Green syntheses of biobased solvents

Article abstract of DOI:10.1016/j.crci.2010.07.008

The design of bioproducts implies the use of renewable carbon but also the conversion of this carbon through clean processes. This step is often a limiting one if we consider the whole life cycle "from the raw materials to the fate of the products". We proposed, in this work, to adapt conventional methods to the conversion of a natural raw material, the fusel oil, a co-product generated by ethanol industry to prepare acetates, carbonates and isovalerates. Selected conditions are compared to conventional routes to quantify their ecoefficiency and to check their potential development for the preparation of new biosolvents. In another step, we have calculated the volatile organic compound amount emitted during the production of a new cosmetic formulation using the fusel oil derivatives. This complete but simple example shows how to identify a real competitive alternative to the usual production chains.

Full text of DOI:10.1016/j.crci.2010.07.008

C. R. Chimie 14 (2011) 636–646
Contents lists available at ScienceDirect
Comptes Rendus Chimie
www.sciencedirect.com
´
Full paper/Memoire
Green syntheses of biobased solvents
Matthieu Bandres a,b, Pascale de Caro a,b, Sophie Thiebaud-Roux a,b,
*
,
Marie-Elisabeth Borredon a,b
a
´
Laboratoire de Chimie Agro-industrielle (LCA), Universite´ de Toulouse, INPT, ENSIACET, 4, alle´e Emile-Monso, BP 44362, 31030 Toulouse, France
b LCA, INRA, 31030 Toulouse, France
A R T I C L E I N F O
A B S T R A C T
Article history:
The design of bioproducts implies the use of renewable carbon but also the conversion of
this carbon through clean processes. This step is often a limiting one if we consider the
whole life cycle ‘‘from the raw materials to the fate of the products’’. We proposed, in this
work, to adapt conventional methods to the conversion of a natural raw material, the fusel
oil, a co-product generated by ethanol industry to prepare acetates, carbonates and
isovalerates. Selected conditions are compared to conventional routes to quantify their
ecoefficiency and to check their potential development for the preparation of new
biosolvents. In another step, we have calculated the volatile organic compound amount
emitted during the production of a new cosmetic formulation using the fusel oil
derivatives. This complete but simple example shows how to identify a real competitive
alternative to the usual production chains.
Received 22 March 2010
Accepted after revision 5 July 2010
Available online 15 September 2010
Keywords:
Green chemistry
Natural products
Alcohol
Esterification
Oxidation
Transesterification
´
ß 2010 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
´
´
R E S U M E
Mots cle´s :
´
L’elaboration de bioproduits implique l’utilisation de carbone renouvelable mais
Chimie verte
Produits naturels
Alcool
e´galement la conversion de ce carbone par des proce´de´s propres. Cette e´tape reste trop
souvent une e´tape limitante lorsqu’on conside`re l’ensemble du cycle « de la matie`re
`
´
´
´
premiere au devenir du produit ». Dans ce travail, nous avons adapte et ameliore les
Este´rification
Oxydation
´
`
methodes conventionnelles de fonctionnalisation des alcools a la transformation d’une
matie`re premie`re naturelle, l’huile de fusel (co-produit ge´ne´re´ par l’industrie sucrie`re)
´
Transesterification
´
´
´
pour preparer des acetates, des carbonates et des isovalerates. Les conditions
´
´ ´
´
´
experimentales retenues ont ete comparees aux methodes usuelles, afin de quantifier
leur e´co-efficacite´ et de ve´rifier leur de´veloppement potentiel pour la pre´paration de
`
´
´
nouveaux biosolvants pour vernis a ongles. Les emissions de composes organiques volatils
´ ´
´
´
(COV) ont ete calculees au cours de la production de nouvelles formulations cosmetiques
utilisant ces de´rive´s de l’huile de fusel. Cet exemple complet mais simple montre comment
identifier une alternative compe´titive vis-a`-vis des filie`res existantes.
´
´
´
´
ß 2010 Academie des sciences. Publie par Elsevier Masson SAS. Tous droits reserves.
1. Introduction
and human health. VOCs that spill into the environment
contribute to tropospheric ozone formation and contami-
Conventional solvents are usually volatile organic
compounds (VOCs), which are harmful for the environment
nate water and soil.
Accordingly, new regulations introduced in the 1990s
(European directives 1999/13/EC, 2001/81/EC, 2004/73/
EC, REACH, Clean Air Act) have forced the industry to find
solutions to reduce their emissions and waste released into
the environment. One potential solution involves the
* Corresponding author.
E-mail address: sophie.thiebaudroux@ensiacet.fr (S. Thiebaud-Roux).
1631-0748/$ – see front matter ß 2010 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.crci.2010.07.008

M. Bandres et al. / C. R. Chimie 14 (2011) 636–646
637
Table 1
Criteria for the selection of new solvents.
Criteria
Measurements
Specifications
Technical
Solvent properties
Solubility parameters
Kauri index
Toxicity/ecotoxicity/biodegradability
Volatility
Solvent properties
Vapor pressure
Boiling point
Evaporation index
Flash point
Sanitary/environmental
Technical/environmental
Flammability
Raw materials
Technical/safety
Origin
Environmental/economic
Availability
Cost
Chemical process
Green chemistry indicators
Cost
Environmental/economic
replacement of conventional solvents by new alternative
solvents, serving as a preventive measure.
ꢀ
technical specifications: the biosolvent has to display
the appropriate levels of performance and security
required for the considered application. The primary
role of a solvent is to dissolve all the components of the
formulation giving a homogeneous solution. Appropri-
ate volatility of the molecules is essential to limit the
drying time of the formulation. However, a compromise
must be found to provide the optimal level of volatility,
keeping VOC emissions to a minimum. Moreover, the
flash point has to be high enough during the production,
conditioning and transportation phases for security
purposes;
environmental and sanitary criteria have to be met to
satisfy the specific regulatory, standards and ecolabel
specifications;
the processes involved in solvent production have to be
eco-compatible: they have to respect most of the 12
principles of green chemistry proposed by Anastas and
Warner;
Biosolvents, based on natural ingredients, have been
developed to offer the advantages required for an
alternative to fossil resources. Such molecules are derived
from vegetable, animal or mineral raw materials, using
chemical and physical processes that are safer for the
environment and humans. The natural synthon must
represent a major part of the final product. Moreover,
because their conception is compatible with sustainable
development, biosolvents are expected to provide
a
positive environmental balance (VOC reduction, biode-
gradability, non ecotoxicity) and to improve safety aspects.
The major classes of biosolvents are esters of natural
organic acids (produced by fermentation of renewable
materials), fatty acid esters, bioethanol, terpenic com-
pounds, isosorbide and glycerol derivatives [1,2].
These biosolvents are incorporated into different
formulations for cleaning applications [3,4], cosmetics
[5,6], inks [7], paintings [8], bituminous flux [9,10] and
agricultural chemicals [11,12].
ꢀ
ꢀ
ꢀ
the selection of renewable raw materials depends on
their availability, their cropping cycle, their physico-
chemical properties and their cost.
In this work, new biosolvents were developed to
substitute the petrochemical solvents used in nail polish
formulations.
To meet the major criteria, we have targeted different
To identify these alternative biosolvents, several crite-
ria have been taken into account (Table 1):
molecules capable to comply with the technical specifica-
tions such as nitrocellulose solubilisation. We observed
Fig. 1. Derivatives prepared from fusel oil.

638
M. Bandres et al. / C. R. Chimie 14 (2011) 636–646
Table 2
Composition (mass percentage of alcohol components) of several fusel oils.
a
Origin & Supplier of Fusel oils
Beet from Tereos
Beet from UNGDAa
Wheat from UNGDA
Ethanol (%)
1.69
0.03
11.32
0.08
17.65
0.09
Propanol (%)
Isopropanol (%)
Butanol (%)
< 0.01
0.14
0.05
< 0.01
0.15
0.06
Isobutanol (%)
3.43
0.25
0.69
b
C5 alcohols (%)
Total (%)c
74.84
80.13
75.73
87.49
57.62
76.20
a
UNGDA: Union nationale des groupements de distillateurs d’alcools (France).
b
c
C5 alcohols correspond to the mixture of isoamyl alcohol (mainly 3-methyl-1-butanol) and active amyl alcohol (2-methyl-1-butanol).
Addition of water content allows one to reach 100%.
that the performing molecules represented in Fig. 1 could
be obtained from short alcohols.
solvents (including chlorinated solvents, hydrocarbons,
ketones and ethers).
So, we started from fusel oil, which represents a cheap
and renewable supply since ethanol production is a rapidly
growing industry. As fusel oil can be derived from
bioethanol of first generation (sugar or starch) and from
second generation (lignocellulosic biomass), the volumes
generated allows one to develop biosolvents for specific
markets. Up to now, only a low amount of fusel oil is
recovered for commercial purposes (food aroma, perfume
industry).
Syntheses were performed with isoamyl alcohol (98%),
obtained by distillation of fusel oils derived from sugar
beets and wheat, in order to facilitate treatment of the
reaction medium and to characterize the final products.
Fusel oils, provided by UNGDA and Tereos, were collected
from several French industrial distilleries. Their composi-
tions are described in Table 2.
All other commercial reagents were used without any
preliminary purification.
Fusel oil corresponds to the pot residue after distilla-
tion of fermented alcohol, either dedicated for beverages
or for biofuels. It consists of a mixture of alcohols, from
C2 to C5, coming from the decomposition of proteins
present in the plant. These short alcohols constitute
between 50 and 70% of the mixture, depending on the
origin (Table 2).
We determined reaction yields by gas chromatography
with ChromPack 9002 apparatus equipped with a polar
column CP WAX 25 m ꢂ 0.32 mm ꢂ 1.2
mm, a flame
ionization detector (FID) and an on-column injector.
2.1. Materials and catalyst for syntheses
In this study, we proposed new synthetic processes for
the production of molecules derived from isoamyl alcohol,
following the principles of green chemistry. To meet
industrial requirements, each method was developed for
use under selective and easy-to-implement conditions.
Therefore, we determined green indicators for each
new reaction from material balances. We have focused on
indicators recommended by Trost and Sheldon, that is to
say, the atom economy (AE), the environmental factor (EF)
according to the following equations:
Acetic acid (99%) and acetic anhydride (99%) were
purchased from Sigma Chemical company, Inc. Isoamyl
acetate (> 99%) was supplied by Fisher Sciencific. The
cation-exchange resin used in this study was Amberlyst1
15 supplied by Rohm & Haas. It is a macroreticular styrene
divinyl benzene resin grafted with sulfonic acid groups.
The wet resin was first washed with methanol to
remove any water that might be sorbed. It was then dried
in a vacuum oven at 353 K for 6 h and stored in a desicator
until further use. Specific surface area was 42 m2/g,
determined using the BET method, with a capacity close to
4.8 meq H+/g.
X
AE ð%Þ ¼ 100: Mproduct
with M ¼ molar weight;
=
Mraw materials
2.2. Syntheses methods
X
EF ¼
Waste ðkgÞ=Product ðkgÞ:
2.2.1. Method 1: heterogeneous esterification of isoamyl
alcohol with acetic acid
Mass productivity can be deduced with the following
formula:
Isoamyl alcohol (454 mmol), glacial acetic acid
(378 mmol) and the cation-exchange resin H+ Amberlyst1
15 (2 g) were stirred for 1 h at 120 8C. Water was
continuously removed through Dean Starck. The catalyst
was separated through filtration by gravity. Isoamyl
acetate (47.7 g, 97%) was obtained as a colorless liquid
by distillation at atmospheric pressure (T = 141–142 8C).
MP (%) = 100/(EF + 1) = 100/Sꢁ1 with Sꢁ1, the mass index
defined by Eissen and Metzger [13].
Calculated green indicators are compared with those of
usual processes carried out with isoamyl alcohol.
2. Experimental part
Several chemical derivatives have been obtained from
the alcohols in fusel oil: isoamyl acetate, methyl isoamyl
carbonate and ethyl isovalerate (Fig. 1).
These derived compounds have moderate volatility
with vapor pressures below the values of conventional
2.2.2. Method 2: heterogeneous esterification of isoamyl
alcohol with acetic anhydride
Isoamyl alcohol (454 mmol), acetic anhydride
(227 mmol) and the cation-exchange resin H+ Amberlyst1
15 (1 g) were stirred at reflux (120 8C) for 2 h to give a

M. Bandres et al. / C. R. Chimie 14 (2011) 636–646
639
conversion rate of 98%. Isoamyl acetate was separated
from acetic acid by distillation at atmospheric pressure.
These hypotheses allow one to compare the different
routes to obtain the targeted product.
1H NMR (300 MHz, CDCl3) :
d (ppm) = 4.05–4.09 (t, 2H,
OCH2), 2.03 (s, 3H, CH3CO), 1.67 (m, 1H, CH), 1.48 (m, 2H,
CH2), 0.90–0.92 (d, 6H, CH3CH).
3. Results and discussion
3.1. Esterification
2.2.3. Method 3: oxidation of isoamyl alcohol with hydrogen
peroxide
Esterification is a well-established process, commonly
used in industry. Industrial processes usually involve a
homogeneous catalyst (strong acid such as sulfuric acid).
This approach, although tightly controlled, leads to the
formation of aqueous pollutants. Therefore, various alter-
natives have been proposed in recent years. In particular,
many ‘cleaner’ synthetic methods have been developed for
the preparation of isoamyl acetate. Such methods have
focused on using milder conditions at room temperature
[14], involving an enzyme [15], or new catalytic systems
such as ionic liquids [16], superacids [17,18], cationic
resins [19] and other specific catalysts [20,21,22,23].
Acetic anhydride has also been used as an esterification
agent to produce ethyl acetate and tert-butyl acetate
[24,25] in a catalyst-free industrial process. This synthetic
method provides a high conversion rate but leads to the
formation of acetic acid, at the same time losing half the
molecule of acetic anhydride, resulting in a poor AE (68%).
We studied the synthesis of isoamyl acetate using a
macroporous acid ion exchange resin as a heterogeneous
catalyst. This method has the advantages that the reaction
medium is easier to handle and the catalyst can be reused
without generating acid effluents.
Tungstic acid (2.2 mmol) was added, in the form of a
yellow powder, to 15 mL of water and 15 mL (175 mmol) of
hydrogen peroxide (35% solution in water). This mixture
was heated at 55 8C until a homogeneous solution was
reached. We then added 3-methyl-1-butanol (113 mmol)
and 35% hydrogen peroxide (33.1 g, 340 mmol) simulta-
neously. The intermediate reaction was stirred at 90 8C for
24 hours. The medium was cooled at room temperature
until the formation of two distinct phases. The organic
phase was separated by settling. The isovaleric acid
dissolved in aqueous gas phase was extracted with
cyclohexane. The two organic phases were collected and
dried on MgSO4. Isovaleric acid (9.2 g, 79%) as a colorless
viscous liquid was obtained by distillation under reduced
pressure (40 mmHg, 85 8C).
2.2.4. Method 4: esterification of isovaleric acid
Isovaleric acid (3-methylbutan-1-oic acid) (196 mmol),
ethanol (392 mmol) and 9 g previously prepared exchange
resin Amberlyst1 15 (cf §2.1 Materials and catalyst)
were stirred at reflux for 4 h (80 8C). Ethyl isovalerate was
recovered as a colorless liquid, by distillation at atmo-
spheric pressure (T = 131–133 8C) with a 79% yield.
Two new methods of isoamyl acetate synthesis were
studied in the presence of an acid ion exchange resin:
1H NMR (400 MHz, CDCl3):
d (ppm) = 4.12–4.14 (q, 2H,
OCH2), 2.2 (d, 2H, CH2CO), 2.10–2.11 (t, 1H, CH), 1.26 (t, 3H,
CH3CH2O), 0.95–0.97 (d, 6H, CH3CH).
ꢀ
ꢀ
esterification of isoamyl alcohol with acetic acid;
esterification of alcohol with limiting acetic anhydride.
2.2.5. Method 5: transcarbonatation of dimethylcarbonate
(DMC) with isoamyl alcohol
Esterification of acetic acid was thus performed with a
catalyst loading of 5% w/w (i.e. weight of dried Amberlyst1
15/weight of alcohol), corresponding to 2% of H+ equiva-
lents. We then determined the effects of variables such as
reaction temperature, molar ratio of reactants and reaction
time (Table 3). Moreover, as the acid-catalysed esterifica-
tion reaction is an equilibrium-limited chemical reaction,
the equilibrium shift was performed by removing water
during its formation (reactions no 7, 8 and 9).
Isoamyl alcohol (196 mmol), dimethyl carbonate (DMC)
(392 mmol) and 1.7 g of K2CO3 catalyst were stirred at
reflux for 2 h (90 8C). The isoamyl carbonate was recovered
as a colorless liquid, by distillation at atmospheric pressure
(T = 157–158 8C) with a 52% yield.
d (ppm) = 4.11–4.12 (t, 2H,
OCH2), 3.78 (s, 3H, OCH3), 1.69–1.71 (dd, H, CH), 1.55 (t, 2H,
OCH2CH2), 0.90–0.92 (d, 6H, CH3).
1H NMR (400 MHz, CDCl3):
These results show that a high temperature facilitates
the crossing of the activation energy barrier to reach the
reaction equilibrium faster.
The removal of water and the addition of a slight excess
of isoamyl alcohol contribute to the equilibrium shift of the
For each synthesis, AE and EF have been calculated.
For the determination of EF, the following materials
have been integrated for the calculation of the amount of
wastes:
reaction, thus obtaining
a better performance level
ꢀ
ꢀ
ꢀ
the non reactant alcohol according to the yield;
the excess of reactant such as acetic acid or DMC;
the aqueous solvent (involved in the oxidation reaction)
and the organic solvents for the conventional methods;
the co-product such as water or methanol;
the catalyst (sulfuric acid, tungstic acid, K2CO3. . .);
the amount of water necessary to remove the homoge-
neous catalysts;
(experiment 8). The unconverted isoamyl alcohol can be
recycled to improve both the environmental and economic
aspects of this method.
Amberlyst1 15 was reused up to four times (each time
for 4 h run), without loss of its catalytic activity. A slight
reduction in yield (8%) was only observed at the second
reaction.
Synthesis of isoamyl acetate from acetic anhydride
without the use of a catalyst leads to a high conversion rate
for isoamyl alcohol, but generates an equimolar amount of
ꢀ
ꢀ
ꢀ
ꢀ
a quater of the macroporous resin weight, since the same
lot of resin can be used four times.

640
M. Bandres et al. / C. R. Chimie 14 (2011) 636–646
Table 3
Esterification of acetic acid under heterogeneous catalysis.
No
Reaction temperature
Molar ratio alcohol:acid
Reaction time (h)
Yield (%)
1
2
70
70
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1.2:1
2:1
1
4
1
4
1
4
1
1
1
9
65
22
66
67
67
81
97
97
3
100
100
120
120
120
120
120
4
5
6
7a
8a
9a
a
equilibrium shifted by Dean-Stark apparatus.
Table 4
Esterification of acetic anhydride acid with isoamyl alcohol.
No
Reaction
Molar ratio alcohol:anhydride
Reaction time (h)
Catalyst amounta (%)
Yield (%)
10
11
100
120
1:1.1
1:0.5
1
2
–
99.8
98
2.5
a
Dried Amberlyst1 15, mass percentage relative to alcohol.
Fig. 2. Equation for esterification, with acetic anhydride as the limiting reactant.
Fig. 3. Esterification reaction with optimized atom economy.
acetic acid, making purification from the medium difficult
(Table 4, experiment 10). Moreover, any trace of acetic acid
confers a stinging odor to isoamyl acetate. To lessen these
effects, the two reactions were combined as shown in
Fig. 2: esterification with acetic anhydride and esterifica-
tion with acetic acid in the presence of a heterogeneous
catalyst.
Both reactions can be implemented in an one-pot
process, as shown in Fig. 3.
These conditions were experimented with assay 11 in
Table 4.
process, with high AE. The conditions used for experiment
11 generated a reduced amount of waste (lower environ-
mental impact factor) and avoided the need for treatment
of aqueous effluents. Removal of this treatment step
contributes to the gained energy.
Mass productivity serves as an essential factor to be
taken into account for evaluation of the relative benefits of
a process. The only waste produced in experiment 11 is
70 g of water for the preparation of 1000 g of isoamyl
acetate.
Our results show a quantifiable yield after two hours of
reaction. This is associated with reduced amounts of
reactant and of waste produced, both aspects being
beneficial for industry. It thus represents a new approach
for the esterification reaction.
We compared the sustainability of the studied reactions
with that of the industrial process currently in general use
to convert primary short alcohols (Table 5).
3.2. Synthesis of ethyl isovalerate
This synthesis involves two steps: the first step involves
the oxidation of isoamyl alcohol to form valeric acid and
the second step is an esterification reaction to form ethyl
isovalerate (Fig. 4).
3.2.1. Isoamyl alcohol oxidation
In the present case, the use of ion exchange resin
provides the means for a cleaner and easier synthetic
Traditionally, the oxidation of primary alcohol to form
carboxylic acid involves the use of stoichiometric inorganic

M. Bandres et al. / C. R. Chimie 14 (2011) 636–646
641
Table 5
Comparison of the green indicators for esterification reactions.
Reagent
Catalyst
H2SO4
Atom Economy Environmental Mass
Waste
(%)
factor E
productivity (%)
Industrial
Homogeneous
CH3COOH
88
2.5
29
Acidic waste
conditionsa catalyst
(H2SO4 + CH3COOH)
None
Method 1
Assay 8
Table 3
Assay 10
Table 4
Method 2
Assay 11
Table 4
a
Heterogeneous CH3COOH
catalyst
Cation exchange 88
resin
0.3
78
No catalyst
Acetic anhydride No catalyst
68
1.1
48
93
Acidic waste
(CH3COOH)
None
Heterogeneous Acetic anhydride Cation exchange 94
catalyst resin
0.07
Experimental conditions: 80 8C, 2h, 2% eq.H+ catalyst, molar ratio alcohol:acetic acid = 1:1, Yield: 69%.
Fig. 4. Preparation of ethyl isovalerate.
oxidants, such as a chromium (VI)-based reactant [26],
manganese or ruthenium salts [27]. Such catalysts are
highly toxic for the environment and incompatible with
cosmetic applications. Therefore, with legislation on heavy
metals becoming more and more stringent, these catalysts
are no longer used. Oxidation methods also involve the use
of toxic reactants, for example periodinane and oxalyl
chloride [28].
and Dow Chemical and for the synthesis of caprolactone by
Sumitomo Chemicals Co. Diluted in water to below 60%, it
maintains its efficiency over several months and can be
stored without risk. Moreover, tungsten occurs naturally as
tungstate (WO42ꢁ) and its level of toxicity is rather lower
than other heavy metals (International Tungsten Industry
association) [31].
Various catalyst amounts and reaction times were
tested to determine the appropriate conditions.
A phase transfer catalyst (PTC) was only added for assay
7 (Table 6).
Our results show that at least 5% mol/ROH of catalyst
is needed for oxidation of isoamyl alcohol, giving a 79%
yield. Overall selectivity for the production of isovaleric
acid was observed after 24 hours. This process is simple
to operate, with hydrogen peroxide acting both as a
To meet economic and environmental demands, other
more recent methods use clean oxidants such as dioxygen,
in the presence of TEMPO (2,2’,6,6-tetramethyl piperidine-
N-oxyl) or PIPO (polymer-immobilized piperidinyl oxyl).
The use of hydrogen peroxide is of particular interest
because water is the only theoretical co-product. More-
over, aqueous H2O2 can be considered as a clean oxidant if
no organic solvent or any other toxic compound is used
[29]. Furthermore, the use, storage and transportation of
low concentrated H2O2 are not problematic in terms of
safety. The most effective catalysts for oxidation with H2O2
reactant and
a reaction solvent, which solubilizes
catalyst. The oxidizing complex in this reaction is
H2[WO(O2)2(OH)2], which is water-soluble and has a
pKa of around 0.1. The inclusion of 2% methyltrioctyl
ammonium salt (Aliquat1 336) as a phase transfer
catalyst (PTC) reduced reaction time from 24 h to 7 h,
with a 82% yield, reflecting a better conversion rate.
However, the addition of PTC also leads to a more difficult
separation of the product.
tend to be early transition metals ions with
a
d0
configuration, such as MoVI, WVI, ReVII for homogeneous
catalysts and TiIV, a heterogeneous catalyst. Such elements
generally display low catalytic activity, preventing H2O2
decomposition.
However, most of these methods are not directly aimed
at the synthesis of the carboxylic acid but rather are
selective for the synthesis of the aldehyde. Noyori et al.
have reported the efficiency of H2O2 coupled with a
tungstate complex and an acidic phase transfer catalyst, for
the oxidation of primary alcohol [30]. Therefore, we tested
the catalytic system H2WO4/H2O2 in the oxidation of
isoamyl alcohol (Fig. 5).
Table 6
Oxidation with oxygenated water: effect of catalyst amount and reaction
time on isovaleric acid production.
H2WO4
Reaction
time (h)
at 90 8C
Yield (%)
(% mol./ROH)
Hydrogen peroxide is used as a clean and cheap
oxidative agent in the oxidation of propylene by BASF
1
2
3
4
5
6
7
1
7
7
11
40
45
45
79
80
82
2
5
7
10
5
7
24
30
7
5
a
2 + PTC
a
PTC = Aliquat 336 (2% mol. /ROH).
Fig. 5. Selected conditions for isovaleric acid synthesis.

642
M. Bandres et al. / C. R. Chimie 14 (2011) 636–646
Table 7
Comparison of green indicators for oxidation reactions.
Method
Substrate
Oxidizing
agent
Catalyst
Solvent
Atom
E-factor
Hazards
(reference)
Economy (%)
[32]
[33]
[34]
Isoamyl
Alcohol
n-amyl
NaOCl
CH3CN /CH3COOH
CH2Cl2
62.9
57.1
70.4
83.6
182
58
Generation of chlorinated
derivatives
NaOCl
NaOCl2
NaOCl
TEMPO
PIPO
CH3CN
Formation of salts and
chlorinated derivates
Generation of chlorinated
derivatives
Alcohol
1-octanol
hexane
no
91
Method 3
Essay 5
Table 6
Isoamyl
Alcool
H2O2 (35%)
H2WO4
6.7
Aqueous solution of H2WO4
TEMPO: 2,2’,6,6-tetramethyl piperidine-N-oxyl; PIPO: Polymer-immobilized piperidinyl oxyl.
This method was compared to conventional oxidation
reactions in Table 7.
The use of the selected catalytic system H2WO4/H2O2 is
an efficient method in terms of AE and leads only to
aqueous effluents.
Despite using a non-toxic catalyst, the usual oxidation
reaction with TEMPO does not respect the whole green
principles (waste production, solvent use) compared to the
studied path.
distilled during the reaction due to a water:ethanol
azeotrop (with a 95.6:4.4 composition at 78.2 8C). The
reaction was selective for the production of ethyl
isovalerate, in all conditions tested. No trace of isoamyl
isovalerate was detected by gas chromatography.
Ethyl isovalerate can be isolated by distillation (boiling
point = 132–134 8C). This was the only purification step
required after successive oxidation and esterification,
leading to a global yield of 67% after a total reaction time
of 11 hours.
3.2.2. Esterification of isovaleric acid
The synthesis of ethyl isovalerate from isovaleric acid
involves an esterification reaction with ethanol. This step
was carried out using similar conditions as used for
isoamyl alcohol esterification. The reaction was per-
formed with ion exchange resin catalysis in refluxing
ethanol, obtained directly from the oxidation medium
containing isovaleric acid and less than 20% of non-
reacted isoamyl alcohol. No intermediate step of purifica-
tion was therefore needed, keeping the process simple to
operate. We studied the effects of changes in ethanol:acid
ratio and amount of resin on the conversion rate. Results
are presented in Table 8.
We observed a decrease in conversion rate with
increasing alcohol:acid molar ratio, which can be
explained by an increasing dilution factor of the resin in
the reaction medium. A high amount of resin led to a
higher conversion of isovaleric acid (85.6%) for a 2:1
alcohol:acid molar ratio. This excess of alcohol shifted the
reaction equilibrium, because the water could not be
3.3. Isoamyl alcohol carboxymethylation
The selective synthesis of unsymmetrical carbonate is
difficult due to the formation of the more stable
symmetrical carbonate (diisoamyl carbonate).
Many methods for the synthesis of alkyl carbonates
from alcohols have thus been exploited. Reactants such as
urea or its carbamate derivatives [35], carbon monoxide
[36] or supercritical CO2 [37,38], lead to low yields for the
preparation of mixed carbonates. The selectivity for mixed
carbonates can be improved using more nucleophilic and
unsymmetrical reagents such as halogenoalcanes [39],
acid halides [40] or haloformates [41]. These syntheses
involve polar solvents such as acetonitrile or dimethyl-
formamide.
However, these unsymmetrical carbonates are still
prepared on an industrial scale from highly toxic starting
materials (such as phosgene COCl2) via methyl chloro-
formiate. New pathways involve carbonated building
Table 8
Conversion of isovaleric acid according to stoichiometry.
Assay
Resin weight
Molar ratio
Conversion vs. isovaleric
acid after 4h (%)
Conversion vs. isovaleric
acid after 7h (%)
(%mass/ethanol)
(ethanol:isovaleric acid)
1
2
5
5
1:1
50.4
30.6
24.9
16.2
6.5
53.6
35.7
28.2
26.0
12.3
–
1:2
3
5
3:1
4
5
5:1
5
5
10:1
1:1
6
50
50
50
50
50
50
75
77.3
80.7
85.6
74.8
56.1
41.7
–
7
1.5:1
2:1
–
8
–
9
3:1
83.6
–
10
11
12
5:1
10:1
3:1
–
86.8

M. Bandres et al. / C. R. Chimie 14 (2011) 636–646
643
Fig. 6. Transesterification of isoamyl alcohol by DMC.
Fig. 7. Selected conditions for the carbonatation of isoamyl alcohol.
blocks such as DMC, which has been shown to be an
efficient methoxycarbonylating agent and can be formed
by a clean synthetic process [42,43].
However, the transesterification of aliphatic alcohols
with DMC is still carried out with toxic catalysts such as (n-
Bu2SnO)6 [44] or requires a phase transfer catalyst with
high temperature and pressure conditions [45].
Recent work by Tundo et al. [46] showed the efficiency
of such a reaction using K2CO3: a high temperature (200 8C)
and a considerable excess of DMC were needed to obtain a
good yield and high selectivity. These conditions require a
batch autoclave, which is not suitable for large-scale
industrial production.
We adapted this process for the methoxycarbonylation
(also called transcarbonatation) of isoamyl methyl car-
bonate with DMC, through a simpler process and under
milder conditions. This reaction is based on the transes-
terification mechanism. DMC, doted of high polarity,
serves as both a solvent and a reactant.
compound such as sodium methylate MeONa, which
behaves as a homogeneous catalyst.
The results presented in Table 9 show high conversion
and selectivity rates for the three catalysts. Moreover,
these conditions can minimize the formation of the
symmetrical carbonate. The kinetics of the reaction with
potassium carbonate was twice as slow as those with the
other catalysts; however, the use of potassium carbonate
also resulted in a higher selectivity for mixed carbonate
production.
Despite its effectiveness, the use of sodium methylate is
not compatible with the principles of green chemistry. Its
miscibility in the reaction medium complicates its disposal
since a washing step with water is needed, involving the
production of large quantities of alkaline waste products.
Additionally, it is not reusable and its low stability during
storage (hydrolysis in methanol) makes its application in
industry difficult.
NaOH and K2CO3 are easily separated from the final
medium because they are not soluble. Moreover, they are
relatively inexpensive and have only very low levels of
toxicity. However, potassium carbonate is a better desiccant
than NaOH, allowing both the catalysis of the reaction and
the capture of water that may be present in the reaction
medium if fusel oil is directly employed as reactant (Fig. 7).
The mixed carbonate was formed through the BAC
2
mechanism (step 1, Fig. 6). The distillation of methanol to
shift the equilibrium is only recommended to produce
diisoamyl carbonate (step 2).
3.3.1. Influence of catalyst
Basic catalysts are effective in the preparation of a
mixed carbonate from DMC and an alcohol. However, the
use of metal catalysts can generate toxic traces of heavy
metals in the final product, requiring costly purification to
meet legislative requirements.
Therefore, we tested non-metallic catalysts: two
inorganic alkali compounds such as sodium hydroxide
NaOH or potassium carbonate K2CO3, and an organic
3.3.2. Influence of molar DMC:alcohol
We tested several molar ratios of DMC:alcohol for
increased selectivity of the reaction. Our results (Table 10)
showed that an excess of DMC favored the reaction
selectivity. The DMC:alcohol ratio was set at 5 to limit
dilution of the medium and to maintain a high conversion
rate.
Table 9
Effect of catalysis on reaction performance.
Assay
Catalyst (1 %) w/w vs alcohol)
Type of catalyst
Reaction time (h)
Conversion (%)
Selectivity (%)
Yield (%)
1
2
3
4
NaOH
MeONa
K2CO3
K2CO3
Heterogeneous
Homogeneous
Heterogeneous
Heterogeneous
1
1
1
2
84
90
54
82
65
60
74
71
55
54
40
58
DMC: isoamyl alcohol = 2 : 1 (mol.), 90 8C (reflux).

644
M. Bandres et al. / C. R. Chimie 14 (2011) 636–646
Table 10
We compared characteristics of green chemistry
between the various methods of isoamyl alcohol methox-
ycarbonylation (with DMC or phosgene) (Table 12).
Reactions involving DMC have reduced effects on the
environment. Moreover, the protocol for heterogeneous
catalysis does not involve toxic substances and avoids the
production of waste products.
Effect of the DMC: alcohol molar ratio on the reaction selectivity.
Ratio DMC: alcohol
2:1
3:1
5:1
Conversion (%)
Selectivity (%)
Yield (%)
82
71
58
79
83
66
75
95
74
Reaction conditions: 90 8C, 2 hours, 1% mass K2CO3 relative to alcohol.
Method 5 is thus a safe alternative for the selective
carboxymethylation of alcohol. This process seems to offer
the best compromise taking into account economical
aspects, performance and environmental concerns.
The use of non-distilled fusel oil containing 7% water
affects the catalytic activity of potassium carbonate,
reducing the reaction rate, so that 10 hours are needed
to obtain the maximal yield (74%), rather than the 2 hours
indicated in Table 10.
3.4. Comparison of volatility characteristics of synthesized
biosolvent
The catalyst was filtered and the medium distilled to
separate the different compounds.
Table 11 shows the composition of the collected
fractions.
Flash point and boiling point are two important
characteristics affecting the drying time of nail polish
formulations. Several formulations have been prepared
with the synthetized solvents and the conventional
solvents. They consist of the following ingredients:
10.5% of nitrocellulose (polish agent), 5% of acetyl tributyl
citrate (plastizicer), 7.5% of polyester resin and 77% of
solvent.
Table 13 shows the drying time of these nail polish
formulations. We compared the data of the new formula-
tions with those of the standard formulation prepared with
a blend of ethyl acetate and butyl acetate.
An energy saving synthetic process was thus devel-
oped with a methoxycarbonylating agent (DMC), which
is biodegradable and non toxic [45]. This process
involves heterogeneous conditions and uses a five-fold
excess of refluxing DMC at 90 8C for a reaction time of
one hour.
A large excess of DMC prevents the formation of
symmetrical carbonate and leads to the production of
isoamyl methyl carbonate with high selectivity (95%).
Distillation is the only purification step required to obtain
methyl isoamyl carbonate. Reaction conditions are com-
patible with large-scale transfer by an economically viable
process.
The drying times of the biosolvent formulations were
longer than those observed for the standard formulation
(30). However, they are still acceptable for the intended use
when a cosolvent is added in the formulation [5].
Table 11
Fractions collected by distillation after methoxycarbonylation of isoamyl alcohol.
Fraction
Temperature (8C)
Composition
Fate
1
2
3
4
63.5
Methanol:DMC (70:30)
DMC (99%)
Difficult purification ! waste
Recyclable
90
132–134
157–158
Isoamyl alcohol (98%)
Methyl isoamyl carbonate (98%)
Recyclable
Table 12
Green indicators of carboxymethylation methods.
No
Reagent
Catalyst
Solvent
Atom economy (%)
E-factor
Mass productivity (%)
Hazards
[47]
Phosgene
DMC
Pyridine
MeONa
Hexane
–
74.7
82
5.4
3.4
16
23
Toxic reactant
Assay 2
Table 9
Method 5
Assay 4
Table 9
Aqueous basic waste
DMC
K2CO3
–
82
1.3
42
Low impact
Table 13
Volatility characteristics for solvents and mixture of solvents used for the nail polish formulations.
Solvents
Formulation flash
Solvent boiling
Time until dry to
touch (min)
Total drying
time (min)
point (8C)
point (8C)
Butyl acetate/ethyl acetate (40/ 60 w/w)
Isoamyl acetate
3
125/77
125
30
120
130
160
3030
13030
150
25
Ethyl isovalerate
26.7
55.5
135.1
157
Isoamyl and methyl carbonate
210

M. Bandres et al. / C. R. Chimie 14 (2011) 636–646
645
Table 14
List of parameters used in Eq. (1).
Symbol
Variable
Production parameters
Ex
Kx
Mx
A
Emissions of VOC species
kg/yr
Gas-phase mass transfer coefficient for VOC species
Molecular weight of VOC species
m/sec
g/mol
10.2 m2
kPa
Surface area of tank opening
Px
H
R
Partial vapor pressure of chemical x at temperature T
Batch time necessary to perform the blend
Universal gas constant at a pressure of 1atm
Ambient Temperature
3 hr
8.31 J/mol/8C
20 8C
T
B
Number of batches per year
300/yr
We calculated the resulting VOC emissions of the
biosolvent with the faster drying time (isoamyl acetate).
The modeling equations can be used to select an
appropriate solvent and to estimate the corresponding
emissions, before more complex analysis is required.
3.5. Evaluation of VOC emissions during the production of a
nail polish
4. Conclusion
The amount of VOC released into the atmosphere during
the production of solvent-based products is controlled by
environmental regulations. Solvent evaporation is seen at
each stage of the commercial production of coatings (for
example, nail polish, paint or ink). Photochemical interac-
tions between VOC and nitrogen oxides(NOx) then generate
ground-level ozone, responsible for bad air quality. To help
industry reduce their VOC emissions, the U.S. Environmen-
tal Protection Agency has published guidelines describing
techniques for estimating the emissions produced during
the manufacture of paints, inks and other coatings [48].
These methods have been applied to processes currently in
use for the manufacture of coatings, to estimate annual VOC
emissions due to solvent use. The generation of emissions
has been assessed for surface evaporation during dispersion
of the ingredients in an open tank according to the Eq. (1)
and Table 14. It is one of the step which releases the highest
proportion of emissions into the atmosphere.
This study has demonstrated that a co-product of the
bioethanol industry can be used as a synthon to produce
safer molecules for the replacement of solvents currently
in use.
Conventional methods such as esterification, oxidation
or transcarbonatation have been modified into ecofriendly
processes. External solvent-free reactions, heterogeneous
catalysis, mild conditions and straightforward purification
are the main parameters which lead to improved green
metrics.
We have shown that green units represent an useful
concept to select the valuable molecules as efficient
competitors towards the petrochemical molecules.
Moreover, VOC emission models provide key tools to
check the environmental benefits for the resulting
biobased formulations.
Eventually, the molecules and the associate processes
which match the targeted criteria for the development of
new biosolvents, deserve a further study for a scale transfer
of their production to industry.
Mx ꢃ Kx ꢃ A ꢃ Px ꢃ 3600 ꢃ H
Ex ¼
ꢃ B
(1)
R ꢃ T
The formulation of a conventional nail polish formula-
tion, with a volatile fraction containing three petrochemi-
cal solvents (ethyl acetate, butyl acetate and isopropanol)
is then compared with the production of a nail polish
formulation in the same conditions using natural-based
solvents (Table 15).
Acknowledgement
Durlin company is gratefully acknowledged for their
financial support and for their cooperation.
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