Heterogeneously Catalyzed Hydrogenation of Squalene to Squalane under Mild Conditions

Article abstract of DOI:10.1002/cctc.201402668

The full chemoselective hydrogenation of highly unsaturated all-trans linear squalene into valuable fully saturated squalane is achieved smoothly under mild conditions over the sol-gel-entrapped Pd catalyst SiliaCat Pd⁰. The catalysis is truly heterogeneous, and the catalyst is stable and recyclable, which opens the route to an easier and less expensive hydrogenation of squalene.

Full text of DOI:10.1002/cctc.201402668

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DOI: 10.1002/cctc.201402668
Heterogeneously Catalyzed Hydrogenation of Squalene to
Squalane under Mild Conditions
Valerica Pandarus,[a, b] Rosaria Ciriminna,[c] Serge Kaliaguine,*[b] FranÅois Bꢀland,*[a] and
Mario Pagliaro*[c]
The full chemoselective hydrogenation of highly unsaturated
all-trans linear squalene into valuable fully saturated squalane
is achieved smoothly under mild conditions over the sol–gel-
entrapped Pd catalyst SiliaCat Pd0. The catalysis is truly hetero-
geneous, and the catalyst is stable and recyclable, which
opens the route to an easier and less expensive hydrogenation
of squalene.
Introduction
Identified originally at the beginning of the 20th century by
Tsujimoto in deep-sea shark-liver oils, the terpenoid squalene
(Figure 1; C30H50) is a strong antioxidant (detoxifying), immuno-
protective, cholesterol-reducing, and anticarcinogenic agent
used widely in traditional medicine and, today, as a nutraceuti-
cal and cosmetic ingredient.[1] Capsules of shark-liver oil (which
contain squalene in concentrations of 40–80% by weight),
have been available commercially for decades.
common practice of stabilization through hydrogenation used
in the fats industry since the early 1920s.[2] Trade-named Cos-
biol by the French cosmetic ingredients company Laserson &
Sabetay, the fully saturated hydrocarbon “perhydrosqualene”,
which had already been synthesized by Tsujimoto in 1916,[3]
was adopted readily by cosmetic formulators because of its re-
markable properties that make it the best known emollient in
the cosmetic and personal care industries.[4]
Although squalene is highly comedogenic, the clear, color-
less, odorless, tasteless, very stable, and nonirritant oil squa-
lane[5] has a unique ability to penetrate the human skin[6] and
imparts flexibility and smoothness to the skin (without an un-
pleasant greasy feel). In addition to skin hydration, squalane in-
creases the absorption of other active substances dramatically.
For decades, the main raw material of squalane has been
the liver oil of small sharks from the deep sea. Approximately
25% of the weight of a deep-sea shark (average weight of
100 kg) is made up of its liver, which contains about 50% oil,
of which 80% is squalene. Squalene, with a purity of >98%, is
obtained directly from the liver oil after a single distillation
step under vacuum at temperatures of 200–2308C. Typically,
the livers of approximately 3000 sharks are required to pro-
duce 1 ton of squalene.
Figure 1. Chemical structure of squalene.
Squalane is the saturated hydrocarbon (2,6,10,15,19,23-hexa-
methyltetracosane, C30H62) obtained by full hydrogenation
of the highly unsaturated all-trans linear squalene
(6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,-
18,22-hexaene).
With six isolated double bonds, the 24-carbon backbone
squalene molecule that bears six methyl groups is very reactive
and unstable towards oxidation into undesirable peroxides.
Hence, in the early 1950s Sabetay extended to squalene the
The massive depletion of the deep-sea shark population led
the European Union to reduce the fishing of deep-sea species
by drastic quotas established in the late 1990s.[7] Required to
replace animal squalene with vegetable raw material, cosmetic
companies switched partly to squalane obtained from olive oil,
which has a squalene content of 0.4–0.6%.[8] As a result of its
low concentration, the extraction of squalene directly from
olive oil is not economically convenient. Gas effluents called
deodorization distillates (DDs) or oil physical refining conden-
sates (OPRC) recovered by condensation are instead used in
place of virgin oil. In detail, 100–300 g of squalene is obtained
per kg of ultrarefined distillate deodorizer oil.[9]
[a] V. Pandarus, Dr. F. Bꢀland
SiliCycle Inc.
2500, Parc-Technologique Blvd, Quebec City
Quebec, G1P 4S6 (Canada)
E-mail: FrancoisBeland@silicycle.com
[b] V. Pandarus, Prof. S. Kaliaguine
Department of Chemical Engineering
Laval University
Quebec City, Quebec, G1V 0A6 (Canada)
E-mail: Serge.Kaliaguine@gch.ulaval.ca
[c] R. Ciriminna, Dr. M. Pagliaro
As a result of unsustainable and expensive sources, in the
last decade squalane use has decreased to 2500 tons from
7500 tons, and recent selling prices are around $30 per liter.[10]
Istituto per lo Studio dei Materiali Nanostrutturati, CNR
via U. La Malfa 153, 90146 Palermo (Italy)
E-mail: mario.pagliaro@cnr.it
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More recently, however, a new phytosqualane product has en-
tered the market. In detail, squalane is obtained from the 15-
carbon sesquiterpene trans-b-farnesene derived from sugar-
cane sucrose fermentation over genetically modified Saccharo-
myces cerevisiae yeast strains.[11]
Recently, many efforts have been devoted to develop sinter-
proof hydrogenation catalysts using preprepared colloidal
metal nanoparticles with tuned size, shape, and composition
that are then “embedded” into porous support shells.[21] The
validity of this approach was shown by McFarland and co-
workers who compared the catalytic performance of Pd parti-
cles deposited either on the outer surface of silica (Pd/SiO2) or
encapsulated within the silica inner pores (Pd@SiO2).[22]
Farnesene is first converted into squalene by catalytic dime-
rization over a Pd catalyst, and squalene is hydrogenated sub-
sequently to squalane to produce a squalane composition that
comprises squalane 92–93% and approximately 4% isosqua-
lane.[12] Trade-named Neossance, sugarcane phytosqualane has
the potential to replace both olive oil and shark squalene as
one hectare of sugarcane plantation can produce up to
2500 kg of squalane.
In this context, we have introduced a new series of catalysts
that comprises noble-metal nanocrystals encapsulated within
the sol–gel cages of mesoporous organosilica xerogels. Trade-
named SiliaCat, these sol–gel catalytic materials are highly se-
lective mediators in a number of important reactions that in-
clude the highly selective hydrogenation of functionalized ni-
troarenes,[23] olefins,[24] and vegetable oils under a H2-filled bal-
loon (1 atm H2) at room temperature.[25] Now we report that
the Pd catalyst SiliaCat Pd0 is a highly selective mediator for
the low-temperature hydrogenation of squalene, which pro-
vides industry with a suitable low-cost process to make a sub-
stance of high demand, the sourcing and production of which
have to be made sustainable.
Whatever the origin, fully saturated squalane for cosmetic
use needs to have more than 92% concentration and an
iodine value lower than 1.00 (and preferably <0.10).[13] Such
high purity levels with commercial Ni-based catalysts require
relatively harsh conditions and extensive purification of the hy-
drogenated product over silica and other adsorbent materials,
which add cost to the hydrogenated product. A typical hydro-
genation process performed in industry makes use of
0.05 wt% nickel-Kieselguhr catalyst under 4 bar of H2 pressure
at 2008C.[14] No solvent is employed and, if the squalene is
from shark-liver oil, after 3–4 h the reaction is complete. Yet, if
the squalene originates from olive oil, the inevitable presence
of residual waxes requires harsher conditions and further pu-
rification.[15] Squalene is first “winterized” to precipitate wax.
Then, the process is performed in two steps: a first 3–4 h step
under 5 bar of H2 pressure, followed by 3 h at 30 bar H2 to
afford complete saturation, followed by further purification.
During the reaction over Ni-based catalysts, extensive bond
migration and dehydrogenation of squalene takes place.[16] Yet,
as the saturation of double bonds is sought, as it is common
in the food industry,[17] low-cost Ni catalysts remain used the
most widely in commercial operations, even though extensive
purification is required to remove most Ni leached into the
squalane product to meet maximum acceptable levels of toxic
Ni compounds (Ni2+ and Ni0) in a cosmetic product (0.2 ppm;
although out of 49 cosmetic products commercialized in
Canada, all were positive for Ni with an average content of
9 ppm).[18]
Results and Discussion
We first performed a series of experiments using a commercial
squalene sample (98 wt% purity, Aldrich) aimed to identify the
best solvent for the catalytic hydrogenation of squalene over
the SiliaCat Pd0 catalyst under a H2-filled balloon (1 atm H2) at
temperatures between 22 and 508C. The results shown in
Table 1 allowed us to identify the best procedures and the
best conditions, namely, 0.5 mol% SiliaCat Pd0 in ethanol
0.50m with respect to the squalene under 1 atm H2 at 508C.
The reaction was in each case truly heterogeneous because
the recovered solution obtained after the catalyst was re-
moved by filtration at 50% substrate conversion (hot filtration
test) showed no further activity from Pd leached in solution.
The reaction slows down if the squalene hydrogenation over
SiliaCat Pd0 is performed without solvent (Table 1, Entries 14
and 15). For instance, entry 14 shows that after 24 h at 308C,
only 66% of the squalene substrate (GC–MS, MW: 410) is con-
verted, which affords a mixture of intermediate hydrogenated
products identified by GC–MS (MW: 412; 414; 416; 418). If the
reaction temperature is increased to 508C (entry 15), after 24 h
the substrate conversion increased to 98% even though the
hydrogenation reaction remained nonselective and afforded
a mixture of intermediate hydrogenated products identified by
GC–MS (MW: 418; 420).
The other hydrogenation catalyst employed on an industrial
scale is Pd/C (5 wt%, with a loading of 0.25 mmolgÀ1 Pd). The
reaction is performed at approximately 150–1608C first under
3 bar and then 70 bar of H2.[12] In each case, the reaction tem-
perature is controlled by cooling to maintain the temperature
at 150–1608C.
Clearly, there is a need for better hydrogenation catalysts to
convert squalene into squalane at low pressure and tempera-
ture, especially now that vegetable squalene is poised to re-
place squalene of animal origin entirely. A large number of
supported Pd0 catalysts for heterogeneous C=C hydrogenation
reactions have been developed and are available commercially,
which include Pd/C, Pd/CaCO3, and Pd/Al2O3.[19] However, such
surface-derivatized catalysts, used normally for the synthesis of
vitamins and other highly functionalized fine chemicals, de-
grade rapidly to further add to the cost of the product.[20]
These results are explained by the significantly lower solubil-
ity of H2 in squalene oil compared to the squalene/ethanol
mixture, and are in full agreement with outcomes shown by
entries 1–8 that show a consistent increase in the yields to
squalane by increasing the EtOH volume and the reaction tem-
perature.[26] These conditions favor a higher solubility of H2 in
the reaction mixture and increase the accessibility of the reac-
tants to the active catalytic sites dispersed throughout the in-
ternal pore structure of the catalyst.
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cial squalene oil sample was also converted completely into
squalane, but the reaction was slower and took twice as long
(8 h).
Table 1. Effect of solvent on squalene hydrogenation over 0.5 mol% Silia-
Cat Pd0.[a]
Entry Solvent
(concentration [m])[b]
T
t
Conversion [%] Yield
However, if an 82 wt% pure olive squalene oil was tested
under the same reaction conditions, complete hydrogenation
and squalane formation was not observed. After 24 h of reac-
tion, only four double bonds were hydrogenated, and no fur-
ther reaction took place even at longer reaction times.
The influence of the amount of SiliaCat Pd0 catalyst on the
conversion of squalene using the 92 wt% squalene commercial
sample under the optimal conditions is shown in Figure 3.
[8C] [h] (yield [%])[c]
[%][d]
1
2
3
4
5
6
EtOH (0.25)
EtOH (0.25)
EtOH (0.25)
EtOH (0.33)
EtOH (0.33)
EtOH (0.50)
22
30
50
30
50
30
6
8
4
6
4
5
4
6
2
4
4
6
8
2
4
100 (24)
100 (71)
100 (53)
100 (100)
100 (71)
100 (100)
100 (62)
100 (100)
100 (72)
100 (100)
100 (30)
100 (75)
100 (100)
100 (70)
100 (99)
–
98.4
99.2
99.2
99.5
98.6
7
EtOH (0.50)
50
98.3
8
9
10
11
12
EtOH (0.75)
EtOH (1.0)
MeOH (0.50)
MeTHF (0.50)
50
50
50
50
24 100 (67)
24 100 (36)
–
–
–
–
–
8
8
4
6
8
100 (32)
100 (45)
100 (75)
100 (98)
95 (0)
MeTHF/EtOH 1:1 v/v (0.50) 50
13
iPrOH (0.50)
neat
neat
50
30
50
–
–
–
14[e]
15[e]
24
24
66 (0)
98 (0)
[a] Experimental conditions: 10 mmol squalene (98% purity), HPLC-grade
EtOH from 40 mL (0.25m squalene in EtOH) to 10 mL (1.00m squalene in
EtOH), and 0.5 mol% SiliaCat Pd0 catalyst (0.2 mmolgÀ1 Pd loading) under
a H2-filled balloon with magnetic stirring (800 rpm). [b] Squalene molar
concentration solutions in HPLC-grade solvent. [c] Conversion of the
squalene/squalane yield evaluated by GC–MS analysis. [d] Isolated yield.
[e] Without solvent.
Effects of the squalene purity
Squalane yields obtained if squalene samples of different
purity were hydrogenated under the identified optimal condi-
tions are presented in Figure 2. The 98 wt% pure squalene
commercial sample was converted into squalane completely
after 4 h (Table 1, entry 7). A less pure (92 wt%, VWR) commer-
Figure 3. Influence of the amount of SiliaCat Pd0 on the rate of squalene hy-
drogenation (92 wt% purity), for: a) 0.33 and b) 0.50m (molar concentration
of squalene ethanol solution).
If 0.5 mol% catalyst was used, the complete conversion to
squalane requires 8 h for both 0.50 and 0.33m squalene solu-
tions. However, over 1.0 mol% catalyst, almost complete con-
version of squalene to squalane was obtained in 4 h for the
0.33m mixture; and in 6 h for the 0.50m squalene solution in
EtOH. Again, the solubility of H2 in the reaction mixture is a cru-
cially important factor for the heterogeneous reaction under
the present mild H2 pressure conditions. We examined the in-
fluence of this parameter by scaling up the hydrogenation re-
action at 508C from 5 to 20 mmol squalene in a 0.33m squa-
lene solution in EtOH.
Early kinetic data shown in Figure 4 reveal that, for a 100 mL
round-bottomed flask capacity, the rate of squalene hydroge-
nation decreases with the increase of the volume of the reac-
Figure 2. Effect of squalene purity on the conversion to squalane over
0.5 mol% SiliaCat Pd0, 1 atm H2, 508C, 0.50m squalene in ethanol.
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substrate solution in a 100 mL round-bottomed flask (Fig-
ure 5a), for the 25 mmol substrate solution in a 250 mL round-
bottomed flask (Figure 5b), and with 50 mmol squalene in
a 500 mL round-bottomed flask (Figure 5c).
We used these conditions to examine squalene hydrogena-
tion for the olive squalene sample of 82 wt% purity. To our de-
light, now complete conversion to squalane could be obtained
also for this low-purity sample. In detail, the complete conver-
sion of squalene to squalane with 99.3% isolated yield re-
quired 8 h reaction.
Leaching and catalyst stability
To investigate the leaching of both Pd and Si from the SiliaCat
Pd0 catalyst during the reaction, we analyzed the crude solid
products by inductively coupled plasma optical emission spec-
troscopy (ICP-OES). In general, the measured values of leached
Pd and Si in the isolated crude product were <5 and
<10 ppm, respectively, independent of temperature, reaction
time, molar concentration, nature of solvent, and the amount
of catalyst used in the reaction (Table 2).
Figure 4. Performance of SiliaCat Pd0 in the scaled-up squalene hydrogena-
tion reaction from 5–20 mmol starting material in a 100 mL round-bottomed
flask.
tion mixture. In the hydrogenation of 5 mmol substrate in
a 17.5 mL reaction mixture (17.5% flask capacity), complete
conversion to squalane was obtained after 4 h with 99.6% iso-
lated yield. If 10 mmol substrate was reacted in 30 mL reaction
mixture (35% flask capacity), the complete conversion to squa-
lane was obtained after 5 h with 99.7% isolated yield.
Reusability of the solid catalyst
The same results were obtained if 15 mmol of squalene was
used in 52.5 mL reaction mixture (at 52.5% flask capacity).
However, if 20 mmol squalene was used in 70 mL of reaction
mixture (70% flask capacity), the complete conversion to squa-
lane required 7 h to afford 99.4% isolated yield. Again these
results may be explained by the lower solubility of H2 in the re-
action mixture if the gas–liquid contact surface is decreased.
We examined the reusability of the catalyst in the heterogene-
ous squalene hydrogenation for the 92% purity sample under
the optimal conditions (1 mol% SiliaCat Pd0, 0.33m squalene in
EtOH, 5 h, 1 atm H2 at 508C). The catalyst employed in the
20 mmol (8.22 g) substrate test was collected by filtration after
the first run, washed extensively (three times with EtOAc),
dried at room temperature, and reused in a subsequent run.
Overall, six consecutive runs were performed by recovering
and washing the catalyst each time as described above. After
each run, the heterogeneous catalyst was separated from the
reaction mixture and the solvent was evaporated. The leaching
of Pd and Si was assessed by ICP-OES analysis of the isolated
crude product in 1,1,2,2-tetrachloroethane solvent (concentra-
tion 100 mgmLÀ1). The results indicate that less than 0.002%
of the Pd in the initial catalyst was leached from the catalyst
inner pores.
Reproducibility of the heterogeneous reaction
The reproducibility of the reaction yield upon scale-up of the
reaction from 10–50 mmol squalene at 35% flask-volume ca-
pacity over 1 mol% SiliaCat Pd0 at 508C is shown in Figure 5.
The complete conversion of squalene to squalane was ob-
tained after 5 h reaction under a H2 balloon for the 10 mmol
In all five consecutive reactions, complete conversion was
obtained in 5 h (Figure 6). Then a slight decrease in activity
was observed that was compensated for by an increase of the
reaction time from 5 to 6 h. Clearly, the SiliaCat Pd0 heteroge-
neous catalyst was stable and robust, which is a crucially im-
portant factor for the practical application of a heterogeneously
catalyzed process using this new sol–gel-entrapped catalyst in
place of conventional Pd/C and Ni-Kieselguhr commercial cata-
lysts.
Conclusions
A recent investigative journalism analysis[27] found that the cos-
metic industry is still supplied largely with animal squalane,
and around 90% of world shark-liver oil production feeds the
needs of the cosmetics industry (which corresponds to 2.7 mil-
lion deep-sea sharks caught every year). Estimates from the
Figure 5. Reproducibility of yield upon scale-up of the squalene hydrogena-
tion reaction after 5 h reaction over 1 mol% SiliaCat Pd0: a) 10, b) 25, and
c) 50 mmol squalene in EtOH (0.33m; 35% flask volume capacity).
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Recently, Tran and co-workers lamented
that “very little work”[29] has been reported on
catalyst development for terpene hydrogena-
tion. For example, during the hydrogenation
of squalene over Ni and Pt catalysts (especial-
ly on Raney nickel) extensive bond migration
and dehydrogenation was observed as early
as of 1956.[16] As we continue to advance the
scope of these materials, we have shown that
the organosilica SiliaCat catalyst doped with
Pd0 nanocrystals is a highly active, selective,
and reusable catalyst for the hydrogenation
of squalene under remarkably mild condi-
tions, namely, 1 atm H2 pressure at 308C, or at
508C if shorter reaction times are needed,
which uses in each case an ultralow amount
of valuable catalyst (0.5–1.0 mol%).
Table 2. Pd and Si leaching from SiliaCat Pd0 in squalene hydrogenation under different
conditions.[a]
[d]
Entry Solvent
Catalyst amount T
t
Conversion [%] Yield Leaching [mgkgÀ1
]
(concentration [m]) [mol%]
[8C] [h] (yield [%])[b]
[%][c] Pd
Si
1
2
3
4
5
6
7
8
9
10
EtOH (0.25)
EtOH (0.25)
EtOH (0.25)
EtOH (0.33)
EtOH (0.50)
EtOH (0.75)
EtOH (1.00)
MeOH (0.50)
MeTHF (0.50)
MeTHF/EtOH 1:1
v/v (0.50)
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
22
30
50
50
50
8
6
6
4
4
100 (71)
–
1.22
n.d.
2.59
n.d.
100 (100)
100 (100)
100 (100)
100 (100)
98.4
99.2
99.5
99
–
–
–
–
–
0.73
1.69
0.39
0.75
0.82
1.80
3.06
1.45
2.65
2.54
3.51
2.45
2.03
2.20
6.30
2.35
50 24 100 (67)
50 24 100 (36)
50
50
50
8
8
6
100 (32)
100 (45)
100 (98)
11
iPrOH (0.50)
0.50
0.50
0.50
0.75
1.00
0.50
0.75
1.00
1.00
50
8
95 (0)
–
–
–
99.6
1.95
3.50
0.82
1.02
2.40
2.94
5.17
3.63
4.84
1.20
3.33
1.50
7.62
12[e] neat
50 24 98 (0)
13[f] EtOH (0.50)
14[f] EtOH (0.50)
15[f] EtOH (0.50)
16[f] EtOH (0.33)
17[f] EtOH (0.33)
18[f] EtOH (0.33)
19[g] EtOH (0.33)
50
50
50
50
50
50
50
8
7
6
8
6
5
8
100 (98)
100 (100)
100 (100)
100 (100)
100 (100)
100 (100)
100 (100)
99.4 <0.5
The extent of hydrogenation depends cru-
cially on the squalene purity. If squalene oil of
olive origin with a typically low (82%) purity
is used, the complete conversion requires the
use of a low flask-volume capacity (35%) to
increase the gas–liquid surface and enhance
the H2 dissolution in the ethanol solution.
99.5
99.6
99.6
99.3
1.50
2.00
1.68
1.15
[a] Experimental conditions: 10 mmol squalene (98 wt% purity) in EtOH from 0.25–1.00m
(molar concentration of squalene) and SiliaCat Pd0 from 0.5–1.0 mol% Pd catalyst (0.2 mmolgÀ1
Pd loading) under a H2-filled balloon at room temperature. [b] Conversion of squalene/squalane
yield evaluated by GC–MS analysis. [c] Isolated yield. [d] Leaching in Pd and Si assessed by ICP-
OES analysis of the isolated crude product in 1,1,2,2-tetrachloroethane (concentration
100 mgmLÀ1
)
and reported as mgkgÀ1 of product. (LODPd =0.50 mgkgÀ1 and LODSi =
Experimental Section
0.20 mgkgÀ1 in the crude product). [e] Without solvent. [f] Squalene of 92% purity was used.
[g] Squalene of 82% purity was used.
The squalene samples with different purities
(98 wt% from Aldrich, 92 wt% from VWR, and
82 wt% from an olive squalene manufacturer
based in Europe) were used as received. All or-
ganic solvents used were of HPLC grade and were used without
purification. All hydrogenation reactions were conducted under
1 atm H2. The organosilica SiliaCat Pd0 catalyst does not swell or
stick to the reactor surface and could be filtered easily and han-
dled and showed no tendency to ignite upon exposure to air.
Catalyst preparation
First described in 2011,[30] the preparation of SiliaCat Pd0 involves
the alcohol-free sol–gel polycondensation of alkoxysilanes such as
methyltrimethoxysilane (MTMS) and TEOS. The resulting SiliaCat
Pd0 catalyst is made of uniformly, highly dispersed Pd nanoparticles
(in the range 3–6 nm) encapsulated within an organosilica matrix.
The commercial catalyst used throughout the present catalytic ex-
periments has 0.2 mmolgÀ1 Pd loading (measured by using
a CAMECA SX100 instrument equipped with an electron probe mi-
croanalyzer; EPMA).
Figure 6. Reusability of the SiliaCat Pd0 catalyst in squalene hydrogenation.
sugarcane phytosqualane manufacturer, however, point to the
following 2012 global squalane market share: 46% olive oil,
44% shark-liver oil, and 10% sugarcane-derived squalane.[28]
As phytosqualene replaces squalene of animal origin, a new
heterogeneous hydrogenation process that can be performed
under low pressure and temperature is required urgently to
decrease the cost of the squalane. The current manufacturing
process, hydrogenation, accounts for approximately 40% of
the overall production cost.[14]
Hydrogenation reactions
Reactions were performed on a 10 mmol substrate scale. Conver-
sion was assessed by TLC analysis (hexane/EtOAc=5:1, using po-
tassium permanganate stain) and by GC–MS analysis. The squalene
substrate was added along with solvent (30 mL, 0.33m) into
a 100 mL round-bottomed two-necked flask, and then SiliaCat Pd0
(1.0 mol%) was added. The flask was charged with a stirring bar
and degassed four times, in which the vacuum was replaced twice
by Ar and twice by H2. The reaction mixture in the flask was con-
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sion MARE/2011/06 (SI2.602201), 2013: http://ec.europa.eu/fisheries/
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nected to a H2-filled balloon through a condenser and stirred vigo-
rously (800 rpm) at 508C until GC–MS analysis showed the maxi-
mum conversion. The catalyst was then collected by filtration and
rinsed with EtOAc (3ꢂ20 mL), and the filtrate was concentrated to
give a crude product.
Reusability test
The hydrogenation was performed at 508C in the presence of
1 mol% sol–gel catalyst. A 200 mL round-bottomed three-necked
flask connected to a H2-filled balloon through a condenser and
charged with a magnetic stirring bar, substrate (20 mmol), EtOH
(60 mL, 0.33m squalene concentration), and SiliaCat Pd0 was de-
gassed four times, in which the vacuum was replaced twice by Ar
and twice by H2. The reaction mixture was stirred vigorously at
508C for 5 h after which the catalyst was recovered by filtration,
rinsed with EtOAc (3ꢂ40 mL), dried under vacuum, and stored
under normal conditions before reuse. The filtrate was concentrat-
ed to give a crude product.
[18] Heavy Metal Hazard, The Health Risks of Hidden Heavy Metals in Face
Makeup, Environmental Defence, Toronto, May 2011: http://environ-
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[19] See for instance: The Catalyst Technical Handbook, Johnson Matthey,
2005, p. 24: http://www.jmcatalysts.com/pct/pdfs-uploaded/Pharma-
ceuticals%20Fine%20Chemicals/Catalyst%20Handbook%20EU.pdf.
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353, 1306–1316.
After each reaction run, the dried catalyst was weighed and the
amount of substrate and the volume of solvent were adjusted ac-
cordingly, by taking into consideration the catalyst loss during iso-
lation and work-up. The leaching of Pd and Si was assessed by ICP-
OES analysis (PerkinElmer Optima 2100 DV) of the isolated crude
product dissolved in 1,1,2,2-tetrachloroethane (concentration
100 mgmLÀ1). Values are reported as mg of metal per kg of prod-
uct. The ICP-OES limit of detection (the lowest quantity of a sub-
stance that can be distinguished from a blank value, LOD) was
LODPd =0.05 ppm in solution or 0.50 mgkgÀ1 in the crude product
and LODSi =0.02 ppm in solution or 0.20 mgkgÀ1 in the crude
product.
[24] V. Pandarus, G. Gingras, F. Bꢀland, R. Ciriminna, M. Pagliaro, Org. Process
Res. Dev. 2012, 16, 1230–1234.
Acknowledgements
[25] V. Pandarus, G. Gingras, F. Bꢀland, R. Ciriminna, M, Pagliaro, Org. Pro-
cess Res. Dev. 2012, 16, 1307–1311.
This article is dedicated to the Vice President of Sicily, Salvatore
Calleri, for all he is doing to start Sicily’s Solar Pole. Thanks to
Mr. Simon Bꢀdard and to Mr. Pierre-Gilles Vaillancourt from the
Quality Control Department of SiliCycle Inc. for their valuable
contribution to the adsorption measurements.
[26] In detail: At 308C, complete conversion of squalene to squalane was
obtained for 0.25 and 0.33m concentrations after 6 h (entries 2 and 4 in
Table 1), whereas 0.50m squalene required 8 h reaction time (entry 6). If
the temperature is increased from 30 to 508C, the complete conversion
to squalane is obtained after 4 h for both the 0.33 and 0.50m concen-
trations (entries 5 and 7). The conversion to squalane further decreases
with the increase of the substrate concentration in the reaction mixture
(entries 8 and 9) because of the lower solubility and diffusivity of H2
gas in the more concentrated reaction mixture. Entries 10–13 show the
results if other solvents, which include methanol, MeTHF, and isopropa-
nol, were tested at 508C for 0.5m squalene. Complete conversion to
squalane was obtained only in a 1:1 MeTHF/EtOH solvent mixture after
6 h (entry 12).
Keywords: encapsulation
·
heterogeneous catalysis
·
hydrogenation · palladium · squalene
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[4] The story of squalane in the cosmetic industry has been recounted re-
cently by one of the industry’s pioneers: F. Laserson, Expression Cosmꢀ-
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[6] Z. R. Huang, Y.-K. Lin, J.-Y. Fang, Molecules 2009, 14, 540–554.
[7] For a detailed discussion see a recent study: H. Ramos, E. Silva, L. Gon-
Åalves, Reduction of the deep-sea shark’s by-catches in the Portuguese
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Received: August 21, 2014
Published online on && &&, 0000
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FULL PAPERS
Sharkless squalane: Full chemoselec-
tive hydrogenation of highly unsaturat-
ed squalene into squalane is achieved
over a sol–gel-entrapped palladium cat-
alyst SiliaCat Pd0. The mild conditions
required (1 atm, 308C, 0.5–1.0 mol%
catalyst) and the catalyst stability and
recyclability are a step towards replac-
ing shark-liver oil as a source of squa-
lene in the medicinal and cosmetic in-
dustries with alternative sources such as
sugarcane.
V. Pandarus, R. Ciriminna, S. Kaliaguine,*
F. Bꢀland,* M. Pagliaro*
&& – &&
Heterogeneously Catalyzed
Hydrogenation of Squalene to
Squalane under Mild Conditions
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