Synthesis and properties of 3-arylcyclohepta[4,5]imidazo[1,2-a]-1,3,5- triazine-2,4(3H)-diones and related compounds: Photo-induced autorecycling oxidation of some amines

Article abstract of DOI:10.1016/j.tet.2005.04.035

Novel 3-phenyl- and 3-(4-nitrophenyl)cyclohepta[4,5]imidazo[1,2-a]-1,3,5- triazine-2,4(3H)-diones and the corresponding imino derivatives 5a,b and 6a,b were synthesized in modest to moderate yields by the abnormal and normal aza-Wittig reaction of 2-(1,3-diazaazulen-2-ylimino)triphenylphosphorane with aryl isocyanates and subsequent heterocyclization reaction with a second isocyanate. The related cationic compound, 1-methyl-3-phenylcyclohepta[4,5] imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-dionylium tetrafluoroborate 7a, was also prepared. The electrochemical reduction of these compounds exhibited more positive reduction potentials as compared with those of the related compounds of 3,10-disubstituted cyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1H,3H)-dione systems. In a search of the oxidizing ability, compounds 5a, 6a, and 7a were demonstrated to oxidize some amines to give the corresponding imines in more than 100% yield under aerobic and photo-irradiation conditions, while even benzylamine was not oxidized under aerobic and thermal conditions at 100°C. The oxidation reactions by cation 7a are more efficient than that by 5a and 6a. Quenching of the fluorescence of 5a was observed, and thus, the oxidation reaction by 5a probably proceeds via electron-transfer from amine to the excited singlet state of 5a. In the case of cation 7a, the oxidation reaction is proposed to proceed via formation of an amine-adduct of 7a and subsequent photo-induced radical cleavage reaction.

Full text of DOI:10.1016/j.tet.2005.04.035

Tetrahedron 61 (2005) 6073–6081
Synthesis and properties of
3-arylcyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-diones
and related compounds: photo-induced autorecycling oxidation
of some amines
*
Makoto Nitta, Daisuke Ohtsuki, Yuhki Mitsumoto and Shin-ichi Naya
Department of Chemistry, Advanced Research Center of Science and Engineering, Waseda University, Shinjuku-ku, Tokyo 169-8555, Japan
Received 23 March 2005; revised 14 April 2005; accepted 14 April 2005
Available online 13 May 2005
Abstract—Novel 3-phenyl- and 3-(4-nitrophenyl)cyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-diones and the corresponding imino
derivatives 5a,b and 6a,b were synthesized in modest to moderate yields by the abnormal and normal aza-Wittig reaction of 2-(1,3-
diazaazulen-2-ylimino)triphenylphosphorane with aryl isocyanates and subsequent heterocyclization reaction with a second isocyanate. The
related cationic compound, 1-methyl-3-phenylcyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-dionylium tetrafluoroborate 7a, was
also prepared. The electrochemical reduction of these compounds exhibited more positive reduction potentials as compared with those of the
related compounds of 3,10-disubstituted cyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1H,3H)-dione systems. In a search of the oxidizing
ability, compounds 5a, 6a, and 7a were demonstrated to oxidize some amines to give the corresponding imines in more than 100% yield
under aerobic and photo-irradiation conditions, while even benzylamine was not oxidized under aerobic and thermal conditions at 100 8C.
The oxidation reactions by cation 7a are more efficient than that by 5a and 6a. Quenching of the fluorescence of 5a was observed, and thus,
the oxidation reaction by 5a probably proceeds via electron-transfer from amine to the excited singlet state of 5a. In the case of cation 7a, the
oxidation reaction is proposed to proceed via formation of an amine-adduct of 7a and subsequent photo-induced radical cleavage reaction.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
convenient preparations of 1,3-dialkylcyclohepta[4,5]pyr-
rolo[2,3-d]pyrimidine-2,4(1H,3H)-diones (2)9 and 3.10-
disubstituted cyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-
2,4(3H,10H)-diones (3) and derivatives,10 which are the
structural isomers of 5-deazaflavin (1) (Fig. 1). Cationic
The importance of fused pyrimidines, which are common
sources for the development of new potential therapeutic
agents,1,2 is well known. Among these, flavins are known to
play an important role as cofactors in a wide variety of
biological redox reactions. Dehydrogenation reactions
represent a major family of processes mediated by the
subclass of flavoenzymes known as oxidase. Included in this
group are the oxidative transformations of alcohols to
carbonyl compounds, of amines to imines, and of fatty acid
esters to their a,b-unsaturated analogs3. In this context,
5-deazaflavin (1) has been studied extensively in both
enzymatic4 and model systems5,6 in the hope of gaining
mechanistic insight into flavin-catalyzed reactions. On the
basis of the above observations and our interest concerning
the unique reactivity afforded by the vinyliminophosphor-
anes7 and related compounds,8 we have previously studied
Keywords: 3-Arylcyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-
diones; aza-Wittig reaction; X-ray analysis; Photo-induced autorecycling
oxidation.
*
Corresponding author. Tel.: C81 3 5286 3236; fax: C81 3 3208 2735;
e-mail: nitta@waseda.jp
Figure 1.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.04.035

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M. Nitta et al. / Tetrahedron 61 (2005) 6073–6081
2. Results and discussion
2.1. Synthesis
The aza-Wittig reaction of iminophosphoranes with iso-
cyanate has proven to be one of the most useful
methodologies for the synthesis of nitrogen-containing
heterocycles.7,8,13 We report herein an abnormal aza-Wittig
reaction observed in the attempted program directed toward
the synthesis of 5a,b along with the corresponding imines
6a,b. The abnormal aza-Wittig reaction involves the
formation of an isocyanate instead of a carbodiimide
intermediate, and reported studies on this reaction are very
limited.14 Starting from the 2-amino-1,3-diazaazulene (8),15
the iminophosphorane (9) was prepared under Mitsunobu
conditions using DEAD and triphenylphosphine (Scheme
1).16 Treatment of the iminophosphorane (9) with phenyl
and 4-nitrophenyl isocyanates (10a,b) afforded 5a,b and
6a,b, along with the known compound N-(1,3-diazaazulen-
2-yl)-N0-phenylurea (15a).17 Reaction conditions and the
yields of the products are summarized in Table 1. The
structures of new compounds 5a,b and 6a,b are confirmed
1
on the basis of the H (Table 2) and 13C NMR spectra, IR,
UV–vis, and mass spectral data, as well as elemental
analyses. In addition, while single crystals of 5a,b were not
obtained, the structural characteristics of 6a,b are revealed
by the X-ray crystal analysis (vide infra). The proposed
mechanistic pathways for the formation of 5a,b and 6a,b are
outlined in Scheme 1. Both intermediates 11a,b and 12a,b
can be formed upon treatment of 9 with 10a,b. Breakdown
of 11a,b involving loss of triphenylphosphinimide results
in the isocyanate intermediates 13a,b as the abnormal aza-
Wittig product. The isocyanates 13a,b can undergo an
intermolecular heterocyclization reaction with a second aryl
isocyanates 10a,b providing compounds 5a,b. In contrast,
intermediates 12a,b can lead to the carbodiimides 14a,b as
the normal aza-Wittig product involving the loss of
triphenylphosphine oxide. Subsequent heterocyclization of
14a,b with a second aryl isocyanate 10a,b results in the
formation of compounds 6a,b. The isocyanate 14a reacts
also with stray water to give the urea 15a. The controlling
factor for the abnormal and normal aza-Wittig reactions is
still unclear. 2-Amino-1-azaazulene is0known to react with
10a to give N-(1-azaazulen-2-yl)-N -phenylurea, which
undergoes heterocyclization with a second 10a to give
3-phenylcyclohepta[4,5]pyrrolo[1,2-a]-1,3,5-triazine-2,4-
(3H)-dione.18 In contrast, the urea 15a, which was obtained
upon treatment of 8 with 10a, does not react with a second
isocyanate 10a, and the expected 5a was not obtained even
in the presence of ZnCl2. Thus, the iminophosphorane (9) is
a key synthon for the formation of the desired ring system of
5a,b. In relation to the studies of the oxidizing ability of
neutral and cationic compounds such as 3 and 4, compound
5a was converted to 7a upon treatment of 5a with MeI and
followed by counter ion exchange reaction by using 42%
Scheme 1. Reagents and conditions: (i) PPh3, DEAD, THF, rt, 4 h;
(ii) benzene or toluene, reflux; (iii) ZnCl2, dioxane, reflux, 50 h.
compounds 4 have also been prepared.11 Compounds 3 and
4 have an appreciable oxidizing ability toward some
alcohols and/or amines under photo-irradiation and aerobic
conditions in an autorecycling process.11,12 Thus, structural
modifications of the uracil-annulated heteroazulenes such
as 2, 3, and 4 are an interesting project in view of the
exploration of novel functions. Much of the motivation for
studying the properties of organic molecules stems from
manipulation of the primary chemical structure. Although
strategies for raising or lowering the HOMO and LUMO
levels include conjugation length control, the introduction
of an electron-withdrawing or donating group or element to
the parent molecular skeleton is also an interesting project.
Based on this concept, we studied here the synthesis,
structural characteristics, and electrochemical properties of
3-arylcyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-
2,4(3H)-diones (5a,b) and related compounds 6a,b, which
involve the 1,3-diazaazulene and triazinedione skeletons
instead of a 1-azaazulene and a pyrimidinedione ring
system, along with cationic compound 7a (Fig. 1). Photo-
induced and thermal autorecycling oxidation of some
amines to give the corresponding imines is studied as
well. We describe here the results in detail.
Table 1. Results for the reaction of 9 with aryl isocyanates 10a,b
Isocyanate
Solventa
Time/h
Product (yield/%)
10a
10a
10b
Benzene
Toluene
Toluene
58
20
24
5a (9)
5a (28)
5b (13)
6a (55)
6a (52)
6b (57)
15a (11)
15a (14)
a Reaction was carried out under reflux.

M. Nitta et al. / Tetrahedron 61 (2005) 6073–6081
Table 2. H NMR spectral data (600 MHz) of 5a,b, 6a,b, and 7a and reference compounds 3 and 4
6075
1
Compd
H5
H6
H7
H8
H9
Remaining signals
5aa
dH
9.17
8.19
8.06
8.32
8.45
7.36 (2H, d, JZ8.2 Hz),
7.45 (1H, t, JZ7.4 Hz),
7.52 (2H, d, JZ8.2,
7.4 Hz)
J
dH
9.8
9.8
10.5
9.8
9.6
9.2
10.5
10.5
5ba
6a
9.19
8.85
8.23
7.88
8.10
7.46
8.35
7.61
8.49
7.99
7.70 (2H, d, JZ9.0 Hz),
8.39 (2H, d, JZ9.0 Hz)
J
dH
6.96 (1H, t, JZ7.5 Hz),
7.04 (2H, d, JZ8.3 Hz),
7.21 (2H, dd,
JZ8.3 Hz, 7.5), 7.41 (2H,
d, JZ8.1 Hz), 7.44 (1H, t,
JZ7.6 Hz), 7.54 (2H,dd,
JZ8.2, 7.6 Hz)
J
dH
11.2
10.8
10.5
10.1
9.5
9.8
6ba
7ab
9.00
7.84
7.92
7.99
8.19
9.16
7.13 (2H, d, JZ8.9 Hz),
7.62 (2H, d, JZ8.9 Hz),
8.12 (2H, d, JZ8.9 Hz),
8.43 (2H, d, JZ8.9 Hz)
J
dH
9.8
m
10.6
10.3
9.98–10.0
8.80–8.95
3.83 (3H, s), 7.44–7.48
(2H, m), 7.61–7.67 (2H,
m)
J
dH
m
3c
4d
9.29
7.66–7.90
5.69 (3H, s), 5.69 (2H, s),
7.26–7.3 (5H, m, Ph)
J
dH
J
10.6
m
m
9.84–9.89
8.46–8.58
m
8.90–8.94 3.41 (3H, s), 3.94 (3H, s)
m
a Recorded in DMSO-d6.
b Recorded in CD3CN.
c Ref. 12.
d Ref. 11.
HBF4 in Ac2O in good yield. The spectroscopic data
involving mass spectral data as well as the elemental
analysis are in good accordance with the proposed structure.
The redox ability of 5a was also investigated. The reduction
of 5a with NaBH4 was carried out to give a mixture of three
regio-isomers 16a, 17a, and 18a. The mixture of the regio-
isomers was not separated, and thus, the structural assign-
ment was based on the high resolution MS spectrum of the
spectrum. The mixture was oxidized by DDQ or under
aerobic conditions to regenerate 5a, and thus, the correlation
of the compounds between 5a and 16a, 17a, and 18a was
assessed (Scheme 2).
2.2. Properties
The 1H NMR spectra of two series of 5a,b and 6a,b
resemble each other, respectively. Unambiguous proton
assignment was successfully made, and the chemical shifts
of the protons of the seven-membered ring and the aryl
group and selected coupling constants are listed in Table 2,
together with those of the reference compounds 310 and
cation 4.11 The chemical shifts of the seven-membered ring
protons (H6–H9) of 5a and 5b are found in the appreciably
lower field (d 8.06–8.46 and d 8.11–8.49) as compared with
those (d 7.66–7.90) of 3. This feature is similarly observed
in the chemical shifts of compounds 6a (d 7.46–7.99) and 6b
(d 7.84–8.19). The chemical shifts of the seven-membered
ring protons of cation 7a are also listed and they are similar
to those of cation 4. In particular, the characteristic H5
signals appearing at around d 9.0–9.9 in the 1H NMR spectra
of the compounds listed in Table 2 are due to the anisotropy
effect of the oxygen atom of the triazinedione and
pyrimidinedione moieties. The vicinal coupling constants
of protons of the seven-membered ring of neutral com-
pounds 5a,b and 6a,b suggest bond alternation in the
cycloheptatriene moiety, while no significant bond alterna-
tion is observed in cation 7a as well as 4. The p-electron
delocalization of cation 7a is much enhanced as compared
1
mixture and the H NMR spectrum of each compounds,
which was assigned independently by using the H–H Cosy
Scheme 2. Reagents and conditions: (i) (a) MeI, (CH2Cl)2, 100 8C, 3 h;
(b) 42% aq. HBF4, Ac2O, 0 8C, 1 h; (ii) NaBH4, MeOH, rt, 0.5 h; (iii) air,
CH2Cl2, 7 days or DDQ, CH2Cl2, rt, 1 h.

6076
M. Nitta et al. / Tetrahedron 61 (2005) 6073–6081
spectrum of cation 7a exhibits a greater extent of blue-shift
as compared with compound 5a, suggesting the much
lowering of the HOMO as compared with the LUMO by
methylation.
The affinity of carbocation toward the hydroxide ion,
expressed by the pKRC value, is the common criterion of
carbocation stability.19 The value of cation 7a was
determined spectrophotometrically as 6.8 in buffer solutions
prepared in 50% CH3CN and indicated in Table 3, along
with that of reference cation 4. The value indicates
that cation 7a is much more unstable than reference
compound 4. The reduction potentials of 5a,b, 6a,b, and
7a are determined by cyclic voltammetry (CV) in CH3CN.
The reduction waves of 5a,b, 6a,b and 7a are irreversible
under conditions of the CV measurements, and thus, their
peak potentials are summarized in Table 3, together with
those of the reference compounds 310 and 4.11 As expected,
the E1red of phenyl-substituted compounds 5a and 6a is
more negative than that of 4-nitophenyl substituted
derivatives 5b and 6b, respectively, due to the electron-
withdrawing property of the 4-nitrophenyl group. The E1red
of dicarbonyl compounds 5a,b is more positive than that
of the imino derivatives 6a,b, respectively, due to the
electron-withdrawing dicarbonyl function. The E1red of
these compounds is less negative than that of the reference
compound 3. In contrast, the E1red of cation 7a is much
more positive than that of 5a,b and 6a,b, and the value is
more positive than that of the reference compound 4,
suggesting an appreciable oxidizing property.
Figure 2. UV–vis spectra of 5a,b, 6a,b and 7a.
with that of 5a,b and 6a,b. The UV–vis spectra of
compounds 5a,b, 6a,b and cation 7a in CH3CN are shown
in Figure 2. The two series of 5a,b and 6a,b are very
similar to each other, respectively. On the other hand, the
Table 3. pKRC values and reduction potentialsa of 5a,b, 6a,b, 7ab and
reference compounds 3 and 4
Compd
pKRC
Reduction potential (V)a E1red
5a
5b
6a
6b
7a
3b
—
—
—
—
6.8
—
11.2
K1.15
K1.12
K1.24
K1.14
K0.66
K1.37
K0.87
4c
a Peak potential in V versus Ag/AgNO3.
The X-ray structure analyses were carried out and the
ORTEP drawings of 6a,b are shown in Figure 3. The
selected bond lengths and bent angles of the two aryl groups
b Ref. 10.
c Ref. 11.
Figure 3. ORTEP drawings of 6a,b with thermal ellipsoid plot (50% probability).

M. Nitta et al. / Tetrahedron 61 (2005) 6073–6081
Table 4. Bond lengths of 6a,b obtained by X-ray structure analysis
6077
a
˚
Bond length /A
Compd.
C3–C4
C4–C5
C5–C6
C6–C7
C7–C8
C8–C9
N4–C9
N4–C10 C3–N3
C10–N3 N1–C10 N1–C1
C1–N2
6a
6b
1.38
1.37
1.40
1.41
1.35
1.36
1.41
1.41
1.37
1.37
1.40
1.41
1.34
1.34
1.34
1.34
1.38
1.40
1.39
1.40
1.30
1.30
1.35
1.36
1.43
1.43
a Numbering is based on the ORTEP drawings in Figure 3.
from the plane of the 7–5–6 p-systems are summarized in
Tables 4 and 5. The bond lengths of C3–C4, C5–C6, and
C7–C8 are shorter than those of C4–C5 and C6–C7,
suggesting bond-length alternation in the seven-membered
ring as demonstrated by vicinal coupling constants of the
1H NMR spectrum (Table 2). Electron delocalization in the
triazine ring is not observed. Both 7–5–6 p-systems of 6a,b
are a nearly planar structure. The twisted angles of the aryl
group against the plane of the 7–5–6 ring system are
summarized in Table 5. The planes of the aryl group on the
amide nitrogens of 6a,b (N2Ar) are twisted 75.7 and 77.98,
respectively, against the plane of the 7–5–6 p-system. This
is probably due to steric hindrance between the aryl group
and the carbonyl-oxygen and imino-nitrogen. Remarkably,
the twisted angle of N5Ar of 6a,b is 2.5 and 58.78,
respectively (Table 1).
we found that both compounds have oxidizing ability
toward benzylamine, 1-phenylethylamine, hexylamine, and
cyclohexylamine. In the amine oxidation, imine is produced
at first; however, it reacts with another amine to result in the
formation of another imine R1R2C]N–CHR1R2 and NH3
(Scheme 3). Then the reaction mixture was diluted with
ether and filtered and the filtrate was treated with
2,4-dinitrophenylhydrazine in 6% HCl to give 2,4-dinitro-
phenylhydrazone of the corresponding carbonyl compound.
Direct irradiation of amines in the absence of 5a, 6a, and 7a
(named ‘blank’) gives the corresponding carbonyl com-
pounds in low to modest yields under similar conditions.
Thus, the yields are calculated by subtraction of the ‘blank’
yield from the total yield of the carbonyl compound in the
presence of 5a and 7a, and the results are summarized in
Table 6 (Entries 1–8). More than 100% yields are obtained
based on 5a and 7a, and thus, autorecycling oxidation
clearly proceeds. In contrast, oxidation reaction by using 6a
does not proceed effectively, and even benzylamine and
1-phenethylamine are oxidized in low yield as compared
Table 5. Torsion angles of 6a,b twisted angle/degree
Compd
N2Ara
N5Ara
6a
6b
75.7
77.9
2.5
58.7
Table 6. Photo-induced autorecycling oxidation of some amines by 5a, 6a,
and 7aa
a Numbering is based on the ORTEP drawings in Figure 3.
Entry
Compd
Amines
Yield (%)b,c Recycling
no.
2.3. Photo-induced autorecycling oxidation
1
2
3
4
5
6
7
8
9
10
5a
5a
5a
5a
7a
7a
7a
7a
6a
6a
PhCH2NH2
PhCH(Me)NH2
Hexylamine
Cyclohexylamine
PhCH2NH2
PhCH(Me)NH2
Hexylamine
Cyclohexylamine
PhCH2NH2
PhCHMeNH2
8322
6733
2000
862
11 818
8457
3143
909
83.2
67.3
20.0
8.6
118.2
84.6
31.4
9.1
Compounds 3,12 4,11 and related compounds20 undergo
photo-induced autorecycling oxidation toward some alco-
hols and some amines under aerobic conditions. In this
context, we examined the oxidation of some amines by
using 5a, 6a, and 7a under aerobic and photo-irradiation
(RPR100, 350 nm lamps) conditions. Although benzyl
alcohol was not oxidized effectively by either 5a or 7a,
909
400
9.1
4.0
a CH3CN solution was irradiated by RPR100, 350 nm lamps.
b Isolated by converting to the corrresponding 2,4-dinitrophenylhydrazone.
c Based on the compound used; the yield is calculated by subtraction of the
‘blank’ yield from the total yield.
Scheme 3.
Figure 4. Time dependence of benzylamine oxidation by 5a.

6078
M. Nitta et al. / Tetrahedron 61 (2005) 6073–6081
with that of 5a and 7a (Table 6, Entries 9 and 10). As the
time of photo-irradiation is prolonged, the yield of oxidation
product by 5a is increased gradually. After 16 h irradiation,
the yield is not increased appreciably (Fig. 4), suggesting
plausible decomposition of 5a. The attempted oxidation
reaction of benzylamine by 5a was not observed under
thermal and aerobic conditions. In a previous study, the
fluorescence spectrum of 1,3-dimethylcyclohepta[b]furo-
[2,3-d]pyrimidine-2,4(1H,3H)-dionylium tetrafluoroborate,
which has oxidizing ability toward some alcohols, is
quenched by addition of 1-phenylethanol, suggesting an
interaction of the singlet excited state of the compound with
the alcohol.21 Thus, in a search of the mechanistic aspect of
the photo-induced oxidation reaction, the fluorescence
spectra of 5a and 7a were studied; the quantum yield (F)
of that for 5a was determined to be 0.075; however, no
fluorescence spectra of 7a was observed. The fluorescence
spectrum of 5a (Fig. 5) was quenched by adding
benzylamine, while quenching of the fluorescence was not
observed by addition of benzyl alcohol, suggesting
interaction of the singlet excited state of 5a with the amine.
Figure 6. UV–vis spectra of 7a.
gives the radical ion pair [R1R2CHNH2%C O2%K] and 7a; the
former ion pair would follow Path A.
3. Conclusion
Novel 3-phenyl- and 3-(4-nitropenyl)cyclohepta[4,5]-
imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-diones and the corre-
sponding imino derivatives 5a,b, 6a,b, and 1-methyl-3-
phenylcyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4-
(1H,3H)-dionylium tetrafluoroborate 7a were synthesized in
modest to moderate yields. Compounds 5a, 6a, and 7a were
demonstrated to oxidize some amines to give the corre-
sponding imines in more than 100% yield under aerobic and
photo-irradiation conditions. Thus, oxidation reaction
proceeds in a photo-induced autorecycling process.
4. Experimental
4.1. General
Figure 5. Fluorescence spectra of 5a.
The postulated mechanistic pathways for the oxidation of
amines (R1R2CHNH2) are depicted in Scheme 3. The
electron transfer from amines to the excited singlet state of
5a would occur to produce a radical anion 5a%K and
R1R2CHNH%2C. In the presence of oxygen, an electron
transfer from 5a%K to O2 may give the radical ion pair
[R1R2CHNH2%C O%2K] and 5a. Then a proton transfer from
R1R2CHNH2%C to O%2K may occur, followed by formation of
product R1R2CH]NH and H2O2 (Path A).22 On the other
hand, there is an alternative pathway (Path B), in which a
mixture of hydrogenated compounds 16a, 17a, and 18a
(Scheme 3) in addition to the imine are generated from 5a%K
and R1R2CH–NH%2C directly; the former compound is
oxidized under aerobic conditions to regenerate 5a. It is
shown that the regeneration of 5a by air oxidation of 16a,
17a, and 18a is slow and seems to be ineffective to achieve
an efficient autorecycling oxidation (Scheme 2, vide supra).
Thus, Path A seems to be favorable. In the case of oxidation
by 7a, photo-induced homolytic cleavage of the initially
formed amine-adduct of 7a, which is detected by UV–vis
spectra as shown in Figure 6, probably occurs to generate
7a% and R1R2CHNH2%C. An electron transfer from 7a% to O2
IR spectra were recorded on a HORIBA FT-710 spectro-
meter. UV–vis spectra were recorded on a Shimadzu
UV-3101PC spectrometer. Mass spectra and high-resolution
mass spectra were run on JMS-AUTOMASS 150 and
JMS-SX102A spectrometers. Unless otherwise specified,
1H NMR and 13C NMR spectra were recorded on an
AVANCE 600 spectrometer using CDCl3 as the solvent,
and the chemical shifts are given relative to internal SiMe4
standard: J-values are given in Hz. Mps were recorded on a
Yamato MP-21 apparatus and are uncorrected. Photo-
irradiation was carried out by using RPR-100 fitted with
350 nm lamps though a Pyrex filter.
4.2. Preparation of 9
To a solution of 8 (435 mg, 3 mmol) and PPh3 (786 mg,
3 mmol) in THF (30 mL) was added DEAD (1.5 mL,
3.3 mmol) at 0 8C, and the mixture was stirred at rt for 4 h.
The reaction mixture was filtered, and the filtrate was
concentrated. The resulting residue was crystallized from
Et2O to give 9 (1.17 g, 86%).

M. Nitta et al. / Tetrahedron 61 (2005) 6073–6081
6079
4.2.1. 2-(1,3-Diazaazulen-2-yl)iminotriphenylphosphor-
ane (9). Pale yellow prisms; mp 212–213 8C (decomp.)
(from AcOEt); 1H NMR (600 MHz) d 7.31 (1H, t, JZ
9.9 Hz, H-6), 7.44 (6H, ddd, JZ7.8, 7.5, 2.9 Hz, m-Ph), 7.53
(3H, td, JZ7.5, 1.7 Hz, p-Ph), 7.58 (2H, dd, JZ10.7,
9.9 Hz, H-5 and H-7), 7.93 (6H, dd, JZ7.8, 1.7 Hz, o-Ph),
7.94 (2H, d, JZ10.7 Hz, H-4 and H-8); 13C NMR
(150.9 MHz) d 124.6 (C-4 and C-8), 128.5 (JPCZ12.2 Hz,
m-Ph), 128.8 (JPCZ100.1 Hz, i-Ph), 129.4 (C-6), 132.1
(JPCZ2.6 Hz, p-Ph), 133.4 (JPCZ10.1 Hz, o-Ph), 133.6
(C-5 and C-7), 165.1 (C-2); 31P NMR (109.3 MHz) d 16.97;
IR (CHCl3, cmK1) 1549, 1470, 1438, 1364, 1114, 957, 926,
882; MS m/z 406 (MCCH); Anal. calcd for C26H21N3P: C,
77.02; H, 4.97; N, 10.36. Found: C, 76.87; H, 4.95; N, 10.46.
163.0, 166.5; IR (KBr, cmK1) 1746, 1683; MS m/z 336
(MCCH); Anal. calcd for C16H9N5O4–1/4CH2Cl2: C,
54.75; H, 2.69; N, 19.64. Found: C, 54.75; H, 2.80; N, 19.39.
4.4.2. 3-(4-Nitrophenyl)-2-(4-nitorophenyl)iminocyclo-
hepta[4,5]imidazo[1,2-a]-1,3,5-triazine-4-one (6b). Red
prisms; mp 258–260 8C (decomp.) (from CHCl3); 13C
NMR (150.9 MHz, DMSO-d6) d 123.6, 123.8, 124.5,
124.9, 130.1, 134.6, 137.3, 138.4, 141.5, 142.1, 145.8,
147.2, 147.8, 149.3, 154.0, 160.1, 168.2, 175.2; IR (CHCl3,
cmK1) 1734; MS m/z 456 (MCCH); Anal. calcd for
C22H13N7O5–CHCl3: C, 48.06; H, 2.46; N, 17.06. Found: C,
48.32; H, 2.58; N, 17.30.
4.5. Preparation of urea 15a
4.3. Preparation of 5a and 6a
A solution of 8 (73 mg, 0.5 mmol) and 10a (179 mg,
1.5 mmol), and ZnCl2 (68 mg, 0.5 mmol) in dioxane
(40 mL) was heated under reflux for 50 h. After evaporation
of the solvent, the reaction mixture was washed with EtOH,
the EtOH layer was concentrated to give 15a (106 mg,
80%). A similar reaction in the absence of ZnCl2 afforded
15a (45 mg, 34%), which is identified on the basis of
comparison of the physical data reported previously.17
A solution of 9 (810 mg, 2.0 mmol) and 10a (714 mg,
6.0 mmol) in a solvent (100 mL) indicated in Table 1 was
refluxed for an adequate time. After evaporation of the
solvent, the residue was dissolved in CH2Cl2, the insoluble
material was col0lected by filtration to give N-(1,3-
diazaazuln-2-yl)-N -phenylurea 15a, and the filtrate was
separated by column chromatography on SiO2. The
fractions eluted with AcOEt gave 6a, and the fractions
eluted with acetone gave 5a. The results are summarized in
Table 1.
4.6. Reaction of 15a with 10a
A mixture of 15a (26 mg, 0.1 mmol) and 10a (24 mg,
0.2 mmol) in the presence or absence of ZnCl2 (14 mg,
0.1 mmol) in dioxane (40 mL) was heated under reflux for
50 h. The reaction mixture was concentrated and the residue
was washed with EtOH. The collected EtOH solution was
concentrated and 15a was isolated in 83% (in the presence
of ZnCl2) and 76% (in the absence of ZnCl2).
4.3.1. 3-Phenylcyclohepta[4,5]imidazo[1,2-a]-1,3,5-tri-
azine-2,4(3H)-dione (5a). Yellow needles; mp 228–
230 8C (decomp.) (from CH2CL2/Et2O); 13C NMR
(150.9 MHz, DMSO-d6) d 124.6, 128.2, 128.6, 128.9,
134.5, 135.6, 138.7, 139.0, 142.7, 145.1, 147.9, 155.0,
162.7, 166.3; IR (KBr, cmK1) 1739, 1707; MS m/z 290
(MC); Anal. calcd for C16H10N4O2–1/4H2O: C, 65.19; H,
3.59; N, 19.01. Found: C, 65.20; H, 3.23; N, 19.14.
4.7. Preparation of 7a
4.3.2.
3-Phenyl-2-phenyliminocyclohepta[4,5]imi-
A solution of 5a (2.9 mg, 0.1 mL) and MeI (2 mL) in
(CH2Cl)2 (4 mL) in a sealed tube was heated at 100 8C for
3 h. The solvent was evaporated and the residue was
dissolved in Ac2O (3 mL) and treated with 42% aq. HBF4
(0.6 mL). To the solution was added ether (5 mL) and
precipitates were collected by filtration to give 7a (36 mg,
92%).
dazo[1,2-a]-1,3,5-triazine-4-one (6a). Dark red prisms;
mp 222–223 8C (decomp) (from AcOEt); 13C NMR
(150.9 MHz) 13C NMR (150.9 MHz) d 122.2, 123.0,
123.1, 128.3, 128.5, 128.7, 129.5, 133.5, 135.7, 136.2,
137.9, 141.3, 146.1, 147.7, 148.0, 148.4, 159.7, 168.2; IR
(CHCl3, cmK1) 1728; MS m/z 366 (MCCH); Anal. calcd
for C22H15N5O: C, 72.32; H, 4.14; N, 19.17. Found: C,
72.02; H, 4.12; N, 19.05.
4.7.1. 1-Methyl-3-phenylcyclohepta[4,5]imidazo[1,2-a]-
1,3,5-triazine-2,4(3H)-dionylium tetrafluoroborate (7a).
Colorless needles; mp 289–291 8C (decomp.) (from
CH3CN/Et2O.); 13C NMR (150.9 MHz, CD3CN) d 32.1,
96.1, 128.7, 130.4, 130.7, 133.7, 134.8, 142.0, 145.0, 147.0,
147.2, 147.7, 148.2, 155.3, 162.8; IR (CHCl3, cmK1) 1726,
1084; MS m/z 305 (MCKBF4). HRMS calcd for
C17H13N4O2BF4: 305.1060 (MKBF4). Found: 305.1021
(MCKBF4). Anal calcd for C17H13N4O2BF4: C, 52.07; H,
3.34; N, 14.29. Found: C, 52.04, H, 3.53; N, 13.95.
4.4. Preparation of 5b and 6b
A solution of 9 (810 mg, 2.0 mmol) and 10b (984 mg,
6.0 mmol) in toluene–dioxane (1/1; 100 mL) was refluxed
for 24 h. After evaporation of the toluene, the residue was
dissolved in CH2Cl2, the insoluble material was filtered and
the filtrate was concentrated and separated by column
chromatography on SiO2. The fractions eluted with AcOEt
afforded 6b, and the fractions eluted with acetone gave 5b.
The results are summarized in Table 1.
4.8. Reduction of 5a
4.4.1. 3-(4-Nitrophenyl)cyclohepta[4,5]imidazo[1,2-a]-
1,3,5-triazine-2,4(3H)-dione (5b). Yellow powder; mp
249–252 8C (decomp.) (from AcOEt); 13C NMR
(150.9 MHz, DMSO-d6) d 124.5, 125.3, 130.7, 135.0,
139.4, 139.5, 141.8, 143.2, 145.2, 147.4, 147.9, 154.7,
A solution of 5a (29 mg, 0.1 mmol) and NaBH4 (23 mg,
0.6 mmol) in MeOH (10 mL) was stirred at rt for 30 min.
The reaction mixture was extracted with CH2Cl2 and the
extract was dried over Na2SO4, and concentrated in vacuo.

6080
M. Nitta et al. / Tetrahedron 61 (2005) 6073–6081
The resulting residue afforded a mixture of 16a, 17a, and
18a (100%) in a ratio of 6:3:1.
(for pH 6.0–8.0) in various portions. For the preparation of
sample solutions, 1 mL portions of the stock solution,
prepared by dissolving 3–5 mg of compound 7a in CH3CN
(20 mL), were diluted to 10 mL with the buffer solution
(8 mL) and CH3CN (1 mL). The UV–vis spectrum was
recorded for cation 7a in 20 different buffer solutions.
Immediately after recording the spectrum, the pH of each
solution was determined on a pH meter calibrated with
standard buffers. The observed absorbance at the specific
absorption wavelength (500 nm) of cation 7a was plotted
against pH to give a classical titration curve, whose
midpoint was taken as the pKRC value.
4.8.1. A mixture of 16a, 17a, and 18a. IR (CHCl3, cmK1
)
1726, 1637, 1084; MS (FAB) m/z 293 (MCCH). HRMS
calcd for C16H13N4O2: 293.1040 (MCH). Found: 293.1044
(MCCH).
4.8.2. Compound 16a. 1H NMR (600 MHz) d 3.73 (2H, d,
JZ6.4 Hz, H-6), 5.54 (1H, dt, JZ10.4, 6.4 Hz, H-7), 6.11
(1H, dd, JZ10.4, 6.1 Hz, H-8), 6.45 (1H, dd, JZ11.5,
6.1 Hz, H-9), 6.90 (1H, d, JZ1.5 Hz, H-10), 7.30–7.56
(5H, m, o-Ph, m-Ph and p-Ph); MS m/z 293 (MC).
4.12. Cyclic voltammetry of 5a,b and 7a
4.8.3. Compound 17a. 1H NMR (600 MHz) d 3.36 (2H, d,
JZ6.3 Hz, H-10), 5.48 (1H, dt, JZ10.2, 6.3 Hz, H-10),
6.08–6.13 (1H, m, H-8), 6.40 (1H, dd, JZ11.5, 6.1 Hz,
H-7), 7.30–7.39 (1H, m, H-6), MS m/z 293 (MC).
The reduction potentials of 5a,b and 7a were determined by
means of CV-27 voltammetry controller (BAS Co). A three-
electrode cell was used, consisting of Pt working and an Ag/
AgNO3 reference electrode. Nitrogen was bubbled through
a CH3CN solution (4 mL) of each sample (1 mmol dmK3
)
1
4.8.4. Compound 18a. H NMR (600 MHz) d 2.50 (2H, t,
JZ7.0 Hz, H-8), 5.36 (1H, dt, JZ10.0, 7.0 Hz, H-7), 5.52–
5.56 (1H, m, H-9), 6.87 (1H, d, JZ10.0 Hz, H-10), 7.20
(1H, d, JZ10.0 Hz, H-6), 7.30–7.56 (5H, m, o-Ph, m-Ph and
p-Ph); MS m/z 293 (MC).
and Bu4NClO4 (100 mmol dmK3 to deaerate it. The
measurements were made at a scan rate of 0.1 V sK1, and
the voltammograms were recorded on an X–Y recorder.
Immediately after the measurements, ferrocene
(0.2 mmol dmK3) (E1/2ZC0.083 V) was added as the
internal standard, and the observed peak potentials were
corrected with reference to this standard.
4.9. Oxidation of a mixture of 16a, 17a, and 18a
A mixture of 16a, 17a, and 18a (29 mg, 0.1 mmol) in
CH2Cl2 (15 mL) was stirred under aerobic conditions for 7
day. The solution was dried over Na2SO4 and concentrated.
The resulting residue was purified by TLC on SiO2
(acetone) to give 5a (17 mg, 59%).
4.13. X-ray structure determination of 6a†
Reddish prisms, C22H15N5O, MZ365.39, triclinic, space
group PK1, aZ7.059(3), bZ10.399(5), cZ11.990(7) A,
˚
aZ100.50(3)8, bZ96.87(3)8, gZ105.17(2)8, VZ
3
822.2(7) A , ZZ2, DcZ1.476 g mLK1, crystal dimensions
˚
A solution of 16a, 17a, and 18a (29 mg, 0.1 mmol) and
DDQ (27 mg, 0.12 mmol) in CH2Cl2 (15 mL) was stirred at
rt for 1 h. The reaction mixture was extracted with CH2Cl2,
and the extract was washed with aq. Na2CO3 and dried over
Na2SO4. The CH2Cl2 was evaporated and the residue was
purified by TLC on SiO2 (acetone) to give 5a (25 mg, 86%).
0.80!0.50!0.30 mm. Data were measured on a Rigaku
RAXIS-RAPID radiation diffractomater with graphite
monochromated Mo Ka radiation. Total 7445 reflections
were collected, using the u–2q scan technique to a
maximum 2q value of 55.08. The structure was solved by
direct methods and refined by a full-matrix least-squares
method using SIR92 structure analysis software, with 268
variables and 2897 observed reflections [IO3.00s(I)]. The
non-hydrogen atoms were refined anisotropically. The
weighting scheme wZ[20.0000!sc(F20)C0.0010!F02C
0.5000]K1 gave satisfactory agreement analysis. The final
R and Rw values were 0.0810 and 0.0990. The maximum
peak and minimum peak in the final difference map were
4.10. General procedure for the photo-induced auto-
recycling oxidation of amines
To a solution of 5a (0.005 mmol) and 7a (0.005 mmol) in
CH3CN (16 mL) was added an amine (2.5 mmol) in a pyrex
tube, and the mixture was irradiated by RPR-100, 350 nm
lamps under aerobic conditions for 16 h. The reaction
mixture was concentrated in vacuo and diluted with ether
and filtered. The filtrate was treated with 2,4-dinitro-
phenylhydrazine in 6% HCl to give the 2,4-dinitrophenyl-
hydrazone of the corresponding carbonyl compound. The
results are summarized in Table 6. In the case of the
benzylamine oxidation, nine samples are irradiated and time
dependency of the yields of 2,4-dinitrophenylhydrazone
was investigated as summarized in Figure 4.
K
3
˚
0.38 and K0.41 e /A .
4.14. X-ray structure determination of 6b‡
Reddish prisms, C23H14Cl3N7O5, MZ574.77, monoclinic,
space group P21/n, aZ13.15(1), bZ14.632(9), cZ
3
˚
˚
13.754(8) A, bZ114.06(5) 8, VZ2417.0(3) A , ZZ4,
DcZ1.579 g mLK1, crystal dimensions 0.80!0.40!
0.20 mm. Data were measured on a Rigaku RAXIS-
RAPID radiation diffractomater with graphite mono-
chromated Mo Ka radiation. Total 21,037 reflections were
collected, using the u–2q scan technique to a maximum 2q
value of 55.08. The structure was solved by direct methods
4.11. Determination of pKRC value of cation 7a
Buffer solutions of slightly different acidities were prepared
by mixing aqueous solutions of potassium hydrogen
phthalate (0.1 M) and HCl (0.1 M) (for pH 2.2–4.0),
potassium hydrogen phthalate (0.1 M) and NaOH (0.1 M)
(for pH 4.1–5.9), and KH2PO4 (0.1 M) and NaOH (0.1 M)
† CCDC reference number 266692.
‡ CCDC reference number 266693.

M. Nitta et al. / Tetrahedron 61 (2005) 6073–6081
6081
references therein. (b) Nitta, M.; Iino, Y.; Mori, S.; Takayasu,
T. J. Chem. Soc., Perkin Trans. 1 1995, 1001–1007.
8. (a) Nitta, M.; Akie, T.; Iino, Y. J. Org. Chem. 1994, 59,
1309–1314. (b) Nitta, M.; Kanda, H. Heterocycles 2002, 57,
491–499.
and refined by a full-matrix least-squares method using
SIR92 structure analysis software, with 357 variables and
2922 observed reflections [IO3.00s(I)]. The non-hydrogen
atoms were refined anisotropically. The weighting scheme
wZ[3.0000!sc(F02)C0.0010!F02C0.5000]K1 gave satis-
factory agreement analysis. The final R and Rw values were
0.0690 and 0.0860. The maximum peak and minimum peak
9. Nitta, M.; Tajima, Y. J. Chem. Res. (S) 1999, 372–373.
10. Nitta, M.; Tajima, Y. Synthesis 2000, 651–654.
11. Naya, S.; Nitta, M. Tetrahedron 2003, 59, 7291–7299.
12. Naya, S.; Iida, Y.; Nitta, M. Tetrahedron 2004, 60, 459–467.
13. For reviews: (a) Gololobov, Y. G.; Kasukhin, L. F. Tetra-
hedron 1992, 48, 1353–1406. (b) Eguchi, S.; Matsushita, Y.;
Yamashita, K. Org. Prep. Proced. Int. 1992, 24, 209.
(c) Molina, P.; Vilaplana, M. J. Synthesis 1994, 1197.
(d) Wamhoff, H.; Richardt, G.; Stolben, S. Adv. Heterocycl.
Chem. 1995, 64, 159–249.
K
3
˚
in the final difference map were 1.01 and K0.78 e /A .
Acknowledgements
Financial support from a Waseda University Grant for
Special Research Project and 21COE ‘Practical Nano-
Chemistry’ from MEXT, Japan, is gratefully acknowledged.
We thank the Materials Characterization Central Labora-
tory, Waseda University, for technical assistance with the
spectral data, elemental analyses, and X-ray analysis.
14. (a) Bruche, L.; Garanti, L.; Zecchi, G. J. Chem. Soc., Perkin
Trans. 1 1986, 2177–2179. (b) Molina, P.; Alajarin, M.; Vidal,
A. Tetrahedron 1990, 46, 1063–1073. (c) Yamamoto, H.;
Ohnuma, M.; Nitta, M. J. Chem. Res., (S) 1999, 173. (M)
1999, 901–919.
15. Nozoe, T.; Mukai, T.; Takase, K.; Murata, I.; Matsumoto, K.
Proc. Jpn. Acad. 1953, 29, 452–456.
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