Synthesis of fragrance compounds from renewable resources: The aqueous biphasic hydroformylation of acyclic terpenes

Article abstract of DOI:10.1039/c4cy01020e

The rhodium-catalyzed hydroformylation of acyclic terpenic compounds, i.e., β-citronellene, linalool and nerolidol, was performed in a water/toluene biphasic system. The addition of the cationic surfactant cetyltrimethylammonium chloride remarkably increased the reaction rates, with the surfactant effect being substrate dependent. A water-soluble phosphine ligand was used to immobilize the rhodium catalyst in water, an environmentally benign solvent, whereas non-polar products were collected in the organic phase. A complete phase separation was easily achieved by switching the magnetic stirrer off and cooling the mixture to room temperature. Linalool and nerolidol gave cyclic hemiacetals with excellent stereoselectivity, whereas the hydroformylation of β-citronellene resulted in two isomeric aldehydes with a linear-to-branched product ratio of approximately 85/15. Several fragrance compounds with pleasant sweet floral and woody scents were obtained in high yields through a simple and green one-pot procedure starting from the substrates easily available from natural bio-renewable resources.

Full text of DOI:10.1039/c4cy01020e

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Synthesis of fragrance compounds from
renewable resources: the aqueous biphasic
hydroformylation of acyclic terpenes
Cite this: DOI: 10.1039/c4cy01020e
Camila G. Vieira, Marina C. de Freitas, Kelley C. B. de Oliveira, Amanda de Camargo Faria,
Eduardo N. dos Santos and Elena V. Gusevskaya*
The rhodium-catalyzed hydroformylation of acyclic terpenic compounds, i.e., β-citronellene, linalool and
nerolidol, was performed in a water/toluene biphasic system. The addition of the cationic surfactant
cetyltrimethylammonium chloride remarkably increased the reaction rates, with the surfactant effect being
substrate dependent. A water-soluble phosphine ligand was used to immobilize the rhodium catalyst in
water, an environmentally benign solvent, whereas non-polar products were collected in the organic
phase. A complete phase separation was easily achieved by switching the magnetic stirrer off and cooling
the mixture to room temperature. Linalool and nerolidol gave cyclic hemiacetals with excellent stereo-
selectivity, whereas the hydroformylation of β-citronellene resulted in two isomeric aldehydes with a
linear-to-branched product ratio of approximately 85/15. Several fragrance compounds with pleasant
sweet floral and woody scents were obtained in high yields through a simple and green one-pot procedure
starting from the substrates easily available from natural bio-renewable resources.
Received 6th August 2014,
Accepted 2nd October 2014
DOI: 10.1039/c4cy01020e
www.rsc.org/catalysis
modified cyclodextrins, supported aqueous phase catalysts
and surfactants, with the latter being one of the most practi-
Introduction
1
9–29
Terpenes are an important class of natural substrates widely
used in the flavor and fragrance industry.
natural aroma compounds contain an aldehyde group, the
hydroformylation of terpenes has been extensively studied
in attempts to obtain aldehydes and compounds derived
cal and effective alternatives.
Although anionic and non-
1
–4
Since many
ionic surfactants have been tested in the systems with indus-
trially used Rh-sulfonated phosphines showing some success,
cationic surfactants provide the most remarkable effects.
The positively charged moiety of the cationic surfactant
is directed to the aqueous phase, favoring the approach
of the anionic Rh-sulfonated phosphine complex to the
water/organic phase interface where the substrate can coordi-
5
–16
from aldehydes with interesting organoleptic properties.
However, the practical application of these processes faces a
general problem of homogeneous hydroformylation, which is
especially crucial for long-chain alkenes: the separation of
high-cost rhodium catalysts. The distillation of high-boiling
terpenic aldehydes in the presence of the catalyst could pro-
mote undesirable side reactions, the catalyst decomposition
and loss of the metal. Aqueous biphasic hydroformylation
represents one of the most promising strategies to overcome
the problem with the catalyst separation; however, it is seri-
ously restricted to short-chain alkenes due to the insufficient
water solubility of higher alkenes.
The alternatives to avoid transfer limitations in aqueous
biphasic hydroformylation and extend the substrate scope to
more hydrophobic alkenes have been recently revised. The
strategies include the use of co-solvents, amphiphilic ligands,
2
0,22
nate to the catalyst.
The hydroformylation of more abundant terpenes, such as
limonene, β-pinene and camphene, was quite extensively
5
–15
studied;
however, the data on the hydroformylation of
5
,30–36
β-citronellene, linalool and nerolidol are really scarce.
Acyclic monoterpenes β-citronellene (dihydromyrcene) and
linalool are produced commercially from one of the most
widespread monoterpene hydrocarbons, α-pinene, a cheap
major constituent of turpentine oils. Both compounds are
used for the industrial synthesis of various vitamins and/or
1
7
3
fragrance ingredients. In addition, linalool, a monoterpenic
1
8
allylic alcohol with a pleasant lily odor, is also found in the
essential oils of various plants, e.g., Brazilian rosewood and
Chinese Ho leaf oils. Nerolidol (also known as peruviol or
melaleucol), a sesquiterpenic allylic alcohol with a delicate
sweet floral woody odor and strong therapeutic potential, is
also available from various essential oils, which may contain
up to 50–90% of nerolidol.
Departamento de Química, Universidade Federal de Minas Gerais, 31270-901,
Belo Horizonte, MG, Brazil. E-mail: elena@ufmg.br; Fax: +553134095700;
Tel: +553134095741
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The hydroformylation of allylic alcohols is a simple and
two diastereoisomers, (2R,3R) and (2S,3R), as the molecule of
the starting β-citronellene has R configuration at asymmetric
carbon C-3 (Scheme 1). The diastereoisomers could not be
separated at GC analysis under the conditions used; however,
their NMR spectra were different.
In the present work, the hydroformylation of β-citronellene
was performed in a water/toluene biphasic system employing
the water-soluble combination of ijRhIJCOD)IJOMe)]2 and
TPPTS under conditions similar to those used in the homoge-
neous system. The results are presented in Table 1. In the
direct method for the synthesis of substituted tetrahydrofurans
since primarily formed hydroxyl aldehydes undergo a sponta-
neous intramolecular cyclization to give five-membered hemi-
acetals. The products resulting from the hydroformylation of
β-citronellene and linalool have been reported as promising
fragrance compounds with fresh floral and/or green citrus
5
odors, and those derived from nerolidol are known to pro-
3
5
vide perfume with the sweet smell of a natural flower.
In continuation of our ongoing project on valorization
of natural ingredients of essential oils, we report herein
for the first time the rhodium-catalyzed hydroformylation of
β-citronellene (1a), linalool (2a) and nerolidol (3a) in a water/
toluene biphasic system giving special attention to the effect
of the cationic surfactant cetyltrimethylammonium chloride
absence of the surfactant at 20 atm (CO/H = 1) and 80 °C, no
2
conversion of β-citronellene was observed after 2 h (Table 1,
run 1). The addition of small amounts of CTAC (2.5 mM, con-
sidering only the volume of the aqueous phase) promoted
the hydroformylation of β-citronellene at a slow rate resulting
in 10% conversion for 2 h (Table 1, run 2). The increase in
the surfactant amount resulted in a gradual increase in the
rate of the reaction which occurred with an excellent selectiv-
ity for aldehydes and a high linearity of ca. 85% (Table 1,
runs 2–5). In the presence of 50 mM of CTAC, a 2 hour reac-
tion resulted in 87% substrate conversion to give aldehydes
(
CTAC) on these reactions.
Results and discussion
We have studied the behavior of β-citronellene (1a), linalool (2a)
and nerolidol (3a) under hydroformylation conditions in a water/
toluene biphasic system using ijRhIJCOD)IJOMe)] as the catalyst
2
1
b and 1c with nearly 100% selectivity. The variation of the
precursor and a water-soluble tris(3-sulfonatophenyl)phosphine
trisodium salt (TPPTS) ligand to keep the catalyst dissolved
in the aqueous phase. Under hydroformylation conditions in
the biphasic system, all three substrates gave one or two
major products derived from the direct carbonylation of their
terminal double bonds. The substrates and corresponding
products are numbered in the present communication by the
same number with the addition of the letter “a” to indicate
the substrate and other letters to indicate the products
derived from this substrate. The total selectivity for the
hydroformylation products in most of the runs was 90–100%
for all substrates.
total pressure of the equimolar gas mixture had no signifi-
cant effect on the β-citronellene hydroformylation (Table 1,
runs 3, 6 and 7). It is noteworthy that switching the magnetic
stirrer off and cooling the reaction mixture to room tempera-
ture result in a rapid and complete phase separation. The
organic phase contains the products, whereas the rhodium
catalyst is well retained in the aqueous phase.
Thus, in the absence of the surfactant, no hydroformylation
of β-citronellene was observed in the biphasic system due to
the low solubility of the substrate in water where the rhodium
Hydroformylation of β-citronellene
The homogeneous hydroformylation of β-citronellene (1a)
occurred smoothly in toluene solutions in the presence of
t
PPh
3
or PIJO-o- BuPh)
3
under mild conditions as reported in
3
2
our previous publications. The linear aldehyde 1b was
formed as the major product (70–85% of the mass balance)
along with the branched isomer 1c detected as a mixture of
Scheme 1 Hydroformylation of β-citronellene (1a).
Table 1 Rhodium-catalyzed hydroformylation of β-citronellene (1a) catalyzed by Rh/TPPTS in an aqueous/toluene biphasic systema
b
Run
CTAC (mmol)
[CTAC] (mM)
P (atm)
Conversion (%)
Selectivity for aldehydes (%) (1b/1c)
1
2
3
4
5
6
7
0
0
2.5
20
20
20
20
20
60
80
60
0
10
40
46
87
36
35
8
—
0.01
0.05
0.10
0.20
0.05
0.05
0
100 (85/15)
100 (87/13)
100 (87/13)
100 (90/10)
98 (84/16)
100 (88/12)
100 (85/15)
12.5
25.0
50.0
12.5
12.5
0
c
8
a
−3
Conditions: β-citronellene, 2.0 mmol; ijRhIJCOD)IJOMe)]
2
, 2.5 × 10 mmol; TPPTS, 0.1 mmol; toluene, 10.0 mL; water, 4.0 mL; 80 °C; CO/H
2
=
b
1
/1; reaction time, 2 h. Conversion and selectivity are based on the substrate reacted. Considering the volume of the aqueous phase.
Reaction time, 6 h.
c
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−
3
catalyst was immobilized. However, the use of the cationic
surfactant allowed one to remarkably increase the reaction
rate. The presence of the surfactant above the critical micelle
concentration results in the formation of a micellar system
with a consequent increase in the interfacial area. The hydro-
phobic molecules of β-citronellene could be solubilized
within the hydrophobic cores of the micelles, thus leading to
water is rather modest (6.7 × 10 M at 25 °C), this value is
−
6
ca. 1000 times higher than that of β-citronellene (7.5 × 10
at 25 °C).
M
The addition of small amounts of CTAC drastically
increased the rate of the hydroformylation of linalool (Table 2,
run 3 vs. run 1). The reactions in the presence of 5.0–25.0 mM
of the surfactant were nearly completed in 2 h with no loss
in the product selectivity (Table 2, runs 4–6). Hemiacetal 2c
was formed in 93–97% chemoselectivity in all runs with an
excellent stereoselectivity of 97–99% for the cis isomer. In a
further study, we have decreased the temperature to slow
down the reaction and be able to more precisely follow the
surfactant effect. At low concentrations, the surfactant signifi-
cantly increased the reaction rate (Table 2, runs 1, 7 and 8);
however, further addition CTAC from 12.5 mM up to 50.0 mM
had only a slight effect on the substrate conversion (Table 2,
runs 8–11).
1
8a,23
the improvement in the mass transfer process.
Besides,
the cationic nature of the surfactant results in the increase in
the concentration of the Rh catalyst in the interfacial layer
due to the electrostatic attraction between the anionic sulfo-
nate group of the TPPTS ligand and the positively charged
micelle surface covered by the cationic moiety of the
1
8a,20,22
surfactant.
Considering the relative amounts of the
liquid phases used in the present work (water/oil ≈ 3/7), the
formation of reverse micelles, i.e., the small droplets of water
containing surfactant molecules on their surface suspended
in the non-polar medium, can also be possible.
2
A 3-fold decrease in the total pressure of the CO/H equi-
molar gas mixture had no significant effect on the hydro-
formylation of linalool, similarly to that observed with
β-citronellene (Table 2, run 12 vs. run 8). After the reaction in
run 13 (Table 2), the aqueous phase containing the catalyst
was separated under argon and reused 5 times without the
loss of activity and selectivity.
The inductively coupled plasma analysis showed <0.005 ppm
of rhodium in the organic phase after the first reaction in
run 13 (<0.008% loss of rhodium) and no rhodium after the
first recycling. To further verify the possible catalyst loss,
fresh linalool was added to the recovered organic phase and
the solution was placed in the autoclave under hydro-
Hydroformylation of linalool
The hydroformylation of linalool (2a) in toluene solutions
gave hemiacetal 2c as the main product (Scheme 2).
31,32
This
product formally results from the intramolecular cyclization
of the primarily formed hydroxy aldehyde 2b, which we have
never detected in the reaction solutions. The hemiacetal was
formed in the homogeneous system as a mixture of cis and
trans isomers with respect to the position of the methyl-
pentenyl and hydroxyl groups around the tetrahydrofuran
ring (Scheme 2), with the ratio between the isomers being
strongly dependent on the reaction variables.
formylation conditions (60 °C, 80 atm of CO/H = 1/1). No
2
In the biphasic system without the surfactant, at 60 atm
and 80 °C, the hydroformylation of linalool occurred slowly,
with 10% of the substrate being converted in 2 h (a standard
reaction time used for comparison in most of the runs) and
further conversion of linalool was observed, which indicated
the lack of significant rhodium leaching to the organic phase
during the biphasic process.
2
4% in 6 h (Table 2, runs 1 and 2). Although in homoge-
Hydroformylation of nerolidol
neous systems in toluene solutions, the rates of the hydro-
3
2
formylation of β-citronellene and linalool were similar, in
the biphasic system, linalool was much more reactive than
β-citronellene. Under the same conditions without the surfac-
tant, 24% of linalool was converted in a 6 hour reaction
There are two natural isomers of nerolidol (3a) which differ
in the geometry of the central double bond: cis IJZ-nerolidol)
and trans (E-nerolidol). The starting substrate was a mixture
of Z and E isomers with a ratio of ca. 40/60. The hydro-
3
6
(
Table 2, run 2), whereas the conversion of β-citronellene was
formylation of nerolidol in both homogeneous and biphasic
systems gave hemiacetal 3c as the main product (Scheme 3).
This product formally results from the intramolecular cycliza-
tion of the primarily formed hydroxy aldehyde 3b, which has
never been detected in the reaction solutions in our studies.
The stereoselectivity of the reaction was only slightly depen-
dent on the reaction variables, and hemiacetal 3c was formed
predominantly (almost exclusively in the biphasic system) as
Z-cis and E-cis isomers in the same Z/E proportion as the
starting substrate.
only 8% (Table 1, run 8). This can be explained by the higher
hydrophilicity of linalool, which allows the reaction to occur
not only in the interface water/organic medium but also in
the aqueous phase. Although the solubility of linalool in
The total selectivity for the hydroformylation products in
most of the runs was 90–95%, with only one minor product
being responsible for almost all the rest of the mass balance.
36
The minor product was identified in our previous work as a
non-functionalized sesquiterpenic acyclic triene, which formally
Scheme 2 Hydroformylation of linalool (2a).
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a
Table 2 Rhodium-catalyzed hydroformylation of linalool (2a) catalyzed by Rh/TPPTS in an aqueous/toluene biphasic system
b
Run
1
CTAC (mmol)
[CTAC] (mM)
T (°C)
Conversion (%)
Selectivity for 2c (%) (cis/trans)
0
0
0
0
2.5
5.0
80
80
80
80
80
80
60
60
60
60
60
60
80
10
24
72
97
98
98
43
58
59
68
71
55
35
33
44
40
41
41
95 (95/5)
95 (95/5)
94 (99/1)
95 (99/1)
93 (99/1)
93 (97/3)
93 (98/2)
94 (98/2)
93 (98/2)
93 (98/2)
90 (92/8)
91 (99/1)
97 (97/3)
97 (97/3)
96 (97/3)
97 (97/3)
97 (97/3)
96 (97/3)
c
2
3
4
5
6
7
8
9
0.01
0.02
0.05
0.10
0.01
0.05
0.10
0.15
0.20
0.05
0.25
12.5
25.0
2.5
12.5
25.0
37.5
50.0
12.5
62.5
1
2
3
4
5
1
1
1
1
0
1
2
3
d
d,e
st recycle
nd recycle
rd recycle
th recycle
th recycle
a
−3
2 2
Conditions: linalool, 2.0 mmol; ijRhIJCOD)IJOMe)] , 2.5 × 10 mmol; TPPTS, 0.1 mmol; toluene, 10.0 mL; water, 4.0 mL; CO/H = 1/1; 60 atm;
b c
reaction time, 2 h. Conversion and selectivity are based on the substrate reacted. Considering the volume of the aqueous phase. Reaction
time, 6 h. 20 atm. TPPTS (0.5 mmol). The aqueous phase containing the catalyst was separated under argon and used in recycling
experiments.
d
e
surfactant concentrations, the micelles begin to expand and
oil/water or water/oil microemulsions might be formed. Thus,
starting from a certain point, the increase in the surfactant
concentration does not result in a significant increase in
the interfacial area and the hydroformylation rate increases
only slowly. However, the fact that the hydroformylation of
β-citronellene has greatly benefited from the surfactant even
above the 12.5 mM concentration (a saturation value for
linalool and nerolidol) suggests that the effect of the surfac-
tant is substrate dependent.
Indeed, we have previously found that the optimal con-
centration of the surfactant (CTAC) at the hydroformylation
of terpenes in the biphasic water/toluene system strongly
Scheme 3 Hydroformylation of nerolidol (3a).
depends on the conformational characteristics of the sub-
strate and its capacity to accommodate among the surfactant
molecules in order to permeate through their layer and reach
3
7
resulted from the dehydration and monohydrogenation of
the nerolidol molecule.
the catalyst in the aqueous phase. In particular for acyclic
monoterpene myrcene, a significant promotion effect was
observed up to the CTAC concentration of ca. 25 mM; after
that, even a slight decrease in the reaction rate occurred. The
promotion by CTAC was less pronounced for monocyclic
monoterpene limonene and turned into an inhibition effect
In the absence of the surfactant at 20 atm and 80 °C, no
conversion of nerolidol was observed after 2 h (Table 3, run 1).
The addition of the surfactant gradually increased the reaction
rate (Table 3, runs 2–6). The reactions with 12.5–50.0 mM of
CTAC were nearly completed in 2 h (Table 3, runs 4–6). Hemi-
acetal 3c was formed in ca. 90% chemoselectivity with an
excellent stereoselectivity of 96–98% for the cis isomers. In a
further study, we have decreased the temperature to slow
down the reaction and be able to more precisely follow the
surfactant effect. The correlation was very similar to that
found for linalool: at low concentrations, the surfactant signifi-
cantly increased the reaction rate, whereas from 12.5 mM up
to 50.0 mM, there was only a slight effect (Table 3, runs 7–9).
The saturation of the surfactant effect observed for linal-
ool and nerolidol could be explained by the fact that at high
3
7
for the bulky bicyclic monoterpene camphene. The surfac-
tant accumulates in the interface water/oil region and the
substrate has to permeate the oriented membrane-like array
of the surfactant molecules to approach the catalyst sites.
For this reason, the excess of the surfactant can inhibit the
contact between the catalyst and the substrate and decrease
the hydroformylation rate.
A similar effect seems to operate for the molecules of
linalool and nerolidol compared to β-citronellene. Due to
their hydrophilic parts, the first two substrates are expected
to have more difficulty than the hydrophobic molecule of
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a
Table 3 Rhodium-catalyzed hydroformylation of nerolidol (3a) catalyzed by Rh/TPPTS in an aqueous/toluene biphasic system
b
Run
CTAC (mmol)
[CTAC] (mM)
T (°C)
Conversion (%)
Selectivity for 3c (%) (cis/trans)
1
2
3
4
5
6
7
8
0
0
2.5
7.5
80
80
80
80
80
80
60
60
60
60
80
0
45
85
90
95
96
48
49
57
75
30
—
0.01
0.03
0.05
0.10
0.20
0.05
0.10
0.20
0.05
0
90 (98/2)
91 (96/4)
91 (98/2)
90 (98/2)
91 (98/2)
92 (98/2)
92 (96/4)
94 (95/5)
90 (95/5)
96 (98/2)
12.5
25.0
50.0
12.5
25.0
50.0
12.5
0
9
1
1
c
0
1
d
a
−3
2 2
Conditions: nerolidol, 2.0 mmol; ijRhIJCOD)IJOMe)] , 2.5 × 10 mmol; TPPTS, 0.1 mmol; toluene, 10.0 mL; water, 4.0 mL; CO/H = 1/1; 20 atm;
b
reaction time, 2 h. Conversion and selectivity are based on the substrate reacted. Considering the volume of the aqueous phase.
c
−3
d
[
2
Rh(COD)(OMe)] , 5.0 × 10 mmol. Reaction time, 6 h; 60 atm.
β-citronellene to permeate through the hydrophobic part of
the surfactant layer that accumulated on the oil side of the
interface water/oil region. For this reason, the strong promot-
ing effect of CTAC for linalool and nerolidol is limited to the
This suggests that a rate-determining step at the nerolidol
hydroformylation in the biphasic system should involve
rhodium species (e.g., substrate coordination to rhodium);
however, the existence of mass transference limitations in the
system cannot be ruled out.
1
2.5 mM concentration. At higher concentrations, the surfac-
tant molecules become more densely packed at the interface
making the approximation of the substrate to the catalytic
centre more difficult. Thus, the increase in the CTAC concen-
tration and in the interfacial area is not fully accompanied by
the increase in the hydroformylation rate.
In order to compare the reactivity of all three terpenes in
the conventional biphasic system without the surfactant, the
reactions were run under the same conditions for 6 h. The
highest conversion was obtained for nerolidol (30%, Table 3,
run 11), followed by linalool (24%, Table 2, run 2) and
β-citronellene (8%, Table 1, run 8).
The total pressure of the equimolar gas mixture had no
significant effect on the hydroformylation of nerolidol (Table 4,
runs 1–3), which is similar to that observed for β-citronellene
and linalool. This could reflect a net result of the opposite
kinetic effects of the gas reagents as it was observed in homo-
Thus, among the acyclic terpenes studied, i.e. nerolidol,
linalool and β-citronellene, the first two substrates can be
hydroformylated in a conventional surfactant-free aqueous
biphasic system at a reasonable rate probably due to their
higher water solubility. The addition of CTAC resulted in a
significant increase in the rate of the hydroformylation of all
three substrates, with the effect being more pronounced for
the substrates with higher water solubility: linalool >
nerolidol > β-citronellene (6.70, 0.02 and 0.0075 mM, respec-
tively, at 25 °C). With small CTAC amounts (12.5 mM), the
reactions with nerolidol and linalool still occurred much
faster than that with β-citronellene (run 6 in Table 1 vs. run 5
in Table 2; run 3 in Table 1 vs. run 4 in Table 3). In the pres-
ence of CTAC, the reactions with linalool were faster than
those with nerolidol (run 12 in Table 2 vs. run 7 in Table 3;
run 8 in Table 2 vs. run 2 in Table 4), which is an inverse
3
1,32,36
geneous systems.
In homogeneous systems, a positive
order in hydrogen and a negative order in carbon monoxide
were found for all three substrates. The accelerating effect of
hydrogen suggested that the oxidative addition of hydrogen
to the rhodium acyl intermediate could be a rate-determining
step at the hydroformylation of these substrates in toluene
solutions. However, in the biphasic system, neither carbon
monoxide (Table 4, cf. runs 3–5) nor hydrogen (Table 4,
cf. runs 1 and 5; runs 3 and 6) partial pressure had a kinetic
effect on the hydroformylation of nerolidol. On the other
hand, we observed a strong positive kinetic effect of the con-
centration of the rhodium catalyst (Table 3, cf. runs 7 and 10).
a
Table 4 Rhodium-catalyzed hydroformylation of nerolidol (3a) catalyzed by Rh/TPPTS in an aqueous/toluene biphasic system: effect of pressure
Run
P (CO) (atm)
P (H
2
) (atm)
Conversion (%)
Selectivity for 3c (%) (cis/trans)
1
2
3
4
5
6
10
30
40
20
10
40
10
30
40
40
40
20
48
45
46
48
42
43
92 (98/2)
94 (99/1)
94 (99/1)
95 (99/1)
92 (96/4)
90 (98/2)
a
−3
Conditions: nerolidol, 2.0 mmol; ijRhIJCOD)IJOMe)]
2
, 2.5 × 10 mmol; TPPTS, 0.1 mmol; toluene, 10.0 mL; water, 4.0 mL; CTAC, 0.05 mmol,
12.5 mM; 60 °C; reaction time, 2 h. Conversion and selectivity are based on the substrate reacted.
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tendency compared to the system without CTAC. The reaction
rate for β-citronellene increases almost linearly with the addi-
tion of CTAC, whereas the surfactant effect on the hydro-
formylation of nerolidol and linalool becomes weaker at
higher CTAC concentrations. As a result, in the presence of
relatively high amounts of surfactant, the reactions with
β-citronellene and nerolidol occurred at comparable rates
reaction was carried out and cooled to room temperature, the
excess CO and H were slowly vented. In all experiments, the
2
emulsion was broken after cooling the mixture to room tem-
perature. In recycling runs, the aqueous phase containing the
catalyst was separated under argon and repeatedly used in
consequent runs.
The products were analyzed in the organic phase by gas
®
(run 5 in Table 1 vs. run 6 in Table 3, [CTAC] = 0.05 M).
chromatography (GC, Shimadzu QP2010, Rtx -5MS capillary
column, FID detector). Conversion and selectivity were deter-
mined by GC. The GC mass balance was based on the sub-
strate charged using dodecane as an internal standard.
The products were identified by GC-MS (Shimadzu
QP2010-PLUS instrument operating at 70 eV). The NMR and
MS data of the products were reported in our previous
Conclusion
The study of the rhodium-catalyzed hydroformylation of
β-citronellene, linalool and nerolidol in a water/toluene
biphasic system revealed a remarkable effect of the cationic
surfactant on the reaction rates. The reactions with all sub-
strates give the same products as in the corresponding homo-
geneous systems in toluene solutions and can be performed
under optimized biphasic conditions at reasonable rates.
A complete phase separation can be achieved by simply
switching the magnetic stirrer off after the reaction and
cooling the mixture to room temperature. Several fragrance
compounds can be obtained in high yields through a simple
and green one-pot procedure starting from the substrates
easily available from natural bio-renewable resources. It
is important to point out that the rhodium catalyst is
immobilized in water, an environmentally benign solvent,
and can be easily separated after the reaction from the prod-
ucts dissolved in the organic phase.
3
1,32,36
publications.
The rhodium content in the organic phase was measured
using a SPECTRO ARCOS ICP-OES (inductively coupled
plasma optical emission spectrometer). Reference solutions
−
1
of Rh (1000 mg L ) with a high degree of analytical purity
(ICP Standard, SpecSol) were used to obtain the calibration
curves. Deionized water (MILLI-Q) was used to prepare all
solutions. The organic medium was evaporated before the
sample digestion, which was carried out at 115 °C for 3 h
3
with 5 mL of HNO . The volume of the samples was then
adjusted to 10 mL using DI water. The rhodium content was
quantified in triplicate for each sample.
Acknowledgements
We acknowledge CNPq, FAPEMIG, and INCT-Catálise (Brazil)
for the financial support.
Experimental section
All chemicals were purchased from commercial sources and
used as received unless otherwise indicated. A mixture of Z and
E isomers of nerolidol ij3,7,11-trimethyl-1,6,10-dodecatrien-3-ol]
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