Preparation of 2,4,5-triarylimidazol-4-ols and their stereoselective rearrangement by 1,5-phenyl migration

Article abstract of DOI:10.1002/jhet.385

(Chemical Equation Presented) Lophine hydroperoxides underwent base-triggered 1,5-phenyl migration in DMSO to afford imidazolones in high yields, instead of amidines with chemiluminescence (CL). The corresponding imidazolols were believed to intermediates

Full text of DOI:10.1002/jhet.385

932
Preparation of 2,4,5-Triarylimidazol-4-ols and Their
Stereoselective Rearrangement by 1,5-Phenyl Migration
Vol 47
Gonghao Lu,a* Akira Katoh,b Zhiqiang Zhang,c Zhizhi Hu,c Peng Lei,c
and Masaru Kimurac
aOrganic Nanotube Team (ONT), Nanoarchitectonics Research Center (NARC), National Institute
of Advanced Industrial Science and Technology (AIST), Tsukuba Central 5-2, 1-1-1 Higashi,
Tsukuba, Ibaraki 305-8565, Japan
bDepartment of Materials and Life Science, Faculty of Science and Technology, Seikei University,
3-3-1 Kichijoji-kitamachi Musashinno, Tokyo 180-8633, Japan
cDepartment of Applied Chemistry, University of Science and Technology Liaoning,
Anshan 114044, People’s Republic of China
*E-mail: ghlu-ro@aist.go.jp
Received July 1, 2009
DOI 10.1002/jhet.385
Published online 18 June 2010 in Wiley InterScience (www.interscience.wiley.com).
Lophine hydroperoxides underwent base-triggered 1,5-phenyl migration in DMSO to afford imidazo-
lones in high yields, instead of amidines with chemiluminescence (CL). The corresponding imidazolols
were believed to intermediates and they were successfully obtained by treating the peroxides with
DMSO without the base. The diminished CL was because of the reduction of the hydroperoxides with
DMSO. The imidazolols subsequently underwent smooth base-mediated rearrangement to afford imida-
zolones. Furthermore, the chiral imidazolols provided stereoselective imidazolones in high enantiomeric
excess (>92%), which supported the mechanism of an intramolecular ring for the migration.
J. Heterocyclic Chem., 47, 932 (2010).
INTRODUCTION
exclusive 1,5-phenyl migration in DMSO to afford imi-
dazolones 4 in high yields via imidazolols (5) as inter-
mediates (Scheme 2) [6]. Further investigation showed
that these imidazolols 5 could be easily obtained under
milder conditions, when treated with DMSO without the
trigger base [6b]. In addition, these imidazolols 5 sub-
sequently underwent base-mediated rearrangement to
afford imidazolones in high yields.
The chemiluminescent reactions of lophine hydroper-
oxides (1) have attracted considerable attention for
many decades [1,2]. Many studies have been reported
[3] and these studies mainly focused on the chemilumi-
nescence (CL) efficiency. The other reactions occurring
in this chemiluminescent process are still not clear.
Recently, we reported that 1 underwent three different
but simultaneous reactions upon treatment with a base
to yield the corresponding amidines (2) accompanied
with CL, imidazoles (3) with singlet oxygen, and a trace
of imidazolones (4) (Scheme 1) [4]. However, the CL of
peroxides 1 can be observed by base-triggered reactions
in typical solvents, but not in DMSO. It is well known
that a CL system like dioxetane can provide the most
efficient CL in DMSO [5]. We first believed that a polar
aprotic solvent like DMSO should enhance the CL effi-
ciency of lophine peroxides. However, the CL efficiency
of hydroperoxides 1 in was so low that it could not be
detected. The results were quite unexpected, and there-
fore, they attracted our attention. The subsequent inves-
tigation showed that hydroperoxides 1 underwent an
Scheme 1
C
V
2010 HeteroCorporation

July 2010
Preparation of 2,4,5-Triarylimidazol-4-ols and Their Stereoselective Rearrangement
by 1,5-Phenyl Migration
933
Scheme 2
RESULTS AND DISCUSSION
The reaction of the peroxides 1 proceeded smoothly
proceeded to afford imidazolols in good yields in DMSO
at room temperature (entries 1–8, Table 1). The reaction
completed within 4–6 h. Aromatic substituents containing
electron-donating as well as electron-withdrawing groups
underwent the elimination of oxygen facilely. In the case
of unstable 1c, which is difficult to isolate, [2] 5c was
consequently prepared by treating the mixture by the pho-
tooxidation of the corresponding imidazole with DMSO.
In the cases of 1g, h, the mixtures with their isomers
(10g, h) were used to afford mixtures of 5g, h with their
isomers (50g, h), as shown in Scheme 3.
On treatment with the base, the imidazolols 5 were
smoothly converted into the imidazolones 4 via phenyl
migration from C4 to C5 within 3 h in good yields in
DMSO at room temperature (Table 1). From the Wood-
ward–Hoffmann rules, the phenyl migration is recog-
nized as a thermally allowed 1,5-sigmatropic migration.
To elucidate the stereochemistry of the migration,
imidazolols 5g, h were successfully isolated from their
mixtures with their isomers 50g, h by crystallization
from 2-propanol, respectively. The chiral imidazolols
(5g and h) were isolated using a chiral HPLC column.
To determine the absolute configurations, the circular
dichroism (CD) spectra were recorded, and the calcu-
lated CD spectra were processed using Gaussian 03w
software package [6a,9]. The absolute configurations
were assigned by comparing the experimental CD spec-
tra with the calculated ones (for details, see Experimen-
tal section). When the chiral imidazolols (5g and h)
Although imidazolol has been long proposed as one
of the intermediate byproducts in the CL reaction of lo-
phine, it has not been obtained thus far because it is
unstable under basic reaction conditions [1b]. The pres-
ent research provides an easy method to obtain these
intermediates, and this should help in completely under-
standing the reactions occurring in the CL reaction of
lophine peroxides. In addition, the sigmatropic migration
of an aryl group is known for 1,2,3,4,5-pentaphenylcy-
clo-pentadienol [7], which is a p-conjugated analogue of
5; however, its stereochemistry has not yet been investi-
gated. In a previous investigation, [6a] the 1,5-phenyl
rearrangement of silyl-protected hydroperoxides was
reported. However, the stereospecificities were low
under thermal conditions and the enantiomeric excesses
(EEs) were less than 60%; these factors made it difficult
to understand the stereochemistry. In the previous study,
we first believed that the low stereospecificities resulted
from the racemization of imidazolones through a ring
Table 1
Preparation of imidazolols and imidazolones.
Entry
Reactants
Producta
Yield (%)b
1
2
1a
1b
1c
1d
1e
5a
5b
5c
5d
5e
5f
77
87
64
76
70
72
78
82
78
85
68
73
70
76
79
74
opening/closing sequence, and therefore,
a control
3
4
experiment was carried out with imidazolone; however,
it was found that it did not racemize. Therefore, we
believed that the alkoxide racemized through a ring
opening/closing sequence under strong thermal condi-
tions that lowered the stereochemical specificities. In
this study, the absence of strong thermal activation pre-
vents ring opening from occurring, as a result of which
imidazolols can serve as a good system for the study of
1,5-phenyl migration.
5
6
7
1f
1gc
1hc
5a
5b
5c
5gc
5hc
4a
4b
4c
4d
4e
4f
8
9
10
11
12
13
14
15
16
5d
5e
5f
5gc
5hc
4g
4h
Furthermore, it should be noted that many natural
compounds include imidazolol and/or imidazolone moi-
eties [8]. In this article, we report the preparation and
the stereoselective 1,5-phenyl rearrangement of imidazo-
lols. We expect that imidazolols will find numerous
applications in the synthesis of natural compounds.
a The structure of products were determined from spectral data (1H
NMR, MS, and E.A.).
b Isolated yields after column chromatography.
c Mixture with its isomer.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

934
G. Lu, A. Katoh, Z. Zhang, Z. Hu, P. Lei, and M. Kimura
Vol 47
Scheme 3
were subjected to phenyl migration under the action of
the base (Scheme 4), the corresponding imidazolones 4g
and h were exclusively obtained in >92% EE in DMSO
(Table 2). When compared with the previous study in
which silyl-protected peroxides under thermal condition
were used, the stereoselectivities were largely increased.
The reaction mechanism was confirmed to be stereose-
lective 1,5-phenyl migration via an intramolecular ring
(Scheme 5).
tive phenyl migration from C4 to C5 under the action of
a base.
EXPERIMENTAL
General procedure. All melting points were measured
using a Yanagimoto micro melting point apparatus. The IR
spectra were recorded by a JASCO FT/IR-5000 spectropho-
tometer. The UV-vis spectra were measured by a JASCO V-
530 spectro-photometer. The 1H and 13C NMR spectra were
recorded using a Varian MERCURY (FT, 300 MHz) spectrom-
eter or a Varian VXR-500 (FT, 500 MHz) spectrometer. Ele-
mental analyses were performed by a Perkin Elmer CHNS/O
In conclusion, we have demonstrated that an imidazo-
lol derivative can easily be prepared in good yield from
the corresponding peroxide. The imidazolol can be
smoothly converted to an imidazolone via a stereoselec-
Scheme 4
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2010
Preparation of 2,4,5-Triarylimidazol-4-ols and Their Stereoselective Rearrangement
by 1,5-Phenyl Migration
935
Table 2
(Mþþ1); E.A. Calcd for C21H16N2O: C, C, 80.75; H, 5.16; N,
8.97. Found: C, 80.70; H, 5.14; N, 8.96.
The analyses of the enantiomeric excess.
2-(p-Nitrophenyl)-4-hydroxy-4,5-diphenyl-4H-isoimidazole
(5b.) Pale yellow powder, mp 168–169ꢂC; IR (KBr) 1633
Productsa,b
1
(C¼¼N), 1524 (NO2), 1350 (NO2) cmꢃ1; H NMR (500 MHz,
Entry
Imidazolols
R-4
S-4
EE (%)
CDCl3) d 7.33–7.38 (m, 3H), 7,43 (dd, J ¼ 8.4, 2.0 Hz, 2H),
7.56 (t, J ¼ 8.1 Hz, 2H), 7.66 (t, J ¼ 8.1 Hz, 1H), 8.09 (d, J
¼ 9.2 Hz, 2H), 8.19 (d, J ¼ 9.2 Hz, 2H), 8.36 (d, J ¼ 8.1 Hz,
2H), 6.94 (s, 1H); MS (FAB) m/z 358 (Mþþ1); E.A. Calcd for
C21H15N3O3: C, 70.58; H, 4.23; N, 11.76. Found: C, 70.53; H,
4.30; N, 11.73%.
1
2
3
4
R-5g
S-5g
R-5h
S-5h
2
97
3
98
3
96
94
94
92
97
4
96
a Yields calculated on the base of HPLC integral quantity.
2-(p-Dimethylaminophenyl)-4-hydroxy-4,5-diphenyl-4H-iso-
imidazole (5c). Orange powder, mp 126–128ꢂC; IR (KBr)
b The conversion was estimated to be 100% because of no other peak
appearing on the 1H NMR spectra.
1603 (C¼¼N) cmꢃ1
;
1H NMR (500 MHz CDCl3) d 3.00 (s,
6H), 6.44 (d, J ¼ 7.5 Hz, 2H), 7.26–7.31 (m, 3H), 7.47 (dd, J
¼ 7.0, 7.53 Hz, 2H), 7.48–7.51 (m, 2H), 7.53 (d, J ¼ 7.53 Hz,
1H), 7.93 (d, J ¼ 7.5 Hz, 2H), 8.35 (d, J ¼ 7.0 Hz, 2H), 6.32
(br s, 1H); MS (FAB) m/z 356 (Mþþ1); E.A. Calcd for
C23H21N3O: C, 77.72; H, 5.96; N, 11.82. Found: C, 77.77; H,
5.98; N, 11.81.
Analyzer 2400. The fast atom bombardment (FAB) mass spec-
tra were recorded by a Micromass 70-SE. 2,4,5-Triarylphenyl-
1H-imidazoles were prepared by the method of Davidson et al.
[6,8a]. 4-Hydroperoxy-2,4,5-triphenyl-4H-imidazoles were pre-
pared by the method of White and Harding [2]. HPLC analy-
ses were performed on a Hitachi 655 liquid chromatography
and recorded on a Hitachi 561 recorder; Column for EE and
optical resolution was Daicel Chiralpak AD-H: 4.6 mm ꢀ 250
2-(p-Hydroxyphenyl)-4-hydroxy-4,5-diphenyl-4H-isoimida-
zole (5d). Yellow powder; mp 103–105ꢂC (dec.); IR (KBr)
3326 (OAH), 1607 (C¼¼N) cmꢃ1
;
1H NMR (500 MHz,
CDCl3) d 7.00–7.03 (m, 2H), 7.30–7.34 (m, 5H), 7.41–7.51
(m, 3H), 7.59 (d, J ¼ 7.5 Hz,2H), 8.29 (d, J ¼ 7.5 Hz, 2H).
MS (FAB) m/z 329 (MþHþ). E.A. Calcd for C21H16N2O2ꢄ1/
2H2O: C, 74.76; H, 5.08; N, 8.30. Found: C, 74.69; H, 5.02;
N, 8.81.
mm. CD spectra were recorded on
spectropolarimeter.
a JASCO J-820
Preparation of imidazolols. A solution of hydroperoxides 1
(0.2 mmol) in DMSO (5 mL) was stirred for 4–6 h at room
temperature. After the reaction, the solution was poured into
water, and the crude product 5 was obtained by filtration. The
crude product was purified by chromatography (silica, hexa-
ne:AcOEt ¼ 10 ꢁ 8:1).
2-(p-Dimethylaminophenyl)-4-hydroxy-4,5-bis(p-fluorophe-
nyl)4H-isoimidazole (5e). Orange powder; mp 138–140ꢂC
(dec.); IR (KBr) 1603 (C¼¼N) cmꢃ1
;
1H NMR (500 MHz,
CDCl3) d 3.04 (s, 6H), 6.64 (d, J ¼ 8.9 Hz, 2H), 6.97 (t, J ¼
8.8 Hz, 2H), 7.15 (t, J ¼ 9.0 Hz, 2H), 7.40 (d, J ¼ 8.8, 2H),
7.98 (d, J ¼ 8.9 Hz, 2H), 8.35 (d, J ¼ 9.0 Hz, 2H), 6.52 (br s,
1H); E.A. Calcd for C23H19F2N3O: C, 67.81; H, 4.70; N,
10.31. Found: C, 67.78; H, 4.76; N, 10.31.
2,4,5-Triphenyl-4-hydroxy-4H-isoiꢃm1idazole (5a). mp 128–
130ꢂC; IR (KBr) 1613 (C¼¼N) cm
,
1H NMR (500 MHz,
CDCl3) d 7.16–7.22 (m, 3H), 7.34 (dd, J ¼ 7.5, 5.5 Hz, 2H),
7.38 (t, J ¼ 7.5 Hz, 2H), 7.47 (t, J ¼ 7.5 Hz, 1H), 7.49 (d, J
¼ 7.5 Hz, 2H), 7.56 (t, J ¼ 7.5 Hz, 1H), 8.16 (d, J ¼ 7.5 Hz,
2H), 8.41 (d, J ¼ 7.5 Hz, 2H), 6.49 (br s, 1H); 13C NMR (300
MHz, CDCl3) d 107.66 (s), 124.9 (d), 128.3 (d), 128.6 (d),
128.7 (d), 128.8 (d), 129.8 (d), 130.2 (d), 130.6 (d), 130.9 (s),
132.5 (d), 133.0 (d), 137.6 (s), 172.5 (s), 194.3 (s); UV-vis
kmax (EtOH) 281 (log e 4.31) nm; MS (FAB) m/z 313
2-(p-Dimethylaminophenyl)-4-hydroxy-4,5-bis(p-chlorophe-
nyl)4H-isoimidazole (5f). Orange powder; mp 142–144ꢂC
(dec.); IR (KBr) 1601 (C¼¼N) cmꢃ1
;
1H NMR (500 MHz,
CDCl3) d 3.02 (s, 6H), 6.65 (d, J ¼ 8.9 Hz, 2H), 6.90 (t, J ¼
8.8 Hz, 2H), 7.12 (t, J ¼ 9.0 Hz, 2H), 7.41 (d, J ¼ 8.8, 2H),
7.86 (d, J ¼ 8.9 Hz, 2H), 8.25 (d, J ¼ 9.0 Hz, 2H), 6.49 (br s,
Scheme 5
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936
G. Lu, A. Katoh, Z. Zhang, Z. Hu, P. Lei, and M. Kimura
Vol 47
mixed solution was stirred for 3 h. Then the reaction mixture
was poured into water and the product 4 was precipitated. The
crude product was purified by chromatography (silica, hexa-
ne:AcOEt ¼ 8:1).
2,5,5-Triphenyl-1H-imidazol-4(5H)-one (4a). mp 222–
224ꢂC (lit.3 220–222ꢂC); IR (KBr) 1721 (C¼¼O), 1628 (C¼¼N),
698 (Phenyl) cmꢃ1 1H NMR (500 MHz, CDCl3) d 7.28 (t, J
;
¼ 7.0 Hz, 2H), 7.34 (t, J ¼ 7.0 Hz, 4H), 7.52 (t, J ¼ 7.5 Hz,
2H), 7.58 (t, J ¼ 7.5 Hz, 1H), 7.60 (d, J ¼ 7.0 Hz, 4H), 7.97
(d, J ¼ 7.5 Hz, 2H), 9.11 (br s, 1H); UV-vis kmax (EtOH) 255
(log e 4.07) nm; MS (FAB) m/z 313 (Mþþ1); E.A. Calcd for
C21H16N2O: C, 80.75; H, 5.16; N, 8.97. Found: C, 80.47; H,
5.06; N, 8.94%.
2-(p-Nitrophenyl)-5,5-diphenyl-1H-imidazol-4(5H)-one (4b.)
Pale yellow powder; mp 205–206ꢂC; IR (KBr) 1524 (NO2),
1350 (NO2) cmꢃ1 1H NMR (CDCl3, 300 MHz) d 7.32 (t,
;
2H), 7,43 (m, 4H), 7.65 (t, 4H), 8.08 (d, J ¼ 9.2 Hz, 2H),
8.18 (d, J ¼ 9.2 Hz, 2H), 9.40 (br s, 1H); MS (FAB) m/z 358
(Mþþ1); E.A. Calcd for C21H15N3O3: C, 66.75; H, 4.13; N,
11.12. Found: C, 66.73; H, 4.00; N, 11.13%.
2-(p-Dimethylaminophenyl)-5,5-diphenyl-1H-imidazol-4(5H)-
one (4c). Orange powder, mp 86–88ꢂC; IR (KBr) 1604 (C¼¼N)
cmꢃ1 1H NMR (500 MHz CDCl3) d 3.04 (s, 6H), 6.45 (d, J
;
¼ 7.5 Hz, 2H), 7.26–7.31 (m, 6H), 7.47–7.51 (m, 4H), 7.93
(d, J ¼ 7.5 Hz, 2H), 9.02 (br s, 1H); MS (FAB) m/z 356
(Mþþ1); E.A. Calcd for C23H21N3O: C, 77.72; H, 5.96; N,
11.82. Found: C, 77.70; H, 6.01; N, 11.80.
Figure 1. HPLC charts for the resolution.
2-(p-Hydroxyphenyl)-4,5-diphenyl-4H-imidazol-4(5H)-one
(4d). Yellow powder; mp 112–114ꢂC (dec.); IR (KBr) 3323
(OAH), 1605 (C¼¼N) cmꢃ1
;
1H NMR (500 MHz, CDCl3) d
1H); E.A. Calcd for C23H19F2N3O: C, 67.81; H, 4.70; N,
10.31. Found: C, 67.35; H, 4.66; N, 10.12.
7.05 (d, J ¼ 7.6 Hz, 2H), 7.25–7.31 (m, 6H), 7.45–7.50 (m,
4H), 7.98 (d, J ¼ 7.6 Hz, 2H), 9.02 (br s, 1H). MS (FAB) m/z
329 (MþHþ). E.A. Calcd for C21H16N2O2: C, 76.81; H, 4.91;
N, 8.53. Found: C, 76.79; H, 4.92; N, 8.51.
Mixture of 2-phenyl-4-hydroxy-4-(p-trifluoromethyl-phe-
nyl)-5-(p-fluorophenyl)-4H-isoimidazole (5g) and 2-phenyl-4-
hydroxy-4-(p-fluorophenyl)-5-(p-trifluoromethyl-phenyl)-4H-
isoimidazole (50g). Molar ratio ¼ 4:1, determined by 1H
NMR. Colorless powder; mp 136–139ꢂC; IR (KBr) 1603
2-(p-Dimethylaminophenyl)-5,5-bis(p-fluorophenyl)-1H-imi-
dazol-4(5H)-one (4e). Orange powder; mp 118–120ꢂC (dec.);
IR (KBr) 1605 (C¼¼N) cmꢃ1
;
1H NMR (500 MHz, CDCl3) d
(C¼¼N), 1325 (CF3), 1272 (CAF) cmꢃ1
; UV-vis kmax
3.06 (s, 6H), 6.67 (d, J ¼ 8.9 Hz, 2H), 6.97–7.15 (t, J ¼ 8.8,
4H), 7.57–7.71 (t, J ¼ 8.8, 4H), 7.92 (d, J ¼ 8.9 Hz, 2H),
9.12 (br s, 1H); MS (FAB) m/z 392 (Mþþ1); E.A. Calcd for
C23H19Cl2N3O: C, 65.10; H, 4.51; N, 9.90. Found: C, 65.12;
H, 4.46; N, 9.92.
(CH2Cl2) 281 (4.28) nm. MS (FAB) m/z 399 (Mþþ1); E.A.
Calcd for C22H14F4N2Oꢄ1/2H2O: C, 64.87; H, 3.71; N, 6.88;.
1
Found: C, 64.83; H, 3.75; N, 6.88%. 5g: H NMR (500 MHz,
CDCl3) d 7.18–7.28 (m, 4H), 7.38–7.44 (m, 1H), 7.55 (d, J ¼
8.5 Hz, 2H), 7.61 (d, J ¼ 8.5 Hz, 2H), 7.97 (d, J ¼ 7.5 Hz,
1
2H), 8.33 (dd, J ¼ 8.5, 5.5 Hz, 2H); 50g: H NMR (500 MHz,
CDCl3) 7.03 (t, J ¼ 8.5 Hz, 2H), 7.18–7.27 (m, 2H), 7.37–
7.44 (m, 3H), 7.78 (d, J ¼ 8.2 Hz, 2H), 7.95 (d, J ¼ 7.5 Hz,
2H), 8.46 (d, J ¼ 8.2 Hz, 2H).
Table 3
Mixture of 2-phenyl-4-hydroxy-4-(p-trifluoromethyl-phe-
nyl)-5-(p-methoxyphenyl)-4H-isoimidazole (5h) and 2-phenyl-
4-hydroxy-4-(p-methoxyphenyl)-5-(p-trifluoro-methylphenyl)-
The conditions of HPLC analysis.
Retention
time/min
Detector
1
4H-isoimidazole (50h). Molar ratio ¼ 10:1, determined by H
NMR. Pale yellow powder; mp 123–125ꢂC; IR (KBr) 1607
(C¼¼N), 1328 (CF3), 1263, 1069 (CAOAC) cmꢃ1; UV-vis
kmax (CH2Cl2) 308 (log e 4.27), 318 (4.16), 347 (4.12) nm;
MS (FAB) m/z 427 (Mþþ1); E.A. Calcd for C23H17F3N2O2:
C, 67.31; H, 4.18; N, 6.83; Found: C, 67.33; H, 4.15; N,
Effluent
wavelength (nm)
I
II
5g
5h
Hexane:2-PrOH
80:20 (V/V)a
Hexane:EtOH
90:10 (V/V)a
EtOH 100%b
EtOH 100%b
281
6.1
7.1
308
6.3
7.8
1
6.85%. 5h: H NMR (500 MHz, CDCl3) d 3.91 (s, 3H), 7.02
(d, J ¼ 9.0 Hz, 2H), 7.28 (t, J ¼ 7.0 Hz, 2H), 7.37 (t, J ¼ 7.0
Hz, 1H), 7.58 (d, J ¼ 9.2 Hz, 2H), 7.62 (d, J ¼ 9.2 Hz, 2H),
8.01 (d, J ¼ 7.0 Hz, 2H), 8.28 (d, J ¼ 9.0 Hz, 2H).
4g
4h
261
259
5.4
7.0
6.4
9.0
a Flow rate 1.0 mL/min.
b Flow rate 0.7 mL/min.
Preparation of imidazolones.. 0.5 ml of TBAF/THF (1.0
N) was added to a solution of 5 (0.1 mmol) in DMSO, and the
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DOI 10.1002/jhet

July 2010
Preparation of 2,4,5-Triarylimidazol-4-ols and Their Stereoselective Rearrangement
by 1,5-Phenyl Migration
937
Figure 2. The CD spectra (above) of 5g, h recorded in EtOH and the calculated CD spectra (below) of 5g, h using the TDDFT-B3LYP method.
Rotational strengths (R) are given in cgs (10ꢃ40 erg esu cm/Gauss).
1
(CAOAC) cmꢃ1; H NMR (500 MHz, CDCl3) d 3.77 (s, 3H),
2-(p-Dimethylaminophenyl)-5,5-bis(p-chlorophenyl)-1H-
imidazol-4(5H)-one (4f). Orange powder; mp 122–124ꢂC
6.86 (d, J ¼ 9.0 Hz, 2H), 7.48 (d, J ¼ 9.0 Hz, 2H), 7.53 (t, J
(dec.); IR (KBr) 1603 (C¼¼N) cmꢃ1
;
1H NMR (500 MHz,
¼ 7.0 Hz, 2H), 7.58 (d, J ¼ 8.3 Hz, 2H), 7.60 (t, J ¼ 7.0 Hz,
1H), 7.75 (d, J ¼ 8.3 Hz, 2H), 8.02 (d, J ¼ 7.0 Hz, 2H); UV-
vis kmax (EtOH) 214 (log e 4.33), 232 (4.41) 259 4.08) nm;
MS (FAB) m/z 411 (Mþþ1); E.A. Calcd for C23H17F3N2O2:
C, 67.31; H, 4.18; N, 6.83; Found: C, 67.40; H, 4.16; N,
6.88%
CDCl3) d 3.03 (s, 6H), 6.65 (d, J ¼ 8.2 Hz, 2H), 6.90–7.12 (t,
J ¼ 8.6 Hz, 4H), 7.61–7.86 (t, J ¼ 8.6, 4H), 7.98 (d, J ¼ 8.2
Hz, 2H), 6.09 (br s, 1H); MS (FAB) m/z 425 (Mþþ1); E.A.
Calcd for C23H19F2N3O: C, 67.81; H, 4.70; N, 10.31. Found:
C, 67.35; H, 4.66; N, 10.12.
HPLC analysis. The resolution of the racemic imidazolols
5 and the analysis of the EE were carried out using a chiral
HPLC column and a HITACHI 561 recorder, as shown in Fig-
ure 1. The conditions are summarized in Table 3.
Assignment of absolute configuration by comparison of
experimental and calculated CD spectra. To determine the
absolute configuration, the CD spectra were recorded and cal-
culated using the Gaussian 03w software package, [9] as
shown in Figures 2 and 3. A geometry optimization was per-
formed using the B3LYP functional with 6-31G* basis sets.
The absolute configurations of 5-I and 5-II in the HPLC spec-
tra were assigned as S-5 and R-5, respectively, as shown in
2-Phenyl-5-(p-fluorophenyl)-5-(p-trifluoromethylphenyl)-1H-
imidazol-4(5H)-one (4g). Colorless crystals; mp 82–88ꢂC; IR
1
(KBr) 1734 (C¼¼O), 1618 (C¼¼N), 1328 (CF3) cmꢃ1; H NMR
(500 MHz, CDCl3) d 7.04 (t, J ¼ 8.8 Hz, 2H), 7.55 (t, J ¼ 7.5
Hz, 2H), 7.57–7.64 (m, 5H), 7.75 (d, J ¼ 8.0 Hz, 2H), 7.98
(d, J ¼ 7.5 Hz, 2H), 9.19 (br s, 1H);UV-vis kmax (EtOH) 214
(log e 4.30), 231 (4.33), 259 (4.02) nm; MS (FAB) m/z 399
(Mþþ1); E.A. Calcd for C22H14F4N2O: C, 66.33; H, 3.54; N,
7.03. Found: C, 66.40; H, 3.56; N, 6.98%.
2-Phenyl-5-(p-methoxyphenyl)-5-(p-trifluoromethyl-phenyl)-
1H-imidazol-4(5H)-one (4h). Colorless crystals; mp 86–90ꢂC;
IR (KBr) 1727 (C¼¼O), 1618 (C¼¼N), 1328 (CF3), 1253, 1071
Figure 3. The CD spectra (above) of 4g, h recorded in EtOH and the calculated CD spectra (below) of 4g, h using the TDDFT-B3LYP method.
Rotational strengths (R) are given in cgs (10ꢃ40 erg esu cm/Gauss).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

938
G. Lu, A. Katoh, Z. Zhang, Z. Hu, P. Lei, and M. Kimura
Vol 47
[7] (a) Allen, C. F. H.; VanAllan, J. A. J Am Chem Soc 1943,
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Figure 2. In the same manner, the absolute configurations of
products 4-I (HPLC: first fraction) and 4-II (HPLC: second
fraction) were also assigned to R-4 and S-4, respectively, as
shown in Figure 3.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet