4H-Imidazoles as functional dyes: synthesis of bichromophores and extension of the merocyanine system

Article abstract of DOI:10.1016/j.tet.2008.05.117

A series of bichromophores consisting of a 'classical' chromophore and 4H-imidazoles were synthesized starting from appropriate cyano and carboxy functionalized systems. In their UV-vis spectra, an additive absorption of both chromophores was detected making them wide range-absorbing dyes. In addition, new properties as redox activity, pH-switchability and metal-chelating substructures are newly introduced into the molecules. In order to achieve more bathochromic absorbing systems, the chromophore of 4H-imidazoles was extended. The 4H-imidazo-[1,2-a]-pyridines, which are easily accessible by cyclization of 2-aminopyridines with bis-imidoylchlorides, show long wavelength absorptions up to 616 nm. Their reduction reversibly yields yellow, blue fluorescent 1-azaindolizines. In contrast to leuco-forms of 4H-imidazoles, these reduction products show a high stability towards oxygen and could only be reoxidized to their starting materials by oxidation agents, such as DDQ.

Full text of DOI:10.1016/j.tet.2008.05.117

Tetrahedron 64 (2008) 7815–7821
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
4H-Imidazoles as functional dyes: synthesis of bichromophores and extension of
the merocyanine system
*
Martin Matschke, Jo¨rg Blumhoff, Rainer Beckert
Institute of Organic and Macromolecular Chemistry, Friedrich-Schiller-University, Humboldt street 10, D-07743 Jena, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of bichromophores consisting of a ‘classical’ chromophore and 4H-imidazoles were synthesized
starting from appropriate cyano and carboxy functionalized systems. In their UV–vis spectra, an additive
absorption of both chromophores was detected making them wide range-absorbing dyes. In addition,
new properties as redox activity, pH-switchability and metal-chelating substructures are newly
introduced into the molecules. In order to achieve more bathochromic absorbing systems, the chro-
mophore of 4H-imidazoles was extended. The 4H-imidazo-[1,2-a]-pyridines, which are easily accessible
by cyclization of 2-aminopyridines with bis-imidoylchlorides, show long wavelength absorptions up to
616 nm. Their reduction reversibly yields yellow, blue fluorescent 1-azaindolizines. In contrast to leuco-
forms of 4H-imidazoles, these reduction products show a high stability towards oxygen and could only
be reoxidized to their starting materials by oxidation agents, such as DDQ.
Received 22 February 2008
Received in revised form 26 May 2008
Accepted 29 May 2008
Available online 3 June 2008
Keywords:
4H-Imidazoles
Merocyanines
Bichromophores
Functional dyes
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
aim was to connect classic chromophores with 4H-imidazoles and
to study the properties of the resulting bichromophores.
The combination of two or more chromophores is of recent in-
terest in material sciences, e.g., for the synthesis of novel antenna
systems. Such antenna systems are widely used by nature to solve
the problem of light harvesting efficiency in the photosynthetic
processes. Antennas are well-organized multicomponent systems
in which several chromophoric subspecies absorb the sunlight and
channel the excitation energy to an acceptor part. In addition to the
solar energy conversion, there is a strong need for antenna systems,
for example, in signal amplification in luminescence sensors, for
light-driven reactions/catalyses and in sensitation of photovoltaics.
All these applications are based on tailor-made multi-chromo-
phores, which are arranged in supramolecular arrays suitably
organized in the dimensions of time, energy and space.
coupling with other chromophores
UV/vis: hypso-/bathochromic shift
by donor/acceptor substituents
Ar
protonation gives cyanines
metal complexation or
cyclization with BR3 (cyanines)
N
N
X
R
deprotonation gives (aza)oxonoles
NH
N
1
UV/vis: hypso-/bathochromic shift
by donor/acceptor substituents
reversible two-step redox system
Ar
Scheme 1. 4H-Imidazolesdcyclic merocyanines and functional dyes.
Typical chromophores, which were often employed are por-
phyrins, the main chromophores of natural photosynthesis. Further
systems used as part of a multi-chromophoric assembly are:
bodypys,1 peryleneimides,2 coumarines,3 eosine4 and others.
In the last decade, in our group the 4H-imidazoles 1 were de-
veloped as a new class of functional dyes: dependent on their
substituents, they show absorptions in a wide range of the visible
spectrum,5 are pH-switchable,6 reversible two-electron-redoxsys-
tems7 and efficient chelating ligands for metals (Scheme 1).8 Our
2. Results and discussion
In the framework of this study, different chromophores were
involved in order to obtain general information concerning the new
bichromophores. A comparison with already existing derivatives,
which contain conjugated9 and non-conjugated10 structural ele-
ments, should clarify the question if an additive behaviour9 of the
subchromophores exists.
The direct coupling of the chromophores was ruled out, due to
the fact that 4H-imidazoles proved to be inactive in all attempts
using metal-catalyzed cross-coupling methods. Therefore, another
synthetic entry was chosen: cycloacylation reactions of amidines 3
* Corresponding author. Tel.: þ49 3641 948230; fax: þ49 3641 948212.
E-mail address: c6bera@uni-jena.de (R. Beckert).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.05.117

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M. Matschke et al. / Tetrahedron 64 (2008) 7815–7821
Cl
Cl
N-Tol
N-Tol
H2N
H2N
N-Tol
N-Tol
NH-Tol
N-Tol
NH
N
N
4
7
X
X
X
COCl
X
X
CN
COOH
2
6
5
NH2
8
3
X = chromophore
Scheme 2. Synthetic pathways for novel bichromophores.
with bis-imidoylchlorides 4 (method A5) and alternatively, cycli-
zation of oxalamidines 7 with carboxylic acid chlorides 6 (method
B11). The easy synthetic entry to the corresponding nitriles 2 or
carboxylic acids 5 was therefore the most important criterion.
Cyano-substituted acridines (2a)10,12 and porphyrines (2b)13,14
as well as carboxylic acids derived from xanthene (5c),15,16 9,10-
anthraquinone (5d, 5e),17,18 triphenylmethane (5f)19 and indigo
(5g)20 were synthesized according to literature procedures.
Employing the two different methods described above, a series of
bichromophores of type 8 were synthesized (Scheme 2).
Due to side reactions and low solubility, neither tri-
phenylmethane 5f nor meso-tetracyanoporphyrine 2b could be
integrated into bichromophores together with 4H-imidazoles.
The new synthesized bichromophores 8 show the characteristic
spectroscopic properties (NMR, IR, MS). The chemical properties
(protonation, deprotonation, reversible reduction to 1H-imidaz-
oles) also agreed with properties of existing compounds.6 Although
most of the 4H-imidazoles do not show fluorescence, the in-
tegration of strong fluorophores such as 5c and 5e leads to fluo-
rescent derivatives. The 3D-fluorescence spectra of these novel
derivatives showed that the maximum intensity of their emission
(8c: lmax,em¼577 nm, 8e: lmax,em¼605 nm) was found by an exci-
tation wavelength of lmax,exc¼480 nm. In addition, derivative 8c
showed a second emission maximum at 412 nm (lmax,exc¼380 nm).
The influence of the second chromophoric system on the chro-
mophore of 4H-imidazoles is apparent upon viewing the data of
absorption wavelengths given in Table 1.
4H-imidazoles at 480–520 nm with extinction coefficients log 3>4,
an additional, mostly less intense but bathochromically shifted ab-
sorption band was observed, which originates from the second
chromophore (Fig. 1). Thus, the connection of the merocyanine-like
system of 4H-imidazoles with long wavelength absorbing chromo-
phores forms bichromophores, which shows an additive absorption
of both single chromophores. As depicted in Figure 1, the combi-
nation of such types of chromophores resulted in radiation ab-
sorption in a wide range of the visible spectra.
In contrast to relatively bright colours of the 2-arylsubstituted
derivatives, solutions of derivatives 8 show reddish-brown to
brownish-purple colours. This wide range absorption makes them
interesting for applications in organic solar cells.21
Generally, 4H-imidazoles, which show absorptions higher than
550 nm, could only be obtained by derivatization reactions and
thus by changing their chromophoric system (Scheme 3, pro-
tonation/deprotonation,6 cyclization with boron compounds22).
Another modification is succeeded by the introduction of auxo-
chromic groups into the arylamino/imino substituents in 4/5-
position. A strong bathochromic shift and hyperchromism of the
products are observed (Ar¼4-Me2NC6H4:
log
>4.5).23
However, the most common method to obtain long wavelength
lmax>560 nm,
3
absorbing 4H-imidazoles is the extension of their pentamethine–
merocyanine chromophore. Already in the 1980s we recognized
the potential of cycloamidine syntheses starting from amino-N-
heterocycles, which others first published over 20 years later.24
Recently, we readopted this method because only a few derivatives
were described and fully characterized. 2-Aminopyridine could be
easily cyclised with bis-imidoylchlorides of oxalic acid 4 giving 4H-
imidazo-[1,2-a]-pyridines 9 in moderate yields (Table 2, Scheme 4).
These deep red to purple coloured systems can be regarded as
ring-fused derivatives of 4H-imidazoles possessing an extended
chromophore.
Obviously, aliphatic/aromatic substituents in 2-position of the
4H-imidazole as well as type and length of the conjugative
bridging unit between the 4H-imidazol-heterocycles have only
a minor influence on position and shape of the long wavelength
absorption bands. This finding, in addition to the tendency to an
increase of extinction coefficients indicates the behaviour of ad-
ditive absorption. The corresponding spectral data of derivatives
8h and 8i with non-conjugated bridges supported this important
observation.
Upon heating of the 2-aminopyridines with 4 in acetonitrile in
the presence of triethylamine, the bicyclic derivatives 9 were iso-
Ar-N
NH-Ar
N
N
O
N
N
N
N
Ar-HN
Ar-N
N-Ar
NH-Ar
N-Ar
NH-Ar
Ar-HN
Ar-N
N
N
N
N
8i
8h
Ar = 4-CH3-C6H4-,λmax (CH2Cl2) = 502 nm (4.3)
Ar = 4-tC4H9-C6H4-,λmax (CHCl3) = 495 nm (4.7)
In particular, the ‘electronic isolation’ of the 4H-imidazole chro-
mophore becomes visible by the integration of long wavelength
absorbing chromophores, such as derivatives of xanthene, indigo or
anthraquinone. In addition to the characteristic absorption bands of
lated in yields up to 55% as dark red to deep purple, mostly crys-
talline solids. Compared with 2-arylsubstituted 4H-imidazoles, the
ring-fused derivatives 9, which also can be described as betaines of
1-aza-2H-indolizine,25 show some differences.

M. Matschke et al. / Tetrahedron 64 (2008) 7815–7821
7817
Table 1
Absorption properties of synthesized chromophores and bichromophores derived from 4H-imidazoles
NH-Ar
NH-Ar
N-Ar
Ar-N
N
N
N
N
N
R
X
N
N-Ar
4H-imidazole
Ar-HN
bis-4H-imidazole
R
Ar
lmax in nm (log
3
)
X
Ar
lmax in nm (log 3)
Aliphatic substituents
Conjugative bridging-units
CH3
.
Ar2
461 (4.2)b
Ar2
Ar1
Ar1
479 (4.2), 533 (4.2)a
511 (4.1), 545 (4.1)a
497 (4.1), 527 (4.0)a
H3C
.
.
CH3
Aromatic substituents
.
.
Ar1
488 (4.2)a
496 (4.2)b
.
.
.
.
Ar1
Ar1
499 (4.2)a
.
.
N
.
OC8H17
.
Ar1
480 (4.3), 520 (4.2)a
Ar1
504 (4.6), 540 (4.4)a
.
H17C8O
CN
Substitution by longwave absorbing chromophores
O
.
Ar1
481 (4.3)b
Ar1
513 (4.4), 544 (4.2)a
.
N
O
8a
8d
O
H
N
.
Ar1
508 (4.0), 595 (3.5)c
Ar1
523 (4.2), 622 (3.6)a
-
+
N
Me2N
O
Cl
.
NMe2
H
O
8c
8g
O
OH
O
.
Ar1
512 (3.9), 615 (3.7)a
Ar1
524 (4.3)a
H9C4
n
N
N nC4H9
O
OH
O
8e
Ar1¼4-CH3-C6H4–, Ar2¼4-t-C4H9–C6H4–.
a
The UV–vis spectra were measured in THF.
The UV–vis spectra were measured in CHCl3.
The UV–vis spectra were measured in MeOH.
b
c
The 1H NMR spectra of the parent compounds 1 show single
negative charges at the imino-nitrogen atoms. However, all at-
tempts to protonate this nitrogen as well as to perform simple
alkylation or acylation reactions failed. Treatment of 9a with
strong alkylating agents such as trialkyloxonium salts led to the
formation of extremely unstable pyridinium salts, which fastly
signal sets caused by a very fast prototropism between peripheric
arylamino/imino-groups, which reflects a high symmetry of the
molecules. In contrast, the NMR spectra of derivatives 9 show
double signal sets. Both mesomeric forms (90 and 900) suggest

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M. Matschke et al. / Tetrahedron 64 (2008) 7815–7821
R
2
1.5
1
+
-
Me2N
R
O
NMe2 Cl
5c: R = COOH
O
H
N
N
H
R
0.5
0
O
5g: R = COOH
NH-Tol
N-Tol
N
450
500
5c
550
wavelength [nm]
600
8g
650
8c, g: R =
.
N
8c
5g
Figure 1. UV–vis spectra of integrated chromophores 5c, g and obtained bichromophores 8c, g.
NH-Ar
N
R
N
N-Ar
merocyanine
λmax 480-520nm
p-N,N-Dimethyl-
phenylendiamine
cat.p-TSA
H+
base
BR3,TEA
Ar
NH-Ar
N
NH-Ar
NH-Ar
N-Ar
N-Ar
N
N
N
N
R
N
R
R
2-
R
R
+
+
R
- B
N-Ar
N
N
N
N
-
Ar
Ar = 4-NMe2-C6H4
cyanine
λmax up to 720nm
(aza)oxonole
λmax 530-560nm
cyanine
λmax up to 620nm
merocyanine
λmax 570-590nm
Scheme 3. Derivatization reactions of 4H-imidazoles.
Table 2
With respect to 4H-imidazoles 1, the most outstanding property
of derivatives 9a–e is their 80–100 nm bathochromic shifted ab-
sorption, which results in a deep purple colour of their solutions.
The integration of the pyridine ring causes extension of the
chromophore of 1 by four methine units forming a new non-
amethine–merocyanine. The strong electron-accepting character of
the nitro-group in derivative 9f resulted in a hypsochromic shift
of the long wavelength absorption in its UV–vis-spectrum as well
as a small hypochromic effect (Table 2).
The integration of additional condensed ring-systems does not
expand the chromophoric system. As demonstrated with the 4H-
imidazo-[1,2-a]-isochinoline 9g, the characteristic chromophore of
4H-imidazoles is predominant. The chromophoric system of tet-
raazafulvalenes, which were also synthesized in our research
group,27 is based on two crossed diazaheptamethine–
Longest wavelength absorptions of synthesized 4H-imidazo-[1,2-a]-pyridines 9
No.
R
Ar
Yield
(%)
lmax in nm
(log ) [CHCl3]
3
9a
9b
9c
9d
9e
9f
R1–R4¼H
4-CH3–C6H4–
41
38
22
21
35
27
55
586 (3.9)
585 (3.9)
531 (3.9)
556 (3.9)
616 (3.9)
534 (3.8)
534 (3.9)
R1–R4¼H
4-n-C4H9–C6H4–
2,6-i-C3H7–C6H3–
2,4,6-CH3–C6H2-
4-CH3–C6H4–
4-CH3–C6H4–
4-CH3–C6H4–
R1–R4¼H
R1–R4¼H
R1¼CH3–
R2¼NO2–
9g
R3, R4¼1,2-C6H4–
decomposed to tolylisocyanide and mixtures of unseparable
compounds. This very low stability might be caused by the far
reaching similarity to other pyridinium salts, known as acyl-
transfer-reagents.26
R3
R3
R3
R4
N
R4
N
R4
N
R3
N
R2
R1
R2
R1
R2
R1
R4
Cl
Cl
N-Ar
N-Ar
R2
R1
2.5 eq. TEA
MeCN
+
N
N
N
+
+
NH2
Ar-N
N-Ar
Ar-N
N-Ar
Ar-N
N-Ar
4
-
-
9''
9
9'
Scheme 4. Synthesis of 4H-imidazo-[1,2-a]-pyridines 9.

M. Matschke et al. / Tetrahedron 64 (2008) 7815–7821
Ar-N
HN
7819
NH-Ar
N
R
N
NH
N-Ar
N
N
N
N
N
N
R
N-Tol
N-Ar
Ar-HN
Tol-N
Ar-HN
Ar-N
N-Ar
tetraazafulvalene
heptamethine
λmax= 530-550nm
9a-f
nonamethine
λmax= 560-610nm
9g
2-phenyl-4H-imidazole
pentamethine
λmax= 480-520nm
pentamethine
λmax= 534nm
Scheme 5. Diazapolymethine–merocyanines based on cycloamidines.
R3
N
R3
N
merocyanines. Their absorptions, which are located in the range of
530–550 nm fit well into the system of merocyanines (Scheme 5).
In comparison to acyclic merocyanines of type (CH3)2N–
(CH]CH)nꢀ1–CH]O,28 which possess the same number of
methine units, the cyclic diazapolymethine–merocyanines show
a bathochromic shift of about 120 nm.
Similar to their parent derivatives 1, the 4H-imidazo-[1,2-a]-
pyridines 9 show quasi-reversibility of the reduction, evidenced
chemically as well as electrochemically. The comparison of the
R4
N
R4
N
R2
R1
R2
R1
aq. Na2S2O4
DDQ
Ar-HN
NH-Ar
Ar-N
N-Ar
9
10
No.
R
10a
10b
10c
10d
10e
10f
R1-R4 = H
R1-R4 = H
R1-R4 = H
375 nm (3.9) 470 nm (382 nm)
391 nm (3.9) 474 nm (392 nm)
376 nm (3.9) 476 nm (375 nm)
450 nm (3.9) 532 nm (454 nm)
475 nm (3.9) 554 nm (479 nm)
470 nm (3.8) 475 nm (470 nm)
440 nm (3.9) 474 nm (438 nm)
N-Tol
Ar-HN
Ar-HN
NH-Ar
NH-Ar
N
N
N
N
N
N
N
N
R1-R4 = H
NH-Tol
Ar-N
N-Ar
-
R
R
1 = CH3
9a-d
2-phenyl-4H-imidazole 1
tetraazafulvalene
-
2 = NO2
2
No.
1
chromophore
pentamethine
pentamethine
heptamethine
nonamethine
nonamethine
nonamethine
nonamethine
ERED1, ERED
KSEM
-
10g
R3,R4 = 1,2-C6H4
-1.26 V, -1.39 V
-0.83 V, -0.98 V
-0.69 V, -0.83 V
-0.80 V, -0.95 V
-0.81 V, -0.95 V
-1.01 V, -1.12 V
-0.88 V, -1.03 V
1.6*102
4.1*102
1.7*102
4.1*102
2.4*102
7.4*101
4.1*102
Scheme 6. Reduction of 9 and absorption/emission data of the 2,3-bis-(arylamino)-1-
azaindolizines 10.
9g
TAF
9a
The reduction of derivatives of type 9 with aqueous sodium
dithionite yields yellow, greenish-blue fluorescent products
(Scheme 6). Elemental analysis, MS and NMR data confirm the
structure of 1-azaindolizines 10. However, in contrast to the re-
duction products of 4H-imidazoles, these leuco-forms were not
reoxidized when exposed to air. Even standing at room tempera-
ture within 1–2 days, they decompose leading to complex mixtures
consisting mainly of 2-aminopyridine and the corresponding
arylamine ArNH2 (TLC). Reoxidation only takes place in the pres-
ence of strong oxidizing agents, e.g., DDQ to give starting material 9.
All attempts to modify the leuco-forms by alkylation or acylation
reactions failed.
9b
9c
9d
0
-10
-20
-30
-40
3. Conclusions
The synthesis of a number of bichromophores starting from
classical chromophores and one or two 4H-imidazoles is reported.
All synthesized derivatives were fully characterized by MS, NMR
and IR. Their UV–vis spectra show an overlap of the chromophores
resulting in wide range-absorbing systems. Due to the integration
of 4H-imidazoles in bi-/multichromophores some useful function-
alities were generated:
-2
-1.5
-1
E [V]
-0.5
0
CV of 9g
Figure 2. Electrochemical data of different diazapolymethine–merocyanine chromo-
phores and cyclovoltammogram of 9g.
ꢁ redox activity (derivates 8 and 9 can be regarded as multi-step
redox sytems)
semiquinone formation constants KSEM of the three azamero-
cyanines (4H-imidazoles, tetraazafulvalenes, 4H-imidazo-[1,2-a]-
ꢁ all systems are pH-switchable
pyridines) indicates
a
low thermodynamic stability of the
ꢁ the peripheric amino/imino substructures of 4H-imidazoles
offer good requirements for the formation of metal chelate
complexes.
intermediates (radical anion¼SEM form), which are not influenced
by the length of the conjugated system (Fig. 2).

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M. Matschke et al. / Tetrahedron 64 (2008) 7815–7821
The concept of cycloamidines could be expanded to non-
(THF) lmax (log 3): 409 (4.1), 512 (3.9), 615 (3.7) nm; Fluorescence
amethine–merocyanines. They can easily be obtained by cyclization
of 2-aminopyridines with bis-imidoylchlorides. The obtained 4H-
imidazo-[1,2-a]-pyridines 9 show long wavelength absorptions up
to 616 nm in their UV–vis spectra. Comparable to 4H-imidazoles,
they are two-step redox systems indicated by electrochemical
measurements, which showed the reversibility of their reduction.
However, the products of chemical reductionsd1-azaindolizines
10dare yellow, blue fluorescent compounds, which proved to be
stable towards oxygen. On treatment with oxidizing agents such as
DDQ, their reoxidation could be realized yielding derivatives 9. In
summary, tailor-made 4H-imidazoles are of interest for applica-
tions in functional dyes.
(THF, 480 nm) lmax,em: 605 nm.
4.1.4. 5,50-Bis-(p-tolylamino)-4,40-bis-(p-tolylimino)-4H,40H-2,20-
(5,50-indigo)-biimidazole (8g)
Yield: 10%, dark red powder, mp>300 ꢂC (decomp.); 1H NMR
(250 MHz, CDCl3):
d
2.28 (s, 12H), 6.99 (m, 10H), 7.08 (d, 3J¼8.3 Hz,
2H), 7.18 (d, 3J¼8.3 Hz, 2H), 7.28 (d, 3J¼8.3 Hz, 8H), 7.95 (s, 2H); 13
C
NMR (62 MHz, CDCl3): d 22.7, 117.8, 119.8, 123.8, 125.5, 128.2, 129.6,
129.7, 129.8, 130.0, 135.8, 151.5, 163.3, 173.2, 191.4; MS (FAB in nba):
m/z (%): 811 (M)þ (9), 721 (12), 578 (14), 505 (18), 461 (23), 327 (39),
281 (45), 265 (51), 219 (89), 207 (100); IR (film): 3648, 3300,
1738 cmꢀ1; UV–vis (THF) lmax (log
3): 408 (3.9), 473 (4.2), 503 (4.3),
523 (4.2), 622 (3.6) nm.
4. Experimental
4.1. General
4.2. General procedure for the synthesis of 4H-imidazo-
[1,2-a]-pyridines (9)
All reactions were monitored by TLC, carried out on 0.25 mm
Merck silica gel plates (60 F254) using UV light. 1H and 13C NMR
spectra were recorded with a Bruker DRX 400 or Bruker AC 250
spectrometer. Melting points are measured with a Galen TM 3 ap-
paratus and are uncorrected. UV–vis spectra were recorded on
a Perkin–Elmer Lambda 19 spectrophotometer. MS spectra were
taken from measurements on a Finnigan MAT SAQ 710 mass spec-
trometer. Electrochemical measurements were carried out with
a Metrohm 663VA Stand using mercury or platinum electrodes and
tetrabutylammoniumhexafluorophosphate as conductive salt.
For synthesis and analytic data of 4H-imidazoles with ali-
phatic10,11 and aromatic substituents including derivatives 8a, 8h
and 8i,10,11,29 as well as bis-4H-imidazoles with conjugative bridg-
ing-units9 (Table 1), see the given literatures. Bichromophores 8c–g
were synthesized according to literature procedures.11
The corresponding aminopyridine (2.0 mmol) or 1-amino-
isoquinoline (288 mg, 2.0 mmol) was added to a solution of
2.0 mmol oxalic acid bis-imidoylcloride in 20 ml of acetonitrile.
After addition of 0.7 ml (5.0 mmol) triethylamine, the reaction
mixture was heated under reflux for about 4–5 h. The deep red-
violet solution was cooled to rt, evaporated to dryness and the
product was isolated by column chromatography (SiO2, toluene/
acetone 100:1). The 4H-imidazo-[1,2-a]-pyridines
9
were
obtained as dark red-violet crystalline solids after removing the
solvents.
4.2.1. 2,3-Bis-(4-tolylimino)-2H-imidazo-[1,2-a]-pyridine (9a)
Yield: 267 mg (41%), golden shining crystals, mp 139–140 ꢂC; 1H
NMR (250 MHz, CDCl3):
d 2.30 (s, 3H), 2.37 (s, 3H), 6.40 (t,
3J¼6.5 Hz, 1H), 6.91 (d, 3J¼9.2 Hz, 1H), 7.10 (d, 3J¼8.0 Hz, 2H), 7.17
(d, 3J¼8.0 Hz, 2H), 7.35 (d, 3J¼8.0 Hz, 2H), 7.43 (d, 3J¼8.0 Hz, 2H),
7.55 (t, 3J¼6.5 Hz, 1H), 8.01 (d, 3J¼6.8 Hz, 1H); 13C NMR (62 MHz,
4.1.1. 9-[5-p-Tolylamino-4-(p-tolylimino)-4H-imidazol-2-yl]-3,6-
bis-(dimethylamino)-xanthyliumchloride (8c)
CDCl3):
d 21.2, 30.9, 109.2, 117.4, 119.8, 122.6, 125.5, 127.6, 128.8,
Yield: 12%, brown solid, mp>250 ꢂC (decomp.); 1H NMR
129.1,129.8,135.5,135.9,141.1,142.5,145.4,145.6; MS (DEI): m/z (%):
328 (Mþ2)þ (82), 311 (43), 235 (21), 222 (33), 209 (51),183 (29),131
(23), 116 (55), 106 (94), 91 (100), 78 (100); IR (ATR): 1649, 1608,
(250 MHz, CDCl3):
d 2.28 (s, 12H), 2.35 (s, 6H), 7.15–7.25 (m, 8H),
7.36 (d, 3J¼8.3 Hz, 4H), 7.88 (d, 3J¼8.2 Hz, 2H); 13C NMR
(62 MHz, CDCl3):
d
21.1, 34.2, 100.0, 115.5, 125.4, 128.3, 129.6,
1568, 1479 cmꢀ1; UV–vis (THF) lmax (log
3): 248 (4.4), 306 (4.2), 505
130.7, 131.6, 132.9, 134.0, 135.8, 148.2, 151.5, 162.2, 170.3; MS
(DEI): m/z (%): 547 (M)þ (17), 546 (33), 396 (43), 268 (83), 220
(100), 205 (90), 177 (29), 145 (35), 133 (46), 105 (35), 91 (43), 57
(69); IR (film): 3640, 1513, 1434 cmꢀ1; UV–vis (MeOH) lmax
(4.0), 543 (4.1), 586 (3.9) nm; CV: E1RED¼ꢀ0.80 V, ER2ED¼ꢀ0.95 V.
Anal. Calcd for C21H18N4: C, 77.28; H, 5.55; N, 17.17. Found: C, 77.03;
H, 5.50; N, 17.47.
(log
3
): 457 (4.1), 480 (4.2), 508 (4.0), 595 (3.5) nm. Fluorescence
4.2.2. 2,3-Bis-(4-n-butylphenylimino)-2H-imidazo-[1,2-a]-
pyridine (9b)
(MeOH, 480 nm) lmax,em
412 nm.
: 577 nm, lmax,exc: 380 nm, lmax,em:
Yield: 312 mg (38%), black violet solid; 1H NMR (400 MHz,
CDCl3):
d 0.96 (s, 3H), 0.99 (s, 3H), 1.35–1.48 (m, 4H), 1.58–1.75 (m,
4.1.2. 5,50-Bis-(p-tolylamino)-4,40-bis-(p-tolylimino)-4H,40H-2,20-
(2,6-anthraquinone)-biimidazole (8d)
4H), 2.62 (t, 3J¼8.0 Hz, 2H), 2.69 (t, 3J¼7.2 Hz, 2H), 6.38 (t, 3J¼6.4 Hz,
1H), 6.72 (d, 3J¼6.4 Hz, 1H), 7.38 (t, 3J¼6.4 Hz, 1H), 7.47 (d,
3J¼8.4 Hz, 2H), 7.50 (d, 3J¼8.4 Hz, 2H), 7.60 (d, 3J¼6.8 Hz, 2H), 7.63
(d, 3J¼7.6 Hz, 2H), 8.00 (d, 3J¼6.4 Hz, 1H); 13C NMR (100 MHz,
Yield: 10%, metallic red shining solid, mp>250 ꢂC (decomp.);
NMR: no valuable spectra were obtained caused by too poor solu-
bility; MS (DEI): m/z (%): 758 (M)þ (8), 653 (10), 506 (29), 492 (33),
370 (26), 363 (44), 248 (40), 234 (35), 106 (100); IR (film): 3345,
CDCl3):
d 14.0, 21.5, 22.3, 33.7, 35.2, 109.3, 115.8, 117.4, 119.9, 122.6,
124.5, 125.3, 125.9, 127.4, 128.1, 128.3, 128.6, 128.9, 129.2, 129.7,
130.4, 130.7, 131.6, 145.4, 145.8, 149.3, 151.3, 157.5, 162.8; MS (DEI):
m/z (%): 411 (Mþ1)þ (51), 355 (39), 309 (47), 259 (71), 228 (74), 208
(65), 166 (69), 149 (73), 106 (74), 91 (100), 57 (27); IR (ATR): 1654,
1676 cmꢀ1; UV–vis (THF) lmax (log
3): 405 (4.2), 429 (4.2), 481 (4.2),
513 (4.4), 544 (4.2) nm; CV: E1RED¼ꢀ0.60 V, ER2ED¼ꢀ1.10 V.
4.1.3. 2-[5-p-Tolylamino-4-(p-tolylimino)-4H-imidazol-2-yl]-5,8-
dihydroxy-9,10-anthraquinone (8e)
1605, 1530, 1489 cmꢀ1; UV–vis (CHCl3) lmax (log
3): 406 (3.9), 498
(3.9), 535 (4.0), 585 (3.9) nm; CV: E1RED¼ꢀ0.81 V, ER2ED¼ꢀ0.95 V.
Anal. Calcd for C27H30N4: C, 78.99; H, 7.36; N,13.65. Found: C, 78.91;
H, 7.50; N, 13.59.
Yield: 8%, red-brown solid, mp>300 ꢂC (decomp.); 1H NMR
(250 MHz, CDCl3):
d
2.28 (s, 6H), 6.99 (s, 1H), 7.07 (d, 3J¼8.5 Hz, 4H),
7.17 (d, 3J¼8.5 Hz,1H), 7.32 (m, 6H), 7.55 (m, 2H); 13C NMR (62 MHz,
CDCl3):
d
21.2, 123.1, 123.2, 125.5, 126.5, 128.3, 130.1, 130.2, 130.6,
4.2.3. 2,3-Bis-(2,6-diisopropylphenylimino)-2H-imidazo-[1,2-a]-
pyridine (9c)
130.7,135.8,139.5,151.5,155.3,167.8,176.4,186.0; MS (DEI): m/z (%):
515 (Mþ1)þ (23), 408 (11), 337 (6), 279 (25), 203 (18), 173 (45), 131
(83), 91 (100), 77 (74); IR (ATR): 3642, 3363 (br), 1743 cmꢀ1; UV–vis
Yield: 205 mg (22%), black violet solid, mp 182–184 ꢂC; 1H NMR
(400 MHz, CDCl3):
d
1.19 (d, 3J¼6.8 Hz,12H),1.25 (d, 3J¼6.8 Hz,12H),

M. Matschke et al. / Tetrahedron 64 (2008) 7815–7821
7821
2.8–3.0 (m, 4H), 6.85 (t, 3J¼6.5 Hz, 1H), 6.87 (t, 3J¼6.5 Hz, 1H), 7.06
(d, 3J¼4.8 Hz, 1H), 7.15–7.20 (m, 3H), 7.23–7.30 (m, 3H), 7.34–7.40
(ATR): 1643, 1612, 1583, 1551, 1494, 1467 cmꢀ1; UV–vis (CHCl3) lmax
(log 3): 272 (4.4), 457 (3.9), 502 (4.0), 534 (3.9) nm; CV:
(m, 2H); 13C NMR (100 MHz, CDCl3):
d
22.0, 22.8, 23.4, 28.3, 28.9,
E1RED¼ꢀ0.83 V, ER2ED¼ꢀ0.98 V. Anal. Calcd for C25H20N4: C, 79.76; H,
109.4, 117.9, 122.6, 122.7, 124.1, 125.3, 128.2, 129.0, 134.9, 136.8,
137.9, 141.7, 145.4, 163.5; MS (DEI): m/z (%): 466 (M)þ (31), 451 (93),
423 (100), 357 (39), 278 (95), 264 (91), 238 (89), 220 (25), 186 (87),
5.35; N, 14.88. Found: C, 79.69; H, 5.25; N, 14.96.
4.3. Reduction of 4H-imidazo-[1,2-a]-pyridine (9a) to 1-
azaindolizine (10a)
170 (43), 91 (35), 43 (27); IR (ATR): 1658, 1604, 1504, 1463 cmꢀ1
;
UV–vis (CHCl3) lmax (log 3): 270 (4.2), 464 (3.9), 492 (4.0), 531
(3.9) nm; CV: ER1ED¼ꢀ1.01 V, ER2ED¼ꢀ1.12 V. Anal. Calcd for
Derivative 9a (168 mg, 0.5 mmol) was dissolved in 15 ml of ac-
etone or THF. While stirring the red-violet solution, 1 equiv of
a 0.06 M aqueous solution of sodium dithionite was added. The
colour of the reaction mixture changes to yellow brown, which
indicates the formation of the 1-azaindolizine 10a. The reduction
product was isolated by removing the organic solvents under re-
duced pressure, extracting the indolizine from the aqueous layer
with methylene chloride, drying the organic layer with anhydrous
sodium sulfate and evaporating to dryness.
C
31H38N4: C, 79.78; H, 8.21; N, 12.01. Found: C, 79.65; H, 8.20;
N, 12.15.
4.2.4. 2,3-Bis-(2,4,6-trimethylphenylimino)-2H-imidazo-[1,2-a]-
pyridine (9d)
Yield: 160 mg (21%), black, metallic shining crystals, mp 101–
103 ꢂC; 1H NMR (400 MHz, CDCl3):
d 2.22 (s, 3H), 2.29 (s, 6H), 2.37
(s, 3H), 2.69 (s, 6H), 6.48 (d, 3J¼8.4 Hz, 1H), 7.10 (s, 2H), 7.1–7.2 (m,
2H), 7.26 (s, 2H), 7.97 (d, 3J¼8.0 Hz, 1H); 13C NMR (100 MHz,
4.3.1. N2,N3-Di-p-tolyl-imidazo-[1,2-a]-pyridine-2,3-diamine (10a)
CDCl3):
d 18.5, 18.9, 20.7, 20.9, 21.4, 109.0, 113.7, 115.8, 125.3, 128.2,
Yield: 100%, yellow brown powder; 1H NMR (250 MHz, acetone-
128.6, 129.0, 129.5, 132.3, 133.0, 135.4, 138.0, 140.4, 140.7, 143.3,
145.3, 147.1, 156.8, 158.3, 162.2; MS (DEI): m/z (%): 381 (Mꢀ1)þ (4),
234 (19), 228 (1), 206 (17), 161 (55), 91 (43), 77 (31), 67 (100), 58
(40), 39 (66), 28 (78); IR (ATR): 1651, 1599, 1499, 1476 cmꢀ1; UV–
d6):
d
2.21 (s, 6H), 6.81 (d, 3J¼8.5 Hz, 4H), 6.9–7.2 (m, 7H), 7.57 (t,
1H); MS (DEI): m/z (%): 328 (M)þ (85), 268 (67), 237 (51), 220 (95),
205 (100), 133 (51), 118 (42), 107 (81), 91 (76), 71 (64), 42 (78); UV–
vis (THF) lmax (log 3): 375 (3.9) nm; Fluorescence (THF, 382 nm)
lmax,em: 470 nm. Anal. Calcd for C21H20N4: C, 76.80; H, 6.14; N,17.06.
Found: C, 76.78; H, 6.23; N, 16.99.
vis (CHCl3) lmax (log 3): 388 (3.7), 398 (3.7), 481 (3.9), 517 (4.0), 556
(3.9) nm; CV: ER1ED¼ꢀ0.88 V, ER2ED¼ꢀ1.03 V. Anal. Calcd for
C
25H26N4: C, 78.50; H, 6.85; N, 14.65. Found: C, 78.45; H, 6.93; N,
14.62.
Acknowledgements
4.2.5. 2,3-Bis-(4-tolylimino)-2H-imidazo-[1,2-a]-5-methyl-
pyridine (9e)
We thank the Deutsche Forschungsgemeinschaft (DFG) for the
generous support.
Yield: 238 mg (35%), black violet solid; 1H NMR (400 MHz,
CDCl3):
d
2.17 (s, 3H), 2.25 (s, 3H), 2.35 (s, 3H), 6.65 (d, 3J¼9.0 Hz,
2H), 6.83 (d, 3J¼7.0 Hz, 1H), 6.87 (d, 3J¼7.0 Hz, 1H), 7.05 (t,
3J¼8.5 Hz, 1H), 7.20 (d, 3J¼8.2 Hz, 2H), 7.65 (d, 3J¼8.2 Hz, 2H), 7.74
References and notes
(d, 3J¼8.2 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 21.2, 30.9, 110.3,
1. Burgess, K.; Gibbs, R. U.S. Patent 6,340,750, 2002; Tsien, R. Y.; Gonzales, J. E. U.S.
Patent 7,087,416, 2006.
2. Langhals, H. U.S. Patent 5,693,808, 1997; U.S. Patent 5,508,137, 1996.
3. Auberson, Y. Patent No. WO 2003/074519, 2003.
4. Phillips, E. D. Patent No. WO 1999/048961, 1999; U.S. Patent 6,734,235, 2004.
5. Atzrodt, J.; Brandenburg, J.; Ka¨pplinger, C.; Beckert, R.; Gu¨nther, W.; Go¨rls, H.;
Fabian, J. J. Prakt. Chem. 1997, 339, 729.
116.0, 119.9, 120.2, 125.3, 128.5, 129.3, 129.4, 129.7, 130.4, 133.0,
135.7, 139.8, 141.3, 141.7, 142.6, 146.1; MS (DEI): m/z (%): 340 (M)þ
(2), 339 (Mꢀ1)þ (4), 338 (Mꢀ2)þ (12), 206 (16), 149 (21), 133 (41),
106 (100), 77 (23); IR (ATR): 1597, 1575, 1457 cmꢀ1; UV–vis (CHCl3)
lmax (log
22H20N4: C, 77.62; H, 5.92; N, 16.46. Found: C, 77.49; H, 5.91;
N, 16.60.
3): 539 (3.9), 575 (4.0), 616 (3.9) nm. Anal. Calcd for
6. Matschke, M.; Beckert, R. Molecules 2007, 12, 723.
C
7. Matschke, M.; Ka¨pplinger, C.; Beckert, R. Tetrahedron 2006, 60, 8586.
8. Blumhoff, J.; Beckert, R.; Walther, D.; Rau, S.; Rudolph, M.; Go¨rls, H.; Plass, W.
Eur. J. Inorg. Chem. 2007, 3, 481.
9. Matschke, M.; Knop, K.; Beckert, R. Struct. Chem., 2008. doi:10.1007/s 11224-
008-9294-y
10. Beckert, R.; Hippius, C.; Gebauer, T.; Sto¨ckner, F.; Lu¨ digk, C.; Weiß, D.; Raabe, D.;
Gu¨nther, W.; Go¨rls, H. Z. Naturforsch. 2006, 61b, 437.
11. Mu¨ ller, D.; Beckert, R.; Weston, J.; Gu¨nther, W.; Go¨rls, H.; Friedrich, M. Eur. J. Org.
Chem. 2001, 4551.
12. Bauer, K. Chem. Ber. 1950, 83, 10.
13. Adler, A. D.; Longo, F.; Shergalis, W. J. Am. Chem. Soc. 1964, 86, 3145.
14. Adler, A. D.; Longo, F.; Finarelli, J.; Goldmacher, J.; Assour, J.; Korsakoff, L. J. Org.
Chem. 1967, 32, 476.
15. Sen, R.; Sinha, N. J. Am. Chem. Soc. 1923, 45, 2984.
16. Jiao, G.; Thoresen, L.; Burgess, K. J. Am. Chem. Soc. 2003, 125, 14668.
17. Staab, H.; Sauer, M. Liebigs Ann. Chem. 1984, 4, 742.
18. Murdock, K. C.; Child, R. G.; Fabio, P. F.; Angier, R. B.; Wallace, R. E.; Durr, F. E.;
Citarella, R. V. J. Med. Chem. 1979, 22, 1024.
19. Sasaki, H.; Ueno, A.; Osa, T. Bull. Chem. Soc. Jpn. 1988, 61, 2321.
20. Witkop, B.; Fiedler, H. Liebigs Ann. Chem. 1947, 558, 91.
21. Ito, S.; Zakeeruddin, S. M.; Humphry-Baker, R.; Liska, P.; Charvet, R.; Comte, P.;
Nazeeruddin, M. K.; Pechy, P.; Takata, M.; Miura, H.; Uchida, S.; Gra¨tzel, M. Adv.
Mater. 2006, 9, 1202.
4.2.6. 2,3-Bis-(4-tolylimino)-2H-imidazo-[1,2-a]-6-nitro-
pyridine (9f)
Yield: 200 mg (27%), dark red solid; 1H NMR (250 MHz, CDCl3):
d
2.28 (s, 3H), 2.41 (s, 3H), 6.83 (d, 3J¼8.0 Hz, 2H), 6.9–7.3 (m, 7H),
7.54 (d, 3J¼8.5 Hz, 1H), 7.91 (d, 3J¼8.3 Hz, 1H); 13C NMR (62 MHz,
CDCl3):
d 20.9, 21.3, 107.3, 117.5, 120.3, 120.9, 129.3, 129.5, 129.9,
130.6, 132.4, 134.7, 136.6, 146.7, 147.3, 154.9, 160.7; MS (DEI): m/z
(%): 371 (M)þ (2), 370 (Mꢀ1)þ (4), 324 (26), 290 (98), 205 (93), 106
(71), 91 (100), 72 (67); IR (ATR): 1638, 1595, 1558, 1505, 1291 cmꢀ1
;
UV–vis (CHCl3) lmax (log 3): 463 (3.7), 494 (3.9), 534 (3.8) nm. Anal.
Calcd for C21H17N5O2: C, 67.91; H, 4.61; N, 18.86. Found: C, 67.85; H,
4.54; N, 18.90.
4.2.7. 2,3-Bis-(4-tolylimino)-2H-imidazo-[1,2-a]-isoquinoline (9g)
Yield: 410 mg (55%), dark red solid, mp>160 ꢂC (decomp.); 1H
NMR (250 MHz, CDCl3):
d 2.38 (s, 3H), 2.39 (s, 3H), 6.64 (d,
22. Gebauer, T.; Beckert, R.; Weiß, D.; Knop, K.; Kapplinger, C.; Gorls, H. Chem.
¨
¨
3J¼7.2 Hz, 1H), 7.15–7.25 (m, 3H), 7.29 (t, 3J¼7.2 Hz, 1H), 7.39 (d,
Commun. 2004, 1860.
23. Atzrodt, J.; Beckert, R.; Gu¨nther, W.; Go¨rls, H. Eur. J. Org. Chem. 2000, 8, 1661.
24. Langer, P.; Wuckelt, J.; Do¨ring, M.; Go¨rls, H. Eur. J. Org. Chem. 2001, 1503.
25. Ollis, W. D.; Ramsden, C. A.; Sanforth, S. P. Tetrahedron 1985, 41, 2239.
26. Katritzky, A. R.; Burton, R. D.; Shipkova, P. A.; Qi, M.; Watson, C. H.; Eyler, J.
J. Chem. Soc., Perkin Trans. 2 1998, 835.
27. Brandenburg, J.; Ka¨pplinger, C.; Beckert, R. Synthesis 1996, 1302.
28. Malhotra, S. S.; Whiting, M. C. J. Chem. Soc. 1960, 3812.
29. Mu¨ller, D.; Beckert, R.; Go¨rls, H. Synthesis 2001, 4, 601.
3J¼8.0 Hz, 2H), 7.55 (d, 3J¼8.0 Hz, 2H), 7.58 (d, 3J¼8.0 Hz, 2H), 7.71
(t, 3J¼6.8 Hz, 1H), 7.79 (d, 3J¼7.2 Hz, 1H), 8.48 (d, 3J¼7.6 Hz, 1H); 13
C
NMR (62 MHz, CDCl3):
d 21.0, 21.5, 109.3, 121.4, 122.1, 125.3, 126.7,
127.1,127.2,128.1,128.2,129.1,129.3,134.0,136.2,143.4,145.2,145.9,
151.3, 157.5, 162.6; MS (DEI): m/z (%): 376 (M)þ (11), 375 (21), 361
(20), 285 (17), 268 (14), 258 (31), 128 (60), 106 (54), 91 (100); IR