A methodical selection process for the development of ketones and esters as bio-based replacements for traditional hydrocarbon solvents

Article abstract of DOI:10.1039/c8gc01132j

A "top down" approach to the development of sustainable, greener, low-polarity solvents is presented. Methyl butyrate, ethyl isobutyrate, methyl pivalate and pinacolone were identified as potential target solvents from trends in Hansen solubility parameters and known physical properties. Solubility, flammability and physical properties were determined which showed their potential to replace traditional, hazardous, volatile, non-polar solvents such as toluene. Each new candidate then demonstrated their suitability to replace these traditional solvents in solubility tests, despite being esters and ketones, each candidate demonstrated their similarity to traditional volatile non-polar solvents in terms of their solubility properties by their ability to dissolve natural rubber, a particularly low-polarity solute. This was reinforced by their performance in a model Menschutkin reaction and a radical-initiated polymerisation for the production of pressure-sensitive adhesives, where their performance was found to be similar to that of toluene. Importantly, a preliminary toxicity test (Ames test) suggested non-mutagenicity in all candidates. Each of the four candidates can be synthesised via a catalytic route from potentially renewable resources, thus enhancing their green credentials.

Full text of DOI:10.1039/c8gc01132j

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A methodical selection process for the
development of ketones and esters as bio-based
replacements for traditional hydrocarbon
solvents†
Cite this: DOI: 10.1039/c8gc01132j
a
b
b
b
Fergal P. Byrne,
Bart Forier, Greet Bossaert, Charly Hoebers,
a
c
Thomas J. Farmer * and Andrew J. Hunt
*
A “top down” approach to the development of sustainable, greener, low-polarity solvents is presented.
Methyl butyrate, ethyl isobutyrate, methyl pivalate and pinacolone were identified as potential target sol-
vents from trends in Hansen solubility parameters and known physical properties. Solubility, flammability
and physical properties were determined which showed their potential to replace traditional, hazardous,
volatile, non-polar solvents such as toluene. Each new candidate then demonstrated their suitability to
replace these traditional solvents in solubility tests, despite being esters and ketones, each candidate
demonstrated their similarity to traditional volatile non-polar solvents in terms of their solubility properties
by their ability to dissolve natural rubber, a particularly low-polarity solute. This was reinforced by their
performance in a model Menschutkin reaction and a radical-initiated polymerisation for the production of
pressure-sensitive adhesives, where their performance was found to be similar to that of toluene.
Importantly, a preliminary toxicity test (Ames test) suggested non-mutagenicity in all candidates. Each of
the four candidates can be synthesised via a catalytic route from potentially renewable resources, thus
enhancing their green credentials.
Received 10th April 2018,
Accepted 26th June 2018
DOI: 10.1039/c8gc01132j
rsc.li/greenchem
6
functionalised with electronegative O atoms, which results in
high polarity. In contrast, traditional non-polar solvents tend
Introduction
7
Volatile, non-polar (VNP) solvents are essential throughout the to be either hydrocarbons (e.g. hexane, cyclohexane, toluene)
chemical industry, with applications in synthetic chemistry, or chlorinated hydrocarbons (e.g. carbon tetrachloride, chloro-
8
,9
coatings industry and liquid–liquid extraction, where facile form).
Removing functionality from biomass to reduce
removal by evaporation is required. Many traditional VNP sol- polarity is possible, but what is left often closely resembles the
vents such as the aliphatic hydrocarbon solvents hexane or traditional target solvents for replacement e.g. removing all
cyclohexane and the aromatic solvents toluene or benzene functionality from glucose could yield hexane but this process
6
suffer from high persistence, bioaccumulation and toxicity would have a low atom economy. Chlorination is an option
1
–4
(PBT).
More specifically, hexane is suspected of damaging but the same toxicity and end-of-life issues that exist with tra-
1
3
fertility, toluene is suspected of damaging the unborn child,
and benzene is a known carcinogen. As such, replacements bio-based alternatives.
ditional chlorinated solvents are likely to persist in chlorinated
4
10–13
for this class of solvent which adhere to the principles of green
chemistry are needed. The challenge with the development of been recently proposed but many have issues of their own. The
A number of alternatives to traditional VNP solvents have
5
non-polar solvents from biomass is that biomass is highly hydrocarbons D-limonene and para-cymene have a suitable
polarity and are bio-based but are much less volatile than tra-
1
4–17
ditional hydrocarbon solvents (T = 177 °C in both cases).
b
a
2-Methyltetrahydrofuran has suitably low polarity and high
volatility (T = 80 °C) but forms hazardous peroxides in
Green Chemistry Centre of Excellence, Department of Chemistry, The University of
York, Heslington, York, YO10 5DD, UK. E-mail: thomas.farmer@york.ac.uk
b
b
18
Nitto Belgium NV, Eikelaarstraat 22, Belgium
ambient conditions. Recently, the unusual ether 2,2,5,5-tetra-
methyltetrahydrofuran (2,2,5,5-tetramethyloxolane (TMO, pre-
viously reported as TMTHF)) has shown great promise to
c
Materials Chemistry Research Center, Department of Chemistry and Center of
Excellence for Innovation in Chemistry, Faculty of Science, Khon Kaen University,
Khon Kaen, 40002, Thailand. E-mail: andrew@KKU.ac.th
7
replace toluene. It shares a very similar boiling point to
†
Electronic supplementary information (ESI) available. See DOI: 10.1039/
c8gc01132j
toluene (T = 112 °C compared to 111 °C for toluene), is of very
b
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7
low polarity and does not form peroxides. However, appli-
Herein, a similar “top-down” approach was utilised in an
cations where TMO is not the optimal solvent will inevitably attempt to identify replacements for traditional VNP solvents,
be identified and as such, more alternatives to traditional such as hexane and toluene among the ester and ketone
hydrocarbons are required. Esters and ketones tend to score family. Trends within esters and ketones were observed using
well in solvent selection guides due to their low-toxicity and HSPiP, after which several candidate molecules with an
6
,8,9
often facile production from biomass.
However, com- optimal balance of polarity and volatility to replace hydro-
monly-used esters and ketones do not possess a combination carbons were discovered. The best candidates were character-
of low-polarity and high volatility (Fig. 1). For example, ethyl ised in terms of their solubility properties using the Kamlet–
2
8–30
acetate is volatile but of medium polarity, whereas n-butyl Abboud–Taft (KAT) parameters
acetate is of medium-to-low polarity but its boiling point is sig- reaction.
and a model Menschutkin
Solubility tests using natural rubber as an indust-
nificantly above that of toluene (T = 126 °C compared to rially-relevant probe solute were also carried out. Physical,
3
1–33
b
1
9–21
1
11 °C for toluene).
flammability and toxicity (Ames test) properties were also
Several intelligent approaches to greener solvent selection determined. Furthermore, the best candidates were tested in
1
1,22,23
and development have been reported in recent years.
the production of a commercial pressure-sensitive adhesive
One such approach, developed by Moity et al., involves design- (PSA) via the radical-initiated polymerisation of acrylate mono-
ing solvents by performing chemical transformations on a mers and subsequently tested by coating of the adhesive
chosen bio-based platform molecule to generate a list of candi- polymer on a carrier film. Finally, a green assessment was
2
4
date solvents. The properties of each candidate are then made on the most promising candidates.
determined and their suitability as solvents is assessed either
2
4
in silico or in practise. Applications for the best candidates
can be identified once their properties are known. This
Results and discussion
Solvent selection process
2
2
approach has been applied to levoglucosenone, itaconic
25
26
27
acid, glycerol and isoamyl alcohol.
Another approach is to design solvents to fit a set of physi- The aim of this article is to find replacements for traditional
cal and solvent property criteria, for which computer-aided hydrocarbon solvents. Traditional hydrocarbons tend to be
1
1
molecular design is often employed.
This approach is volatile and of low-polarity. As such, boundaries were set as to
applied when a greener solvent is required to dissolve a known what was acceptable in terms of polarity and boiling point for
target solute or when a traditional solvent has been identified new replacement solvents. The boiling point of toluene
for replacement. Such an approach has been reported before (111 °C) was set as the upper limit, while natural rubber
by Jin et al. to identify replacement solvents for chlorinated (20 wt% concentration) was chosen as a low-polarity probe
1
1
hydrocarbons such as dichloromethane and chloroform.
Importantly, this approach highlighted the need for toxicity Hydrocarbon solvents such as toluene and hexane are tra-
testing at an early stage in the solvent development process. ditionally used for the dissolution of natural rubber and it is
Moity et al. reported the use of a hybrid of the abovemen- insoluble in medium- to high-polarity solvents.
solute to compare potential candidates in terms of polarity.
tioned approaches; nitrocellulose was chosen as a target solute
HSPs are a useful tool in characterising solvents and
HSP divides the
solvent properties into three parameters which describe a
3
4,35
and glycerol was chosen as a bio-based platform in a “top- solutes with respect to their polarity.
23
down” methodology.
molecules dipolarity (δ ), hydrogen-bonding ability (δ ) and
P
H
dispersion forces (δ
solved by solvents with similar HSPs. By plotting δ
D
) separately, and solutes tend to be dis-
3
4
H
against
δP, solvent properties can be easily visualised on two-dimen-
sional solvent polarity maps. As such, HSPs were employed to
identify trends within the target solvent classes (esters and
ketones).
The relationship between structure, polarity and T
b
in
esters and ketones was examined by adding alkyl groups to
1
2
fundamental ester and ketone structures (R COOR and
3
4
R COR respectively) in both a linear and branched manner
until all permutations of esters/ketones as far as C7 were gen-
erated. The search was stopped at C7 as this was the point at
b
which T became higher than the boundaries set in this work.
The total polarity of cyclic esters (lactones) and ketones is
higher compared to their acyclic equivalents and therefore
were not included. All permutations of ester and ketones were
Fig. 1 HSP solvent polarity map showing all permutations of esters
with T <111 °C (green) and >111 °C (orange). Natural rubber is rep-
H P
plotted on solvent maps of δ against δ , as shown in Fig. 1
b
resented by a blue circle.
and 2. Esters and ketones highlighted in green have T ’s below
b
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Fig. 3 The optimal ester and ketones candidates in terms of polarity
and T .
b
3
7
b b
with a T of 134 °C, compared to pentyl butyrate with a T
Fig. 2 HSP solvent polarity map showing all permutations of ketones
3
8
with T
resented by a blue circle.
b
<111 °C (green) and >111 °C (orange). Natural rubber is rep- of 186 °C. tert-Butyl pivalate provides an alternative ester
option for applications where low polarity is more essential
than volatility. Similarly, the highly branched 2,2,4,4-tetra-
methyl-3-pentanone (shown in Fig. 3) possesses the optimal
b
polarity/T ratio in ketones (Fig. 2), and provides an alterna-
tive ketone option for such applications. However, both tert-
butyl pivalate and 2,2,4,4-tetramethyl-3-pentanone fall
b
outside the T limit set in this work and so were not tested
1
11 °C while those in orange have T ’s above 111 °C (T ’s of
39
b
b
each ester and ketone were obtained from the ChemSpider
database). The molecules highlighted in green that are closest
to natural rubber (Fig. 1 and 2) are likely to be able to dissolve
natural rubber, whilst maintaining an acceptable T . The
b
molecules highlighted in green that are furthest from the
natural rubber have lower T ’s but are of higher polarity and
thus, of greater disparity from hydrocarbon solvents.
Several trends were observed within the ester and ketone
classes. Firstly, the polarity of the target solvent decreased
any further.
The thirteen esters and six ketones with T ≤111 °C (high-
b
lighted in green in Fig. 1 and 2) were tested for their ability to
dissolve natural rubber and the results are shown in Table S1
b
(
ESI†). Only methyl pivalate, methyl butyrate, ethyl isobuty-
rate (esters) and pinacolone (ketone) could dissolve the
rubber and as such, were selected as the best candidates. The
remaining esters and ketones were omitted. Thus, the 19
esters and ketones were reduced down to four, as shown in
Fig. 4.
(HSPs approached 0) as alkyl groups were added to the funda-
mental ester and ketone structure. Secondly, increased branch-
ing in alkyl groups in esters and ketones resulted in lower Tb
and lower polarity than their linear alkyl equivalents with the
same number of carbon atoms. This is demonstrated by tert-
butyl acetate and n-butyl acetate, whose T ’s are 96 °C and
b
2
0,36
1
26 °C respectively.
In addition, tert-butyl acetate is less
polar. Thirdly, in the case of esters, the carboxylate side of the
ester tended to have more influence on polarity than the
alcohol side, as demonstrated by solubility testing using
natural rubber. For example, the C6 ester with a C3 carboxylate
group, propyl propionate, was experimentally found to be
unable to dissolve natural rubber whereas the C5 ester with a
C4 carboxylate group, methyl butyrate, could. The cut-off for
carboxylate groups able to dissolve the natural rubber
appeared to be C4: butyrates and isobutyrates. Finally, the
HSPs of esters and ketones showed that in general, esters have
lower dipolarity (due to two O atoms competing against one
another for electron density) but higher hydrogen-bonding
ability (due to the presence of two O atoms with four hydro-
gen-bond accepting lone-pairs) than ketones.
Knowledge of these four trends led to the optimal polarity/
T ratio in esters and ketones. Pivalate esters, particularly
b
tert-butyl pivalate (shown in Fig. 3), were of noticeably lower
polarity than the other esters due to their higher degree of
branching (Fig. 1). Branching also maintained a relatively low
Tb, as demonstrated by the two C9 esters, tert-butyl pivalate Fig. 4 Screening process of esters and ketones.
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Characterisation of the best candidates
bond donating and accepting abilities and dipolarity/polarisa-
bility respectively. The KAT parameters are useful in generating
A range of solvent properties for ethyl isobutyrate, methyl buty- linear solvation-energy relationships (LSERs) for model reac-
3
2,33
14
rate, methyl pivalate and pinacolone are shown in Table 1 in tions such as Menschutkin,
amidation and esterifica-
1
4
comparison to the traditional hydrocarbon solvents, toluene tion reactions.
and hexane. While toluene possesses a lower permanent dipole than the
The T ’s of each candidate are lower than toluene meaning four candidates (shown by δ ), it is more polarisable due to the
b
P
facile removal by evaporation is possible. Low melting points delocalised electrons in the aromatic ring (shown by δD),
indicate that all candidates are liquids at room temperature, resulting in very similar π* values (KAT measurement of dipo-
while all are less dense than water, and similar to toluene. larity and polarisability combined) between the four candi-
Importantly, the autoignition temperatures (AIT) of all candi- dates and toluene. Like toluene, none of the candidates are
dates are >200 °C (the threshold set in the CHEM21 solvent protic (α = 0.00). However, the key difference between the four
9
guide ) which is vital for the safe use of volatile organic liquids candidates and toluene is in their hydrogen-bond accepting
and all are comparable to toluene and far superior to hexane. ability. The presence of lone-pairs on the O atoms in the four
In addition, methyl pivalate, methyl butyrate and pinacolone candidates mean that a degree of basicity is present (β =
have a superior (i.e. higher, all 1.3%) lower explosion limit 0.45–0.58), whereas the lack of lone-pairs on toluene mean its
(
LEL) to toluene (1.1%) and hexane (1.1%). Only ethyl isobuty- basicity is far weaker (β = 0.11). The slight basicity is due to
rate had a lower LEL (0.9%). However, when the density and the slight interaction between the electron-rich aromatic ring
molecular weight (M ) is considered, all candidates are with protic substrates.
w
superior to toluene in terms of explosion limits (calculations
shown in ESI†).
However, such a low polarity, like traditional hydrocarbon
solvents, is not required for most applications. This is exempli-
An Ames test showed that none of the four candidates were fied in the solubility tests where very low-polarity natural
41,42
mutagenic (Fig. S2†).
While the Ames test is a useful pre- rubber could successfully be dissolved by solvents of higher
liminary assessment, extended in vitro and in silico investi- polarity. In the past many traditional non-polar hydrocarbon
gations are currently underway to further explore the safety solvents were chosen due to their volatility and low cost.
profile of these candidate compounds. The octanol/water par- Although each candidate must be assessed for their suitability
tition coefficient (log Po/w) shows that all four candidates are to replace hydrocarbon solvents in a case-by-case basis, each of
immiscible with water (log Po/w > 1), allowing aqueous extrac- the four candidates has demonstrated an ability to dissolve the
tion and washing during work-up. However, none have log Po/w very low-polarity natural rubber, suggesting that issues with
values large enough to suggest that they are likely to bioaccu- their slightly higher polarity are unlikely.
4
3,44
mulate (in all cases log Po/w < 4.5).
Odour is another issue which is important to consider in
The Kamlet–Abboud–Taft (KAT) parameters are an empiri- industrial processes, especially those in open systems. Methyl
cal measurement of polarity based on solvatochromism. The pivalate and ethyl isobutyrate have pleasant apple and straw-
absorbances of probe dyes are used to determine values for berry odours respectively, while pinacolone has a characteristic
2
8
29
30
three parameters α,
β
and π*, which represent hydrogen- ketone odour, much like acetone or 2-butanone (MEK).
Table 1 Solvent properties of the four best candidates compared to toluene and hexane
Ester
Ketone
Pinacolone
Aromatic hydrocarbon
Toluene
Aliphatic hydrocarbon
Hexane
Solvent property
Methyl pivalate
116.16
Methyl butyrate
102.13
Ethyl isobutyrate
116.16
/g mol−
1
100.16
105–106
92.14
86.18
M
w
a
a
a
a
a
a
T
T
b
/°C
100–101
100–102
108–110
111
69
a
a
a
a
a
a
m
/°C
−70
−85
−88
−53
−93
−95
−1
a
a
a
a
a
a
ρ/g ml
0.875
0.898
0.865
0.803
0.867
0.661
b
b
b
b
b
a
AIT/°C
LEL/%
Ames test
log P(o/w)
α
443
428c
451c
428c
522c
225c
c
1.3
1.3
0.9
1.3
1.1
1.1
d
d
d
d
d
d
Pass
Pass
Passd
Passd
Pass
2.73
Pass
4.00
d
d
e
e
1.74f
1.20f
1.54
1.21
f
f
f
f
0.00
0.45
0.49
0.00
0.48
0.51
0.00g
0.00g
0.00g
0.00g
g
g
β
0.48
0.49
0.58
0.59
0.10
0.51
0.00
0.00
h
h
h
h
h
h
π*
i
0.5
δ
δ
D
/MPa
15.0
3.8
5.0
15.8
4.9
6.2
15.4
4.3
5.1
15.1
5.5
3.3
18.0
1.4
2.0
14.9
0.0
0.0
i
0.5
P
/MPa
i
0.5
Δ
H
/MPa
a
b
c
d
e
40 f
Pubchem. Carried out by ITS testing services. Carried out by Chilworth Technology. This work. Sangster. Assumed value as molecule is
g
h
i
aprotic. This work, using N,N-diethyl-4-nitroaniline and 4-nitroaniline dyes. This work, using N,N-diethyl-4-nitroaniline dye. Predicted using
HSPiP.
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However, the smell of methyl butyrate is similar to butyric acid between 1-methylimidazole and the longer chained 1-bro-
and is very unpleasant, which may hinder its use in open mooctadecane (C18) was used in this work to compare the
systems.
esters and ketone with toluene and ethyl acetate due to the
insolubility of the C8 product, 1-octyl-3-methylimidazolium
bromide, in the lower polarity candidate solvents (Fig. 5). The
Synthetic routes to the four best candidates from biomass
Each of the four candidates (methyl butyrate, ethyl isobutyrate, integrated second-order rate equation was used to calculate
1
methyl pivalate and pinacolone) can be produced from renew- the reaction rate based on peak integration using H NMR
able resources. The synthesis of butyric acid and isobutyric spectroscopy.
acid from glycerol in excellent selectivities has been reported
A selection of other solvents was also used to generate the
4
5
previously by Coskun et al. A potential flow diagram for LSER: NMP, DMF, MEK, acetone, chlorobenzene, THF, triethyl-
large-scale production, analogous to that of the Cativa process, amine, TMO and limonene. The LSER in Fig. 5 shows a corre-
is shown in Fig. S4 (ESI†). Glycerol can be sourced renewably lation between rate and π* among the solvents with π* ≥ ∼0.4,
from used cooking oil and has previously been used for which plateaus for solvents with π* < ∼0.4 (triethylamine,
2
6,46–48
solvent production.
limonene and TMO). The cause of the plateau in low polarity
The precursor to methyl pivalate and pinacolone is pivalic solvents is likely to be due to micelle formation due to the
5
2
acid, which can be produced by the carbonylation of isobutene highly charged “head” and lipophilic “tail” of the product.
with carbon monoxide in a Koch reaction. Isobutene can be The charged centre of the micelle could host reactions
produced by fermentation of sugars, a process that has between trapped 1-methylimidazole and 1-bromooctadecane at
49
recently been commercialised by Global Bioenergies, ketoni- a rate greater than what would be expected in low π* solvents.
5
0
51
sation of pivalic acid using acetone or acetic acid to The reaction rates in each of the esters was very similar and all
produce pinacolone in good yields has previously been were slightly higher than that of toluene. The reaction rate in
reported.
toluene was slightly slower than what would be expected in a
Esterification of butyric, isobutyric and pivalic acids with solvent with π* = 0.51 according the LSER in Fig. 5. This can
the corresponding alcohols to yield methyl butyrate, ethyl iso- be explained by toluene’s high polarisability concealing its low
butyrate and methyl pivalate respectively was carried out as dipolarity when measured using solvatochromic dyes, but
part of this work (Fig. S3†). Almost full conversions (99%) of which is revealed when measured in the Menschutkin reac-
butyric and isobutyric acids using the corresponding alcohols tion. The rate of reaction in pinacolone was slightly quicker
were obtained after 45 minutes using methanesulfonic acid than the candidate esters, consistent with its higher π* (0.59),
as the catalyst in a reactive distillation apparatus. The rate of
pivalic acid conversion was slightly slower due to the bulky
tert-butyl group on the acid, with 88% conversion of the acid
observed after 45 minutes. The heterogeneous acid catalyst,
Amberlyst 15, also achieved high conversions of butyric acid
(
>95%) and pivalic acid (71%) with methanol in the same
reactive distillation apparatus after 45 minutes. Despite the
rate of carboxylic acid conversion being slightly slower than
methanesulfonic acid, Amberlyst 15 has the advantage of
being non-corrosive and reusable, adding to its greenness
and meaning acid resistant steel is not required in large-scale
production.
Application testing: Menschutkin reaction
The Menshutkin reaction was the first model reaction to be
3
1–33
used to correlate solvent polarity with reaction rate.
The
reaction of triethylamine with iodethane to form the quatern-
ary ammonium salt was the original probe reaction and it was
found that high solvent dipolarity increased the reaction rate
3
1
due to transition state stabilisation. More recently, a similar
reaction between 1-methylimidazole with 1-bromooctane (C8)
was exploited for the characterisation of the bio-based dipolar
3
2
33
aprotic solvents, cyrene and N-butylpyrrolidinone (NBP), in
comparison with a selection of traditional dipolar protic
solvents.
Although not dipolar aprotic solvents, the four candidates
can be compared to toluene in terms of their π* using a
similar Menschutkin reaction. The Menschutkin reaction Fig. 5 Menschutkin reaction scheme and LSER.
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although this rate of reaction was still slightly slower than
A proposed mechanism of radical formation resulting in
what would be expected according to the LSER; the LESR chain termination in ethyl isobutyrate is shown in Fig. S6
would suggest a rate similar to that of THF. This could poten- (ESI†). A hydrogen atom can be abstracted from the solvent
5
5
tially be explained by the presence of a small amount of the molecule, terminating the chain.
The newly formed
enol form of pinacolone (Fig. S5, ESI†). Protic solvents are radical on the solvent molecule can also react with a radical
5
5
known to inhibit the reaction rate severely due to stabilising on the polymer, again, terminating the chain. For chain
5
3
interactions with 1-methylimidazole.
1-Methylimidazole transfer to the solvent to occur, stable radicals must be able
5
5
could in turn stabilise the enol form of pinacolone just to form on the solvent molecules. It was thought that if
enough to cause the slight reduction in reaction rate observed ethyl isobutyrate was undergoing chain transfer with the
in Fig. 5.
polymer, it may also undergo autoxidation to form per-
Overall, despite limitations in the use of the Menschutkin oxides, like ethers such as 2-MeTHF, and that this peroxide
reaction to assess the polarity of lower polarity solvents (π* < formation could be directly proportional to its radical
0
.4), it was useful in comparing the esters and pinacolone to formation.
toluene in terms of their π* and highlighted their similarities. To test this hypothesis, the four candidates were exposed to
In spite of pinacolones higher π*, it was shown to behave more ultra-violet light and bubbling air, conditions which are
like a lower polarity solvent such as ethyl acetate.
known to promote peroxide formation, and the results can be
seen in Table 3. Significant amounts of peroxide were formed
in ethyl isobutyrate in three hours under the peroxide for-
mation accelerating conditions (0 ppm → 10–30 ppm).
Application testing: pressure sensitive adhesive production
A radical-initiated polymerisation for the production of an Peroxides were also formed in the other candidates, but at a
industrial relevant commercial available pressure sensitive slower rate than ethyl isobutyrate. The rate of peroxide for-
adhesive (PSA) was carried out using each of the four candi- mation in methyl pivalate was 0 ppm → 3–10 ppm, methyl
date solvents in comparison to toluene. A selection of acrylic butyrate was 0 ppm → 3 ppm in three hours, and in pinaco-
monomers, which cannot be disclosed, were used in the poly- lone was 3 ppm → 10–30 ppm (3 ppm peroxide was present in
merisation reaction. In general, PSA production requires high the bottle of pinacolone before use). The rate of peroxide for-
−
1
M
w
polymers (>30 000 g mol but often far higher) and there- mation reflects the M
w
’s obtained in the polymerisation tests.
fore solvent choice is important. VNP solvents such as Ethyl isobutyrate was subject to the greatest chain transfer,
toluene and hexane are commonly used for this application at resulting in the lowest M ’s, and quickest peroxide formation.
5
4
w
present, but due to REACH restrictions on the use of toluene As such, ethyl isobutyrate may not be ideal for the production
3
in adhesives and spraypaints and a CoRAP on hexane, greener of this type of polymer, however, it could be useful for the pro-
1
alternatives are required.
w
duction of lower M polymers or non-radical-initiated poly-
The polymerisation results can be seen in Table 2. The mers and remains an excellent candidate to replace toluene in
−
1
target Mw of the polymer was 500 000 g mol , which all four many applications.
candidates achieved. In addition, adhesion, cohesion and tack
It is important to note that while peroxide formation in sol-
were found to be acceptable for use in PSAs. However, when vents is undesirable, peroxides were only observed under
ethyl isobutyrate was used as the solvent the conditions had to extreme conditions (air and UV light) for each of the esters. As
be altered as sufficiently high M
has previously been shown that chain transfer occurred when vents, were exposed to the same conditions where they too
-methyltetrahydrofuran was used as the solvent in the radical- were found to form peroxides (0 ppm → 1–3 ppm and 0 ppm
initiated polymerisation of butyl acrylate (100 g) and methyl → 3–10 ppm respectively, Table 3). No peroxide formation was
w
’s could not be obtained. It a comparison, ethyl acetate and MEK, two commonly used sol-
2
7
acrylate (5 g), resulting in low M
transfer was suspected of being the cause of the lower M ’s in bottle in ambient conditions. Some peroxide formation was
w
polymers. Therefore, chain observed in any of the esters after one year of storage in a glass
w
ethyl isobutyrate.
observed in pinacolone in the same storage conditions, so it is
Table 2 Results of an acrylate polymerisation using the fours candidate esters and ketones in comparison to toluene
a
/g mol−1
b
c
−1
d
e
Solvent
M
w
Conversion /%
Adhesion /cN 20 mm
Cohesion/days
Tack/g
Methyl butyrate
Ethyl isobutyrate
Methyl pivalate
Pinacolone
601 000
630 000
581 000
589 000
600 000
95.5
97.6
95.2
96.3
94.6
1506
1641
1532
1646
1587
>10
>10
>10
>10
>10
655
681
727
856
900
Toluene
a
b
c
Measured by GPC at Nitto Europe. Percent of solid polymer dissolved in solvent. Measured by the breaking load test at Nitto Europe.
d
e
Measured by the shear adhesion test at Nitto Europe, values shown are the time of failure in days. Measured by the rolling ball test at Nitto
Europe.
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Table 3 Peroxide test results of the four best candidates
Solvent
Experiment
Control
T = 0 hours (ppm)
T = 3 hours (ppm)
Ethyl isobutyrate
0
0
0
0
0
0
3
0
Test
10–30
Methyl butyrate
Methyl pivalate
Pinacolone
Control
Test
0
3
Control
Test
0
3–10
Control
3
Test
3
0
0
0
0
10–30
0
Ethyl acetate
MEK
Control
Test
1–3
0
Control
Test
3–10
a
Tested using QUANTOFIX® Peroxide 100 test strips.
recommended to take necessary precautions in its use (use of
peroxide formation inhibitor).
Conclusions
In conclusion, a “top-down” approach, focussing on esters and
ketones was utilised to identify greener solvents with the
potential to replace hazardous VNP solvents such as toluene
Green credentials
Limited toxicity data is publicly available in the literature and hexane. Four top candidates – methyl butyrate, ethyl iso-
for the candidate solvents but, what is available can be butyrate, methyl pivalate and pinacolone – were identified as
seen in Table S2 (ESI†). The LD50 for rats (administered the best candidates. Each candidate was characterised in
−
1
orally) is only available for pinacolone and is 611 mg kg
,
terms of its solubility (HSP and KAT parameters), physical (T
T , density), flammability (AIT and LEL), and toxicity (Ames
m
b
,
which is very similar to that of toluene, 636 mg kg− . All
1
candidates passed an Ames mutagenicity test (Fig. S2†). test) properties, where they were all shown to have excellent
The IGC50 for Tetrahymena pyriformis (48 h) for each of the potential to replace traditional VNP solvents. Despite being
−
1
candidates are similar (1800–2772 mg L ) and are far esters and ketones, each demonstrated their similarity to tra-
−
1
superior to that of toluene (52 mg L ). The LC50 for the ditional VNP solvents in terms of their solubility properties by
fathead minnow (96 h) is only available for pinacolone their ability to dissolve natural rubber, a particularly low-
(
87 mL L− ) and is better than that of toluene (34 mL L ). polarity solute. This was reinforced by their performance in a
1
−1
Further in vitro and in silico investigations are currently model Menschutkin reaction, where their performance was
underway to verify their beneficial safety profile. found to be similar to that of toluene.
Eventually, a final testing proposal will be established to
meet REACH requirements.
In a radical-initiated polymerisation of acrylic monomers
for the production of PSAs, each of the four candidates were
5
6
The four candidates can be produced via a catalytic route found to produce PSAs of comparable quality to toluene. Some
principle 7) from renewable resources (principle 9): glycerol interesting effects were noticed in ethyl isobutyrate which were
(
from used cooking oil, isobutene and ethanol from fermenta- explained using peroxide tests. It was found that ethyl isobuty-
tion and CO and methanol from syngas. The atom economies rate formed peroxides at a faster rate than other commonly-
of each of the proposed synthetic routes are high (>80% in all used esters and ketones and this is suspected of being linked
cases), with water and carbon dioxide as benign by-products to its poorer performance in the radical-initiated polymeris-
(
principle 2). The low T
’s of each candidate allows facile ation. As such, the use of antioxidant additives is rec-
b
removal by evaporation, reducing the energy demand where ommended for ethyl isobutyrate. Peroxide formation was also
products are isolated by such means (principle 6).
observed in the other candidates, but this is common in many
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Green Chemistry
traditional solvents in harsh conditions, demonstrated by a
comparison with ethyl acetate and MEK. Importantly, each of
the four candidates can be synthesised via a catalytic route
from potentially renewable resources, thus enhancing their
green credentials. Overall, these esters and ketones of low
polarity and volatility provide several options for industry for
the replacement of hazardous VNP solvents for a range of
processes.
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11 S. Jin, F. Byrne, C. R. McElroy, J. Sherwood, J. H. Clark and
A. J. Hunt, Faraday Discuss., 2017, 202, 157–173.
There are no conflicts to declare.
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2 Dichloromethane
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Acknowledgements
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The authors thank Nitto Belgium NV for funding the project.
This publication also includes results from the ReSolve
project. This project has received funding from the Bio-Based
Industries Joint Undertaking under the European Union‘s
Horizon2020 research and innovation programme under agree-
ment No 745450. The publication reflects only the authors’
view and the JU is not responsible for any use that may be
made of the information it contains. The authors would also
like to thank Dr James Sherwood and Dr Con Robert McElroy
for discussions throughout this work; the Biorenewable
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