Novel synthesis and properties of 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborate: Autorecycling oxidation of some alcohols under photo-irradiation

Article abstract of DOI:10.1016/S0040-4020(03)00118-2

Three-step reactions starting from 2-chlorotropone with barbituric acid afforded novel 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborate (9·BF₄^-), which is the isoelectronic compound of the 5-ethyl-3-methyllumiflavinium ion. The stability of cation 9 is expressed by the pK_R+ value, which was determined spectrophotometrically, as ca. 6.0. The electrochemical reduction of 9 exhibited low reduction potential at -0.58 (V vs Ag/AgNO₃), upon cyclic voltammetry (CV). In a search for the reactivity, reactions of 9·BF₄^- with some nucleophiles, hydroxide, hydride, amines, thiols, and methanol, were carried out to exhibit that the introduction of nucleophiles is dependent on the nucleophile itself. The photo-induced oxidation reactions of some alcohols catalyzed by 9·BF₄^- under aerobic conditions were carried out to give the corresponding carbonyl compounds in more than 100% yield [based on compound 9·BF₄^-], suggesting the oxidizing function of 9·BF₄^- toward alcohols in the autorecycling process. The UV-vis and fluorescence spectra of 9 were studied to suggest the electron transfer from alcohols to the excited 9.

Full text of DOI:10.1016/S0040-4020(03)00118-2

Tetrahedron 59 (2003) 1811–1821
Novel synthesis and properties of 7,9-dimethylcyclohepta[b]-
pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborate:
autorecycling oxidation of some alcohols under photo-irradiation
*
Shin-ichi Naya, Hisashi Miyama, Kenji Yasu, Tohru Takayasu and Makoto Nitta
Department of Chemistry, School of Science and Engineering, Waseda University, Shinjuku-ku, Tokyo 169-8555, Japan
Received 27 November 2002; accepted 8 January 2003
Abstract—Three-step reactions starting from 2-chlorotropone with barbituric acid afforded novel 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]-
furan-8(7H),10(9H)-dionylium tetrafluoroborate (9·BF24 ), which is the isoelectronic compound of the 5-ethyl-3-methyllumiflavinium ion.
The stability of cation 9 is expressed by the pKRþ value, which was determined spectrophotometrically, as ca. 6.0. The electrochemical
reduction of 9 exhibited low reduction potential at 20.58 (V vs Ag/AgNO3), upon cyclic voltammetry (CV). In a search for the reactivity,
reactions of 9·BF24 with some nucleophiles, hydroxide, hydride, amines, thiols, and methanol, were carried out to exhibit that the introduction
of nucleophiles is dependent on the nucleophile itself. The photo-induced oxidation reactions of some alcohols catalyzed by 9·BF24 under
aerobic conditions were carried out to give the corresponding carbonyl compounds in more than 100% yield [based on compound 9·BF24 ],
suggesting the oxidizing function of 9·BF24 toward alcohols in the autorecycling process. The UV–vis and fluorescence spectra of 9 were
studied to suggest the electron transfer from alcohols to the excited 9. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
5-deazaflavin (1a) and 5-deaza-10-oxaflavin (1b), and their
function in oxidizing some alcohols to the corresponding
carbonyl compounds.8 In relation to the studies, we have
investigated the synthesis and properties of heteroazulene-
substituted methyl cations9–12 and tropylium ions.13 In the
studies, the reduction potentials and pKRþ values of these
cations were clarified to be strongly dependent on the
heteroatoms in the heteroazulene moiety. Moreover, the
heteroazulenes are demonstrated to stabilize not only
cations but also radical species. On the other hand, the
photo-induced oxidizing reaction of amines by 3-methyl-
lumiflavin (3) and its related 5-ethyl-3-methyllumiflavinium
ion (4) has been investigated to clarify the mechanistic
aspects.14 In addition, photo-induced oxidizing reaction by
using the acridinium ion have also been reported.15–17 The
oxidation of p-xylene to p-tolualdehyde was initiated by
The importance of fused uracils, which are common sources
for the development of new potential therapeutic agents, is
well known.1,2 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 oxidases. 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 analogs.3 In this relation, 5-deaza-
flavins (1a) has been studied extensively in both enzymatic4
and model systems5,6 in the hope of providing mechanistic
insight into flavin-catalyzed reactions. In addition, 5-deaza-
10-oxaflavin (1b) (2H-chromeno[2,3-d]pyrimidine-2,4(3H)-
dione, Fig. 1), in which the nitrogen atom of the
5-deazaflavin (1a) is replaced by an oxygen, has been
synthesized and found to possess a strong function to
oxidize alcohols to the corresponding carbonyl com-
pounds.7 On the basis of the above observations, we have
previously studied convenient preparations of 6,9-disubsti-
tuted cyclohepta[b]pyrimido[5,4-d]pyrole-8(6H),10(9H)-
diones (2a) and 9-methylcyclohepta[b]pyrimido[5,4-d]-
furan-8,10(9H)-dione (2b), which are structural isomers of
Keywords: 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-
dionylium tetrafluoroborate; tropylium cation; oxidizing function; photo-
reaction.
*
Corresponding author. Tel.: þ81-3-5286-3236; fax: þ81-3-3208-2735;
e-mail: nitta@waseda.jp
Figure 1.
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00118-2

1812
S. Naya et al. / Tetrahedron 59 (2003) 1811–1821
Scheme 1. Reagents and conditions: (i) ButNH2, CH2Cl2, rt, 24 h; (ii) 3%
HCl; (iii) 42% aq. HBF4, propanoic anhydride, 08C, 1 h; (iv) aq. NaHCO3,
CH3CN, rt, 6 h.
photo-induced electron transfer from p-xylene to the singlet
excited state of the 10-methyl-5-phenylacridinium ion under
photo-irradiation.17 Thus, in search for the reactivity and
oxidizing function of uracil-annulated heteroazulenes, we
studied the synthesis and properties of novel 7,9-dimethyl-
cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionyl-
ium tetrafluoroborate (9·BF42). The photo-induced oxidizing
reaction of 9·BF24 toward some alcohols to give the corre-
sponding carbonyl compounds was studied as well. We
report herein the results in detail.
Scheme 2. Reagents and conditions: (i) ButNH2, CH2Cl2, rt, 24 h; (ii) 3%
HCl; (iii) 42% aq. HBF4, propionic anhydride, 08C, 1 h.
of the deuterated compounds were based on the HRMS and
assigned 1H NMR spectra (Section 4). Thus, the cyclization
reaction of 8 giving furan moiety is also confirmed to
proceed via C-1 attack, but not C-3 attack, on the tropone
nucleus (Scheme 2).
2. Results and discussion
2.1. Synthesis
Reactions of 2-chlorotropone (5) with dimethylbarbituric
acid (6) was performed in CH2Cl2 in the presence of
ButNH2 at rt for 24 h to give 7 as yellow solid, which is
contaminated with ButNH3Cl (Scheme 1). The solid of 7
was dissolved in 3% HCl and extracted with CH2Cl2 to give
8 as colorless prisms in 94% yield. Compounds 7 and 8 were
treated with aq. HBF4 in Ac2O at 08C for 1 h to result in the
formation of 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]-
furan-8(7H),10(9H)-dionylium tetrafluoroborate (9·BF24 )
in 91 and 96% yields, respectively. Compound 9·BF24 was
easily hydrolyzed by aq NaHCO3 to regenerate 8 in good
yield. Nucleophilic substitution onto a tropone carrying a
mobile substituent is known to take place at C-2 (usual
substitution) or at C-7 (unusual substitution) to give
2-substituted tropones.18 In order to confirm this point and
the cyclization pathways to give 9·BF24 , the reaction of
2-chloro-3,5,7-trideuteriotropone 5-d3 with 6 was studied
(Scheme 2). Reaction of 5-d3 with 6 afforded a mixture of
7-4,6d2 and 7-3,5d2 in a ratio of 9:1, suggesting that the
nucleophilic attack of 6 occurred at both C-7 and C-2 of the
tropone nucleus in that ratio. Treatment of a mixture of
7-4,6d2 and 7-3,5d2 with 3% HCl afforded 8-4,6d2 and
8-3,5d2 in a ratio of 9:1. The mixture was treated with aq.
HBF4 in Ac2O to afford a mixture of 9-2,4d2·BF24 and
9-1,3d2·BF24 in a similar ratio. The structures and the ratios
2.2. Properties
Compounds 7, 8, and 9·BF24 were fully characterized on the
basis of IR, UV–vis, mass spectral data as well as elemental
analyses or X-ray structure analysis. In the 1H NMR
spectrum, protons of the seven-membered ring of 7
appeared as sharp signals in DMSO-d6. On the contrary,
these protons of 8 exhibited broad signals in DMSO-d6,
CDCl3, and CD3CN and an active methyne-proton (H-5 in
the barbituric acid moiety) signal appeared at d 4.16 in
CDCl3. In CD3OD, these protons of 8 exhibited sharp
signals and the active methyne-proton signal disappeared.
The features show that compound 8 exists as the keto-form
in DMSO-d6, CDCl3, and CD3CN and as the enol-form in
CD3OD. In addition, broad signals of the seven-membered
ring protons of 8 are probably due to the large steric
hindrance between the carbonyl functions of barbituric acid
and the troponyl moieties restricting free rotation in the
NMR time scale. Moreover, the tautomeric change depend-
ing on the solvent was confirmed by 13C NMR and UV–vis
spectra. In a 13C NMR spectrum of 8, an active methyne-
carbon signal appeared at d 57.2 (CDCl3), although
this carbon signal appeared at d 97.3 in CD3OD. Other
carbon signals exhibited slight change. The signal of the

S. Naya et al. / Tetrahedron 59 (2003) 1811–1821
1813
Figure 4. UV–vis spectrum of 9 in CH3CN.
Figure 2. UV–vis spectra of 7 and 8.
expressed by the pKRþ value, is the most common criterion
of carbocation stability.19 The pKRþ value of cation 9 was
determined spectrophotometrically in buffer solutions pre-
pared in 50% aqueous CH3CN and summarized in Table 1,
along with those of reference compounds 4,20 10,21 and 11
(Fig. 5).22 On treatment with aqueous NaHCO3 solution,
compound 9·BF24 undergoes ring-opening reaction to give 8
(Scheme 1). Thus, the sharp titration curve for neutralization
of cation 9 was not obtained, and the pKRþ value of 9 was
estimated to be ca. 6.0. The pKRþ value of 9 is larger than
that of 1021 (pKRþ, 3.9) and it is smaller by about 1.0 pH
unit than those of the corresponding parent cation 11 (pKRþ
6.9).22 In addition, the pKRþ value of 9 is larger than that of
4.
corresponding carbon of 7 appeared at d 89.5 (DMSO-d6),
and thus, the structure of 8 in CD3OD exists as the enol
form. UV–vis spectra of 8 in CH3CN and CH2Cl2 as well as
7 and 8 in MeOH are shown in Figure 2. The spectra of 8
in CH3CN and CH2Cl2 are similar, while the spectrum of
8 in MeOH shows remarkable change. In contrast, the
spectra of 7 and 8 in MeOH are similar, suggesting that 8
exists as the enol-form in MeOH. Although the single
crystal of 9·BF24 could not be obtained, the X-ray crystal
analysis clarified the structural details of 8, and the ORTEP
drawing is shown in Figure 3. The troponyl moiety is nearly
planar. The angles of C2–C8–C9, C2–C8–C10, and
C9–C8–C10 are 111.8, 110.3, and 115.28, respectively.
These values show that the C8 atom exists in sp3
hybridization. The dihedral angle of H–C8–C2–C1 is
179.28, suggesting that the troponyl moiety and the
barbituric acid moiety are nearly perpendicular to each
other.
The reduction potential of 9 was determined by cyclic
voltammentry (CV) in CH3CN. The reduction wave of 9
was irreversible under the conditions of the CV measure-
ments; the peak potential is summarized in Table 1, together
with those of the reference compound 2b as well as 414 and
10.21 The irreversible nature is probably due to the
formation of tropyl radical and its dimerization. This
The characteristic band for the counter anion BF24 was
observed at 1084 cm21 in the IR spectrum of 9·BF24 . The
UV–vis spectrum of cation 9 in CH3CN is shown in Figure
4. The longest wavelength of absorption maximum of 9 is
397 nm. These spectroscopic properties as well as the NMR
spectral data are in good accordance with the structure of
9·BF24 .
Table 1. pKRþ Values and reduction potentials (peak potential in V vs
Ag/AgNO3) of cations 9 (Reversible process is shown in parentheses. Salts
9·BF24 were used for the measurement; the measurement was made at a scan
rate of 0.1 V s21) and reference compounds 2b, 4, 10, and 11
The affinity of carbocations toward the hydroxide ion,
Compd.
pKRþ
Reduction potential E1red (V)
9
ca. 6.0
–
20.58
21.12a
(þ0.29)c
20.51
–
2b
4
4.15b
3.9
10d
11e
6.9
a
This work.
Ref. 20.
Ref. 14.
Ref. 21.
Ref. 22.
b
c
d
e
Figure 3. An ORTEP drawing of 8 with thermal ellipsoid plot (50%
˚
probability). Selective bond lengths (A) and angles (8); O1–C1 1.244(2),
C1–C2 1.466(2), C2–C3 1.357(2), C3–C4 1.424(3), C4–C5 1.345(3),
C5–C6 1.418(3), C6–C7 1.352(3), C7–C1 1.445(2), C2–C8–C9 111.8(1),
C2–C8–C10 110.3(1), C9–C8–C10 115.2(1).
Figure 5.

1814
S. Naya et al. / Tetrahedron 59 (2003) 1811–1821
Table 2. Results for the addition reaction of cations 9·BF24 with some nucleophiles
Entry
Nucleophile
Product (combined Yield)
Ratio of adduct
Regeneration of cation
1-Adduct
3-Adduct
5-Adduct
5a-Adduct
9·BF24 /%
1
2
3
4
5
6
NaBH4
BnNH2
Et2NH
PhSH
BnSH
MeOH
12–14 (97%)
17 (95%)
18 (100%)
19, 20 (60%)
21–23 (100%)
24–26 (100%)
12 (29)
13 (12)
14 (59)
90
91
100
99
60
95
17 (100)
18 (100)
19 (58)
21 (59)
24 (40)
20 (42)
22 (32)
25 (47)
23 (9)
26 (12)
Table 3. 1H NMR spectral data (500 MHz) of addition products
Compd.
H-1
H-2
H-3
H-4
H-5
Remaining signals
12
13
14
19
20
21
22
23
24
25
26
dH
J
dH
J
dH
J
dH
J
dH
J
dH
J
dH
J
dH
J
3.42
7.00
7.02
5.60
6.96
5.36
7.12
7.00
5.75
7.04
7.29
5.51
5.44
6.40
5.80
5.71
5.73
5.58
6.31
6.16
5.60
6.85
6.03
2.50
6.11
6.05
4.52
6.12
3.89
6.21
6.51
3.62
6.60
6.27
5.39
5.47
5.83
5.65
6.18
5.47
5.76
6.55
5.54
6.73
6.62
6.63
3.36
6.28
6.67
6.58
6.62
4.95
6.93
6.64
5.97
3.39 (Me), 3.54 (Me)
3.42 (Me), 3.59 (Me)
3.39 (Me), 3.53 (Me)
6.2
9.4
10.5
6.3
6.3
6.9
11.4
9.7
11.2
7.8
6.3
10.4
7.3
6.2
3.37 (Me), 3.52 (Me), 7.11-7.29 (5H, m, Ph)
3.39 (Me), 3.54 (Me), 7.11–7.29 (5H, m, Ph)
3.39 (Me), 3.49 (Me), 3.78 (2H, s, CH2), 7.11–7.32 (5H, m, Ph)
3.41 (Me), 3.56 (Me), 3.67 (2H, s, CH2), 7.11–7.32 (5H, m, Ph)
3.39–3.78 (8H, s, CH2, Me), 7.11–7.32 (5H, m, Ph)
3.42 (Me), 3.60 (Me), 3.23 (3H, s, OMe)
11.2
7.8
11.7
10.5
11.4
10.5
8.1
10.2
8.0
8.5
11.0
7.4
7.2
10.8
11.1
7.3
7.6
7.3
11.0
7.9
dH
J
dH
J
dH
J
10.3
4.7
10.3
10.3
10.8
3.42 (Me), 3.60 (Me), 3.42 (3H, s, OMe)
10.0
7.3
4.8
3.44 (Me2), 3.14 (3H, s, OMe)
11.2
7.6
reduction behavior seems to be a typical property of
tropylium ions.23 Since the E1red of 9 is more positive by
0.54 V than that of 2b, 9 is thus expected to have higher
oxidation ability. In addition, the E1red of 9 is more negative
by 0.87 V than that of 4. This feature suggests that the
oxidizing ability of 9 may be lower than that of 4.
2.3. Reactivity of 9·BF42
The reactions of heteroazulenylium ion 9·BF24 with some
nucleophiles were carried out. The reaction site of the cation
showed remarkable difference depending on the nucleo-
phile. The results are summarized in Table 2. Since the
products were unstable on SiO2 and Al2O3, regio-isomers
except 25 could not be separated. Thus, the structural
assignments were based on the 1H and 13C NMR spectra and
IR spectra as well as high-resolution mass spectra of the
1
mixtures. The H NMR spectra of the mixtures of each
regio-isomer except the ring-opened products, 17 and 18,
could be assigned by using H–H COSY spectra, and they
are summarized in Table 3.
Reduction of 9·BF42 with NaBH4 in CH3CN afforded a
mixture of three compounds 12, 13, and 14, and the mixture
was oxidized by DDQ to regenerate 9·BF24 in good yield
(Scheme 3, Table 2, entry 1).
The reactions of 9·BF24 with benzylamine and diethylamine
afforded single products 17 and 18, respectively, which
derive from 5a-adducts 15 and 16, respectively (Scheme 4,
Table 2, entries 2 and 3). The physical data (Section 4) could
rationalize their structures. The coupling constants of
protons on the seven-membered ring of 18 are 8.4, 10.8,
7.1, and 11.6, respectively, suggesting the bond-length
Scheme 3. Reagents and conditions: (i) NaBH4, CH3CN, rt, 1 h;
(ii) (a) DDQ, CH2Cl2, rt, 1 h; (b) 42% aq. HBF4, Ac2O, 08C, 1 h.

S. Naya et al. / Tetrahedron 59 (2003) 1811–1821
1815
Scheme 6. Reagents and conditions: (i) MeOH, NaHCO3, CH3CN, rt;
(ii) 42% HBF4, Ac2O.
19–23 were obtained in good combined yields. The
mixtures of addition products regenerated 9·BF24 in good
yields upon treatment with aq. HBF4 in Ac2O. The addition
products were obtained preferentially in the order of
1.3.5-adducts. In compounds 19 and 21, the coupling
constants between H-1 and H-2 are large. Similarly, the
coupling constant between H-4 and H-5 in compound 23 is
large. Thus, these coupling constants suggest that the sulfide
groups are located at the pseudo-axial position in the
cycloheptatriene moiety.24
Scheme 4. Reagents and conditions: i (a), BnNH2 or Et2NH, CH3CN, rt,
0.5 h; (b) 3% HCl; (ii) 42% HBF4, Ac2O.
The reaction of 9·BF24 with MeOH afforded a mixture of
compound 24, 25, and 26 in a ratio of 40: 47: 12 as a reddish
oil. As mentioned below, since these products rearrange
each other, this ratio depends on the reaction time (Scheme
6, Table 2, entry 6). A mixture of compounds 24, 25, and 26
was characterized by the 1H and 13C NMR and IR spectra as
well as high-resolution mass spectra. In the 13C NMR of a
mixture of compounds 24–26, twelve signals of the
sp3-carbon were observed. Nine of these signals were
assigned to three methyl groups of three addition products
and the remaining three signals were assigned to the MeO-
introduced carbons. Regarding the H–C COSY spectra
(HMQC), one of these signals is not coupled with a proton,
suggesting the introduction of the methoxy-group to the
alternation and important contribution of canonical struc-
ture 18-A rather than 18-B. The 13C NMR spectral datum of
18 was fully assigned by using the H-C COSY spectra
(HMQC and HMBC). Signals of C-5, C-4(6), and C-10
appearing at dc 87.3, 162.1, and 174.4, respectively, are
similar to those of 7 (C-5: 89.8; C-4(6): 160.8; C-10: 188.2).
Furthermore, two ethyl groups of 18 are not equivalent, and
thus, 18 has a structure involving imminium and enol
characters. Upon treatment with aq. HBF4 in Ac2O,
compounds 17 and 18 regenerated 9·BF24 in good yields.
The reactions of 9·BF24 with benzenethiol and benzylmer-
captane were carried out (Scheme 5, Table 2, entries 4 and
5). The addition reactions of 9 occurred at 1-, 3-, and
5-positions, and a mixture of two or three regio-isomers,
1
5a-position in compound 26. The H NMR signals of the
seven-membered ring support also this characterization.
Only compound 25 was crystallized partially from CCl4
solution of 24–26, and, the analytical data of 25 is not
satisfactory because of its instability under recrystallization,
however, correct HRMS is obtained. Although 25 is inert in
CDCl3 and CD3CN, isomerization reaction was observed by
addition of a drop of CD3OD. To verify this rearrangement,
the reaction of 25 was monitored by NMR spectroscopy in
CD3OD (Scheme 7, Table 4). Compound 25 isomerized
gradually to 240 and 260, and hydrolysis of 260 in the
presence of stray H2O gave 8. In this reaction, the signal of d
3.14, which is a methyl proton of MeOH in CD3OD, was
observed. Only compounds 24–26 undergo rearrangement,
and compounds 17–23 do not undergo rearrangement in the
presence of a nucleophile, respectively.
2.4. Autorecycling oxidation of alcohols by 9·BF42
Scheme 5. Reagents and conditions: (i) PhSH or BnSH, NaHCO3, CH3CN,
rt; (ii) 42% HBF4, Ac2O.
3-Methyllumiflavin (3) and cationic species 4 have been

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S. Naya et al. / Tetrahedron 59 (2003) 1811–1821
Table 6. Time dependency of autorecycling oxidation of 1-phenylethanol
and methyl 1-phenylethyl ether in the presence of 9·BF24 under photo-
irradiation
Time (h)
Alchohol or ether
Yielda of acetophenoneb (%)
5
6
10
15
40
15
PhCH(OH)Me
PhCH(OH)Me
PhCH(OH)Me
PhCH(OH)Me
PhCH(OH)Me
PhCH(OMe)Me
793
873
1433
1960
1173
780
Acetonitrile solution was irradiated by 450-W high-pressure Hg lamp.
a
Based on 9·BF24 ; the yield, called the 9·BF24 blank, is subtracted from the
total yield of ketone in the presence of 9·BF24 .
Isolated as acetophenone 2,4-dinitrophenylhydrazone.
b
Scheme 7.
from the dehydration of alcohols, probably because of the
generation of HBF4 (Table 5). Moreover, time dependency
of the photo-induced oxidation reaction of 1-phenylethanol
was investigated in dilute CH3CN solution, and the results
are summarized in Table 6. As the time of photo-irradiation
was prolonged, the yield of acetophenone was increased
gradually. After 15 h irradiation, the highest yield of
acetophenone is obtained, while after 40 h irradiation, the
yield is decreased, suggesting plausible decomposition of
the catalyst 9·BF24 . Furthermore, 9·BF42 oxidize methyl
1-phenylethyl ether, but the rate of oxidation seems to be
slower than that of 1-phenylethanol (Table 6). Thus, the
formation of ether caused by generation of HBF24 reduces
Table 4. Time dependent rearrangement of 25
Time (h)
Ratio
25
240
260
8
0
0.1
1
6
24
48
100
73
53
29
0
0
27
47
22
0
0
0
0
49
35
0
0
0
0
0
65
100
0
0
1
studied to oxidize some amines under photo-irradiation.14
We have previously reported that compounds 2a,b oxidize
some alcohols to the corresponding carbonyl compounds.8
In this context and in a search for functions of 9·BF24 , we
examined the oxidation of some alcohols by using 9·BF24 .
We have found that compound 9·BF24 has remarkable
oxidizing ability toward some alcohols, 1-phenylethanol,
diphenylmethanol, and 9-fluorenol, to give acetophenone,
benzophenone, and 9-fluorenone, respectively, under
aerobic and photo-irradiation conditions. The results are
summarized in Table 5. Although direct irradiation of the
alcohols in the absence of 9·BF24 gives the corresponding
carbonyl compounds in a trace or modest amount, they are
obtained in more than 100% yield [based on compound
9·BF24 ] under photo-irradiation in the presence of 9·BF24 ,
and thus, autorecycling oxidation clearly proceeds (Table
5). Since decoloration of acidic aqueous KMnO4 was
observed by addition of photo-irradiated solution, the
generation of H2O2 during the photo-induced oxidation
was thus suggested. In the case of 1-phenyethanol and
diphenylmethanol, photo-induced oxidation reactions
afforded not only ketones but also ethers, which derive
the rate of alcohol oxidation. The H NMR monitoring of
the photo-oxidation reaction of 1-phenylethanol in the
presence of 9·BF24 was studied, and the ratios of alcohol,
ketone, and ether were plotted against the reaction time (Fig.
6). As the ratio of alcohol decreases simply, the ratio of
ketone increases. In contrast, the ratio of ether is nearly
constant.
In a search for the mechanistic aspect of the present photo-
induced oxidation reaction, the fluorescence spectral studies
of 9·BF24 were carried out. The fluorescence spectrum of 9
in CH3CN under irradiation of the longest wavelength of the
absorption maximum is shown in Figure 7. The wavelength
of the fluorescence of 9 was 491 nm, and then, storks-shift
was 94 nm. The quantum yield (F) of 9 was determined to
be 0.087 by using quinine bisulfate as standard.25 By
addition of 1-phenylethanol to the solution of 9, quenching
of the fluorescence was observed, suggesting interaction of
the singlet excited state of 9 with the alcohol (the
fluorescence was quenched completely by gradual
addition of 1-phenylehtanol). Moreover, 9-fluorenol was
oxidized to give 9-fluorenone. This fact would suggest that
Table 5. Autorecycling oxidation of some alcohols by 9·BF24 under photo-irradiation
Entry
Additive
Alcohol
Ketone
Yielda (%)
Yieldb (%)
Ether
Yielda (%)
1
2
3
4
5
6
9·BF24
None
9·BF24
None
9·BF24
None
PhCH(OH)Me
PhCH(OH)Me
Ph2CHOH
Ph2CHOH
9-Fluorenol
9-Fluorenol
PhCOMe
–
Ph2CO
Ph2CO
9-Fluorenone
9-Fluorenone
4
–
8
1
12
6
200
–
356
–
311
–
(PhMeCH)2O
–
(Ph2CH)2O
–
–
–
30
–
41
–
–
–
Acetonitrile solution was irradiated by 450-W high-pressure Hg lamp.
a
Based on alcohol used.
Based on 9·BF24 ; the yield, called the 9·BF42 blank, is subtracted from the total yield of ketone in the presence of 9·BF24 .
b

S. Naya et al. / Tetrahedron 59 (2003) 1811–1821
1817
Figure 6. 1H NMR monitoring of autorecycling oxidation of 1-phenyl-
ethanol by 9·BF24 .
electron-transfer reaction from 9-fluorenol to the excited 9
seems to be favorable rather than direct hydride-transfer
reaction, which would generate an antiaromatic fluorenyl
cation. Thus, the postulated mechanistic pathways for the
present photo-induced oxidation of alcohols are depicted in
Scheme 8. The electron-transfer from alcohol to the excited
cation 9 generates a radical species 27 and 28; the latter
reacts with molecular oxygen to afford a carbonyl
compound, hydroperoxyl radical, and proton. The radical
species 27 would undergo radical coupling to give dimers
29 (Path A). This feature is suggested by the irreversible
E1red of 9 (vide supra). Furthermore, transformation of
bitropyl 30 into the corresponding tropylium ion 32 by
photo-induced electron transfer (Scheme 8) has been
reported.26 Thus, the radical species 27 as well as its dimers
29 would be oxidized to regenerate cation 9 under photo-
irradiation and aerobic conditions. On the other hand, there
is an alternative mechanistic pathway (Pathway B), in which
compounds 12–14 in addition to the carbonyl compound
are generated from 27 and 28; the former compounds are
oxidized under aerobic conditions to regenerate 9. The
reduced-products 12, 13, and 14, prepared by NaBH4
reduction (Table 2), are easily oxidized to give 9·BF24 by
aerobic and photo-irradiation conditions in the presence of
NaBF4. Thus, autorecycling oxidation would also be
possible in this Path B. However, attempted detection of
Scheme 8. Reagents and conditions: (i) CH3CN, rt, aerobic, hn.
compound 27 and its dimer or compounds 12, 13, and 14
was unsuccessful in the present photo-oxidation reaction.
Thus, further investigations are required to clarify the
mechanistic aspect of the reaction.
3. Conclusion
Convenient synthesis of novel 7,9-dimethylcyclohepta[b]-
pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoro-
borate (9·BF24 ), which is isoelectronic system of 5-ethyl-3-
methyllumiflavinium ion (4), was accomplished. The
properties of 9·BF24 were clarified by measurements of the
pKRþ value, reduction potential, UV–vis spectrum, and
fluorescence spectrum. Moreover, the reactions with some
nucleophiles were carried out to clarify reactivities of
9·BF24 . Photo-induced autorecycling oxidation reaction of
9·BF24 toward some alcohols was carried out for the first
time to afford the corresponding carbonyl compounds in
autorecycling process. Thus, a preliminary mechanistic
aspect of the autorecycling oxidation reaction is postulated.
Further studies concerning synthesis, properties, and
functions including mechanistic aspects of other uracil-
annulated heteroazulenylium ions are under way.
Figure 7. Fluorescence spectrum of 9 in CH3CN.

1818
S. Naya et al. / Tetrahedron 59 (2003) 1811–1821
4. Experimental
give a mixture of 7-4,6d2 and 7-3,5d2, which is contami-
nated with ButNH3Cl. The crystals were dissolved in 3%
HCl and extracted with CH2Cl2. The extract was dried over
Na2SO4 and concentrated in vacuo to give a mixture of
8-4,6d2 and 8-3,5d2 (185 g, 71%).
4.1. General
IR spectra were recorded on a HORIBA FT-710 spectro-
meter. Mass spectra and high-resolution mass spectra were
run on JMS-AUTOMASS 150 and JMS-SX102A spectro-
4.3.1. A mixture of 7-4,6d2 and 7-3,5d2. HRMS calcd for
C13H9N2O4D2þC4H12N: 263.0985 (MþH2ButNH2). Found:
263.0968 (MþþH2ButNH2). 7-4,6d2. 1H NMR (500 MHz,
DMSO-d6) d 1.25 (9H, s, But), 3.07 (6H, s, NMe), 6.60 (1H,
br s, H-7), 6.64 (1H, br s, H-5), 7.56 (1H, br s, H-3), 7.87
(3H, br s, NH3). 7-3,5d2. 1H NMR (500 MHz, DMSO-d6) d
1.25 (9H, s, But), 3.07 (6H, s, NMe), 6.60 (1H, br d, J¼
12.0 Hz, H-7), 6.86 (1H, br s, H-4), 6.91 (1H, br d, J¼
12.0 Hz, H-6), 7.87 (3H, br s, NH3).
1
meters. Unless otherwise specified, H NMR spectra and
13C NMR spectra were recorded on JNM-AL 400, JNM-
lambda 500, and AVANCE 600 spectrometers 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 were
uncorrected. Photo-irradiation was carried out by using a
450-W high-pressure Hg lamp Pyrex filter.
4.2. Preparation of 1,3-dimethyl-5-(10-oxocyclohepta-
4.3.2. A mixture of 8-4,6d2 and 8-3,5d2. HRMS calcd
for C13H10N2O4D2: 263.1001 (MþH). Found: 263.1033
trien-20-yl)-pyrimidine-2(1H),4(3H),6(5H)-trione (8)
1
(MþþH). 8-4,6d2. H NMR (500 MHz, CD3OD) d 3.30
A solution of 2-chlorotropone (5) (1.41 g, 10 mmol), 1,3-di-
methyl-2(1H),4(3H),6(5H)-pyrimidinetrione (6) (1.56 g,
10 mmol), and ButNH2 (1.83 g, 25 mmol) in CH2Cl2
(50 mL) was stirred at rt for 24 h. After evaporation of the
CH2Cl2 and ButNH2, the residue was filtered and washed
with Et2O to give 7, which is contaminated with ButNH3Cl.
The crystals were dissolved in 3% HCl and extracted with
CH2Cl2. The extract was dried over Na2SO4 and concen-
trated in vacuo to give 8 (2.44 g, 94%).
(6H, s, NMe), 7.10 (1H, br s, H-7), 7.30 (1H, br s, H-5), 7.73
(1H, br s, H-3). 8-3,5d2. H NMR (500 MHz, CD3OD) d
1
3.30 (6H, s, NMe), 7.10 (1H, br d, J¼12.5 Hz, H-7), 7.30
(1H, br s, H-4), 7.45 (1H, br d, J¼12.5 Hz, H-6).
4.4. Preparation of 7,9-dimethylcyclohepta[b]pyrimido-
[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborate
(9·BF24 ) or a mixture of 9-4,6d2·BF24 and 9-3,5d2·BF24
A solution of 8 (130 mg, 0.5 mmol) [or a mixture of 8-4,6d2
and 8-3,5d2 (185 mg, 0.7 mmol)] in propanoic anhydride
(2.5 mL) and 42% aq. HBF4 (0.5 mL) was stirred at 08C
for 1 h. To the mixture was added Et2O (50 mL) and the
precipitates were collected by filtration to give 9·BF42
(158 mg, 96%) [or a mixture of 9-2,4d2·BF24 and
9-1,3d2·BF24 (154 mg, 83%)].
4.2.1. tert-Butylammonium 1,3-dimethyl-2,6-dioxo-5-(10-
oxocycloheptatrien-20-yl)-1,3H-pyrimidin-4-oxide (7).
1
Yellow powder; H NMR (500 MHz, DMSO-d6) d 1.24
(9H, s, But), 3.07 (6H, s, NMe), 6.60 (1H, d, J¼12.0 Hz,
H-7), 6.64 (1H, dd, J¼11.6, 7.8 Hz, H-5), 6.86 (1H, dd,
J¼11.6, 9.2 Hz, H-4), 6.91 (1H, dd, J¼12.0, 7.8 Hz,
H-6), 7.56 (1H, d, J¼9.2 Hz, H-3), 7.87 (3H, br s, NH3);
13C NMR (125.7 MHz) d 26.9, 27.1, 51.0, 89.5, 128.2,
131.8, 132.5, 133.0, 135.3, 150.2, 152.6, 160.6, 188.4;
IR (KBr) n 3428, 1665, 1576 cm21; MS (FAB) m/z 261
(MþþH2ButNH2).
4.4.1. Compound 9·BF24 . Yellow powder; mp 243–2448C
(from CH3CN–AcOEt, decomp.); 1H NMR (500 MHz,
CD3CN) d 3.43 (3H, s, Me), 3.73 (3H, s, Me), 8.73–8.76
(2H, m, H-3, 4), 8.82–8.86 (1H, m, H-2), 9.07–9.09 (1H,
m, H-5), 9.53 (1H, d, J¼10.1 Hz, H-1); 13C NMR
(125.7 MHz) d 29.2, 31.6, 98.2, 135.3, 139.9, 144.8,
148.2, 148.7, 149.3, 150.6, 157.8, 163.1, 166.2; IR (KBr)
n 1722, 1683, 1657, 1084 cm21; MS (FAB) m/z 243
(Mþ2BF4); HRMS calcd for C13H11BF4N2O3: 243.0770
(M2BF4). Found: 243.0760 (Mþ2BF4). Anal. calcd for
C13H11BF4N2O3: C, 47.31; H, 3.36; N, 8.49. Found: C, 47.2
H, 3.2; N, 8.5.
4.2.2. Compound 8. Colorless needles; mp 217–2188C
1
(from AcOEt); H NMR (500 MHz) d 3.36 (6H, s, NMe),
4.16 (1H, s, CH), 7.08–7.14 (3H, m), 7.23–7.30 (1H, m),
7.48–7.52 (1H, m); 1H NMR (400 MHz, DMSO-d6) d 3.17
(6H, s, NMe), 4.93 (1H, s, CH), 7.01 (1H, d, J¼12.0 Hz),
7.25–7.34 (2H, m), 7.40–7.47 (1H, m), 7.72–7.78 (1H, m);
1H NMR (400 MHz, CD3CN) d 3.23 (6H, s, NMe), 4.42
(1H, s, CH), 7.02 (1H, d, J¼12.0 Hz), 7.15–7.25 (2H, m),
7.32–7.38 (1H, m), 7.58–7.64 (1H, m); 13C NMR
(125.7 MHz) d 28.9, 57.2, 133.7, 135.4, 137.3, 140.2,
141.3, 148.7, 151.7, 166.4, 185.2; 13C NMR (125.7 MHz,
CD3OD) d 28.9, 97.3, 135.6, 137.1, 139.7, 141.5, 142.7,
150.2, 153.2, 168.7, 187.2; IR (CHCl3) n 1681 cm21; MS
(FAB) m/z 261 (MþþH); Anal. calcd for C13H12N2O4: C,
60.00; H, 4.65; N, 10.76. Found: C, 59.8; H, 4.7; N, 10.9.
4.4.2. A mixture of 9-2,4d2·BF24 and 9-1,3d2·BF42. HRMS
calcd for C13H9BF4N2O3D2: 245.0895 (M2BF4). Found:
245.0930 (Mþ2BF4). 9-2,4d2·BF24 . H NMR (500 MHz,
1
CD3CN) d 3.43 (3H, s, Me), 3.73 (3H, s, Me), 8.74 (1H,
br s, H-3), 9.08 (1H, br s, H-5), 9.53 (1H, br s, H-1).
1
9-1,3d2·BF24 . H NMR (500 MHz, CD3CN) d 3.43 (3H, s,
Me), 3.73 (3H, s, Me), 8.73 (1H, br d, J¼9.5 Hz, H-4), 8.83
(1H, br s, H-2), 9.08 (1H, br d, J¼9.5 Hz, H-5).
4.3. Preparation of a mixture of 8-4,6d2 and 8-3,5d2
4.5. Direct preparation of 9·BF24 from 5 and 6
A solution of 5-d3 (141 mg, 1 mmol), 6 (156 mg, 1 mmol),
and ButNH2 (183 mg, 2.5 mmol) in CH2Cl2 (10 mL) was
stirred at rt for 24 h. After evaporation of the CH2Cl2 and
ButNH2, the residue was filtered and washed with Et2O to
A solution of 7 (3.686 g, contaminated with ButNH3Cl),
which was prepared by the reaction of 6 (1.56 g, 10 mmol),
5 (1.41 g, 10 mmol), and ButNH2 (1.83 g, 25 mmol), in

S. Naya et al. / Tetrahedron 59 (2003) 1811–1821
1819
propanoic anhydride (50 mL) and 42% aq. HBF4 (10 mL)
was stirred at 08C for 1 h. To the mixture was added Et2O
(300 mL) and the precipitates were collected by filtration to
give 9·BF24 (3.00 g, 91%).
dish needles; mp 198–1998C (from CHCl3); 1H NMR
(500 MHz, DMSO-d6) d 3.23 (6H, s, Me), 4.76 (2H, s,
PhCH2), 7.31–7.61 (8H, m, Ph, H-5, 6, 7), 7.78 (1H, dd, J¼
10.2, 9.6 Hz, H-4), 8.21 (1H, d, J¼9.6 Hz, H-3), 9.76 (1H,
br s, OH); 13C NMR (125.7 MHz, DMSO-d6) d 27.2, 47.1,
89.0, 123.6, 126.9, 127.4, 128.5, 134.0, 135.4, 138.0, 142.2,
143.6, 145.8, 152.5, 160.7, 166.0; IR (KBr) n 3259, 1672,
1592 cm21; MS (FAB) m/z 350 (MþþH); Anal. calcd for
C20H19N3O3: C, 68.75; H, 5.48; N, 12.03. Found: C, 68.4;
H, 5.3; N, 11.9.
4.6. Reaction of 9·BF24 with NaHCO3
To a solution of 9·BF42 (165 mg, 0.5 mmol) in CH3CN
(10 mL) was added saturated aqueous NaHCO3 solution
(1 mL), and the mixture was stirred at rt for 6 h. To the
mixture was added 3% HCl, and the solution was extracted
with CH2Cl2. The extract was dried over Na2SO4 and
concentrated in vacuo to give 8 (130 mg, 100%).
4.9.2. 5-(20-Diethylaminocyclohepta-20,40,60-trienylidene)-
pyrimidine-2(1H),4(3H),6(5H)-trione (18). Orange pow-
1
der; mp 167–1688C (from AcOEt); H NMR (500 MHz) d
4.7. Reaction of 9·BF24 with NaBH4
1.05 (3H, t, J¼7.3 Hz, CH3), 1.36 (3H, t, J¼7.3 Hz, CH3),
3.34 (6H, s, NMe), 3.50 (2H, q, J¼7.3 Hz, CH2), 3.69 (2H,
q, J¼7.3 Hz, CH2), 6.66 (1H, dd, J¼10.8, 7.1 Hz, H-3), 6.79
(1H, d, J¼11.6 Hz, H-5), 6.98 (1H, dd, J¼11.6, 7.1 Hz,
H-4), 7.07 (1H, dd, J¼10.8, 8.4 Hz, H-2), 8.69 (1H, d, J¼
8.4 Hz, H-1); 13C NMR (125.7 MHz) d 11.3 (CH3), 11.8
(CH3), 27.7 (NCH3), 44.2 (CH2), 46.3 (CH2), 87.3 (C-5),
113.0 (C-70), 123.20(C-30), 124.5 (C-50), 127.2 (C-20), 129.8
(C-600), 133.2 (C-4 ), 152.7 (C-2), 162.1 (C-4, 6), 174.4
(C-1 ); IR (CHCl3) n 1672, 1603, 1580, 1431 cm21; MS
(FAB) m/z 316 (MþþH); HRMS calcd for C17H21N3O3:
316.1661 (MþH). Found: 316.1672 (MþþH). Anal. calcd
for C17H21N3O3: C, 64.75; H, 6.71; N, 13.32. Found: C,
64.5; H, 6.7; N, 13.4.
A solution of 9·BF42 (989 mg, 3.0 mmol) and NaBH4
(114 mg, 3.0 mmol) in CH3CN (50 mL) was stirred at rt
for 1 h. To the mixture was added saturated aqueous NH4Cl
solution, and the mixture was extracted with CH2Cl2. The
extract was dried over Na2SO4 and concentrated in vacuo to
give a mixture of 12–14 (711 mg, 97%) (Table 2).
4.7.1. A mixture of 1,7-dihydro-7,9-dimethylcyclohepta-
[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dione (12), 3,7-di-
hydro-7,9-dimethylcyclohepta[b]pyrimido[5,4-d]furan-
8(7H),10(9H)-dione (13), and 5,7-dihydro-7,9-dimethyl-
cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dione
(14). Yellow powder; mp 85–868C (from EtOH); 13C NMR
(150.9 MHz) d 21.8, 26.8, 27.5, 28.1, 28.1, 28.2, 29.4, 29.4,
29.5, 96.0, 96.1, 115.1, 117.0, 117.9, 118.3, 118.6, 120.4,
120.8, 121.3, 122.3, 124.3, 127.2, 127.3, 128.4, 128.4,
140.1, 146.6, 149.5, 150.5, 150.6, 150.7, 154.4, 154.7,
156.4, 158.5, 158.5, 158.7 (two carbons overlapping); IR
(KBr) n 1707, 1666 cm21; MS (FAB) m/z 245 (MþþH);
HRMS calcd for C13H12N2O3: 245.0927 (MþH). Found:
245.0907 (MþþH). Anal. calcd for C13H12N2O3: C, 63.93;
H, 4.95; N, 11.47. Found: C, 63.4; H, 4.6; N, 11.4.
4.10. Reaction of 9·BF24 with PhSH or BnSH
To a suspension of 9·BF24 (66 mg, 0.2 mmol) and NaHCO3
(168 mg, 2.0 mmol) in CH3CN (2 mL) was added PhSH
(22 mg, 0.2 mmol) [or BnSH (25 mg, 0.2 mmol)], and the
mixture was stirred at rt for 1 h. The mixture was filtered
and the filtrate was concentrated in vacuo. The residue was
dissolved in CH2Cl2 and filtered to remove NaBF4, and
the filtrate was evaporated to give a mixture of 19 and 20
[or 21–23] (Table 2).
4.8. Oxidation of a mixture of 12–14
4.10.1. A mixture of 1,7-dihydro-7,9-dimethyl-1-phenyl-
thiocyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-
dione (19) and 3,7-dihydro-7,9-dimethyl-3-phenylthio-
cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dione
(20). Yellow oil; 13C NMR (150 MHz) d 28.1, 28.2, 29.4,
29.5, 43.2, 46.5, 95.6, 117.1, 118.2, 118.6, 120.9, 121.5,
122.5, 122.7, 125.6, 125.7, 125.8, 127.2, 127.5, 128.3,
128.5, 128.7, 129.1, 129.2, 129.4, 130.7, 132.2, 133.0,
135.6, 147.2, 150.5, 155.9, 158.0, 158.3; IR (CHCl3) n 1709,
1276 cm21; HRMS calcd for C19H17N2O3S: 353.0960
(MþH). Found: 353.1005 (MþþH).
To a solution of a mixture of 12–14 (122 mg, 0.5 mmol) in
CH2Cl2 (5 mL) was added DDQ (176 mg, 0.75 mmol), and
the mixture was stirred at rt for 1 h. After evaporation of the
CH2Cl2, the residue was dissolved in a mixture of acetic
anhydride (5 mL) and 42% HBF4 (1 mL) at 08C and the
mixture was stirred for another 1 h. To the mixture was
added Et2O (50 mL) and the precipitates were collected by
filtration to give 9·BF24 (149 mg, 90%).
4.9. Reaction of 9·BF24 with benzylamine and
diethylamine
4.10.2. A mixture of 1-benzylthio-1,7-dihydro-7,9-di-
methylcyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-
dione (21), 3-benzylthio-3,7-dihydro-7,9-dimethylcyclo-
hepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dione (22),
and 5-benzylthio-5,7-dihydro-7,9-dimethylcyclohepta-
[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dione (23). Yellow
oil. 13C NMR (150 MHz) d 28.1, 28.1, 28.2, 28.9, 29.3,
29.5, 34.4, 34.5, 34.9, 38.9, 41.6, 43.3, 53.5, 95.8, 96.0,
118.0, 118.1, 119.1, 120.6, 121.2, 121.3, 122.2, 122.6,
122.1, 122.8, 125.3, 125.9, 16.5, 126.7, 126.8, 127.0, 127.0,
128.0, 128.2, 128.4, 128.5, 128.6, 128.7, 128.8, 128.8,
A solution of 9·BF24 (165 mg, 0.5 mmol) and benzylamine
(214 mg, 2.0 mmol) [or diethylamine (147 mg, 0.5 mmol)]
in CH3CN (10 mL) was stirred at rt for 0.5 h. After
evaporation of the CH2Cl2 and excess amine, the residue
was acidified with 3% HCl and extracted with CH2Cl2. The
extract was dried over Na2SO4 and concentrated in vacuo to
give 17 (166 mg, 95%) [or 18 (158 mg, 100%)] (Table 2).
4.9.1. 1,3-Dimethyl-4-hydroxy-5-(10-benzyliminocyclo-
heptatrien-20-yl)pyrimidine-2(3H),6(1H)-dione (17). Red-

1820
S. Naya et al. / Tetrahedron 59 (2003) 1811–1821
128.9, 137.9, 138.1, 141.1, 146.5, 149.0, 150.4, 150.5,
154.7, 155.6, 158.2, 158.3 (two carbons overlapping); IR
(CHCl3) n 1708, 1277 cm21; HRMS calcd for C20H19N2O3S:
367.1117 (MþH). Found: 367.1083 (MþþH).
solution was determined on a pH meter calibrated with
standard buffers. The observed absorbance at the specific
absorption wavelengths (394 nm) of cation was plotted
against pH to give a classical titration curve, whose
midpoint was taken as the pKRþ value (Table 1).
4.11. Reaction of 9·BF24 with MeOH
4.14. Cyclic voltammetry of cation 9·BF42
To a suspension of 9·BF42 (165 mg, 0.5 mmol) and NaHCO3
(420 mg, 5.0 mmol) in CH3CN (5 mL) was added MeOH
(5 mL) and the mixture was stirred at rt for 2 h. The mixture
was filtered and concentrated in vacuo. The residue was
dissolved in CH2Cl2 and filtered to remove NaBF4. The
resulting filtrate was evaporated to give a mixture of 24–26
(Table 2).
The reduction potentials of 9·BF24 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 CH3CN solution (4 mL)
of cation 9·BF24 (0.5 mmol dm23) and Bu4NClO4
(0.1 mol dm23) to deaerate it. The measurements were
made at a scan rate of 0.1 V s21 and the voltammograms
were recorded on a WX-1000-UM-019 (Graphtec Co) X-Y
recorder. Immediately after the measurements, ferrocene
(0.1 mmol) (E1/2¼þ0.083) was added as the internal
standard, and the observed peak potentials were corrected
with reference to this standard. The compounds exhibited no
reversible reduction wave: the reduction potential was
measured through independent scan (Table 1).
4.11.1. A mixture of 1,7-dihydro-7,9-dimethyl-1-methoxy-
cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dione
(24), 3,7-dihydro-7,9-dimethyl-3-methoxycyclohepta[b]-
pyrimido[5,4-d]furan-8(7H),10(9H)-dione (25), and 5a,7-
dihydro-7,9-dimethyl-5a-methoxycyclohepta[b]pyri-
mido[5,4-d]furan-8(7H),10(9H)-dione (26). Reddish oil.
13C NMR (150 MHz) d 27.9, 28.2, 28.7, 29.0, 29.5, 29.6,
54.6, 55.2, 56.4, 67.3, 77.5, 89.4, 114.2, 115.0, 116.3, 117.6,
118.5, 122.7, 122.8, 122.9, 123.9, 125.2, 125.6, 125.8, 127.4,
128.8, 130.5, 133.7, 138.3, 139.8, 145.2, 148.4, 149.1, 150.5,
150.7, 153.0, 154.9, 156.0, 158.4, 158.4, 163.0, 164.6; IR
(CHCl3) n 1710, 1668, 1265 cm21; HRMS calcd for
C14H14N2O4: 275.1032 (MþH). Found: 275.1021 (MþþH).
4.15. X-Ray structure determination of 8†
Colorless prisms, C13H12N2O4, M¼260.25, monoclinic,
space group P21/c, a¼11.1404(7), b¼7.6870(3), c¼
3
˚
˚
14.9663(7) A, b¼110.982(3)8, V¼1196.7(1) A , Z¼4,
Dc¼1.444 g cm23, crystal dimensions 0.50£0.20£0.20 mm3.
Data were measured on a Rigaku RAXIS-RAPID radiation
diffractomater with graphite monochromated Mo Ka radia-
tion. A total 10,804 reflections were collected, using the
v–2u scan technique to a maximum 2u 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,27 with 185 variables and 2224 observed
reflections [I.3.00s(I)]. The non-hydrogen atoms were
refined anisotropically. The weighting scheme w¼[s2c(F0)þ
0.0070F20]21 gave satisfactory agreement analysis. The final
R and Rw values were 0.060 and 0.089. The maximum peak
and minimum peak in the final difference map were 0.62 and
4.11.2. Compound 25. Colorless powder; mp 151–1548C
(from CCl4, decomp.); 13C NMR (100 MHz) d 28.2, 29.5,
56.4, 77.5, 89.4, 114.2, 117.6, 122.7, 122.8, 123.9, 149.1,
150.5, 154.9, 158.4; IR (CHCl3) n 1710, 1668, 1265 cm21
;
MS (ret. int.) m/z 274 (Mþ, 36), 259 (17), 243 (45), 186 (87),
58 (100%); HRMS calcd for C14H14N2O4: 275.1032
(MþH). Found: 275.1024 (MþþH). Anal. calcd for
C14H14N2O4: C, 61.31; H, 5.14; N, 10.21. Found: C, 60.6;
H, 4.3; N, 10.5.
4.12. Reaction of 17, 18, a mixture of 19 and 20, a
mixture of 21–23, and a mixture of 24–26 with HBF4
23
20.35 e2
A
.
˚
A solution of each of 17, 18, a mixture of 19 and 20, a
mixture of 21–23, and a mixture of 24–26 (0.5 mmol) in
acetic anhydride (10 mL) and 42% aq. HBF4 (2 mL) was
stirred at 08C for 1 h. To the mixture was added Et2O
(50 mL) and the precipitates were collected by filtration to
give 9·BF24 . The results are summarized in Table 3.
4.16. General procedure of autorecycling oxidation of
some alcohols by 9·BF42
An CH3CN (1 mL) solution of compound 9·BF24 (16.5 mg,
0.05 mmol) and an alcohol (2.5 mmol, 50 equiv.) in a Pyrex
tube was irradiated by 450-W high-pressure Hg lamp under
aerobic conditions for 40 h. The reaction mixture was
concentrated in vacuo and separated by column chroma-
tography on SiO2. The results are summarized in Table 5.
4.13. Determination of pKR1 value of 9·BF42
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)
(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 mg of cation 9·BF24 in CH3CN
(20 mL), were diluted to 10 mL with the buffer solution
(5 mL) and MeCN (4 mL). The UV–vis spectrum was
recorded for cation 9a in 30 different buffer solutions.
Immediately after recording the spectrum, the pH of each
4.17. Time dependency of autorecycling oxidation of
1-phenylethanol by 9·BF42
A CH3CN (16 mL) solution of compound 9·BF24 (16.5 mg,
0.05 mmol) and 1-phenylethanol (305 mg, 2.5 mmol) in a
Pyrex tube was irradiated by 450-W high-pressure Hg
lamp under aerobic conditions for the periods indicated in
†
CCDC reference number 194281.

S. Naya et al. / Tetrahedron 59 (2003) 1811–1821
1821
7. Yoneda, F.; Hirayama, R.; Yamashita, M. Chem. Lett. 1980,
1157–1160.
Table 6. The reaction mixture was concentrated in vacuo
and diluted with ether and filtered. The filtrate was treated
with 2,4-dinitrophenylhydrazine in 6% HCl to give 2,4-
dinitrophenylhydrazone. The results are summarized in
Table 6.
8. Takayasu, T.; Mizuta, Y.; Nitta, M. Heterocycles 2001, 54,
601–606. Nitta, M.; Tajima, Y. Synthesis 2000, 651–654.
9. Naya, S.; Nitta, M. J. Chem. Soc., Perkin Trans. 1 2000,
2777–2781.
1
4.18. H NMR monitoring of autorecycling oxidation of
1-phenylethanol by 9·BF42
10. Naya, S.; Nitta, M. J. Chem. Soc., Perkin Trans. 2 2000,
2427–2735.
11. Naya, S.; Nitta, M. J. Chem. Soc., Perkin Trans. 2 2001,
275–281.
A CD3CN (0.5 mL) solution of compound 9·BF42
(0.660 mg, 0.002 mmol) and 1-phenylehtanol (12.2 mg,
0.10 mmol) in NMR tube was irradiated by 450-W high-
pressure Hg lamp under aerobic conditions. The NMR
measurement was carried out at intervals, and the ratios of
1-phenylethanol, acetophenone, and di(1-phenylethyl) ether
were plotted against them (Fig. 6).
12. Naya, S.; Isobe, M.; Hano, Y.; Nitta, M. J. Chem. Soc., Perkin
Trans. 2 2001, 2253–2262.
13. Naya, S.; Sakakibara, T.; Nitta, M. J. Chem. Soc., Perkin
Trans. 2 2001, 1032–1037.
14. Kim, J.; Bogdan, M. A.; Mariano, P. S. J. Am. Chem. Soc.
1993, 115, 10591–10595.
15. Ohba, Y.; Kubo, K.; Igarashi, T.; Sakurai, T. J. Chem. Soc.,
Perkin Trans. 2 2001, 491–493.
Acknowledgements
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Financial support from a Waseda University Grant for
Special Research Project is gratefully acknowledged. We
thank the Materials Characterization Central Laboratory,
Waseda University, for technical assistance with the
spectral data, elemental analyses, and X-ray crystal
analyses.
19. Freedman, H. H. In Carbonium Ions; Olah, G. A., Schleyer, P.,
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