Amphiphilic antioxidants from "cashew nut shell liquid" (CNSL) waste

Article abstract of DOI:10.1039/c0ob01040e

Hydrogenated cardanol and cardols, contained in industrial grade cardanol oil and obtained by distillation of the raw "cashew nut shell liquid" (CNSL), are easily transformed into efficient 4-thiaflavane antioxidants bearing a long alkyl chain on A ring a

Full text of DOI:10.1039/c0ob01040e

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Amphiphilic antioxidants from “cashew nut shell liquid” (CNSL) waste†
Riccardo Amorati,*a Orazio A. Attanasi,b Gianfranco Favi,b Stefano Menichetti,*c Gian Franco Pedullia and
Caterina Viglianisic
Received 17th November 2010, Accepted 22nd December 2010
DOI: 10.1039/c0ob01040e
Hydrogenated cardanol and cardols, contained in industrial
grade cardanol oil and obtained by distillation of the raw
“cashew nut shell liquid” (CNSL), are easily transformed into
efficient 4-thiaflavane antioxidants bearing a long alkyl chain
on A ring and a catechol group on B ring.
Fig. 1 Components of industrial grade cardanol oil.
nanotubes7 and fullerenes,8 or in fine chemistry for the preparation
of benzo[b]furanes.9 The alkyl phenol skeleton of compounds 1–
3 suggested their possible activity as lipophilic antioxidants, or
antiradicals, for the stabilization of plastics and other materials.
However, as expected, the ability of hydrogenated cardanol 1 (3-
n-pentadecylphenol), or cardols 2 (5-n-pentadecylresorcinol) and
3 (2-methyl-5-n-pentadecylresorcinol), as radical scavengers was
found to be too low in comparison to commercial antioxidants, as
BHT (2,6-di-t-butyl-4-methyl phenol, i.e. Butyl Hydroxy Toluene)
or related derivatives.10 We have recently demonstrated that hy-
droxy 4-thiaflavanes are efficient radical scavengers able to mimic
the mechanism of action of Flavonoids and Tocopherols, the two
more important families of natural polyphenolic antioxidants.11–16
This interesting peculiarity is achieved by assembling the 4-
thiaflanic skeleton through an inverse electron demand hetero
Diels–Alder reaction between an ortho-thioquinone, acting as
electron-poor diene, and a styrene used as electron-rich dienophile
(Scheme 1).17 We reasoned that, using derivatives 1–3 for the
formation of the ortho-thioquinone and the 3,4-dihydroxy styrene
as electron-rich alkene, respectively, we could build-up some new
4-thiaflavanes bearing a n-C15H31 aliphatic chain on A ring and
a catechol group on B ring. If successful, this strategy should
allow the connection of lipophilicity of the long n-C15H31 alkyl tail
with the antioxidant ability of the 1,2-dihydroxy phenyl (catechol)
moiety, an advantageous combination in the field of stabilizers as
well as in the prevention of lipid peroxidation.18–22
The manufacture of edible goods from vegetable sources quite
often causes the production of large amount of wastes. Their
disposal is a serious environmental problem but, at the same time,
these materials can be precious resources of organic renewable
substrates, which, regrettably, are frequently lost. The recovering
of such compounds by transformation into valuable chemicals
represents a ‘double green’ action since recycling a waste goes
along with the elimination of an expensive disposal. The shell
of the cashew nut (Anacardium occidentale L.) contains an
alkylphenolic oil internationally named “cashew nut shell liquid”
(CNSL), which constitutes nearly 25% of the total weight of the
nut, in turn produced in roughly 5 ¥ 105 tons per year.1,2 This
oil, derived from the roasting of the cashew nuts because of
the high edible value of the kernels, is composed of anacardic
acid, and smaller amounts of cardanol, cardol, and methylcardol,
and appears as a dark, partially polymerized tar-like stuff.3 In
all cases, the long alkyl chain may be saturated, mono- (8), di-
(8, 11), and tri-olefinic (8, 11, 14). Thermal treatment of cashew
nuts and CNSL induces the partial decarboxylation of anacardic
acid, which is completed by the subsequent purifying distillation.
The result is industrial grade cardanol, in the form of yellow oil
containing cardanol 1 (about 90%), with a smaller percentage of
cardol 2 and methylcardol 3 (Fig. 1).2
On the light of the above concepts, the possibility to use
cardanols as a renewable feedstock has been deeply investigated4
as well as its potential applications in the preparation of function-
alized polymers,5 or in material science, coupled with porphyrines,6
aDipartimento di Chimica Organica “A. Mangini” Universita` di Bologna, Via
S. Giacomo 11, 40126, Bologna, Italy. E-mail: riccardo.amorati@unibo.it;
Fax: +39-051-2095688
bCentro di Studio delle Sostanze Organiche di Origine Naturale, Universita`
di Urbino “Carlo Bo”, Via I Maggetti 24, 61029, Urbino, Italy
cDipartimento di Chimica “Ugo Schiff” Polo Scientifico e Tecnologico
Universita` di Firenze, Via della Lastruccia 3-13, 50019, Sesto Fiorentino,
Italy. E-mail: stefano.menichetti@unifi.it; Fax: +39-055-4573531
Scheme 1 Inverse electron demand hetero Diels–Alder disconnection
approach to 4-thiaflavanes.
† Electronic supplementary information (ESI) available: Experimetal de-
tails for the preparation of derivatives 8–10 and their precursors, equations
used to obtain kinh and additional oxygen consumption traces are available.
See DOI: 10.1039/c0ob01040e
Thus, following our original procedure, hydrogenated cardanol
1 was reacted with phthalimidesulfenyl chloride 4 (PhtNSCl, Pht =
Phthaloyl) in dry chloroform to obtain the corresponding less
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Scheme 2 Reagents and condition: a) PhtNSCl (4) 1 equiv, dry CHCl3, rt, 24h, 82%; b) Et3N 1 equiv, 6 1.5 equiv, dry CHCl3, 60 ◦C, 24h, 64%; c)
TBAF∑3H2O 2 equiv, dry THF, -10 ◦C, 1h, 98%.
hindered23 2-hydroxy-4-pentadecyl-N-thiophenyl phthalimide 5
in 82% yield. Reacting 5 with 1 equiv of Et3N in dry CHCl3
at 60 ◦C causes the formation of the corresponding ortho-
thioquinone which reacts with the bis-dimethyl-t-butyl-silylether
of 3,4-dihydroxystyrene 6 to give cycloadduct 7 isolated in 64%
yield. Desilylation of benzoxathiine 7 with 2 equiv of tetrabutyla-
◦
monium fluoride hydrate (TBAF∑3H2O) in dry THF at -10 C24
gave amphiphilic hydroxy thiaflavane 8 in nearly quantitative yield
as reported in Scheme 2. The reaction sequence was validated
transforming also the minor components 2 and 3 into the catechol
containing thiaflavanes 9 and 10 (Scheme 2).25
As it is reported below, we evaluated the antioxidant activity
of derivatives 8–10 by studying their ability to inhibit the
autoxidation of an oxidizable organic substrate (reactions 1–
Fig. 2 Hydrophilic and hydrophobic model radical scavengers used in
this study.
6). Data obtained were compared with those of cardanol 1,
pentamethyl chromanol 11, 4-methyl catechol 12 and 4-thiaflavane
1311,12 (Fig. 2).
Fig. 3 Plot of oxygen consumption observed during the autoxidation of
styrene (4.3 M) initiated by AIBN (0.05 M) at 30 ◦C without inhibitor
(U), inhibited by 12 (panel a, [12] = 6.3 mM), and inhibited by 10 (panel b,
[10] = 8.2 mM) in homogeneous solution (solid lines) and in the two-phases
system (dashed lines).
The rate constants for the reaction with peroxyl radicals (kinh
,
reaction 5) were measured by studying the autoxidation of styrene
at 30 ◦C, inhibited by small amounts (5–50 mM) of compounds 1
and 8–13 (see Fig. 3).26 Autoxidations, initiated by the thermal de-
composition of 2,2¢-azobisisobutyronitrile (AIBN), were followed
by measuring the oxygen uptake by a gas-recording apparatus
built in our laboratory which has been previously described.10 The
experiments were performed either in homogeneous solutions,
using chlorobenzene as solvent, or in a two-phases system,27
consisting of a mixture of water and styrene in 1 : 1 vol/vol
ratio. The oxygen consumption rate observed during the non-
inhibited autoxidation of styrene was not influenced by the
presence of water, indicating that reactions 1–6 take place in
the lipophilic phase (see ESI†). Therefore, the rate constants of
propagation (kp) and termination (2kt) of the styrene autoxidation
in the two-phases system were assumed to be equal to those
measured in homogeneous solution (41 M-1s-1 and 4.2 ¥ 107 M-1s-1
respectively).26,28
The values of kinh were obtained from the slope of the oxygen
consumption during the inhibited period (see ESI†), while the
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Table 1 Inhibition rate constants (kinh) obtained by studying the AIBN
initiated autoxidation of styrene at 303 K in homogeneous solution using
chlorobenzene (PhCl) as a solvent, or in the two-phases water/styrene
system
k
inh/105 M-1s-1
Styrene/PhCl
Styrene/H2Oa
kinh (H2O/PhCl)
1
ª0.1
ª0.1
1
8
4.8 0.4
7.0 0.5
3.9 0.4
5.2 0.5
5.3 0.5
0.8
0.7
0.9
1
0.07
<0.01
9
10
11
12
13
7
1
Fig. 4 Autoxidation scheme in the two-phase system.
32b
35
0.7 0.1
<0.1
3
9.4 0.5
6.8c
H2O was checked by measuring the UV-Vis absorbance of aqueous
solutions of 12 and 13 before and after the addition of an equal
amount of styrene, that is, under conditions similar to those used
in the autoxidation experiments. The molar fractions of 12 and
13 in the organic phase are 0.4 0.1 and 0.20 0.06 respectively,
indicating that these phenols are mainly in the H2O layer, while
their concentration in the lipophilic phase, where the autoxidation
takes place, is reduced.
a Concentrations of the reacting species are referred to the total volume of
the sample (styrene and H2O). b From ref. 26 c From ref. 14.
number of radicals trapped by each antioxidant (n) was determined
from the length of the inhibited period (t) by equation 7.
Rit
[AH]
The presence of the long alkyl chain in the cardanol or cardol
derivatives 8, 9 and 10 ensures their partitioning in the organic
phase, so that their kinh are more or less the same under the two
experimental settings. Although this model explains qualitatively
the experimental results, it may be noticed that the reactivity
decrease of 12 and 13 is larger than that expected on the basis
of their percentages in the organic phase, indicating that other
processes contribute in determining the kinh values.30 Further
work will be devoted to fully clarify these aspects, for instance
by using water-soluble initiators. The two-phases system used in
the present work can be considered a simplified model to study
antioxidants in biphasic or emulsified systems, as for instance
in cosmetics or foods. It is known that, in these cases, apolar
antioxidants are more active than their polar counterparts (the so
called “polar paradox”).31 On the basis of the present results, this
well-known observation can be explained in term of partitioning
of hydrophilic antioxidants in the aqueous phase, whereas the
autoxidation reaction takes place only in the organic layer. Of
course, in emulsified systems more complex phenomena are also
expected, such as the relevance of the diffusion of inhibitors among
the oil droplets, which gives rise to non-linear dependence of the
antioxdant activity on its lipophilicity.32
In conclusion, we have demonstrated that properly substituted
4-thiaflavanes, prepared using industrial cardanol oil components
as starting materials, are amphiphilic valuable antioxidants with
rate constants, for the reaction with peroxyl radicals, from 50
to 70 times higher than cardanol 1, independently from the
medium used, an apolar solvent or a 1 : 1 H2O/styrene mixture,
to run the measures. The goal of this study to transform a
waste into potentially useful fine chemicals has been achieved and
the ability of this new class of amphiphilic antioxidants as fat
stabilizers and/or lipid peroxidation inhibitors is currently under
investigation.
n =
(7)
The n coefficients showed no differences among the two experi-
mental settings, and were determined as 2.0 0.2 for compounds 8,
11 and 12, and 3.6 0.3 for compounds 9 and 10. As each phenolic
or catecholic moiety traps two ROO∑ radicals,26 this indicates that
in 9 and 10 the A and B rings act independently (catechin-like plus
tocopherol-like behaviour).11–15 In the case of weak antioxidants,
capable only to retard the oxygen consumption (kinh £ 105 M-1s-1,
see Table 1), n could not be determined.
From the kinh values collected in Table 1, it can be inferred that
in homogeneous solution all the synthesized compounds show
good antioxidant activity, and are much better antioxidants than
unmodified hydrogenated cardanol (1). This is due to the presence
of the catechol moiety, which efficiently donates H atoms to ROO∑
radicals in apolar solvents.29 Their reactivity is smaller than that
of 4-methylcatechol (12), probably because of the inductive effect
of the oxathiin endocyclic oxygen which reduces the electron
donating ability of the methyl group. The presence of additional
hydroxyl groups in 9 and 10 respect to 8 gives an additional
inhibiting activity, which can be seen at the end of the strong
induction period due to the catechol moiety (see Fig. 3B). From
the slopes of this retarded oxygen consumption, the kinh of the OH
groups on the ring A were estimated as about 1–2 ¥ 105 M-1s-1,
with no detectable differences between 9 and 10. If considering
the results obtained in the two-phases water/styrene system, the
synthesized compounds 8, 9 and 10 were found to possess a
stronger antioxidant activity compared to the reference phenols
12 and 13.
In Table 1 it is shown that this observation is due to a dramatic
reactivity decrease of 12 and 13 in the biphasic system, while
the reactivity of 8–10 remains almost unaffected. In the biphasic
system, inhibition constants calculated from the slopes of the
oxygen consumption traces actually depend on the molar fraction
of the antioxidant that is located in the lipophilic phase (Xlipo
)
Acknowledgements
as shown by the equation: kinh = Xlipo kinh¢. The value of kinh¢, the
inhibition constant in the lipophilic phase, is expected to be very
similar to that measured in styrene/chlorobenzene (see Fig. 4).
The relevance of antioxidant partitioning between styrene and
Financial support from MIUR (research projects “Radicals and
Radical Ions: Basic Aspects and Role in Chemistry, Biology,
and Material and Environmental Sciences” by R. A. and G. P.,
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and “Stereoselection in Organic Synthesis: Methodology and
Application” by S. M.) is gratefully acknowledged.
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