Imidazolium salts from amino acids-a new route to chiral zwitterionic carbene precursors?

Article abstract of DOI:10.1016/j.tetasy.2010.02.015

Chiral, carboxylic acid-functionalised imidazolium zwitterions were synthesised from the corresponding l-amino acids phenyl alanine, alanine and glycine (achiral). They form infinite C₁¹ (10) chain structures in the solid state. The incorporation of water is dependent upon the creation of suitable cavities by the steric demands of the amino acid side chains.

Full text of DOI:10.1016/j.tetasy.2010.02.015

Tetrahedron: Asymmetry 21 (2010) 393–397
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Imidazolium salts from amino acids—a new route to chiral zwitterionic
carbene precursors?
b
Olaf Kühl a, , Gottfried Palm
*
a Bioinorganic Research Group, Institut für Biochemie, EMA Universität Greifswald, Felix-Hausdorff-Str. 4, D-17489 Greifswald, Germany
b Molecular Structural Biology, Institut für Biochemie, EMA Universität Greifswald, Felix-Hausdorff-Str. 4, D-17489 Greifswald, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Chiral, carboxylic acid-functionalised imidazolium zwitterions were synthesised from the corresponding
L
-amino acids phenyl alanine, alanine and glycine (achiral). They form infinite C11 (10) chain structures in
Received 18 December 2009
Accepted 19 February 2010
Available online 16 March 2010
the solid state. The incorporation of water is dependent upon the creation of suitable cavities by the steric
demands of the amino acid side chains.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Following the publication of the first stable carbene,1,2 the intro-
duction of functional groups into the carbene’s wingtip groups has
increasingly become the focus of research.3–5 Important functional-
ities introduced through the wingtip groups include chirality,6,7
phosphanes,8–10 amines,11–13 aryl- and alkoxides,14–16 carboxylic
acids,17–19 esters17 and amides.20–22 Often, anionic functional
groups provide anchor units that bind strongly to the metal, carbox-
ylic acids and carboxylic acid amides are used to influence the prop-
erties of the corresponding transition metal carbene complexes
through supramolecular hydrogen-bonding patterns.21–23
The reaction of 2 equiv of aminoacid with glyoxal and p-formal-
dehyde in water at 90 °C for onehour afforded theproduct in 45–73%
yield (see Fig. 1). Workup is very simple and involves the removal of
water in vacuo and subsequent washing of the residue with acetone.
The imidazole zwitterions are soluble in water and DMSO, but barely
soluble in almost every other solvent. Characterisation of the
imidazole zwitterions was possible through multi-nuclear NMR
spectroscopy (1H in D2O; 13C in D2O/DMSO-d6), elemental analysis,
IR-spectroscopy and crystal structure analysis (glycine 1, alanine 2
and phenylalanine 3).
We are interested in the facile synthesis of a functionalised car-
bene with additional chirality, whose stereoelectronic properties
can be easily modified using a modular approach. In addition,
the starting materials should be readily available commercially
and the synthesis should be economical. To this end, we synthes-
ised various carboxylic acid-functionalised imidazolium salts from
The solid state structures of the zwitterionic imidazolium com-
pounds 1–3 contain infinite chains C11 (10)26,27 created by hydrogen
bonding between the COOÀ and COOH groups of the neighbouring
molecules as the central structural motif (see Fig. 2). Normally,
carboxylic acids form dimers with the familiar R22 (8) ring as the
central motif.26,27 This motif was not possible in our case, since only
one COOH group is present. The COOÀ group on the other wingtip
has the greater basicity and thus forms a hydrogen bond with the
COOH group from a neighbouring molecule. This prevents the for-
mation of the more familiar R22 (8) motif and creates the infinite C11
(10) chains instead.
L-amino acids. It is known that the reaction between glycine,
formaldehyde and glyoxal results in a carboxylic acid zwitterion
that forms infinite chain structures through hydrogen bonding be-
tween the carboxylate and carboxylic acid ends of the neighbour-
ing molecules.19 In another synthesis, Erker et al. converted
histidine into functionalised N-heterocyclic carbenes NHC,24
whereas Meldal et al. embedded their NHC in a growing oligopep-
tide chain.25 By employing chiral amino acids such as alanine and
phenylalanine, we used the reaction of Velisek et al.19 to introduce
both chirality and carboxylic acid functionalities into the NHC li-
gand system.
The OÁ Á ÁO distance of the hydrogen bond within the C11 (10)
chain is 247 pm 1, 244 pm 2 and 242 pm 3, respectively. The bond
lengths and angles within the imidazole ring are unremarkable
(see Table 1). The N–C–N angle seems to steadily decrease from
109.22(14)° for 1 over 108.6(2)° for 2 to 107.4(7)° for 3, although
the absolute variations do not rise above 3r. The steric demand
of the amino acid side chain increases from H 1 over Me 2 to CH2Ph
3 causing the density of the crystal to decrease accordingly
(1: 1.555; 2: 1.404; 3: 1.311 g/cm3) as the chains move away from
each other. The neighbouring chains are embedded in a 2D or 3D
hydrogen bond network that changes in accordance with the grow-
ing steric demand of the amino acid side chain.
* Corresponding author.
E-mail address: dockuhl@gmail.com (O. Kühl).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.02.015

394
O. Kühl, G. Palm / Tetrahedron: Asymmetry 21 (2010) 393–397
-OOC
R
O
R
NH3
O
+
H
H
H
O
N
N
90oC
H2O
O
+nH2O
+
H
O
OH
+
R = H 1, Me 2, CH2Ph 3
NH3
R
n = 0, 1
O
-OOC
R
Figure 1. Synthesis of the double carboxylic acid-functionalised zwitterionic imidazolium compounds 1–3.
Figure 2. Crystal structure representation of compound 3. Shown is a chain fragment containing three formula units. The lattice water is represented by the oxygen atom. For
better refinement, alternating COOÀ/COOH groups are represented as COOH/COOH with each proton having only 50% occupancy.
In compound 1, the chains are parallel within the same layer,
Table 1
but antiparallel between consecutive layers (see Fig. 3). The three
hydrogen atoms of the central imidazole ring are engaged in inter-
molecular hydrogen bonds towards the carboxyl groups of the
neighbouring chains. Whereas H4 and H5 (282 pm) bond to the
antiparallel chains immediately above, H2 (290 pm) binds to a
chain facing it (the chain below in a neighbouring stack). The C–
HÁ Á ÁO angles are very small with 109 and 134°, which is indicative
of rather weak interactions. The result is a 3D hydrogen bond
network.
The steric demand of the methyl group in the side chain of ala-
nine causes a disruption in the antiparallel stacking of the chains as
the distances between the hydrogen bond donors and acceptors
would be too long for meaningful interactions to occur. As a result,
Selected bond lengths and bond angles for 1–3
119
1
2
3
Bond lengths [pm]
N1–C2
N3–C2
N1–C5
N3–C4
C4–C5
OÁ Á ÁO
132.6(2)
132.5(2)
138.1(2)
138.0(2)
135.2(2)
246.3(2)
132.66(19)
131.5(2)
137.7(2)
137.1(2)
134.8(2)
247
133.3(3)
132.9(3)
138.7(3)
137.0(3)
134.9(4)
244
133.0(8)
131.0(8)
134.0(10)
136.0(10)
136.1(7)
242
Bond angles [°]
N1–C2–N3
C2–N1–C6
109.4(2)
123.8(2)
124.1(2)
109.22(14)
123.64(14)
124.09(14)
108.6(2)
125.8(2)
124.4(2)
107.4(7)
123.9(7)
123.8(6)
C2–N3–C7
Figure 3. An ORTEP plot showing the packing in compound 1.

O. Kühl, G. Palm / Tetrahedron: Asymmetry 21 (2010) 393–397
395
alternate chains rotate by approximately 90° generating a criss-
cross pattern of alternate layers (see Fig. 4). This allows the rees-
tablishment of the hydrogen-bonding interactions between the
neighbouring chains. In compound 2, only two of the three hydro-
gen atoms of the imidazole ring are engaged in intermolecular
hydrogen bonds. H2 (254 pm) and H4 (273 pm) bond to carboxyl-
ate groups in two different neighbouring chains in neighbouring
chain becomes too sterically demanding for imidazole-H participa-
tion. Due to the apparent weakness of the hydrogen bonds, we ten-
tatively assign the ordering principle for the secondary structure to
the steric demand of the side chain. The hydrogen bond pattern
then only decides which of the sterically possible structures is fi-
nally realised.
The existence of only weak hydrogen-bonding interactions
emanating from the hydrogen atoms of the imidazole ring is
unsurprising, since the pKa values of imidazolium-based NHC are
generally above 20.28,29 The NMR spectra confirm this observation.
In the 1H NMR spectra, the chemical shifts for the H2 proton are
8.80 1, 8.91 2 and 9.30 3, close to a value of 8.96 of the non-func-
tionalised imidazolium cation [N(But)CHN(But)C2H2]+.30 Annelated
imidazolium salts with more acidic H2 protons feature downfield
shifted signals at 9.77 (benzannelated), 9.92 (naphthoannelated)
and 10.50 (quinoxannelated).31 A similar observation is made in
the 13C NMR spectrum, where 1–3 exhibit signals for C2 of 139.3
layers, thereby creating
a 3D hydrogen bond network. H5
(296 pm) is engaged in an intramolecular hydrogen bond with
one of its own carboxylate groups.
In compound 3, the steric demand of the phenyl group in the
phenylalanine side chain becomes so large that direct hydrogen-
bonding interactions between the neighbouring chains become
all but impossible. Instead, the phenyl groups cause a parallel ori-
entation of the chains within and between the layers (see Fig. 5). In
addition, the phenyl groups create a void that can be filled by an
isolated water molecule. Interestingly, only one of the two possible
positions is normally filled and even that water molecule is disor-
dered making the unambiguous location of the hydrogen atoms of
this water molecule impossible. The apparent disorder is con-
firmed by an H–O–H angle of 140°. However, the water molecule
seems to be held in place by a hydrogen-bonding interaction of
1, 136.92
2 and 136.41 3 close to the value of 132.1 for
[N(But)CHN(But)C2H2]+,30 and upfield from the signals of the ann-
elated imidazolium salts at 144.1, 147.6 and 153.2, respectively.31
The IR signals for the three compounds show a signal for the
COOÀ group at 1608 1, 1621 2 and 1626 3 cmÀ1, in line with a
decreasing OÁ Á ÁO distance between neighbouring molecules in
the same direction. A weak signal indicating the N–C–COO group
is detected at 2121 3 and 2111 2 cmÀ1, but not observed for 1.
The solid state structures show that the methyl (alanine) and
phenylmethyl (phenylalanine) residues defining the chirality in
the NHC side chains have a direct and significant influence on
the hydrogen-bonding network formed by the neighbouring COOH
and COOÀ groups. It is the steric demand of the hydrocarbon resi-
dues that determines the nature and orientation of this network.
These functionalised carbene precursors are intended as ligands
for transition metals with a view to asymmetric catalysis. It is ex-
pected that the chirality originating from the amino acids will im-
print itself onto the metal of the catalyst in the same manner as it
determines the hydrogen-bonding network of the ligand.
one of the two hydrogen atoms to the p-electron sextet of the phe-
nyl ring (272–306 pm). The other hydrogen atom interacts with
the carboxylate group of the other wingtip group on the same mol-
ecule (236 pm). The oxygen atom of this water molecule engages in
a hydrogen bond interaction with the H5 atom of a neighbouring
molecule of the same layer (C5Á Á ÁO 315 pm; H5Á Á ÁO 222 pm). The
C5–H5Á Á ÁO angle is 176° indicating a strong hydrogen bond. As
hydrogen bonding is predominantly intramolecular with only a
solitary H5Á Á ÁO hydrogen bond connecting neighbouring chains
with a parallel alignment, the hydrogen bond network is now re-
duced to a 2D pattern.
The three imidazolium zwitterions 1–3 have a primary struc-
ture formed by infinite C11 (10) chains that are generated by a
COOÀÁ Á ÁHOOC hydrogen bond. The chains order themselves by
predominantly weak hydrogen bonds into a 2D or 3D secondary
structure that is dependent on the steric demand of the amino acid
side chain. The hydrogen atoms participating in this secondary
structure are the acidic hydrogen atoms either of the central
imidazole ring or of an incorporated water molecule, when the side
Experiments to synthesise transition metal complexes of these
and similar functionalised NHC precursors for use in asymmetric
catalysis are currently underway in our research group.
3. Conclusion
We have synthesised a series of carboxylate-functionalised chi-
ral imidazolium zwitterions in a facile one-pot synthesis from
readily available amino acids. The solid state structures are domi-
nated by infinite C11 (10) chains formed by hydrogen bonds be-
tween the carboxylic acid group of one molecule and the
corresponding deprotonated carboxylate of another. The chains or-
der themselves into secondary structures that are controlled by the
steric demand of the amino acid side chain and supported by weak
hydrogen bond interactions involving the hydrogen atoms on the
central imidazole ring. Further studies with functionalised and
non-functionalised amino acids are in progress.
4. Experimental
4.1. Methods
Crystals were cryocooled in a nitrogen stream at 110 K (Cryo-
stream, Oxford Cryosystems, Oxford, UK) or used at room temper-
ature for X-ray diffraction data collection. With Cu K X-rays from
a
a Micromax007 rotating anode generator and a Saturn92 CCD
detector (Micromax007, Cu K radiation, Osmic multilayer mirrors,
a
Rigaku MSC, Kemsing, UK) data were collected to at least 0.85 Å
resolution. The data were integrated with CRYSTALCLEAR,
32 scaled with
Figure 4. An ORTEP plot showing the packing in compound 2.

396
O. Kühl, G. Palm / Tetrahedron: Asymmetry 21 (2010) 393–397
Figure 5. An ORTEP plot showing the packing in compound 3.
33
34
SCALA
and the structures were solved and refined with SHELX.
However, a significant decrease in the quality of the final structure
was not observed. Owing to a disordered water molecule, the qual-
ity of structure 3 is not as high as that of 1 and 2.
Most hydrogen atoms were not refined. In consequence, discus-
sion of hydrogen bonding can only be taken as an approximation.
Nonetheless, the apparent weakness of most observed hydrogen
bonds is beyond doubt.
Refinement involved anisotropic least squares refinement with rid-
ing hydrogens.
Compound 1 was recrystallised from water. A single crystal
(100 Â 50 Â 20
ature. Compound 2 was crystallised from water. A single crystal
(300 Â 100 Â 50
m3) was used for data collection at room
temperature. Compound 3 was crystallised from water. A single
l
m3) was used for data collection at room temper-
l
crystal (100 Â 50 Â 20
l
m3) was used for data collection at 110 K
4.2. Preparation of 1,3-bis(carboxymethyl)imidazole 1
(Table 2).
Measurements were performed on a diffractometer optimised
for macromolecules, which determines cell parameters less
accurately and does not allow the collection of a data set at high
resolution as complete as that for the known structure of 1.19
At first, 3.75 g (50 mmol) glycine, 3.85 ml (28%) glyoxal in water
and 750 mg (25 mmol) para-formaldehyde were heated in water at
95 °C for 2 h. The water was then removed in vacuo and the residue
was washed with a small amount of water. The residue was
Table 2
Crystal data and structure refinement for 1–3
119
1
2
3
Formula
Mr
C7H8N2O4
184.154
SUP 44962
296
C7H8N2O4
184.15
749326
293(2)
1.54178 (Cu K
C9H12N2O4
212.21
749327
293(2)
1.54178 (Cu K
C21H20N2O5
380.39
749325
110(2)
1.54178 (Cu K
Triclinic
P1
6.01(1)
8.29(1)
10.23(1)
104.55
94.40
100.04
481.89(11)
1
1.311
200
CCDC reference number
Temperature (K)
k (Å)
Crystal system
Space group
a (Å)
0.7107 (Mo K
a)
a)
a)
a)
Triclinic
Triclinic
Monoclinic
ꢀ
ꢀ
P1 21
1
P1
P1
7.482(4)
7.698(5)
8.202(3)
107.24(4)
106.94(4)
106.77(4)
393.6(3)
2
7.48(1)
7.69(1)
8.20(1)
107.06
106.98
106.81
393.35(9)
2
5.47(1)
8.45(1)
10.95(1)
90.00
97.43
90.00
501.88(12)
2
1.404
224
b (Å)
c (Å)
a
(°)
b (°)
c
(°)
V (Å3)
Z
q
calc. (Mg mÀ3
)
1.553(3)
192
1.555
192
F (0 0 0)
Crystal size (
l
m)
)
750 Â 650 Â 500
100 Â 50 Â 20
300 Â 100 Â 50
100 Â 50 Â 20
Abs. coef. (mmÀ1
0.121
1.117
0.948
0.782
2
Hmax (°)
35.14
35.25
36.04
Reflections (coll.)
Reflections (ind.)
Rint
3482
2818
0.052
1364
1256
0.059
993
979
0.066
1259
1216
0.077
Parameters
127
148
254
R (I > 2
wR2 (all data)
Abs. struct. p.
r
(I))
0.0483
0.1803
0.0446
0.1380
0.2(3)
À0.405
0.368
0.0616
0.1823
À0.3(5)
À0.300
0.316
0.064
(
(
D
D
/
/
q
q
)
)
(e ÅÀ3
)
)
À0.33
À0.524
min
(e ÅÀ3
0.38
0.292
max

O. Kühl, G. Palm / Tetrahedron: Asymmetry 21 (2010) 393–397
397
transferred with methanol into a round-bottomed flask and the
solvent was removed in vacuo to yield 2.75 g (60%) of an off-white
5.20 (dd, 3JHH = 3.9 Hz, 2JHH = 11.3 Hz, 2H, CH), 3.45 (d,
2
3JHH = 3.8 Hz, 1H, CH2), 3.20 (d, JHH = 10.4 Hz, 1H, CH2), 3.15 (d,
powder. NMR (D2O, d ppm): 1H 8.80 (t, JHH = 1.4 Hz, 1H, H2), 7.46
2JHH = 10.4 Hz, 1H, CH2), the peak for the missing CH-proton is hid-
den underneath the water signal (at ca. 3.5 ppm, visible in D2O);
13C–{1H} 168.57 (C@O), 136.41 (C2), 128.69 (o-Ph), 128.53 (m-
Ph), 126.81 (p-Ph), 121.57 (C4/C5), 64.68 (CH), 38.20 (CH2).
IR (KBr, cmÀ1): 3431 (str) OH, 2121 (w) N–C–COO, 1626 (s) COO,
1559 (s) imidazole ring vibration, 1496 (s) phenyl ring vibration.
Elemental Anal. Calcd for C21H20N2O4 (364.53): C, 69.19; H, 5.53;
N, 7.72. Found: C, 69.13; H, 5.83; N, 7.01.
4
4
(d, JHH = 1.4 Hz, 2H, H4/H5), 4.94 (s, 4H, CH2); 13C–{1H} 172.24
(C@O) 139.23 (C2), 124.88 (C4/C5), 52.57 (CH2). IR (KBr, cm-1):
3441 (s) OH, 1734 (s) C@O, 1668 (s) C@O, 1608 (s) COO, 1573 (s)
imidazole ring vibration. Elemental Anal. Calcd for C7H8N2O4
(184.27): C, 45.63; H, 4.38; N, 15.27. Found: C, 45.92; H, 4.82; N,
15.37.
4.3. Preparation of (S,S)-1,3-bis(1,carboxyethyl)imidazole 2
References
At first, 4.5 g (50 mmol) alanine, 3.85 ml (28%) glyoxal in water
and 750 mg (25 mmol) para-formaldehyde were heated in water at
95 °C for 2 h. The water was then removed in vacuo and the residue
was washed with a small amount of water. The residue was trans-
ferred with methanol into a round-bottomed flask and the solvent
was removed in vacuo to yield 3 g (45%) of an off-white powder
1. Bourissou, D.; Guerret, O.; Gabbaï, F. P.; Bertrand, G. Chem. Rev. 2000, 100, 39.
2. Arduengo, A. J., III; Harlow, R. L.; Kline, M. L. J. Am. Chem. Soc. 1991, 113, 361.
3. Kühl, O. Chem. Soc. Rev. 2007, 36, 592.
4. Hahn, F. E.; Jahnke, M. C. Angew. Chem., Int. Ed. 2008, 47, 3122.
5. Kühl, O. Functionalised N-Heterocyclic Carbene Complexes; Wiley
Chichester, 2010.
& Sons:
6. Perry, M. C.; Burgess, K. Tetrahedron: Asymmetry 2003, 14, 951.
(2 Â 0.5 alanine). Mp: 207 °C (softening), 225 °C (decomp.) NMR
7. César, V.; Bellemin-Laponnaz, S.; Gade, L. H. Chem. Soc. Rev. 2004, 33, 619.
8. Focken, T.; Raabe, G.; Bolm, C. Tetrahedron: Asymmetry 2004, 15, 1693.
9. Lee, H. M.; Chiu, O. L.; Zeng, J. Y. Inorg. Chim. Acta 2004, 357, 4313.
10. Gischig, S.; Togni, A. Organometallics 2005, 24, 203.
11. Spencer, L. P.; Winston, S.; Fryzuk, M. D. Organometallics 2004, 23, 3372.
12. Mungur, S. A.; Liddle, S. T.; Wilson, C.; Sarsfield, M. J.; Arnold, P. L. Chem.
Commun. 2004, 2738.
13. Tulloch, A. A. D.; Danopoulos, A. A.; Kleinhenz, S.; Light, M. E.; Hursthouse, M.
B.; Eastham, G. Organometallics 2001, 20, 2027.
14. Arnold, P. L.; Scarisbrick, A. C.; Blake, A. J.; Wilson, C. Chem. Commun. 2001,
2340.
15. Arnold, P. L.; Mungur, S. A.; Blake, A. J.; Wilson, C. Angew. Chem., Int. Ed. 2003,
42, 5981.
16. Van Veldhuizen, J. J.; Garber, S. B.; Kingsbury, J. S.; Hoveyda, A. H. J. Am. Chem.
Soc. 2002, 124, 4954.
17. Fei, Z.; Zhao, D.; Geldbach, T. J.; Scopelliti, R.; Dyson, P. J. Chem. Eur. J. 2004, 10,
4886.
4
(D2O,
d
ppm): 1H; 8.91 (t, JHH = 1.5 Hz, 1H, H2), 7.52 (d,
4JHH = 1.5 Hz, 2H, H4/H5), 5.08 (q, JHH = 7.4 Hz, 2H, CH), 3.87 (q,
3
3JHH = 7.3 Hz, 0.5H, CH, alanine), 1.75 (d, JHH = 7.4 Hz, 6H, CH3),
3
1.44 (d, JHH = 7.3 Hz, 1.5H, CH3, alanine); 13C–{1H} 175.69 (C@O,
3
alanine), 175.60 (C@O), 136.77 (C2), 123.19 (C4/C5), 60.97 (CH),
51.16 (CH, alanine), 18.88 (CH3), 17.28 (CH3, alanine). IR (KBr,
cmÀ1): 3430 (m) OH, 2111 (w) N–C–COO, 1690 (s) C@O, 1621 (s)
COO, 1586 m) imidazole ring vibration. Elemental Anal. Calcd for
C9H12N2O4 (+0.5 alanine + H20): C, 50.40; H, 5.86; N, 13.62. Found:
C, 49.62; H, 6.46; N, 13.33.
Recrystallisation from water yields pure 2 as colourless crystals.
NMR (DMSO-d6, d ppm): 1H; 8.92 (t, 4JHH = 1.5 Hz, 1H, H2), 7.53 (d,
3
4JHH = 1.6 Hz, 2H, H4/H5), 5.10 (q, JHH = 7.4 Hz, 2H, CH), 1.74 (d,
18. Meyer, A.; Taige, M. A.; Strassner, T. J. Organomet. Chem. 2009, 694, 1861.
19. Kratochvil, B.; Ondracek, J.; Velisek, J.; Hasek, J. Acta Cryst. 1988, C44, 1579.
20. Shi, M.; Qian, H.-X. Appl. Organomet. Chem. 2005, 19, 1083.
21. Ray, L.; Shaikh, M. M.; Ghosh, P. Organometallics 2007, 26, 958.
22. Ray, L.; Katiyar, V.; Raihan, M. J.; Nanavati, H.; Shaikh, M. M.; Ghosh, P. Eur. J.
Inorg. Chem. 2006, 3724.
3JHH = 7.4 Hz, 6H, CH3); 13C–{1H}; 175.34 (C@O), 136.92 (C2),
123.24 (C4/C5), 60.77 (CH), 18.84 (CH3).
4.4. Preparation of (S,S)-1,3-bis(1-carboxyphenylethyl)-
imidazole 3
23. Velisek, J. J. Food Sci. 1989, 54, 1544.
24. Hannig, F.; Kehr, G.; Fröhlich, R.; Erker, G. J. Organomet. Chem. 2005, 690, 5959.
25. Jensen, J. F.; Worm-Leonhard, K.; Meldal, M. Eur. J. Org. Chem. 2008, 3785.
26. Etter, M. C. Acc. Chem. Res. 1990, 23, 120.
27. Davis, R. E.; Bernstein, J. Trans. Am. Crystallogr. Assoc. 1998, 33, 7.
28. Alder, R. W.; Allen, P. R.; Williams, S. J. Chem. Commun. 1995, 1267.
29. Denk, M. K.; Rodezno, J. M. J. Organomet. Chem. 2000, 608, 122.
30. Herrmann, W. A.; Böhm, V. P. W.; Gstöttmayr, C. W. K.; Grosche, M.; Reisinger,
C.-P.; Weskamp, T. J. Organomet. Chem. 2001, 617–618, 616.
31. Kühl, O.; Saravanakumar, S.; Ullah, F.; Kindermann, M. K.; Jones, P. G.;
Köckerling, M.; Heinicke, J. Polyhedron 2008, 27, 2825.
At first, 11.07 g (67 mmol) phenylalanine, 5.3 ml (28%) glyoxal
in water and 1.0 g (33 mmol) para-formaldehyde were heated in
water at 95 °C for 2 h. The water was then removed in vacuo and
the residue was washed with a small amount of water. The residue
was transferred with methanol into a round-bottomed flask and
the solvent was removed in vacuo to yield 9.37 g (73%) of an off-
white powder.
32. Pflugrath, J. W. Acta Crystallogr., Sect. D 1999, 55, 1718.
33. Evans, P. R. Acta Crystallogr., Sect. D 2005, 62, 72.
34. Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112.
4
NMR (DMSO, d ppm): 1H 9.30 (t, JHH = 1.3 Hz, 1H, H2), 7.45 (d,
4JHH = 1.3 Hz, 2H, H4/H5), 7.16 (m, 6H, o/p-Ph), 6.96 (m, 4H, m-Ph),