Renewable pyridinium ionic liquids from the continuous hydrothermal decarboxylation of furfural-amino acid derived pyridinium zwitterions

Article abstract of DOI:10.1039/c5gc00913h

Fully renewable pyridinium ionic liquids were synthesised via the hydrothermal decarboxylation of pyridinium zwitterions derived from furfural and amino acids in flow. The functionality of the resulting ionic liquid (IL) can be tuned by choice of differen

Full text of DOI:10.1039/c5gc00913h

View Article Online
View Journal
Green
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: S. Kirchhecker, S.
Tröger-Müller, S. Bake, M. Antonietti, A. Taubert and D. Esposito, Green Chem., 2015, DOI:
10.1039/C5GC00913H.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/greenchem

Page 1 of 10
Green Chemistry
View Article Online
DOI: 10.1039/C5GC00913H
Renewable Pyridinium ionic Liquids from the continuous hydrothermal Decarboxylation of
Furfural-Amino Acid derived Pyridinium Zwitterions
Sarah Kirchhecker,a Steffen Tröger-Müllera, Sebastian Bake,b Markus Antonietti,a Andreas
Taubertb and Davide Esposito*a
a: Max-Planck-Institute of Colloids and Interfaces, 14424 Potsdam, Germany
b: University of Potsdam, Institute of Chemistry, D-14469 Potsdam, Germany
*Corresponding Author
E-Mail: davide.esposito@mpikg.mpg.de
Fully renewable pyridinium ionic liquids were synthesised via the hydrothermal decarboxylation of
pyridinium zwitterions derived from furfural and amino acids in flow. The functionality of the
resulting IL can be tuned by choice of different amino acids as well as different natural carboxylic
acids as the counterions. A representative member of this new class of ionic liquids was
successfully used for the synthesis of ionogels and as a solvent for the Heck coupling.
The development of new methodologies for the synthesis of fine chemicals on the basis of renewable
resources is a unique opportunity to increase the sustainability of modern chemistry. In recent years,
lignocellulosic biomass has been identified as a promising source of building blocks and platform
chemicals, including small carboxylic acids and alcohols, as well as 5-hydroxymethylfurfural and its
oxidised version, furandicarboxylic acid1. N-heterocycles are a versatile class of molecules which find
application as building blocks in the synthesis of many different types of compounds. However, the
synthesis of nitrogen-containing heterocycles from lignocellulosic biomass remains elusive due to the
lack of nitrogen in this resource. Complementing lignocellulose-derived molecules with other
renewable N-containing precursors can sensibly increase the chemical space accessible in a
sustainable manner. In this regard, amino acids have been evoked as an interesting candidate2.
Amino acids are a rich class of renewable amine containing compounds, which provide
enantiomerically pure molecules with diverse properties, due to their different side chains. Specific
amino acids can be produced by fermentation3, while huge amounts of protein waste, such as
feathers from the poultry industry4, are untapped resources to be utilised as soon as efficient
separation protocols will be developed2.
Many nitrogen heterocycles, most notably imidazole and pyridine, can be converted into ionic liquids
by quaternisation. Ionic liquids (ILs) have received a lot of attention for their application as green
solvents5, as electrolytes6, gas absorbents7 and more, due to properties including very low vapour
pressure and high thermal and chemical stabilities. Despite such desirable properties, widespread
application of ILs is still hindered by a relatively high production cost. From a sustainability
standpoint, moreover, the generation of ionic liquids on the basis of renewable resources should be
addressed.
1

Green Chemistry
Page 2 of 10
View Article Online
DOI: 10.1039/C5GC00913H
We recently reported a green synthesis of ionic liquids via the hydrothermal decarboxylation of
imidazolium zwitterions (ImZw)8 in which the nitrogens are obtained from amino acids and the
carbons from carbohydrate-derivable synthons (Figure 1). These compounds could be
decarboxylated in superheated water in the presence of acetic acid or salt to give ionic liquids. The
decarboxylation of free amino acids is still difficult and requires a high energy input in combination
with catalysts. The catalysts employed for the chemical decarboxylation of amino acids generally
contain conjugated aldehydes that react with the amino acid to form an imine 9, as in the case of the
terpenoid carvone10, while nature employs the cofactor pyridoxal-5-phosphate (PLP) present in
decarboxylase enzymes. In the latter case, the amino acid binds to the aldehyde group of PLP
forming an imine, which in this case is conjugated to the pyridinium ring of PLP. The ring works as an
electron sink facilitating decarboxylation at physiological temperature via the formation of a
“quinonoid” intermediate11.
In our previous work, we demonstrated that the imidazolium ring contained in amino acid derived
zwitterions exerts a catalytic effect promoting the decarboxylation of the α-amino acid side chain.
Interestingly, the β-alanine derived compound could not be decarboxylated under those conditions,
suggesting that the mechanism of decarboxylation may involve the formation of an intermediate
ylide species in which the developing carbanion is stabilised by the charge on the aromatic ring
system.
The conditions for hydrothermal decarboxylation are essentially green, since are based on the use of
water as reaction medium, do not require reagents to be used in excess and incorporate the catalytic
auxiliary in the final product, bypassing the need for catalyst separation and recycling. In principle,
such methodology should be applicable for other aromatic nitrogen heterocycles derived from α-
amino acids, in which the ring system is in the alpha position with respect to the carboxylic group. In
this way, new classes of renewable ILs with different cations could be accessed, in which the
quaternary nitrogen substitution is obtained via amino acid decarboxylation rather than traditional
quaternisation with alkylating agents. In this work, a group of fully renewable pyridinium ILs derived
from furfural and amino acids was prepared by means of hydrothermal decarboxylation of the
corresponding pyridinium zwitterions.
Fig. 1 Proposed decarboxylation mechanism for amino acid derived imidazolium and pyridinium
zwitterions.
2

Page 3 of 10
Green Chemistry
View Article Online
DOI: 10.1039/C5GC00913H
Furfural is one of the longer established biomass-derived chemicals. Discovered in 1821 by
Doebereiner as a side product from the distillation of dead ants12, soon it was found that it could be
produced from various crop residues via the acid-catalysed depolymerisation of hemicellulose and
subsequent dehydration of xylose. Industrial production of furfural was started by the Quaker Oats
company in 192113, and with the development of lignocellulosic biorefineries it can be expected to be
produced at high volume and lower cost in the near future14.
It is known that furfurylamines can be converted into 3-hydroxy-pyridines under oxidative
conditions15, and these compounds are recognised as important intermediates in the production of
fine chemicals such as pesticides and pyridostigmine type cholinergic drugs. Alapyridaine, a flavor
enhancing compound which forms during the Maillard reaction between glucose and the amino acid
alanine, was synthesised from 5-hydroxymethyl furfural (HMF) and alanine, following a similar
synthetic route16, which was later extended to include other amino acids17. We decided to
investigate the decarboxylation of pyridinium zwitterions (PyrZw) derived from the reductive
amination of furfural with different amino acids, followed by oxidation to the corresponding 3-
pyridinol carboxylate. For this purpose we synthesised a small library of pyridinium zwitterions from
different amino acids (Table 1). While the optimisation of this synthetic route (Figure 2) was not the
goal of this work, we modified the reported synthetic strategies in such a way that all reaction steps
could be performed in one-pot, in order to minimise the use of quenching reagents and solvents for
purification.
Fig. 2 Synthetic route for the pyridinium zwitterions from furfural and amino acids.
Briefly, in this one-pot synthesis the sodium salt of the amino acid was formed by reaction with
NaOH, followed by addition of furfural, to generate the corresponding furfurylimine (after solvent
removal). The imine was reduced to the furfurylamine using sodium borohydride and then converted
to the pyridinium zwitterion by oxidation with hydrogen peroxide in HCl (Figure 2). The reduction
step can be optimised for a more sustainable protocol, for example by using a heterogeneous metal
catalyst and hydrogen gas. The selective reduction of furfurylimines and related compounds is
3

Green Chemistry
Page 4 of 10
View Article Online
DOI: 10.1039/C5GC00913H
currently being investigated in our group, but was out of the scope of the current work. Using the
method described above, a small library of pyridinium zwitterions could be produced, in which the
polarity of each compound is modulated by the different amino acid side chains.
Table 1.
Pyridinium zwitterions synthesised from amino acids and furfural
R = amino acid side chain
Entry
Amino acid
Product
Yielda [%]
1
2
3
Gly
78.0
71.9
93.8
β-Ala
Ala
4
Phe
55.4
5
Leu
100
4

Page 5 of 10
Green Chemistry
View Article Online
DOI: 10.1039/C5GC00913H
Reaction conditions: 1) 1 eq amino acid, 1 eq NaOH, 1 eq furfural, 60 °C, 30 min, 2) 1.05 eq NaBH4,
MeOH, 0 °C, 1 h, 3) 3 M HCl, 2 eq H2O2, 100 °C, 30 min; a) yield determined by NMR using 2-methyl
imidazole as an internal standard.
Employing our continuous hydrothermal decarboxylation strategy, all PyrZw derived from alpha
amino acids were decarboxylated affording the desired pyridinium IL in high yields. Results are
shown in Table 2. Interestingly, the optimum temperatures for this reaction was found to be around
250 °C, ca 50 °C lower than for the imidazolium compounds reported earlier. This is probably the
result of a larger stabilising effect of the pyridinium ring compared to the imidazolium one, combined
with the fact that a single decarboxylation event has to occur to generate the product, unlike the
case of imidazolium zwitterions. As in the case of ImZw, the reactions could be completed within
remarkably short times (4 min) and the beta-alanine derived compound 2 did not form the
decarboxylated product, indicating again that the ring stabilisation is effective only for α-substituted
carboxylic groups as described in Figure 1.
In this work we focused on hydrophobic amino acids to generate ionic liquids with the typical alkyl
chains, as well as the aromatic phenylalanine. In fact, all hydrophobic amino acid derived compounds
gave high yields, whereas the glycine-derived compound 6 formed in a slightly lower yield of 68.8 %.
The decarboxylated compounds were analysed by DSC and all showed glass transition temperatures
(Tgs) below room temperature, with the Tg decreasing for increasing alkyl chain length, in the case of
acetate counterion. The Tg for the phenylalanine derived compound 8 was the highest at – 7.6 °C
among all acetates.
In our previous work we demonstrated the decarboxylation of different compounds using acetic acid,
or alternatively NaCl as another source of counterion. Herewe wanted to expand on the use of
different acids as counterions. Leucine-derived pyridinium 5 was chosen for these experiments due
to the fact that its acetate salt has the lowest Tg and, due to the longest alkyl chain, it can be
expected to be characterised by the lowest viscosity also in presence of different counterions. In
theory, the decarboxylation method should be compatible with any medium strength acid that does
not corrode the reactor coil at the used temperatures or degrades the PyrZw. To demonstrate the
scope of this method we chose two non-toxic carboxylic acids which are available from biomass,
namely L-lactic acid and succinic acid. For lactic acid and succinic acid the reaction conditions were
optimal using stoichiometric amounts of PyrZw and acid. The results are shown in entry 5 and 6 of
Table 2.
Table 2.
Pyridinium ionic liquids synthesised via hydrothermal decarboxylation of zwitterions.
R = amino acid side chain
Yielda [%]
Entry
Product
Tg [°C]
5

Green Chemistry
Page 6 of 10
View Article Online
DOI: 10.1039/C5GC00913H
1
2
68.8
91.0
-13.0
-18.9
3
81.0
-7.6
4
80.7
-32.0
5
6
84.0
82.4
-6.0
-11.7
Reaction conditions: Entries 1,2,4: 0.1 M pyridinium zwitterion in water, 2 eq HOAc, 250 °C, 120 bar,
4 min residence time, entry 3: 0.05 M, 4 eq HOAc,50:50 H2O:EtOH, 200 °C, 100 bar, 4 min. Entries 5
and 6: 1 eq acid, 250 °C, 120 bar, 4 min; a) isolated yield reported as the average of two reactions.
Also with these acids the decarboxylation yields were very high. DSC analysis showed slightly higher
Tgs compared to the corresponding acetate IL, probably due to increased hydrogen bonding of the
anions. Therefore, all in all the hydrothermal decarboxylation strategy could be successfully
6

Page 7 of 10
Green Chemistry
View Article Online
DOI: 10.1039/C5GC00913H
transferred to renewable pyridinium zwitterions and extended to other acids as the source of
counterions.
Noteworthy, the price of the ILs synthesised in this way is quite competitive. Simply using the prices
for the reagents (furfural, amino acids, NaBH4, etc.) from the Sigma Aldrich catalogue we calculated
the price for IL 9 to come around £ 1000/Kg. With the optimisation of the reduction reaction and the
availability of cheaper amino acids the price is expected to be much lower in the future. The purity of
the ILs generated by this method is generally ≥ 97 % (see SI). This is well within the range of
commercially available pyridinium ILs, which range from 97 % (Sigma) to 99 % from specialist
suppliers.
At this stage, we decided to illustrate the usefulness of our new sustainable ILs as a test case for the
production of ionogels (IGs). This rather new class of multifunctional hybrid materials is based on the
incorporation of an IL into a polymeric or inorganic matrix. The resulting IG combines the properties
of the IL such as catalytic activity, electrochemical addressability and color change upon action of
external stimuli, with the properties of the matrix, such as mechanical properties for example. As a
result, IGs have been used or suggested for a wide variety of applications18. Recently, the
electrospinning of ionogels has also attracted increasing attention due to the fact that
electrospinning provides a fairly simple way to achieve surface modification19.
The preparation of IGs requires moderate to large quantities of ILs to be available. In order to
challenge the robustness of our methodology for the production of sustainable pyridinium ILs,
production of 9 was scaled up injecting a solution of 5 (0.09 M) in the microreactor running in
continuou for 420 min, producing 6.8 g of compound. Thus, 9 was employed in combination with
poly(methyl methacrylate) (PMMA) for ionogel production via solution casting using acetone as the
solvent.
Figure 2 shows the full IR spectrum of an ionogel along with the spectrum of the PMMA used as the
matrix. Spectra of pure PMMA show a strong band at 1730 cm-1 from the PMMA carbonyl group. The
bands at 2950, 2925, 1434, 1238, 958, 838, and 746 cm-1 are assigned to aliphatic C–H vibrations. The
bands at 1270, 1140, and 983 cm-1 are assigned to C-O-C stretching vibrations of PMMA. The IR
spectrum of the ionogel is dominated by the absorption bands of the PMMA matrix. The fact that this
band does not shift when the IL is incorporated into the PMMA matrix suggests that the interaction
between the IL and the PMMA is either rather weak or does not primarily occur through interaction
via the PMMA carbonyl groups. This is consistent with previous literature20 21
.
DSC curves only show one glass transition at ca. 80-82 °C, in agreement with earlier work based on
traditional ILs20 (Figure 2 C). The Tg is lower than the Tg of the pure PMMA at ca. 103 °C, but is much
higher than the Tg of IL 9 at -32 °C. This indicates that the mixing between the IL and the PMMA is
homogeneous, as otherwise two glass transitions would have been obsereved (IL and PMMA).
In terms of application potential, ionogels have been proposed for many different fields. Among
others, surface modification – by way of the different chemical composition of the ILs available today
– is interesting for many areas such as medicine, engineering, or construction. We have thus
evaluated the wetting of our ionogel. Indeed, the addition of IL 9 to the PMMA lowers the static
contact angle by ca. 20 °. In principle, proper selection of the IL, whose polarity can be now tuned by
changing the amino acid, will enable the formation of surfaces with a tailored wetting behaviour
from quite hydrophilic to rather hydrophobic. Such surfaces are interesting for microfluidic
7

Green Chemistry
Page 8 of 10
View Article Online
DOI: 10.1039/C5GC00913H
applications, where controlled wetting and dewetting is in some cases necessary to ensure proper
function of the device. The potential of the ILs prepared in this study for controlled surface
modification will be explored in more detail in forthcoming work.
Figure 2. (A) Full IR spectrum of the PMMA matrix and an ionogel with 20% of IL. (B) Magnified view
of the low wavenumber region. (C) DSC curve of the ionogel.. Inset is a photograph of the ionogel. (D)
Photographs of a water droplet on the pure PMMA (CAPMMA) and the ionogel (CAIG) showing the
different contact angles.
Besides the preparation of gels, we also employed a representative IL as a solvent for the Heck
coupling between iodobenzene and methyl acrylate. Hydrophobic pyridinium ILs have been
previously reported as efficient solvents for Pd catalysed reactions,22 due to their stabilising effects
on metal nanoparticles (NPs). This obviates the need for elaborate metal complexes and, instead,
simple Pd salts can be used. For the Heck coupling, a batch of compound 9 was produced, followed
by anion methathesis with LiTFSI. A standard Heck coupling was performed using Pd(OAc)2 as the
catalyst (see SI). The desired product could be isolated in 98% yield after 3 hours. No precipitate of
Pd black was visible after the reaction, indicating the stabilisation of Pd by the IL. The in depth
evaluation of this system as medium for cross coupling reaction will be the object of future studies.
In conclusion, we described a new methodology for the generation of substituted pyridinium ILs via
the continuous hydrothermal decarboxylation of pyridinium zwitterions, which are in turn generated
via the condensation of amino acids and furfural. Since the starting materials employed for the
synthesis are entirely based on renewable resources and the employed decarboxylation strategy is
essentially based on the use of water, the method reported represents a convenient solution for the
green and sustainable preparation of pyridinium based ILs. The method shows a relatively broad
8

Page 9 of 10
Green Chemistry
View Article Online
DOI: 10.1039/C5GC00913H
scope, as different amino acids can be employed with good results, offering a convenient possibility
to tune the polarity of the final molecule. In addition, the obtained compounds are characterised by
properties which are equivalent to the ones of analogous ILs obtained on the basis of non-renewable
resources, as demonstrated in the preparation of ionogels and the use as solvent for the Heck
coupling. Finally, it is worth mentioning that all pyridinium ILs introduced in this work present a
phenolic functionality that may be exploited for further derivatisation and may influence their
general redox properties as well as the acid-base behaviour, which will be the object of future
studies.
References
1
2
3
4
5
6
7
D. Esposito and M. Antonietti, Chem. Soc. Rev., 2015, DOI: 10.1039/C4CS00368C.
C. O. Tuck, E. Pérez, I. T. Horváth, R. a Sheldon and M. Poliakoff, Science, 2012, 337, 695–9.
W. Leuchtenberger, K. Huthmacher and K. Drauz, Appl. Microbiol. Biotechnol., 2005, 69, 1–8.
P. G. Dalev, Bioresour Technol, 1994, 48, 265–267.
T. Welton, Chem. Rev., 1999, 99, 2071–2084.
M. Galiński, A. Lewandowski and I. Stępniak, Electrochim. Acta, 2006, 51, 5567–5580.
N. M. Yunus, M. I. A. Mutalib, Z. Man, M. A. Bustam and T. Murugesan, Chem. Eng. J., 2012,
189-190, 94–100.
8
S. Kirchhecker, M. Antonietti and D. Esposito, Green Chem., 2014, 16, 3705–3709.
Z. Xiang, J. Mol. Struct., 2013, 1049, 149–156.
9
10
11
12
13
14
15
16
US 20140275569, 2014.
M. D. Toney, Arch. Biochem. Biophys., 2005, 433, 279–287.
J. W. Döbereiner, Ann. der Pharm., 1832, 3, 141–146.
H. J. Brownlee and C. S. Miner, Ind. Eng. Chem., 1948, 40, 201–204.
C. M. Cai, T. Zhang, R. Kumar and C. E. Wyman, J. Chem. Technol. Biotechnol., 2014, 89, 2–10.
C. Müller, V. Diehl and F. W. Lichtenthaler, Tetrahedron, 1998, 54, 10703–10712.
R. Villard, F. Robert, I. Blank, G. Bernardinelli, T. Soldno and T. Hofmann, J. Agric. Food Chem.
2003, 51, 4040–4045.
,
17
T. Soldo and T. Hofmann, J. Agric. Food Chem., 2005, 53, 9165–9171.
9

Green Chemistry
Page 10 of 10
View Article Online
DOI: 10.1039/C5GC00913H
18
19
20
J. Le Bideau, L. Viau and A. Vioux, Chem. Soc. Rev., 2011, 40, 907–25.
A. Taubert, Eur. J. Inorg. Chem., 2015, 2015, 1148–1159.
M. A. B. H. Susan, T. Kaneko, A. Noda and M. Watanabe, J. Am. Chem. Soc., 2005, 127, 4976–
83.
21
22
Z.-L. Xie, A. Jelicic, F.-P. Wang, P. Rabu, A. Friedrich, S. Beuermann and A. Taubert, J. Mater.
Chem., 2010, 20, 9543–9549.
M. H. G. Prechtl, J. D. Scholten, J. Dupont, Molecules, 2010, 15, 3441-3461.
10