Synthesis of new cardanol derivatives through combined iodination/ palladium-catalysed cross-coupling reactions

Article abstract of DOI:10.1055/s-2006-942434

A versatile approach to the synthesis of new cardanol derivatives through a combination of aromatic iodination of 3-n-pentadecylphenol and palladium-catalysed cross-coupling reactions has been developed. The extent of aromatic iodination is controlled by

Full text of DOI:10.1055/s-2006-942434

PAPER
2523
Synthesis of New Cardanol Derivatives through Combined
Iodination/Palladium-Catalysed Cross-Coupling Reactions
I
odination/Palladiu
n
m-Catalysed
t
Cross
o
Coupling
R
e
n
actions of
C
i
ardanolo Arcadi,*a Orazio. A. Attanasi,b Stefano Berretta,b Gabriele Bianchi,a Paolino Filipponeb
a
Dipartimento di Chimica, Ingegneria Chimica e Materiali, Università dell’Aquila, via Vetoio, 67100 L’Aquila, Italy
Centro di Studio delle Sostanze Organiche di Orgine Naturale, Università di Urbino, Via Sasso 75, 61029 Urbino, Italy
Fax +39(0862)433753.; E-mail: arcadi@univaq.it
b
Received 10 March 2006; revised 21 March 2006
trienyl)phenol] polyketide long-chain phenols, with an
average value of two double bonds per molecule.
Abstract: A versatile approach to the synthesis of new cardanol de-
rivatives through a combination of aromatic iodination of 3-n-pen-
tadecylphenol and palladium-catalysed cross-coupling reactions
has been developed. The extent of aromatic iodination is controlled
by stoichiometry and affords either the mono-, di- or tri-iodo-car-
danol derivatives. Suzuki, Heck and Sonogashira protocols were
successfully applied for the vinylation, arylation and alkynylation
of the iodo-cardanols. 2,4-Diiodo-5-n-pentadecylphenol underwent
an unusual sequential regioselective dehalogenation/vinylation re-
action. Sequential alkynylation/cyclisation of 2-iodo-3-n-pentade-
cylphenol derivatives were also investigated.
Pure saturated 3-n-pentadecylphenol of homogeneous
chemical composition can be easily obtained by simple
hydrogenation of technical-grade distilled cardanol and
subsequent purifying distillation and/or crystallisation.
Cardanol derivatives represent a simple entry point for the
preparation of additives for lubricants, diesel engine fuels,
pour-point depressants, flame retardants, resins, inks, hy-
drorepellents, and antioxidants.2 Selective oxidation of
cardanol derivatives by methylrhenium trioxide has also
been reported.3 Furthermore, cardanol derivatives of
phthalocyanines,4 porphyrins5 and fullerenes6 showed that
the introduction of a cardanol moiety in these compounds
was important in order to improve their solubility in or-
ganic solvents. The corresponding cardanol-based deriva-
tives have also enabled a new class of dyes to be
developed that have real prospects not only for photocat-
alytic processes, but also for other technological applica-
tions.7
Key words: aromatic substitution, halogenation, palladium, Heck
reaction, cross-coupling
Currently, the vast majority of organic chemicals synthe-
sised stem from petroleum feedstocks. Nevertheless, agri-
cultural and biological feedstocks can be excellent
alternative, renewable raw materials. At present, it has
shown that a host of agricultural products can be trans-
formed into consumer products, however the search for
biological sources of alternative feedstocks need not be
limited to agricultural products: agricultural waste may
also provide important raw materials for the production of
consumer compounds. The use of an otherwise unused
waste product that would need to be disposed of is very at-
tractive for obvious environmental and economic reasons.
In this context the utilisation of cardanol derivatives
seems very attractive.
Continuing the investigations on the functionalisation of
cardanol, we wish to present our results for the prepara-
tion of new cardanol derivatives through a combination of
iodination and palladium-catalysed cross coupling reac-
tions.
In recent years, iodophenols8 have assumed increasing
importance in chemistry. This interest can be ascribed to
the facile oxidative addition of aryl iodides to low-valent
transition metals. The chemistry of the resulting Ar-M-I
intermediates has been widely investigated, leading to
valuable new syntheses of useful compounds. While aryl
bromides/chlorides can often also be used in these reac-
tions, there are cases in which the use of the more reactive
aryl iodides has special value. This is particularly true in
the case of aryl halides substituted by electron-donating
groups such as hydroxyl.
Cardanol1 is an industrial-grade yellow oil obtained by
vacuum distillation of ‘Cashew Nut Liquid’ (CNSL), the
international name for the alkyl phenolic oil contained in
the spongy mesocarp of the cashew nut shell (Anacardium
occidentale L.).
Because of the large demand and high commercial value
of the edible kernel, world-wide cashew nut production
has shown an increasing trend over the past five to ten
years. As a consequence, CNSL now represents a renew-
able, widely available, and relatively low-cost organic
natural material. Distilled cardanol is as a mixture of sat-
urated (3-n-pentadecylphenol), mono-olefinic [3-(n-pen-
tadeca-8-enyl)phenol], di-olefinic [3-(n-pentadeca-8,11-
dienyl)phenol] and tri-olefinic [3-(n-pentadeca-8,11,14-
OH
OH
OH
I
+
C15H31
C15H31
C15H31
I
2b (44%)
1a
2a (54%)
Scheme
1
Reagents and conditions: 1a:NaI:NaOH:NaOCl
SYNTHESIS 2006, No. 15, pp 2523–2530
Advanced online publication: 26.06.2006
x
x.
x
x
.
2
0
0
6
(1.5:1:1:1), MeOH, 0 °C for 1 h and r.t. for 120 h.
DOI: 10.1055/s-2006-942434; Art ID: Z05006SS
© Georg Thieme Verlag Stuttgart · New York

2524
A. Arcadi et al.
PAPER
OH
OH
OH
OH
I
I
I
I
I
I
i
+
+
C15H31
C15H31
C15H31
2d (20%)
2e (84%)
C15H31
I
I
2e (14%)
2a
2c (43%)
ii
2c
Scheme 2 Reagents and conditions: (i) 2a:NaI:NaOH:NaOCl (1:1:1:1), MeOH, r.t., 3 h; (ii) 2c:NaI:NaOH:NaOCl (1:1:1:1), MeOH, 50 °C,
2 h.
Although regioselective bromination of cardanol
derivatives9 has been previously studied, the correspond-
ing iodination has thus far remained unexplored. The di-
rect iodination of 3-n-pentadecylphenol 1a may be
achieved in aqueous alcohol solvents by the action of a re-
agent prepared in situ from sodium hypochlorite and sodi-
um iodide.10 The extent of iodination can be controlled by
stoichiometry. Mono iodination of 1a was carried out with
one equivalent of the iodinating agent leading to the for-
mation of 2-iodo-5-n-pentadecylphenol (2a; 54%) and 4-
iodo-3-n-pentadecylphenol (2b; 44%) in excellent com-
bined yield (Scheme 1).
OH
C15H31
R1
3
R1
OH
OH
ArB(OH)2
Ar
C15H31
4
H
C15H31
I
OH
R2
2
R2
C15H31
5
Analogously, the preparation of diiodinated and the tri-
iodinated derivatives (Scheme 2) was effected smoothly, Scheme 4
under the same reaction conditions, starting from 2a and
temperature,14 bromo derivatives of 3-n-pentadecylphe-
nol (1a) proved to be inert to a variety of these reactions
conditions.
2c respectively. The iodinated products reported in this
study were isolated by column chromatography over sili-
ca gel and characterised by standard analytical means.
Iodination at the 2-position of 1a was easily accomplished
when the 4,6-positions were already occupied. Indeed, the
2-iodo-3-n-pentadecyl-4,6-dibromophenol (2f) was
smoothly prepared in good yield from the 2,4-dibromo-5-
n-pentadecylphenol (1b) (Scheme 3). The bromine on 2f
was considered a potential protecting group since debro-
mination could be achieved both selectively and regiose-
lectively.11
Monoiodo derivatives 2a–b underwent palladium-cataly-
sed Heck reaction with both the activated, electron-defi-
cient olefin methyl vinyl ketone and with styrene to afford
the corresponding vinyl derivatives 3a–c in good yield
(Table 1, entries 1–3).15 The successful application of the
Heck reaction with styrene is significant as this creates a
new entry point for the synthesis of powerful antioxi-
dants.16 In agreement with previous results,17 3a,c exhibit
antioxidant activity similar to those of other cardanol de-
rivatives and commercial antioxidants.18
OH
OH
Br
Br
I
Surprisingly, the 2,4-diiodo-5-n-pentadecylphenol (2c)
provided 3a in 98% yield (Scheme 5).
C15H31
C15H31
Br
Br
O
1b
2f (75%)
O
OH
Me
Scheme
3
Reagents and conditions: 1b:NaI:NaOH:NaOCl
7
(1:1:1:1), MeOH, r.t., 2 h.
2c
C15H31m
3a (98%)
The potential of iodo derivatives 2 as suitable precursors
for increasing molecular complexity via palladium-catal-
ysed cross-coupling reactions12 was then investigated. In
particular the aryl iodophenols 2 were exploited as sub-
strates for the synthesis of the corresponding aryl-, vinyl-
and alkynyl cardanol derivatives following Suzuki, Heck
and Sonogashira protocols, respectively (Scheme 4). It is
worth noting that, despite advances in the scope of cross-
coupling reactions such as the use of less reactive aryl ha-
lides as substrates13 and the coupling of hindered sub-
strates at very low catalyst loadings and at room
Scheme
5
Reagents and conditions: 2c:7:Pd(OAc)2:KOAc
(1:6:0.05:3), DMF, 100 °C, 24 h.
The regioselectivity and halogen discrimination in this se-
quential vinylation/dehalogenation reaction should be
considered as two major issues. Reductive dehalogenation
of 2,4,6-triiodophenol by sulfite/bisulfate was reported to
give only the para-deiodinated product 2,6-diiodophe-
nol.19 Conversely, the ortho-iodine was reported to be se-
lectively removed under the influence of tertiary amines/
Synthesis 2006, No. 15, 2523–2530 © Thieme Stuttgart · New York

PAPER
Iodination/Palladium-Catalysed Cross-Coupling Reactions of Cardanol
2525
OH
water by a nonreductive deiodination reaction, without af-
fecting para-iodine.20 It is thus very likely that, because of
the presence of two iodine atoms which slow down the
rate of the Heck reaction, the competitive C-4 reductive
dehalogenation of 2c took place to give 2a which in turn
led to the formation of 3a. The exact mechanism of the de-
halogenation is not yet clearly understood and further ex-
ploration is needed.
Ph
Ph
Ph
C15H31
4f (61%)
+K–F3B
8
2e
Ph
Scheme 6
Reagents and conditions: 2e:8:K3PO4:Pd(OAc)2:
n-Bu4NBr (1:3.6:6:0.05:0.005), EtOH, 80 °C, 24 h.
The palladium-catalysed cross-coupling reaction of aryl
halides and organoboron reagents is one of the most wide-
ly used synthetic protocols in modern chemistry and in in-
dustrial applications. Aryl boronic acids are almost ideal
as reagents because they are largely unaffected by the
presence of water, tolerate a broad range of functionalities
and yield non toxic by-products which can be readily sep-
arated from the desired product. We thus examined the
palladium-catalysed cross-coupling reaction of 2 with a
variety of boronic acids under different reaction condi-
tions. While these reactions have been known for 30
years, there continues to be a significant amount of re-
search devoted to identifying mild reactions conditions
that allow the coupling to proceed in the presence of air
and use more economic palladium species as catalyst.23
‘Ligandless’ palladium species have been developed that
give fast coupling reactions where the phosphine-related
side reaction can be suppressed.24 Considerable improve-
ments are observed when the reactions are carried out in
protic solvents, for example, in H2O25 or ethanol.26 Etha-
nol represented the optimal reaction media for our iodo-
cardanol derivatives. The cross-coupling of 2a,b,f with a
variety of aryl boronic acids were examined under the op-
timal reaction conditions [ratio of 2:aryl boronic
acid:Pd(OAc)2:n-Bu4NBr:K3PO4 = 1:1.1:0.05:0.05:1 in
ethanol at reflux]. The resulting biaryl derivatives 4a–e
were obtained in good yields (Table 1, entries 4–8) show-
ing that the reaction was efficient both with electron-
donating and electron-withdrawing substituents on the
aryl moiety of the boronic acid derivatives. Under our
conditions the results seem to indicate that the reaction
outcome is not affected by electronic factors. Although
the ability to prepare extremely hindered biaryls via Suzu-
ki–Miyaura coupling reactions has historically proven to
be a difficult task, especially with substrates that contain
ortho,ortho¢-substituents, the coupling the 2-iodo-3-n-
pentadecyl-4,6-dibromophenol (2f) proceeded as well as
that of the less hindered substrates 2a–b. As expected,
chemoselective functionalisation of the C–I bond oc-
curred when both C–I and C–Br groups were present in
the phenol moiety. Furthermore, according to recent ap-
plications which suggest that alkenyltrifluoroborates28 are
exceptional partners in the Suzuki–Miyaura cross-cou-
pling reaction, providing advantages over other orgaboron
substrates, the reaction of the triiododerivative 2g with
potassium b-styryltrifluoro borate (8) accomplished the
formation of the corresponding 3-pentadecyl-2,4,6-
tris[(E)-styryl]phenol (4f) (Scheme 6).
OH
OH
OH
OH
H
9
2d
C15H31
5c (70%)
Scheme 7
Reagents and conditions: 2d:9:Et3N:PdCl2(PPh3)2:CuI
(1:2.6:2.6:0.02:0.04), THF, 60 °C, 4 h.
ing alkynyl derivatives 5a–b (Table 1, entries 9–10).
Analogously, the diiodo derivative 2d gave 5c
(Scheme 7).
It is worth noting that, in contrast to the usual outcome of
the palladium-catalysed reactions of ortho-iodophenol de-
rivatives with 1-alkynes,29 the product derived by the se-
quential alkynylation/cyclisation reaction was observed
only in trace amounts. The formation of this latter deriva-
tive should be favoured in the presence of electron-with-
drawing substituents in the aromatic moiety of 2 and,
indeed, the palladium-catalysed reaction of 4,6-dibromo-
2-iodo-3-pentadecylphenol (2f )with 3-methyl-1-pentyn-
3-ol (9) afforded 2-(5,7-dibromo-4-pentadecylbenzofu-
ran-2-yl)butan-2-ol (6) as the major product (Scheme 8).
HO
O
9
Br
2f
C15H31
Br
6 (40%)
Scheme 8
Reagents and conditions: 2f:9:Et3N:PdCl2(PPh3)2:CuI
(1:1.3:1.3:0.02:0.04), THF, 60 °C, 24 h.
In summary, we have developed a versatile route for the
synthesis of new cardanol derivatives through a combined
aromatic iodination/palladium-catalysed cross-coupling
process. The extent of aromatic iodination is controlled by
stoichiometry. 2-Iodo- and 2,4-diiodo-5-n-pentadecyl-
phenol, and 2,6-diiodo-, 4-iodo-, 2,4,6-triiodo-, and 2-
iodo-4,6-dibromo-3-n-pentadecylphenol derivatives have
been synthesised. Suzuki, Heck and Sonogashira proto-
cols were found to be useful tools for the vinylation, ary-
lation and alkynylation of these iodo cardanol derivatives.
2,4-Diiodo-5-n-pentadecylphenol undergoes an unusual
sequential regioselective dehalogenation/vinylation reac-
tion. Sequential alkynylation/cyclisation of 2-iodo-3-n-
pentadecylphenol derivatives promises an easy entry
point to polysubstituted benzo[b]furans.
The Sonogashira coupling28 of the monoiodides 2a–b
with 3-methyl-1-pentyn-3-ol (9) afforded the correspond-
Synthesis 2006, No. 15, 2523–2530 © Thieme Stuttgart · New York

2526
A. Arcadi et al.
PAPER
Table 1 Palladium-Catalysed Cross-Coupling Reactions of Iodo-3-n-pentadecylphenol Derivatives 2a,b,f
Entry Iodo-cardanol derivatives Cross-coupling reagents Reaction conditionsb Products
Yielda (%)
1
A
60
OH
O
O
OH
I
7
7
C15H31
C15H31
2a
2a
3a
2
A
55
OH
C15H31
3b
3
A
86
OH
O
C15H31
HO
C15H31
I
3c
2b
2a
4
5
B
B
85
80
B(OH)2
OH
MeO
MeO
C15H31
4a
2b
B(OH)2
F
HO
C15H31
F
4b
6
7
B
B
78
80
OH
Br
B(OH)2
OH
Br
I
Br
C15H31
C15H31
Br
2f
2f
4c
Me
B(OH)2
Me
OH
Br
C15H31
Br
4d
8
9
2f
B
C
56
40
B(OH)2
OH
Br
OMe
MeO
C15H31
Br
4e
5a
2a
OH
H
OH
Me
OH
Me
C15H31
9
9
10
2b
C
72
OH
HO
C15H31
5b
a Isolated yield after flash chromatography.
b Reaction conditions: (A) DMF, 24 h at 100 °C, molar ratios 2:alkene:Pd(OAc)2:AcOK = 1:3:0.05:3; (B) EtOH, 24 h at 80 °C, molar ratios
2:boric acid:Pd(OAc)2:K3PO4:n-Bu4NBr = 1:1.2:0.05:2:0.05; (C) THF, 24 h at 60 °C, molar ratios 2:9:PdCl2(PPh3)2:CuI:Et3N =
1:1.3:0.02:0.04:1.3.
Synthesis 2006, No. 15, 2523–2530 © Thieme Stuttgart · New York

PAPER
Iodination/Palladium-Catalysed Cross-Coupling Reactions of Cardanol
IR (KBr): 3320, 1470, 640 cm–1.
2527
All starting materials were commercially available and were used as
purchased without further purification, unless otherwise stated. The
products, after conventional workup, were purified by flash chro-
matography on silica gel, eluting with n-hexane–ethyl acetate mix-
tures. 1H NMR (200 MHz) and 13C NMR (50.3 MHz) spectra were
recorded on a Bruker AC 200 spectrometer in CDCl3. EI and ESI
mass spectra were recorded respectively on a ThermoFinnigan
Trace DSQ-GC equipped with direct exposition probe and on a
ThermoFinnigan LCQ DecaXP equipped with an orthogonal ESI
source. IR spectra were recorded in KBr pellets or neat in NaCl
disks using a Perkin-Elmer 683 spectrometer. 3-n-Pentadecylphe-
nol (1a) was kindly supplied by Oltremare SpA (Bologna, Italy) and
2,4-dibromo-5-n-pentadecylphenol (1b) was prepared according to
the literature.9
1H NMR (200 MHz, CDCl3): d = 0.88 (t, J = 5.9 Hz, 3 H), 1.54–
1.25 (m, 26 H), 2.59 (t, J = 7.2 Hz, 2 H), 5.25 (s, 1 H), 6.86 (s, 1 H),
8.00 (s, 1 H).
13C NMR (50.3 MHz, CDCl3): d = 14.1, 22.7, 29.2, 29.3, 29.4, 29.5,
29.7, 29.9, 31.9, 40.3, 83.1, 93.2 115.6, 146.4, 147.7, 155.1.
ESI-MS: m/z (%) = 555.1 (100) [M – 1]–.
Anal. Calcd for C21H34I2O: C, 45.34; H, 6.16. Found: C, 45.50; H,
6.25.
2,6-Diiodo-3-pentadecylphenol (2d)
Purified by column chromatography (n-hexane–EtOAc, 99:1).
White solid; yield: 0.489 g (20%).
IR (KBr): 3330, 1460, 640 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.87 (t, J = 6.0 Hz, 3 H), 1.25 (br
s, 24 H), 1.53–1.60 (m, 2 H), 2.66 (t, J = 7.3 Hz, 2 H), 6.00 (br s,
1 H), 6.56 (d, J = 8.1 Hz, 1 H), 7.50 (d, J = 8.1 Hz, 1 H).
13C NMR (50.3 MHz, CDCl3): d = 14.1, 22.7, 27.9, 29.3, 29.4, 29.5,
29.7, 29.9, 31.9, 33.6, 119.3, 121.6, 123.4, 136.5, 141.9, 150.7.
ESI-MS: m/z (%) = 557.62 (10) [M + 1]+, 268.02 (80), 141 (100).
Iodination; General Procedure
3-n-Pentadecylphenol derivative (6.6 mmol of 1a or 4.4 mmol of
1b) was dissolved in MeOH (50 mL) and NaI (0.660 g, 4.4 mmol)
followed by NaOH (0.176 g, 4.4 mmol) were added, and the solu-
tion was cooled to 0 °C. Sodium hypochlorite aq (0.326 g, 4.0%
NaOCl) was added dropwise over 30 min at 0 °C and the mixture
was stirred for 1 h at 0 °C then at r.t. until the starting 3-pentade-
cylphenol derivative was completely consumed (monitored by
TLC). After completion the mixture was adjusted to pH 7 using aq
HCl (5%). EtOAc (100 mL) was added, and the organic layer taken,
dried (Na2SO4) and the solvent was evaporated. Column chromato-
graphic purification on silica gel (230-400 mesh), eluting with n-
hexane–EtOAc mixtures afforded the corresponding pure 3-n-pen-
tadecylphenol iodo derivative.
Anal. Calcd for C21H34I2O: C, 45.34; H, 6.16. Found: C, 45.20; H,
6.01.
2,4,6-Triiodo-3-pentadecylphenol (2e)
Purified by column chromatography (n-hexane–EtOAc, 99:1).
White solid; yield: 2.520 g (84%).
IR (KBr): 3410, 1460, 710 cm–1.
2-Iodo-5-pentadecylphenol (2a)
Purified by column chromatography (n-hexane–EtOAc, 98:2).
1H NMR (200 MHz, CDCl3): d = 0.88 (t, J = 5.4 Hz, 3 H), 1.44–
1.25 (m, 26 H), 2.87 (t, J = 7.2 Hz, 2 H), 5.25 (s, 1 H), 8.09 (s, 1 H).
13C NMR (50.3 MHz, CDCl3): d = 14.1, 22.7, 28.0, 29.2, 29.4, 29.5,
29.7, 31.9, 47.1, 78.9, 87.4, 88.5, 145.6, 147.3, 154.1.
White solid; yield: 1.021 g (54%).
IR (KBr): 3330, 1410, 600 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.88 (t, J = 6.7 Hz, 3 H), 1.25–129
(m, 24 H), 1.55–1.60 (m, 2 H), 2.52 (t, J = 5.2 Hz, 2 H), 5.24 (s,
1 H), 6.51 (dd, J = 8.0, 2.0 Hz, 1 H), 6.82 (d, J = 2.0 Hz, 1 H), 7.52
(d, J = 8.0 Hz, 1 H).
13C NMR (50.3 MHz, CDCl3): d = 14.1, 22.7, 29.2, 29.4, 29.5, 29.6,
29.7, 30.0, 30.1, 31.1, 31.9, 35.4, 81.8, 115.1, 122.9, 137.7, 145.8,
154.6.
ESI-MS: m/z (%) = 681.0 (40) [M – 1]–, 589.2 (100).
Anal. Calcd for C21H33I3O: C, 36.97; H, 4.88. Found: C, 36.50; H,
4.90.
4,6-Dibromo-2-iodo-3-pentadecylphenol (2f)
Purified by column chromatography (n-hexane–EtOAc, 99:1).
ESI-MS: m/z (%) = 431.5 (6) [M + 1]+, 107.2 (100).
White solid; yield: 1.940 g (75%).
IR (KBr): 3420, 1420, 650 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.88 (t, J = 6.8 Hz, 3 H), 1.25 (br
s, 24 H), 1.36 (br s, 2 H), 2.98 (t, J = 6.4 Hz, 2 H), 5.98 (s, 1 H) 7.67
(s, 1 H).
Anal. Calcd for C21H35IO: C, 58.60; H, 8.20. Found: C, 58.50; H,
8.15.
4-Iodo-3-pentadecylphenol (2b)
Purified by column chromatography (n-hexane–EtOAc, 95:5).
13C NMR (50.3 MHz, CDCl3): d = 14.1, 22.7, 27.9, 29.3, 29.4, 29.6,
White solid; yield: 0.8322 g (44%).
IR (KBr): 3330, 1460, 610 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.87 (t, J = 6.8 Hz, 3 H), 1.25 (br
s, 24 H), 1.47–1.54 (m, 2 H), 2.60 (t, J = 7.3 Hz, 2 H), 6.41 (dd,
J = 8.5, 3.0 Hz, 1 H), 5.25 (br s, 1 H), 6.70 (d, J = 3.0 Hz, 1 H), 7.60
(d, J = 8.5 Hz, 1 H).
13C NMR (50.3 MHz, CDCl3): d = 14.1, 22.7, 28.0, 29.3, 29.4, 29.6,
29.7, 30.1, 31.9, 33.6, 40.8, 89.1, 115.0, 116.5, 139.9, 146.8, 155.7.
ESI-MS: m/z (%) = 429.8 (52) [M+], 233.7 (100), 106.9 (59).
29.7, 31.9, 42.2, 46.9, 90.6, 105.4, 113.4, 135.2, 145.0, 151.1.
ESI-MS: m/z (%) = 590.5 (6) [M + 1]+, 588.6 (13) [M + 1]+, 586.6
(8) [M + 1]+, 392.9 (22), 390.97 (48), 388.9 (25), 266.9 (48), 264.93
(100), 262.9 (58).
Anal. Calcd for C21H33Br2IO: C, 42.88; H, 5.65. Found: C, 42.69;
H, 5.50.
Palladium-Catalysed Cross-Coupling of Iodo Derivatives 2a,b
with Alkenes; General Procedure
A round-bottom flask was charged with a solution of Pd(OAc)2 (11
mg, 0.05 mmol), the iododerivative 2 (1.0 mmol), the appropriate
alkene (2.0 mmol) and AcOK (0.294 g, 3.0 mmol) in DMF (2 mL).
The reaction mixture was stirred for 24 h at 100 °C then diluted with
EtOAc (100 mL). The organic layer was washed with H2O (10 mL),
and the aqueous layer was extracted with EtOAc (3 × 10 mL). The
combined organic layers were washed with brine (30 mL) and dried
Anal. Calcd for C21H35IO: C, 58.60; H, 8.20. Found: C, 58.33; H,
8.25.
2,4-Diiodo-5-pentadecylphenol (2c)
Purified by column chromatography (n-hexane–EtOAc, 99:1).
White solid; yield: 1.052 g (43%).
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(Na2SO4). After removal of the solvent, the residue was purified by
column chromatography on silica gel, eluting with n-hexane–
EtOAc mixtures to give corresponding pure product 3.
(Na2SO4). After removal of the solvent, the residue was purified by
column chromatography on silica gel, eluting with n-hexane–
EtOAc mixtures to give corresponding pure product 4.
(E)-4-(2-Hydroxy-4-pentadecylphenyl)but-3-en-2-one (3a)
Purified by column chromatography (n-hexane–EtOAc, 95:5).
3¢-Methoxy-4-pentadecylbiphenyl-2-ol (4a)
Purified by column chromatography (n-hexane–EtOAc, 90:10).
Yellowish solid; yield: 0.223 g (60%).
IR (KBr): 3310, 1730, 710 cm–1.
White solid; yield: 0.349 g (85%).
IR (neat): 3450, 690 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.87 (t, J = 6.8 Hz, 3 H), 1.25 (m,
24 H), 1.50–1.75 (m, 2 H), 2.41 (s, 3 H), 2.53 (t, J = 8.4 Hz, 2 H),
6.25 (s, 1 H), 6.66–6.75 (m, 2 H), 6.99 (d, J = 16.4 Hz, 1 H), 7.37
(d, J = 8.5 Hz, 1 H), 7.84 (d, J = 16.4 Hz, 1 H).
1H NMR (200 MHz, CDCl3): d = 0.88 (t, J = 6.5 Hz, 3 H), 1.26 (br
s, 24 H), 1.50–1.55 (m, 2 H), 2.59 (t, J = 7.7 Hz, 2 H), 3.83 (s, 3 H),
5.36 (br s, 1 H), 6.78–7.04 (m, 5 H), 7.15 (d, J = 8.2 Hz, 1 H), 7.37
(t, J = 8.2 Hz, 1 H).
13C NMR (50.3 MHz, CDCl3): d = 14.1, 22.7, 26.7, 29.4, 29.5, 29.7,
31.04, 31.9, 35.9, 116.5, 119.0, 120.8, 126.6, 129.5, 141.0, 148.0,
156.4, 200.9.
13C NMR (50.3 MHz, CDCl3): d = 14.1, 22.7, 29.4, 29.5, 29.3, 29.7,
31.3, 31.9, 35.7, 55.3, 113.4, 114.5, 115.6, 120.9, 121.1, 129.7,
130.3, 138.5, 144.6, 150.1, 160.3.
ESI-MS: m/z (%) = 371.5 (100) [M – 1]–.
ESI-MS: m/z (%) = 411.3 (30) [M + 1]+, 214.9 (100).
Anal. Calcd for C25H40O2: C, 80.59; H, 10.82. Found: C, 80.64; H,
10.60.
Anal. Calcd for C28H42O2: C, 81.90; H, 10.31. Found: C, 81.50; H,
10.20.
5-Pentadecyl-2-[(E)-styryl]phenol (3b)
Purified by column chromatography (n-hexane–EtOAc, 98:2).
4¢-Fluoro-2-pentadecylbiphenyl-4-ol (4b)
Purified by column chromatography (n-hexane–EtOAc, 95:5).
Yellowish solid; yield: 0.224 g (55%).
IR (KBr): 3580, 830 cm–1.
White solid; yield: 0.318 g (80%).
IR (neat): 3350, 800 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.87 (t, J = 5.8 Hz, 3 H), 1.25 (br
s, 24 H), 1.37–1.57 (m, 2 H), 2.53 (t, J = 7.8 Hz, 2 H), 5.18 (s, 1 H),
6.62 (d, J = 8.1 Hz, 1 H), 6.76 (d, J = 7.8 Hz, 1 H), 7.07 (d, J = 16.5
Hz, 1 H), 7.23–7.26 (m, 2 H), 7.34 (d, J = 16.5 Hz, 1 H), 7.38–7.44
(m, 3 H), 7.50 (d, J = 7.4 Hz, 1 H).
13C NMR (50.3 MHz, CDCl3): d = 14.1, 22.7, 29.4, 29.6, 29.7, 31.2,
31.3, 31.9, 34.4, 35.6, 35.8, 115.9, 120.9, 121.4, 122.0, 126.4,
126.9, 127.4, 128.6, 129.4, 137.8, 144.2, 152.8.
1H NMR (200 MHz, CDCl3): d = 0.87 (t, J = 6.8 Hz, 3 H), 1.14–
1.25 (m, 24 H), 1.45–1.70 (m, 2 H), 2.41–2.56 (m, 2 H), 5.52 (br s,
1 H), 6.72–6.76 (m, 3 H), 6.99–7.11 (m, 2 H), 7.12–7.18 (m, 1 H),
7.20 (d, J = 8.8 Hz, 1 H).
13C NMR (50.3 MHz, CDCl3): d = 14.1, 22.7, 29.9, 31.3, 31.9, 33.0,
33.7, 35.8, 112.6, 114.6, 115.2 (d, JC–F = 17.6 Hz), 130.8, 131.1 (d,
JC–F = 12.5 Hz), 133.7, 142.3, 143.0, 154.6, 161.9 (d, JC–F = 251.2
Hz).
ESI-MS: m/z (%) = 405.6 (100) [M – 1]–.
ESI-MS: m/z (%) = 399.3 (25) [M + 1]+, 202.0 (60), 107.99 (100).
Anal. Calcd for C29H42O: C, 80.66; H, 10.41. Found: C, 80.59; H,
10.35.
Anal. Calcd for C27H39FO: C, 81.36; H, 9.86. Found: C, 81.45; H,
9.50.
(E)-4-(4-Hydroxy-2-pentadecylphenyl)but-3-en-2-one (3c)
Purified by column chromatography (n-hexane–EtOAc, 95:5).
3,5-Dibromo-6-pentadecylbiphenyl-2-ol (4c)
Purified by column chromatography (n-hexane–EtOAc, 95:5).
White solid; yield: 0.320 g (86%).
IR (KBr): 3310, 1730, 710 cm–1.
White solid; yield: 0.419 g (78%).
IR (neat): 3520, 860 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.87 (t, J = 6.7 Hz, 3 H), 1.26 (br
s, 24 H), 1.53–1.57 (m, 2 H), 2.36 (s, 3 H), 2.71 (t, J = 8.0 Hz, 2 H),
6.56 (d, J = 15.9 Hz, 1 H), 6.73–677 (m, 2 H), 7.52 (d, J = 15.9 Hz,
1 H), 7.81 (d, J = 15.9 Hz, 1 H), 8.42 (br s, 1 H).
13C NMR (50.3 MHz, CDCl3): d = 14.1, 22.8, 27.5, 29.3, 29.4, 29.6,
29.8, 30.1, 30.5, 30.9, 31.7, 32.0, 33.4, 114.1, 116.9, 124.4, 125.3,
128.4, 140.9 145.4, 159.3, 198.4.
1H NMR (200 MHz, CDCl3): d = 0.87 (t, J = 6.0 Hz, 3 H), 1.04–
1.34 (br s, 26 H), 2.37–2.45 (m, 2 H), 5.18 (s, 1 H), 7.18–7.23 (m,
2 H), 7.41–7.48 (m, 3 H), 7.68 (s, 1 H).
13C NMR (50.3 MHz, CDCl3): d = 14.2, 22.7, 28.9, 29.2, 29.4, 29.5,
29.6, 29.7, 31.9, 33.7, 107.3, 115.4, 128.1, 128.4, 129.0, 130.4,
134.7, 135.3, 141.3, 149.3.
ESI-MS: m/z (%) = 540.4 (12) [M + 1]+, 536.2 (22) [M + 1]+, 182.2
(82), 181.0 (100).
ESI-MS: m/z (%) = 373.3 (100) [M + 1]+.
Anal. Calcd for C25H40O2: C, 80.59; H, 10.82. Found: C, 80.70; H,
10.50.
Anal. Calcd for C27H38Br2O: C, 60.23; H, 7.11. Found: C, 60.30; H,
7.13.
Palladium-Catalysed Cross-Coupling of Iodo Derivatives 2a,b,f
with Organoboron Compounds; General Procedure
3,5-Dibromo-4¢-methyl-6-pentadecylbiphenyl-2-ol (4d)
Purified by column chromatography (n-hexane–EtOAc, 95:5).
A round-bottom flask was charged with a solution of Pd(OAc)2 (5
mg, 0.02 mmol), the iodo derivative 2 (1.0 mmol), the appropriate
boronic acid (1.3 mmol), K3PO4 (0.424 g, 2.0 mmol), n-Bu4NBr
(0.016 g, 0.05 mmol) in EtOH (2 mL). The reaction mixture was
stirred for 24 h at 80 °C then the mixture was diluted with EtOAc
(100 mL). The organic layer was washed with H2O (10 mL), and the
aqueous layer was extracted with EtOAc (3 × 10 mL). The com-
bined organic layers were washed with brine (30 mL) and dried
White solid; yield: 0.442 g (80%).
IR (neat): 3540, 1310, 810 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.87 (t, J = 6.8 Hz, 3 H), 1.14–
1.30 (br s, 26 H), 2.37 (m, 5 H), 5.16 (s, 1 H), 7.09 (d, J = 8.0 Hz,
2 H), 7.3 (d, J = 8.0 Hz, 2 H), 7.67 (s, 1 H).
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Iodination/Palladium-Catalysed Cross-Coupling Reactions of Cardanol
2529
13C NMR (50.3 MHz, CDCl3): d = 14.1, 21.3, 22.7, 28.9, 29.2, 29.3,
29.4, 29.7, 31.9, 33.6, 107.1, 115.3, 128.7, 129.6, 129.8, 131.9,
134.6, 138.4, 141.4, 149.4.
2-(3-Hydroxy-3-methylpent-1-ynyl)-5-pentadecylphenol (5a)
Purified by column chromatography (n-hexane–EtOAc, 90:10).
Oil; yield: 0.160 g (40%).
ESI-MS: m/z (%) = 551.4 (100) [M – 1]–.
IR (neat): 3420, 1470, 810 cm–1.
Anal. Calcd for C28H40Br2O: C, 58.07; H, 7.58. Found: C, 58.10; H,
7.65.
1H NMR (200 MHz, CDCl3): d = 0.87 (t, J = 6.2 Hz, 3 H), 1.10 (t,
J = 7.3 Hz, 3 H), 1.25 (br s, 26 H), 1.58 (s, 3 H), 1.79 (q, J = 7.3 Hz,
2 H), 2.67 (t, J = 8.0 Hz, 2 H), 6.10 (s, 1 H), 6.67 (dd, J = 7.9, 1.6
Hz, 1 H), 6.77 (d, J = 1.6 Hz, 1 H), 7.19 (d, J = 7.9 Hz, 1 H).
13C NMR (50.3 MHz, CDCl3): d = 9.2, 14.1, 22.7, 27.8, 29.0, 29.2,
29.4, 29.5, 29.6, 29.7, 31.0, 31.9, 35.9, 36.6, 69.5, 78.0, 99.0, 106.2,
114.7, 120.6, 131.4, 146.2, 156.6.
3,5-Dibromo-3¢-methoxy-6-pentadecylbiphenyl-2-ol (4e)
Purified by column chromatography (n-hexane–EtOAc, 95:5).
White solid; yield: 0.318 g (56%).
IR (KBr): 3490, 1430, 570 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.79 (t, J = 6.0 Hz, 3 H), 1.17 (m,
26 H), 2.30–2.38 (m, 2 H), 3.74 (s, 3 H), 5.08 (s, 1 H), 6.67–6.73
(m, 2 H), 6.86–6.92 (m, 1 H), 7.32 (t, J = 7.9 Hz, 1 H), 7.60 (s, 1 H).
Anal. Calcd for C27H44O2: C, 80.47; H, 8.91. Found: C, 80.67; H,
8.98.
4-(3-Hydroxy-3-methylpent-1-ynyl)-3-pentadecylphenol (5b)
Purified by column chromatography (n-hexane–EtOAc, 90:10).
13C NMR (50.3 MHz, CDCl3): d = 14.2, 22.7, 28.9, 29.4, 29.7, 31.9,
33.7, 55.3, 107.2, 114.3, 115.1, 115.4, 122.0, 130.2, 134.6, 134.8,
136.4, 141.2, 149.2, 160.0.
Oil; yield: 0.160 g (72%).
ESI-MS: m/z (%) = 570.5 (12) [M + 1]+, 568.5 (24) [M + 1]+, 556.6
IR (neat): 3330, 1450, 900 cm–1
(24) [M + 1]+, 212.1 (58), 211.0 (100).
1H NMR (200 MHz, CDCl3): d = 0.87 (t, J = 6.1 Hz, 3 H), 1.10 (t,
J = 7.5 Hz, 3 H), 1.25 (br s, 26 H), 1.57 (s, 3 H), 1.74 (q, J = 7.5 Hz,
2 H), 2.67 (t, J = 8.0 Hz, 2 H), 5.62 (s, 1 H), 6.57 (dd, J = 8.2, 2.6
Hz, 1 H), 6.65 (d, J = 2.6 Hz, 1 H), 7.25 (d, J = 8.2 Hz, 1 H).
Anal. Calcd for C28H40Br2O2: C, 59.16; H, 7.09. Found: C, 59.25;
H, 7.30.
3-Pentadecyl-2,4,6-tris[(E)-styryl]phenol (4f)
13C NMR (50.3 MHz, CDCl3): d = 9.1, 14.1, 22.7, 27.8, 29.0, 29.3,
29.5, 29.6, 29.7, 30.6, 31.9, 34.8, 36.7, 69.5, 78.1, 94.4, 112.8,
114.2, 115.7, 133.8, 147.1, 155.8.
A round-bottom flask was charged with a solution of Pd(OAc)2 (10
mg, 0.04 mmol), 2,4,6-triiodo-3-pentadecylphenol (2e; 0.296 g,
0.43 mmol), potassium b-styryltrifluoroborate (8; 0.327 g, 1.56
mmol), K3PO4 (0.551 g, 2.598 mmol) and n-Bu4NBr (0.012 g, 0.04
mmol) in EtOH (2 mL). The reaction mixture was stirred at 80 °C
until the iododerivative 2e was completely consumed (monitored by
TLC). The mixture was diluted with EtOAc (100 mL), the organic
layer was washed with H2O (10 mL) and the aqueous layer was ex-
tracted with EtOAc (3 × 10 mL). The combined organic layers were
washed with brine (30 mL) and dried (Na2SO4). After removal of
the solvent, the residue was purified by column chromatography on
silica gel (n-hexane–EtOAc, 99:1) to give pure 4f (0.160 g, 61%) as
a yellowish solid.
ESI-MS: m/z (%) = 383.56 (90) [M – H2O]+.
Anal. Calcd for C27H44O2: C, 80.94; H, 11.07. Found: C, 80.87; H,
10.88.
2,6-Bis(3-hydroxy-3-methyl-1-pent-1-ynyl)-3-pentadecylphe-
nol (5c)
A round-bottom flask was charged with a solution of PdCl2(PPh3)2
(3 mg, 0.004 mmol), CuI (0.002 g, 0.008 mmol), 2,4-diiodo-3-pen-
tadecylphenol (2d; 0.117 g, 0.2 mmol), 3-methyl-1-pentyn-3-ol (9;
0.053 g, 0.55 mmol) and Et3N (0.051 g, 0.55 mmol) in THF (2 mL).
The reaction mixture was stirred for 4 h at 60 °C then diluted with
EtOAc (100 mL). The organic layer was washed with H2O (10 mL),
and the aqueous layer was extracted with EtOAc (3 × 10 mL). The
combined organic layers were washed with brine (30 mL), dried
(Na2SO4) and the solvent was removed. The residue was purified by
column chromatography on silica gel (n-hexane–EtOAc, 90:10) to
give pure 5c (0.073 g, 70%) as an oil.
IR (KBr): 3520, 1460, 680 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.87 (t, J = 5.5 Hz, 3 H), 1.25 (br
s, 26 H) 2.80–2.95 (m, 2 H), 5.95 (s, 1 H), 6.64 (d, J = 17.9 Hz,
1 H), 6.95 (d, J = 14.9 Hz, 1 H), 7.21–7.44 (m, 19 H), 7.53 (s, 1 H).
13C NMR (50.3 MHz, CDCl3): d = 14.1, 22.7, 29.4, 29.7, 30.6, 31.9,
122.4, 122.7, 122.9, 123.1, 123.7, 125.6, 126.1, 126.5, 126.6, 127.3,
127.6, 127.9, 128.1, 128.6, 128.9, 129.2, 129.8, 130.0, 130.1, 135.8,
136.9, 138.1.
IR (neat): 3420, 1450, 700 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.88 (t, J = 6.7 Hz, 3 H), 1.09 (t,
J = 7.8 Hz, 6 H), 1.26 (br s, 27 H), 1.58 (s, 6 H), 1.99 (q, J = 7.8 Hz,
4 H), 2.69 (t, J = 7.8 Hz, 2 H), 6.72 (d, J = 7.9 Hz, 1 H), 7.14 (d,
J = 7.9 Hz, 1 H).
ESI-MS: m/z (%) = 609.5 (45) [M – 1]–.
Anal. Calcd for C45H54O: C, 80.94; H, 11.07. Found: C, 80.87; H,
10.88.
13C NMR (50.3 MHz, CDCl3): d = 8.3, 14.0, 24.4, 27.2, 29.5, 29.7,
30.5, 31.9, 32.9, 33.3, 66.6, 72.9, 81.9, 87.9, 101.9, 118.6, 124.8,
127.4, 128.4, 132.0, 136.4, 162.7.
Palladium-Catalysed Cross-Coupling of Iodo Derivatives 2a,b
with 3-Methyl-1-pentyn-3-ol (9); General Procedure
A round-bottom flask was charged with a solution of PdCl2(PPh3)2
(14 mg, 0.02 mmol), CuI (0.08 g, 0.04 mmol), the iodo derivative 2
(1.0 mmol), 3-methyl-1-pentyn-3-ol (9; 0.128 g, 1.3 mmol) and
Et3N (0.131 g, 1.3 mmol) in THF (2 mL). The reaction mixture was
stirred for 24 h at 60 °C then the mixture was diluted with EtOAc
(100 mL). The organic layer was washed with H2O (10 mL), and the
aqueous layer was extracted with EtOAc (3 × 10 mL). The com-
bined organic layers were washed with brine (30 mL) and dried
(Na2SO4). After removal of the solvent, the residue was purified by
column chromatography on silica gel eluting with n-hexane–EtOAc
mixtures to give corresponding pure product 5.
ESI-MS: m/z (%) = 497.39 (5) [M+], 441.44 (15), 405.25 (100).
Anal. Calcd for C33H52O3: C, 79.79; H, 10.55. Found: C, 79.80; H,
10.54.
2-(5,7-Dibromo-4-pentadecylbenzofuran-2-yl)butan-2-ol (6)
A round-bottom flask was charged with a solution of PdCl2(PPh3)2
(0.003 g, 0.004 mmol), CuI (0.002 g, 0.008 mmol), 4,6-dibromo-2-
iodo-3-pentadecylphenol (2f; 0.118 g, 0.2 mmol), 3-methyl-1-pen-
tyn-3-ol (9; 0.026 g, 0.26 mmol) and Et3N (0.026 g, 0.26 mmol) in
THF (2 mL). The reaction mixture was stirred for 24 h at 60 °C then
the mixture was diluted with EtOAc (100 mL). The organic layer
Synthesis 2006, No. 15, 2523–2530 © Thieme Stuttgart · New York

2530
A. Arcadi et al.
PAPER
was washed with H2O (10 mL), and the aqueous layer was extracted
with EtOAc (3 × 10 mL). The combined organic layers were
washed with brine (30 mL), dried (Na2SO4) and the solvent was re-
moved. The residue was purified by column chromatography on sil-
ica gel (n-hexane–EtOAc, 85:15) to give pure 6 (0.044 g, 40%) as a
white solid.
(8) Adimurthy, S.; Ramachandraiah, G.; Ghosh, P. K.; Bedekar,
A. V. Tetrahedron Lett. 2003, 44, 5099 and references
therein..
(9) Attanasi, O. A.; Buratti, S.; Filippone, P. Org. Prep. Proced.
Int. 1995, 6, 645.
(10) Edgar, K. J.; Falling, S. N. J. Org. Chem. 1990, 55, 5287.
(11) (a) Effenberg, F. Angew. Chem. Int. Ed. 2002, 41, 1699.
(b) Choi, H. Y.; Chi, D. Y. J. Am. Chem. Soc. 2001, 123,
9202.
(12) For a recent review on the palladium-catalysed cross-
coupling reactions, see: Nicolaou, K. C.; Bulger, P. C.;
Sarlah, D. Angew. Chem. Int. Ed. 2005, 44, 4442.
(13) Little, A. F.; Fu, G. C. Angew. Chem. Int. Ed. 2002, 41, 4176.
(14) Barder, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald, S.
L. J. Am. Chem. Soc. 2005, 127, 4685.
IR (neat): 400, 1450, 920 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.85–0.95 (m, 6 H), 1.25 (br s,
27 H), 1.59 (s, 3 H), 1.95–2.00 (m, 2 H), 2.86 (t, J = 7.9 Hz, 2 H),
6.66 (s, 1 H), 7.61 (s, 1 H).
13C NMR (50 MHz, CDCl3): d = 8.2, 14.1, 22.7, 26.3, 29.1, 29.3,
29.4, 29.7, 30.0, 31.9, 33.1, 34.2, 72.4, 101.3, 117.3, 127.5, 129.9,
134.4, 134.8, 163.9.
ESI-MS: m/z (%) = 561.74 (6) [M + 1]+, 559.61 (15) [M + 1]+,
(15) Arcadi, A.; Cacchi, S.; Marinelli, F.; Morera, E.; Ortar, G.
558.72 (27) [M + 1]+, 557.80 (35) [M + 1]+, 529.60 (100).
Tetrahedron 1990, 46, 7151.
Anal. Calcd for C27H42Br2O2: C, 58.07; H, 7.58. Found: C, 58.10;
H, 7.65.
(16) Guiso, M.; Marra, C.; Farina, A. Tetrahedron Lett. 2002, 43,
597.
(17) Amorati, R.; Pedulli, G. F.; Valgimigli, L.; Attanasi, O. A.;
Filippone, P.; Fiorucci, C.; Saladino, R. J. Chem. Soc.,
Perkin Trans. 2 2001, 2142.
Acknowledgment
(18) The antioxidant properties of 3a,c were determined by
kinetic measurements (inhibition rate constants Kinh M–1s–1);
The inhibition rate constants for 3a,c are 6.2 × 10–3 M–1s–1
and 6.5 × 10–3 M–1s–1, respectively. For comparison, the
inhibition rate constant of the commercial antioxidant 2,6-
di-tert-butyl-4-methylphenol (BHT) is 2.6 × 10–4 M–1s–1.
(19) Adimurthy, S.; Ramachandraiah, G. Tetrahedron Lett. 2004,
45, 5251.
(20) Talekar, R. S.; Chen, G. S.; Lai, S.-Y.; Chern, J.-W. J. Org.
Chem. 2005, 70, 8590.
(21) Suzuki, A. Chem. Commun. 2005, 4759.
(22) (a) Christmann, U.; Vilar, R. Angew. Chem. Int. Ed. 2005,
44, 366. (b) Dupont, J.; Consorti, C. S.; Spencer, J. Chem.
Rev. 2005, 105, 2527. (c) Miura, M. Angew. Chem. Int. Ed.
2004, 43, 2201.
(23) Shaughnessy, K. H.; DeVasher, R. B. Curr. Org. Chem.
2005, 9, 585.
(24) Moreno-Mannas, M.; Pajuclo, F.; Pleixatas, R. J. Org.
Chem. 1995, 60, 2396.
(25) Arcadi, A.; Cerichelli, G.; Chiarini, M.; Correa, M.; Zorzan,
D. Eur. J. Org. Chem. 2003, 4080.
Work was supported by the Ministero dell’Università e della Ricer-
ca Scientifica e Tecnologica, Rome, and by the University of
L’Aquila and the University of Urbino (Italy).
References
(1) Tyman, J. H. P. Synthetic and Natural Phenols; Elsevier:
Amsterdam, 1996.
(2) (a) Attanasi, O. A.; Filippone, P. Chim. Ind. (Milan) 2003,
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Synthesis 2006, No. 15, 2523–2530 © Thieme Stuttgart · New York