Regioselective synthesis of cis- and trans-2,4,5-triarylimidazolines and 2,4,5-triarylimidazoles from available reagents

Article abstract of DOI:10.1023/A:1023915024572

Novel data were obtained concerning the reaction of aromatic aldehydes with ammonia. A preparative method for the synthesis of new substituted 1,3,5-triaryl-2,4-diazapenta-1,4-dienes was developed. These products are the starting reactants for syntheses of cis- and trans-2,4,5-triaryl-2-imidazolines and 2,4,5-triarylimidazoles.

Full text of DOI:10.1023/A:1023915024572

674
Russian Chemical Bulletin, International Edition, Vol. 52, No. 3, pp. 674—678, March, 2003
Regioselective synthesis of cisꢀ and transꢀ2,4,5ꢀtriarylimidazolines
and 2,4,5ꢀtriarylimidazoles from available reagents*
ꢀ
N. A. Lozinskaya, V. V. Tsybezova, M. V. Proskurnina, and N. S. Zefirov
Department of Chemistry, M. V. Lomonosov Moscow State University,
Leninsky Gory, 119992 Moscow, Russian Federation.
Fax: +7 (095) 939 0290. Eꢀmail: natasha@org.chem.msu.su
Novel data were obtained concerning the reaction of aromatic aldehydes with ammonia.
A preparative method for the synthesis of new substituted 1,3,5ꢀtriarylꢀ2,4ꢀdiazapentaꢀ1,4ꢀ
dienes was developed. These products are the starting reactants for syntheses of cisꢀ and
transꢀ2,4,5ꢀtriarylꢀ2ꢀimidazolines and 2,4,5ꢀtriarylimidazoles.
Key words: aromatic aldehydes, 1,3,5ꢀtriarylꢀ2,4ꢀdiazapentaꢀ1,4ꢀdienes, hydrobenzamide,
imidazolines, imidazoles.
It is known1,2 that benzaldehyde reacts with ammonia
Previously, such strong bases as sodium amide and
phenyllithium were used for the ring closure of triꢀ
phenyldiazapentadiene (1а) to cisꢀimidazoline cisꢀ2a
along with the thermal ring closure, which occurs in a low
yield. To synthesize transꢀtriphenylimidazoline (transꢀ2a),
the twoꢀstep method was proposed, including the syntheꢀ
sis of cisꢀimidazoline (cisꢀ2a)9,10 and its isolation folꢀ
lowed by recyclization under the action of a strong base
(PhLi, ButOK in ButOH, and NaOH in diethylene glyꢀ
col). The ring closure of triphenyldiazapentadiene (1a) by
a 0.41 N solution of ButOK in ButOH at 100 °С was also
described.11 However, the yield of compound 3а was low.
The attempt12 to use ultraviolet irradiation for the direct
ring closure of the anion of triphenyldiazapentadiene (1а)
to form transꢀimidazoline transꢀ2a was unsuccessful: the
reaction occurred in a low yield (7—16%).
to form the trimeric product, viz., 1,3,5ꢀtriphenylꢀ2,4ꢀ
diazapentaꢀ1,4ꢀdiene (1a). The thermal ring closure of
compound 1a affords cisꢀ2,4,5ꢀtriphenylꢀ2ꢀimidazoline
(cisꢀ2a).2—4 The third isomer, transꢀ2,4,5ꢀtriphenylꢀ2ꢀ
imidazoline (transꢀ2а), was prepared by the treatment of
the cisꢀisomer with a strong base (Scheme 1).3—7
Scheme 1
We synthesized several 1,3,5ꢀtriarylꢀ2,4ꢀdiazapentaꢀ
dienes 1a—f (77—94% yields) by the interaction of the
corresponding aromatic aldeꢀ
hydes with an ammonia soluꢀ
tion to use them in subsequent
ring closure.
The interaction of 2,6ꢀdiꢀ
chlorobenzaldehyde with an
ammonia solution in ethanol
Reagent and conditions: i. NaOH/ethylene glycol, 150 °С.
Ar = Ph (a), 4ꢀBrC6H4 (b),
4ꢀMeOC6H4 (c),
2ꢀthienyl (d),
3ꢀNO2C6H4 (e),
4ꢀFC6H4 (f)
immediately afforded the corꢀ
responding cisꢀ2,4,5ꢀtriarylꢀ
imidazoline cisꢀ2g in 97%
yield. This fact can be exꢀ
Substituted cisꢀimidazolines cisꢀ2 and transꢀimidꢀ
azolines transꢀ2 are, as known, of great synthetic interest
as the starting reactants in the synthesis of mesoꢀ and
d,lꢀisomers of vicinal diamines4—6 and imidazole derivaꢀ
tives.8 Therefore, the ring closure of 1,3,5ꢀtriarylꢀ2,4ꢀ
diazapentaꢀ1,4ꢀdienes 1 is a convenient synthetic method.
plained by a greater easiness of proton elimination in the
formed compound 1g, which facilitates ring closure even
under the action of such a weak base as ammonia.
To check this assumption, we studied the reactions of
2ꢀnitrobenzaldehyde and 3ꢀnitrobenzaldehyde with amꢀ
* Dedicated to Academician I. P. Beletskaya on the occasion of
her anniversary.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 646—650, March, 2003.
1066ꢀ5285/03/5203ꢀ674 $25.00 © 2003 Plenum Publishing Corporation

2,4,5ꢀTriarylimidazolines and ꢀimidazoles
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 3, March, 2003
675
Scheme 3
monia. We found that the nature of products of the reacꢀ
tions of these aldehydes with ammonia depends on the
chosen solvent. For example, the interaction of 2ꢀ and
3ꢀnitrobenzaldehydes with a saturated alcoholic solution
of ammonia (ethyl, isopropyl, and tertꢀbutyl alcohols were
used) afforded hexahydrotriazines 3a,b (Scheme 2), and
when a saturated solution of ammonia in THF was used,
the corresponding cisꢀimidazolines cisꢀ2e,h immediately
formed. Anhydrous solvents decrease the yield of byꢀprodꢀ
ucts. It is known that the formation of triazine structure is
more characteristic of aliphatic than aromatic aldeꢀ
hydes9,13 because, in the case of aromatic aldehydes, simiꢀ
lar triazines can transform with ejection of an ammonia
molecule into diazapentadienes 1. This transformation
readily occurs on slight heating.14 1,3,5ꢀTriaryldiazaꢀ
pentadiene 1e was synthesized from 3ꢀnitrobenzaldehyde
by the reaction with a saturated ammonia solution in
methylene chloride or benzene. Under these conditions,
2ꢀnitrobenzaldehyde transformed into the 1 : 1 mixture of
the corresponding diazapentadiene and hexahydrotriazine.
Ar = Ph (2a, 4a), 4ꢀBrC6H4 (2b, 4b), 4ꢀMeOC6H4 (2c, 4c),
2ꢀthienyl (2d, 4d), 3ꢀNO2С6H4 (cisꢀ2e, 4e), 4ꢀFC6H4 (cisꢀ2f),
4ꢀpyridyl (4f)
the reaction is performed with the stoichiometric amount
of ButOK in DMSO at 50 °С for 2 h. Products of ring
closure of compound 1a can easily be identified, because
the structures of cisꢀ2a and transꢀ2а are known and their
cisꢀ and transꢀconfigurations have been proved earlier7 by
Xꢀray diffraction analysis.
Scheme 2
The presence of acceptor substituents in the aroꢀ
matic cycle is shown to facilitate both the ring closure
and subsequent oxidation to imidazole. For example,
2,4,5ꢀtris(pyridinꢀ4ꢀyl)imidazole (4f) forms already in
the interaction of pyridineꢀ4ꢀcarbaldehyde with an
aqueous solution of ammonia, while the syntheses of
2,4,5ꢀtris(2ꢀthienyl)imidazole (4d) and 2,4,5ꢀtris(4ꢀmethꢀ
oxyphenyl)imidazole (4c) require drastic conditions: reꢀ
fluxing of the starting diazapentadienes or imidazolines
cisꢀ2 and transꢀ2 with ButOK in DMSO in an oxygen flow
for 1—7 days, the yield being ∼50%. In these cases, it is
difficult to oxidize imidazolines to imidazoles likely beꢀ
cause the reaction proceeds through deprotonation at the
nitrogen atom to form an anionic structure, and the
deprotonation is hindered by donor substituents.
In studying the ring closure of various diazapentaꢀ
dienes, we faced the problem of identification of cisꢀ and
transꢀproducts of the reaction, because
The results obtained for 2ꢀ and 3ꢀnitrobenzaldehydes
correlate well with the previous data for the reaction of
pyridineꢀ2ꢀcarbaldehyde with ammonia.13
Studying the ring closure of compounds 1 by the acꢀ
tion of ButOK, we showed that a change in the reaction
conditions allowed one to easily obtain any of three deꢀ
sired products (cisꢀ2, transꢀ2, or 4) in a high yield. This
procedure provides the easy isolation of all these comꢀ
pounds. A simple and convenient method for syntheses of
cisꢀ and transꢀ2,4,5ꢀtriarylꢀ2ꢀimidazolines cisꢀ2 and
transꢀ2 and 2,4,5ꢀtriarylimidazolines 4 using the ring cloꢀ
sure of the corresponding 1,3,5ꢀtriarylꢀ2,4ꢀdiazapentaꢀ
1,4ꢀdienes was proposed (Scheme 3).
it has previously been reported for the
only wellꢀstudied similar compounds,
viz., benzaldehyde derivatives, that sigꢀ
The reaction of triphenyldiazapentadiene (1а) with
the stoichiometric amount of ButOK in anhydrous
THF at –10 °С for 20 min affords the corresponding
cisꢀimidazoline cisꢀ2а in 80% yield. The reaction in anꢀ
hydrous THF on boiling for 15 min results in the formaꢀ
tion of transꢀimidazoline transꢀ2а in 90% yield, and
2,4,5ꢀtriphenylimidazole 4a forms in ∼100% yield when
nals from the Ha and Нb protons in the
1H NMR spectrum coincide for cisꢀ and
transꢀimidazolines.
To prove the structure, imidazolines were either transꢀ
formed into those acylated at the nitrogen atom of the
system, which allowed one to distinguish signals from the
cisꢀ and transꢀprotons,9 or Xꢀray diffraction analysis was

676
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 3, March, 2003
Lozinskaya et al.
Table 1. Chemical shifts of the Ha and Hb protons in the 1H NMR
spectra and melting points of imidazolines cisꢀ2 and transꢀ2*
1,3,5ꢀTriphenylꢀ2,4ꢀdiazapentaꢀ1,4ꢀdiene (1а).4 A solution
(100 mL) of ammonia in 95% ethanol and ammonium chloride
(1 g) were added to benzaldehyde (20 g, 0.188 mol). The mixꢀ
ture was stirred for 6 h at ∼20 °C. Colorless crystals were filtered
off. The yield was 80% (15 g), m.p. 105 °С (95% ethanol).
1,3,5ꢀTris(4ꢀbromophenyl)ꢀ2,4ꢀdiazapentaꢀ1,4ꢀdiene (1b).
A solution of ammonia (50 mL) in ethanol and ammonium
chloride (0.5 g) were added to 4ꢀbromobenzaldehyde (10 g,
0.054 mol). The mixture was stirred for 24 h at ∼20 °C. Colorless
crystals were filtered off. The yield was 79% (7.6 g), m.p. 120 °С
(95% ethanol). 1H NMR (300.13 MHz, СDCl3), δ: 5.90 (s, 1 H);
7.35 (d, 2 Н, J = 13 Hz); 7.50 (d, 2 Н, J = 13 Hz); 7.55 (d, 4 Н,
J = 12 Hz); 7.70 (d, 4 Н, J = 12 Hz); 8.49 (s, 2 Н). Found (%):
С, 47.06; Н, 3.04; N, 6.02., С21Н15Br3N2. Calculated (%):
С, 47.14; Н, 2.83; N, 5.24.
Comꢀ
pound
R
δ
M.p./°С
cisꢀ2
а
Ph
5.25—5.35
129
(br.s, 2 Н)
b
c
d
e
4ꢀBrC6H4
4ꢀMeOC6H4
2ꢀThienyl
5.40 (s, 2 Н)
5.25 (s, 2 Н)
5.53 (s, 2 Н)
5.55 (d, 1 Н)
5.85 (d, 1 H)
5.38 (br.s, 2 Н)
6.05 (d, 1 Н),
6.45 (d, 1 Н)
5.98 (d, 1 Н)
6.18 (d, 1 Н)
120
86
97
3ꢀNO2C6H4
150—154
f
g
4ꢀFC6H4
2,6ꢀCl2C6H4
123—125
138—143
1,3,5ꢀTris(4ꢀmethoxyphenyl)ꢀ2,4ꢀdiazapentaꢀ1,4ꢀdiene (1c).
A saturated solution of ammonia (100 mL) in ethanol and amꢀ
monium chloride (0.5 g) were added to 4ꢀmethoxybenzaldehyde
(10 g, 0.073 mol). The mixture was stirred for 24 h at ∼20 °C.
Colorless crystals of compound 1c were filtered off (8 g, 84%),
h
2ꢀNO2C6H4
Ph
244—246
202
transꢀ2
а
1
4.85—5.00
m.p. 127 °С (95% ethanol). H NMR spectrum (300.13 MHz,
(br.s, 2 Н)
DMSOꢀd6/СCl4), δ: 5.81 (s, 1 H); 6.85 (d, 2 Н, J = 10 Hz); 6.95
(d, 4 Н, J = 11 Hz); 7.35 (d, 2 Н, J = 10); 7.75 (d, 4 Н, J =
11 Hz); 8.48 (s, 2 Н). Found (%): С, 74.29; Н, 6.38; N, 7.32.
C24H24N2О3. Calculated (%): С, 74.21; Н, 6.23; N, 7.21.
1,3,5ꢀTris(2ꢀthienyl)ꢀ2,4ꢀdiazapentaꢀ1,4ꢀdiene (1d). A satuꢀ
rated solution of ammonia (100 mL) in ethanol and ammonium
chloride (1 g) were added to thiopheneꢀ2ꢀcarbaldehyde (20 g,
0.178 mol). The mixture was stirred for 6 h at ∼20 °C. Colorless
crystals of compound 1d were filtered off. The yield was 14.9 g
(84%), m.p. 120 °С (95% ethanol). 1H NMR (300.13 NHz,
DMSOꢀd6/СCl4), δ: 6.18 (s, 1 H); 6.90 (t, 1 Н, J = 6 Hz); 7.03
(d, 1 Н, J = 6 Hz); 7.12 (t, 2 Н, J = 6 Hz); 7.45 (d, 1 Н, J =
6 Hz); 7.50 (d, 2 Н, J = 6 Hz); 7.65 (d, 2 Н, J = 6 Hz); 8.65
(s, 2 Н). Found (%): С, 56.33; Н, 3.77; N, 9.05. С14Н13N2S3.
Calculated (%): С, 56.93; Н, 3.82; N, 8.85.
b
c
d
4ꢀBrC6H4
4ꢀMeOC6H4
2ꢀThienyl
4.75 (s, 2 Н)
4.66 (c, 2 H)
5.05 (d, 1 Н),
5.15 (d, 1 Н)
196
135
158—160
* Signals from the Ha and Hb protons in compounds cisꢀ2e,
cisꢀ2g, and transꢀ2d have the shape of doublets, which is caused
by hindrances of internal rotation about the R—C(4) and
R—C(5) bonds. The spinꢀspin coupling constants are presented
in Experimental.
used.7 We propose to use a DMSOꢀd6/ССl4 (1 : 2) system
for recording H NMR spectra. Since the configuration
1
for compounds cisꢀ2a and transꢀ2a has previously7 been
proved by Xꢀray diffraction analysis, at first the signals of
the indicated protons in transꢀ and cisꢀimidazolines were
exactly assigned. It was found that in the DMSOꢀd6/ССl4
(1 : 2) system the signals from Ha and Нb differed for the
cisꢀ and transꢀisomers and, as expected, for cisꢀimidꢀ
azolines the signals of protons demonstrated downfield
shifts compared to the transꢀisomers. The established
cisꢀ and transꢀconfigurations were indirectly confirmed
by the regularities in the melting temperatures: the meltꢀ
ing point is higher for the transꢀisomer (Table 1).
1,3,5ꢀTris(3ꢀnitrophenyl)ꢀ2,4ꢀdiazapentaꢀ1,4ꢀdiene (1e).
Compound 1e was obtained from 3ꢀnitrobenzaldehyde (5 g,
0.033 mol) and a saturated solution (40 mL) of ammonia in
methylene chloride or benzene. The yield was 4.5 g (94%), white
1
crystals, m.p. 178 °С (95% ethanol). H NMR (399.95 MHz,
DMSOꢀd6/СCl4), δ: 6.35 (s, 1 Н); 7.70 (t, 1 Н, J = 9 Hz); 7.85
(t, 2 Н, J = 8 Hz); 8.00 (d, 1 Н, J = 9 Hz); 8.15 (d, 1 Н, J =
8 Hz); 8.30 (m, 4 Н); 8.40 (s, 1 Н); 8.70 (s, 2 Н); 8.85 (s, 2 Н).
Found (%): С, 57.96; Н, 3.47; N, 16.99. С21Н17N5O7. Calcuꢀ
lated (%): С, 58.20; Н, 3.49; N, 16.16.
1,3,5ꢀTris(4ꢀfluorophenyl)ꢀ2,4ꢀdiazapentaꢀ1,4ꢀdiene (1f).
Compound 1e was synthesized from pꢀfluorobenzaldehyde (10 g,
0.054 mol), an aqueous 25% solution of ammonia (50 mL), and
ammonium chloride (0.5 g). The yield was 6 g (77%), colorless
crystals, m.p. 93—95 °С (95% ethanol). 1H NMR (300.13 MHz,
DMSOꢀd6/СCl4), δ: 5.95 (s, 1 Н); 7.10 (t, 2 Н, J = 9 Hz); 7.20
(t, 4 Н, J = 9 Hz); 7.50 (t, 2 Н, J = 7 Hz); 7.20 (t, 4 Н, J =
7 Hz); 8.69 (s, 2 Н). Found (%): С, 71.68; Н, 4.25; N, 8.12.
C21H15F3N2. Calculated (%): С, 71.58; Н, 4.29; N, 7.95.
2,4,6ꢀTris(2ꢀnitrophenyl)hexahydroꢀ1,3,5ꢀtriazine (3a).
A saturated solution of ammonia (50 mL) in anhydrous ethanol
and ammonium chloride (0.1 g) were added to 2ꢀnitrobenzꢀ
aldehyde (4.7 g, 0.031 mol). The mixture was stirred for 48 h at
∼20 °C, and a light pink precipitate was filtered off from
the formed dark cherryꢀcolored solution. The yield was 2 g
The validity of determination of the configuration of
imidazolines from the 1Н NMR spectrum was verified for
compound cisꢀ2g, for which we assumed the cisꢀconfiguꢀ
ration due to the strong upfield shift of characteristic proꢀ
tons. The proposed configuration was confirmed by the
Xꢀray diffraction data to be published elsewhere.
Experimental
1
H NMR spectra were recorded on Bruker ACꢀ300, Bruker
ACꢀ200, and Varian 400 instruments. Melting points were deꢀ
termined in a glass capillary.

2,4,5ꢀTriarylimidazolines and ꢀimidazoles
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 3, March, 2003
677
1
(44.7%), m.p. 117 °С (95% ethanol). H NMR (200.13 MHz,
cisꢀ2,4,5ꢀTris(4ꢀmethoxyphenyl)ꢀ2ꢀimidazoline (cisꢀ2c) was
synthesized from 1c (0.5 g, 1.3 mmol) and ButOK (0.3 g,
2.6 mmol) in anhydrous THF (10 mL). The yield was 0.47 g
DMSOꢀd6/СCl4), δ: 2.41 (t, 3 Н, J = 10 Hz); 5.55 (t, 3 Н,
J = 10 Hz); 7.48 (t, 3 Н, J = 7 Hz); 7.61 (t, 3 Н, J = 7 Hz);
7.68—7.79 (m, 6 Н). Found (%): С, 55.88; Н, 4.00;
N, 18.56. C21H18N6О3. Calculated (%): С, 56.00; Н, 4.03;
N, 18.66.
2,4,6ꢀTris(3ꢀnitrophenyl)hexahydroꢀ1,3,5ꢀtriazine (3b). A
saturated solution of ammonia (50 mL) in anhydrous ethanol
was added to 3ꢀnitrobenzaldehyde (5 g, 0.033 mol). The mixture
was stirred for 5 days at ∼20 °C. A light yellow crystalline preꢀ
cipitate was filtered off from the formed dark cherryꢀcolored
1
(94%), m.p. 86 °С. H NMR (300.13 MHz, DMSOꢀd6/СCl4),
δ: 3.65 (s, 6 Н); 3.85 (s, 3 Н); 5.25 (s, 2 Н); 6.55 (d, 4 Н, J =
9 Hz); 6.85 (d, 4 Н, J = 9 Hz); 6.95 (d, 2 Н, J = 9 Hz); 7.98 (d,
2 Н, J = 9 Hz). Found (%): С, 81.69; Н, 6.71; N, 8.00.
С24Н24N2O3. Calculated (%): С, 81.78; Н, 6.86; N, 7.95.
cisꢀ2,4,5ꢀTris(2ꢀthienyl)ꢀ4ꢀimidazoline (cisꢀ2d) was syntheꢀ
sized from 1d (0.5 g, 1.6 mmol) and ButOK (0.3 g, 2.6 mmol) in
anhydrous THF (10 mL). The yield was 0.5 g (100%), m.p.
97 °С. 1H NMR (300.13 MHz, DMSOꢀd6/СCl4), δ: 5.53
(s, 2 Н); 6.65 (d, 2 Н, J = 4 Hz); 6.75 (t, 2 Н, J = 4 Hz); 7.10
(d, 2 Н, J = 3 Hz); 7.20 (t, 1 Н, J = 3 Hz); 7.61 (d, 1 Н, J =
3 Hz); 7.75 (d, 1 Н, J = 3 Hz). Found (%): С, 56.82; Н, 3.81;
N, 8.73. С15Н12N2S3. Calculated (%): С, 56.93; H, 3.82; N, 8.85.
cisꢀ2,4,5ꢀTris(3ꢀnitrophenyl)ꢀ4ꢀimidazoline (cisꢀ2e). A. Comꢀ
pound cisꢀ2e was synthesized from diazapentadiene 1e (1.3 g,
2.8 mmol) and ButOK (0.4 g, 3.5 mmol) in a mixture of anhyꢀ
drous THF (10 mL) and anhydrous DMF (5 mL). The yield was
1.3 g (100%).
1
solution. The yield was 3.82 g (80%), m.p. 118 °С. H NMR
(300.13 MHz, DMSOꢀd6/СCl4), δ: 2.45 (t, 3 Н, J = 10 Hz);
5.25 (t, 3 Н, J = 10 Hz); 7.65 (t, 3 Н, J = 7 Hz); 8.15 (d, 3 Н, J =
7 Hz); 8.20 (d, 2 Н, J = 7 Hz); 8.55 (s, 3 Н). Found (%):
С, 55.93; Н, 4.08; N, 18.66. C21H18N6О3. Calculated (%): С,
56.00; Н, 4.03; N, 18.66.
cisꢀ2,4,5ꢀTris(2,6ꢀdichlorophenyl)ꢀ2ꢀimidazoline (cisꢀ2g).
2,6ꢀDichlorobenzaldehyde (4.7 g, 0.027 mol) was stirred in 95%
ethanol in the presence of ammonium chloride (0.2 g) at ∼20 °C
for 8 days. The precipitate was filtered off. The yield was 4.15 g
(99%), colorless crystals, m.p. 138—143 °С (95% ethanol).
1H NMR (300.13 MHz, DMSOꢀd6/СCl4), δ: 6.05 (d, 1 Н, J =
17 Hz); 6.45 (d, 1 Н, J = 17 Hz); 7.05—7.20 (m, 4.5 Н);
7.43—7.60 (m, 1 Н); 8.5 (d, 1 Н, J = 4 Hz). Found (%): С, 50.06;
Н, 2.34; N, 5.25. С21Н10Сl6N2. Calculated (%): С, 49.94;
Н, 2.39; N, 5.55.
B. Compound cisꢀ2e was synthesized by the reaction of
3ꢀnitrobenzaldehyde (1 g) with a saturated solution of NH3
(20 mL) in anhydrous THF for 3 days. The yield was 0.8 g
(73%), m.p. 150—154 °С.
1H NMR (399.95 MHz, DMSOꢀd6/СDCl3), δ: 5.55 (d, 1 Н,
J = 14 Hz); 5.85 (d, 1 Н, J = 14 Hz); 7.2 (t, 2 Н, J = 7 Hz); 7.3
(t, 2 Н, J = 7 Hz); 7.7 (t, 1 Н, J = 7 Hz); 7.5 (s, 1 Н); 7.80—7.85
(m, 3 Н); 8.3 (d, 2 Н, J = 7 Hz); 8.50 (d, 2 Н, J = 7 Hz); 9.0
(s, 1 Н). Found (%): С, 57.40; Н, 2.99; N, 15.54. С21Н17N5O7.
Calculated (%): С, 58.20; Н, 3.49; N, 16.16.
cisꢀ2,4,5ꢀTris(2ꢀnitrophenyl)ꢀ2ꢀimidazoline (cisꢀ2h) was synꢀ
thesized from 2ꢀnitrobenzaldehyde (1.5 g, 0.01 mol) and a satuꢀ
rated solution of ammonia (50 mL) in anhydrous THF. The yield
1
was 0.71 g (50%), m.p. 244—246 °С. H NMR (300.13 MHz,
DMSOꢀd6), δ: 5.98 (d, 1 Н, J = 9 Hz); 6.18 (d, 1 Н, J = 9 Hz);
7.25—7.56 (m, 6 Н); 7.65 (d, 1 H, J = 7 Hz); 7.73 (d, 1 H, J =
7 Hz); 7.80 (d, 1 H, J = 7 Hz); 7.88 (t, 1 H, J = 7 Hz); 8.00 (d,
1 Н); 8.50 (d, 1 H); 8.30 (s, 1 Н). Found (%): С, 58.26; Н, 3.39;
N, 16.42. С21Н15N5O6. Calculated (%): С, 58.20; Н, 3.49;
N, 16.16.
Synthesis of cisꢀ2,4,5ꢀtriarylꢀ2ꢀimidazolines cisꢀ2 (general
procedure). Diazapentadienes 1 were dissolved in a minor amount
of anhydrous THF, the solution was cooled to –20 °С, argon
was passed through the solution for 5 min, and ButOK was
added with vigorous stirring. The solution changed its color to
intense blue or violet and then became colorless. As soon as the
color of the solution changed to light yellow, the reaction was
stopped adding a threefold excess of cold water. The precipitate
that formed was recrystallized from an ethyl acetate—hexane
(1 : 6) mixture.
cisꢀ2,4,5ꢀTriphenylꢀ2ꢀimidazoline (cisꢀ2a) 7 was synthesized
from 1a (1 g, 3.3 mmol) and ButOK (0.3 g, 2.6 mmol) in anhyꢀ
drous THF (10 mL). The yield was 0.9 g (90%), m.p. 129 °С.
1H NMR (300.13 MHz, DMSOꢀd6/СDCl3), δ: 5.25 (d, 1 Н, J =
8 Hz); 5.35 (d, 1 Н, J = 8 Hz); 5.65—5.75 (br.s, 1 Н); 6.9—7.05
(m, 10 Н); 7.48—7.55 (m, 3 Н); 7.95 (d, 2 Н).
cisꢀ2,4,5ꢀTris(4ꢀbromophenyl)ꢀ2ꢀimidazoline (cisꢀ2b) was
synthesized from 1b (0.5 g, 0.9 mmol) and ButOK (0.3 g,
2.6 mmol) in anhydrous THF (10 mL). The yield was 0.3 g
(60%), m.p. 120 °С. 1H NMR (300.13 MHz, DMSOꢀd6/СCl4),
δ: 3.0 (s, 1 Н); 5.4 (s, 2 Н); 6.9 (d, 4 Н, J = 11 Hz); 7.2 (d, 4 Н,
J = 8 Hz); 7.65 (d, 2 Н, J = 8 Hz); 8.00 (d, 2 Н, J = 8 Hz).
Found (%): С, 47.00; Н, 2.69; N, 5.15. С21Н15Br3N2. Calcuꢀ
lated (%): С, 47.14; Н, 2.83; N, 5.24.
cisꢀ2,4,5ꢀTris(4ꢀfluorophenyl)imidazoline (cisꢀ2f) was syntheꢀ
sized from diazapentadiene 1f (1 g, 2.8 mmol) and ButOK (0.3 g,
2.6 mmol) in anhydrous THF (10 mL). The yield was 1 g (100%),
m.p. 123—125 °С. 1H NMR (300.13 MHz, DMSOꢀd6/СCl4), δ:
5.38 (br.s, 2 Н); 6.74 (t, 4 Н, J = 3 Hz); 6.85—6.89 (m, 4 Н);
7.14 (t, 2 Н, J = 3 Hz); 7.91—7.96 (m, 2 Н). Found (%):
С, 67.97; Н, 4.27; N, 7.98. С21Н15N2F3•Н2О. Calculated (%):
С, 68.10; Н, 4.68; N, 7.56.
Synthesis of transꢀ2,4,5ꢀtriarylꢀ2ꢀimidazolines transꢀ2 (genꢀ
eral procedure). Diazapentadiene 1 was dissolved in a minor
amount of anhydrous THF (in the case of donating substituents,
in anhydrous DMSO), argon was passed through the solution
for 5 min, and ButOK was added with vigorous stirring. The
solution changed its color to intense blue or violet, which then
gradually disappeared. The mixture was heated for 0.3—24 h,
monitoring the formation of a recyclization product by TLC
using an ethyl acetate—hexane (1 : 1) mixture as eluent. The
reaction was stopped by the addition of a triple excess of cold
water. The precipitate that formed was washed with a hot ethyl
acetate—hexane (1 : 6) mixture.
transꢀ2,4,5ꢀTriphenylꢀ2ꢀimidazoline (transꢀ2а)7 was syntheꢀ
sized from 1a (1 g, 3.3 mmol) and ButOK (0.3 g, 2.6 mmol) on
refluxing for 2 h in anhydrous THF (10 mL). The yield was 0.9 g
(90%), m.p. 202 °С. 1H NMR (300.13 MHz, DMSOꢀd6/СCl4),
δ: 4.85—5.00 (br.s, 2 Н); 5.35—5.50 (br.s, 1 Н); 7.25—7.40
(m, 10 Н); 7.42—7.55 (m, 3 Н); 7.95 (d, 2 Н, J = 3 Hz).
transꢀ2,4,5ꢀTris(4ꢀbromophenyl)ꢀ2ꢀimidazoline (transꢀ2b)
was synthesized from 1b (0.5 g, 0.9 mmol) and ButOK (0.3 g,
2.6 mmol) in anhydrous THF (10 mL). The yield was 0.3 g
(60%), m.p. 196 °С. 1H NMR (300.13 MHz, DMSOꢀd6/СCl4),

678
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 3, March, 2003
Lozinskaya et al.
δ: 3.0 (s, 1 Н); 4.75 (s, 2 Н); 7.22 (d, 4 Н, J = 10 Hz); 7.50 (d,
4 Н, J = 10 Hz); 7.65 (d, 2 Н, J = 10 Hz); 7.95 (d, 2 Н, J =
10 Hz). Found (%): С, 47.12; Н, 2.72; N, 5.23. С21Н15Br3N2.
Calculated (%): С, 47.14; Н, 2.83; N, 5.24.
transꢀ2,4,5ꢀTris(4ꢀmethoxy)ꢀ2ꢀimidazoline (transꢀ2c) was
synthesized from 1c (0.5 g, 1.3 mmol) and ButOK (0.3 g,
2.6 mmol) in THF (10 mL). The yield was 0.47 g (94%), m.p.
86 °С. 1H NMR (300.13 MHz, DMSOꢀd6/СCl4), δ: 3.65
(s, 6 Н); 3.85 (s, 3 Н); 4.66 (s, 2 Н); 6.50 (d, 4 Н, J = 9 Hz); 6.75
(d, 4 Н, J = 9 Hz); 6.95 (d, 2 Н, J = 9 Hz); 7.98 (d, 2 Н, J =
9 Hz). Found (%): С, 74.19; Н, 6.21; N, 7.10. С24Н24N2O3.
Calculated (%): С, 74.21; Н, 6.23; N, 7.21.
transꢀ2,4,5ꢀTris(2ꢀthienyl)ꢀ2ꢀimidazoline (transꢀ2d) was synꢀ
thesized from 1d (1 g, 3.2 mmol) and ButOK (0.3 g, 2.6 mmol)
in DMSO (10 mL). The yield was 0.6 g (60%), m.p. 158—160 °С.
1H NMR (300.13 MHz, DMSOꢀd6/СCl4), δ: 5.05 (d, 1 Н, J =
6 Hz); 5.15 (d, 1 Н, J = 6 Hz); 6.90—7.10 (m, 3 Н); 7.15—7.20
(t, 1 Н, J = 4 Hz); 7.40 (d, 1 Н, J = 4 Hz); 7.50 (d, 1 Н, J =
4 Hz); 7.65 (d, 1 Н, J = 4 Hz); 7.75 (d, 1 Н, J = 4 Hz); 8.15
(br.s, 1 Н). Found (%): С, 56.88; Н, 3.85; N, 8.94. С15Н12N2S3.
Calculated (%): С, 56.93; H, 3.82; N, 8.85.
Synthesis of 2,4,5ꢀtriarylimidazoles 4 (general procedure).
Compound 1 was dissolved in a minor amount of anhydrous
DMSO, and ButOK was added with vigorous stirring. The color
of the solution changed to intense blue or violet and then graduꢀ
ally transformed into intense crimson. The mixture was heated
for some time, passing an air or oxygen flow to accelerate the
process and monitoring the formation of an oxidation product
by TLC using an ethyl acetate—hexane (1 : 1) mixture as eluent.
The mixture was poured into cold water. The precipitate that
formed was recrystallized from an ethyl acetate—hexane (1 : 1)
mixture.
Н, 3.30; N, 9.13. С15Н10N2S3. Calculated (%): С, 57.29;
H, 3.21; N, 8.91.
2,4,5ꢀTris(3ꢀnitrophenyl)imidazole (4e) was synthesized from
1e (0.5 g, 1.2 mmol) and ButOK (0.2 g, 1.8 mmol) on refluxing
in anhydrous DMSO (6 mL) for 3 h. The yield was 0.2 g (40%),
m.p. 235 °С. 1H NMR (300.13 MHz, DMSOꢀd6/СCl4), δ: 7.65
(t, 2 Н, J = 9 Hz); 7.75 (t, 1 Н, J = 9 Hz); 7.95 (m, 3 Н); 8.2
(m, 3 Н); 8.45 (s, 3 Н); 8.60 (d, 1 Н, J = 9 Hz); 9.00 (s, 1 Н);
13.20—13.40 (br.s, 1 Н). Found (%): С, 56.59; Н, 3.61; N, 15.97.
С21Н15N5O7•Н2О. Calculated (%): С, 56.13; Н, 3.36; N, 15.58.
2,4,5ꢀTris(4ꢀpyridinꢀ4ꢀyl)imidazole (4f). Pyridineꢀ4ꢀcarbꢀ
aldehyde (2 g, 0.018 mol) and a saturated solution of ammonia
(50 mL) in 95% ethanol in the presence of ammonium chloride
(0.2 g) were stored at ∼20 °C for 8 days. The yield was 1.36 g
1
(72%), m.p. 333 °С. H NMR (300.13 MHz, DMSOꢀd6), δ:
7.50 (s, 4 Н); 8.00 (s, 2 Н); 8.60 (d, 5.5 Н, J = 8 Hz); 13.2 (br.s,
1 Н). 13С NMR (100.13 MHz, DMSOꢀd6), δ: 120, 122.9, 136.8,
145.1, 149.9, 150, 163.8. Found (%): С, 68.28; Н, 4.83; N, 23.12.
С18Н13N5•Н2О. Calculated (%): С, 68.13; Н, 4.76; N, 22.07.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 01ꢀ03ꢀ
33085).
References
1. A. Laurent, С. R. Ann., 1837, 21, 130.
2. A. Laurent, С. R. Acad. Sci. (Paris), 1844, 19, 353; R. B.
Bates, D. W. Gosselink, and J. A. Kaczynski, Tetrahedron
Lett., 1967, 205.
3. L. Ekman, Ann., 1859, 112; H. L. Snape and A. Broke,
Trans. Chem. Soc. (London), 1899, 77, 208.
4. S. N. Svetozarskii, E. N. Zil´berman, and A. N.
Finkel´shtein, Zh. Obshch. Khim., 1961, 31(5), 1717 [J. Gen.
Chem., 1961, 31 (Engl. Transl.)].
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4466; H. H. Strain, J. Am. Chem. Soc., 1927, 49, 1558; D. H.
Hunter and S. K. Sim, Can. J. Chem., 1972, 50, 669.
6. D. Lucet, Le Gall Thierry, and C. Mioskowski, Angew.
Chem., Int. Ed., 1998, 37, 2580.
2,4,5ꢀTriphenylimidazole (4а) was synthesized from 1a (1 g,
3 mmol) and ButOK (0.3 g, 2.6 mmol) on refluxing for 2 h in
anhydrous DMSO (20 mL). The yield was 1 g (100%), m.p.
270 °С. 1H NMR (300.13 MHz, DMSOꢀd6/СCl4), δ: 7.25—7.60
(m, 10 Н); 8.10 (d, 2 Н, J = 4 Hz); 12.45 (s, 1 Н). Found (%):
С, 85.80; Н, 5.42; N, 9.45. С21Н10Сl6N2. Calculated (%):
С, 85.11; Н, 5.44; N, 9.45.
2,4,5ꢀTris(4ꢀbromophenyl)imidazole (4b) was synthesized
from 1b (0.5 g, 0.9 mmol) and ButOK (0.1 g, 0.8 mmol) on
refluxing in anhydrous DMSO (14 mL) for 12 h. The yield was
7. E. J. Corey and F. N. Kuhle, Tetrahedron Lett., 1997,
38, 8631.
1
0.47 g (94%), m.p. 235 °С. H NMR (300.13 MHz, СDCl3), δ:
8. D. H. Hunter and S. K. Sim, J. Am. Chem. Soc., 1969,
91, 6202.
9. A. T. Nielsen, R. L. Atkins, D. W. Moore, R. Scott,
D. Mallory, and J. M. LaBerge, J. Org. Chem., 1973, 38, 3288.
10. K. Saigo, N. Kubota, S. Takebayashi, and M. Hasegawa,
Bull. Chem. Soc. Jpn., 1986, 59, 931.
4.85—5.00 (br.s, 2 Н); 5.35—5.50 (br.s, 1 Н); 7.25—7.40
(m, 10 Н); 7.42—7.55 (m, 3 Н); 7.95 (d, 2 Н, J = 9 Hz).
Found (%): С, 47.28; Н, 2.43; N, 5.20. С21Н13Br3N2. Calcuꢀ
lated (%): С, 47.32; Н, 2.46; N, 5.26.
2,4,5ꢀTris(4ꢀmethoxyphenyl)imidazole (4c) was synthesized
from 1c (0.5 g, 1.3 mmol) and ButOK (0.2 g, 1.8 mmol) on
refluxing in anhydrous DMSO (10 mL) for 4 days. The yield was
11. V. R. Sandel, S. V. McKinley, and H. H. Freedman, J. Am.
Chem. Soc., 1968, 90, 495.
1
0.2 g (40%), m.p. 215 °С. H NMR (399.95 MHz, СDCl3), δ:
12. J. Nicholson and R. Porets, Can. J. Chem., 1965, 43, 3067.
13. M. L. Larter, M. Phillips, F. Ortega, G. Aguirre,
R. Somanathan, and P. J. Walsh, Tetrahedron Lett., 1998,
39, 4785.
3.80 (s, 3 Н); 6.80—6.90 (m, 6 Н); 7.39—7.43 (d, 4 Н, J =
10 Hz); 7.78—7.82 (d, 2 Н, J = 10 Hz). Found (%): С, 74.51;
Н, 5.70; N, 7.16. С24Н22N2O3. Calculated (%): С, 74.59;
Н, 5.74; N, 7.25.
14. A. Kamal, A. Ahmad, and A. A. Qureshi, Tetrahedron Lett.,
1963, 19, 869.
2,4,5ꢀTris(2ꢀthienyl)imidazole (4d) was synthesized from 1d
(1 g, 3.2 mmol) and ButOK (0.3 g, 2.6 mmol) on refluxing in
anhydrous DMSO (10 mL) for 2 days. The yield was 0.6 g (60%),
m.p. 270—272 °С. 1H NMR (300.13 MHz, DMSOꢀd6/СCl4), δ:
7.10 (m, 3 Н); 7.30 (d, 2 Н, J = 4 Hz); 7.55 (m, 3 Н); 7.75
(d, 1 Н, J = 4 Hz); 13.20 (br.s, 1 Н). Found (%): С, 57.28;
Received May 24, 2002;
in revised form November 12, 2002