The chemiexcitation of the chemiluminescence of lophine peroxide anions via a partially cyclic transition state

Article abstract of DOI:10.1002/ejoc.201300976

It was shown that acyclic intermediates play a role in the chemiexcitation of the chemiluminescence (CL) of lophine peroxides in addition to the dioxetane intermediates. Because the CL efficiencies of position-isomers (R)-9 and (R)-10, which theoretically give the common dioxetane intermediate, were different, the different CL efficiencies are attributable to the CL mechanism involving a partially cyclic transition structure at the chemiexcitation step. The study of isomeric 2-phenyl-4-p-X-phenyl-5-p-Y-phenyl-4-silylated peroxy-isoimidazals [(R)-9: X = CF₃, Y = F and (R)-10: X = F, Y = CF₃] confirmed the existence of lophine peroxide anion intermediates in the chemiluminescence of lophine peroxides in addition to the dioxetane intermediates. Copyright

Full text of DOI:10.1002/ejoc.201300976

FULL PAPER
DOI: 10.1002/ejoc.201300976
The Chemiexcitation of the Chemiluminescence of Lophine Peroxide Anions via
a Partially Cyclic Transition State
Gonghao Lu,[a] Jun Wada,[b] Takashi Kimoto,[b] Hiroshi Iga,[b] Hideki Nishigawa,[b]
Masaru Kimura,*[a,b] and Zhizhi Hu[a]
Keywords: Luminescence / Charge transfer / Peroxides / Anions / Reaction mechanisms / Reactive intermediates
It was shown that acyclic intermediates play a role in the
chemiexcitation of the chemiluminescence (CL) of lophine
peroxides in addition to the dioxetane intermediates. Be-
cause the CL efficiencies of position-isomers (R)-9 and (R)-
10, which theoretically give the common dioxetane interme-
diate, were different, the different CL efficiencies are attrib-
utable to the CL mechanism involving a partially cyclic tran-
sition structure at the chemiexcitation step.
Introduction
In many studies of bioluminescence (BL) and chemilumi- mediate species.[1c] The proposed transition structure was
nescence (CL), four-membered cyclic peroxide intermedi- based on the observations of anion emission in the CL of
ates such as dioxetanes and dioxetanones are believed to be the 9-acridinepercarboxylate anion.[1c] Furthermore, White
key intermediates in the chemiexcitation steps.[1] It has been suggested that the study of isomeric lophine peroxides such
established that in the CL of lophine peroxide 1, a cyclic as 4-hydroperoxy-2-phenyl-4-(4-X-phenyl)-5-(4-Y-phenyl)-
dioxetane intermediate 2 is involved in the chemiexcitation 4H-isoimidazoles (7, X = CF3, Y = F and 8, X = F, Y =
step (Scheme 1).[2–4] In studies on the related CL of 9-acrid- CF3) could confirm the existence of partially cyclic transi-
inecarboxylate, however, White et al. proposed that a true tion states in the chemiexcitation step. This is because these
dioxeatanone is not an intermediate, but instead the “open positional isomers can give distinguishable “open form”
form” dioxetane transition state 4 (Scheme 1) is a key inter- transition state structures in the course of CL reactions,
Scheme 1. CL reaction of lophine peroxide 1 involving dioxetane intermediate 2 and amidine anion 3. “Open form” partially cyclic
transition structure 4 for CL of 9-acridinecarboxylate.
[a] School of Chemical Engineering, University of Science and
which should display different CL efficiency. Instead, if the
CL mechanism proceeds in accord with the dioxetane inter-
mediate, compounds 7 and 8 should share a common inter-
mediate with identical CL efficiencies (Scheme 2). In this
study, we investigated White’s proposal with the intent of
gaining a fuller, more detailed understanding of the CL
mechanism.
Technology Liaoning,
185 Qianshan Zhong Road, Anshan, Liaoning, China
E-mail: masarukimura1226@yahoo.co.jp
http://www.ustl.edu.cn/
[b] Chemistry and Biology, Graduate School of Natural Science
and Technology, Okayama University,
3-1-1 Tsushima-Naka, Okayama 700-8530, Japan
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300976.
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Chemiluminescence of Lophine Peroxide Anions
Results and Discussion
We began by synthesizing isomeric compounds 7 and 8
(Scheme 2). First, 5-(4-fluorophenyl)-2-phenyl-4-[4-(tri-
fluoromethyl)phenyl]imidazole (6) was prepared from 4-
fluoro-4Ј-(trifluoromethyl)benzil (5)[5] and benzaldehyde.[6]
A mixture of isomeric peroxides 7 and 8 was then obtained
from imidazole 6 and singlet oxygen (Scheme 2). Attempts
to separate and isolate peroxides 7 and 8 by fractional
crystallization and column chromatography were unsuc-
cessful, in part due to the instability of the peroxy group.
We then protected the reactive functionality with tert-butyl-
dimethylsilylchloride, introducing a protecting group that
Figure 1. HPLC chart for the isolation of (R)-9 and (R)-10.
The CL reaction of the silylated peroxides was initiated
could be readily removed to initiate CL.[6] A mixture of 4- by the addition of a 0.1 m solution of tetrabutylammonium
tert-butyldimethylsilylperoxy-2-phenyl-4-(4-X-phenyl)-5-(4-
Y-phenyl)-4H-isoimidazoles (9, X = CF3, Y = F and 10, X sities were measured by using a photodiode array Photonic
= F, Y = CF3) were obtained as shown in Scheme 3. Multi-channel Analyzer (Hamamatsu Photonics Model C-
fluoride (TBAF) in tetrahydrofuran (THF). The CL inten-
The ratio of 9 and 10 was determined by 1H NMR analy- 249). The results of the reaction are summarized in Table 1.
sis to be 4:1. Racemic 9 was isolated by fractional In acetone, the decomposed compounds of the correspond-
recrystallization with 2-propanol; however, the position-iso- ing amidines were obtained as byproducts.[2b] In CHCl3 and
mer 10 was not isolated by this method. We were able to acetone, (R)-9 and (R)-10 gave the same amount of the
separate a mixture of 9 and 10 into three groups of peaks common amidine 11, respectively (Table 2). The ΦCL of the
by using HPLC with a Daicel Chiralpak AD-H column de- resulting mixture of silylated peroxides (9/10, 4:1) was mea-
veloped with hexane/ethanol (9:1) (Figure 1). The first frac- sured in four solvents [CH2Cl2, CHCl3, N,N-dimethylform-
tion (F-I) was composed of a mixture of (S)-9 and (S)-10, amide (DMF), and acetone], and the order of the efficien-
the second fraction (F-II) was optically active (R)-9, and cies with respect to the solvent was: CH2Cl2 [ΦCL(ϫ10–6)
the third fraction (F-III) was optically active (R)-10. There- = 13.8Ϯ1.0] Ͼ CHCl3 (10.9Ϯ0.3) Ͼ acetone (4.12Ϯ0.2)
fore, only optically active (R)-10 was available as a represen- Ͼ DMF (4.00Ϯ0.2). The efficiency of CL was highest in
tative sample of 10. The stereochemistry of (R)-9, (S)-9, CH2Cl2, but the experimental error was also higher. The
(R)-10, and (S)-10 was assigned by comparison of their CD efficiency was lowest in CH3CN. Solvents CHCl3 and acet-
spectra with their calculated spectra.[6]
one were selected as representative solvents for subsequent
Scheme 2. Introduction of the common intermediate from position-isomeric peroxides 7 and 8.
Scheme 3. Synthetic scheme for isomeric peroxides.
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M. Kimura et al.
FULL PAPER
CL experiments upon consideration of the CL efficiency, suggests that the common DO12– plays a main role in the
the dielectric constant of the solvent, and the experimental chemiexcitation. The CL spectra of (R)-9 and (R)-10 in
error (S.D).
acetone and CHCl3 are shown in Figure 2. Furthermore, to
investigate the relationship between the efficiencies and the
reaction rates, which reflects the height of the barrier on
ground state surface, these peroxides were subjected to rate
determination. Both in acetone and in CHCl3 at 25 °C, the
Table 1. Products of the CL reaction of (R)-9 or (R)-10.[a]
Peroxide Solvent
Conversion
[%]
6
11
Byproduct
[%][b]
[%]
[%]
CL decay rates for (R)-9 (kacetone = 0.165 s–1, kCHCl3
0.0312 s–1) were slower than those for (R)-10 (kacetone
=
=
(R)-9
CHCl3
acetone
CHCl3
acetone
100
100
100
100
17
0
14
0
83
93
86
90
0
7
0
(R)-9
(R)-10
(R)-10
0.226 s–1, kCHCl3 = 0.0335 s–1). In acetone, the activation of
the free energy level for (R)-9 in the partially cyclic transi-
tion state (TS-pc) seems to be higher than that for (R)-10.
The isomer (R)-9 seems to have an advantage over (R)-10
in CL efficiency. In CHCl3, (R)-9 and (R)-10 seem to mainly
pass a common intermediate because the reaction rates are
similar and the CL efficiencies are the same within error.
10
[a] Trigger base = TBAF (0.1 m) in THF. [b] Decomposed products
of amidine 11.
Table 2. CL efficiencies and CL peaks (λmax, nm) of racemic 9,
optical active (R)-9 and optical active(R)-10.[a]
Peroxide Solvent
Concentration
λmax
[nm]
ΦCL
SD
[m]
(ϫ10–6)
9
CHCl3
CHCl3
acetone
acetone
CHCl3
acetone
1ϫ10–2
1ϫ10–2
1ϫ10–2
1ϫ10–2
1ϫ10–2
1ϫ10–2
564
564
564
564
557
557
10.3
10.6
4.35
4.35
10.2
3.07
0.2
0.5
0.4
0.2
0.5
0.5
(R)-9
9
(R)-9
(R)-10
(R)-10
[a] Trigger base = TBAF (0.1 m) in THF.
In acetone, (R)-9 and (R)-10 provided clearly different
ΦCL(ϫ10–6) values of 4.35Ϯ0.4 and 3.07Ϯ0.5, along with
the amidine 11 at 93 and 90% yields, respectively, ac-
companied by the corresponding dibenzoylamine and ben-
zoylamine as byproducts.[6,7] If the formation of dioxetane
12– (DO) as the common intermediate is inevitable in the
CL reaction of lophine peroxides, the CL efficiencies should
be the same for both position isomers (R)-9 and (R)-10.
The different CL efficiencies are attributed to a mechanism
involving different partially cyclic transition states (TS-pc 9
and TS-pc 10).
Because the CL reactions of (R)-9 and (R)-10 afforded
the common excited amidine anion 11–* with different effi-
ciencies, it is unlikely that only common DO12– is involved
in the excitation step.[1c] In CHCl3, the CL efficiencies [ΦCL
(ϫ10–6)] for (R)-9 and (R)-10 were 10.6Ϯ0.5 and
Figure 2. CL spectra for the CL reaction of (R)-9 and (R)-10 with
TBAF/THF in acetone (bottom) and in chloroform (top).
These findings are rationalized by considering that two
10.15Ϯ0.2, and the yields of common amidine 11 were 83 intermediates, cyclic DO12– and acyclic peroxide anions
and 86%, respectively. In CHCl3, the CL efficiencies of (R)- (AC9– and AC10–), are involved in chemiexcitation
9 and (R)-10 were equal within experimental error, which (Scheme 4). Even in the case of the different CL efficiencies
Scheme 4. The chemiluminescence mechanism of lophine peroxides.
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Chemiluminescence of Lophine Peroxide Anions
in acetone, a contribution of cyclic DO12– to chemiexcit- of the imidazole moiety. Calculated energies were obtained
ation cannot be discounted. It is possible that the contri- under the condition that bond formation between C5···O7
bution of TS-pc is larger in acetone than in CHCl3.
(R), and bond elongation at bonds O6···O7 (r1), C4···C5
To investigate the heat of formation and the net-charge (r2), and C4–O6 (r3) take place simultaneously. The opti-
of intermediates AC (9– and 10–), TS-pc, DO, Po (11– at the mized geometries of ST, TS-pc, DO, P0 and P* were ob-
ground state), and P* (11– at the excited state) on the CL tained. The relative energies and net charges for the starting
reaction surface, B3LYP energy-gradient calculations were state (ST), the partially cyclic transition state (TS-pc), the
performed. We employed a qualitative procedure by using cyclic state (DO), product at the ground state P0 and at the
the GAUSSIAN 03w software package.[8] First, the confor- excited state P* for the reaction are given in Table 3. Even
mation diagram was examined to find the most stable start- at the starting stage of the reaction, the sizeable negative
ing anion against the torsion angles of N(3)–C(4)–O(6)– charge on the peroxide oxygen fed into the imidazole ac-
O(7) (Figure 3). As shown in Scheme 4, the reaction starts ceptor moiety. From computational results, r3 and R at TS-
with the approach of the peroxide oxygen atom to the C=N pc are different, and the molecular structure at TS-pc re-
sembles that at ST. During the process from the TS-pc to
the product ground state P0, the computational results sup-
port the existence of a common cyclic intermediate (DO)
because the optimized DO from 9– and that from 10– are
equivalent (Table 3). The energy of P* is lower than those
of peroxide anions (AC’s) and DO, and the energies of the
peroxide anions 9– and 10– are sufficient as a new CL key
intermediate.
Figure 3. The model of AC for calculation of energies of heat of
We would like to propose that an acyclic mechanism such
formation and net charges for ST, TS-pc DO, and the final product
as that shown in Scheme 4 is an important, although not
exclusive, pathway in the CL process. Step 1 leads to the
amidine in the ground state (Po) and in the excited state (P*);
C5···O7 (R), O6–O7 (r1), C4–C5 (r2), C4–O6 (r3).
Table 3. Heat of formation and net charge of peroxide anions 9–, 10–, 11– and 12–; r1, r2 and r3 against C5···O7 distance (R).
Solvent
CHCl3
Anion
State
SCF energy
[A.U.]
E – EP0
[kcal]
Bond length [Å]
R
r1
r2
r3
9–
ST
TS-pc
ST
TS-pc
P0
P*
DO
–1505.48849685
–1505.46996343
–1505.48628965
–1505.46815947
–1505.65733589
–1505.61936641
–1505.50617927
105.95
117.58
107.33
118.71
0
23.83
94.85
3.17652
2.14355
3.18961
2.25640
1.23948
1.28221
1.47802
1.46419
1.48761
1.45918
1.48723
1.55860
1.56456
1.55403
1.56399
1.41558
1.38605
1.42152
1.38405
1.24297
1.24376
1.47610
10–
11–
12–
1.49663
1.61145
9–
ST
TS-pc
ST
TS-pc
P0
P*
DO
–1505.50417728
–1505.48760860
–1505.50192519
–1505.48560385
–1505.67181936
–1505.63185254
–1505.52030062
105.19
115.59
106.61
116.85
0
25.08
95.08
3.18052
2.16587
3.20310
2.21114
1.24159
1.24400
1.47873
1.46695
1.48987
1.46392
1.48855
1.55918
1.56799
1.55547
1.56599
1.41598
1.38737
1.42057
1.38571
1.24441
1.28421
1.47893
10–
11–
12–
Acetone
1.49651
C5
1.60856
O6
Solvent Anion
Mulliken atomic charges
C4
N1
C2
N3
O7
9–
–0.583095
–0.610816
–0.579488
–0.577311
–0.583997
–0.594384
–0.625929
0.421028
–0.516062
–0.567115
–0.512703
–0.538878
–0.596793
–0.576802
–0.625732
0.337594
0.395904
0.333007
0.399308
0.521641
0.510166
0.355970
0.277928
0.316305
0.274463
0.302366
0.531620
0.496216
0.360902
–0.385789
–0.409324
–0.379863
–0.402055
–0.584891
–0.541564
–0.374355
–0.545499
–0.518755
–0.538069
–0.534178
–0.575869
–0.643912
–0.372559
0.414572
0.419580
0.413428
0.441599
0.443946
0.409595
10–
CHCl3
11–
12–
9–
–0.581054
–0.588940
–0.575454
–0.58313
–0.582400
–0.595061
–0.632384
0.419614
0.409067
0.417854
0.411248
0.429369
0.436146
0.401340
–0.526134
–0.571220
–0.522323
–0.55505
–0.594009
–0.574950
–0.633859
0.339615
0.399396
0.336858
0.399352
0.514868
0.503916
0.355522
0.276079
0.289835
0.272174
0.296101
0.524600
0.490197
0.360700
–0.397885
–0.396217
–0.393616
–0.39914
–0.595249
–0.551354
–0.378245
–0.562481
–0.512671
–0.556919
–0.52342
–0.588262
–0.654826
–0.377637
10–
Acetone
11–
12–
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M. Kimura et al.
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Infrared (IR) spectra were recorded with a JASCO FT/IR-5000
spectrometer. The UV/Vis spectra were measured with a HITACHI
UV-288 spectrophotometer. The H NMR spectra (chemical shifts
referenced to residual CHCl3 in CDCl3 at 7.26) were recorded with
a Varian VXR-300 spectrometer operating at 300 MHz, or with a
Varian VXR-500 spectrometer operating at 500 MHz. The elemen-
tal analysis was performed with a Yanagimoto CHN recorder MI-
2 type. Benzil was purchased from the Aldrich Chemical Company
Inc. Lophine peroxide 1 was prepared by a modified method de-
scribed by White et al.[2b] 4-(3-Hydroxyphenyl)-4-methoxyspiro[1,2-
TS-pc from which the excitation step (Step 2) to P* and the
conversion (Step 3) into DO also occurs. Regardless of the
nature of the intermediate, the reaction proceeds further to
give product P* and P0. The involvement of the acyclic
mechanism in solvent acetone is consistent with the dif-
ferent observed CL efficiencies between 9– and 10–. Since
the lophine peroxide system consists of a π-conjugated
imidazole (charge acceptor) and a part of the peroxide
anion (charge donor), the charge transfer (CT) from the
1
donor to the acceptor may stabilize the energy at the transi- dioxetane-3,2Ј-adamantane] was prepared by a modified method
described by Blonstain.[9]
tion state.
Because the C=N bond in 10– has a conjugated moiety
Measurement of Chemiluminescence (CL) Efficiency: The CL was
with more electron-withdrawing substituent CF3, the acti-
vation energy for 10– is lower than that of 9–, which has the PHOTONICS), which recorded integrated light yield in terms of
measured by using a photodiode array (PMA, HAMAMATSU
the number of photons. First, the CL emissions of silylated perox-
ides 9, (R)-9, and (R)-10 (1ϫ10–2 m) in CH2Cl2, CHCl3, acetone,
or DMF (1 mL) were counted by PMA by initiation with 0.2 mL
of a THF solution of tetrabutylammonium fluoride (TBAF; 0.1 m)
at 25 °C. Second, the CL emission of 4-(3-hydroxyphenyl)-4-meth-
oxyspiro[1,2-dioxetane-3,2Ј-adamantane] (1ϫ10–5 m) in DMSO
(1 mL) was measured by PMA by initiation with a solution of
TBAF in DMSO (3 m, 0.2 mL) at 25 °C.[10] The CL efficiency was
estimated by comparison with that of dioxtane as a standard (ΦCL
= 0.22).[11] The error (SD) is the deviation from the average of three
C=N conjugated with the substituent F. The C=N bond
possessing F in 9– is likely to be a higher TS-pc than that
of 10– possessing CF3. This substituent effect is parallel to
that of CL reaction of 2-(p-dimethylaminophenyl)-4,5-di(p-
X-phenyl)-1,4-hydroperoxy-4H-isoimidzole, for which in
the case of X = F the efficiency is higher than that of X =
CF3.[4] A TS-pc with higher energy is favorable to transfer
to the surface of P* (Figure 4). These findings support the
presence of a new acyclic peroxide anion intermediate at
chemiexcitation in addition to the dioxetane intermedi- measurements.
ate.[1d,9]
Measurement of CL Decay Rate: The CL decay rates were mea-
sured with a CLD-300 (TOHOKU DENSHI). After an initial rise
of intensity (I), CL exponential (ln) decay followed. The CL decay
rates followed first-order kinetics. A plot of lnI, measured at 15 °C,
against time (in seconds) gave a straight line and the rates were
measured by the least square method (see the Supporting Infor-
mation).
Calculation of Energy, Net Charge, and Translation State: The cal-
culations were carried out by using GAUSSIAN 03w, with the
B3LYP method, and molecular structures were visualized with
GaussView.
The most stable conformations of the peroxide anions are shown
in Figure 5. It can clearly be seen that the peroxidic anions are
positioned between the two phenyl groups. The negative charge is
delocalized over the π-conjugated imidazole ring with two phenyl
groups even at the most stable conformation. The heat of formation
of anion 9 is higher than that of anion 10 (Table 3).
Figure 4. Potential energy profile for CL of peroxides 9 and 10 in
acetone.
Conclusions
Acyclic intermediates play a role in the chemiexcitation
of the chemiluminescence (CL) of lophine peroxides in ad-
dition to the dioxetane intermediates. Because the CL effi-
ciencies of position-isomers (R)-9 and (R)-10, which theore-
tically give the common dioxetane intermediate, were dif-
ferent, the different CL efficiencies are attributable to the
CL mechanism involving a partially cyclic transition struc-
ture at the chemiexcitation step.
Figure 5. The most stable conformations of the peroxide anions
were calculated by using the B3LYP functional with 6-31G* basis
sets.
Experimental Section
Materials and Methods: Melting points were determined with a
Assignment of Absolute Configuration: The isolated fractions were
determined as a mixture of 9 and 10 (F-I), 9 (F-II), and 10 (F-III)
by 1H NMR analysis. To determine the absolute configuration, the
Yanagimoto micro melting-point apparatus and are uncorrected.
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Chemiluminescence of Lophine Peroxide Anions
Figure 6. The CD spectra of F-I, F-II, and F-III recorded in ethanol and the calculated CD spectra of 9 and 10 by using the TDDFT-
B3LYP method. Rotational strengths (R) are given in cgs (10–40 erg esu cm/G).
CD spectra of F-I, F-II, and F-III were recorded, and the calcula-
tion of CD spectra were carried out based on the GAUSSIAN 03w
software package, as show in Figure 6. A geometry optimization
was performed by using the B3LYP functional with 6-31G* basis
sets. The absolute configurations were assigned by comparison of
the CD spectra with the calculated CD spectra. The absolute con-
figurations of F-I, F-II, and F-III were assigned as a mixture of
(S)-9 and (S)-10, (R)-9, and (R)-10, respectively, as illustrated in
Figure 6.
was added dropwise to a Grignard reagent prepared from 4-
fluorobenzyl chloride (5.23 g, 36.3 mmol) and Mg (895 mg,
36.8 mmol). The reaction mixture was stirred, first at room tem-
perature and then heated to reflux for 3 h, and decomposed with
ice and hydrochloric acid. The product was extracted with diethyl
ether, washed with water, and dried with MgSO4. After the removal
of the solvent, recrystallization from CH2Cl2/hexane gave 4-(tri-
fluoromethyl)phenyl 4-fluorobenzyl ketone (7.72 g, 82%). SeO2
(3.71 g, 33.0 mmol) was dissolved in glacial acetic acid, and 4-(tri-
fluoromethyl)phenyl 4-fluorobenzyl ketone (9.31 g, 33.0 mmol) was
added to the hot solution and the mixture was heated to reflux for
3 h. The Se precipitate was filtered off, the solvent was removed
under reduced pressure, and the residue was dissolved in ethyl acet-
ate and washed with aqueous NaHCO3, water and dried with
MgSO4. After the removal of the solvent, 5 (9.24 g, 31.2 mmol,
94%) was obtained by recrystallization (CH2Cl2/hexane) as yellow
4-Fluoro-4Ј-(trifluoromethyl)benzil (5)
crystals; m.p. 111–113 °C. IR (KBr): ν = 1665 (C=O), 1330
˜
1
(CF3) cm–1. H NMR (300 MHz, CDCl3): δ = 7.14 (t, J = 8.4 Hz,
2 H), 7.70 (d, J = 9.2 Hz, 2 H), 7.96 (m, 2 H), 7.96 (d, J = 9.2 Hz,
2 H) ppm. C15H8F4O2: C, 60.82; H, 2.72; found C, 61.20; H, 1.73.
5-(4-Fluorophenyl)-2-phenyl-4-[4-(trifluoromethyl)phenyl]imidazole
(6): Prepared by the method used by Davidson et al.[12] A solution
of benzaldehyde (309 mg, 2.91 mmol), 4-fluoro-4Ј-(trifluorometh-
yl)benzil (5; 595 mg, 2.01 mmol), and ammonium acetate (2.64 g,
34.3 mmol) in acetic acid was heated to reflux under N2 (the pro-
The procedure developed by Lalezari et al. was used.[5] (Trifluoro-
methyl)benzonitrile (5.70 g, 36.3 mmol) in anhydrous diethyl ether
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M. Kimura et al.
FULL PAPER
gress of the reaction was followed by TLC). Upon completion of
the reaction, the cooled solution was poured into ice-cooled water
to precipitate the product. The crude product was recrystallized-
from ethanol to give 6 (457 mg, 59%) as transparent crystals need-
their 1H NMR spectra. 1H NMR (300 MHz, CDCl3) spectra of
(R)-9 was same as that of 9.
1
Compound (R)-9: M.p. 69–72 °C. H NMR (300 MHz, CDCl3): δ
= 0.155 (s, 3 H), 0.213 (s, 3 H), 0.843 (s, 9 H), 7.14 (t, J = 9.0 Hz,
2 H), 7.42 (d, J = 8.4 Hz, 2 H), 7.51–7.61 (m, 5 H), 8.22 (dd, J =
9.0, 5.4 Hz, 2 H), 8.45 (d, J = 6.6 Hz, 2 H).
les; m.p. 252–254 °C. IR (KBr): ν = 1622 (C=N), 1520 (C=C), 1323
˜
(CF3), 1228 (C–F) cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.03
and 7.11 (t, J = 8.7 Hz, 2 H), 7.39–7.53 (m, 5 H), 7.58 (d, J =
8.7 Hz, 2 H), 7.69 (d, J = 8.4 Hz, 2 H), 7.93 (dd, J = 8.4 Hz, 1.2 Hz,
2 H), 9.37 and 9.46 (s, 1 H, NH) ppm. UV/Vis (EtOH): λmax
[log(ε/m–1 cm–1)] = 303 (4.39), 227 (4.30), 208 (4.31) nm. MS (FAB):
m/z = 383 [M+ + 1]. HRMS (FAB): calcd. for C22H15F4N2
383.1171; found 383.1128. C22H14F4N2·1/2CH3CH2OH: C, 68.14;
H, 4.23; N, 6.91; found C, 68.07; H, 3.74; N, 6.92.
1
Compound (R)-10: M.p. 42–45 °C. H NMR (300 MHz, CDCl3): δ
= 0.017 (s, 3 H), 0.072 (s, 3 H), 0.843 (s, 9 H), 6.98 (t, J = 8.7 Hz,
2 H), 7.51–7.61 (m, 5 H), 7.72 (d, J = 8.4 Hz, 2 H), 8.32 (d, J =
8.4 Hz, 2 H), 8.46 (d, J = 6.6 Hz, 2 H) ppm. C28H28F4N2O2Si: C,
63.62; H, 5.34; N, 5.30; found C, 63.58; H, 5.29; N, 5.43.
N-(4-Fluorobenzyl)-NЈ-[4-(trifluoromethyl)benzyl]benzamidine (11):
A solution of peroxides 7/8 (107 mg) in acetone (1 mL) was added
to TBAF/THF solution. When chemiluminescence was finished,
the solution was neutralized with acetic acid. Components in the
solution were isolated by chromatography (silica; hexane/EtOAc,
3:1), from which amidine 11 was obtained (33 mg) as a colorless
5-(4-Fluorophenyl)-4-hydroperoxy-2-phenyl-4-[4-(trifluoromethyl)-
phenyl]-4H-isoimidazole (7) and 4-(4-Fluorophenyl)-4-hydroperoxy-
2-phenyl-5-[4-(trifluoromethyl)phenyl]-4H-isoimidazole (8): Pre-
pared by the method used by White et al.[2b] A mixed solution of
6 (150 mg, 0.39 mmol) in CH2Cl2 and a catalytic amount of meth-
ylene blue in methanol (1 mL) was cooled to –78 °C and irradiated
with a sunlamp discharging O2 gas through a UV-cutoff filter for
1.5 h. The reaction was followed by TLC. Upon completion of the
reaction, the sensitizer was removed by syringe column chromatog-
raphy (silica, CH2Cl2). The mixture was concentrated under re-
duced pressure maintaining a temperature below 15 °C. When the
CH2Cl2 was removed, one milliliter of alcohol was added to the
solvent to give the product as a powder, which was filtered and
washed with alcohol. A regioisomeric mixture of compounds 7 and
8 (154 mg, 95%) was obtained as a colorless powder (7/8 = 4:1
powder; m.p. 121–128 °C. IR (KBr): ν = 1707 (C=O), 1328 (CF ),
˜
3
1238 (C-F in the phenyl group) cm–1. 1H NMR (500 MHz, CDCl3):
δ = 7.27 (t, J = 8.5 Hz, 2 H), 7.51 (t, J = 8.0 Hz, 2 H), 7.61 (t, J =
8.0 Hz, 1 H), 7.86 (d, J = 8.0 Hz, 2 H), 7.97 (d, J = 7.0 Hz, 2 H),
8.09 (br. t, J = 1.0 Hz, 2 H), 8.22 (d, J = 8.0 Hz, 2 H), 10.71 (br. s,
1 H) ppm. UV/Vis (EtOH): λmax [log(ε/m–1 cm–1)] = 247 (4.38) nm.
MS (FAB): m/z = 415 [M+ + 1].
Supporting Information (see footnote on the first page of this arti-
cle): 1H NMR spectra of 6–10, and the decay rates of CL reactions
of (R)-9 and (R)-10.
based on 1H NMR analysis); m.p. 135–137 °C. IR (KBr): ν = 1603
˜
(C=N), 1325 (CF3), 1272 (C–F) cm–1
.
1H NMR (500 MHz,
CDCl3): δ = 7.18–7.27 (m, 4 H), 7.37–7.44 (m, 1 H), 7.55 (d, J = Acknowledgments
8.5 Hz, 2 H), 7.60 (d, J = 8.5 Hz, 2 H), 7.95 (d, J = 7.5 Hz, 2 H),
8.35 (dd, J = 8.5, 5.5 Hz, 2 H) ppm. UV/Vis (CH2Cl2): λmax
[log(ε/m–1 cm–1)] = 233 (4.22), 289 (4.29) nm. MS (FAB): m/z = 415
[M+ + 1]. HRMS (FAB): calcd. for C22H15F4N2O2 415.1070; found
415.1135; C22H14F4N2O2·1/2H2O: C, 62.41; H, 3.57; N, 6.62; found
C, 62.63; H, 3.45; N, 6.32.
The authors would like to thank the SC-NMR Laboratory of
Okayama University for performing the NMR spectral measure-
ments and Professor Masaaki Kojima (Okayama University) for
performing the CD measurements. Financial assistance provided
by the Ministry of Education, Science, Sports, and Culture of the
Japanese Government through a Grant-in-Aid for Science Research
is gratefully acknowledged. Professor Bruce Branchini (Connecti-
cut College) is thanked for encouragement.
4-(tert-Butyldimethylsilylperoxy)-5-(4-fluorophenyl)-2-phenyl-4-
[4-(trifluoromethyl)phenyl]-4H-isoimidazole [9 and (R)-9] and 4-
(tert-Butyldimethylsilylperoxy)-4-(4-fluorophenyl)-2-phenyl-5-[4-(tri-
fluoromethyl)phenyl]-4H-isoimidazole [(R)-10]: Prepared by the
method used by Corey et al.[13] A Mixture of hydroperoxides 7 and
8 (209.0 mg, 0.504 mmol), imidazole (171.4 mg, 2.52 mmol), and
tert-butyldimethylsilyl chloride (304.2 mg, 2.02 mmol) in pyridine
(1 mL) was stirred for 20 min at 0 °C. Upon completion of the reac-
tion, the solvent was removed under reduced pressure. The residue
was washed with hexane, filtered, and the filtrate was purified by
chromatography (silica; hexane/EtOAc, 40:1). After combining and
concentrating the fractions, a regioisomeric mixture of products 9
and 10 was obtained as transparent crystals (234.2 mg, 88%; molar
ratio, 9/10 = 4:1, based on 1H NMR analysis). Recrystallization
from 2-propanol gave 9 (89.0 mg, 38%) as colorless crystals; m.p.
[1] a) F. McCapra, Methods Enzymol. 2000, 305, 3–47; b) T. Wil-
son, Photochem. Photobiol. 1995, 62, 601–606; c) E. H. White,
D. F. Roswell, A. C. Dupont, A. A. Wilson, J. Am. Chem. Soc.
1987, 109, 5189–5196; d) G. B. Schuster, Acc. Chem. Res. 1979,
12, 366–373; e) Y. Takano, T. Tsunesada, H. Isobe, Y.
Yoshioka, K. Yamaguchi, I. Saito, Bull. Chem. Soc. Jpn. 1999,
72, 213–225; f) F. McCapra, Y. C. Chang, Chem. Commun.
1967, 1011–1012.
[2] a) E. H. White, M. J. C. Harding, Photochem. Photobiol. 1965,
4, 1129–1155; b) M. Kimura, G. H. Lu, H. Nishigawa, Z. Q.
Zhang, Z. Z. Hu, Luminescence 2007, 22, 72–76.
[3] M. Tsunenaga, H. Iga, M. Kimura, Tetrahedron Lett. 2005, 46,
1877–1880.
93–94 °C. IR (KBr): ν = 2934 (C–H), 1605 (C=N), 1325 (CF ),
˜
3
[4] M. Kimura, H. Nishikawa, H. Kura, H. Lim, E. H. White,
Chem. Lett. 1993, 505–508.
[5] I. Lalezari, M. Hatefi, M. A. Khyoi, N. Guiti, F. Abtahi, J.
Med. Chem. 1971, 14, 1138–1140.
1223 (C–F) cm–1. 1H NMR (300 MHz, CDCl3): δ = 0.155 (s, 3 H),
0.213 (s, 3 H), 0.843 (s, 9 H), 7.13 (t, J = 9.0 Hz, 2 H), 7.42 (d, J
= 8.4 Hz, 2 H), 7.51–7.61 (m, 5 H), 8.22 (dd, J = 9.0, 5.4 Hz, 2 H),
8.46 (d, J = 6.6 Hz, 2 H) ppm. UV/Vis (CH2 Cl2 ): λm a x
[log(ε/m–1 cm–1)] = 281 (4.26). C28H28F4N2O2Si: C, 63.62; H, 5.34;
N, 5.30; found C, 63.61; H, 5.28; N, 5.52.
[6] M. Kimura, G. H. Lu, H. Iga, M. Tsunenaga, Z. Q. Zhang,
Z. Z. Hu, Tetrahedron Lett. 2007, 48, 3109–3113.
[7] Probable emitters are the corresponding amidines 3–, but the
resulting solutions were not all fluorescent.
The residue (3:1 mixture of 9 and 10) was subjected to the HPLC
with a Daicel Chiralpak AD-H column (hexane/2-propanol, 9:1).
The structures of (R)-9 and (R)-10 were assigned by analysis of
[8] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb J. R. Cheeseman, J. A. Montgomery Jr., T. Vreven,
K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tom-
1218
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 1212–1219

Chemiluminescence of Lophine Peroxide Anions
asi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega,
G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota,
R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda,
O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratch-
ian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E.
Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli,
J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Sal-
vador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D.
Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck,
K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Ba-
boul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Lia-
shenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T.
Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M.
Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W.
Wong, C. Gonzalez, J. A. Pople, Gaussian 03, revision B.01,
Gaussian, Pittsburgh PA, 2003.
M. Kimura, K. Akaki, Y. Mishima, A. Hiroyuki, T. Fukai,
Heterocycles 2009, 79, 1019–1024.
I. Y. Bronstein, US 5177241, 1993.
[9]
[10]
[11]
M. Matsumoto, N. Arai, N. Watanabe, Tetrahedron Lett. 1996,
37, 8535–8538.
[12] D. Davidson, M. Weiss, M. Jelling, J. Org. Chem. 1937, 2, 319–
327.
[13] E. J. Cory, A. Venkateswarlu, J. Am. Chem. Soc. 1972, 94,
6190–6191.
Received: July 12, 2013
Published Online: December 12, 2013
Eur. J. Org. Chem. 2014, 1212–1219
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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