New generation ionic liquids: Cations derived from amino acids

Article abstract of DOI:10.1039/b504256a

Two families of a new generation of ionic liquids, in which the chiral cations are directly derived from naturally occurring α-amino acids and α-amino acid ester salts, have been obtained via very simple preparations. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b504256a

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COMMUNICATION
www.rsc.org/chemcomm | ChemComm
New generation ionic liquids: cations derived from amino acids{
Guo-hong Tao, Ling He, Ning Sun and Yuan Kou*
Received (in Cambridge, UK) 29th March 2005, Accepted 3rd May 2005
First published as an Advance Article on the web 9th June 2005
DOI: 10.1039/b504256a
Two families of a new generation of ionic liquids, in which the
chiral cations are directly derived from naturally occurring
a-amino acids and a-amino acid ester salts, have been obtained
via very simple preparations.
The rapidly growing research interest in ionic liquids (ILs) is
1–4
undoubtedly stimulated by the development of green chemistry.
ILs have been widely considered as greener alternatives to volatile
5,6
organic solvents. Commonly used ILs, however, are synthetic
chemicals and are therefore not as green as desired. Development
of bio-renewable ILs to take the place of the synthetic quaternary
nitrogen cations such as alkylammonium, dialkylimidazolium, and
pyridinium usually used in ILs, is thus of great importance. Amino
acids and their derivatives are the most abundant natural source of
quaternary nitrogen precursors, however they have rarely been
directly used to prepare the cations in ILs. In this paper, we report
two families of a new generation of ILs, in which the cations
involved are derived directly from natural a-amino acids and
a-amino acid ester salts. More than one hundred ILs have been
obtained via very simple preparations. The chiral centers present in
the original a-amino acids have been successfully retained in the
final ILs.
Fig. 1 Schematic strategy for the synthesis of amino acid-based ionic
liquids.
The formation of [AA]X is a simple protonation reaction
carried out by mixing the correct molar ratio of amino acid and
relevant strong acid in water, followed by evaporation of the
water in air and finally under vacuum. This one-step procedure
is a typical atom-economic reaction without any poisonous
ILs are composed entirely of ions. Use of bio-renewable natural
compounds as starting materials for the preparation of the ions in
7
ILs is a promising ongoing approach. Successful procedures for
the preparation of ions, some of which contain chiral centers, have
8
,9
been reported for a variety of precursors including lactates,
10
11
12
sugars, sugar substitutes and amino acids. Chirality continues
1
3
to receive significant attention from chemists and biologists.
Table 1 The properties of amino acid salts ([AA]X)
Preparation of chiral cations from natural materials has resulted in
14–18
several publications,
a
c
20
21
20d
No. Product
T
m
/uC
T
dec/uC
4 D
d /g?cm (¡5%) [a]
however these studies surprisingly tend to
1
2
3
4
5
6
7
8
GlyCl
GlyNO
GlyBF
186
111
116
101
159
195
192
220
157
168
241
176
119
193
169
167
147
138
236
168
206
192
1.40
1.22
1.51
1.37
1.26
1.44
1.33
1.02
1.55
1.06
1.05
1.86
1.38
1.63
1.56
1.58
1.48
—
—
—
—
use the natural materials merely as precursors for multi-step
3
syntheses of more complex materials: for example, use of amino
17,18
acids to prepare imidazolium-based cations.
4
GlyPF
AlaNO
6
Our strategy using amino acids to prepare ILs is shown in Fig. 1.
Some representative materials obtained by the one-step acidifica-
tion of amino acids, which results in the formation of the amino
3
+15.9u
+11.6u
+8.4u
+8.6u
+9.1u
+27.2u
+40.3u
210.8u
229.7u
226.8u
224.0u
238.7u
236.1u
AlaBF
4
78
b
AlaPF
AlaCF
6
3
COO 82
2
2
2
2
22
acid salts [AA]X (X 5 Cl , NO , BF4 , PF6 , 1/2SO4
2
,
9
10
Ala
ValNO3
IleNO
ThrNO
ProNO3
ProBF
ProPF
Pro SO
ProCF
Melting points (T
2
SO
4
141
134
3
3
CF COO ), is illustrated in Table 1. The products are named
1
1
1
2
3
105
using the general three-letter symbols for amino acids and the
b
3
b
chemical formula of the anion: for example, AlaNO represents
3
13
14
15
16
4
76
alanine nitrate (Table 1).
b
6
2
4
92
{ Electronic supplementary information (ESI) available: Experimental
details. See http://www.rsc.org/suppdata/cc/b5/b504256a/
State Key Laboratory for Structural Chemistry of Unstable and Stable
Species, College of Chemistry and Molecular Engineering, Peking
University, Beijing 100871, China. E-mail: yuankou@pku.edu.cn;
Fax: 86-10-62751708; Tel: 86-10-62757792
17
3
COO 78
a
m
) were determined by DTA, heating at
b
21
5
uC min
Decomposition temperatures (Tdec
under nitrogen. No melting transition observed.
were determined by TGA,
c
)
21
d
heating at 5 uC min
c 5 2.
3
under nitrogen. Solution in CH OH and
*yuankou@pku.edu.cn
3
562 | Chem. Commun., 2005, 3562–3564
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1
9
by-product. It can be seen from Table 1 that half of the products
near 200 uC and decompose at that temperature, they can be
completely tranformed into ideal ILs by anion replacement. The
ILs obtained are thermally stable up to 150 to 200 uC, a little lower
than those of imidazolium ILs, but much higher than the
minimum 100 uC criterion described by Wasserscheid for chiral
ILs. All the [AAE]Y ILs have the same glassy state character as
that of commonly used ILs. The glass transition temperatures were
determined by differential scanning calorimetry (DSC) from the
first heating cycle, after initially cooling samples to 270 y
(
8 out of 17) are white solids, of which several have been used to
20–23
prepare amino acid crystals.
having melting points lower than 100 uC. Of these, AlaPF
ThrNO are both viscous liquids at room temperature while
ProNO and ProPF are genuine room temperature ILs.
The other 9 samples are ILs
6
and
3
16
3
6
It is reasonable to assume that the high melting points of some
of the [AA]X salts result mainly from strong hydrogen bonds
involving the carboxylic acid group. Esterification is an appro-
priate way to minimize such hydrogen bonding. A general
synthetic strategy based on the family of amino acid ester salts,
g
2100 uC. All of them had a glass transition temperature (T ) in the
range 210 to 240 uC. Then, as the temperature increased, the
solid samples showed clear melting peaks on the DSC curves. For
example, AlaC NO showed a T at 234 uC with m.p. at 61 uC
2
2
2
2
2
2
[
AAE]Y (Y 5 NO
3
2
3
CH CH(OH)COO ), has therefore been proposed in order to
, BF
4
, PF
6 2 3
, NTf , SCN , CH COO ,
1
3
g
prepare a greater variety of room temperature ILs, as shown in
Fig. 1. In principle, such a strategy makes an extensive family of
more than one hundred ILs immediately available. Esterification
reduces the amount of hydrogen bonding, resulting in a significant
decrease in the melting points of the salts whilst having little
influence on the quaternary nitrogen cations, and a series of lower
melting point salts or ILs have been successfully obtained. Some
representative examples are summarised in Table 2. We again use
the general symbols to represent the amino acids, and use the
number of carbon atoms to represent the alkyl groups: for
(
Fig. 2). The room temperature liquid samples have different
characteristics however, showing solid–solid transitions at lower
temperatures and solid–liquid transitions at higher temperatures.
A typical DSC curve, for IleC
1 3
NO , is illustrated in Fig. 2. After
cooling in a dry ice/acetone bath to 270 uC, IleC NO became a
1
3
1 3
example, alanine methyl ester nitrate is denoted AlaC NO . Since
amino acid ester hydrochlorides, [AAE]Cl, are available commer-
cially, the preparation of [AAE]Y ILs is as straightforward as that
of the [AA]X salts. Furthermore, it should be noted that
esterification provides the possibility of adjusting the properties
of the resulting ILs, and the ‘‘designer solvent’’ character of ILs is
therefore potentially enhanced.
It is clear from Table 2 that half of the products (12 out of 22)
are room temperature ILs and almost all of the products are ILs
below 100 uC. It is interesting to note that although the [AAE]Cl
salts used as precursors in this work usually have melting points
Fig. 2 Differential scanning calorimetry (DSC) trace of [AAE]Y-based
ionic liquids (AlaC NO and IleC NO ).
1
3
1
3
Table 2 The properties of amino acid ester salts ([AAE]Y)
a
a
b
20
21
/g?cm (¡5%)
20c
20c
D
No.
IL
T
m
/uC
T
g
/uC
T
dec/uC
d
4
[a]
D
[AAE]Cl [a]
Viscosity/cP (¡5%)
92(70 uC)
1
2
3
4
5
6
7
8
9
GlyC
GlyC
1
NO
NO
3
44
226
210
234e
248
235e
261
238
223
224e
245
229
233
231e
236
232e
232
230e
267
220
222
220e
250
178
182
186
230
209
150
139
172
77
1.50
1.67
1.26
1.53
1.36
1.55
1.27
—
—
—
—
2
3
49
61
AlaC
AlaC
AlaC
AlaC
AlaC
AlaC
AlaC
AlaC
AlaC
ValC
LeuC
IleC NO
PheC
ThrC
SerC
ProC
ProC
ProC
ProC
ProC
1
1
1
1
1
1
1
2
2
NO
BF
PF
NTf
3
+6.2u
+5.6u
+5.8u
+5.8u
+5.2u
+6.2u
+6.2u
+6.2u
+6.2u
+6.2u
+6.2u
+6.2u
+2.9u
+2.9u
+22.3u
+17.6u
+37.8u
+18.1u
29.4u
+3.7u
234.5u
234.5u
234.5u
234.5u
236.4u
d
4
218d
96(30 uC)
103(80 uC)
2030(30 uC)
1550(80 uC)
6
d
2
217
62
SCN
Ace
Lac
d
38
217
1.20
1.29
1.19
1.31
1.15
1.35
1.16
1.72
1.44
1.53
1.45
1.47
1.22
1.57
24.5u
+4.7u
d
10
11
12
13
14
15
16
17
18
19
20
21
22
a
NO
Lac
3
187
82
75
74
75
25.7u
+22.5u
+15.4u
+32.7u
+21.1u
29.5u
+7.3u
1
NO
3
195
210
172
224
156
179
159
234
221
140
183
1
NO
3
d
1
3
214
92
212
105
1
NO
3
d
1
NO
3
1
NO
NO
BF
3
d
1
3
216d
236.4u
220.7u
232.2u
223.8u
230.9u
186(30 uC)
1
1
1
2
4
d
d
PF
6
Lac
NO
d
3
217
g m
Glass transition temperatures (T ) and melting points (T ) from the onset position were determined by DSC from the first heating cycle, after
b
21
initially cooling samples to 270y 2100 uC. Decomposition temperatures (Tdec) were determined by TGA, heating at 5 uC min under
c
nitrogen. Solution in CH
temperature.
d
OH and c 5 2. No melting transition observed or solid–liquid transition temperature. Solid–solid transition
e
3
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being carried out in our laboratory. In evaluating any such work
concerning the preparation of ILs from natural materials, we want
to emphasize that (1) the natural properties of the materials, i.e.,
the bio-renewable/bio-degradable properties should be retained; (2)
the chiral centers in the synthetic precursors should be unchanged;
and (3) the ‘‘designer solvent’’ properties of ILs, i.e., the fact that
the physical/chemical properties of the ILs can be adjusted by
changing a side-chain connected to the core, should be maintained.
The work described here completely satisfies these criteria.
Furthermore, the simple preparation involved encourages the
commercialization of processes based on [AA] and [AAE]-type
ILs.
For financial support, we acknowledge the ‘973’ Program of the
Chinese Ministry of Science and Technology (G-2000048002).
1
1 3 6
Fig. 3 H NMR spectrum of AlaC NO in d -DMSO.
hard transparent solid. On heating, this became a very viscous
Notes and references
opaque material near 235 uC and subsequently a transparent
1
J. D. Holbrey and K. R. Seddon, Clean Products and Processes, 1999, 1,
23–236.
K. R. Seddon, Nature Materials, 2003, 2, 363–365.
liquid near 215 uC.
The H NMR spectrum of AlaC
2
1
NO , as an example of
1 3
2
[
AAE]Y, is shown in Fig. 3. The broad peak at 8.32 ppm that can
+
3 R. D. Rogers and K. R. Seddon, Science, 2003, 302, 792–793.
4 D. B. Zhao, M. Wu, Y. Kou and E. Z. Min, Catal. Today, 2002, 74,
be assigned to the RNH
3
hydrogen, is similar to that of the 2-H of
157–189.
imidazolium cations, indicating a certain acidity for the [AAE]Y
21
ILs. The pH value of AlaC NO , measured in a 1 mol L
1 3
5
6
T. Welton, Chem. Rev., 1999, 99, 2071–2083.
P. Wasserscheid and W. Keim, Angew. Chem. Int. Ed., 2000, 39,
3772–3789.
aqueous solution, was 3.5, showing weak Brønsted acidity. Since
2+
7 S. T. Handy, Chem. Eur. J., 2003, 9, 2938–2944.
only a single positive ion (C
4
H10NO , m/z 5 104.0706) was found
8
M. J. Earle, P. B. McCormac and K. R. Seddon, Green Chem., 1999, 1,
3–25.
J. Pernak, I. Goc and I. Mirska, Green Chem., 2004, 6, 323–329.
for AlaC NO by secondary ion mass spectrometry (SIMS), the
1
3
2
acidity is believed to come from the hydrogen of the quaternary
nitrogen.
9
10 S. T. Handy, M. Okello and G. Dickenson, Org. Lett., 2003, 5,
513–2515.
1 E. B. Carter, S. L. Culver, P. A. Fox, R. D. Goode, I. Ntai,
2
It is very important to this work that the chiral centers in the
synthetic precursors, whether amino acids or amino acid esters, are
retained in the resulting ILs. Some asymmetric carbon atoms in
chiral ILs have been reported to undergo racemization after a
1
M. D. Tickell, R. K. Traylor, N. W. Hoffman and J. H. Davis, Chem.
Commun., 2004, 630–631.
12 K. Fukumoto, M. Yoshizawa and H. Ohno, J. Am. Chem. Soc., 2005,
127, 2398–2399.
24
certain time. In Table 2, the specific rotations in degrees of the
ILs are compared with those of the corresponding synthetic
precursors, [L-AAE]Cl. It can be seen that most of the ILs almost
have the same specific rotation values as those of the precursors.
When L-lactate is the anion (items 9, 11 and 21 in Table 2)
however, the specific rotation values are altered significantly,
indicating that two independent chiral centers exist in solution.
Furthemore, regular monitoring indicated that the chirality of all
the samples shown in Table 2 showed no change even after one
month or longer, demonstrating that [AAE]-type ILs offer a new
family of easily-prepared chiral ILs.
1
3 C. Baudequin, J. Baudoux, J. Levillain, D. Cahard, A.-C. Gaumont and
J.-C. Plaqueventa, Tetrahedron Asymmetry, 2003, 14, 3081–3093.
14 J. Levillain, G. Dubant, I. Abrunhosa, M. Gulea and A. C. Gaumont,
Chem. Commun., 2003, 2914–2915.
1
5 G. Vo Thanh, B. Pegot and A. Loupy, Eur. J. Org. Chem., 2004,
112–1116.
6 P. Wasserscheid, A. B o¨ smann and C. Bolm, Chem. Commun., 2002,
200–201.
7 W. L. Bao, Z. M. Wang and Y. X. Li, J. Org. Chem., 2003, 68, 591–593.
1
1
1
18 H. Clavier, L. Boulanger, N. Audic, L. Toupet, M. Mauduit and
J. C. Guillemin, Chem. Commun., 2004, 1224–1225.
9 Ionic Liquids in Synthesis, (Eds: P. Wasserscheid, T. Welton), Wiley-
VCH, Weinheim, 2003.
1
2
2
0 I. Nemec, I. Cisarova and Z. Micka, J. Mol. Struct., 1999, 476, 243–253.
1 B. J. M. Rajkumary and V. Ramakrishnan, J. Raman Spectrosc., 2000,
1, 1107–1112.
2 D. Rajan Babu, D. Jayaraman, R. Mohan Kumar and R. Jayavel,
J. Cryst. Growth, 2002, 245, 121–125.
3 S. Dhanuskodi and J. Ramajothi, Cryst. Res. Technol., 2004, 39,
92–597.
4 J. J. Jodry and K. Mikami, Tetrahedron Lett., 2004, 45, 4429–4431.
5 K. R. Seddon, A. Stark and M. Torres, Pure Appl. Chem., 2000, 72,
2275–2287.
Table 2 also gives viscosity data for some [AAE]Y ILs when
they are in the liquid state. From these data it can be concluded
that [AAE]Y ILs display qualitatively similar viscosity behaviour
3
2
25
to common imidazolium ILs.
2
Development of [AA]- and [AAE]-type cations provides a great
opportunity to prepare novel green ILs, which are promising
alternatives to commonly used ILs. Combination of [AAE] cations
with suitable natural anions in order to prepare fully natural ILs is
5
2
2
3
564 | Chem. Commun., 2005, 3562–3564
This journal is ß The Royal Society of Chemistry 2005