4
136
P. Sukarsaatmadja et al. / Tetrahedron Letters 50 (2009) 4135–4137
5
). The substitution of CuCl
not give 1. Therefore, Li cation probably plays a role as a
template for cyclization.11 Three molecules of
should
2 2 2
, ZnCl , or MgCl for LiCl also did
2
form a steric arrangement of cyclic trimer with the aid of Li
cation.
Solubility of 1 in various solvents has been investigated. Tri-
mer 1 is poorly soluble in common organic solvents, while it
is highly soluble in aqueous acids. In addition, when 3 M equiv
of MgCl is added to the solution, 1 becomes readily soluble in
2
polar organic solvents such as methanol, ethanol, and dimethyl
sulfoxide. Excess amount of LiCl also acts as a solubilizer in
these solvents. Other metal salts such as CuCl
not show any solubilizing effect. Though the exact working
mechanism of MgCl and LiCl is not yet clearly understood, we
2
and NaCl did
2
suggest that three Mg cations bind to the carbonyl oxygen and
N3 of 1 to form a chelate complex.
Figure 1 shows the absorption spectra of 1 in ethanol con-
taining MgCl
strong peak at ca. 280 nm and
2
(3 equiv) and in H
2
SO
a
4
. Cyclic trimer 1 has a
small broad one at ca.
Figure 1. Absorption spectra of (a) 1 and 2 in ethanol containing 3 M equiv of
MgCl and (b) 1 in 0.18, 0.90, and 1.26 N H SO
4
00 nm. The former corresponds to the absorption by the build-
2
2
4
.
ing block 2 (see Fig. 1(a)). The latter indicates the extended con-
jugation between the amide bonds and the imidazole rings in 1.
When the concentration of H SO is changed from 0.18 M to
2 4
1
.26 M, the former peak shifts by about À20 nm, showing that
the protonation of basic N3 atoms in 1 occurs in strong acid
solution.
Single crystals of the sulfate salt of 1Á3H
analysis was obtained by slowly evaporating the solution of 1 in
.6 M H SO
. The X-ray structure (Fig. 2)12 shows that the three
N3 imidazole nitrogens in 1Á3H SO are protonated, which corre-
2 4
SO suitable for X-ray
3
2
4
2
4
sponds to the observation in the absorption spectra. The three
amide hydrogens point toward the center of the macrocycle, while
two of them direct slightly upward and the other one slightly
downward from the macrocycle. The distance between the amide
hydrogens is 2.19–2.69 Å. As mentioned above, the absorption
spectra indicate that the imidazole rings and the amide bonds
are conjugated in 1. The conjugation state can be evaluated
through the analysis of the planarity and the amide bond length
of 1. The three imidazole rings of 1 lie nearly on the same plane:
the root-mean-square deviation of the imidazole N and C atoms
from their mean plane is 0.136 Å. However, the amide bonds are
tilted on average 38.4° out of the mean plane of the imidazole
rings. Further, the lengths of the amido bond and the carbonyl
bond are 1.368 and 1.216 Å, respectively. The double bond charac-
ter of the amide bonds in 1 is weaker than that of typical amide
bonds in proteins, of which the C–N and C–O lengths are in the
1
3
ranges of 1.325–1.350 Å and 1.245–1.220 Å, respectively. So,
the conjugation between imidazole rings and amide bonds in 1 is
rather weak.
Figure 2. X-ray crystal structure of 1Á3H SO . Three HSO4À are omitted for clarity.
2
4
In conclusion, we have synthesized and characterized a novel
imidazole based cyclic trimer 1. The cyclic trimer was prepared
by one-step condensation reaction of ethyl-4-amino-1-methylim-
idazole-5-carboxylate, 2 in the presence of LiCl as a template for
the cyclization. Three imidazole rings construct a macrocycle with
arrays of N1, C2, and N3 of imidazole rings projecting outward
from the macrocycle. The basic N3 at the outer accessible site will
allow further chemical modifications, which would contribute to
the development of new classes of liquid crystals and metal
chelators.
References and notes
1.
(a) Gonzalez-Alvarez, A.; Alfonso, I.; Dias, P.; Garcia-Espana, E.; Gotor-
Vernandez, V.; Gotor, V. J. Org. Chem. 2008, 73, 374; (b) Cruz, C.; Delgado, R.;
Drew, M. G. B.; Felix, V. J. Org. Chem. 2007, 72, 4023; (c) Choi, K.; Hamilton, A. D.
J. Am. Chem. Soc. 2003, 125, 10241.
Table 1
Effect of NaOMe and LiCl in preparation of 1
2.
(a) Kang, S. O.; Hossain, M. A.; Bowman-James, K. Coord. Chem. Rev. 2006, 250,
3
038; (b) Choi, K.; Hamilton, A. D. Coord. Chem. Rev. 2003, 240, 101; (c) Gale, P.
Entry
Equiv of NaOMe
Equiv of LiCl
Yield (%)
A. Coord. Chem. Rev. 2001, 213, 79.
1
2
3
4
1.2
2.0
0.5
1.2
3.2
3.2
3.2
0
53
59
0
3. Ranganathan, D.; Lakshmi, C.; Haridas, V.; Gopikumar, M. Pure Appl. Chem.
2000, 72, 365.
4.
5.
6.
Haberhauer, G.; Rominger, F. Tetrahedron Lett. 2002, 43, 6335.
Burnett, F. N.; Hosmane, R. S. Tetrahedron 2002, 58, 9567.
Bridson, P. G.; Wang, X. Synthesis 1995, 7, 855.
0