Synthesis and properties of 4,9-methanoundecafulvenes and their transformation to 3-substituted 7,12-methanocycloundeca[4,5]furo[2,3-d] pyrimidine-2,4(1H,3H)-diones: Photo-induced autorecycling oxidizing reaction toward amines

Article abstract of DOI:10.1016/j.tet.2005.05.069

The synthesis and properties of 4,9-methanoundecafulvene [5-(4,9-methanocycloundeca-2′,4′,6′,8′, 10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-trione] derivatives 8a,b were studied. Their structural characteristics were investigated on the basis of the ¹H and ¹³C NMR and UV-vis spectra. The rotational barrier (ΔG^?) around the exocyclic double bond of 8a was found to be 12.55 kcal mol^-1 by the variable temperature ¹H NMR measurement. The electrochemical properties of 8a,b were also studied by CV measurement. Furthermore, the transformation of 8a,b to 3-substituted 7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1H,3H)-diones 16a,b was accomplished by oxidative cyclization using DDQ and subsequent ring-opening and ring-closure. The structural details and chemical properties of 16a,b were clarified. Reaction of 16a with deuteride afforded C13-adduct 19 as the single product, and thus, the methano-bridge controls the nucleophilic attack to prefer endo-selectivity. The photo-induced oxidation reaction of 16a and a vinylogous compound, 3-methylcyclohepta[4,5]furo[2,3-d]pyrimidine-2,4(3H)-dione 2a, toward some amines under aerobic conditions were carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) with the recycling number of 6.1-64.0 (for 16a) and 2.7-17.2 (for 2a), respectively.

Full text of DOI:10.1016/j.tet.2005.05.069

Tetrahedron 61 (2005) 7384–7391
Synthesis and properties of 4,9-methanoundecafulvenes and their
transformation to 3-substituted 7,12-methanocycloundeca[4,5]
furo[2,3-d]pyrimidine-2,4(1H,3H)-diones: photo-induced
autorecycling oxidizing reaction toward amines
*
Shin-ichi Naya, Yohei Yamaguchi and Makoto Nitta
Department of Chemistry, Advanced Research Center of Science and Engineering, Waseda University, Shinjuku-ku, Tokyo 169-8555, Japan
Received 9 May 2005; revised 24 May 2005; accepted 24 May 2005
Available online 15 June 2005
Abstract—The synthesis and properties of 4,9-methanoundecafulvene [5-(4,9-methanocycloundeca-20,40,60,80,100-pentaenylidene)
1
pyrimidine-2,4,6(1,3,5H)-trione] derivatives 8a,b were studied. Their structural characteristics were investigated on the basis of the H
and 13C NMR and UV–vis spectra. The rotational barrier (DG‡) around the exocyclic double bond of 8a was found to be 12.55 kcal molK1 by
the variable temperature 1H NMR measurement. The electrochemical properties of 8a,b were also studied by CV measurement. Furthermore,
the transformation of 8a,b to 3-substituted 7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1H,3H)-diones 16a,b was
accomplished by oxidative cyclization using DDQ and subsequent ring-opening and ring-closure. The structural details and chemical
properties of 16a,b were clarified. Reaction of 16a with deuteride afforded C13-adduct 19 as the single product, and thus, the methano-bridge
controls the nucleophilic attack to prefer endo-selectivity. The photo-induced oxidation reaction of 16a and a vinylogous compound,
3-methylcyclohepta[4,5]furo[2,3-d]pyrimidine-2,4(3H)-dione 2a, toward some amines under aerobic conditions were carried out to give the
corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) with the recycling number of 6.1–64.0 (for
16a) and 2.7–17.2 (for 2a), respectively.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
corresponding carbonyl compounds.5,6 Furthermore, the
synthesis, properties, and reactivity of cationic derivative
Flavins are known to play an important role as co-factors in
a wide variety of biological redox reactions.1 The flavin-
redox systems have been investigated extensively through
synthetic model systems and theoretical calculations.2
Among these, 5-deazaflavins3 and 5-deaza-10-oxaflavins4
(2H-chromeno[2,3-d]pyrimidine-2,4(3H)-diones) have also
been studied extensively in the hope of gaining mechanistic
insight into flavin-catalyzed reactions. On the basis of the
above observations, we have previously studied convenient
preparations of 3,10-disubstituted cyclohepta[4,5]-
pyrrolo[2,3-d]pyrimidine-2,4(3H)-diones 1a–c and
3-substituted
cyclohepta[4,5]furo[2,3-d]pyrimidine-
2,4(3H)-diones 2a–c (Fig. 1), which are the structural
isomers of 5-deazaflavin and 5-deaza-10-oxaflavin, respect-
ively, and their ability to oxidize some alcohols to the
Keywords: 5-(4,9-Methanocycloundeca-20,40,60,80,100-pentaenylidene)-
pyrimidine-2,4,6(1,3,5H)-trione; Rotational barrier; 7,12-Methanocyclo-
undeca[4,5]furo[2,3-d]pyrimidine-2,4(1H,3H)-diones; Photo-induced auto-
recycling 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.2005.05.069

S. Naya et al. / Tetrahedron 61 (2005) 7384–7391
7385
are vinylogous compounds of 5a–c. From the variable
temperature NMR and CV measurements, their properties
and structural characteristics were studied. Furthermore, the
transformation of 8a,b to novel methano-bridged com-
pounds 16a,b, which are vinylogous compounds of 2a–c,
was accomplished by the oxidative cyclization and
subsequent ring-opening and ring-closure. The structural
details and chemical properties of 16a,b were investigated,
and the photo-induced oxidizing reaction of 16a and a
vinylogous compound 2a toward some amines were studied
as well. We report herein the results in detail.
Scheme 1. Reagents and conditions: (i) Ac2O, 120 8C, 1 h.
2. Results and discussion
3aC$BF4K,7 and its sulfur and nitrogen analogues8,9 as well
as their novel photo-induced autorecycling oxidizing
reactions toward some alcohols were investigated.
2.1. 4,9-Methanoundecafulvenes (8a,b)
Since heptafulvenes 5a–c were synthesized by the reaction
of tropone with corresponding barbituric acids,18 the
method was applied to synthesize novel 4,9-methano-
undecafulvenes 8a,b (Scheme 1). Condensation reactions
of 4,9-methano[11]annulenone 619 with monosubstituted
barbituric acids 7a,b in Ac2O afforded 8a,b as dark reddish
or reddish powder in modest yields (Table 1). Compounds
On the other hand, heptafulvenes have intrigued chemists
for several decades, especially in the context of the concept
of aromaticity.10–12 The properties and chemical behavior of
substituted heptafulvenes are usually rationalized in terms
of the differing contribution of the zwitterionic canonical
structure. Thus, various heptafulvenes, such as 8,8-
dicyanoheptafulvene (4a) (Fig. 1) and its derivatives 4b–d
have been synthesized and their properties and X-ray
structure analyses have been studied.13–15 Furthermore, the
chemistry of the heptafulvenes derived by insertion of more
complicated conjugated p-systems has also been studied in
relation to the molecular design of organic dyes, highly
polarized compounds, and electron acceptors or electron
donors.16,17 In this context, we have reported the synthesis
and properties of novel heptafulvenes 5a–c.18 The contri-
butions of their zwitterionic canonical structures and
rotational barrier (DG‡) around the exocyclic double bond
have been clarified. Thus, the structurally modified
heptafulvenes are interesting from the viewpoint of their
novel properties and molecular functions. Based on this
concept, we have now investigated the synthesis of 4,9-
methanoundecafulvene derivatives 8a,b (Scheme 1), which
1
8a,b were fully characterized on the basis of the H NMR,
13C NMR, IR. UV–vis, and mass spectral data as well as
elemental analyses. In the 13C NMR spectra, the C5 carbon
signals of the barbituric acid moiety in 8a,b appear at low
field (dC 108.2 and 108.0), suggesting the low electron
density as compared with those of the C5 of 5a,b (5a: dC
101.7, 5b: dC 102.2) (Table 2).18 Thus, contribution of the
zwitterionic canonical structure B of 8a,b (Scheme 1) seems
to be less important as compared with those of 5a,b;
however, the 1,6-methano[11]annulenylium ion 9C (pKRC
,
6.2)20 is more stable than the tropylium ion 10C (pKRC, 3.9)
(Fig. 2).21 This feature is similar to the cases of dicyano-
substituted heptafulvene and 4,9-methanoundecafulvene;
the C12 carbon signal of 12,12-dicyano-4,9-methano-
undecafulvene (dc 83.6)22 is shifted to lower field as compared
with the C8 carbon signal of 8,8-dicyanoheptafulvene 4a (dc
Table 1. Results for the preparation of 8a,b, cations 13a,bC$BF4K and 14a,bC$BF4K, and 16a,b
Run
Compound
Condensation
Oxidative cyclization
Ring-opening and
ring-closure
Product (yield/%)
Product (yield/%)
Ratio of 13C/14C
Product (yield/%)
1
2
7a
7b
8a (23)
8b (30)
13aC$BFK4 (28), 14aC$BFK4 (56)
13bC$BFK4 (23), 14bC$BFK4 (47)
1: 2
1:2
16a (61)
16b (44)
Table 2. 1H and 13C NMR spectral data and rotational barriers (DG‡) of
methanoundecafulvenes 8a,b and reference compounds 5a,b
Compound
NMR data
13C/da
Rotational barrier
Tc/K
DG‡/kcal/
mol
1H/d
8a
7.24b
7.19b
108.2
108.0
101.7
102.2
258
—
300
308
12.55
—
14.51
14.70
8b
5ac
5bc
9.31, 9.33d
9.28, 9.39d
a C5 of the barbituric acid moiety.
b H20 and H110.
c Ref. 18.
d H20 and H70.
Figure 2.

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S. Naya et al. / Tetrahedron 61 (2005) 7384–7391
Table 3. UV–vis spectral data of 8a,b and 16a,b in CH3CN
conditions of CV measurements, and thus, the peak
potentials are summarized in Table 4. The first reduction
potentials (E1red) of 8a,b are similar to those of 5a,b, while
the first oxidation potentials (E1ox) of 8a,b are less positive
than those of 5a,b.18 These features support that compounds
8a,b have the elongated p-conjugation as the vinylogous
compounds of 5a,b.
Compound
lmax/nm (log 3/dm3 molK1 cmK1
)
8a
8b
473 (3.99), 339 (4.05), 304 (4.11)
472 (3.67), 339 (3.79), 304 (3.88)
16a
16b
546 (4.04), 506 (3.70), 358 (3.82), 307 (3.67), 253 (3.58)
545 (4.44), 507 (4.12), 358 (4.22), 306 (4.08), 251 (3.94)
Table 4. Redox potentials of 8a,b and 16a,b and reference compounds 2a,b and 5a,b
Compound
Redox potentiala
Compound
Redox potentiala
E1red
E1ox
E1red
E1ox
8a
K1.16
K1.15
K1.15
K1.19
C0.83
C0.78
C1.08
C1.09
16a
16b
2ac
2bc
K0.89
K0.90
K1.12
K1.12
—
—
—
—
8b
5ab
5bb
a V versus Ag/AgNO3; cathodic and anodic peak potentials.
b Ref. 18.
c This work.
70.1).23 Furthermore, the proton signals of the H20 and the
H110 of 8a,b appearing at d 7.19–7.24 are remarkably shifted
to higher field as compared with those of 5a,b (d 9.28–9.39).18
These features are ascribed to the bending structure of the 11-
membered ring o0f compounds 8a,b, which do not allow the
H20 and the H11 to locate in the deshielding region of the
carbonyl groups in the barbituric acid moiety. In the 1H NMR
spec0tra of 8a,b at room temperature, the signals of H20 and
H11 (Scheme 1) appear as equivalent, while they appear as
two sharp doublets at low-temperature (K60 8C). Thus, rapid
free rotation around the exocyclic double bond of 8a,b clearly
occurs on the NMR time scale at room temperature. The fact
shows that the enantiomers (R)-8a,b and (S)-8a,b isomerize
each other. Through variable temperature 1H NMR measure-
ment of 8a, the coalescence temperature was determined to be
258 K. In0addition, the chemical shift difference between H-20
and H-11 of 8a was 20.0 Hz. Consequently, rotational barrier
(DG‡) around the exocyclic double bond for 8a was
determined to 0be 12.55 k0cal molK1 (Table 2). The signals of
H20, H30, H10 , and H11 overlap for 8b at low temperature,
and thus, their rotational barriers (DG‡) could not be
determined. The value (DG‡) of 8a is smaller by
1.96 kcal molK1 than that of 5a (14.51 kcal molK1).18 The
feature is rationalized on the basis of the structural change of
8a in the transition state of the rotation around the exocyclic
double bond. Atthe transition state, the 11-membered ringand
the barbituric acid moiety have to be twisted to become
perpendicular to each other, and thus, the 11-membered ring
would have a positive charge as the depicted structure 11 in
Figure 2. Since the 1,6-methano[11]annulenylium ion 9C
(pKRC, 6.2)20 is more stable than the tropylium ion 10C
(pKRC, 3.9),21 the transition state of the rotation of 8a would
be more stabilized than that of 5a. Thus, the rotational barrier
(DG‡) of 8a would be smaller than that of 5a.
2.2. 7,12-Methanocycloundeca[4,5]furo[2,3-d]pyrimi-
dine-2,4(1H,3H)-diones (16a,b)
As novel methodology for synthesizing the furan-ring, we
have previously reported the oxidative cyclization of 5a by
using DDQ to give a mixture of 3bC$BF4K and 3cC$BF4K
(Fig. 1), and thus, the transformation of 8a,b to 16a,b was
investigated. Oxidation reactions of 8a,b with DDQ in
CH2Cl2 at room temperature and subsequent anion
exchange reaction by using 42% aq HBF4 in Ac2O afforded
possible racemic mixtures of 13a,bC$BF4K and
14a,bC$BFK4 , respectively (Scheme 2). The yields and
ratios of 13a,bC$BF4K and 14a,bC$BFK4 are summarized in
Table 1. Upon treatment with an alkaline solution, the
mixtures of 13a,bC$BF4K and 14a,bC$BFK4 were hydro-
lyzed to give 15a,b, which were recyclized by using TFA to
The UV–vis spectra of 8a,b are similar and the absorption
maxima are summarized in Table 3. The longest wavelength
absorption maxima of 8a,b are longer by ca. 40 nm than that
of 5a (432 nm),18 suggesting the elongated p-conjugation of
compounds 8a,b as compared with that of 5a. Furthermore,
the redox property of 8a,b was determined by cyclic
voltammetry (CV) in acetonitrile. The oxidation and
reduction waves of 8a,b were irreversible under the
Scheme 2. Reagents and conditions: (i) (a) DDQ, CH2Cl2, rt, 2 h, (b) 42%
aq HBF4, Ac2O, 0 8C, 1 h; (ii) aq K2CO3, EtOH, rt, 16 h, (iii) TFA, CH2Cl2,
rt, 1 h.

S. Naya et al. / Tetrahedron 61 (2005) 7384–7391
7387
afford 16a,b in moderate to good yields, respectively.60
Apparently, the oxidative cyclization of 8a,b at the C2
position and the C4-carbonyl group gives (R)-
13a,bC$BFK4 , while the cyclization at the C110 position
and the C4-carbonyl group affords (S)-13a,bC$BF4K.
Furthermore, the oxidative cyclization of 8a,b at the C20
position and the C6-carbonyl group gives (R)-
14a,bC$BFK4 , while the cyclization at the C110 position
and the C6-carbonyl group affords (S)-14a,bC$BF4K. Thus,
the oxidative cyclization results in the formation of
racemic compounds (R),(S)-13a,bC$BF4K and (R),(S)-
14a,bC$BFK4 . Accordingly, compounds 16a,b are also
racemic compounds (R),(S)-16a,b. Unfortunately,
attempted optical resolution by means of recrystallization
and chromatography is unsuccessful. Thus, racemic
compounds (R),(S)-13a,bC$BF4K, (R),(S)-14a,bC$BFK4 ,
and (R),(S)-16a,b are represented as 13a,bC$BF4K,
14a,bC$BFK4 , and 16a,b.
protons appear in the aromatic region (d 7.68 to 8.97),
suggesting a large diatropic ring current.26 The differences
in vicinal coupling constants in 16a are larger than those
found in vinylogous compound 2a and delocalized cationic
species 17C$BFK4 , while they are smaller than those found
in 18. The fact suggests that the bond alternation of 16a is
larger than those of 2a and 17C$BF4K and is smaller than
that of 18.
The reduction potentials of 16a,b were determined by cyclic
voltammentry (CV) in CH3CN. The reduction waves of
16a,b were irreversible under the conditions of the CV
measurements; the peak potentials are summarized in
Table 4, together with those of the vinylogous compound
2a,b. The E1red of 16a,b are less negative by 0.23 and
0.22 V than that of 2a,b, respectively. This feature is
rationalized by the elongated p-conjugation of 16a,b as
compared with 2a,b. The irreversible nature is probably due
to the formation of a radical species and its dimerization, as
reported to be a typical property of uracil-annulated
heteroazulenes.5,6
Compounds 16a,b were fully characterized on the basis of
the 1H and 13C NMR, IR, UV–vis, and mass spectral data, as
well as elemental analyses. The UV–vis spectra of 16a,b in
CH3CN are similar and the absorption maxima are
summarized also in Table 3. The longest wave length
absorption maxima (lmax) of 16a,b show a red-shift by ca.
107 nm as compared with those of 2a (439 nm), suggesting
the elongated p-conjugation of 16a,b: the HOMO becomes
higher and the LUMO becomes lower as compared with
those of 2a, respectively. The 1H NMR spectra of 16a,b are
noteworthy, since the chemical shifts of bridged-annulene
systems are quite useful in determining such structural
properties as diatropicity and bond alternation.
Unambiguous proton assignment was made by analyzing
1H NMR, H–H COSY, and NOE spectra. Since a similar
feature is observed in a series of 16a,b, the chemical shifts
of the bridge protons and selected coupling constants of the
peripheral protons of 16a are shown in Figure 3 together
with those of the reference compounds 2a,6 17C$BF4K,24
and 18.25 The large geminal coupling constant of the
methylene protons (JE,ZZ11.3 Hz) supports the absence of
a norcaradiene structure for 16a. The bridge protons of 16a
appear at high-field (d K0.05 and d 0.47), and the peripheral
In order to clarify the reactivity, the reactions of 16a with
some nucleophiles were investigated. The reaction of 2a
with NaBH4 proceeded at the C5, C7, and C9 to afford a
mixture of three regio-isomers 20–22 (Scheme 3).6 In
contrast, the reaction of 16a with NaBD4 in CD3OD in an
NMR tube indicated clean formation of 19, the deuterium of
which locates at endo-position of the C13, and thus, the
methano-bridge controls the nucleophilic attacks to prefer
endo-selectivity. The results show that the methano[11]-
annulene system has a possibility for a novel chiral
auxiliary. Compound 19 is unstable under aerobic con-
ditions and could not be isolated in pure form; however,
satisfactory 1H NMR spectral data are obtained. The
mixture of three regio-isomers 20–22 was oxidized under
aerobic conditions to regenerate 2a quantitatively.6 The
CD3OD solution of 19 was stirred at room temperature
under aerobic conditions for 24 h; however, 19 was
decomposed to result in the formation of a trace amount
of 16a in addition to a substantial quantity of unidentified
materials. While we have reported the reactions of 2a and
17C$BF4K with some amines,5,24 reactions of 16a with
diethylamine and benzylamine did not proceed and the
starting 16a was recovered quantitatively.
Scheme 3. Reagents and conditions: (i) NaBD4, CD3OD, rt, 1 h;
(ii) aerobic, CD3OD, rt, 24 h; (iii) NaBH4, CH3OH, rt, 1 h; (iv) aerobic,
CH2Cl2, rt, 24 h.
Figure 3. Chemical shifts and coupling constants of 16a, 2a, 17C$BF4K
and 18.
,

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S. Naya et al. / Tetrahedron 61 (2005) 7384–7391
imines by using 16a are larger than the yields of the imines
by using 2a. Furthermore, the yields of photo-induced
oxidation of normal amines are larger than those of
secondary alkyl amines by using compounds 16a
(Table 5, runs 1–4). A similar feature is observed in the
oxidation by using 2a. Thus, the photo-induced oxidizing
reaction by using 16a and 2a is more effective for the
normal amines. We propose that the present autorecycling
oxidation proceeds via electron-transfer from amine to the
excited compounds 16a and 2a as shown in Scheme 45,27
The electron-transfer from amine to the excited state of 16a
and 2a would occur to produce anion radicals of 16a and 2a
and a cation radical 23. An electron transfer from anion
radical species 16a and 2a to molecular oxygen may give
the superoxide anion radical and 16a and 2a, since tropyl
radical derivatives are known to be oxidized readily by
molecular oxygen.28 Then, a proton-transfer from cation
radical 23 to the superoxide anion radical may occur, and
followed by formation of the products 25 and H2O2.
Compound 25 reacts with excess amine to give imine 26.
Scheme 4. Reagents and conditions: (i) hn, aerobic, CH3CN, rt, 16 h.
2.3. Autorecycling oxidation of amines
3. Conclusion
We have previously reported that compounds 1a,5
3aC$BF4K,27 and 17C$BFK4 24 undergo autorecycling
oxidation toward some amines under photo-irradiation. In
this context and in a search for the functions of 16a, we
examined the oxidation of some amines (Scheme 4). We
found that compound 16a has oxidizing ability toward
benzylamine, 1-phenylethylamine, hexylamine and cyclo-
hexylamine to give the corresponding imines under aerobic
and photo-irradiation conditions. Imine R1R2C]NH 25 is
produced at first; however, it reacts with another amine to
result in the formation of R1R2C]N–CHR1R2 26.
Oxidation reaction of some amines using 2a was also
carried out under similar conditions. The results are
summarized in Table 5. Direct irradiation of the amines in
the absence of 16a and 2a (named ‘blank’) gives the
corresponding imines in low to modest yields. Thus, the
yields are calculated by subtraction of the blank yield from
the yield of the imine in the presence of 16a and 2a. The
recycling numbers are more than one (Table 5, runs 1–8),
and thus, autorecycling oxidation clearly proceeds. In the
photo-induced oxidation of each amine, the yields of the
Novel 4,9-methanoundecafulvene derivatives 8a,b were
synthesized for the first time. Their structural characteristics
were clarified on the basis of the 1H and 13C NMR and UV–
vis spectra. Through the variable temperature 1H NMR
measurement, the rotational barrier (DG‡) around the
exocyclic double bond of 8a was determined to be
12.55 kcal molK1, which is smaller by 1.96 kcal molK1
than that of the seven-membered vinylogue 5a due to the
higher stability of 1,6-methano[11]annulenylium ion 9C.
The electrochemical properties of 8a,b were also clarified
by CV measurement. Furthermore, the transformation of
8a,b to 3-substituted 7,12-methanocycloundeca[4,5]-
furo[2,3-d]pyrimidin-2,4(1H,3H)-diones 16a,b was accom-
plished by oxidative cyclization and subsequent ring-
opening and ring-closure. The physical properties of 16a
1
were studied by measurement of the UV–vis spectra, H
NMR, and redox potentials. Reaction of 16a with deuteride
afforded C13-adduct 19 as the single product, and thus, the
methano-bridge controls the nucleophilic attacks to prefer
endo-selectivity. The results show that the methano[11]-
annulene system has a possibility for a novel chiral
auxiliary. The photo-induced autorecycling oxidation of
16a and 2a toward some amines under aerobic conditions
was carried out to give the corresponding imines (isolated
by converting to the corresponding 2,4-dinitrophenyl-
hydrazones) with the recycling number 6.1–64.0 (for 16a)
and 2.7–17.2 (for 2a), respectively.
Table 5. Autorecycling oxidation of some amines by 16a and 2a under
photo-irradiationa
Run
Compound
Amine
Yield/
mmolb,c
Recycling
no.d
1
2
3
4
5
6
7
8
16a
16a
16a
16a
2a
2a
2a
2a
PhCH2NH2
PhCH(Me)NH2
Hexylamine
Cyclohexylamine
PhCH2NH2
PhCH(Me)NH2
Hexylamine
Cyclohexylamine
320.0
227.0
237.5
30.6
86.0
79.5
64.0
45.4
47.5
6.1
17.2
15.9
13.2
2.7
4. Experimental
4.1. General
66.0
13.6
a An CH3CN (16 mL) solution of compound 16a or 2a (5 mmol) and amines
(2.5 mmol, 500 equiv) was irradiated by RPR-100, 350 nm lamps under
aerobic conditions for 16 h.
IR spectra were recorded on a HORIBA FT-710 spec-
trometer. 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 and
13C NMR spectra were recorded on JNM-lambda500 and
b Isolated by converting to the corresponding 2,4-dinitrophenylhydrazone.
c The yield is calculated by subtraction of the ‘blank’ yield from the total
yield.
d Recycling number of 16a and 2a.

S. Naya et al. / Tetrahedron 61 (2005) 7384–7391
7389
AVANCE600 spectrometers, 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 were uncorrected.
(400 MHz, CDCl3) d K1.31 (1H, d, JZ11.2 Hz, HZ),
K0.47 (1H, d, JZ11.2 Hz, HE), 3.37 (3H, s, NMe), 8.35–
8.44 (2H, m, H-8 and H-11), 8.49 (1H, d, JZ7.8 Hz, H-8 or
H-11), 8.60 (1H, d, JZ8.1 Hz, H-11 or H-8), 9.18 (1H, d,
JZ10.7 Hz, H-6), 9.63 (1H, d, JZ10.7 Hz, H-5), 9.66 (1H,
s, H-13), 9.81 (1H, bs, NH). (14aC$BF4K) 1H NMR
(400 MHz, CDCl3) d K1.26 (1H, d, JZ11.2 Hz, HE),
K0.46 (1H, d, JZ11.2 Hz, HE), 3.67 (3H, s, NMe), 8.35–
8.44 (2H, m, H-8 and H-11), 8.49 (1H, d, JZ7.8 Hz, H-8 or
H-11), 8.60 (1H, d, JZ8.1 Hz, H-11 or H-8), 9.16 (1H, d,
JZ10.7 Hz, H-6), 9.52 (1H, d, JZ10.7 Hz, H-5), 9.68 (1H,
s, H-13), 9.81 (1H, bs, NH).
4.2. Preparation of 8a,b
A solution of each barbituric acid 7a (568 mg, 4 mmol) and
7b (736 mg, 4 mmol) and 4,9-methano[11]annulenone 6
(170 mg, 1 mmol) in Ac2O (2 mL) was heated at 120 8C for
1 h. After the reaction was completed, the reaction mixture
was concentrated in vacuo. The resulting residue was
purified by column chromatography on Al2O3 by using
AcOEt as the eluent to give the products 8a (68 mg, 23%)
and 8b (101 mg, 30%).
4.3.2. A mixture of compounds 13bC$BF4K and
14bC$BF4K. Dark brown powder; (13bC$BFK4 ) H NMR
1
(400 MHz, CDCl3) d K1.26 (1H, dt, JZ11.5, 1.7 Hz, HZ),
K0.42 (1H, d, JZ11.5 Hz, HE), 1.12 (3H, t, JZ7.3 Hz,
Bu-4), 1.43 (2H, sext., JZ7.3 Hz, Bu-3), 1.68 (2H, quint.,
JZ7.3 Hz, Bu-2), 4.04 (2H, t, JZ7.3 Hz, Bu-1), 8.38–8.47
(2H, m, H-9 and H-10), 8.53 (1H, d, JZ7.8 Hz, H-8 or
H-11), 8.61 (1H, d, JZ8.1 Hz, H-11 or H-8), 9.22 (1H, d,
JZ10.6 Hz, H-6), 9.69 (1H, s, H-13), 9.69 (1H, d, JZ
10.6 Hz, H-5). (14bC$BF4K) 1H NMR (400 MHz, CDCl3) d
K1.21 (1H, dt, JZ11.5, 1.7 Hz, HZ), K0.41 (1H, d, JZ
11.5 Hz, HE), 1.01 (3H, t, JZ7.3 Hz, Bu-4), 1.50 (2H, sext.,
JZ7.3 Hz, Bu-3), 1.86 (2H, quint., JZ7.3 Hz, Bu-2), 4.24
(2H, td, JZ7.3, 2.0 Hz, Bu-1), 8.38–8.47 (2H, m, H-9 and
H-10), 8.53 (1H, d, JZ7.8 Hz, H-8 or H-11), 8.61 (1H, d,
JZ8.1 Hz, H-11 or H-8), 9.19 (1H, d, JZ10.5 Hz, H-6),
9.58 (1H, d, JZ10.5 Hz, H-5), 9.69 (1H, s, H-13).
4.2.1. Compound 8a. Dark reddish powder; mp 271–272 8C
(from AcOEt); H NMR (500 MHz, CDCl3) d K0.27 (1H,
1
d, JZ11.0 Hz, HE), 1.58 (1H, d, JZ11.0 Hz, HZ), 3.34 (3H,
s, NMe), 7.08–7.10 (2H, m, H-50, H-80), 7.19 (2H, d, JZ
0
0
0
11.5 Hz, H-3 , H-10 ), 7.24 (2H, d, JZ11.5 Hz, H-2 ,
H-110), 7.41 (2H, m, H-60, H-70), 7.86 (1H, s. NH); 13C
NMR (150.9 MHz, CDCl3) d 27.6, 34.1, 108.2, 116.2,
122.5, 123.5, 127.0, 131.6, 132.2, 135.0, 135.1, 147.0,
150.3, 161.1, 162.7, 165.3 (one carbon overlapping); IR
(CHCl3) nmax 1729, 1686, 1652, 1599, 1486, 1406,
1317 cmK1; EIMS (70 eV) m/z (rel. intens) 294 (MC,
1.4), 58 (100). Anal. Calcd for C17H14N2O3$H2O: C, 65.38;
H, 5.16; N, 8.97. Found: C, 65.20; H, 4.96; N, 8.82.
4.2.2. Compound 8b. Reddish powder; mp 119–120 8C
(from AcOEt); 1H NMR (500 MHz, CDCl3 60 8C) d K0.23
(1H, d, JZ10.9 Hz, HE), 0.96 (3H, t, JZ7.4 Hz, Bu-4), 1.41
(2H, sext., JZ7.4 Hz, Bu-3), 1.64 (2H, quint., JZ7.4 Hz,
Bu-2), 1.67 (1H, d, JZ11.5 Hz, HZ), 3.91 (2H, t, JZ7.4 Hz,
Bu-1), 7.03–7.05 (2H, m, H-50, H-80), 7.14 (2H, d, JZ
11.9 Hz, H-30, H-100), 7.19 (2H, d, JZ11.9, Hz, H-20,
H-110), 7.38 (2H, m, H-60, H-70), 7.62 (1H, s, NH); 13C
NMR (150.9 MHz, CDCl3) d 13.8, 20.2, 30.2, 34.1, 41.0,
108.0, 111.4, 116.3, 122.5, 131.6, 132.0, 133.9, 136.5,
136.8, 138.2, 150.0, 161.1, 162.5, 165.2 (one carbon
overlapping); IR (CHCl3) nmax 2966, 2369, 2326, 1714,
1683, 1651, 1560, 1538, 1489, 1457, 1405 cmK1; MS
(MALDI) m/z 336 (MC). Anal. Calcd for C20H20N2O3$
AcOEt: C, 69.46; H, 6.36; N, 7.36. Found: C, 69.77; H,
6.01; N, 7.36.
4.4. Preparation of 16a,b
To a solution of each mixture of 13a,bC$BF4K and
14a,bC$BFK4 (0.05 mmol) in EtOH (2 mL) was added
2 M aq K2CO3 (1 mL), and the mixture was stirred at rt for
16 h. To the mixture was added satd aq NH4Cl, and the
mixture was extracted with CH2Cl2. The CH2Cl2 extract
was dried over Na2SO4 and concentrated in vacuo. The
residue was dissolved in CH2Cl2 (2 mL) and TFA (0.2 mL),
the mixture was stirred at rt for 1 h until the reaction was
completed. To the solution was added satd aq NaHCO3, and
the mixture was extracted with CH2Cl2, and the extract was
dried over Na2SO4 and concentrated in vacuo. The resulting
residue was purified by column chromatography on SiO2 by
using MeOH as the eluent to give the products 16a (8.9 mg,
61%) and 16b (7.3 mg, 44%).
4.3. Preparation of mixtures of 13a,bC$BF4K and
14a,bC$BFK4
4.4.1. Compound 16a. Reddish powder; mpO280 8C (from
AcOEt); 1H NMR (600 MHz, CDCl3) d K0.05 (1H, d, JZ
11.3 Hz, HE), 0.47 (1H, d, JZ11.3 Hz, HZ), 3.47 (3H, s,
NMe), 7.68–7.71 (1H, m, H-8), 7.73–7.76 (1H, m, H-11),
7.83–7.87 (2H, m, H-9, H-10), 8.24 (1H, d, JZ11.5 Hz,
H-6), 8.58 (1H, s, H-13), 8.97 (1H, d, JZ11.5 Hz, H-5); 13C
NMR (150.9 MHz, CDCl3) d 27.8, 35.0, 103.7, 13.6, 125.0,
131.7, 132.2, 132.3, 135.0, 135.2, 145.3, 147.0, 152.6,
158.6, 161.4, 174.1 (one carbon overlapping); IR (CHCl3)
nmax 1696, 1621, 1577, 1313 cmK1; MS (FAB) m/z 293
(MCCH). HRMS calcd for C17H12N2O3: 293.0950 (MC
H). Found: 293.0943 (MCCH).
To a solution of each 8a (59 mg, 0.2 mmol) and 8b (67 mg,
0.2 mmol) in CH2Cl2 (2 mL) was added DDQ (70 mg,
0.3 mmol) and the mixture was stirred at rt for 2 h until the
reaction was completed. After evaporation of the CH2Cl2,
the residue was dissolved in Ac2O (5 mL) and 42% HBF4
(1 mL) at 0 8C, and the mixture was stirred for 1 h. To the
mixture was added Et2O (100 mL), and the precipitates
were collected by filtration to give a mixture of 13aC$BF4K
and 14aC$BF4K (64 mg, 84%) and a mixture of 13bC$BF4K
and 14bC$BFK4 (59 mg, 70%).
4.3.1. A mixture of compounds 13aC$BF4K and
4.4.2. Compound 16b. Reddish powder; mpO280 8C
(from AcOEt); H NMR (600 MHz, CDCl3) d K0.02 (1H,
1
1
14aC$BF4K. Dark brown powder; (13aC$BFK4 ) H NMR

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S. Naya et al. / Tetrahedron 61 (2005) 7384–7391
d, JZ11.4 Hz, HE), 0.55 (1H, dt, JZ11.4, 1.8 Hz, HZ), 0.97
(3H, t, JZ7.3 Hz, Bu-4), 1.43 (2H, sext., JZ7.3 Hz, Bu-3),
1.70 (2H, quint., JZ7.3 Hz, Bu-2), 4.08 (2H, m, Bu-1),
7.64–7.67 (1H, m, H-8), 7.69–7.72 (1H, m, H-11), 7.81–
7.84 (2H, m, H-9, H-10), 8.19 (1H, d, JZ11.4 Hz, H-6),
8.54 (1H, s, H-13), 8.96 (1H, d, JZ11.4 Hz, H-5); 13C NMR
(150.9 MHz, CDCl3) d 13.9, 20.4, 30.2, 35.1, 41.0, 77.4,
101.0, 123.5, 124.9, 131.5, 131.7, 132.0, 134.9, 135.0,
145.3, 146.8, 152.7, 158.0, 161.3, 174.1, (one carbon
overlapping); IR (CHCl3) nmax 2361, 2333, 1712, 1624,
1575, 1546, 1510, 1303 cmK1; MS (FAB) m/z 335 (MCC
H). HRMS calcd for C20H18N2O3: 335.1430 (MCH).
Found: 335.1375 (MCCH). Anal Calcd for C20H18N2-
O3$2AcOEt: C, 65.87; H, 6.71; N, 5.49. Found: C, 65.13; H,
6.57; N, 5.22.
4.8. General procedure for autorecycling oxidation of
amines in the presence of 16a and 2a
An CH3CN (16 mL) solution of compound 16a (1.47 mg,
5 mmol) or 2a (1.14 mg, 5 mmol) and amines (2.5 mmol,
500 equiv) in a Pyrex tube was irradiated by RPR-100,
350 nm lamps under aerobic conditions for 16 h. The
reaction mixture was concentrated in vacuo and diluted with
Et2O and filtered. The 1H NMR spectra of the filtrates
revealed the formation of the corresponding imines. The
filtrate was treated with a saturated solution of 2,4-
dinitrophenylhydrazine in 6% HCl to give 2,4-dinitro-
phenylhydrazone of the corresponding carbonyl
compounds. The results are summarized in Table 5.
4.5. Cyclic voltammetry of 8a,b and 16a,b
Acknowledgements
The redox potentials of 8a,b and 16a,b were determined by
means of CV-27 voltammetry controller (BAS Co). A three-
electrode cell was used, consisting of Pt working and
counter electrodes and a reference Ag/AgNO3 electrode.
Nitrogen was bubbled through an acetonitrile solution
(4 mL) of each compound (0.5 mmol dmK3) and Bu4NClO4
(0.1 mol dmK3) to deaerate it. The measurements were
made at a scan rate of 0.1 V sK1 and the voltammograms
were recorded on a WX-1000-UM-019 (Graphtec Co) X-Y
recorder. Immediately after the measurements, ferrocene
(0.1 mmol) (E1/2ZC0.083) was added as the internal
standard, and the observed peak potentials were corrected
with reference to this standard. The compounds exhibited
no reversible redox wave: each of the redox potentials
was measured through independent scan, and they are
summarized in Table 4.
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 and elemental analyses.
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