A sustainable one-pot synthesis of cinnamyl acetate in triacetin

Article abstract of DOI:10.1016/j.tetlet.2012.06.066

A sustainable one-pot synthesis of cinnamyl acetate from cinnamaldehyde is demonstrated for the first time using immobilized Baker's yeast and free or immobilized acid as catalysts and triacetin as solvent. Employing the immobilized yeast and Amberlyst-36 allowed full conversion and 91% selectivity for cinnamyl acetate after 96 h at room temperature, and both the catalysts and triacetin were successfully recycled.

Full text of DOI:10.1016/j.tetlet.2012.06.066

Tetrahedron Letters 53 (2012) 4565–4567
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Tetrahedron Letters
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A sustainable one-pot synthesis of cinnamyl acetate in triacetin
⇑
Adi Wolfson , Christina Dlugy, Anna Karanet, Dorith Tavor
Green Processes Center, Sami Shamoon College of Engineering, Bialik/Basel Sts., 84100 Beer-Sheva, Israel
a r t i c l e i n f o
a b s t r a c t
Article history:
A sustainable one-pot synthesis of cinnamyl acetate from cinnamaldehyde is demonstrated for the first
time using immobilized Baker’s yeast and free or immobilized acid as catalysts and triacetin as solvent.
Employing the immobilized yeast and Amberlyst-36 allowed full conversion and 91% selectivity for cin-
namyl acetate after 96 h at room temperature, and both the catalysts and triacetin were successfully
recycled.
Received 10 April 2012
Revised 29 May 2012
Accepted 14 June 2012
Available online 19 June 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Green chemistry
Sustainable solvent
One-pot reaction
Glycerol triacetate
Cinnamyl acetate is used as a flavor and a fragrance ingredient
in the perfume, cosmetics, and food industries.1 It can be produced
via a two step synthesis from cinnamaldehyde, which is a steam
distillate from the oil of cinnamon bark, by way of a cinnamyl alco-
hol intermediate, as illustrated in Scheme 1.
amount of waste disposed, that is, green chemistry.5 Inherent to
the goal of actualizing green chemistry solutions is the use of
renewable raw materials and the increase of reaction atom effi-
ciency while using environmentally friendly solvents and more
efficient separation procedures.
The first reaction step is selective hydrogenation of the alde-
hyde group of cinnamaldehyde, which is an a,b-unsaturated alde-
We recently reported glycerol and its derivatives as sustainable
reaction mediums in both catalytic and non-catalytic organic syn-
theses.6 As with other green solvents, glycerol-based solvents pos-
sess beneficial physicochemical properties, such as a high boiling
point and low vapor pressure, which support their low environ-
mental hazard potential. Making equally important contributions
to their green credentials, however, are their production from a
renewable source and their low toxicity and high biodegradability.
Moreover, owing to their excellent dielectric properties, glycerol-
based solvents can also be considered the solvents of choice in
many microwave-assisted reactions.7
hyde.2 Since hydrogenation of the carbon–carbon double bond is
thermodynamically favored over hydrogenation of the carbonyl
group, selective hydrogenation is usually performed at high hydro-
gen pressure over transition metal complexes or supported noble
metal catalysts. Yet specific metal catalysts and controlled reaction
conditions are usually required to yield full selectivity for cinnamyl
alcohol. Alternatively, bio-reduction using yeast or free enzymes in
water or organic solvents can also be employed at mild tempera-
ture and in the absence of hydrogen gas.3
The second reaction step, which involves the production of cin-
namyl acetate from cinnamyl alcohol, can be performed via several
catalytic methods, differing in the type of the acyl donor: direct
esterification using carboxylic acids, transesterification (alcoholy-
sis) using esters as the acyl donor, and acylation of the alcohol
by acyl halides, anhydrides, or vinyl alkanoates. Various homoge-
nous and heterogeneous chemo- and bio-catalysts, such as acids,
bases, and lipases, can be employed to catalyze all the alcohol
esterification routes.4
In this study, we describe for the first time, a sustainable one-pot
synthesis of cinnamyl acetate from cinnamaldehyde (Scheme 1)
under mild conditions using glycerol triacetate (triacetin) as the
solvent and acyl donor.
The investigation was initiated by selecting the solvent, cata-
lysts, and reaction conditions to perform the reaction with mini-
mum environmental impact while considering the final aim to
Environmental awareness and concern have driven the chemi-
cal industry to find new methods for the efficient utilization of re-
sources while minimizing air, water, and land pollution and the
O
H
OH
OAc
cinnamaldeyde
cinnamyl alcohol
cinnamyl acetate
⇑
Corresponding author.
E-mail address: adiw@sce.ac.il (A. Wolfson).
Scheme 1. Two-step synthesis of cinnamyl acetate.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.06.066

4566
A. Wolfson et al. / Tetrahedron Letters 53 (2012) 4565–4567
Table 2
couple the two steps. As the first reaction requires a catalyst that
can reduce the carbonyl bond selectively, employing Baker’s yeast
(Saccharomyces cerevisiae) for the reduction is advantageous over
metal catalysts since the reaction can proceed at low temperature
and in the absence of hydrogen pressure while producing only cin-
namyl alcohol.3 Moreover, using the whole cell instead of purified
enzymes for the reduction is more attractive from economical,
environmental, and handling points of view.
Though water is the natural solvent of choice for bio-catalysis,
the reduction of organic compounds in water is often limited by
the low solubility of the organic substrate within the solution, as
in the case of cinnamaldehyde. Moreover, the second reaction step
is esterification of the produced cinnamyl alcohol, which definitely
cannot be performed in water.
Transesterification of cinnamyl alcohol in triacetina
Catalyst
Time (h)
Conversion (%)
H2SO4
H2SO4
Amberlyst-36
Amberlyst-36
Candida Antarctica lipase B
Candida Antarctica lipase B
Novozyme-435
Novozyme-435
1
21
1
21
1
21
1
21
43
100
35
90
15
22
21
27
a
Reaction conditions: 0.1 g cinnamyl alcohol, 0.01 g catalyst, 5 mL triacetin,
37 °C.
Reduction with Baker’s yeast in an organic solvent is a viable
alternative, though the solvent may affect yeast cell vitality and
the conformation of the enzymes and hence, may affect catalytic
performance. However, Baker’s yeast catalyzed reductions have
been successfully performed in various petroleum-based organic
solvents.3
Our previous work showed that glycerol and its derivatives can
be used as sustainable solvents for yeast reductions and that using
triacetin as the solvent also preserved yeast cell viability for up to
48 h.8 Triacetin is also suitable for simultaneous use as a solvent
and acyl donor for the transesterification of alcohols.9 Thus it ap-
pears to be the best solvent candidate for the one-pot synthesis
of cinnamyl acetate from cinnamaldehyde.
sidered the preferable choice as it can be easily separated and recy-
cled. The low conversions in the presence of free and immobilized
lipase can be attributed to the low reaction temperature. Thus, the
coupled reactions were to be tested with sulfuric acid and Amber-
lyst-36.
One-pot multistep catalytic processes present a method for
reducing or eliminating the separation, storage, and handling of
intermediates and replacing hazardous with benign chemicals.
Although some successful one-pot syntheses of fine chemicals
have been previously reported, the compatibility of the different
catalytic reactions with similar reaction conditions and intermedi-
ates or by-products renders the coupling of catalysts difficult, espe-
cially in the case of chemo-catalysts. Moreover, transition metal
complexes or enzymes acting as active and selective catalysts in
many homogenous reactions, generate complex separation and
recycling problems that significantly affect their performances.
Although this issue has been known for many years, only recently
have multifunctional systems that combine reaction and separa-
tion processes become a viable alternative.
The one-pot conversion of cinnamaldehyde into cinnamyl ace-
tate in triacetin was performed at 37 °C in the presence of IBY
and sulfuric acid or Amberlyst-36 (Scheme 2).13 Reaction conver-
sion and the selectivity toward cinnamyl acetate increased with
time with either catalyst (Table 3) and reached full conversion
and high selectivity after 96 h. As was previously shown, using
Amberlyst-36 gave lower conversions, but resulted in higher
selectivity.
Finally, recycling of both catalysts together with triacetin was
tested in three modes (Table 3). In the first recycling method
(M1), the product was extracted from the reaction mixture, which
contained the two catalysts after 24 h, and the second cycle was
performed by adding fresh cinnamaldehyde. The much lower
activity and selectivity observed with either free or immobilized
acids were probably the result of damage to the catalyst during
the extraction procedure. Thus, in the second recycling procedure
(M2), the two heterogeneous catalysts were filtered at the end of
the first reaction cycle, followed by extraction of the product and
addition to the used triacetin of the two recovered catalysts to-
gether with fresh cinnamaldehyde. Indeed, the conversion and
selectivity were higher than for the first recycling procedure, but
were still lower than that of the first cycle. It can be postulated that
the presence of residual extraction solvent or glycerol and glycerol
di- or mono-acetate, produced during the transesterification step
in the first cycle, was the reason for the lower performance. Hence,
in the third recycling procedure (M3), the two heterogeneous cat-
The reduction of cinnamaldehyde to cinnamyl alcohol was
tested in triacetin with both free and immobilized yeast (FBY and
IBY,10 respectively) at an optimal temperature of 37 °C using glu-
cose as the hydrogen source (Table 1).11
As indicated in Table 1, the reaction progressed with either FBY
or IBY and reached full conversion after 48 h. The reaction with FBY
was faster probably because the total amount of yeast cells was
higher compared to IBY, which was prepared from 2 g of free yeast
cells. Yet a comparison of the turnover frequencies of both systems
based on the number of molecules reacted per active site showed
only a small difference between the homogeneous and the hetero-
geneous systems. IBY is advantageous from an operational point of
view as it can be mixed more easily during the reaction and is sim-
pler to separate afterward, which also allows easy product recov-
ery. Thus, it was chosen for use in the coupled reaction studies.
As previously mentioned, triacetin can be simultaneously used
as a reaction solvent and as an acyl donor in the transesterification
of cinnamyl alcohol to cinnamyl acetate employing various homo-
geneous and heterogeneous bio- and chemo-catalysts.4 Thus, the
transesterification of cinnamyl alcohol in triacetin was tested with
representative homogeneous and heterogeneous acids and lipases.
In addition, the reaction was performed at a low temperature of
37 °C, which is necessary for optimal yeast performance in the first
reaction step (Table 2).12
The results in Table 2 clearly indicate that an acid catalyst is
preferable, and as expected, free sulfuric acid yielded higher con-
version into cinnamyl acetate than immobilized sulfuric acid
(Amberlyst-36). However, the immobilized catalyst should be con-
Table 1
Baker’s yeast catalyzed reduction of cinnamaldehydea
Time (h)
FBY-conversion (%)
IBY-conversion (%)
b
b
24
48
89 (5.6 Â 10À5
)
32 (5.1 Â 10À5
)
Immobilized Baker's yeast
Amberlyst-36
O
100
100
OAc
H
a
Reaction conditions: 1 g cinnamaldehyde, 5 g catalyst, 5 g glucose, 50 mL tri-
acetin, 37 °C.
triacetin
b
Turnover frequency.
Scheme 2. One-pot synthesis of cinnamyl acetate.

A. Wolfson et al. / Tetrahedron Letters 53 (2012) 4565–4567
4567
Table 3
4. Shirae, Y.; Mino, T.; Hasegawa, T.; Sakamoto, M.; Fujita, T. Tetrahedron Lett.
2005, 46, 5877–5879; Grasa, G. A.; Singh, R.; Nolan, S. P. Synthesis 2004, 7, 971–
985.
One-pot synthesis of cinnamyl acetate from cinnamaldehydea
Time (h)
IBY + H2SO4
Conv. (%)
Select. (%)b
IBY + Amberlyst-36
Conv. (%)
Select. (%)b
5. Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice; Oxford
University Press, 2000; Dunn, P.; Wells, A.; Williams, M. T. Green Chemistry in
the Pharmaceutical Industry; Wiley-VCH, Weinheim: Germany, 2010.
6. Wolfson, A.; Dlugy, C.; Shotland, Y. Environ. Chem. Lett. 2007, 5, 67–71;
Wolfson, A.; Dlugy, C.; Tavor, D. In Homogeneous Catalysts: Types, Reactions and
Applications; Poehler, A. C., Ed.; Nova Publishers, 2011; Wolfson, A.; Dlugy, C.
Chem. Papers 2007, 61, 228–232; Wolfson, A.; Dlugy, C.; Shotland, Y.; Tavor, D.
Tetrahedron Lett. 2009, 50, 5951–5953; Wolfson, A.; Snezhko, A.; Meyouhas, T.;
Tavor, D. Green Chem. Lett. Rev. 2012, 5, 7–12.
7. Cravotto, G.; Orio, L.; Gaudino, E. C.; Martina, K.; Tavor, D.; Wolfson, A.
ChemSusChem 2011, 4, 1130–1134.
8. Wolfson, A.; Dlugy, C.; Tavor, D.; Blumenfeld, J.; Shotland, Y. Tetrahedron:
Asymmetry 2006, 17, 2043–2045; Wolfson, A.; Haddad, N.; Dlugy, C.; Tavor, D.;
Shotland, Y. Org. Commun. 2008, 1, 9–16.
24
48
96
97
100
100
40
—
54
67
73
22
—
87
92
96
7
64
63
56
82
91
35
61
60
24 (M1)c
24 (M2)d
24 (M3)e
—
—
a
Reaction conditions: 1 g cinnamaldehyde, 5 g immobilized Baker’s yeast, 0.1 g
acid, 5 g glucose, 50 mL triacetin, 37 °C.
b
Selectivity for cinnamyl acetate.
Re-use of triacetin and both catalysts without catalyst filtration.
Re-use of triacetin and both catalysts with catalyst filtration.
Re-use of both catalysts after catalyst filtration.
c
9. Dlugy, C.; Wolfson, A. Bioprocess Biosystems Eng. 2007, 30, 327–330; Wolfson,
A.; Saidkarimov, D.; Dlugy, C.; Tavor, D. Green Chem. Lett. Rev. 2009, 2, 107–110;
Wolfson, A.; Atyya, A.; Dlugy, C.; Tavor, D. Bioprocess Biosystems Eng. 2009, 33,
363–366.
d
e
10. Buque, E. M.; Chin-Joe, I.; Straathof, A. J. J.; Jongejan, J. A.; Heijnen, J. J. Enzyme
Microbial. Technol. 2002, 31, 656–664.
11. Representative procedure for cinnamaldehyde reduction with FBY and IBY in
triacetin: 5 g of FBY (SIGMA, type II) or 5 g of IBY (prepared as described in
Buque et al.10 was added to a mixture of 50 mL of triacetin (99% Aldrich.) in a
250 mL bottle which was shaken for 30 min. Then 5 g of glucose was added and
the bottle shaken for 10 min before 1 g of cinnamaldehyde was added. The
bottle was shaken at 300 rpm for 48 h at 37 °C. At the end of the reaction the
products were extracted with CH2Cl2 (3 Â 50 mL). The organic phase was
concentrated under reduced pressure, and the resulting crude product was
alysts were filtered at the end of the first reaction cycle and added,
together with fresh cinnamaldehyde, to fresh triacetin. As illus-
trated in Table 3, the performance was similar to that of the second
recycling method, indicating that the catalysts were probably
deactivated during the reaction.
The one-pot synthesis of cinnamyl acetate from cinnamalde-
hyde was successfully performed in triacetin under mild condi-
tions using IBY and soluble or solid acid catalysts. This novel
procedure resulted in high conversion and selectivities as well as
easy product separation and catalyst and solvent recycling. It is
envisaged that this simple, sustainable procedure can be trans-
ferred to the synthesis of a variety of symmetric and asymmetric
organic esters and amides.
analyzed by GC analysis using an HP-5 column (30 m  0.25 mm, 0.25
lm
thickness).
12. In a typical procedure, 0.1 g of cinnamyl alcohol and 0.01 g of catalyst were
added to a vial with 5 mL of triacetin (all purchased from Aldrich). The mixture
was placed in a preheated oil bath and heated to the required temperature
(37 °C), after which it was magnetically stirred for 1–21 h. At the end of the
reaction, the mixture was cooled and extracted with CH2Cl2 (3 Â 10 mL). The
organic phase was concentrated under reduced pressure, and the resulting
crude product was analyzed by GC analysis using an HP-5 column
(30 m  0.25 mm, 0.25
lm thickness). The isolated yield of cinnamyl acetate
was 94%.
13. In
a typical procedure 5 g of IBY (prepared from FBY-SIGMA, type II, as
References and notes
described in Buque et. al.10) was added to 50 mL of triacetin (99% Aldrich) in a
250 mL bottle which was shaken for 30 min. Then 5 g of glucose was added and
the bottle was shaken for 10 min before 1 g of cinnamaldehyde was added
together with 0.1 g of the acid catalyst. The bottle was shaken at 300 rpm and
37 °C. At the end of the reaction the product was extracted with CH2Cl2
(3 Â 50 mL). The organic phase was concentrated under reduced pressure, and
the resulting crude product analyzed by GC analysis using an HP-5 column
1. Opdyke, D. L. J. Food Cosmetics Toxicol. 1973, 11, 1063–1064.
2. Gllezot, P.; Richard, D. Catal. Rev. 1998, 40, 81–126; Singh, U. K.; Vannice, M. A.
App. Catal. A 2001, 213, 1–24.
3. Servi, S. Synthesis 1990, 1–25; Fuganti, C.; Grasselli, P. In Biocatalysis in
Agricultural Biotechnology; Whitaker, J. R., Sonnet, P. E., Eds., 1989; Vol. 389, pp
359–370; Bowen, W. R.; Lambert, N.; Pug, S. Y. R.; Taylor, F. J. Chem. Tech.
Biotech. 1986, 36, 267–272.
(30 m  0.25 mm, 0.25
lm thickness). The isolated yield of cinnamyl acetate
was 94%.