Nucleophilic substitution of 4H-imidazoles - A key step in the synthesis of fused imidazoles and new chromophores

Article abstract of DOI:10.1002/(SICI)1099-0690(200004)2000:8<1661::AID-EJOC1661>3.0.CO;2-1

The electrophilic properties of the 4H-imidazoles 1 and their protonated derivatives 2 permit the introduction of nucleophilic building blocks, as illustrated by reactions of 1 with selected amines. Depending on the nature of the amine and the substituents R¹ on the heterocycle 1, single (3) or double (4) transamination is observed. The ¹H-NMR spectra of the products, as well as X-ray structure analyses of compounds: 3f and 4c, confirm that the residues at the 4- and/or 5-positions of 1 are exchanged. The tautomerism between 3e-h and 3e'-h' seems to be central to the chemistry of these mixed substituted derivatives. Using orthoesters and acetophenone dimethylacetal as cyclization partners, the imidazo[4,5-d]imidazoles 5 and the 4H-imidazo[4,5- b]pyrazines 6 are obtained, respectively. Reduction of 3e with Zn/HCl or H₂S leads to the air-sensitive, strongly fluorescent leuco compounds 8. Quenching of 8 by addition of aromatic aldehydes results in a condensation reaction and, coupled with the subsequent redox disproportionation, this conversion constitutes an alternative route to imidazo[4,5-d]imidazoles of type 11. The unexpected reaction of 3e-h with Lawesson's reagent allows synthesis of the 6-azapentafulvenes 14. The relevant spectral data show 14 to be members of a new chromophoric system, in which an electron-rich five-membered ring is coupled with an electron-deficient ring.

Full text of DOI:10.1002/(SICI)1099-0690(200004)2000:8<1661::AID-EJOC1661>3.0.CO;2-1

FULL PAPER
Nucleophilic Substitution of 4H-Imidazoles – A Key Step in the Synthesis of
Fused Imidazoles and New Chromophores
Jens Atzrodt,[a] Rainer Beckert,*[a] Wolfgang Günther,[a] and Helmar Görls[a]
Dedicated to Professor Dirk Walther, Jena, on the occasion of his 60th birthday
Keywords: 4H-Imidazoles / Nucleophilic substitution / 1,3,6-Triazapentafulvenes / Pseudo-azulenes / Fused heterocycles
The electrophilic properties of the 4H-imidazoles 1 and their
protonated derivatives 2 permit the introduction of nucleo-
philic building blocks, as illustrated by reactions of 1 with
selected amines. Depending on the nature of the amine and
the substituents R1 on the heterocycle 1, single (3) or double
(4) transamination is observed. The 1H-NMR spectra of the
products, as well as X-ray structure analyses of compounds
3f and 4c, confirm that the residues at the 4- and/or 5-posi-
tions of 1 are exchanged. The tautomerism between 3e–h
and 3eЈ-hЈ seems to be central to the chemistry of these
mixed substituted derivatives. Using orthoesters and aceto-
phenone dimethylacetal as cyclization partners, the imid-
azo[4,5-d]imidazoles 5 and the 4H-imidazo[4,5-b]pyrazines 6
are obtained, respectively. Reduction of 3e with Zn/HCl or
H2S leads to the air-sensitive, strongly fluorescent leuco com-
pounds 8. Quenching of 8 by addition of aromatic aldehydes
results in a condensation reaction and, coupled with the sub-
sequent redox disproportionation, this conversion constitutes
an alternative route to imidazo[4,5-d]imidazoles of type 11.
The unexpected reaction of 3e–h with Lawesson’s reagent
allows synthesis of the 6-azapentafulvenes 14. The relevant
spectral data show 14 to be members of a new chromophoric
system, in which an electron-rich five-membered ring is
coupled with an electron-deficient ring.
Introduction
iminium salts, the delocalization of a positive charge in sys-
tems of type 2 could possibly be expected to allow the intro-
duction of nucleophilic building blocks. Such nucleophilic
substitutions have previously been described for donor–ac-
ceptor substituted cyclopentadienylium salts[5] and their
corresponding heterocyclic systems.[6] This stimulated us to
investigate whether or not the 4H-imidazoles 1 or their pro-
tonated forms 2 are able to undergo substitution reactions
with nucleophiles.
The bathochromic shift of about 150 nm observed upon
protonation of the recently described derivatives of 4H-im-
idazoles 1[1] can be attributed to transformation of the cyc-
lic mero-polymethine-type chromophore into the polyme-
thinic π-bond system of the iminium salt 2. On the basis of
the donor–acceptor concept devised by Gompper et al.,[2]
the resulting cation can also be regarded as an anti-aro-
matic 1,3-diazacyclopentadienylium salt 2Ј. Application of
NICS (nucleus independent chemical shift) calculations, as
described by Schleyer et al.,[3] as a classification scheme of
cyclic conjugated systems on the basis of their magnetic
properties, led to Fabian’s[4] prediction of weak anti-aro-
matic bonding character (δ ϭ ϩ4.8) for 1. A larger NICS
factor of δ ϭ ϩ7.8 was calculated for protonated 2, indicat-
ing at least an involvement of the 4n(π) system 2Ј. Con-
sidering the π electrons of the amino residues, an extension
of delocalization is possible. The resonance structure 2ЈЈ
thus seems to be favoured for the bonding state in such
heterocyclic systems.
Results and Discussion
In order to experimentally evaluate the aforementioned
possibility, we reacted 1 with various substituted anilines
(Scheme 1). In most cases, that a substitution reaction had
indeed occurred was evident from a rapid color change. Ad-
dition of a catalytic amount of acid, thereby generating the
protonated heterocycle 2, led to a shortening of the reaction
times, but was found not to be essential for the substitution
reaction. The aromatic residue R1 in the 4- and 5-positions
could, in principle, be singly (3) or doubly (4) exchanged.
As a consequence, an equilibrium between 3 and 4 was ob-
served in the course of the substitution reaction. The posi-
tion of this equilibrium was seen to be strongly influenced
by the nature of the amine as well as by the substituents R1
at the heterocycle 1. For example, both tolyl residues are
replaced in near quantitative yield when 1a is reacted with
donor-substituted aromatic amines such as anisidine or 4-
dimethylaminoaniline to form the derivatives 4a and 4b. Be-
cause of the higher yield obtained in this reaction as com-
pared to a previously described synthesis,[1] this twofold
In any case, protonation of 1 should be accompanied by
an increase in the electrophilic character of the ring carbon
atoms, especially at the 4- and 5-positions of the heterocy-
cle. By analogy with well-known substitution reactions of
[a]
Institut für Organische und Makromolekulare Chemie der
Friedrich-Schiller-Universität,
Humboldtstraße 10, D-07743 Jena, Germany
Fax: (internat.) ϩ49 (0)3641/948–212
E-mail: c6bera@rz.uni-jena.de
[b]
Institut für Anorganische und Analytische Chemie der
Friedrich-Schiller-Universität,
August-Bebel-Strasse 2, D-07743 Jena, Germany
Eur. J. Org. Chem. 2000, 1661Ϫ1668
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0408Ϫ1661 $ 17.50ϩ.50/0
1661

J. Atzrodt, R. Beckert, W. Günther, H. Görls
FULL PAPER
Scheme 1
transamination is the method of choice for the synthesis of
the deep-blue compound 4b.
In contrast, only single transamination was observed for
the 4H-imidazoles 1b and 1c. Thus, treatment of 1b and 1c
with p-toluidine resulted in the unsymmetrically substituted
derivatives 3a and 3b as the main products. As is evident
from the 1H-NMR spectra of compounds 3, the specific
nature of the substituents in the 4- and 5-positions leads to
a suppression of the strong intermolecular proton-transfer
that is usually a characteristic feature of solutions of 4H-
imidazoles of type 1.[1] For example, the signal due to the
1
exocyclic NH proton was detected at δ ϭ 5.26 in the H-
NMR spectrum of 3a.
Aliphatic 4H-imidazoles have not previously been ob-
tained through cycloacylation reactions with benzamidine
owing to the low stability of aliphatic bis(imidoyl) chlorides
of oxalic acid.[7] Moreover, the aminolysis of 2,4,5-tri-
chloro-2-phenyl-2H-imidazole[8] is, as far as we are aware,
a non-selective reaction that often leads to mixtures of
products. In contrast to these known procedures, 1a reacts
Figure 1. X-ray structure of 4c; the numbering corresponds to that
˚
used for the X-ray analysis; selected distances [A] and angles [°]:
C1–N1 1.378(2), C3–N1 1.351(2), N2–C3 1.375(2), N2–C2
1.358(2), C1–C2 1.508(2), C1–N3 1.297(2), C2–N4 1.308(2); N1–
C1–N3 127.4(1), N2–C2–N4 126.7(1), N1–C3–N2 118.7(1), N2–
C2–C1 108.3(1), N1–C1–C2 107.3(1)
almost quantitatively with solutions of methyl- or assignment of this compound, as shown in Figure 1. The
ethylamine to form the desired bis(alkyl)-substituted 4H- structural details found for 4c are very similar to those re-
imidazoles 4c and 4d. Unfortunately, distillation resulted in ported for the bis(aryl)-substituted 4H-imidazole 1a.[1] For
removal of the aliphatic amines, which led to a retro reac- example, 1 and 4c have very similar C–N bond lengths in
˚
tion with toluidine. As a consequence, the corresponding their heterocyclic moieties (1.35 to 1.37 A). In keeping with
unsymmetrical derivatives 3c and 3d could be detected by the crystal structure of 1a, the C1–C2 bond length in 4c
˚
TLC and characterized by MS.
[1.508(2) A] is considerably longer than typical Csp2–Csp2
The methyl derivative 4c, having a less extended π-sys- bonds found in conjugated systems.[9]
tem, shows an absorption at λmax ϭ 403 nm (cf. 1a: λmax Due to the possibility of carrying out further synthetic
ϭ
483 nm) in its UV/vis spectrum. A remarkable yellowish transformations, the synthesis of 5-amino-4H-imidazol-4-
fluorescence is also observed for solutions of 4c. Single- imine was of special interest. Treatment of 1a with aqueous
crystal X-ray analysis allowed an unambiguous structural ammonia, however, resulted only in one transamination,
1662
Eur. J. Org. Chem. 2000, 1661Ϫ1668

Nucleophilic Substitution of 4H-Imidazoles
FULL PAPER
after which the aryl-substituted 4H-imidazoles 3e–h could of tetraazafulvalenes,[11] however, we succeeded in reacting
be isolated in good yields. Twofold substitution could not less electrophilic orthoesters with 1 to give the imidazo[4,5-
be realized by varying the reaction conditions (solvent, tem- d]imidazoles 5 (Scheme 2).
perature, and/or addition of acids), nor by using excess gas-
eous ammonia.
The X-ray crystal structure of compound 3f, which is rep-
resentative of these unsymmetrically substituted 4H-imida-
zoles, is illustrated in Figure 2. Both NH protons are seen
to be bound to a single nitrogen atom. Pronounced intra-
and intermolecular hydrogen bonds lead to the formation
of discrete dimeric subunits showing an essentially in-plane
arrangement of the two imidazole substructures. Two dis-
tinct broad singlets due to the NH protons are observed at
1
δ ϭ 8.90 and 8.57 in the H-NMR spectrum of 3f at –60
°C. A fixed tautomeric form at the aryl nitrogen could be
excluded by NOESY experiments. Instead, the observed in-
tramolecular cross-peaks indicate that there is hindered ro-
tation about the C3–N3 bond.
Scheme 2
An unexpected complex redox process ensued when ace-
tophenone dimethylacetal was employed as the cyclization
partner. A new 4H-imidazo[4,5-b]pyrazine 6 was obtained,
in which the methyl group of the acetal had been trans-
formed into a methine unit of a six-membered ring. The π
systems of such conjugated bicycles are isoelectronic with
that of azulene and hence they can be classified as pseudo-
azulenes.[12] Compounds of type 6 show relatively hypsoch-
romic absorptions at λmax ϭ 406 nm in their UV/vis spectra,
similar to those observed for the structurally isomeric pur-
ines.[13] The high regioselectivity of the cyclization with re-
spect to the CH group of the pyrazine system was con-
firmed by 2D NMR experiments. All attempts to synthesize
Figure 2. Perspective drawing of 3f; the numbering corresponds to
˚
precursors of dihydrotetraazapentalenes of type 7 by using,
for example, benzophenone dimethylacetal as the cycliza-
tion reagent were unsuccessful.
that used for the X-ray analysis; selected distances [A] and angles
[°]: C3–N1 1.329(2), N1–C1 1.408(2), C1–N2 1.329(2), N2–C2
1.399(2), C2–C3 1.511(2), C3–N3 1.319(2); C3–N1–C1 102.7 (1),
C1–N2–C2 103.3(1), N2–C2–N4 131.1(1), N1–C3–N3 127.3(1)
As observed for the parent compounds of type 1,[14] it
In analogy to the aliphatic derivatives, the hydrazino-sub- was found that derivatives 3e–h could easily be reduced with
stituted imidazole 3i could be isolated upon treatment of 1a sodium dithionite, ascorbic acid, or Zn/HCl. In the pres-
with N,N-dimethylhydrazine. 2D NMR experiments show a ence of air, the strongly fluorescent leuco compounds 8
stronger fixation of the NH protons on the aryl-substituted were quickly reoxidized with formation of the starting mat-
nitrogen in 3i.
erial 1 and hydrogen peroxide. Treatment of 8 with aromatic
In order to exploit the utility of 4H-imidazoles in the aldehydes resulted in condensation reactions that yielded
synthesis of fused imidazo heterocycles, dinucleophiles were azomethines of type 9; these products could not be isolated,
treated with 1. Neither aromatic diamines such as o-pheny- but were detectable by TLC. Compounds 9 may undergo
lenediamine nor aliphatic derivatives such as ethylenediam- cyclization to give the bicycles 10 (Scheme 3). Because of
ine were found to react with 1a in an exchange reaction. In the well-known lability of the electron-rich tetraaminoe-
the first case, as a result of benzamidine elimination, 2,3- thene substructure with respect to oxidative processes,[15]
diaminoquinoxalines could be isolated and characterized. the derivative 11 was the finally isolated product. The re-
Such quinoxalines are, however, more easily obtained by duction equivalents are transferred to the carbonyl system
aminolysis of 2,3-dichloroquinoxaline or by cyclization of in a Cannizzaro-like redox process. On using an excess of
o-phenylenediamine with bis(imidoyl) chlorides of oxalic benzaldehyde, benzyl alcohol could be detected by GC. The
acid.[10] In contrast to these results, mixed substituted deriv- 1H-NMR spectra of compounds 11 feature a singlet due to
atives of types 3e–h were expected to be more suitable for the XH proton at δ ϭ 12.94, further confirming the occur-
the synthesis of fused systems. Initial attempts to prepare rence of redox disproportionation had taken place. Further-
bicyclic compounds involving the π-bond system of 1 using more, the structure of the imidazo[4,5-d]imidazole 11b was
bis-electrophilic building blocks such as oxalyl chloride confirmed by X-ray analysis (Figure 3). In contrast to the
were fruitless. Applying these findings to the modification alkyloxy derivatives 5a–c, in the solid-state structure of 11b
Eur. J. Org. Chem. 2000, 1661Ϫ1668
1663

J. Atzrodt, R. Beckert, W. Günther, H. Görls
FULL PAPER
the NH proton is held in position by strong hydrogen
bonds, which lead to dimeric units with a head-to-tail ar-
rangement.
In order to obtain new thioxo compounds, further experi-
ments were carried out in which 3e–h were reacted with
sulfur transfer reagents. In all cases, deep-green compounds
were isolated as the main products when P2S5 or the more
advantageous Lawesson’s reagent was used. Elemental ana-
lyses and MS data showed that these compounds were sul-
fur-free, thus indicating that an unexpected reaction had
taken place. On the basis of high-resolution MS data, we
concluded that imidazo-substituted 4H-imidazoles 14 had
been formed (Scheme 4). Due to the dynamic nature of
compounds 14, a structural determination by 1H NMR was
not possible, not even at low temperatures. A 15N-labelled
derivative (14b) showed signal coalescence at room temper-
ature that was only partly resolved at –60 °C. The appear-
ance of a twofold set of signals as well as of five discrete
signals for the five different NH protons (three doublets due
to 15N-1H coupling; two singlets) indicates that 14 exists in
a temperature-dependent equilibrium mixture of tauto-
meric forms.
Scheme 3
Heating the samples up to 60 °C resulted in spectra of
dynamic structures, in which the aromatic rings of the two
heterocycles give rise to only a single set of signals and the
NH proton signals are not separate. The remarkable ba-
thochromic UV/vis absorption observed (14a: λmax
ϭ
662 nm) is due to the similarity of 14a to the push-pull
chromophores found in indigoid systems. In the present
case, the aza nitrogen connects the π-systems of the two
diazafulvene units. Electron delocalization is thus possible
over the entire system.
Figure 3. Representation of the molecular structure of 11b; the
numbering corresponds to that used for the X-ray analysis; selected
˚
distances [A] and angles [°]: C1–C2 1.361(2), C2–N2 1.369(2), N2–
C4 1.369(2), C4–N1 1.386(2), N1–C1 1.376(2), C1–N3 1.374(2),
N3–C3 1.346(2), C3–N4 1.398(2), N4–C2 1.389(2); C4–N2–C2
102.2(1), C4–N1–C1 105.2(1), C1–N3–C3 102.9(1), C3–N4–C2
105.6(1)
The tautomerism observed between 3e–h and 3eЈ-hЈ
(Scheme 2) is most probably central to the formation of 14.
Scheme 4
1664
Eur. J. Org. Chem. 2000, 1661Ϫ1668

Nucleophilic Substitution of 4H-Imidazoles
FULL PAPER
Crystal Data for 3f:[20] C15H12N4CH3CN, Mr ϭ 289.34 gmol–1, or-
We therefore propose that Lawesson’s reagent first reacts
with 3eЈ-hЈ to form the non-isolable thioxo derivative 12.
Indeed, a few thionation reactions of substituted imines
with H2S have been reported, giving comparable results
with those presented here.[16] A subsequent condensation
reaction between the thioxo group and the primary amino
group in 3e–h leads to 13 under elimination of hydrogen
sulfide. The sulfide finally acts as a reducing agent towards
the 4H-imidazole system in 13, leading to the more stable
14. In independent parallel experiments, it was shown that
H2S is capable of reducing 4H-imidazoles of type 1 in a
smooth reaction, thereby forming 4,5-diaminoimidazoles.
We will report on this selective reduction and its application
to aromatic and aliphatic thiols in a forthcoming article. All
attempts to oxidize 14 to the bridged 4H-imidazoles 13 us-
ing various oxidizing agents were unsuccessful. Similarly, it
proved impossible to reduce 14 to two bridged imidazoles.
It is thus obvious that these compounds are members of a
new covalently-bonded redox system characterized by
highly dynamic molecules. Methylation of 14 using methyl
iodide occurs under mild conditions with elimination of hy-
ange prism, size 0.32 ϫ 0.30 ϫ 0.22 mm3, monoclinic, space group
˚
P21/c, a ϭ 5.4438(2), b ϭ 20.1625(7), c ϭ 13.9434(5) A, β ϭ
3
˚
98.211(2)°, V ϭ 1514.75(9) A , T ϭ –90 °C, Z ϭ 4, ρcalcd ϭ 1.269
gcm–3, µ (Mo-K() ϭ 0.8 cm–1, F(000) ϭ 608, 5795 reflections in h(–
6/6), k(–25/25), l(–17/17), measured in the range 3.37° Θ 26.38°,
completeness Θmax ϭ 99.5%, 3092 independent reflections, Rint
0.030, 2299 reflections with Fo Ͼ 4σ(Fo), 259 parameters, R1obs
ϭ
ϭ
0.044, wR2
ϭ 0.105, R1all ϭ 0.068, wR2 ϭ 0.114, GOOF ϭ
obs
all
3
˚
1.046, largest difference peak and hole: 0.176/–0.198 eA .
Crystal Data for 4c:[20] C11H12N4, Mr ϭ 200.25 gmol–1, colourless
prism, size 0.30 ϫ 0.20 ϫ 0.10 mm3, triclinic, space group P-1, a ϭ
˚
7.5225(7), b ϭ 7.9419(7), c ϭ 10.0397(7) A, α ϭ 70.007(4), β ϭ
3
˚
84.091(5), γ ϭ 66.893(4)°, V ϭ 518.10(8) A , T ϭ –90 °C, Z ϭ 2,
ρcalcd ϭ 1.284 gcm–3, µ (Mo-K() ϭ 0.82 cm–1, F(000) ϭ 212, 3772
reflections in h(–9/9), k(–10/10), l(–13/13), measured in the range
3.42°
Θ 27.48°, completeness Θmax ϭ 97.8%, 2318 independent
reflections, Rint ϭ 0.035, 1761 reflections with Fo Ͼ 4σ(Fo), 188
parameters, R1obs ϭ 0.049, wR2
ϭ 0.113, R1all ϭ 0.0705,
obs
wR2 ϭ 0.123, GOOF ϭ 1.023, largest difference peak and hole:
all
3
˚
0.183/–0.186 eA .
Crystal Data for 11b:[20] C24H20N4O, Mr ϭ 380.44 gmol–1, colour-
less prism, size 0.30 ϫ 0.20 ϫ 0.10 mm3, monoclinic, space group
1
drogen iodide. The H-NMR spectrum of the methylation
˚
P21/c, a ϭ 7.9494(2), b ϭ 11.7431(3), c ϭ 20.909(1) A, β ϭ
product 15 clearly shows a restriction of exchange processes
(four different aromatic spin systems are present at room
temperature). The existence of cross-peaks between the aro-
matic tolyl protons and the introduced methyl group in
NOESY experiments is indicative of exocyclic substitution.
3
˚
93.754(2)°, V ϭ 1947.7(1) A , T ϭ –90 °C, Z ϭ 4, ρcalcd ϭ 1.297
gcm–3, µ(Mo-K() ϭ 0.82 cm–1, F(000) ϭ 800, 8319 reflections in h(–
10/10), k(–13/14), l(–27/27), measured in the range 3.10° Θ 27.47°,
completeness Θmax ϭ 98.4%, 4405 independent reflections, Rint
0.042, 3047 reflections with Fo Ͼ 4σ(Fo), 342 parameters, R1obs
ϭ
ϭ
0.058, wR2
ϭ 0.122, R1all ϭ 0.099, wR2 ϭ 0.137, GOOF ϭ
obs
all
–3
˚
1.046, largest difference peak and hole: 0.197/–0.278 eA .
Experimental Section
General Procedure for Nucleophilic Substitution Reactions of the
4H-Imidazoles 1. – Method A: To a solution of 1 (1.0 mmol) in
THF (30 mL), a catalytic amount (3 drops) of concentrated hydro-
chloric acid was added. An immediate colour change was observed
owing to formation of the protonated heterocycle 2. Then, either
an excess of a monofunctional amine (5.0 mmol) or o-phenylenedi-
amine (1.5 mmol) was added. The resulting mixture was heated un-
der reflux and the progress of the reaction was monitored by TLC
(typically, a mixture of 3 and 4 was detected). Reactions were gen-
erally allowed to proceed for 1–4 h. After filtration, the filtrate was
concentrated in vacuo and the residue was purified either by col-
umn chromatography (eluent: ethyl acetate/n-heptane, 1:5) or by
recrystallization from acetone/heptane, to yield the products 3 and/
or 4.
General: All reagents were of commercial quality (Aldrich, Fluka,
Merck) and were used as received. 15N-labelled aniline (99%) was
purchased from MSD isotopes. Solvents were dried and purified
using standard techniques. – Reactions were monitored by TLC on
plastic plates coated with neutral alumina containing a fluorescence
indicator (Polygram ALOX N/UV254 from Macherey–Nagel). –
Flash chromatographic separations were carried out on neutral alu-
mina (Merck, neutral aluminium oxide 90, activity grade V, particle
size 0.063–0.2 mm, 70–230 mesh ASTM). – Melting points were
measured with a Galen III (Boetius system) from Cambridge In-
struments and are uncorrected. – UV/vis spectra were recorded on
a Perkin–Elmer Lambda 19 spectrophotometer. – The 1H- and 13C-
NMR spectra were recorded on Bruker DRX 400 (400 MHz) and
Bruker AC 250 (250 MHz) spectrometers (1H NMR shifts relative
to 1H signals of the solvent). – MS spectra were measured on a
Finnigan MAT SAQ 710 mass spectrometer. – Elemental analyses
were carried out in-house using a LECO CHNS 932 automatic an-
alyzer.
Method B: To a solution of 1 (1.0 mmol) in THF (30 mL), aqueous
ammonia solution (25%, 20 mL) or an aqueous solution of the ap-
propriate alkylamine (33%, 10 mL) was added. The reaction mix-
ture was then heated under reflux with vigorous stirring. After
completion of the reaction (TLC control), the solution was cooled
to room temperature. The organic layer was separated, and the
aqueous layer was washed with two 50 mL portions of ethyl acet-
ate. The combined organic fractions were then dried over anhyd-
rous Na2CO3, filtered, and the solvent was removed in vacuo. The
residue was chromatographed on alumina using ethyl acetate/hept-
ane as eluent, yielding compounds 3e–h and 4c,d. In the case of 3e,
the combined organic layers were concentrated and the product
was precipitated by adding n-heptane; this material proved suffi-
ciently pure to be used without further purification.
Crystal Structure Determination. – Data Collection: The intensity
data for the compounds were collected on a Nonius KappaCCD
diffractometer using graphite-monochromated Mo-Kα radiation.
Data were corrected for Lorentz and polarization effects, but not
for absorption.[17] The structures were solved by direct methods
(SHELXS[18]) and refined by full-matrix least-squares techniques
against Fo (SHELXL-97).[18] The hydrogen atoms were located by
2
difference Fourier synthesis and refined isotropically. All non-hy-
drogen atoms were refined anisotropically.[19] XP (Siemens Analyt-
ical X-ray Instruments, Inc.) was used for structure representations.
5-[4-(Methoxy)phenylamino]-2-phenyl-4-(4-tolylimino)-4H-
imidazole (3a): Method A; yield: 0.18 g (49%), red crystals; m.p.
Eur. J. Org. Chem. 2000, 1661Ϫ1668
1665

J. Atzrodt, R. Beckert, W. Günther, H. Görls
FULL PAPER
1
188 °C. – H NMR (250 MHz, CDCl3): δ ϭ 8.56 (d, 2 H), 8.06 (d,
5-(NЈ,NЈ-Dimethylhydrazino)-2-phenyl-4-(4-tolylimino)-4H-
2 H), 7.89 (d, 2 H), 7.51 (m, 3 H), 7.25 (d, 2 H), 6.97 (d, 2 H), 5.26
imidazole (3i): Method A; yield: 0.26 g (85%), yellow crystals; m.p.
1
(br. s, 1 H, NH), 3.85 (s, 3 H, OCH3), 2.37 (s, 3 H, CH3-Tol). – 177–178 °C. – H NMR (400 MHz, [D6]DMSO): δ ϭ 9.28 (s, 1 H,
13C NMR (62 MHz, CDCl3): δ ϭ 187.7, 164.8, 159.2, 135.6, 133.5, NH), 8.20 (d, 2 H), 7.98 (d, 2 H), 7.45 (m, 3 H), 7.15 (d, 2 H), 3.85
133.6, 132.2, 130.5, 130.4, 129.8, 129.8, 128.5, 127.6, 123.6, 121.7,
55.5, 21.2. – MS: m/z (%) ϭ 369 [M ϩ Hϩ] (100), 337 (10). – UV/ CDCl3): δ ϭ 172.7, 164.3, 142.0, 137.8, 134.7, 132.9, 131.3, 130.6,
[s, 6 H, N(CH3)2], 2.27 (s, 3 H, CH3-Tol). – 13C NMR (100 MHz,
vis (CH2Cl2): λmax (lg ε) ϭ 273 nm (4.26), 341 (4.16), 414 (4.09),
494 (4.32), 522 (4.22). – C23H20N4O (368.42): calcd. C 74.98, H
5.47, N 15.20; found C 75.10, H 5.89, N 15.09.
129.2, 129.1, 119.3, 47.6, 22.0. – MS (DEI): m/z (%) ϭ 305 [Mϩ]
(31), 261 [M – N(CH3)2ϩ] (83), 247 [M – NHN(CH3)2] (100), 129
(14), 104 (13), 91 (91). – UV/vis (CH2Cl2): λmax (lg ε) ϭ 277 nm
(4.32), 341 (4.32), 434 (4.25). – C18H19N5 (305.37): calcd. C 70.80,
H 6.27, N 22.93; found C 70.60, H 6.53, N 21.93.
5-[4-(Dimethylamino)phenylamino]-2-phenyl-4-(4-tolylimino)-4H-
imidazole (3b): Method A; yield 0.21 g (56%) purple crystals; m.p.
1
185–186 °C. – H NMR (250 MHz, [D8]THF): δ ϭ 8.52 (d, 2 H),
5-[4-(Methoxy)phenylamino]-4-[4-(methoxy)phenylimino]-2-phenyl-
4H-imidazole (4a): Method A; yield 0.34 g (88%), red crystals.
Spectral data were in agreement with those reported in ref.[1]
8.16 (d, 2 H), 8.03 (d, 2 H), 7.52 (m, 3 H), 7.21 (d, 2 H), 6.80 (d,
2 H), 4.71 (br. s, 1 H, NH) 3.06 [s, 6 H, N(CH3)2], 2.35 (s, 3 H,
CH3). – 13C NMR (62 MHz, [D8]THF): δ ϭ 151.4, 146.8, 134.2,
133.1, 130.6, 130.1, 123.0, 129.0, 125.7, 115.1, 112.7, 40.3, 21.1. –
MS: m/z (%) ϭ 382 [M ϩ Hϩ] (100), 337 (15), 269 (8), 108 (38). –
UV/vis (CH2Cl2): λmax (lg ε) ϭ 292 nm (4.18), 460 (3.81), 574
(4.29). – C24H23N5 (381.46): calcd. C 75.57, H 6.08, N 18.36; found
C 76.07, H 6.06, N 18.00.
5-[4-(Dimethylamino)phenylamino]-4-[4-(dimethylamino)-
phenylimino]-2-phenyl-4H-imidazole (4b): Method A; yield 0.33 g
(81%), blue crystals. Spectral data were in agreement with those
reported in ref.[1]
5-Methylamino-4-methylimino-2-phenyl-4H-imidazole (4c): Method
B; yield 0.11 g (58%), yellow crystals; m.p. 147 °C. – 1H NMR
(250 MHz, CDCl3): δ ϭ 8.39 (d, 2 H), 7.52 (m, 3 H), 5.47 (br. s, 1
H, NH), 3.42 (s, 6 H). – 13C NMR (62 MHz, CDCl3): δ ϭ 186.8,
167.9, 133.2, 132.1, 129.9, 128.4, 119.8, 34.7. – MS: m/z (%) ϭ 201
[M ϩ Hϩ] (100), 145 (3), 103 (12). – UV/vis (CH2Cl2): λmax (lg
ε) ϭ 300 nm (4.40), 403 (3.62). – C11H12N4 (200.24): calcd. C 65.98,
H 6.04, N 27.98; found C 65.83, H 6.17, N 27.85.
5-Amino-2-phenyl-4-(4-tolylimino)-4H-imidazole (3e): Method B;
yield 0.23 g (88%), yellow crystals; m.p. 178–180 °C. – 1H NMR
(250 MHz, CDCl3): δ ϭ 8.34 (d, 2 H, o-Ph), 7.85 (d, 2 H, Tol),
7.59 (t, 1 H, p-Ph), 7.49 (t, 2 H, m-Ph), 7.23 (d, 2 H, Tol), 2.39 (s,
3 H, CH3-Tol). – 13C NMR (62 MHz, CDCl3): δ ϭ 186.6, 172.3,
159.8, 143.8, 138.5, 133.5, 131.7, 129.9, 129.6, 128.6, 127.2, 21.4. –
MS: m/z (%) ϭ 263 [M ϩ Hϩ] (100), 247 [M – NH2ϩ] (9), 117 (15),
89 (10). – UV/vis (CHCl3): λmax (lg ε) ϭ 311 nm (4.14), 444
(3.98). – C16H14N4 (262.30): calcd. C 73.26, H 5.38, N 21.36; found
C 73.18, H 5.76, N 21.24.
5-Ethylamino-4-ethylimino-2-phenyl-4H-imidazole (4d): Method B;
yield 0.12 g (53%), yellow crystals; m.p. 134–137 °C. – 1H NMR
(400 MHz, CDCl3): δ ϭ 8.37 (d, 2 H), 7.54 (t, 1 H), 7.45 (t, 2 H),
5-Amino-2-phenyl-4-(phenyl-15N-imino)-4H-imidazole (3f): Method
B; yield 0.20 g (82%), yellow crystals; m.p. 193 °C. – 1H NMR
(400 MHz, [D8]THF): δ ϭ 8.37 (d, J ϭ 7.12 Hz, 2 H), 7.87 (d, J ϭ
7.87 Hz, 2 H), 7.56 (t, J ϭ 7.50 Hz, 1 H), 7.46 (t, J ϭ 7.50 Hz,
3
3
5.52 (s, 1 H, NH), 3.79 (q, J ϭ 7.30 Hz, 4 H, CH2), 1.30 (t, J ϭ
7.32 Hz, 6 H, CH3). – 13C NMR (100 MHz, CDCl3): δ ϭ 186.8,
166.7, 133.1, 132.2, 129.9, 128.4, 42.6, 15.2 – MS (DEI): m/z (%) ϭ
228 [Mϩ] (100), 213 (9), 200 (27), 159 (14), 129 (25), 103 (57). –
C13H16N4 (228.30): calcd. C 68.39, H 7.06, N 24.54; found C 68.02,
H 7.12, N 24.84.
1
2 H), 7.37 (t, J ϭ 7.86 Hz, 2 H), 7.19 (t, J ϭ 7.59 Hz, 1 H). – H
NMR (400 MHz, [D8]THF, 258 K): δ ϭ 8.90 (br. s, 1 H, NH), 8.57
(br. s, 1 H, NH). – 13C NMR (100 MHz, [D8]THF): δ ϭ 174.7,
174.5, 148.3, 133.8, 133.7, 130.9, 129.2, 129.2, 129.0, 127.7, 127.6. –
MS(EI): m/z (%) ϭ 249 [Mϩ] (23), 242 (52), 121 (35), 104 (34), 94
(100). Ϫ UV/vis (CHCl3): λmax (lg ε) ϭ 297 nm (4.16), 437 (3.76). –
C15H12N315N (249.27): calcd. C 72.28, H 4.85, N 22.87; found C
71.63, H 5.14, N 22.05.
General Procedure for the Synthesis of Imidazo[4,5-d]imidazoles 5:
A mixture of 3e–h (1.0 mmol) and 30 mL of the appropriate trialkyl
orthoformate was heated under reflux for 3 h. The excess ester was
then removed in vacuo and the residue was purified by column
chromatography eluting with a 5:1 mixture of ethyl acetate and n-
heptane. The eluate was concentrated (to ca. 5 mL) and then kept
at –78 °C overnight, whereupon compounds 5 were deposited as
colourless crystalline solids.
5-Amino-4-[4-(tert-butyl)phenylimino]-2-phenyl-4H-imidazole (3g):
Method B; yield 0.23 g (76%), yellow crystals; m.p. 184–186 °C. –
1H NMR (250 MHz, CDCl3): δ ϭ 8.34 (d, 2 H), 7.87 (d, 2 H), 7.59
(t, 1 H), 7.48 (t, 2 H), 7.45 (d, 2 H), 1.34 (s, 9 H). – 13C NMR
(62 MHz, CDCl3): δ ϭ 186.7, 172.4, 160.0, 151.5, 143.7, 133.5,
131.6, 130.0, 128.6, 126.8, 125.9, 34.8, 31.3. – MS: m/z (%) ϭ 305
[M ϩ Hϩ] (100), 289 [M – NH2ϩ] (8), 249 (20), 247 [M – C(CH3)3]
(35), 150 (24), 134 (15), 94 (27). – UV/vis (CHCl3): λmax (lg ε) ϭ
313 nm (4.22), 442 (4.10). – C19H20N4 (304.38): calcd. C 75.00, H
6.62, N 18.41; found C 75.36, H 6.82, N 18.01.
2-Methoxy-5-phenyl-1-(4-tolyl)-1,6-dihydroimidazo[4,5-d]imidazole
(5a): Yield 0.19 g (66%), colourless crystals; m.p. 234 °C. – 1H
NMR (400 MHz, CD2Cl2): δ ϭ 10.8 (br. s, 1 H, NH), 7.85 (d, 2
H), 7.44 (d, 2 H), 7.37 (t, 2 H), 7.28 (d, 2 H), 7.26 (t, 1 H), 3.98 (s,
3 H, OCH3), 2.41 (s, 3 H, CH3).
–
13C NMR (62 MHz,
[D6]DMSO): δ ϭ 152.6, 141.1, 135.2, 134.1, 133.1, 131.6, 129.7,
128.7, 127.1, 124.1, 121.5, 120.3, 57.2, 20.5. – MS: m/z (%) ϭ 305
[M ϩ Hϩ] (100), 269 (85), 186 (2), 118 (4). – C18H16N4O (304.33):
calcd. C 71.03, H 5.29, N 18.41; found C 70.49, H 5.57, N 18.21.
5-Amino-4-[4-(methoxy)phenylimino]-2-phenyl-4H-imidazole (3h):
Method B; yield 0.16 g (57%), yellow crystals; m.p. 188 °C. – 1H
NMR (250 MHz, CDCl3): δ ϭ 8.36 (d, 2 H), 8.04 (d, 2 H), 7.57 2-Ethyloxy-5-phenyl-1-(4-tolyl)-1,6-dihydroimidazo[4,5-d]imidazole
(t, 1 H), 7.47 (t, 2 H), 6.95 (d, 2 H). – 13C NMR (62 MHz, CDCl3): (5b): Yield 0.23 g (72%), colourless crystals; m.p. 212–214 °C. – 1H
δ ϭ 186.0, 172.4, 160.0, 158.4, 139.8, 133.4, 131.7, 129.9, 129.7,
128.6, 114.3, 55.5. – MS: m/z (%) ϭ 279 [M ϩ Hϩ] (100), 247 (8), H), 7.75 (d, 2 H), 7.40 (t, 2 H), 7.34 (d, 2 H), 7.27 (t, 1 H), 4.48
133 (3). – UV/vis (CHCl3): λmax (lg ε) ϭ 274 nm (4.17), 294 (4.17),
(q, 3J ϭ 6.88 Hz, 2 H), 2.35 (s, 3 H), 1.39 (t, 3J ϭ 6.72 Hz, 3 H). –
458 (4.24). – C16H14N4O (278.29): calcd. C 69.05, H 5.07, N 20.13; 13C NMR (100 MHz, [D6]DMSO): δ ϭ 152.1, 141.9, 135.4, 134.2,
NMR (400 MHz, [D6]DMSO): δ ϭ 12.80 (s, 1 H, NH), 7.90 (d, 2
found C 68.45, H 5.38, N 19.70.
133.2, 131.7, 130.8, 129.5, 128.6, 127.1, 124.5, 122.1, 66.4, 21.0,
1666
Eur. J. Org. Chem. 2000, 1661Ϫ1668

Nucleophilic Substitution of 4H-Imidazoles
FULL PAPER
14.2. – MS (DEI): m/z (%) ϭ 318 [Mϩ] (40), 289 (17), 247 (8), 186
stirred at 50 °C for 2 h, in the course of which a deep-turquoise
(30), 118 (100), 91 (28). – C19H18N4O (318.38): calcd. C 71.68, H colour developed. After completion of the reaction (TLC control),
5.70, N 17.60; found C 71.31, H 6.05, N 16.86.
the solvent was evaporated and the residue was chromatographed
using n-heptane/ethyl acetate (5:1) as eluent to give the pure prod-
ucts 14.
2-Methoxy-1,5-diphenyl-1,6-dihydroimidazo[4,5-d]imidazole
(5c):
Yield 0.18 g (63%), colourless crystals; m.p. 206 °C. – 1H NMR
(250 MHz, CDCl3): δ ϭ 9.32 (s, 1 H, NH), 7.90 (d, 2 H), 7.66 (d,
2 H), 7.51–7.35 (m, 3 H), 7.31–7.17 (m, 3 H), 4.10 (s, 3 H). – 13C
NMR (62 MHz, CDCl3): δ ϭ 136.3, 134.5, 131.4, 129.3, 128.9,
126.1, 125.6, 124.7, 122.1, 119.8, 57.2. – MS: m/z (%) ϭ 291 [M ϩ
Hϩ] (64), 241 (100), 120 (4), 93 (10). – C17H14N4O (290.31): calcd.
C 70.33, H 4.86, N 19.30; found C 70.13, H 5.28, N 18.64.
Diimidazolyl Derivative 14a: Yield 0.18 g (73%), black crystals; m.p.
1
324 °C. – H NMR (400 MHz, [D6]DMSO, 333 K): δ ϭ 8.26 (d, 4
H), 7.89 (d, 4 H), 7.59–7.51 (m, 6 H), 7.23 (d, 4 H), 2.32 (s, 6 H). –
1H NMR (400 MHz, [D8]THF, 223 K): δ ϭ 13.78 (s, 1 H, NH),
12.23 (s, 1 H, NH), 10.45 (s, 1 H, NH), 9.09 (s, 1 H, NH), 8.93 (s,
1 H, NH), 8.38 (d, 4 H), 8.15 (d, 2 H), 8.01 (d, 2 H), 7.95 (d, 4 H),
7.78 (d, 2 H), 7.57–7.48 (m, 10 H), 7.21 (m, 6 H), 7.14 (d, 2 H),
2.33 (s, 12 H). – 13C NMR (100 MHz, [D6]DMSO, 338 K): δ ϭ
158.1, 137.2, 133.4, 131.0, 130.1, 129.0, 128.6, 128.3, 128.3, 126.8,
120.1, 118.5, 19.9. – MS: m/z (%) ϭ 510 [M ϩ Hϩ] (100), 403 (31),
353 (7), 263 (8), 134 (13), 108 (41). – UV/vis (CHCl3): λmax (lg ε) ϭ
310 nm (4.43), 662 (4.74). – C32H28N7 (510.24): calcd. C 75.32, H
5.53, N 18.22; found C 75.82, H 5.54, N 18.29. – HR-MS (ESI):
calcd. 510.2406; found 510.2404.
2,6-Diphenyl-4-(4-tolyl)-4H-imidazo[4,5-b]pyrazine (6): A solution
of 3e (0.26 g, 1.0 mmol) and acetophenone dimethylacetal (5 mL)
in THF (30 mL) was stirred under reflux for 5 h. The solvent was
then removed in vacuo and the residue was chromatographed using
n-heptane/ethyl acetate (6:1) as eluent. Yield 0.22 g (62%), yellow
crystals; m.p. 247–249 °C. – 1H NMR (400 MHz, CDCl3): δ ϭ 8.58
(d, 2 H), 8.07 (d, 2 H), 8.01 (s, 1 H, CH), 7.79 (d, 2 H), 7.47 (m, 8
H), 2.50 (s, 3 H). – 13C NMR (100 MHz, CDCl3): δ ϭ 178.9, 163.5,
144.2, 141.9, 138.1, 137.2, 134.4, 132.6, 131.5, 130.7, 130.3, 130.1,
129.5, 127.5, 125.9, 120.7, 118.6, 22.3. – MS: m/z (%) ϭ 363 [M ϩ
Hϩ] (100), 269 (4), 181 (3). – UV/vis (CH2Cl2): λmax (lg ε) ϭ
280 nm (4.33), 406 (4.24). – C24H18N4 (362.41): calcd. C 79.54, H
5.01, N 15.46; found C 79.24, H 5.27, N 14.58.
Diimidazolyl Derivative 14b: 1H NMR (400 MHz, [D6]DMSO,
333 K): δ ϭ 8.25 (d, 4 H), 7.99 (d, 4 H), 7.54 (m, 6 H), 7.40 (t, 4
H), 7.04 (t, 2 H). – 1H NMR (400 MHz, [D8]THF, 223 K): δ ϭ
1
13.78 [d, J(15N,1H) ϭ 87.22 Hz, 1 H, 15NH], 12.26 (s, 1 H, NH),
1
1
9.11 [d, J(15N,1H) ϭ 92.36 Hz, 1 H, 15NH], 9.02 [d, J(15N,1H) ϭ
92.16 Hz, 1 H, 15NH], 8.41 (t, 4 H), 8.16 (m, 4 H), 8.07 (d, 4 H),
7.59–7.38 (m, 16 H), 7.02 (m, 4 H). – C30H23N515N2 (483.56).
General Procedure for the Synthesis of Imidazo[4,5-d]imidazoles 11:
In a Schlenk vessel, 3e–h (1.0 mmol) was dissolved in 30 mL of
THF under argon and reduced either by heating the solution with
0.5 g of Zn and 3 drops of concentrated hydrochloric acid, or by
passing a steady stream of H2S through the reaction mixture for
1 h. In both cases, a clear colourless solution was obtained, to
which an excess of the appropriate aromatic aldehyde (1.6 mmol)
was added. Stirring at room temperature was continued for 2 h, in
the course of which the colour of the solution turned to yellow. The
solvent was then removed in vacuo and the residue was subjected to
chromatography eluting with ethyl acetate/n-heptane, 1:1. In the
course of this procedure, a cyclization occurred leading to a colour-
less solution with a strong blue fluorescence. This solution was con-
centrated (to ca. 5 mL) and then kept at –78 °C overnight, where-
upon 11 was deposited as a crystalline solid.
Diimidazolyl Derivative 14c: Yield 0.20 g (68%), black crystals; m.p.
264–266 °C. – 1H NMR (250 MHz, [D6]DMSO): δ ϭ 13.6 (br. s, 1
H, NH), 13.1 (br. s, 1 H, NH), 9.7 (br. s, 1 H, NH), 8.28 (br. m, 4
H), 7.99 (br. m, 4 H), 7.56 (br. m, 6 H), 7.45 (d, 4 H), 1.31 (s, 18
H). – MS: m/z (%) ϭ 594 [M ϩ Hϩ] (43), 305 (14), 153 (5), 150
(70), 122 (26), 104 (100), 94 (51). – UV/vis (CHCl3): λmax (lg ε) ϭ
289 nm (4.25), 446 (3.85), 610 (4.35) – C38H37N7 (593.74): calcd. C
76.86, H 6.28, N 16.51; found C 76.63, H 6.82, N 15.87.
Diimidazolyl Derivative 15: To a solution of 14a (0.25 g, 0.5 mmol)
in acetonitrile (10 mL), methyl iodide (0.5 mL) was added and the
mixture was refluxed for 5 h. The solvent was then removed in va-
cuo and the residue was purified by column chromatography elut-
ing with toluene/acetone, 3:1. Yield: 0.09 g (36%), black crystals. –
1H NMR (400 MHz, CDCl3): δ ϭ 8.28 (d, 2 H), 8.08 (d, 2 H), 7.55
(d, 2 H), 7.52–7.43 (m, 7 H), 7.32 (d, 2 H), 7.27 (d, 2 H), 7.16 (d,
2 H), 6.67 (s, 1 H, NH), 2.44 (s, 3 H), 2.33 (s, 3 H). – 13C NMR
(100 MHz, CDCl3): δ ϭ 168.0, 158.8, 156.1, 153.6, 143.5, 141.4,
136.7, 135.5, 132.3, 132.2, 130.7, 130.4, 130.1, 129.8, 129.6, 128.9,
128.5, 127.9, 126.6, 126.0, 118.2, 41.1, 21.2, 20.8. – MS: m/z (%) ϭ
524 [M ϩ Hϩ] (100), 403 (11), 262 (4), 122 (13), 108 (5). – UV/
vis (CHCl3): λmax (lg ε) ϭ 310 nm (4.23), 425 (4.14), 654 (4.45). –
C33H30N7 (524.25): calcd. C 75.61, H 5.77, N 18.70; found C 75.42,
H 5.48, N 19.10.
2,5-Diphenyl-1-(4-tolyl)-1,4-dihydroimidazo[4,5-d]imidazole (11a):
Yield 0.27 g (78%), colourless crystals; m.p. 311 °C. – 1H NMR
(250 MHz, [D6]DMSO): δ ϭ 12.9 (br. s, 1 H, NH), 7.94 (t, 2 H),
7.59 (t, 1 H), 7.50–7.40 (m, 11 H), 2.37 (s, 3 H). – 13C NMR
(62 MHz, [D6]DMSO): δ ϭ 167.5, 145.9, 145.5, 137.5, 134.2, 132.6,
131.1, 130.1, 129.2, 128.8, 128.5, 128.3, 128.2, 128.1, 126.0, 124.8,
20.7. – MS (DEI): m/z (%) ϭ 350 [Mϩ] (100), 143 (21), 122 (47),
117 (83), 91 (46), 77 (58). – C23H18N4 (350.42): calcd. C 78.83, H
5.18, N 15.99; found C 77.87, H 5.52, N 15.59.
2-[4-(Methoxy)phenyl]-5-phenyl-1-(4-tolyl)-1,4-dihydroimidazo[4,5-
d]imidazole (11b): Yield 0.31 g (81%), colourless crystals; m.p. 320
°C. – H NMR (400 MHz, [D6]DMSO): δ ϭ 12.94 (s, 1 H, NH),
1
Acknowledgments
7.93 (d, 2 H), 7.42 (t, 2 H), 7.36–7.28 (m, 7 H), 6.88 (d, 2 H), 3.74
(s, 3 H), 2.37 (s, 3 H). – 13C NMR (100 MHz, [D6]DMSO): δ ϭ
159.2, 145.7, 145.3, 140.8, 137.4, 137.3, 134.4, 131.4, 130.1, 129.7,
128.8, 128.0, 126.0, 124.7, 123.6, 113.8. – MS: m/z (%) ϭ 381 [M
ϩ Hϩ] (100), 134 (7), 89 (37). – C24H20N4O (380.45): calcd. C
75.77, H 5.30, N 14.73; found C 74.98, H 5.62, N 14.38.
The support of the Fonds der Chemischen Industrie, the Thüringer
Ministerium für Wissenschaft, Forschung und Kultur, and the
Deutsche Forschungsgemeinschaft (SFB 436) is gratefully acknow-
ledged.
[1]
J. Atzrodt, J. Brandenburg, Ch. Käpplinger, R. Beckert, W.
Günther, H. Görls, J. Fabian, J. Prakt. Chem./Chem.-Ztg. 1997,
General Procedure for the Synthesis of Diimidazolyl Derivative 14:
To a solution of 3e–h (1.0 mmol) in THF (30 mL), Lawesson’s re-
agent (0.4 g, 1.0 mmol) was added. The resulting mixture was then
339, 729–734.
[2]
R. Gompper, H.-U. Wagner, Angew. Chem. 1988, 100, 1492–
1511; Angew. Chem. Int. Ed. Engl. 1988, 27, 1437–1455.
Eur. J. Org. Chem. 2000, 1661Ϫ1668
1667

J. Atzrodt, R. Beckert, W. Günther, H. Görls
FULL PAPER
[3]
[14]
[15]
´
P. von Rague Schleyer, P. K. Freeman, H. Jiao, B. Goldfuss,
J. Atzrodt, R. Beckert, H. Görls, Heterocycles 1999, 51, 763–
Angew. Chem. 1995, 107, 332–335; Angew. Chem. Int. Ed. Engl.
783.
1995, 34, 334–337.
J. Fabian, H. Görls, R. Beckert, J. Atzrodt, J. Prakt. Chem./-
Chem.-Ztg. 1997, 339, 735–741.
R. Gompper, Th. Geßner, Angew. Chem. 1985, 97, 997–998;
Angew. Chem. Int. Ed. Engl. 1985, 24, 982–983.
R. Gompper, H. Glöckner, Angew. Chem. 1984, 96, 48–49; An-
gew. Chem. Int. Ed. Engl. 1984, 23, 53–54; R. Gompper, M.
Junius, H.-U. Wagner, Tetrahedron Lett. 1981, 2973–2976; R.
Gompper, K. P. Bichlmayer, Tetrahedron Lett. 1980, 2879–
2882.
R. W. Hoffmann, Angew. Chem. 1968, 80, 823–834; Angew.
Chem. Int. Ed. Engl. 1968, 7, 754–765; N. Wiberg, Angew.
Chem. 1968, 80, 809–822; Angew. Chem. Int. Ed. Engl. 1968, 7,
766–779.
E. Ziegler, C. Mayer, J. G. Zwainz, Z. Naturforsch. 1975, 30b,
760; R. Kh. Freidlina, R. G. Petrova, B. V. Kopylova, I. I.
Kaudror, T. D. Churkin, Dokl. Chem. (Engl. Transl.) 1986,
27–30.
Z. Otwinowski, W. Minor, Processing of X-ray Diffraction Data
Collected in Oscillation Mode, in Methods in Enzymology, Vol.
276, Macromolecular Crystallography, Part A (Eds.: C. W.
Carter, R. M. Sweet), Academic Press, 1997, pp. 307–326.
[4]
[5]
[6]
[16]
[17]
[7]
D. Lindauer, Dissertation 1994, Friedrich-Schiller-Universität,
Jena.
[8]
[9]
[18]
[19]
K. H. Büchel, H. Erdmann, Chem. Ber. 1976, 109, 1638–1642.
T. H. Allen, O. Kamard, D. G. Watson, L. Brammer, A. Guy
Orpen, R. Taylor, J. Chem. Soc., Perkin Trans. 2 1987, S1–S19.
R. Beckert, K. Waisser, Ch. Käpplinger, D. Lindauer, R.
Walther, Pharmazie 1997, 52, 638–639.
Ch. Käpplinger, R. Beckert, W. Günther, H. Görls, Liebigs
Ann. 1997, 617–622; J. Brandenburg, Ch. Käpplinger, R.
Beckert, Synthesis 1996, 1302–1304; Ch. Käpplinger, R.
Beckert, W. Imhoff, J. Prakt. Chem./Chem.-Ztg. 1998, 323–333.
H. J. Timpe, Z. Chem. 1975, 15, 172–184.
G. M. Sheldrick, Acta Crystallogr. Sect. A 1990, 46, 467–473.
G. M. Sheldrick, SHELXL-97, University of Göttingen, Ger-
many, 1993.
[10]
[11]
[20]
Further details of the crystal structure investigations
are available on request from the director of the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, U.K. [Fax (internat.) ϩ44 (0)1223 336033; E-mail:
deposit@ccdc.cam.ac.uk] on quoting the depository nos.
CCDC-132525 (3f), CCDC-132527 (4c), and CCDC-132526
(11b), the names of the authors, and the full journal citation.
Received July 22, 1999
[12]
[13]
Z. Towsend, D. Miles, S. Manning, H. Eyring, J. Heterocycl.
Chem. 1973, 10, 419–421.
[O99452]
1668
Eur. J. Org. Chem. 2000, 1661Ϫ1668