Preparation of functional styrenes from biosourced carboxylic acids by copper catalyzed decarboxylation in PEG

Article abstract of DOI:10.1039/c4gc00256c

A general protocol for the copper-catalyzed decarboxylation of α,β-unsaturated carboxylic acids in PEG, particularly of biosourced cinnamic acid analogues, is reported. Moderate to high isolated yields (31-96%) towards the styrene derivatives were obtained. For the first time, decarboxylation of α-amino acids to the corresponding amines was successfully performed with good to high yields and extended to the decarboxylation of a few condensed heterocyclic compounds. Both the use of PEG as a green solvent and direct separation of the pure product of the reaction by distillation permitted the reuse of the solvent and the Cu-based catalytic system over several cycles without deactivation. This was extended to the synthesis of 4-vinylguaiacol on the laboratory scale in an average 92% yield. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4gc00256c

Green Chemistry
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PAPER
Preparation of functional styrenes from
biosourced carboxylic acids by copper catalyzed
decarboxylation in PEG†
Cite this: Green Chem., 2014, 16,
3089
Stéphane Cadot, Nelly Rameau, Stéphane Mangematin, Catherine Pinel and
Laurent Djakovitch*
A general protocol for the copper-catalyzed decarboxylation of α,β-unsaturated carboxylic acids in PEG,
particularly of biosourced cinnamic acid analogues, is reported. Moderate to high isolated yields (31–96%)
towards the styrene derivatives were obtained. For the first time, decarboxylation of α-amino acids to the
corresponding amines was successfully performed with good to high yields and extended to the decar-
boxylation of a few condensed heterocyclic compounds. Both the use of PEG as a green solvent and
direct separation of the pure product of the reaction by distillation permitted the reuse of the solvent and
the Cu-based catalytic system over several cycles without deactivation. This was extended to the synthesis
of 4-vinylguaiacol on the laboratory scale in an average 92% yield.
Received 14th February 2014,
Accepted 21st March 2014
DOI: 10.1039/c4gc00256c
www.rsc.org/greenchem
ways to produce at the laboratory scale the required vinyl
compounds.23–26 Although they have indisputable practical
Introduction
Functional styrenes, such as vinylphenols, represent a specific aspects the latter procedures remain limited to gram scale pro-
class of styrene.1 They received particular attention due to duction. A solution can be the development of transition-
their widespread applications in polymer, pharmaceutical, metal (i.e.: TM) catalyzed decarboxylation procedures that can
agrochemical and food industries.2–6 Despite their availability be easily implemented in chemical industries.
from petrochemical and/or natural sources, the increasing
Modern TM-catalyzed decarboxylation methodologies were
demand from the chemical industries is not fully satisfied. To developed under the impulsion of Goossen’s group as a part
circumvent this situation many synthetic routes have been of the Pd/Cu-catalyzed decarboxylative cross-coupling
described but most of them required either toxic and expens- reactions.27–30 Limited to the strict protodecarboxylation
ive reagents or harsh reaction conditions.7–11 Additionally, methodologies, these studies focused particularly on the
when dealing specifically with phenol derivatives, protection/ copper-catalyzed transformation of substituted benzoic
deprotection procedures are often necessary.
acids,31–33 and only a few examples related to cinnamic deriva-
A more elegant route to access functional styrene derivatives tives were reported. Goossen’s group initially described a Cu-
is the decarboxylation of cinnamic acid derivatives like couma- catalyzed efficient procedure for the protodecarboxylation of
ric, ferulic or sinapic acids. These compounds are readily avail- various benzoic acids (i.e. 5 mol% Cu2O, 10 mol% 1,10-phen-
able from renewables either as extracts from annual plants12–15 anthroline, 4 equiv. quinoline, NMP, 170 °C).34 However, this
or as by-products from lignin depolymerization.16
procedure failed to convert some o-substituted or hetero-
Decarboxylation of such conjugated acid derivatives is gen- benzoic acids as well as cinnamic derivatives. Goossen et al.
erally conducted by microbial,17–19 biocatalytic,20 acid21 or developed a silver catalyzed procedure (i.e. 5 mol% AgOAc,
base22 (i.e. high temperature chemical) pathways. Besides 15 mol% K2CO3, NMP, 120–160 °C) to successfully perform the
these classical routes, the microwave-assisted base-catalyzed Cu-catalyzed methodology.35 Under such conditions, cinnamic
decarboxylation procedures are subject to intensive develop- acid gave the corresponding styrene with good conversion
ments since they can be considered as ecofriendly and rapid (76%). Interestingly, Zou and co-workers recently reported the
protodecarboxylation of various 2,3-diaryl acrylic acids using a
CuI/1,10-phenanthroline/PEG-400 system under microwave
Université de Lyon, CNRS, UMR 5256, IRCELYON, Institut de recherches sur la cata-
conditions giving generally good to high yields of the expected
stilbene derivatives.36
lyse et l’environnement de Lyon, 2 avenue Albert Einstein, F-69626 Villeurbanne,
France. E-mail: Laurent.Djakovitch@ircelyon.univ-lyon1.fr; Fax: +33472445399;
The field was recently extended to gold catalysis by Nolan
and co-workers who described gold-catalyzed decarboxylation
Tel: +33472445381
†Electronic supplementary information (ESI) available. See DOI:
of aromatic carboxylic acids using gold(I)-N-heterocyclic
10.1039/c4gc00256c
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carbene complexes that led to the corresponding gold(I)-aryl
complexes (i.e. [Au(IPr)(OH)] (with IPr: (1,3-bis(2,6-diisopropyl-
phenyl)imidazol-2-ylidene)), 1,4-dioxane, 110 °C, 1–70 h).37
This catalyst is tolerant to a wide range of aryl and heteroaryl
substrates; however, from the first reported data no proto-
decarboxylation occurred due to the formation of stable gold
complexes and the synthetic applications toward the corres-
ponding ArylH were limited. Recently, while revisiting the
reaction conditions (i.e. 2 mol% [Au(SIPr)(O2CAd)] (with SIPr:
1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene) and
Ad: adamantyl), anhydrous toluene or DMAc, 120–165 °C,
16–20 h) the authors reported a new procedure for transform-
ation of aromatic carboxylic acids to ArH in moderate to good
yields (46–97%) but it was not applied to the transformation of
cinnamic derivatives.38
In the field of our ongoing research toward greener syn-
thesis of styrene, stilbene and bibenzyle derivatives,3,4,7,8,39–46
we are interested in evaluating the synthesis of various func-
tional styrenes from biosourced substrates. To achieve the pro-
cedure in agreement with environmental concerns, studies
aiming at decarboxylating selectively cinnamic acids under
TM-catalysis and optimizing the reaction conditions were
realized.
Fig. 1 Evaluating various TM-salts for the protodecarboxylation of
cinnamic acid. Reaction conditions: cinnamic acid (0.5 mmol), [Ag]- or
[Cu]-catalyst (0.6 mmol), 1,10-phenanthroline (when mentioned,
0.05 mmol), K2CO3 (when mentioned, 0.6 mmol), NMP (5 mL), 150 °C,
16 h. The yield is determined by GC using dodecane as an external stan-
dard for quantitative determination.
Table 1 Improving the catalytic activity by adding a ligand
Entry
Ligand (mol%)
Base
Yielda (%)
1
2
3
4
5
6
7
1,10-Phenanthroline (10)
2,2′-Bipyridine (10)
2,2′-Bipyridine (20)
—
—
—
—
83
59
76
93
74
95
5
Results and discussion
2,2′-Bipyridine (30)
The activity of various silver and copper salts used in stoichio-
metric amounts in the decarboxylation of the cinnamic acid
(Scheme 1) was initially evaluated. In the absence of an
additional ligand, no reaction was observed in the presence of
Cu or Ag salts under neutral conditions. However addition of a
base leads to the formation of styrene with up to 23% yield in
the presence of Ag2CO3. Moreover, Fig. 1 clearly demonstrates
that among the TM-salts used, Ag2CO3 and Cu(OH)2 associated
with the 1,10-phenanthroline ligand gave the highest yields of
the corresponding styrene of 60% and 79%, respectively. Other
silver and copper salts, despite the addition of K2CO3 and
1,10-phenanthroline, did not give such an activity.
In view of these results, given the highly positive influence
on the reaction yields of adding
(0.05 mmol) of 1,10-phenanthroline as a ligand, we next
turned to develop a Cu-catalyzed procedure by associating
Cu(OH)2 with various ligands, possibly in the presence of a
base (Table 1).
1,10-Phenanthroline (10)
1,10-Phenanthroline (10)
1,10-Phenanthroline (10)
Quinoline
TMEDA
K2CO3
Reaction conditions: cinnamic acid (0.5 mmol), [Cu(OH)2] (10 mol%),
ligand (when mentioned, 10–30 mol%), base (when mentioned,
0.5 mmol), NMP (5 mL), 150 °C, 16 h. a The yield was determined by
GC using dodecane as an external standard for quantitative
determination.
Cu(OH)2 versus 1 equiv. with 1,10-phenanthroline). Interest-
ingly, addition of TMEDA as a base to the Cu(OH)2/1,10-phen-
anthroline catalytic system allowed us to achieve a quantitative
conversion and high yield toward the corresponding styrene
(entry 6), a trend already observed by Cahiez and co-workers in
a study related to the protodecarboxylation of benzoic acids.33
Surprisingly, addition of potassium carbonate inhibited the
catalytic activity (entry 7), despite the good results observed
with Malachite (i.e. CuCO3·Cu(OH)2, Fig. 1).
a catalytic amount
The results show that the Cu(OH)2/1,10-phenanthroline
system can be used catalytically (10 mol%) without any loss of
activity reaching 83% yield (Table 1, entry 1) versus 79% when
Cu(OH)2 is used in a stoichiometric amount (Fig. 1). The use
of 2,2′-bipyridine allowed us to achieve almost a quantitative
yield (entry 4), however with an excess of ligand (3 equiv./
Further optimizations were achieved by evaluating the influ-
ence of the solvent. While good results were observed in NMP,
other solvents were evaluated due to greener characteristics
(Fig. 2a and 2b). Two catalytic systems were evaluated:
Cu(OH)2/1,10-phenanthroline (1 : 1; 10 mol%) and Cu(OH)2/
2,2′-bipyridine (1 : 2; 10 mol%).
Among “classical” solvents used (Fig. 2a), regardless of the
catalytic system, NMP and DMAc gave the highest yields of
styrene of 97% and 89%, respectively. Water completely inhi-
bits the catalytic activity and acetonitrile or benzonitrile gave
poor results (resp. ca. 15% and ca. 10%) with both systems.
Scheme 1
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Fig. 2 Optimisation of the solvent in the decarboxylation of cinnamic acid. Reaction conditions: cinnamic acid (0.5 mmol), Cu(OH)2 (10 mol%),
■
■
ligand: ( ) 1,10-phenanthroline (10 mmol%) or ( ) 2,2’-bipyridine (20 mol), solvent (5 mL or 5 g for PEGs), 150 °C, 16 h. The yield is determined by
GC using dodecane as an external standard for quantitative determination. * PEG BioUltra grade was used.
The different yields observed between the two catalytic systems
(i.e. Cu(OH)2/1,10-phenanthroline (1 : 1; 10 mol%Cu or
Table 3 Influence of adding water to the reaction mixture on the yield
of styrene
)
Cu(OH)2/2.2′-bipyridine (1 : 2; 10 mol%Cu) could be related to
the relative stability of the intermediate {Cu/ligand} complexes
in the chelating solvent.
Water content
Entry
Amount of added water (μL)
mg
mmol
Yield (%)a
Interestingly, while the yield of styrene is clearly lower,
PEG-2000 used as the solvent gave useful results regarding the
environmentally friendly features. This encourages us to evalu-
ate different PEG-solvents varying their molecular mass or
purity grade (Table 2, Fig. 2b). The results showed that higher
purity (i.e. PEG-2000 BioUltra grade for molecular biology
versus “standard” PEG-2000; Fig. 2) as well as higher molecular
mass (i.e. PEG BiolUltra grade with MW varying from 2000 to
6000 g mol−1) allowed us to increase considerably the catalyst
activity. Thus, in PEG-6000 BioUltra grade, 91% yield of styrene
using the Cu(OH)2/1,10-phenanthroline (1 : 1; 10 mol%) was
obtained. The differences observed can be correlated both
with the presence of protic impurities as water traces and the
number of terminal hydroxy groups (that is related to the
average molecular mass for each PEG) that are detrimental to
the catalytic activity or stability. This conclusion is supported
by further experiments in which a controlled amount of water
was added in the reaction mixture (Table 3). These results
clearly indicate that an increase of the water content results in
decreased reaction yields.
1
2
3
0
50
113
12.5
62.5
125
0.7
3.5
6.9
87
44
32
Reaction conditions: cinnamic acid (0.5 mmol), Cu(OH)2 (10 mol%),
1,10-phenanthroline (10 mmol%), PEG-2000* (5 g), 150 °C, 16 h. a The
yield was determined by GC using dodecane as an external standard
for quantitative determination.
leading to the highest chemical yields (Fig. 3). In both NMP
and PEG-6000*, an induction period of ca. 1 hour was
observed and attributed to the complexation of Cu(OH)2 by the
1,10-phenanthroline ligand and to the dissolution of the
copper salt. It was observed experimentally that insoluble
copper species initially present were solubilized in the reaction
medium (i.e. after 1 hour at 150 °C only 8% of introduced
We were next interested in comparing more deeply the
activity of the Cu(OH)2/1,10-phenanthroline (1 : 1; 10 mol%)
catalytic system in both NMP and PEG-6000*, the two solvents
Table 2 Analytic al data for PEGs (from suppliers, see the ESI for more
details)
Number of hydroxyla
(mg KOH g−1
)
Fig. 3 Yield of styrene versus the time for the {Cu(OH)2/1,10-phen-
anthroline (1 : 1)} catalytic system. Reaction conditions: cinnamic acid
(0.5 mmol), Cu(OH)2 (10 mol%), 1,10-phenanthroline (10 mol%), solvent
(5 mL for NMP or 5 g for PEG-6000*), 150 °C. For the “PEG-6000* pre-
mix” experiment, Cu(OH)2 and 1,10-phenanthroline were mixed together
in PEG-6000* at 150 °C for 1 h before adding the cinnamic acid. The
yield is determined by GC using dodecane as an external standard for
quantitative determination.
Solvent
Theoretical
Experimental
Water contentb (wt%)
PEG-2000
PEG-600*
PEG-2000*
PEG-6000*
56
187
56
51–62
172–204
51–62
0.5
Not provided
0.25
0.16
19
17–22
a Test method: ASTM D – 4252. b Test method: ASTM D – 1744.
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Cu(OH)2 was solubilized in the absence of ligand, versus >99% 1,10-phenanthroline in PEG gave, after reduction of Cu(II)- to
in the presence of 1,10-phenanthroline). Then, the reaction Cu(I) species, probably by some of the remaining hydroxyl
rate increased to give finally 95% and 85% yield after 24 h, groups of the solvent, a {Cu(I)(1,10-phenanthroline)(OH)}-
respectively. Interestingly, the TOF of the catalytic system was complex A. This complex A reacts with the cinnamic acid to
slightly affected by the solvent raising 1.9 0.2 h−1 in both give a carboxylate intermediate B releasing water in the reac-
NMP and PEG-6000* (Fig. 3) making PEG particularly interest- tion medium before leading to decarboxylation under the reac-
ing given its non-toxicity compared to NMP. Under these con- tion conditions to provide a organo-copper derivative C. Either
ditions, we were able to develop
separation of styrene directly under low vacuum, giving the namic acid, C forms the expected styrene regenerating either
pure compound in 59% isolated yield. the initially active complex A (cycle I) or carboxylate intermedi-
a procedure allowing upon hydrolysis, or by reaction with a new molecule of cin-
In order to gain deeper insights concerning the induction ate B (cycle II) engaging thus a new catalytic cycle (Fig. 4). This
period observed in previous experiments, we conducted a test proposed mechanism can also explain the inhibitory effect
in PEG-6000* in which the catalytic system (Cu(OH)2/1,10-phen- observed in the presence of water, assuming that cycle II is
anthroline (1 : 1; 10 mol%)) was pre-mixed for 1 hour at 150 °C more efficient that cycle I.
before adding the cinnamic acid, setting at this time the reac-
This preliminary work validates the catalytic decarboxyla-
tion time to t = 0 (Fig. 3, PEG-6000* pre-mix). During the pre- tion of cinnamic acid in the presence of the copper complex.
mixing time, formation of metallic copper in the form of Then, we evaluated the scope and limitations of the procedure
copper mirror was observed. After addition of cinnamic acid, involving continuous distillation of the product from the reac-
the first period was observed during which the reaction rate tion medium. We engaged in the reaction various substituted
remains limited to 0.6 0.1 h−1. This rate closely corresponds cinnamic and benzoic acids working on a 15 mmol scale in
to the one observed during the induction period for the reac- the presence of only 5 mol% catalytic metal (i.e. carboxylic acid
tions conducted in NMP or PEG-6000* without pre-mixing. (15 mmol), Cu(OH)2/1,10-phenanthroline (1 : 1;
5 mol%),
After this time, dissolution of the metallic copper was observed PEG-6000 (20 g)). To face with the difference in reactivity of the
and the reaction rate increased to reach finally 1.8 0.2 h−1 various carboxylic acids involved in this set of experiments, the
like in the experiment performed in PEG-6000* without reaction mixture was heated up to the effective reaction temp-
pre-mixing.
erature (i.e. 130–230 °C) as attested by CO2 release and carried
These results suggest that the induction period observed in out under vacuum (i.e. 0.5–1 mbar) until no more product is col-
these experiments is not only due to the dissolution of the lected in the collecting flask, corresponding to complete conver-
original Cu(OH)2 to give with 1,10-phenantroline a soluble sion of the substrate. The results are summarized in Table 4.
copper complex, but also to the reduction of Cu(II)- to active
Considering cinnamic derivatives (entries 1–9), except for
Cu(I)-species, these being suspected from the pre-mix experi- p-coumaric acid and caffeic acid that did not give the expected
ment. To support this hypothesis, an experiment with Cu2O as compounds under the reaction conditions due to rapid
the Cu(I)-source was carried out (Fig. 4). In that case, no induc- polymerization (entries 6 and 5, respectively), useful to good
tion period was observed and the initial reaction rate reached yields were achieved for all evaluated substrates. The main
1.3 0.1 h−1 in the same range as in previous experiments.
difficulty remains the effective and rapid separation of the
A reaction mechanism is proposed (Fig. 5) to explain the pure substituted styrene derivative prior to its polymerization
observed results and is in agreement with previous reports in in the reaction flask.
the literature.36,38 Initially, the mixture of Cu(OH)2 and
The decarboxylation methodology was found to be efficient
to convert nitrobenzoic acids (entries 10–12) in shorter reac-
tion time compared to the reported procedure using Cu2O or
AgOAc in the case of the ortho derivative (entry 10 versus 1334
and 14,35 respectively). Interestingly, the procedure gave
encouraging results when engaging sorbic acid that gave the
corresponding 1,3-pentadiene, however in a non-optimized
limited 14% yield despite its direct separation, mainly due to
its loss under vacuum (entry 15). For the first time, we report
here the direct Cu-catalyzed decarboxylation of α-amino acids.
DL-Phenylalanine and DL-tyrosine gave the corresponding
amines, respectively the 2-phenylethylamine and the
4-(2-aminoethyl)phenol both in 68% yields (entries 16 and 17).
L-Valine, D-leucine and DL-methionine gave reaction mixtures.
In the case of L-valine, the distillate contains a mixture of three
compounds that were quantified through 1H NMR and GC-MS:
the starting L-valine (ca. 45%), the expected 2-methylpropan-
1-amine47 (ca. 45%) and the third product identified as
Fig. 4 Yield of styrene versus the time for the {Cu(OH)2/1,10-phen-
anthroline (1 : 1)} catalytic system. Reaction conditions: cinnamic acid
(0.5 mmol), Cu2O (10 mol%), 1,10-phenanthroline (10 mol%),
PEG-6000* (5 g), 150 °C. The yield determined by GC using dodecane
as an external standard for quantitative determination.
2-amino-1-(isobutylamino)-3-methylbut-1-en-1-ol48
resulting
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Fig. 5 Proposed reaction mechanism.
Table 4 Scope and limitation of the decarboxylation procedure with various carboxylic acid derivatives
Entry
1
Substrate
T °C
Time
1h00
Product
Yield (%)
68
210
2
210
1h45
52
3
4
200
140
2h30
1h00
73
96
a
5
6
130
130
0h30
1h30
—
a
—
7
8
130
195
1h10
2h30
31
59
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Table 4 (Contd.)
Entry
Substrate
T °C
Time
5h00
Product
Yield (%)
54
9
180
10
165
1h00
90
11
12
210
220
3h00
3h30
55
46
1334
1435
170
120
12h
16h
87
92
15
16
180
210
5h00
2h00
14
68
17
18
210
180
5h00
3h00
68
Mixture
19
20
21
185
3h00
4h00
15h
Mixture
Mixture
—
210
Up to 230
Decomposition
Decomposition
22
23
Up to 230
195
15h
—
2h30
75
24
25
26
190
190
230
4h00
4h00
5h00
82
75
—
CH3(CH2)10CO2H
No reaction
Reaction conditions: carboxylic acid (15 mmol), Cu(OH)2 (10 mol%), 1,10-phenanthroline (10 mmol%), PEG-6000 BioUltra grade (20 g), T (°C),
time. All reported yields are isolated yields of the pure compound obtained by direct distillation. a Despite the observed decarboxylation
(CO2 bubbling) no product could be isolated due to the polymerization.
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from the reaction between L-valine and the obtained amine
(ca. 10%) (entry 19). D-Leucine and DL-methionine gave a
complex reaction mixture of compounds that could not be
fully identified despite the presence of the expected amine
observed by GC-MS in both cases (entries 19 and 20). L-Histi-
dine and L-tryptophan led to decomposition (entries 21 and
22). Suspecting an inhibiting effect due to the presence of het-
erocycles in the two last examples, we evaluated the decarboxy-
lation of the 1H-indole-2-carboxylic acid, the benzofurane-2-
carboxylic acid and the benzo[b]thiophene-2-carboxylic acid;
all gave good to high isolated yields toward the expected het-
erocycles, respectively, the 1H-indole (68%), the benzofurane
(82%) and the benzo[b]thiophene (68%) demonstrating thus
that the presence of heterocycles in the structure did not affect
the performances of the Cu(OH)2/1,10-phenanthroline catalytic
system (entries 23–25). Finally, decarboxylation of aliphatic
acids like lauric acid failed (entry 26). Together with the
examples of L-histidine and L-tryptophan, this result shows a
limitation to the procedure.
Finally, in order to improve the beneficial impact on the
environment of this new procedure we evaluated the possibility
to reuse both the catalytic system and the PEG-solvent for
several runs. This was evaluated for the decarboxylation of
relatively cheap ferulic acid to the 4-vinylguaiacol, a high
added-value compound finding numerous applications in
pharmaceutical and food industries, like for synthesizing
vanillin.49 The procedure corresponds to the following: an
initial catalytic run was conducted under the standard reaction
conditions using a fresh copper catalyst (10 mol%) and
PEG-6000 solvent (50 g) on a 30 mmol scale (5.8 g). Once the
4-vinylguaiacol production ends as attested by the absence of
both CO2 bubbling and product distillation, a new charge of
Table 5 Reuse of the catalytic system (i.e. Cu(OH)2/1,10-phenanthro-
line/PEG-6000-Fig. 6) for several runs in the protodecarboxylation of
ferulic acid
Run
Time (min)
Gram yield
Yield (%)
TOF (min−1
)
1
2
3
4
55
50
50
55
3.80
4.36
4.07
4.34
84
97
90
96
0.15
0.19
0.18
0.18
ferulic acid was added after cooling in the boiler and a new
run is performed. The procedure was then repeated twice
(Fig. 6). The results reported in Table 5 show that the catalytic
system (i.e.: Cu-catalyst and solvent) remains stable upon reuse
without deactivation. On each run, full conversion was
achieved giving a high isolated yield of the 4-vinylguaiacol
target that corresponds to an average TON of 9.2 per run, and
a cumulative TON of 37 over the 4 runs. Small differences in
yield were observed between the first run and the following
runs due to condensation on the glassware apparatus of
4-vinylguaiacol during the first run. That was not the case
during successive runs.
Conclusion
In summary, a new protocol for the copper-catalyzed decarbox-
ylation of cinnamic acid derivatives in PEG has been develo-
ped. The procedure gave generally moderate to high isolated
yields of the target molecules. It was found that our procedure
can be used to transform aromatic acids, heterocycle-2-car-
boxylic acids and more generally α,β-unsaturated acids, and for
the first time α-amino acids. The use of the more environmen-
tally friendly PEG solvent allowed to perform the transformation
under reduce pressure to isolate directly the product by continu-
ous distillation, preventing therefore its possible rapid polymer-
ization. Furthermore, it allowed the reuse of both the solvent
and catalytic system (i.e. Cu/ligand) to perform several cycles
without observing any deactivation. Thus, the high added-value
4-vinylguaiacol could be prepared in relatively short reaction
time (50 min) at an interesting laboratory large scale (ca. 4 g).
This protocol, additionally to be practical, is thus suitable
for easily synthesizing a variety of molecules derived from bio-
sourced carboxylic acids including styrene derivatives from cin-
namic compounds, olefins from the acrylic moiety or amines
from amino acids.
Experimental
General information
All glassware was base-, acid- and water-washed and oven
dried. The catalytic reactions were carried out under low
Fig. 6 Recycling the {Cu(OH)2/1,10-phenanthroline/PEG-6000} cata-
lytic system in the protodecarboxylation of ferulic acid (Table 1).
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vacuum in distillation apparatus consisting of a two-necked vacuum (i.e. 0.5–1 mbar) until quantitative conversion. After
flask equipped with a condenser, a vacuum adapter and a col- collecting the pure 4-vinylguaiacol from the receiving flask, a
lecting flask.
new charge of ferulic acid (30 mmol; 5.8 g) is added in the
The qualitative and quantitative analysis of the reactants boiling flask and the decarboxylation procedure was repeated,
and the products was made by Gas Phase Chromatography constituting thus a new run of the catalytic mixture (i.e. cata-
using dodecane as an external standard.
lyst and solvent). The overall cycle is repeated twice.
All chemicals were purchased from Acros and Aldrich
Chemicals in their highest purity. All solvents were used as
supplied without further purification.
Acknowledgements
Liquid-state NMR spectra were recorded on a BRUKER
AC-250 or BRUKER DRX300 spectrometer. All chemical shifts The authors gratefully acknowledge the National Agency of
1
were measured relative to the residual H NMR resonances in Research (CHEMLIVAL N° ANR-12-CDII-0001_01) for funding.
1
the deuterated solvents: CDCl3, δ 7.26 ppm for H NMR; D2O, N.R. thanks the Ministry of Research and Education for grant.
1
4.79 ppm for H NMR. Data are reported as follows: chemical The authors warmly thank F. Rataboul and C. Colomban for
shift, multiplicity (s = singlet, d = doublet, t = triplet, proof-reading the manuscript.
q = quartet, m = multiplet, br = broad) and coupling constants
(in Hz), integration and assignments in that order.
Thin layer chromatography was performed on a Fluka Silica
Gel 60 F254. GC analyses were performed on a Shimadzu
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3096 | Green Chem., 2014, 16, 3089–3097
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1
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