The synthesis of carboxy- and cyano-substituted 4H-imidazoles: Redoxactive ligands as starting materials for metal-metal multiply bonded compoundsand heterobimetallic complexes

Article abstract of DOI:10.1515/znb-2009-0606

Cyanobenzoic acids proved to be suitable starting materials for the transformation into multifunctional products of the 4H-imidazole type. Employing two different pathways, the new derivatives 1b-d which possess carboxy/cyano groups were synthesized. In addition, derivative 1d formed the basis for the construction of novel bis-4H-imidazoles with two different complexation spheres. The structures of all new derivatives were confirmed by NMR spectroscopy, mass spectrometry, elemental analysis, UV/Vis-/fluorescence spectroscopy, and electrochemical measurements.

Full text of DOI:10.1515/znb-2009-0606

The Synthesis of Carboxy- and Cyano-substituted 4H-Imidazoles:
Redoxactive Ligands as Starting Materials for Metal-Metal Multiply
Bonded Compounds and Heterobimetallic Complexes
Martin Matschkea, Jo¨rg Blumhoffa, Rainer Beckerta, and Wolfgang Imhofb
a Institute of Organic and Macromolecular Chemistry, Friedrich Schiller University, Humboldtstr. 10,
07743 Jena, Germany
b Institute of Inorganic and Analytical Chemistry, Friedrich Schiller University, August-Bebelstr. 2,
07743 Jena, Germany
Reprint requests to Prof. Dr. R. Beckert. E-mail: Rainer.Beckert@uni-jena.de
Z. Naturforsch. 2009, 64b, 624 – 628; received March 16, 2009
Dedicated to Professor Gerhard Maas on the occasion of his 60th birthday
Cyanobenzoic acids proved to be suitable starting materials for the transformation into multifunc-
tional products of the 4H-imidazole type. Employing two different pathways, the new derivatives
1b–d which possess carboxy/cyano groups were synthesized. In addition, derivative 1d formed the
basis for the construction of novel bis-4H-imidazoles with two different complexation spheres. The
structures of all new derivatives were confirmed by NMR spectroscopy, mass spectrometry, elemental
analysis, UV/Vis-/fluorescence spectroscopy, and electrochemical measurements.
Key words: 4H-Imidazoles, Nitriles, Benzoic Acids, Ligands, Functional Dyes
Introduction
In the last decade, 4H-imidazoles 1 were developed
in our group as a new class of functional dyes: de-
pending on the nature of their substituents, they show
absorptions in a wide range of the visible spectrum
[1], are pH-switchable [2] reversible two-electron re-
dox systems [3] and efficient chelating ligands for met-
als [4] (Scheme 1).
A further goal was to synthesize 4-carboxyphenyl-
substituted 4H-imidazoles and in addition cyanoaryl-
substituted derivatives (R = C6H4COOH, C6H4CN)
with coordinating centers for the synthesis of special
metal-containing chromophores. We are presently fo-
cussing on the synthesis of so called “paddlewheel”
complexes by coordinating multiply bonded Mo2, W2
or Ru2 entities to the carboxylate functions in 4-
position of the 4H-imidazoles. Related Mo2 tetracarb-
oxylates have been shown to exhibit photochemical
Scheme 1. 4H-Imidazoles as multi-functional molecules.
easy conversion of cyano groups into amidines opens
the synthetic entry to bis-4H-imidazoles which possess
two different arylic peripheries.
Results and Discussion
4H-Imidazoles 1 with a high variability of aryl sub-
properties that are comparable to those of the well stituents in 2-position were synthesized in the past [6],
known [Ru(bipy)3]2+ complexes when the carboxyl- however the introduction of carboxy and cyano groups
ate functions are connected to electron-poor aromatic failed because of the difficult synthetic entry and low
systems [5]. The intensity and range of the absorptions stability of the starting materials. Based on extended
obtained make them interesting candidates for appli- research activities in respect to synthetic pathways for
cations in the harvesting of photons. In addition, the 4H-imidazoles [1, 6], the easily accessible cyanobenz-
c
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M. Matschke et al. · Carboxy- and Cyano-substituted 4H-Imidazoles
625
Scheme 2. Conversion of cyanobenzoic
acids into 4H-imidazoles.
oic acids of type 2 were tested as building blocks
for 4H-imidazoles. They are of interest for two rea-
sons: the easy conversion of the cyano groups into
amidine functions should allow a subsequent cyclo-
acylation with bis-imidoyl chlorides of oxalic acid 4
to give finally carboxy-substituted 4H-imidazoles. On
the other hand, the appropriate cyanobenzoylchlorid-
es proved to be suitable reaction partners for oxal-
amidines 5 which can then be cyclized to 4H-imid-
azoles bearing a cyanoaryl substructure in 2/4-position.
Thus, in a two-step one-pot reaction, 4-cyanobenzo-
Scheme 3. Synthesis of the unsymmetrical 4H-imidazole 1e.
ic acid 2b was first converted into the corresponding
persilylated amidine using an excess of LiHMDS fol- values higher than 4.0; the infrared spectra show char-
lowed by quenching by chlorotrimethylsilane. As fi- acteristic bands at 2237 cm−1 for the cyano-groups in
nal step, the cyclization with bis-tolylimidoyl chloride 1c, d. As demonstrated before, 4H-imidazoles 1b–d
4a yielded the 4-carboxy-substituted4H-imidazole 1b. behave as electrophores which can easily be switched
Despite a broad variation of reaction conditions, all between oxidized and reduced forms [3]. In the first
attempts to obtain the corresponding ortho-carboxy- step, the corresponding radical anion is generated.
phenyl-substituted derivative were unsuccessful. In the By a subsequent electron transfer step the dianion of
meantime however, we developed another synthetic the respective leuco-form is then produced. Both con-
entry using the cyclization reaction of disubstituted ox- secutive single-electron transfer processes could be
alamidines with phthalic acid anhydride [2]. Neverthe- recorded by electrochemical measurements. Employ-
less, the cyano derivatives 1c and 1d were synthesized ing difference pulse polarographic measurements, two
by cyclization of cyanobenzoic acid chlorides 3a, b peaks can clearly be ascribed to two different single-
with the oxalamidine 5 in the presence of n-BuLi in electron transfer steps. The quasi-reversibility of the
a smooth reaction (Scheme 2).
reduction was confirmed by cyclovoltammetric mea-
surements (∆ERED,OX > 0.059 V). The redox po-
tentials of 4H-imidazoles 1b–d are listed in Table 1.
Chemically induced reduction could be achieved by
treating a solution of the 4H-imidazoles with sodium
dithionite in THF. The color of the reaction mixture
1,2
The newly synthesized 4H-imidazoles 1b–d are sol-
uble in polar aprotic solvents and have essentially
the same properties as the phenyl-substituted deriva-
tives [1]. Their longest wavelength absorption in the
UV/Vis spectra is approximately 530 nm, with log(ε)
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626
M. Matschke et al. · Carboxy- and Cyano-substituted 4H-Imidazoles
c
Compound E1
E2
λmax (logε)a λmax (logε)b λmax (logε)c λmax,em. (λexc.
)
Table 1. Redox potentials (in V), and
UV/Vis- and fluorescence data (λ in nm)
for the cyano derivatives 1b–1c.
Red
Red
1b
1c
1d
−0.87 −0.99
−0.81 −1.25
−0.92 −1.05
532 (4.1)
528 (4.0)
532 (4.0)
638 (4.1)
649 (4.0)
651 (4.0)
398 (4.0)
410 (4.0)
406 (4.0)
570 (402)
566 (408)
558 (409)
In THF; b protonated form; c reduced form.
a
Scheme 4. Redox behav-
ior of bis-4H-imidazole
1e.
changed from red to light-yellow, indicating the for- cessful pathway to obtain the first unsymmetrical bis-
mation of 1H-imidazoles. These nearly colorless, but 4H-imidazole 1e (Scheme 3). The new bifunctional
fluorescent products (see Table 1) are immediately re- derivative 1e was isolated as dark red microcrystals
oxidized when exposed to air.
and was fully characterized by elemental analysis, MS
and NMR spectroscopy. It showed the same reduction
behavior as other bis-4H-imidazoles [1c, e], exempli-
fied by the formation of a deep blue quinomethide-like
SEM-form 1e-SEM (λmax = 635 nm; log ε = 4.3). The
latter can be reduced to finally yield the yellowish bis-
1H-imidazole (1e-RED) which immediately was reox-
idized to 1e upon contact with air (Scheme 4).
A further interesting feature of 4H-imidazoles 1b–d
is the protonation-deprotonation reaction with acids or
bases. While the neutral species is based on a mero-
cyanine system, the formation of the protonated or de-
protonated 4H-imidazole causes an alteration of their
chromophoric systems and consequently of their long
wavelength absorption in the UV/Vis spectra [1d].
Compared to the neutral species, both the protonat-
ed (cyanine, Table 1) and the deprotonated 4H-imid-
azole (azaoxonole) display a bathochromic shift in
their UV/Vis spectra.
The cyano-/carboxy-phenyl-substituted 4H-imid-
azoles are not only novel examples in the series of
these switchable heterocycles, but also offer a way to
synthesize unsymmetrical bis-4H-imidazoles. The lat-
ter have attracted considerable interest due to the fact
that Pd and Ru complexes of 4H-imidazoles display
intense long-wavelength absorptions in their UV/Vis
spectra, and in addition, are electrochemically switch-
able [4]. Therefore, the synthesis of unsymmetrical
bis-4H-imidazoles could be the decisive step in the
synthesis of heterobimetallic complexes. Different pe-
ripheric groups permit a differentiation of the ligand
sphere and consequently a selective complexation.
Conclusions
Cyanobenzoic acids proved to be useful build-
ing blocks for 4H-imidazoles 1c–d possessing carb-
oxyaryl/cyanoaryl substructures. Furthermore, the first
unsymmetrical bis-4H-imidazole 1e was obtained,
starting from the para-cyanophenyl-substituted 4H-
imidazole 1d. This transformation allows the build-up
of two different chelation spheres and thus could be
the decisive step for the synthesis of heterobimetallic
complexes.
Experimental Section
The reagents described in the following section were pur-
chased from commercial sources and were used directly un-
less stated otherwise in the text. All solvents were of reagent
grade and were dried according to common practice and dis-
tilled prior to use. Reactions were monitored by TLC using
aluminium plates coated with Al2O3 or SiO2 from Fluka.
Melting points were measured with a digital detector sys-
tem KSPS 1000 from Kru¨ss and with a B-545 (Boetius sys-
tem) from Bu¨chi and are uncorrected. The 1H and 13C NMR
spectra were obtained on a Bruker AC 250 (250 MHz) or
a Bruker DRC-400 (400 MHz) spectrometer; shifts are rel-
ative to the signals of the solvent. Mass spectra were mea-
sured on a spectrometer Trio 2000 from Fisons. UV/Vis
In order to build up a second 4H-imidazole sub-
structure in the same molecule, both functional groups
in 1b–d may serve as electrophilic (carboxylic acid
chloride from 1b) or nucleophilic (amidines from
1c, d) building blocks as described above. Unfortu-
nately, all attempts to convert the 4H-imidazoles 1b
into the acid chlorides failed, and only decomposition
took place. Starting from derivative 1d via its sily-
lated amidine and subsequent cycloacylation with bis-
imidoyl chloride 4b, however, turned out to a be suc- spectra were recorded on a Perkin-Elmer Lambda 19 spec-
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M. Matschke et al. · Carboxy- and Cyano-substituted 4H-Imidazoles
627
trophotometer. The fluorescence spectra were recorded with column chromatography (SiO2, toluene/acetone = 10/1). Re-
a JASCO P-6500 instrument. Elemental analyses were car- crystallization from acetonitrile gave pure products 1c and
ried out with an automatic analyzer Varion EL III from Ele- 1d.
mentar Analysensysteme GmbH. Electrochemical measure-
2-(2-Cyanophenyl)-5-p-tolylamino-4-p-tolylimino-4H-
imidazole (1c)
ments were carried out with a Metrohm 663VA Stand us-
ing mercury or platinum electrodes and tetrabutylammonium
hexafluoro-phosphate as conductive salt.
The compound was obtained as a dark red solid
(106 mg, 28 % yield), m. p. > 130 ◦C (decomp.). – 1H NMR
(250 MHz, CDCl3): δ = 2.37 (s, 6H), 6.89 (d, 3J =
8.2 Hz, 1H), 7.25 (d, 3J = 8.3 Hz, 4H), 7.38 (d, 3J =
8.2 Hz, 1H), 7.70 – 7.80 (m, 2H), 7.97 (d, 3J = 8.3 Hz,
4H). – 13C NMR (62 MHz, CDCl3): δ = 21.3, 112.9,
118.7, 121.5, 127.9, 131.9, 132.5, 135.3, 135.5, 136.5, 146.8,
162.7, 168.6, 176.5. – MS (DEI): m/z = 377 [M]+, 376
[M–1]+, 274, 265, 248, 147, 130, 106, 91. – IR (ATR): ν =
2237, 3309 cm−1. – UV/Vis (THF): λmax (logε) = 285 nm
(4.3), 412 (3.8), 500 (4.2), 528 (4.0). – C24H19N5 (377.4):
calcd. C 76.37, H 5.07, N 18.55; found C 76.50, H 5.18,
N 18.38.
The N,N’-bis-aryloxaldiimidoyl chloride 4b [7] and the
oxalamidine 5 [6] were synthesized according to literature.
The cyano-substituted benzoyl chlorides 3a, b were synthe-
sized by heating of the appropriate cyanobenzoic acid with
an excess of thionyl chloride and a catalytic amount of DMF
under reflux for 3 h.
4-{5-p-Tolylamino-4-[p-tolylimino]-4H-imidazol-2-yl}-
benzoic acid (1b)
To a suspension of 1 mmol (147 mg) of 4-cyanobenzo-
ic acid 2b in 20 mL of THF in a Schlenk tube, 2 mmol of
Li-hexamethyldisilazide (1 M solution in THF) was added
dropwise. The reaction mixture was then stirred for 1 d at r. t.
The solution was evaporated to dryness, and the residue was
suspended in toluene. 2 mmol (0.26 mL) of chlorotrimethyl-
silane was added, and the reaction mixture was heated under
reflux for 12 h. The mixture was again evaporated to dry-
ness, and the remaining residue was reacted with 1 mmol
(305 mg) of bis-imidoylchloride 4a in the presence of
4 mmol (232 mg) of KF and a catalytic amount of 18-crown-
6 ether in THF. For the completion of the reaction the mixture
was stirred for 24 h at r. t. Recrystallization from acetoni-
trile gave 1b as dark red microcrystals (80 mg, 20 % yield),
m. p. > 200 ◦C (decomp.). – 1H NMR (250 MHz, [D8]THF):
δ = 2.37 (s, 6H), 7.25 (d, 3J = 8.5 Hz, 4H), 7.78 (d, 3J =
8.5 Hz, 2H), 7.99 (d, 3J = 8.5 Hz, 4H), 8.56 (d, 3J = 8.5 Hz,
2H). – 13C NMR (62 MHz, [D8]THF): δ = 18.4, 122.0,
125.5, 126.2, 127.3, 127.9, 130.0, 131.5, 132.9, 134.2, 163.0,
164.9, 176.2. – MS (DEI): m/z = 397 [M+1]+, 396 [M]+,
394, 234, 146, 130, 106. – IR (ATR): ν = 1726, 3303 cm−1. –
UV/Vis (THF): λmax (logε) = 281 nm (4.4), 337 (4.3), 397
(4.2), 410 (4.1), 496 (4.2), 523 (4.1). – C24H20N4O2 (396.4):
calcd. C 72.71, H 5.08, N 14.13; found C 72.60, H 5.15,
N 14.29.
2-(4-Cyanophenyl)-5-p-tolylamino-4-p-tolylimino-4H-
imidazole (1d)
The compound was obtained as a dark red solid (196 mg,
52 % yield), m. p. 252 – 254 ◦C. – 1H NMR (250 MHz,
CDCl3): δ = 2.33 (s, 6H), 7.20 (d, 3J = 8.3 Hz, 4H), 7.71
(d, 3J = 8.3 Hz, 2H), 7.81 (d, 3J = 8.3 Hz, 4H), 8.53 (d, 3J =
8.3 Hz, 2H). – 13C NMR (62 MHz, CDCl3): δ = 21.7, 116.4,
118.9, 124.3, 130.3, 130.9, 132.5, 136.6, 137.8, 139.6, 163.6,
180.0. – MS (DEI): m/z = 377 [M]+, 362, 268, 248, 234, 132,
117, 107, 91. – IR (ATR): ν = 2237, 3304 cm−1. – UV/Vis
(CHCl3): λmax (logε) = 287 nm (4.3), 390 (3.9), 415 (3.9),
504 (4.1), 530 (4.0). – C24H19N5 (377.4): calcd. C 76.37,
H 5.07, N 18.55, found C 76.39, H 5.11, N 18.40.
Bis-4H-imidazole 1e
In a Schlenk tube equipped with a magnetic stirrer, to a
solution of 0.5 mmol (189 mg) of 4H-imidazole 1d in 15 mL
of dry THF was added dropwise 1 mmol of Li-hexamethyl-
disilazide (1 M solution in THF). The reaction mixture was
then stirred for 2 d at r. t. The solution was evaporated to
dryness, and the residue was suspended in toluene. 1 mmol
(0.13 mL) of chlorotrimethylsilane was added, and the re-
action mixture was heated under reflux for 12 h. The mix-
ture was again evaporated to dryness, and the residue was
General procedure for the synthesis of cyano-substituted 4H-
imidazoles 1c, d
In a Schlenk tube equipped with a magnetic stirrer, reacted with 0.5 mmol ( 223 mg) of bis-imidoylchloride
1 mmol (182 mg) of the corresponding cyanobenzoic acid 4b in the presence of 2 mmol (116 mg) of KF and a cat-
chloride 3a, b was added to a THF solution containing the alytic amount of 18-crown-6 ether in 15 mL of THF by
deprotonated oxalamidine, produced by deprotonation of heating under reflux for 5 h. The dark red product was pu-
1 mmol (266 mg) of 5 with 0.8 mL of n-BuLi (2.5 M so- rified by column chromatography (SiO2, toluene/acetone =
lution in n-hexane). For the completion of the reaction the 100/1). The bis-4H-imidazole 1e was obtained as a red solid
◦
1
mixture was stirred for 20 h at r. t. The reaction mixture was (66 mg, 17 %, yield), m. p. > 240 C (decomp.). – H NMR
evaporated to dryness, and the red residue was purified by (250 MHz, CDCl3): δ = 1.28 (d, 3J = 7.0 Hz, 24H), 2.38
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M. Matschke et al. · Carboxy- and Cyano-substituted 4H-Imidazoles
(s, 6H), 2.84 (m, 4H) 6.92 (d, 3J = 7.5 Hz, 2H), 7.2 – 7.4 (3.7), 474 (3.9), 503 (4.1), 535 (4.0). – C50H54N8 (767.0):
(m, 4H), 7.58 (d, 3J = 8.0 Hz, 4H), 7.82 (d, 3J = 8.3 Hz, calcd. C 78.30, H 7.10, N 14.61; found C 78.39, H 7.21,
4H), 8.65 (d, 3J = 8.0 Hz, 4H), 9.34 (s, br, 2H). – 13C NMR N 14.80.
(62 MHz, CDCl3): δ = 21.3, 22.9, 28.9, 116.0, 119.8, 123.3,
Acknowledgement
125.8, 129.7, 129.9, 130.2, 130.5, 135.3, 135.8, 142.2, 157.5,
163.2. – MS (DEI): m/z = 766 [M]+, 664, 376, 362, 268, 186,
133, 116, 106, 91. – UV/Vis (THF): λmax (logε) = 418 nm
We thank the Deutsche Forschungsgemeinschaft (DFG)
for generous support.
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