OH
OH
OH
OH
O2N
NO2
O2N
NO2
2HNO3 65%
+
+
MEOH, rt,
30 min.
C15H31
C15H31
C15H31
C15H31
NO2
NO2
5
9
10
11
75%
7%
1%
OH
OH
O2N
NO2
3HNO3 65%
MEOH, rt,
30 min.
C15H31
C15H31
NO2
5
12
86%
Scheme 1.

O. A. Attanasi et al. / Tetrahedron 62 (2006) 6113–6120
6115
In the past few years methylrhenium trioxide (MeReO3,
MTO)13 has been shown to possess interesting catalytic
properties in oxidation reactions with environmental friendly
hydrogen peroxide (H2O2) as an oxygen atom donor.14
Methoxy-substituted benzenes are oxidized with the
MeReO3/H2O2 system in acetic acid to yield the correspond-
ing alkoxy-substituted para-benzoquinones,15 some of
which show important biological activities.16 Cardanol
derivatives bearing bromine atoms as electron-withdrawing
substituents were also found to be reactive substrates under
these experimental conditions to give para-benzoquinone or
catechol derivatives. A similar behaviour was observed with
polymer supported rhenium catalysts based on the hetero-
genation of MeReO3 on poly(4-vinylpyridine) 2% and
25% (PVP-2, PVP-25) cross-linked with divinylbenzene.17
Higher conversions and yields of benzoquinones were ob-
tained with PVP heterogeneous catalysts than with MeReO3
in homogeneous phase, probably because of a support-
mediated molecular recognition process based on hydrogen-
bonding interactions between the pyridinyl moiety and the
phenolic group of cardanol.18
side-chain to give unexpected O-pentadeca-acyl cardanol
derivatives probably by a side-chain intermolecular transfer
process between two molecules of substrate.
Oxidations were performed by treating the appropriate sub-
strate with an excess of H2O2 (8.0 equiv 35% aqueous solu-
tion) in acetic acid (1.0 mL) at 80 ꢀC in the presence of
catalytic amount of MeReO3 (2% in weight of catalyst).
Results of oxidations are reported in Scheme 3 and Table 1.
The oxidation of 5-n-pentadecyl-2-nitrophenol 6 gives
O-pentadecanoyl-5-n-pentadecyl-2-nitrophenol 17, as the
main reaction product, besides a low amount of pentadeca-
noic acid 18 as side-product (Table 1, entry 1).
Traces of aromatic ketone derivative 19 and 1,3-dihydroxy-
6-nitrobenzene 20 were also detected in the reaction mixture
by GC–MS analysis (see Scheme 3 for structures of
compounds 19 and 20) after derivatization with N,O-bis-
trimethylsilyltrifluoroacetamide (BSTFA). It is reasonable
to suggest that compound 17 can be formed by an inter-
molecular acyl transfer process from a first formed side-
chain oxidized product. In particular, the reaction initially
may proceed through oxidation of the reactive benzylic
position to give 19. The catalytic efficacy of MeReO3 to
afford a Bayer–Villinger rearrangement is known from the
literature. In accordance with these data, ketone 19 can be
further oxidized to corresponding aryl ester derivative (not
shown), which can act as an electrophilic species transfer-
ring the acyl side-chain to a second molecule of substrate
to give compounds 17 and 20. In accordance with this hy-
pothesis, treatment of a small amount of isolated ketone 19
with MTO under similar conditions afforded compounds
17 and 20 in detectable amounts. The hypothesized reaction
Moreover, during the oxidation of cardanol derivatives with
novel microencapsulated MeReO3 systems, an unprece-
dented oxidative degradation of the aromatic moiety to bio-
logically active g-lactone derivatives was observed in the
absence of C-2 substituents.17
We report here that MeReO3 is an efficient and selective cat-
alyst for the activation of H2O2 in the oxidation of relatively
unreactive nitrocardanol derivatives. Because of the high
value of the redox-potential of the aromatic moiety of these
compounds, the oxidation proceeded mainly in the alkyl
O
OH
O
CH2(CH2)12CH3
O
O2N
O2N
O2N
MTO/H2O2
HO
CH2(CH2)12CH3
CH3COOH
80 °C
C15H31
C15H31
45%
6
17
18
OH
OH
O2N
CH2(CH2)12CH3
OH
O
20
19
O
O
CH2(CH2)12CH3
NO2
OH
O
MTO/H2O2
HO
CH2(CH2)12CH3
CH3COOH
80 °C
C15H31
51%
C15H31
NO2
7
22
18
O
O
CH2(CH2)12CH3
OH
O
NO2
MTO/H2O2
HO
CH2(CH2)12CH3
CH3COOH
80 °C
C15H31
55%
C15H31
NO2
8
21
18
Scheme 3.

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O. A. Attanasi et al. / Tetrahedron 62 (2006) 6113–6120
Table 1. Oxidation of nitrocardanol derivatives 6–8, 15 with MeReO3 and
H2O2
OH
O
OH
a
NO2
NO2
C15H31
NO2
H O
MTO/
2
2
+
Entry Substrate H2O2 (equiv) Conversion (%) Product(s) Yield(s)
CH3COOH
80°C
C15H31
C15H31
1
2
3
4
6
7
8
15
6.0
6.0
6.0
6.0
75
55
65
70
17(18)
22(18)
21(18)
23(24)
45(8)
51(6)
55(6)
25(26)
O
OH
15
23
24
23%
24%
Scheme 5.
a
Reactions were performed with an excess of H2O2 (8.0 equiv) in
CH3COOH (1 mL) in the presence of 2% in weight of MeReO3. Yields
are calculated on converted substrate. The low mass-balance observed
in some cases, is probably due to the formation of over-oxidation products
not recovered under our experimental conditions.
2.3. Reductive carbonylation of 5-n-pentadecyl-2-nitro-
phenol
Benzoxazolinones are a known class of commercially avail-
able compounds that are widely used in agriculture and in-
dustry. Traditionally, these compounds are produced by the
intramolecular cyclization of phenyl N-(2-hydroxyphenyl)
carbamate, which is produced by the reaction of ortho-
aminophenol with phenyl chloroformate.19 This route needs
a large number of steps from commercially available starting
materials. Various catalytic systems have been found for the
preparation of benzoxazolinone in one step from readily
available starting materials. For example, Fe/Pd as well as
Na2[Fe(CO)4] were used as catalysts for the reductive cyclo-
carbonylation of ortho-nitrophenol 25 to benzoxazol-2-one
26,20 more recently, a selenium-based catalyst has been
used to perform this reaction (Scheme 6).21 Recently,
some of us reported that palladium(II) acetate Pd(OAc)2
and 1,4-bis(diphenylphosphino)butane (dppb) catalyze the
cyclocarbonylation of o-allyl phenol as well as o-allyl
cardanol derivatives.22 In this context, we report the cyclo-
carbonylation reaction of 5-n-pentadecyl-2-nitrophenol 6
carried out under mild conditions in the presence of the
homogeneous catalytic system Pd(OAc)2/dppb and a 1:1
mixture of CO/H2 to produce the benzoxazol-2-one deriva-
tive 28 in good yield (85%) (Scheme 7). FTIR spectrum of
5-n-pentadecyl-2-nitrophenol 6 used as starting material
shows characteristic bands centred at 1623, 1580, 1528 cmꢁ1
(asymmetric stretch) and 1330 cmꢁ1 (symmetric stretch)
due to the NO2 group. As expected, these signals are not
present in the IR spectrum of the cyclocarbonylated product
and a new strong peak characteristic of carbonyl compounds
is found at 1742 cmꢁ1. In this reaction the formation of an
isocyanate 27 as intermediate is presumed. The isocyanate
27 reacts further with the hydroxyl group to give the final
product.
pathway for the oxidation of 6 is schematically reported in
Scheme 4.
OH
OH
O2N
O2N
MTO/H2O2
CH2(CH2)12CH3
C15H31
6
O
19
OH
O2N
Bayer-Villinger
O
O
CH2(CH2)12CH3
O
OH
O
CH2(CH2)12CH3
C15H31
O2N
O2N
6
OH
20
17
Scheme 4.
The low mass-balance observed for compound 20 is probably
due to formation of high-polarity over-oxidation products
not detectable under our experimental conditions. To the
best of our knowledge this is one of the few examples of
a multifunctional catalytic behaviour showed by MeReO3
during the oxidation of natural substances with H2O2 as
primary oxidant. To evaluate the generality of this transfor-
mation isomeric nitrocardanol derivatives 3-n-pentadecyl-
4-nitrophenol 7 and 3-n-pentadecyl-2-nitrophenol 8 were
oxidized under similar experimental conditions. Irrespective
of the position of the nitro substituent on the aromatic ring,
the corresponding O-acyl derivatives, O-pentadecanoyl-3-n-
pentadecyl-4-nitrophenol 21 and O-pentadecanoyl-3-n-penta-
decyl-2-nitrophenol 22, were recovered as the main reaction
products in acceptable yields (Table 1, entries 2 and 3).
O
O
OH
NH
NO2
CO
In accordance with data previously obtained on the oxidation
of cardanol derivatives with MeReO3,12 the presence of an
alkyl substituent on the C-2 position of the aromatic ring
modified the selectivity of the reaction.
Pd - cat.
25
26
Scheme 6.
Thus, the oxidation of 3-n-pentadecyl-6-tert-butyl-2-nitro-
phenol 15, performed under similar experimental conditions,
gave the para-benzoquinone 23 and para-hydroquinone
24 as main products. (Scheme 5, Table 1, entry 4). In this
case O-acylated products were not observed in the reac-
tion mixture suggesting that the presence of the electron-
donating alkyl substituent enhances the redox-potential of
the aromatic ring, as would be expected.
O
OH
O
OH
O
C
N
HN
CO/H2
Pd - cat.
C15H31
O2N
C15H31
C15H31
85%
28
6
27
Scheme 7.

O. A. Attanasi et al. / Tetrahedron 62 (2006) 6113–6120
6117
3. Conclusion
For the synthesis of products 9–11, 16 nitric acid (65%)
(2 mmol) in methanol (20 mL) while for the synthesis of
product 12 nitric acid (65%) (3 mmol) in methanol
(30 mL) were used. The reactions can be carried out in
acetonitrile and isolated reaction products can be crystal-
lized from cyclohexane.
In the present paper we describe the reaction of 3-n-penta-
decylphenol and 3-n-pentadecylphenol derivatives with
nitric acid providing the corresponding nitro derivatives.
The reaction occurred in mild conditions, with high yields
and easy work-up procedures. The starting material with a
long alkyl chain in meta position, not easily accessible
directly by synthetic means, is a natural compound
easily available from processing of cashew kernel (A. occi-
dentale L.).
4.1.1.1. 5-n-Pentadecyl-2-nitrophenol 6. Bright yellow
crystals. 1H NMR (400 MHz, CDCl3): d 0.87 (3H, t,
J¼6.8 Hz, CH3), 1.19–1.38 (24H, m, CH2), 1.61 (2H, m,
ArCH2CH2), 2.62 (2H, t, J¼7.6 Hz, ArCH2), 6.80 (1H, dd,
J¼8.8 Hz, 1.6 Hz, H-4), 6.94 (1H, d, J¼1.6 Hz, H-6), 7.99
(1H, d, J¼8.8 Hz, H-3), 10.61 (1H, s, OH). 13C NMR
(100 MHz, CDCl3): d 14.5, 23.1, 27.3, 29.6, 29.8, 29.9,
30.1, 30.8, 32.3, 36.4, 119.1, 120.9, 125.0, 131.8, 154.6,
The nitro derivatives were processed with MeReO3 and pro-
vided an interesting application of this oxidative system.
One of these derivatives has been cyclocarbonylated to the
corresponding benzoxazole-2-one in high yield.
155.2. IR nmax(Nujol) 3623, 1623, 1580, 1330 cmꢁ1
.
EIMS: m/z (relative intensity) 349 (M+, 10), 332 (42), 314
(100). Anal. Calcd for C21H35NO3 (349.51): C, 72.17; H,
10.09; N, 4.01. Found C, 72.23; H, 10.22; N, 4.18%.
4. Experimental
4.1. General
4.1.1.2. 3-n-Pentadecyl-4-nitrophenol 7. Brown solid.
1H NMR (400 MHz, CDCl3): d 0.87 (3H, t, J¼6.8 Hz,
CH3), 1.21–1.40 (24H, m, CH2), 1.58–1.68 (2H, m,
ArCH2CH2), 2.89 (2H, t, J¼8.0 Hz, ArCH2), 5.88 (1H, s,
OH), 6.71–6.78 (2H, m, Ar), 7.97 (1H, d, J¼9.6 Hz, H-5).
13C NMR (100 MHz, CDCl3): d 14.1, 22.6, 29.5, 29.7,
30.4, 31.9, 33.8, 113.5, 118.0, 128.0, 141.9, 142.2, 159.6.
All solvents are ACS reagent grade and used without further
purification. IRFT spectra were performed in Nujol mulls.
Mass spectra EI were obtained at an ionizing voltage of
70 eV. 1H NMR, 13C NMR were recorded at 400 and
100 MHz, or 200 and 50 MHz, respectively, All NMR spec-
tra were recorded in CDCl3. Chemical shifts (dH) are
reported in parts per million (ppm), relative to TMS as inter-
nal standard. All coupling constants (J) values are given in
Hertz. Chemical shifts (dC) are reported in parts per million
(ppm), relative to CDCl3, as internal standard in a broad band
decoupled mode. The abbreviations used are as follows:
s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br,
broad. Gas-chromatography and mass spectrometry were
performed by the use of HP5890 gas-chromatograph and
by a Shimadzu GC–MS QP5050A spectrometer equipped
with an AllthechÒ AT-20 column (0.25 mm, 30 m). TGA/
DSC were carried out on a LABSYSTM TGA/DSC. Chro-
matographic purifications were performed on columns
packed with Merck silica gel 60, 230–400 mesh for flash
technique. Thin layer chromatography was carried out using
Merck platen Kieselgel 60 F 25G. All new compounds
showed satisfactory elemental analysis (Cꢂ0.35; Hꢂ0.30;
Nꢂ0.30). Some overlaps in 13C NMR of CH2 resonances
of long aliphatic chain occur.
IR nmax(Nujol) 3382, 1615, 1597, 1513, 1324 cmꢁ1
.
EIMS: m/z (relative intensity) 349 (M+, 32), 332 (15), 314
(100). Anal. Calcd for C21H35NO3 (349.51): C, 72.17; H,
10.09; N, 4.01. Found C, 72.31; H, 10.24; N, 3.92%.
4.1.1.3. 3-n-Pentadecyl-2-nitrophenol 8. Brown solid.
1H NMR (400 MHz, CDCl3): d 0.87 (3H, t, J¼6.7 Hz,
CH3), 1.20–1.45 (24H, m, CH2), 1.52–1.64 (2H, m,
ArCH2CH2), 2.90 (2H, t, J¼8.0 Hz, ArCH2), 6.82 (1H, d,
J¼7.6 Hz, H-4), 6.98 (1H, dd, J¼8.0 Hz, 1.2 Hz, H-6),
7.38 (1H, t, J¼8.0 Hz, H-5), 9.94 (1H, s, OH). 13C NMR
(100 MHz, CDCl3): d 14.3, 22.9, 27.1, 29.6, 29.8, 29.9,
30.4, 30.8, 32.2, 34.7, 117.2, 123.0, 134.7, 135.5, 140.7,
154.5. IR nmax(Nujol) 3190, 1609, 1589, 1533, 1345 cmꢁ1
.
EIMS: m/z (relative intensity) 349 (M+, 15), 332 (35), 314
(100). Anal. Calcd for C21H35NO3 (349.51): C, 72.17; H,
10.09; N, 4.01. Found C, 72.09; H, 10.21; N, 4.12%.
4.1.1.4. 5-n-Pentadecyl-2,4-dinitrophenol 9. White
powder. 1H NMR (400 MHz, CDCl3): d 0.88 (3H, t,
J¼7.5 Hz, CH3), 1.21–1.39 (24H, m, CH2), 1.58–169 (2H,
m, ArCH2CH2), 2.99 (2H, t, J¼8.0 Hz, ArCH2), 7.13 (1H,
s, H-6), 8.86 (1H, s, H-3), 10.79 (1H, s, OH). 13C NMR
(100 MHz, CDCl3): d 14.4, 22.9, 29.5, 29.6, 29.7, 29.8,
29.9, 30.4, 32.2, 34.0, 122.7, 123.6, 131.1, 141.5, 149.3,
4.1.1. General procedure for the nitration reactions. To
a magnetically stirred solution of 3-n-pentadecylphenol 5
(1 mmol) in methanol (10 mL) a stoichiometric amount of
nitric acid (65%) (1 mmol) in methanol (10 mL) was added
dropwise over 30 min at room temperature. The reaction
mixture was dried over anhydrous sodium sulfate, the sol-
vent was evaporated under reduced pressure and then
extracted with ethyl acetate (40 mLꢃ3). The organic layer
was washed with water and dried with sodium sulfate. After
evaporation of the solvent, products 6–8 were separated by
chromatography on a silica gel column (cyclohexane ethyl
acetate mixtures) as oils.
157.2. IR nmax(Nujol) 3294, 1633, 1582, 1540, 1342 cmꢁ1
.
EIMS: m/z (relative intensity) 394 (M+, 12), 377 (100).
Anal. Calcd for C21H34N2O5 (394.51): C, 63.93; H, 8.69;
N, 7.10. Found C, 63.78; H, 8.79; N, 7.23%.
4.1.1.5. 3-n-Pentadecyl-2,4-dinitrophenol 10. White
powder. 1H NMR (400 MHz, CDCl3): d 0.87 (3H, t,
J¼6.6 Hz, CH3), 1.17–1.35 (24H, m, CH2), 1.58–1.65 (2H,
m, ArCH2CH2), 2.98 (2H, t, J¼8.0 Hz, ArCH2), 6.96 (1H,
d, J¼9.2 Hz, H-6), 8.15 (1H, d, J¼9.2 Hz, H-5), 10.88
(1H, s, OH). 13C NMR (100 MHz, CDCl3): d 14.3, 22.9,
The same procedure was used for preparation of products 14
and 15 from 5-n-pentadecyl-2-tert-butylphenol 13.

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O. A. Attanasi et al. / Tetrahedron 62 (2006) 6113–6120
27.1, 29.6, 29.7, 29.9, 30.3, 32.1, 34.9, 121.1, 126.1, 132.5,
142.1, 145.4, 147.5. IR nmax(Nujol) 3256, 1618, 1585,
1546, 1349 cmꢁ1. EIMS: m/z (relative intensity) 394 (M+,
12), 377 (100). Anal. Calcd for C21H34N2O5 (394.51): C,
63.93; H, 8.69; N, 7.10. Found C, 63.75; H, 8.82; N, 7.21%.
4.1.2. General procedure for MeReO3 oxidation of carda-
nol derivatives. To the suspension of the appropriate nitro-
cardanol derivative (1 mmol) and MTO (2% in weight) in
acetic acid (1.0 mL) was added 35% hydrogen peroxide
(ca. 8.0 mmol) in several batches. The reaction mixture
was stirred at 80 ꢀC under a nitrogen atmosphere for 4
days. The reaction was monitored by TLC (ethyl ester/ethyl
acetate¼9.5:0.5).
4.1.1.6. 3-n-Pentadecyl-2,4,6-trinitrophenol 12. Deep
brown solid. H NMR (400 MHz, CDCl3): d 0.88 (3H, t,
1
J¼7.6 Hz, CH3), 1.24–1.46 (24H, m, CH2), 1.57–1.66 (2H,
m, ArCH2CH2), 2.91 (2H, t, J¼8.0 Hz, ArCH2), 8.97 (1H,
s, H-5), 11.12 (1H, s, OH). 13C NMR (100 MHz, CDCl3):
d 14.2, 22.8, 28.9, 29.2, 29.4, 29.6, 29.7, 29.9, 30.3, 32.0,
123.5, 131.2, 140.4, 140.6, 143.1, 149.5. IR nmax(Nujol)
3273, 1635, 1593, 1536, 1356 cmꢁ1. EIMS: m/z (relative
intensity) 440 (M+, 56), 422 (15), 404 (100). Anal. Calcd
for C21H33N3O7 (439.50): C, 57.39; H, 7.57; N, 9.56. Found
C, 57.29; H, 7.65; N, 9.68%. TGA/DSC were carried out by
controlled heating under a flow of dry air or nitrogen at
a heating rate of 25 ꢀC/min. Under a flow of dry air an
enthalpy of ꢁ1074.91 and a total percentage weight lose
of 36.5% was observed at 284 ꢀC. Under a flow of nitrogen
an enthalpy of ꢁ1169.35 and a total percentage weight lose
of 32.3% was observed at 284 ꢀC.
The reaction mixture was diluted with ethyl acetate (40 mL)
and a small amount of MnO2 was added to decompose the
excess of H2O2. After filtration of MnO2 the organic layer
was washed with NaCl saturated solution (5 mLꢃ3), dried
with Na2SO4 and evaporated under reduced pressure. The
products were obtained by chromatographic purification
(cyclohexane ethyl acetate mixtures) and identified by spec-
troscopic analyses, mass spectroscopy and comparison with
authentic samples.
4.1.2.1. O-Pentadecanoyl-5-n-pentadecyl-2-nitrophe-
nol 17. Yellow oil. H NMR (200 MHz, CDCl3): d 0.92
1
(6H, m, CH3), 1.23–1.65 (50H, m, CH2), 2.49–2.60 (2H,
m, CO–CH2), 2.91–3.05 (2H, m, ArCH2), 6.80 (1H, d, J¼
10.0 Hz, H-4), 6.92 (1H, s, H-6), 8.0 (1H, d, J¼10.0 Hz,
H-3). 13C NMR (50 MHz, CDCl3): d 14.1, 14.3, 22.5,
22.7, 25.0, 29.0, 29.3, 29.4, 29.5, 29.7, 31.9, 32.1, 32.5,
33.7, 35.8, 124.7, 125.3, 128.5, 139.2, 147.2, 148.0, 168.9.
EIMS: m/z (relative intensity) 573 (M+, 100), 558 (25),
544 (39), 376 (43), 348 (55). Anal. Calcd for C36H63NO4
(573.88): C, 75.34; H, 11.06; N, 2.44. Found C, 75.37; H,
11.10; N, 2.39%.
4.1.1.7. 2-tert-Butyl-5-n-pentadecyl-4-nitrophenol 14.
White powder. H NMR (400 MHz, CDCl3): d 0.87 (3H, t,
1
J¼7.2 Hz, CH3), 1.18–1.36 (24H, m, CH2), 1.41 (9H, s,
C(CH3)3), 1.57–1.68 (2H, m, ArCH2CH2), 2.84 (2H, t,
J¼8.0 Hz, ArCH2), 5.55 (1H, s, OH), 6.56 (1H, s, H-6),
7.99 (1H, s, H-3). 13C NMR (100 MHz, CDCl3): d 14.4,
22.9, 29.4, 29.6, 29.8, 29.9, 30.7, 32.1, 33.4, 34.7, 119.2,
125.6, 135.2, 139.1, 142.0, 158.3. IR nmax(Nujol) 3326,
1629, 1582, 1496, 1335 cmꢁ1. EIMS: m/z (relative intensity)
405 (M+, 2), 388 (45), 375 (22), 357 (5), 169 (100). Anal.
Calcd for C25H43NO3 (405.61): C, 74.03; H, 10.69; N,
3.45. Found C, 74.11; H, 10.79; N, 3.36%.
4.1.2.2. O-Pentadecanoyl-3-n-pentadecyl-4-nitrophe-
nol 21. Yellow oil. H NMR (200 MHz, CDCl3): d 0.93
1
(6H, m, CH3), 1.23–1.75 (50H, m, CH2), 2.31–2.46 (2H,
m, CO–CH2), 2.84–2.99 (2H, m, ArCH2), 6.71 (1H, s,
H-2), 6.74 (1H, d, J¼8.5 Hz, H-6), 7.97 (1H, d, J¼8.5 Hz,
H-5). 13C NMR (50 MHz, CDCl3): d 14.2, 22.5, 22.7,
25.0, 29.0, 29.3, 29.4, 29.5, 29.6, 29.7, 29.8, 31.8, 31.9,
32.6, 33.5, 121.1, 121.9, 126.3, 132.7, 147.2, 156.7, 171.8.
EIMS: m/z (relative intensity) 573 (M+, 100), 558 (21),
544 (31), 376 (48), 348 (49). Anal. Calcd for C36H63NO4
(573.88): C, 75.34; H, 11.06; N, 2.44. Found C, 75.38; H,
11.13; N, 2.38%.
4.1.1.8. 3-n-Pentadecyl-6-tert-butyl-2-nitrophenol 15.
White powder. H NMR (400 MHz, CDCl3): d 0.89 (3H, t,
1
J¼7.4 Hz, CH3), 1.18–1.36 (24H, m, CH2), 1.43 (9H, s,
C(CH3)3), 1.56–1.64 (2H, m, ArCH2CH2), 2.84 (2H, t,
J¼8.0 Hz, ArCH2), 6.75 (1H, d, J¼8.0 Hz, H-5), 7.39
(1H, d, J¼8.0 Hz, H-4), 10.56 (1H, s, OH). 13C NMR
(100 MHz, CDCl3): d 14.1, 22.6, 29.2, 29.4, 29.6, 29.7,
30.5, 31.9, 34.4, 35.2, 122.0, 132.1, 136.2, 137.5, 138.2,
153.7. IR nmax(Nujol) 3319, 1621, 1565, 1488, 1329 cmꢁ1
.
4.1.2.3. O-Pentadecanoyl-3-n-pentadecyl-2-nitrophe-
nol 22. Yellow oil. H NMR (200 MHz, CDCl3): d 0.80–
EIMS: m/z (relative intensity) 405 (M+, 3), 388 (35), 375
(7), 169 (100). Anal. Calcd for C25H43NO3 (405.61):
C, 74.03; H, 10.69; N, 3.45. Found C, 74.16; H, 10.53; N,
3.36%.
1
0.92 (6H, m, CH3), 1.23–1.70 (50H, m, CH2), 2.24–2.38
(2H, m, CO–CH2), 2.80–2.96 (2H, m, ArCH2), 6.77–6.84
(1H, m, Ar), 6.86–6.95 (1H, m, Ar), 7.26–7.35 (1H, m,
Ar). 13C NMR (50 MHz, CDCl3): d 14.1, 14.3, 22.7, 25.0,
29.0, 29.3, 29.4, 29.5, 29.6, 29.7, 31.8, 31.9, 32.6, 33.7,
118.2, 129.3, 132.7, 132.9, 143.0, 147.2, 168.9. EIMS: m/z
(relative intensity) 573 (M+, 100), 558 (21), 544 (55), 530
(45), 376 (48), 348 (37). Anal. Calcd for C36H63NO4
(573.88): C, 75.36; H, 11.06; N, 2.44. Found C, 75.39; H,
11.12; N, 2.34%.
4.1.1.9. 3-n-Pentadecyl-6-tert-butyl-2,4-dinitrophenol
16. White powder. H NMR (400 MHz, CDCl3): d 0.87
1
(3H, t, J¼7.5 Hz, CH3), 1.20–1.35 (24H, m, CH2), 1.44
(9H, s, C(CH3)3), 1.64 (2H, m, ArCH2CH2), 2.89 (2H, t,
J¼8.0 Hz, ArCH2), 7.92 (1H, s, H-5), 9.63 (1H, s, OH).
13C NMR (100 MHz, CDCl3): d 14.6, 23.1, 28.8, 29.3,
29.4, 29.8, 29.9, 30.1, 30.3, 30.5, 32.3, 36.1, 127.8, 132.7,
137.9, 138.9, 143.1, 154.5. IR nmax(Nujol) 3332, 1615,
1575, 1475, 1334 cmꢁ1. EIMS: m/z (relative intensity) 450
(M+, 2), 435 (12), 434 (30), 433 (100). Anal. Calcd for
C25H42N2O5 (450.61): C, 66.64; H, 9.39; N, 6.22. Found
C, 66.55; H, 9.51; N, 6.30%.
1
4.1.2.4. para-Benzoquinone 23. Yellow oil. H NMR
(200 MHz, CDCl3): d 0.75–0.87 (3H, m, CH3), 1.15–1.34
(24H, m, CH2), 1.28(9H, s, C(CH3)3), 1.45–1.68 (2H, m,
ArCH2CH2), 2.29–255 (2H, m, ArCH2), 6.51–6.62 (1H, s,
Ar). 13C NMR (50 MHz, CDCl3): d 14.3, 22.7, 25.6, 29.0,

O. A. Attanasi et al. / Tetrahedron 62 (2006) 6113–6120
6119
5. Attanasi, O. A.; Ciccarella, G.; Filippone, P.; Mele, G.;
Spadavecchia, J.; Vasapollo, G. J. Porphyrins Phthalocyanines
2003, 7, 52–57.
6. Attanasi, O. A.; Del Sole, R.; Filippone, P.; Mazzetto, S. E.;
Mele, G. J.; Vasapollo, G. J. Porphyrins Phthalocyanines
29.1, 29.3, 29.4, 29.5, 29.6, 29.8, 31.9, 35.8, 132.8, 147.1,
147.4, 160.6, 175.4, 177.7. EIMS: m/z (relative intensity)
419 (M+, 100), 404 (71), 390 (46), 376 (41), 362 (39).
Anal. Calcd for C25H41NO4 (419.6): C, 71.56; H, 9.85; N,
3.34. Found C, 71.60; H, 9.79; N, 3.41%.
`
`
2003, 7, 52–57; Attanasi, O. A.; Del Sole, R.; Garcıa-Lopez,
E.; Mazzetto, S. E.; Filippone, P.; Mele, G.; Palmisano, L.;
Vasapollo, G. Green Chem. 2004, 6, 604–608.
1
4.1.2.5. para-Hydroquinone 24. Yellow oil. H NMR
(200 MHz, CDCl3): d 0.82–0.95 (3H, m, CH3), 1.18–1.35
(24H, m, CH2), 1.37 (9H, s, C(CH3)3), 1.48–1.69 (2H, m,
ArCH2CH2), 2.50–2.68 (2H, m, ArCH2), 6.67 (1H, s, Ar).
13C NMR (50 MHz, CDCl3): d 14.2, 22.7, 25.4, 29.3, 29.4,
29.5, 29.6, 29.8, 30.0, 30.3, 31.9, 33.3, 113.1, 116.1,
130.6, 137.4, 143.9, 148.8. EIMS: m/z (relative intensity)
421 (M+, 100), 406 (63), 392 (51), 378 (48), 364 (37).
Anal. Calcd for C25H43NO4 (421.6): C, 71.22; H, 10.28;
N, 3.32. Found C, 71.24; H, 10.21; N, 3.39%
7. Attanasi, O. A.; Del Sole, R.; Filippone, P.; Ianne, R.; Mazzetto,
S. E.; Mele, G.; Vasapollo, G. Synlett 2004, 799–802.
8. Biernat, J. F.; Luboch, E.; Wagner-Wysiecka, E. J. Supramol.
Chem. 2002, 2, 279–291.
9. Wasserman, D.; Dawson, C. R. J. Org. Chem. 1950, 72, 4994–
4997; Latham, G.; May, E. L.; Mosetting, E. J. Org. Chem.
1951, 16, 995–998.
10. Kremers, R. E. U.S. Patent 2,488,472, 1950; Chem. Abstr.
1950, 44, 12752; Dawson, C. R.; Wasserman, D. U.S. Patent
2,502,708, 1950; Chem. Abstr. 1950, 44, 33509.
11. Baylis, C. J.; Odle, S. W. D.; Tyman, J. H. P. J. Chem. Soc.,
Perkin Trans. 1 1981, 132–136; Lam, S. K.; Tyman, J. H. P.
J. Chem. Soc., Perkin Trans. 1 1981, 1942–1945; Attanasi,
O. A.; Filippone, P. Italian Patent, RM93a000 605, 09/09/
1993. Attanasi, O. A.; Buratti, S.; Filippone, P. Org. Prep.
Proced. Int. 1995, 27, 645–650.
12. Coletta, M.; Colucci, C.; Filippone, P.; Marini, S.; Mincione,
E.; Neri, V.; Saladino, R. J. Chem. Soc., Perkin Trans. 1
2000, 581–586.
13. Beattie, I. R.; Jones, P. J. Inorg. Chem. 1979, 18, 2318–2319;
Fischer, R. W.; Hermann, W. A.; Mrz, D. W. Chem. Rev.
1997, 97, 3197–3246; See for example: Fischer, R. W.;
Hermann, W. A.; Marz, D. W. Angew. Chem., Int. Ed. Engl.
1991, 30, 1638–1641; Al-Ajlouni, A. M.; Espenson, J. H.
J. Org. Chem. 1996, 61, 3969–3976; Adam, W.; Mitchell,
4.1.3. Procedure for the cyclocarbonylation reaction. Pal-
ladium(II) acetate (0.01 mmol) and dppb (0.04 mmol) were
dissolved in of dry toluene (5 mL) and 5-n-pentadecyl-2-
nitrophenol 6 (1 mmol) was added. The autoclave was
purged three times with CO and pressurized with CO
(300 psi) and H2 (300 psi). The reaction mixture was heated
with stirring for 24 h at 100 ꢀC (oil bath temperature). The
reaction mixture was cooled to room temperature, the solu-
tion was concentrated and the residue was extracted with
ether. The benzoxazol-2-one 28 was purified by chromato-
graphy using petroleum ether and diethyl ether as eluant.
1
White solid. H NMR (200 MHz, CDCl3): d 0.88 (3H, t,
J¼6.5 Hz, CH3), 1.15–2.30 (26H, m, CH2), 2.63 (2H, t,
J¼7.5 Hz, ArCH2), 7.03 (1H, s, Ar), 7.25–8.00, (2H, m,
Ar). 13C NMR (50 MHz, CDCl3): d 14.5, 23.1, 29.6, 29.8,
29.9, 30.0, 30.1, 32.2, 32.4, 36.3, 110.1, 124.1, 129.2,
131.1, 132.3, 144.6, 157.0. IR nmax(Nujol) 3277, 1742,
1498, 1255, 1170 cmꢁ1. EIMS: m/z (relative intensity) 345
(M+, 59), 317 (7), 162 (12), 148 (100). Anal. Calcd for
C22H35NO2 (345.52): C, 76.47; H, 10.21; N, 4.05. Found
C, 76.61; H, 10.32; N, 3.92%.
´
C. M. Angew. Chem., Int. Ed. 1996, 35, 535–553; Coperet,
C.; Adolfsson, H.; Sharpless, K. B. Chem. Commun. 1997,
1565–1566; Herrmann, W. A.; Kratzer, R. M.; Ding, H.; Thiel,
W. R.; Glas, H. J. J. Organomet. Chem. 1998, 555, 293–295;
Adam, W.; Mitchell, C. M.; Saha Moller, C. R.; Weachold,
O. J. Am. Chem. Soc. 1999, 121, 2097–2103; Carlucci, P.;
Cortese, M.; Crestini, C.; Danti, M. P.; Mincione, E.; Saladino,
R. Tetrahedron 2000, 56, 10031–10037; Aliotta, M.; Bernini,
R.; Cortese, M.; Mincione, E.; Saladino, R. Tetrahedron Lett.
Acknowledgements
´
´
2001, 42, 5401–5404; Begne, J. P.; Bonnet-Delpon, D.; Iskra,
J. Tetrahedron Lett. 2002, 43, 1001–1003; Espenson, J. H.;
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This work was supported by financial assistance from the
`
Ministero dell’Universita dell’ Istruzione e della Ricerca
(MIUR)—Rome, and the Universita degli Studi di Urbino
14. Adam, W.; Hermann, W. A.; Saha-Moller, C. R.; Shimizu, M.
J. Mol. Catal. A 1995, 97, 15–20.
`
‘Carlo Bo’. We are grateful to MIUR COFIN 2003: ‘La
catalisi dei metalli di transizione nello sviluppo di strategie
sintetiche innovative’.
15. Adam, W.; Schimizu, M. Synthesis 1994, 560–562; Adam, W.;
Ganeshpure, P. A. Synthesis 1993, 280–282.
16. Attanasi, O. A.; Filippone, P.; Mincione, E.; Saladino, R. Tetra-
hedron 2002, 58, 8493–8500.
17. Attanasi, O. A.; Filippone, P.; Mincione, E.; Saladino, R. Pure
Appl. Chem. 2003, 75, 261–268.
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