Hydrothermal decarboxylation of amino acid derived imidazolium zwitterions: A sustainable approach towards ionic liquids

Article abstract of DOI:10.1039/c4gc00564c

Ionic liquids were prepared via hydrothermal decarboxylation of zwitterionic imidazolium compounds derived from amino acids and carbohydrate related dicarbonyl compounds. Two of these ionic liquids were used successfully as solvents in the Heck reaction a

Full text of DOI:10.1039/c4gc00564c

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Davide Esposito et al.
Hydrothermal decarboxylation of amino acid derived imidazolium
zwitterions: a sustainable approach towards ionic liquids

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Hydrothermal decarboxylation of amino acid
derived imidazolium zwitterions: a sustainable
approach towards ionic liquids†
Cite this: Green Chem., 2014, 16,
3705
Received 31st March 2014,
Accepted 7th May 2014
Sarah Kirchhecker, Markus Antonietti and Davide Esposito*
DOI: 10.1039/c4gc00564c
www.rsc.org/greenchem
Ionic liquids were prepared via hydrothermal decarboxylation of generation of amines from amino acids has been considered
zwitterionic imidazolium compounds derived from amino acids
and carbohydrate related dicarbonyl compounds. Two of these
ionic liquids were used successfully as solvents in the Heck reac-
tion and for the dissolution of cellulose.
as a sustainable alternative to petrochemicals. Substantial
quantities of protein waste are being generated by the food
and biotechnology industries and could become a cheap
source of amino acids. Decarboxylation of amino acids
however is not trivial and is usually performed with the help of
enzymes.6 Alternatively, conjugated carbonyl compounds have
been employed as catalysts mimicking enzymatic processes,
albeit at high temperatures. In these cases, decarboxylation
proceeds via the formation of a conjugate imine that stabilises
the developing negative charge at the site of decarboxylation.
In principle, the imidazolium moiety in the novel IMzw could
act in analogy to a conjugate imine and promote decarboxyla-
tion of the incorporated amino acid in a similar fashion. In
this way, imidazolium based ionic liquids could be obtained
using exclusively amino acids and dicarbonyl compounds
derived from biomass in a simple two-step process (Fig. 1).
Recently, hydrothermal processes have gained interest as
convenient and green methods for the processing of biomass7
with interesting advantages as reaction media for the upgrad-
ing of cellulose8 and fatty acids.9 In addition, continuous pro-
cessing has been recognised by fine chemical manufacturers
as one of the major opportunities to improve the sustainability
of industrial syntheses.10 Microreactors enable more efficient
mixing and heat transfer, thereby reducing reaction times and
increasing safety. They also allow for working in the near- and
supercritical regions, which opens up new possibilities for
green synthesis, making use of the unique properties of
benign solvents such as water under these conditions.11
Due to the environmental and societal problems associated
with the use of fossil feedstocks, there is an ever growing
demand to switch not only fuel production, but also that of
fine chemicals to sustainable processes using renewable
resources. Imidazolium moieties are found in a variety of fine
chemicals, and in recent years they played a prominent role
within the field of ionic liquids (ILs). At first, this new class of
solvents was hailed as green without hesitation, due to pro-
perties such as negligible vapor pressure, high thermal and
chemical stability compared to traditional molecular solvents,
as well as their tuneability to specific tasks. This still holds
true, but it is now known that many ionic liquids are toxic,1
and they are often produced from petroleum-derived chemi-
cals via relatively long quaternisation routes.2 For ionic liquids
to become greener, toxicity issues have to be addressed, and at
the same time more sustainable synthetic approaches need to
be designed. In this regard, ionic liquids based wholly or par-
tially on natural compounds have been reported.3 For instance,
amino acid ionic liquids have been designed, in which amino
acids are used without much modification either as cation or
anion, or both.4 Nevertheless, a sustainable approach towards
imidazolium cation based ILs is still missing.
We recently reported the sustainable synthesis of a small
library of homosubstituted imidazolium zwitterions (IMzw)
based on a modification of the Debus–Radziszewski reaction,
in which amino acids are incorporated into the imidazolium
ring via the amino group.5 With the same efficiency aliphatic
amines can replace amino acids in such a methodology,
leading to the formation of standard ionic liquids. The
In this work we present a simple strategy to synthesise
halogen free imidazolium ILs via continuous hydrothermal
decarboxylation of IMzw. As the internal negative charge of
the zwitterion is removed during decarboxylation, an external
counterion is required for the formation of the IL. Initially we
chose acetic acid as a benign and renewable source of anion.
Hydrothermal decarboxylation of pyruvaldehyde-derived
IMzw with two equivalents of acetic acids in flow gave the
corresponding imidazolium acetates in good yields ranging
between 65 and 90% (Table 1). Only for the leucine-derived
Max Planck Institute of Colloids and Interfaces, Department of Colloid Chemistry,
14424 Potsdam, Germany. E-mail: davide.esposito@mpikg.mpg.de
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4gc00564c
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Fig. 1 Hydrothermal decarboxylation of imidazolium zwitterions. R1, R2 = H, CH3; R = amino acid side chain.
Table 1 Ionic liquids derived by hydrothermal decarboxylation from corresponding zwitterionic compounds
Entry
Amino acid
Gly
Product
Reaction conditions
NMR yield [%]
Isolated yield [%]
90.0
Tg [°C]
Tm [°C]
1
0.25 M
a
100
93
65.1
c
2
3
Ala
0.125 M
a
69
46
65.4d
−88.5
−20.0
c
Phe
0.05 M
b
99
90
89.4
c
4
Leu
0.03 M
a
41
17.9d
n/d
n/d
5
6
Gly
Gly
0.25 M
a
100
100
95.9
98.0
−51.7
0.125 M
a
125.9
7
Ala
0.125 M
a
21
12.5d
−13.4
Reaction conditions: a 300 °C, 150 bar, 4 min, H2O. b 250 °C, 120 bar, 4 min, 50 : 50 H2O–EtOH. c Direct injection of a mixture of amino acid,
acetic acid, formaldehyde and dicarbonyl compound. d Calculated after metathesis with LiN(Tf)2; n/d none detected down to −150 °C.
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compound 4 the yield was lower (41%) (Table 1, entry 4). Free below 100 °C, the majority of them being room temperature
amino acids could not be decarboxylated under the same con- ionic liquids (Table 1). Noteworthily, ILs generated in this way
ditions, confirming the beneficial role of the imidazolium ring are assumed to be halogen-free, as no quaternisation reactions
during decarboxylation.
have been employed during their synthesis. Moreover, all start-
With the aim to expand the scope of the methodology, we ing materials are almost quantitatively incorporated into the
also performed the decarboxylation on imidazolium com- final product. C2 substitution on the imidazolium ring is
pounds obtained using glyoxal- as well as 2,3-butadione as the known to increase the melting point and viscosity of ionic
dicarbonyl compound. Like pyruvaldehyde, glyoxal can be liquids, and one could expect a similar effect by introducing
derived from biomass,12 while butadione is produced by fer- substituents on C4 and C5.14 Accordingly, a clear trend is seen
mentation, and it is present in dairy products such as butter towards increasing phase transition temperatures going from
and alcoholic beverages.13 The glyoxal- and butadione- derived 5 with a Tg of −51.7 °C, to 1 (Tm = 65.1 °C) and finally 6
compounds could be obtained with comparable yields using (Tm = 125.9 °C).
the same method applied for the preparation of pyruvaldehyde
We further evaluated some physicochemical properties for
derived IMzw (see ESI†). Such compounds were then efficiently a selected subsection of the newly obtained ILs. We focused on
decarboxylated (entries 5 and 6), with exception of the glyoxal- alanine derived compounds due to some structural similarity
derived alanine compound, which to our surprise afforded 7 to the commercially available Emim derivatives. Interestingly,
in only 21% yield.
the viscosities of compounds 2 and 8 (Table 2) were measured
Since the imidazolium zwitterions are produced within to be very similar to the ones reported for the asymmetrical
minutes in a simple one-pot reaction of amino acids, dicarbo- Emim OAc and bis(trifluoromethane)sulfonamide, anticipat-
nyl compound, formaldehyde and a slight excess of acetic acid ing their potential application as solvents. To demonstrate the
as catalyst, we also evaluated the direct hydrothermal treat- usability of the so generated ionic liquids, we chose to employ
ment of such a reaction mixture without any intermediate them as solvents for the Heck reaction and the dissolution of
purification of the in situ formed IMzw. Indeed, for the cellulose, two applications where ionic liquids show unique
glycine- and phenylalanine-derived compounds 1 and 3 such advantages compared to other solvents. For the Heck reaction
an approach gave similar yields (93% instead of 100% and we chose the hydrophobic IL 2 and for the cellulose dissol-
90% instead of 99% respectively), whereas for alanine-derived ution the more hydrophilic compound 8. Since under the
ionic liquid 2 the yield was slightly lower (46% compared to current microreactor setup we could only synthesise ILs on a
69%).
scale of ca. 500 µL, compounds 2 and 8 were prepared on a
ILs with different counterions can be readily produced by multigramme scale by the Debus–Radziszewski reaction using
decarboxylation of the zwitterions in the presence of salts or pyruvaldehyde and ethylamine (see ESI†). Analysis of the spec-
acids of the corresponding anion. Apart from the acetate, we tral data confirmed that the compounds synthesised in this
also obtained the chloride of compound 3 in 47.6% yield way were identical to the ones obtained via the decarboxylation
using 2 equivalents of NaCl during decarboxylation. Anions route. The Heck reaction is a very important carbon–carbon
can also be exchanged by classical metathesis, which can serve bond forming reaction.15 Traditionally, this is performed with
at the same time as an easy and efficient way of purification, homogeneous palladium catalysts containing phosphine
when applied to the crude reaction solution. For instance, the ligands. To reduce cost, there have been efforts to simplify the
acetate of compounds 2, 4 and 7 could easily be exchanged by catalyst and improve its recyclability. Recently, ligand-free
anion metathesis using lithium bis(trifluoromethane)sulfoni- Heck protocols for the Heck reaction have appeared in the
mide (LiN(Tf)2).
literature,16 with different approaches for the recycling of the
All the pyruvaldehyde-derived compounds qualify as ionic formed Pd black after each cycle. The benefit of using ionic
liquids with melting points or glass transition temperatures liquids for this reaction is that the Pd catalyst is immobilised
Table 2 Physicochemical properties of ILs used for solvent applications
Density [g cm−1
]
Viscosity [mPa s]
Ionic liquid
Water content [%]
0.07
25 °C
1.452
90 °C
25 °C
38.3
90 °C
6.8
Conductivity [mS cm−1
]
Tg/Tm [°C]
−88.5a
Td [°C]
1.389
1.027
2.98
443.0
6.675
1.070
50.0
5.8
2.70
−62.0b
242.4
a Tg, b Tm.
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in the ionic liquid phase and stabilised in the form of Pd of triethylammonium iodide resulted in a decreased activity.
nanoparticles, while the reaction products can be easily In this case, unreacted iodobenzene was detected by GC-MS
extracted and the catalyst can be reused, thereby reducing cost analysis and the isolated yield resulted to be lower (85%).
and environmental impact.17 For our Heck reaction we chose However, washing of the ionic liquid-Pd phase with water fol-
the hydrophobic ionic liquid 2 as the solvent and a palladium lowed by drying restored the full catalytic activity for consecu-
loading of 0.2 mol% with respect to iodobenzene. The reaction tive runs 4 and 5 (Fig. 2).
between iodobenzene and methyl acrylate in the presence of
A second important area of application for ionic liquids is
triethylamine proceeded with full conversion (as assessed by the field of biomass processing. ILs are among the very few
GC-MS and NMR), with an average isolated yield of 94% compounds able to solubilise cellulose and even wood.19 To
(Fig. 2). Transmission electron microscopy showed the for- date, one of the most efficient ILs is Emim acetate, which has
mation of uniform Pd-nanoparticles stabilised in the IL been reported to dissolve more than 20 wt% of cellulose.20 An
(Fig. 3) in agreement with previously published literature.18 To extensive network of inter- and intramolecular hydrogen
verify the recyclability of the catalyst, the ionic liquid phase bonds between strands prevents dissolution of cellulose in tra-
was reused after extraction of the product with toluene over ditional solvents. Dissolution in ILs is assumed to work via the
five reaction cycles (Fig. 2). After the 3rd run, the large build-up disruption of this network and the formation of new hydrogen
bonds between the IL ions and cellulose strands. This is
accompanied by a transition from the native cellulose type I
crystallinity pattern to type II.21 To demonstrate that the renew-
able ionic liquid 8 can be considered as an efficient alternative
to Emim OAc and other ILs, dissolution experiments with
microcrystalline cellulose (MCC) were performed. Dissolution
was assessed visually and confirmed by light microscopy (see
ESI†), revealing that 8 could solubilise 16.9 weight percent of
microcrystalline cellulose at 100 °C. Powder X-ray diffraction
analysis of a sample of cellulose dissolved in compound 8,
precipitated with water and dried was additionally used to
confirm dissolution, and showed the loss of the pattern of
microcrystalline cellulose with the formation of a more amor-
phous structure (Fig. 4).
In conclusion, we have demonstrated a sustainable and
efficient method to convert fully renewable amino acid derived
imidazolium zwitterions into ionic liquids. Employing a con-
tinuous hydrothermal process, we generated a library of
halogen free ILs via formal decarboxylation of the amino
acids. Differently substituted molecules were tested and the
methodology proved to be general, within the limits of the
study. The applicability of representative compounds was
Fig. 2 Heck reaction performed in IL 2 and yields after recycling of
catalyst-IL phase.
Fig. 3 TEM image of Pd nanoparticles formed in IL 2 after the first run
of the Heck reaction.
Fig. 4 XRD pattern of microcrystalline cellulose (a) before and (b) after
dissolution in 8.
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demonstrated by using them as solvents for the Heck reaction
and for the dissolution of cellulose. The reported method rep-
resents a valuable quaternisation-free alternative route for the
P. Dell’Orco, H. Noorman, S. Yee, R. Reintjens, A. Wells,
V. Massonneau and J. Manley, Org. Process Res. Dev., 2011,
15, 900–911.
preparation of ILs in which the nitrogen substitution is for- 11 S. Kobayashi, Sub- and supercritical water, Science of Syn-
mally obtained via amino acid decarboxylation. Finally, we
expect to expand the scope of this decarboxylative method-
ology by applying it to other amino acid-derived systems other
than the imidazolium ion, in order to generate a broader
family of ionic liquids. The possible implementation of this
method on a multigramme preparative scale is currently under
investigation.
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