Glycerol-glycerol triacetate mixtures as green reaction mediums

Article abstract of DOI:10.1139/cjc-2013-0488

Three representative organic reactions were performed in various glycerol-triacetin mixtures to tune the polarity of the reaction mixture and thus to increase both the solubility of reactants and the product yields. In all reactions, it was found that reaction performance was affected by the glycerol to triacetin ratio as the solubility of the substrates in the solvent determined product yield. Thereby, employing optimal glycerol to triacetin ratio will result in maximum product yield.

Full text of DOI:10.1139/cjc-2013-0488

240
ARTICLE
Glycerol − glycerol triacetate mixtures as green reaction
mediums
A. Wolfson, C. Dlugy, I. Mordechaiev, T. Sliman, and D. Tavor
Abstract: Three representative organic reactions were performed in various glycerol−triacetin mixtures to tune the polarity of
the reaction mixture and thus to increase both the solubility of reactants and the product yields. In all reactions, it was found
that reaction performance was affected by the glycerol to triacetin ratio as the solubility of the substrates in the solvent
determined product yield. Thereby, employing optimal glycerol to triacetin ratio will result in maximum product yield.
Key words: glycerol, triacetin, green chemistry, sustainable solvent.
Résumé : Trois réactions organiques représentatives ont été réalisées dans différents mélanges réactionnels de glycérol et
triacétine afin d’ajuster la polarité de ces mélanges et d’accroître ainsi a` la fois la solubilité des réactants et les rendements de
produit. Pour toutes ces réactions, il a été constaté que le rendement de réaction était affecté par les proportions de glycérol et
de triacétine et que le rendement de produit était déterminé par la solubilité des substrats dans le solvant. Ainsi, l’utilisation de
proportions optimales de glycérol et de triacétine permettra d’obtenir un rendement de produit maximum. [Traduit par la
Rédaction]
Mots-clés : glycérol, triacétine, chimie verte, solvant écologique.
Introduction
organic compounds in glycerol-based solvents, thereby improving
reaction performance. Three representative reactions were inves-
tigated: nucleophilic substitution of benzyl chloride with sodium
or ammonium acetate (Fig. 1a), Suzuki−Miyaura cross-coupling of
iodobenzene and phenylboronic acid (Fig. 1b), and transfer hy-
drogenation of olefins using glycerol simultaneously as solvent
and hydrogen donor (Fig. 1c). The effects of the glycerol to triacetin
ratio on reaction performance were examined.
Since our first report on the use of glycerol as a reaction me-
1
dium, it has been successfully employed as an alternative green
solvent in a wide variety of catalytic and noncatalytic organic
reactions and synthesis methodologies.
origin, beneficial physicochemical properties (Table 1), reusabil-
ity, and its ability to tolerate nonconventional heating and mixing
techniques, such as are used in ultrasound- and microwave-
2
–9
Glycerol’s renewable
1
0,11
assisted reactions,
hint at its promise as a sustainable solvent
Experimental
All chemicals were purchased from Aldrich.
for organic reactions. Furthermore, in many reactions, the pres-
ence of glycerol as a solvent improved product yields and selectiv-
ities and enabled catalyst recycling.
Nucleophilic substitution
However, the relatively high polarity of glycerol resulted in low
solubility of highly hydrophobic compounds and thus led to low
catalytic performance where such molecules were employed as
substrates. One of the routes to overcome this limitation is to use
less polar glycerol derivatives whose properties can be tailored,
tuned, and adjusted according to the requirement of each reaction.
Several examples of organic synthesis in representative glycerol-
based solvents, and especially glycerol triacetate − triacetin, were
reported in the literature by our and other research groups, demon-
In a typical nucleophilic substitution procedure, 0.80 mmol of
benzyl chloride and the corresponding amount of salt (0.88 mmol)
were added together to 5.0 g of solvent. After mixing, the reaction
mixture was heated in an oil bath to the required temperature
(
80 °C). The reactions ran for 1 or 2 h and the mixtures were then
allowed to cool. The product was separated after cooling by ex-
traction with 3 mL of petroleum ether (60–80 °C). The organic
phase was concentrated under reduced pressure, and to deter-
mine product yield, the resulting crude was analyzed by gas chro-
matography (GC) using an HP-1 column.
12,13
strating their potential use as green reaction mediums.
It was
illustrated that the performance and product separation of the reac-
tion and catalyst recycling were affected by the type and the polarity
of the solvent. In addition, it was suggested that substrate sol-
ubility was the main determinant of reaction activity, while the
solubility of the product in the solvent determined the effec-
tiveness of its extraction.
In our ongoing efforts to design a viable protocol that will facil-
itate the acceptance of glycerol and its derivatives as sustainable
solvents, several mixtures of glycerol and glycerol triacetate (tri-
acetin) were used as green solvents to optimize the solubility of
Suzuki−Miyaura cross-coupling
Suzuki−Miyaura cross-coupling typically involved adding 10 ␮mol
of palladium acetate or the corresponding amount of 5% Pd/C to a
vial containing 5.0 g of solvent including 0.5 mmol of iodobenzene,
0.6 mmol of phenylboronic acid, and 0.6 mmol of sodium carbon-
ate. The mixture was placed in a preheated oil bath at 80 °C and
magnetically stirred for 2.5 h. At the end of the reaction, the
mixture was cooled and extracted with 3 mL of petroleum ether
(60–80 °C). The organic phase was concentrated under reduced
Received 30 October 2013. Accepted 17 December 2013.
A. Wolfson, C. Dlugy, I. Mordechaiev, T. Sliman, and D. Tavor. Green Processes Center, Sami Shamoon College of Engineering, 36 Bialik Sts.,
Beer-Sheva 84100, Israel.
Corresponding author: A. Wolfson (e-mail: adiw@sce.ac.il).
Can. J. Chem. 92: 240–242 (2014) dx.doi.org/10.1139/cjc-2013-0488
Published at www.nrcresearchpress.com/cjc on 9 January 2014.

Wolfson et al.
241
Table 1. Glycerol and triacetin properties.
Table 2. Nucleophilic substitution in representative glycerol−triacetin
mixtures.
Property
Glycerol
Triacetin
259
0.0023
Product yield (%)
Boiling point (°C)
290
0.00025a
12 600
400
b
Vapor pressure at 20–25 °C (mmHg)
LD50 oral-mouse (mg/kg)
Autoignition temperature (°C)
Flash point (°C)
Dielectric constant at 25 °C
log P
BzCl + NaOAc
(1 h)
BzCl + NaOAc
(2 h)
BzCl + NH OAc
(1 h)
4
3000
433
140
Solvent (wt%)
Glycerol
30
32
74
25
0
60
62
96
42
0
100
76
74
71
193
42.5a
b
Gly-Tri (70/30)
Gly-Tri (50/50)
Gly-Tri (30/70)
Triacetin
7.3
−4.15
1410
221.9
91.7
0.25
23
389.0
85.7
1.1562
Viscosity at 20 °C (cP)
Heat capacity at 25 °C (J/(mol K))
Heat of vaporization (kJ/mol)
Density at 25 °C (g/mL)
a
0
Note: Reaction conditions: 0.8 mmol of benzyl chloride, 0.88 mmol of salt,
5.0 g of solvent, 80 °C.
1.4746
2
5 °C.
uously generated by the biodiesel industry are increasing, it is
vital that we search for economical uses for glycerol to defray the
cost of biodiesel production.
b20 °C.
Fig. 1. Representative reactions.
While the key property of a reaction solvent is its solvation
capability, i.e., its ability to facilitate the combination of reactants
and catalysts, many organic reactions also require salts and or-
ganic compounds or hydrophilic and hydrophobic molecules to
2
0,21
be dissolved simultaneously.
Hence, it was suggested that the
drawbacks outlined above in the use of glycerol as a solvent for
the dissolution of a hydrophobic substrate can be overcome by
using mixtures of glycerol and triacetin, both of which are inex-
pensive and commercially available and sustainable solvents
whose use enables the polarity of the reaction medium to be
tailored to the reaction requirements. The properties of glycerol
and triacetin as solvents are summarized in Table 1.
To examine this hypothesis, catalyst-free nucleophilic substitu-
tion of benzyl halides with sodium or ammonium acetate22 was
employed as the first example of organic transformation in a
glycerol−triacetin (Gly-Tri) mixture (Fig. 1a). Because this reaction
requires the dissolution of a nonpolar organic compound with a
polar ionic salt, reaction medium polarity is expected to have an
influence. The investigation began by testing the yields of benzyl
acetate in the nucleophilic substitution of benzyl chloride with
sodium and ammonium acetate in several Gly-Tri mixtures and in
the two pure solvents (Table 2). As illustrated in Table 2, the reac-
tion proceeded in pure glycerol, but no reaction was detected in
pure triacetin. This outcome may be attributed to the fact that for
the substitution to occur, the salt must split into ions, a phenom-
enon that occurs only in polar solvents. Likewise, performing the
reaction in different Gly-Tri mixtures also yielded benzyl acetate.
In addition, replacing sodium acetate with ammonium acetate
produced higher yields in glycerol and in all Gly-Tri mixtures, a
result possibly due to the lower ionization energy of ammonium
acetate due to the higher ionic radius of the ammonium ion.
Finally, the product extraction resulted in highly pure benzyl ac-
etate (>98%).
The effect of the glycerol to triacetin ratio on the yield of benzyl
acetate was also dissimilar with the two different salts. When
sodium acetate was the salt, maximum product yield was detected
in a mixture of 50%–50% Gly-Tri, while the highest product yield
with ammonium acetate was in pure glycerol. Furthermore, al-
though addition of triacetin to glycerol (up to 70 wt%) when am-
monium acetate was used as the salt resulted in lower product
yields compared to running the reaction in pure glycerol, the
amount of triacetin in the mixture did not significantly affect
product yield. These results can also be explained by the lower
ionization power of ammonium acetate and the fact that it may
also form hydrogen bonds with glycerol, which enhances its sep-
aration into ions relative to sodium acetate in all reaction mix-
tures.
pressure and the resulting crude was analyzed to determine prod-
uct yield by GC using an HP-1 column.
Transfer hydrogenation
In a typical procedure, 0.1 g of 1-octene and 0.01 g of palladium
acetate were added to a vial with 5.0 g of reaction mixture. The
mixture was placed in a preheated oil bath and heated to 80 °C,
after which it was magnetically stirred for 48 h. At the end of the
reaction, the reaction mixture was cooled and extracted with 3 mL
of petroleum ether (60–80 °C). Finally, the ether phase was re-
duced under vacuum and analyzed by GC analysis using an HP-5
column (30 m × 0.25 mm, 0.25 ␮m thick) to determine the product
yield.
Results and discussion
Organic chemistry is traditionally carried out in solution to
dissolve reactants and (or) catalysts and to affect the transfer of
mass, heat, or momentum.14 However, solvents are responsible
for a large part of the waste and pollution generated by chemical
processes, as their discharge into the environment leads to their
accumulation in the air, water, and land. Thus, various green
solvents have been introduced and studied during the last three
decades, some of them specific to particular reactions and others
for more general use.1
5–19
The most commonly used and accepted
green solvent families comprise water, ionic liquids, fluorous phase,
supercritical solvents, especially super critical CO , and bio-based
2
solvents such as ethanol and glycerol and its derivatives.
As a nontoxic, nonhazardous, nonvolatile, biodegradable, and
recyclable liquid produced as a by-product in the transesterifica-
tion of oil from renewable sources, glycerol has been shown to be
a promising alternative and sustainable solvent for organic trans-
The effect of the glycerol to triacetin ratio on reaction perfor-
mance was also studied in the palladium-catalyzed Suzuki−Miyaura
cross-coupling reaction of iodobenzene and phenylboronic acid
1
–11
23
formations.
Moreover, as the amounts of glycerol being contin-
(Fig. 1b). This reaction requires the simultaneous dissolution of
Published by NRC Research Press

242
Can. J. Chem. Vol. 92, 2014
Table 3. Suzuki−Miyaura cross-coupling of
iodobenzene and phenylboronic acid in repre-
sentative glycerol−triacetin mixtures.
Fig. 2. Transfer hydrogenation of 1-octene in representative
glycerol−triacetin mixtures. Reaction conditions: 0.1 g of 1-octene,
0.01 g of palladium acetate, 5.0 g of solvent, 80 °C, 48 h.
Product yield (%)
Solvent (wt%)
5% Pd/C
Pd(OAc)2
Glycerol
81
84
79
76
75
87
69
67
59
71
Gly-Tri (70/30)
Gly-Tri (50/50)
Gly-Tri (30/70)
Triacetin
Note: Reaction conditions: 0.5 mmol of iodobenzene,
.6 mmol of phenylboronic acid, 10 ␮mol of palladium,
.6 mmol of sodium carbonate, 5.0 g of solvent, 80 °C,
0
0
2.5 h.
polar and apolar organic substrates with a palladium catalyst and
a strong inorganic base, which activates the reaction, and thus
it is usually performed in an organic polar solvent that allows
the simultaneous dissolution of all components. Here, the Suzuki−
Miyaura cross-coupling of iodobenzene and phenylboronic acid
was performed in representative Gly-Tri mixtures and in each
pure solvent (Table 3). As the more polar solvent, glycerol was
expected to easily dissolve the phenylboronic acid and the inor-
ganic base. Likewise, triacetin, the more hydrophobic solvent, was
expected to dissolve the iodobenzene better. However, as can be
seen from the results in Table 3, when a heterogeneous palladium
catalyst was used, the polarity of the Gly-Tri mixtures did not
actually affect the yield of the reaction product, biphenyl, al-
though the yield in a mixture of 70%–30% Gly-Tri was slightly
higher. On the other hand, the ratio of glycerol to triacetin mark-
edly affected the biphenyl yield when palladium acetate was used
as the catalyst, giving an unexpected minimum product yield in a
employing optimal glycerol to triacetin ratio will result in maxi-
mum product yield.
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