Novel synthesis and oxidizing ability of tropylium ions annulated with two 2,4-dimethylfuro[2,3-d]pyrimidine-1(2H),3(4H)-diones

Article abstract of DOI:10.1021/jo049668c

Convenient preparation of novel tropylium ions annulated with two 2,4-dimethylfuro[2,3-d]pyrimidine-1(2H),3(4H)-diones, 12^a+· BF₄^- and 12^b+·BF₄ ^-, consists of a reaction of 2-methoxytropone with dimethylbarbituric acid to give 7,9-dimethyl-3-[1′,3′-dimethyl-2′(1′H), 4′(3′H),6′(5′H)-trioxopyrimidin-5′-ylidene] cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dione 8 and the following oxidative cyclization by using DDQ or photoirradiation under aerobic conditions. On the basis of the MO calculations, the selectivity of two types of oxidative cyclization reactions of 8 was rationalized. X-ray crystal analyses and MO calculations were carried out to clarify the structural characteristics of 12^a+·BF₄^- and 12^b+· BF₄^-. The stability of cations 12a⁺ and 12b⁺ is expressed by the pK_R+ values which were determined spectrophotometrically as 8.8 and 8.6. The electrochemical reduction of 12a⁺ and 12b⁺ exhibited reduction potential at -0.63 and -0.62 (V vs Ag/AgNO₃), respectively. Reactions of 12 ^a+·BF₄^- and 12^b+· BF₄^- with some nucleophiles, hydride and diethylamine, were carried out to clarify that the reactivity of 12^a+· BF₄^- and 12^b+·BF₄^- was substantially dependent on the annulating position. The oxidizing ability of 12^a+·BF₄^- and 12^b+-BF ₄^- toward alcohols and amines in the autorecycling process was demonstrated as well.

Full text of DOI:10.1021/jo049668c

Novel Syn th esis a n d Oxid izin g Ability of Tr op yliu m Ion s
An n u la ted w ith Tw o
2,4-Dim eth ylfu r o[2,3-d ]p yr im id in e-1(2H),3(4H)-d ion es
Shin-ichi Naya, Takeshi Tokunaka, and Makoto Nitta*
Department of Chemistry, School of Science and Engineering, Waseda University,
Shinjuku-ku, Tokyo 169-8555, J apan
nitta@waseda.jp
Received February 27, 2004
Convenient preparation of novel tropylium ions annulated with two 2,4-dimethylfuro[2,3-d]-
pyrimidine-1(2H),3(4H)-diones, 12a +‚BF4- and 12b+‚BF4-, consists of a reaction of 2-methoxytropone
with dimethylbarbituric acid to give 7,9-dimethyl-3-[1′,3′-dimethyl-2′(1′H),4′(3′H),6′(5′H)-trioxopy-
rimidin-5′-ylidene]cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dione 8 and the following oxida-
tive cyclization by using DDQ or photoirradiation under aerobic conditions. On the basis of the
MO calculations, the selectivity of two types of oxidative cyclization reactions of 8 was rationalized.
X-ray crystal analyses and MO calculations were carried out to clarify the structural characteristics
of 12a +‚BF4- and 12b+‚BF4-. The stability of cations 12a + and 12b+ is expressed by the pKR values
+
which were determined spectrophotometrically as 8.8 and 8.6. The electrochemical reduction of
12a + and 12b+ exhibited reduction potential at -0.63 and -0.62 (V vs Ag/AgNO3), respectively.
Reactions of 12a +‚BF4 and 12b+‚BF4 with some nucleophiles, hydride and diethylamine, were
carried out to clarify that the reactivity of 12a +‚BF4- and 12b+‚BF4- was substantially dependent
on the annulating position. The oxidizing ability of 12a +‚BF4- and 12b+‚BF4- toward alcohols and
amines in the autorecycling process was demonstrated as well.
-
-
In tr od u ction
flavin-catalyzed reactions. In this relation, 5-deaza-10-
oxaflavin 1b (2H-chromeno[2,3-d]pyrimidine-2,4(3H)-di-
one), in which the nitrogen atom is replaced by an oxygen,
has been synthesized and found to possess a strong
ability to oxidize alcohols to the corresponding carbonyl
compounds.6 On the basis of the above observations, the
synthesis and properties of polycyclic flavin derivative
2a 7 and its analogue 2b8 (double 5-deazaflavin) have been
reported. The double 5-deazaflavins 2a and 2b have an
extended conjugation and a more positive reduction
potential as compared with 1a . Thus, 2a and 2b are more
effective than 1a for oxidation of alcohols.
On the other hand, we have previously studied con-
venient preparations of 6-substituted 9-methylcyclo-
hepta[b]pyrimido[5,4-d]pyrrole-8(6H),10(9H)-diones9 and
9-methylcyclohepta[b]pyrimido[5,4-d]furan-8,10(9H)-di-
one,10 which are structural isomers of 1a and 1b ,
respectively, and their reactions in oxidizing some alco-
Flavins are known to play an important role as
cofactors in a wide variety of biological redox reactions.1
Dehydrogenation reactions represent a major category
of processes mediated by a subclass of flavoenzymes
known as oxidases. Included in this group are the oxi-
dative transformations of alcohols to carbonyl com-
pounds, of amines to imines, and of fatty acid esters to
their R,â-unsaturated analogues.2 The flavin-redox sys-
tems have been investigated extensively through syn-
thetic model systems and theoretical calculations.3 Among
these compounds, 5-deazaflavins 1a (Figure 1) have been
studied extensively in both enzymatic4 and model sys-
tems,5 in the hope of providing mechanistic insight into
* Address correspondence to this author. Phone: +81-(0)3-5286-
3236. Fax: +81-(0)3-3208-2735.
(1) Mu¨ller, F. Chemistry and Biochemistry of Flavoenzymes; Mu¨ller,
F., Ed.; CRC Press: Boca Raton, FL, 1991; Vol. 1, pp 1-71 and
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therein. (b) Yoneda, F.; Tanaka, K. Med. Res. Rev. 1987, 4, 477-506
and references therein.
(5) Yoneda, F.; Kokel, B. Chemistry and Biochemistry of Flavoen-
zymes; Muller, F., Ed.; CRC Press: Boca Raton, FL, 1991; Vol. 1, pp
121-169 and references therein.
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1157-1160.
(7) (a) Yoneda, F.; Koga, M.; Ibuka, T.; Yano, Y. Chem. Pharm. Bull.
1986, 34, 2653-2655. (b) Yoneda, F.; Koga, M. J . Chem. Soc., Perkin
Trans. 1 1988, 1809-1812. (c) Yoneda, F.; Koga, M.; Ibuka, T.
Tetrahedron Lett. 1984, 25, 5345-5346.
(8) Yondea, F.; Koga, M.; Yano, Y. J . Chem. Soc., Perkin Trans. 1
1988, 1813-1817.
(9) Nitta, M.; Tajima, Y. Synthesis 2000, 651-654.
(2) Hamilton, G. A. Progress in Bioorganic Chemistry; Kaiser, E.
T., Kezdy, F. J ., Eds.; Wiley: New York, 1971; Vol. 1, p 83.
(3) (a) Chiu, C. C.; Pan, K.; J ordan, F. J . Am. Chem. Soc. 1995, 117,
7027-7028. (b) Kim, J .; Hoegy, S. E.; Mariano, P. S. J Am. Chem. Soc.
1995, 117, 100-105. (c) Murahashi, S.; Ono, S.; Imada, Y. Angew.
Chem., Int. Ed. 2002, 41, 2366-2368. (d) Bergstad, K.; J onsson, S.;
Ba¨ckvall, J . J . Am. Chem. Soc. 1999, 121, 10424-10425. (e) Van
Houten, K. A.; Kim, J .; Bogdan, M. A.; Ferri, D. C.; Mariano, P. S. J .
Am. Chem. Soc. 1998, 120, 5864-5872. (f) Zheng, Y.; Ornstein, R. L.
J . Am. Chem. Soc. 1996, 118, 9402-9408. (g) Breinlinger, E. C.;
Keenan, C. J .; Rotello, V. M. J . Am. Chem. Soc. 1998, 120, 8606-8609.
(h) Hasford, J . J .; Rizzo, C. J . J . Am. Chem. Soc. 1998, 120, 2251-
2255. (i) Antony, J .; Medvedev, D. M.; Stuchebrukhov, A. A. J . Am.
Chem. Soc. 2000, 122, 1057-1065.
10.1021/jo049668c CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/03/2004
4732
J . Org. Chem. 2004, 69, 4732-4740

Synthesis and Oxidizing Ability of Tropylium Ions
SCHEME 1 a
F IGURE 1.
hols to the corresponding carbonyl compounds. In this
relation, we have reported the oxidative cyclization of
heptafulvenes 3a and 3b by using DDQ to afford cyclo-
hepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tet-
-
rafluoroborates 4a +‚BF4 and 4b+‚BF4-, respectively.11
Novel photoinduced autorecycling oxidizing reactions of
-
4a +‚BF4 toward some alcohols were studied as well.12
a
Reagents and conditions: (i) Ac2O, reflux, 0.5 h; (ii) Et3N,
On the other hand, the π-conjugation mode in polycyclic
conjugated π-systems containing more than one (4n+2)
conjugation loop is an important subject from both theo-
retical and experimental viewpoints. A combination of
more than one π-system can endow the original π-system
with new properties. From this viewpoint, we have
recently reported the synthesis, properties, and oxidizing
ability of 9,11-dimethylbenzocyclohepta[6,7-b]pyrimido-
CH3CN, rt, 2 h; (iii) xylene, 90 °C, 3 h.
properties as well as the photoinduced oxidizing reaction
of 12a +‚BF4 and 12b+‚BF4 toward some alcohols and
-
-
amines are investigated as well.
Resu lts a n d Discu ssion
[5,4-d]furan-10(9H),12(11H)-dionylium ion 5+‚BF4- 13 The
.
Syn th esis. Preparation of 1,3,8,10-tetramethyldipy-
rimido[6,5-b:6′,5′-b′]cyclohepta [1,2-d:5,4-d′]difura n-
2(1H),4(3H),7(8H),9(10H)-tetraonylium tetrafluorobo-
properties and reactivity of compound 5+‚BF4- were much
perturbed by the benzo-annulation on 4a +‚BF4-. Thus,
the aromatic ring-annulation onto 3a and 4a +‚BF4- is a
very interesting project from the viewpoint of exploration
of novel functions. In this study, we report the synthesis
and properties of a novel type of heptafulvene 8 (Scheme
1), which is converted to novel tropylium ions annulated
with two 2,4-dimethylfuro[2,3-d]pyrimidine-1(2H),3(4H)-
rate 12a +‚BF4 and its isomer 12b+‚BF4 was easily
accomplished by the reaction of 2-methoxytropone 6 with
dimethylbarbituric acid 7 and subsequent oxidative cy-
clization. The reaction of 2-methoxytropone 6 with 2
molar equiv of dimethylbarbituric acid 7 in Ac2O under
reflux for 0.5 h afforded a novel heptafulvene, 7,9-
dimethyl-3-[1′,3′-dimethyl-2′(1′H),4′(3′H),6′(5′H)-trioxopy-
rimidin-5′-ylidene]cyclohepta[b]pyrimido[5,4-d]furan-
8(7H),10(9H)-dione 8 (38% based on 6 used) and a mix-
ture of 1,7-, 3,7-, and 5,7-dihydro-7,9-dimethylcyclohepta-
[b]pyrimido[5,4-d]furan-8(7H),10(9H)-diones 9a -c12 (50%
based on 6 used) (Scheme 1). The reaction of 6 with even
1 molar equiv of 7 did not afford 4a + but afforded 8 and
9a -c in lower yields and compound 6 was not recovered
in the reaction. Thus, compound 11 is postulated as the
intermediate for the formation of 8 and 9a -c. The
-
-
diones, 12a +‚BF4 and 12b+‚BF4 (Scheme 2). Com-
-
-
-
-
pounds 12a +‚BF4 and 12b+‚BF4 are expected to be a
double uracil-annulated heteroazulene having an ex-
tended conjugation. The structural details and chemical
(10) Takayasu, T.; Mizuta, Y.; Nitta, M. Heterocycles 2001, 54, 601-
606.
(11) Naya, S.; Nitta, M. Tetrahedron 2003, 59, 3709-3718.
(12) Naya, S.; Miyama, H.; Yasu, K.; Takayasu, T.; Nitta, M.
Tetrahedron 2003, 59, 1811-1821.
(13) Naya, S.; Tokunaka, T.; Nitta, M. J . Org. Chem. 2003, 68,
9317-9321.
J . Org. Chem, Vol. 69, No. 14, 2004 4733

Naya et al.
SCHEME 2 a
a
Reagents and conditions: (i) (a) DDQ, CHCl3, reflux, 1 h; (b) 42% aq HBF4, Ac2O, 0 °C, 1 h; (ii) (a) hv, aerobic, 42% aq HBF4, CH3CN-
(CH2Cl)2, rt, 48 h; (b) 42% aq HBF4, Ac2O, 0 °C, 1 h;
reaction of 4a +‚BF4 with 7 in the presence of Et3N
afforded compound 11 quantitatively. The structure of
which is generated by one-electron oxidation of 8, un-
dergoes a cyclization reaction to give intermediates 14a
and 14b, the hydrogen abstraction of which gives cations
12a + and 12b+, respectively. Subsequent anion exchange
reaction with aq HBF4 solution results in the formation
-
11 was determined on the basis of the H and 13C NMR
1
and IR spectral data, as well as elemental analysis. A
careful study of the NMR signals of 11 led us to conclude
it is a 3:2 chromatographically inseparable mixture of
meso and racemic forms. However, FABMS of 11 gives
only the (M + H)+ peak of 8 instead of the (M + H)+ peak
of 11 probably due to easy elimination of 9a -c. A solution
of 11 in xylene was heated at 90 °C for 3 h to afford 8
(83%) and a mixture of 9a -c (33%). Thus, the reaction
of 6 with 7 giving 8 and 9a -c would proceed as follows:
the condensation of 2-methoxytropone 6 with dimethyl-
barbituric acid 7 gives intermediate 10, which undergoes
demethoxylating cyclization to give cation 4a +. The
addition reaction of 4a + with another dimethylbarbituric
acid 7 occurs quickly to give the intermediate 11, which
undergoes an elimination reaction to give 8 and 9a -c.
The reaction of 8 with DDQ in CHCl3 under reflux for
1 h and subsequent anion exchange reaction by using aq
of 12a +‚BF4 and 12b+‚BF4-. On the other hand, oxida-
-
tive cyclization of 8 was also accomplished by photoirra-
diation (RPR-100, 350-nm lamps) under aerobic condi-
tions in the presence of 42% aq HBF4. The reaction
proceeded selectively to give 12a +‚BF4 as a single
-
product in quantitative yield. The photoinduced oxidative
cyclization of 8 would proceed as shown also in Scheme
2. The photoinduced 10π-cyclization of 8 gives intermedi-
ate 15, which would undergo 1,7-hydrogen shift and
oxidation under photoirradiation and aerobic conditions
in the presence of 42% aq HBF4 leading to 12a +‚BF4
.
-
To clarify the selectivity of the two cyclizations, MO
calculations of 8 and 13 were carried out with use of the
AM1 method (MOPAC97).14 At C2 and C4, the charge
density of 8 and 13 as well as the coefficients of LUMOs
of 8 and 13 are depicted in Figure 2. Regarding the
charge density and the coefficients of the LUMO for
radical cation 13, both values are larger for C2 than those
for C4, suggesting that intramolecular radical addition
of the former position occurs preferentially to that of the
latter position, irrespective of whether addition occurs
charge controlled or frontier orbital controlled. On the
contrary, the photoinduced 10π-cyclization of 8 would
-
HBF4 in Ac2O afforded a mixture of 12a +‚BF4 and
12b+‚BF4 in a good combined yield (90%, Scheme 2).11
-
The ratio of 12a +‚BF4 and 12b+‚BF4 is determined to
-
-
1
be 1:4 from the H NMR spectrum of the mixture. The
mixture of 12a +‚BF4 and 12b+‚BF4 was separated by
fractional recrystallization from CH3CN/AcOEt to give
pure samples of 12a +‚BF4- and 12b+‚BF4-. According to
the redox properties of 8 under CV measurement (vide
infra), the DDQ-prompted oxidative cyclization of 8 would
proceed via a similar pathway to that of compounds
3a ,b11 as outlined in Scheme 2. The radical cation 13,
-
-
(14) Dewar, M. J . S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J . J . P.
J . Am. Chem. Soc. 1985, 107, 3902. Dewar, M. J . S.; Zoebisch, E. G.
THEOCHEM 1988, 180, 1.
4734 J . Org. Chem., Vol. 69, No. 14, 2004

Synthesis and Oxidizing Ability of Tropylium Ions
F IGURE 3.
that protonation of 3a would not occur. The feature is
rationalized by the difference in thermodynamic stability
+
between 4a + (pKR , ca. 6.0) and simple tropylium ion 17
+
18
+
(pKR , 3.9). However, the absorption of 8 did not
disappear completely by addition of a larger amount of
TFA, suggesting that the basicity of 8 is not so high, and
thus, the complete protonation of 8 does not occur. The
mixture regenerated 8 quantitatively upon the addition
of Et3N, and thus, the protonation-deprotonation cycle
is completely reversible.
The redox property of 8 was determined by cyclic
voltammetry (CV) in acetonitrile. The reduction and
oxidation waves of 8 were irreversible under the condi-
tions of CV measurements, and the peak potentials are
-1.16 (E1red) and +0.87 V (E1ox). At the first reduction
potential (E1red) of 8, a radical anion would be generated.
The value (E1red) of 8 is similar to those of 3a ,b (3a , -1.15
V; 3b, -1.13 V).11 On the other hand, radical cation 13
(Scheme 2) seems to be generated at the first oxidation
potential (E1ox). The value (E1ox) of 8 is more negative
than those of 3a ,b (3a , +1.08 V; 3b, +1.11 V)11 due to
the larger stability of 4a + as compared with tropylium
ion 17+. After the first cycle of CV measurement of 8,
another reduction wave was recorded at -0.62 V. This
wave is suggested to be the reduction waves of 12a + and
12b+, which are generated by oxidative cyclization reac-
tions of 8 under CV measurement. This feature is similar
to the behavior of compounds 3a ,b .11 Thus, DDQ-
prompted oxidative cyclization of 8 affording cations 12a +
and 12b+ would proceed via a similar pathway to that of
compounds 3a ,b (vide supra).
F IGURE 2.
occur frontier orbital controlled. Regarding the coef-
ficients of the LUMO for 8, the value is much larger for
C4 than for C2, suggesting that the 10π-cyclization of
the former position occurs preferentially to that of the
latter position. Consequently, 15 would be generated
selectively to result in the formation of only 12a +‚BF4
.
-
Thus, the selectivity of the two cyclizations of 8 seems
to be rationalized.
P r op er ties. The structure of 8 was determined on the
basis of the 1H and 13C NMR, IR, and mass spectral data,
as well as elemental analysis. Two methyl groups on the
N1′ and N3′ of the pyrimidine moiety appear equivalent.
This is probably due to the free rotation around the
exocyclic double bond of the fulvene system on the NMR
time scale. In the 13C NMR spectrum, a signal of the C5′
of the barbituric acid moiety in 8 appears at similar field
(δC 103.7) to those of 3a ,b (3a , δC 102.7; 3b, δC 101.2),11
suggesting a similar electron density. Thus, a polariza-
tion of the exocyclic double bond of the fulvene system of
8 seems to be similar to that of 3a ,b. In the UV-vis
spectrum, the longest wavelength absorption maximum
(λmax) of 8 appears at a longer wavelength (487 nm) than
that of 3a 11 (431 nm), and thus the difference in the
wavelength (∆λ) between 8 and 3a is 56 nm. Although
42% aq HBF4 was added to the solution, the visible region
of the spectrum of 8 was not changed. By addition of TFA
to the CH3CN solution of 8, new absorption appeared at
420 nm, which probably corresponds to the absorption
of the 7,9-dimethyl-3-[1′,3′-dimethyl-2′(1′H),4′(3′H)-dioxo-
6′-hydroxypyrimidin-5′-yl]cyclohepta[b]pyrimido[5,4-d]fu-
ran-8(7H),10(9H)-dionylium ion 16+ (Figure 3) generated
by protonation on the baribituric acid moiety in 8. In
contrast, addition of TFA to the CH3CN solution of 3a
causes no change in the UV-vis spectrum, suggesting
-
In a similar fashion, compounds 12a +‚BF4 and
12b+‚BF4 were fully characterized on the basis of the
-
1H and 13C NMR, IR, UV-vis, and mass spectral data,
as well as the elemental analyses. In the UV-vis spectra,
the longest wavelength absorption maxima (λmax) of 12a +
and 12b+ appear at longer wavelength (12a +, 460 nm;
(15) Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, M.;
Giacovazzo, C.; Guagliardi, A.; Polidori, G. J . Appl. Crystallogr. 1994,
27, 435.
(16) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J . R.; Zakrzewski, V. G.; Montgomery, J . A.,
J r.; Stratmann, R. E.; Burant, J . C.; Dapprich, S.; Millam, J . M.;
Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J .;
Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo,
C.; Clifford, S.; Ochterski, J .; Petersson, G. A.; Ayala, P. Y.; Cui, Q.;
Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.;
Foresman, J . B.; Cioslowski, J .; Ortiz, J . V.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.;
Fox, D. J .; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; J ohnson, B. G.; Chen,
W.; Wong, M. W.; Andres, J . L.; Head-Gordon, M.; Replogle, E. S.;
Pople, J . A. Gaussian 98, revision A.11; Gaussian, Inc.: Pittsburgh,
PA, 2001.
(17) Freedman, H. H. Carbonium Ions; Olah, G. A., Schleyer, P.,
Eds.; Wiley-Insterscience: New York, 1973; Vol. 4, pp 1501-1578.
(18) Okamoto, K.; Takeuchi, K.; Komatsu, K.; Kubota, Y.; Ohara,
R.; Arima, M.; Takahashi, K.; Waki Y.; Shirai, S. Tetrahedron 1983,
39, 4011-4024 and references therein.
J . Org. Chem, Vol. 69, No. 14, 2004 4735

Naya et al.
+
TABLE 1. λm a x a n d p KR Va lu es a n d Red u ction
formation of the tropyl radical and its dimerization,
which seems to be a typical property of tropylium ions.19
The E1red values of dodecyl derivatives of 2a ,b (2a , -0.84
V; 2b, -0.99 V) have been reported to be less negative
than that of a dodecyl derivative of 1a (-1.44 V).7,8 On
the contrary, the E1red of 12a + and 12b+ are slightly more
negative by 0.04 and 0.05 V than that of 4a +, but the
values are less negative than those of 1a , 2a , and 2b.
P oten tia lsa of Ca tion s 12a + b a n d 12b+ b a n d Refer en ce
Ca tion s 4a +, 5+, a n d 17+
reduction potential/V
+
compd
λmax
pKR
E1red
E2red
12a +
12b+
4a + c
5+ d
460
456
397
441
273
8.8
8.6
ca. 6.0
4.7
-0.63
-0.62
-0.58
-0.46
-0.51
-
Rea ctivity. While the reaction of 4a +‚BF4 with
-1.07
17+ e
3.9
NaBH4 proceeded at the 1-, 3-, and 5-positions to afford
a mixture of three regioisomers 9a -c,12 the reduction of
12a +‚BF4- and 12b+‚BF4- occurs on the C12 to afford 18a
and 18b, respectively, in good yields due to two closed
furopyrimidine-rings (Scheme 3). The reaction is similar
V vs Ag/AgNO3; cathodic peak potential. Salt 12a +‚BF4- and
a
b
12b+‚BF4- were used for the measurement. c Reference 12. Ref-
d
erence 13. e Reference 18.
to that of 5+‚BF4- 13 Upon hydride abstraction with DDQ
.
12b+, 456 nm) than those of 4a + 12 and 5+ 13 (4a +, 397
nm; 5+, 441 nm), suggesting that cations 12a + and 12b+
have a more extended conjugation as compared with
those of 4a + and 5+ (Table 1). X-ray crystal analyses of
and subsequent anion exchange reaction, compounds 18a
and 18b regenerated 12a +‚BF4- and 12b+‚BF4-, respec-
tively, in quantitative yields. On the other hand, the
reaction of 4a +‚BF4 with diethylamine afforded a C5a-
-
-
-
12a +‚BF4 and 12b+‚BF4 were performed, and the
ORTEP drawings are shown in Figure 4.15 Compounds
12a +‚BF4- and 12b+‚BF4- have a nearly planar structure.
On both compounds 12a +‚BF4- and 12b+‚BF4-, the bond
lengths of O1-C15 and O2-C9 are shorter than those
of O1-C2 and O2-C6, suggesting that the former bonds
have a larger bond order. Furthermore, on compound
adduct, which underwent a ring-opening reaction to give
22 (Scheme 4).12 In contrast, the diethylamine addition
of 5+‚BF4- occurred at only C7 to give 23, which is stable
and does not undergo a further isomerization reaction.13
-
-
Thus, the reactivity of 12a +‚BF4 and 12b+‚BF4 with
diethylamine is very interesting, and the reaction of
12a +‚BF4- with diethylamine was monitored by 1H NMR
spectroscopy in CD3CN. Initially, diethylamine addition
12a +‚BF4-, the bond length of C4-C5 is shorter than
those of C3-C4 and C5-C7. On compound 12b+‚BF4
,
-
-
to 12a +‚BF4 occurred at C12 to afford 19a (Scheme 4).
the bond length of C1-C2 is shorter than that of C1-
C7. These facts suggest the existence of bond alternation
as shown in the canonical structures of 12a ,b+-B and
12a ,b+-C (Figure 5). The feature shows also that cations
12a + and 12b+ have a more extended conjugation as
compared with 4a + and 5+.12,13 MO calculations of 12a +
and 12b+ were carried out by the 6-31G* basis set of the
MP2 level,16 and it was found that the bond length
alternations obtained by the MO calculations are very
similar to those obtained by the X-ray analyses.
Although compound 19a is stable in dilute solution, it
decomposes during concentration in vacuo. Satisfactory
1H and 13C NMR spectra were obtained for 19a . While
the C12-adduct 19a is stable under 1H NMR measure-
ment (1 h), a slow isomerization reaction seemed to occur
(48 h) to give 20a , which underwent ring-opening reac-
tion to afford 21a (Scheme 4). On the other hand, a
reaction of 12b+‚BF4- with diethylamine gives only C6a-
adduct 20b, which undergoes ring-opening reaction to
give 21b. Compound 21b was stable and no isomerization
The affinity of the carbocation toward hydroxide ions
1
+
reaction was observed. On the basis of the study of H
expressed by the pKR value is the most common criterion
and 13C NMR, we have reported that compound 22 has
a larger contribution of the canonical structure 22-B.12
On the contrary, considering the large coupling constant
(10.4 Hz) between the H1 and H2, as well as the high-
field chemical shift of C4 (δC 125.0 ppm), compound 21a
has a larger contribution of the canonical structure
21a -A, probably due to the stability of the closed furan
ring. The large coupling constant (11.4 Hz) between the
H1 and the H2 and the low-field chemical shift of C4 (δC
175.4 ppm) suggest that compound 21b has a larger
contribution of the canonical structure 21b-B, probably
due to the stability of the closed furan ring. Upon
treatment with aq HBF4 in Ac2O, compounds 19a , 21a ,
of carbocation stability.17 The pKR values of cations 12a
+
+
and 12b+ were determined spectrophotometrically in
buffer solutions prepared in 50% aqueous CH3CN and
are summarized in Table 1, along with those of reference
cations 4a +,12 5+,13 and tropylium ion 17+.18 The pKR
+
values of 12a + and 12b+ (12a +, pKR , 8.8; 12b , pKR
,
,
+
+
+
8.6) are larger than those of 4a + (pKR , ca. 6.0), 5+ (pKR
+
+
4.7), and 17+ (pKR , 3.9), suggesting that the two 2,4-
dimethylfuro[2,3-d]pyrimidine-1(2H),3(4H)-dione moi-
eties stabilize the tropylium ion quite effectively. While
the benzo-annulation onto 4a + has a destabilization effect
on the cation 5+, one more annulation of the furopyri-
+
midine-ring onto 4a + has a stabilizing effect on the
and 21b regenerated 12a +‚BF4 and 12b+‚BF4 in good
yield.
-
-
cations 12a + and 12b+. Although the pKR value of 12a
+
+
is larger than that of 12b+, the difference is small,
suggesting that the difference in perturbations due to the
position of annulation by the furopyrimidine-ring is
small.
Au tor ecyclin g Oxid a tion . The double 5-deazaflavins
2a and 2b have been studied as photocatalysts for
cyclohexanol under photoirradiation.7,8 Moreover, we
-
have previously reported that compound 4a +‚BF4 acts
The reduction potentials of 12a + and 12b+ were
determined by cyclic voltammentry (CV) in CH3CN. The
reduction waves of 12a + and 12b+ were irreversible
under the conditions of the CV measurements; the peak
potential is also summarized in Table 1, together with
those of the reference cations 4a +,12 5+,13 and tropylium
ion 17+.18 The irreversible nature is probably due to the
as a photocatalyst for some alcohols under photoirradia-
tion.12 In this context and in a search for functions of
(19) (a) Doering, W. von E.; Knox, L. H. J . Am. Chem. Soc. 1954,
76, 3203-3206. (b) Doering, W. von E.; Knox, L. H. J . Am. Chem. Soc.
1957, 79, 352-356. (c) Okamoto, K.; Komatsu, K.; Kinoshita, T.;
Shingu, H. Bull. Chem. Soc. J pn. 1970, 43, 1901-1902.
4736 J . Org. Chem., Vol. 69, No. 14, 2004

Synthesis and Oxidizing Ability of Tropylium Ions
F IGURE 4. ORTEP drawings of 12a +‚BF4- and 12b+‚BF4- with thermal ellipsoid plot (50% probability). Selected bond lengths
(Å) of 12a +‚BF4
: O1-C2 1.392(4), O1-C15 1.341(4), O2-C6 1.390(4), O2-C9 1.348(5), C1-C2 1.361(5), C2-C3 1.423(5),
-
C3-C4 1.421(5), C4-C5 1.373(5), C5-C7 1.413(5), C6-C7 1.424(5), C1-C6 1.374(5), C3-C14 1.426(5), C7-C8 1.416(5), C8-C9
1.364(5), C14-C15 1.371(5). Selected bond lengths (Å) of 12b +‚BF4
: O1-C2 1.394(3), O1-C15 1.345(3), O2-C6 1.384(3),
-
O2-C9 1.347(3), C1-C2 1.366(3), C2-C3 1.436(3), C3-C4 1.401(3), C4-C5 1.376(3), C5-C6 1.383(3), C6-C7 1.420(3), C1-C7
1.409(3), C3-C14 1.417(3), C7-C8 1.428(3), C8-C9 1.358(3), C14-C15 1.369(3).
SCHEME 3 a
a
Reagents and conditions: (i) NaBH4, CH3CN, rt, 1 h; (ii) (a)
DDQ, CH2Cl2, rt, 1 h; (b) 42% aq HBF4, Ac2O, 0 °C, 1 h
12b+‚BF4- (named “blank”) gives the corresponding car-
bonyl compounds in small amounts. Thus, the yield in
Table 2 is calculated by subtraction of the “blank” yield
from the yield of the carbonyl compound in the presence
-
of 12a +‚BF4 or 12b+‚BF4-. Carbonyl compounds are
obtained in more than 100% yield [based on salts
F IGURE 5.
12a +‚BF4 or 12b+‚BF4-] under photoirradiation, and
-
12a +‚BF4- and 12b+‚BF4-, we examined the oxidation of
thus the autorecycling oxidation clearly proceeds. At-
tempted detection of the intermediate such as reduced
compounds 18a and 18b in the oxidation reaction of
some alcohols and amines by using 12a +‚BF4 and
-
12b+‚BF4-. We found that salts 12a+‚BF4- and 12b+‚BF4
-
alcohols and amines was unsuccessful at the present
stage. We propose that the present autorecycling oxida-
tion proceeds via electron transfer from alcohol or amine
can oxidize benzyl alcohol and cyclohexanol to give
benzaldehyde and cyclohexanone, respectively, under
aerobic and photoirradiation conditions. Furthermore, we
to the excited cation 12a +‚BF4 or 12b+‚BF4
;
how-
-
- 12,20
-
-
found that salts 12a +‚BF4 and 12b+‚BF4 can oxidize
benzylamine and 1-phenylethylamine to give the corre-
sponding imines. The photooxidation results are sum-
marized in Table 2. Oxidation of benzyl alcohol and
benzylamine with reference salt 4a +‚BF4- under similar
conditions was also carried out (Table 2, entries 9 and
10). Those reactions gave better yields as compared with
those of 12a +‚BF4- and 12b+‚BF4-. Direct irradiation of
ever, further investigations are required to clarify details
of the present autorecycling oxidation reaction.
In summary, a convenient synthesis of novel tropylium
ions annulated with two 2,4-dimethylfuro[2,3-d]pyrimi-
dine-1(2H),3(4H)-diones 12a +‚BF4 and 12b+‚BF4 was
-
-
accomplished. On the basis of MO calculations of a novel
the alcohols and amines in the absence of 12a +‚BF4 or
(20) Naya, S.; Iida, Y.; Nitta, M. Tetrahedron 2004, 60, 459-467.
J . Org. Chem, Vol. 69, No. 14, 2004 4737
-

Naya et al.
SCHEME 4 a
a
Reagents and conditions: (i) Et2NH, CD3CN, rt, 30 s; (ii) 42% aq HBF4, Ac2O, 0 °C, 1 h; (iii) Et2NH, CH3CN, rt, 48 h;
of 12a +‚BF4 and 12b+‚BF4 were studied by X-ray
crystal analyses and MO calculations. The physical
properties of 12a +‚BF4- and 12b+‚BF4- were investigated
-
-
TABLE 2. Au tor ecyclin g Oxid a tion of Som e Alcoh ols
a n d Am in es by 12a +‚BF 4-, 12b+‚BF 4-, a n d Refer en ce Sa lt
-
4a +‚BF 4 u n d er P h otoir r a d ia tion a
alcohol or
amine
carbonyl
compdb
+
by measurement of the UV-vis spectra, the pKR values,
entry
salt
yieldc/%
and the reduction potentials. Reactivity of 12a +‚BF4- and
12b+‚BF4- with diethylamine was substantially depend-
ent on the annulating position. The photoinduced au-
-
1
2
3
4
5
6
7
8
9
12a +‚BF4- PhCH2OH
12b+‚BF4- PhCH2OH
12a +‚BF4- cyclohexanol
12b+‚BF4- cyclohexanol
12a +‚BF4- PhCH2NH2
12b+‚BF4- PhCH2NH2
PhCHO
PhCHO
cyclohexanone
cyclohexanone
PhCHdNCH2Ph
PhCHdNCH2Ph
2224
1429
669
432
7699
6601
-
torecycling oxidation reaction of 12a+‚BF4- and 12b+‚BF4
toward some alcohols and amines was carried out to
afford the corresponding carbonyl compounds in yields
of more than 100%.
12a +‚BF4- PhCH(Me)NH2 PhMeCdNCHMePh 5213
12b+‚BF4 PhCH(Me)NH2 PhMeCdNCHMePh 3600
4a +‚BF4- e PhCH2OH
PhCHO
PhCHdNCH2Ph
4468
8161
- d
10 4a +‚BF4
PhCH2NH2
Exp er im en ta l Section
a
CH3CN solution was irradiated by RPR-100, 350-nm lamps
General experimental conditions and spectroscopic instru-
mentation used have been previously described.11
b
under aerobic conditions. Isolated by conversion to 2,4-dinitro-
-
-
phenylhydrazone. c Based on 12a +‚BF4 or 12b+‚BF4 used; the
P r epa r a tion of 7,9-Dim eth yl-3-[1′,3′-d im eth yl-2′(1′H),4′-
(3′H),6′(5′H)-tr ioxop yr im id in -5′-ylid en e]cycloh ep ta [b]p y-
r im id o[5,4-d ]fu r a n -8(7H),10(9H)-d ion e (8). A solution of
2-methoxytropone 6 (136 mg, 1 mmol) and dimethylbarbituric
acid 7 (313 mg, 2 mmol) in Ac2O (2 mL) was heated under
reflux for 0.5 h. After the reaction was completed, the mixture
was concentrated in vacuo. The resulting residue was chro-
yield is calculated by subtraction of the “blank” yield from the total
yield of carbonyl compound in the presence of 12a +‚BF4 or
-
12b+‚BF4
.
Reference 12. e This work.
-
d
heptafulvene 8, the selectivity of two types of oxidative
cyclization was clarified. The structural characteristics
4738 J . Org. Chem., Vol. 69, No. 14, 2004

Synthesis and Oxidizing Ability of Tropylium Ions
-
-
matographed on SiO2 with AcOEt as the eluent to give 8 (150
mg, 38%) and a mixture of 9a -c (122 mg, 50%). The mixture
of compounds 9a -c was identified on the basis of the com-
parison of the physical data with those reported in the
literature.12
Rea ction of 12a +‚BF 4 or 12b+‚BF 4 w ith Na BH4. A
solution of 12a +‚BF4 or 12b+‚BF4 (482 mg, 1 mmol) and
NaBH4 (38 mg, 1 mmol) in CH3CN (10 mL) was stirred at room
temperature 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 compound 18a (396 mg, 100%) or 18b (396
mg, 100%), respectively.
-
-
In d ep en d en t P r ep a r a tion of Com p ou n d s 11. A solution
of 4a +‚BF4
(132 mg, 0.4 mmol) and 7 (31 mg, 0.2 mmol) in
- 11
CH3CN (5 mL) in the presence of Et3N (50 mg, 0.5 mmol) was
stirred at room temperature for 2 h. To the mixture was added
H2O, and the mixture was extracted with CH2Cl2. The extract
was dried over Na2SO4 and concentrated in vacuo to give
compound 11 (128 mg, 100%).
Oxid a tion of 18a a n d 18b. To a stirred solution of 18a or
18b (198 mg, 0.5 mmol) in CH2Cl2 (5 mL) was added DDQ
(176 mg, 0.75 mmol), and the mixture was stirred at room
temperature for 1 h. After evaporation of the CH2Cl2, the
residue was dissolved in a mixture of Ac2O (5 mL) and 42%
aq HBF4 (1 mL) at 0 °C, and the mixture was stirred for
another 1 h. To the mixture was added Et2O (50 mL) and the
Th er m a l Elim in a tion Rea ction of 11. A solution of 11
(192 mg, 0.3 mmol) in xylene (5 mL) was heated at 90 °C under
N2 for 3 h. After evaporation of the solvent, the residue was
separated by column chromatography on SiO2 (hexane-AcOEt,
1:1) to give 8 (99 mg, 83%) and 9a -c (24 mg, 33%).
Oxid a tive Cycliza tion of 8 w ith DDQ. To a stirred
solution of 8 (396 mg, 1 mmol) in CHCl3 (20 mL) was added
DDQ (467 mg, 2 mmol) and the mixture was heated under
reflux for 1 h until the reaction was complete. After evapora-
tion of the CHCl3, the residue was dissolved in a mixture of
Ac2O (10 mL) and 42% aq HBF4 (2 mL) at 0 °C and the mixture
was stirred for 1 h. To the mixture was added Et2O (200 mL)
and the precipitate was collected by filtration and washed with
Et2O to give a mixture of 12a +‚BF4- and 12b+‚BF4- (431 mg,
90%) in the ratio of 4:1.
precipitate was collected by filtration to give 12a +‚BF4 (241
-
mg, 100%) or 12b+‚BF4 (241 mg, 100%), respectively.
-
1H NMR Mon itor in g of th e Rea ction of 12a +‚BF 4- a n d
-
-
12b+‚BF 4 w ith Dieth yla m in e. To a solution of 12a +‚BF4
or 12b+‚BF4- (0.01 mmol) in CD3CN (0.5 mL) in a NMR tube
was added diethylamine (7.3 mg, 0.1 mmol). The NMR
measurement was carried out immediately (after ca. 30 s).
R ea ct ion of 12a +‚BF 4 a n d 12b+‚BF 4 w it h Diet h yl-
-
-
a m in e. A solution of 12a +‚BF4 (241 mg, 0.5 mmol) and
-
diethylamine (147 mg, 2 mmol) in CH3CN (10 mL) was stirred
at room temperature for 48 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 21a (234 mg, 100%).
Oxid a tive Cycliza tion of 8 by P h otoir r a d ia tion . A
solution of 8 (198 mg, 0.5 mmol) and 42% aq HBF4 (2 mL) in
CH3CN (180 mL) and (CH2Cl)2 (20 mL) in a Pyrex tube was
irradiated by RPR-100, 350-nm lamps under aerobic conditions
for 48 h until the reaction was complete. The mixture was
concentrated in vacuo, and the resulting residue was dissolved
in a mixture of Ac2O (10 mL) and 42% aq HBF4 (2 mL) at
0 °C. The mixture was stirred for 1 h. To the mixture was
added Et2O (100 mL) and the precipitate was collected by
Rea ction of 12b+‚BF 4 w ith Dieth yla m in e. A solution
-
of 12b+‚BF4 (241 mg, 0.5 mmol) and diethylamine (147 mg,
-
2 mmol) in CH3CN (10 mL) was stirred at room temperature
for 1 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 21b (224 mg, 97%).
-
filtration to give 12a +‚BF4 (238 mg, 99%).
Rea ction of 19a w ith HBF 4. To a solution of 19a (0.05
mmol) and diethylamine in CH3CN, prepared by the reaction
of 12a +‚BF4- (0.05 mmol) with diethylamine (7.3 mg, 0.1 mmol)
in CH3CN (20 mL), was added a mixture of Ac2O (5 mL) and
42% aq HBF4 (1 mL) at 0 °C. The mixture was stirred for 1 h.
To the mixture was added Et2O (50 mL) and the precipitate
-
Det er m in a t ion of p KR + Va lu es of 12a +‚BF 4 a n d
12b+‚BF 4-. Buffer solutions of slightly different acidities were
prepared by mixing aqueous (H2O-CH3CN 5:4) solutions of
potassium hydrogen phthalate (0.1 M) and NaOH (0.1 M) (for
pH 4.1-5.9), KH2PO4 (0.1 M) and NaOH (0.1 M) (for pH 6.0-
8.0), KH2PO4 (0.1 M) and NaOH (0.1 M) (for pH 6.0-8.0),
Na2B4O7 (0.025 M) and HCl (0.1 M) (for pH 8.2-9.0), and
Na2B4O7 (0.025 M) and NaOH (0.1 M) (for 9.2-10.8) in various
portions. For the preparation of sample solutions, 1-mL
portions of the stock solution, prepared by dissolving 3 mg of
compounds 12a +‚BF4- and 12b+‚BF4- in CH3CN (20 mL), were
diluted to 10 mL with the buffer solution (9 mL). The UV-vis
spectrum was recorded for each cation 12a + and 12b+ 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 absor-
bance at the specific absorption wavelength (12a +, 458 nm;
12b+, 453 nm) of cations 12a + and 12b+ was plotted against
pH to give a classical titration curve, whose midpoint was
-
was collected by filtration to give 12a +‚BF4 (24 mg, 100%).
Rea ction of 21a a n d 21b w ith HBF 4. A solution of 21a
or 21b (234 mg, 0.5 mmol) in Ac2O (10 mL) and 42% aq HBF4
(2 mL) was stirred at
0 °C for 1 h. To the mix-
ture was added Et2O (50 mL) and the precipitate was collected
-
by filtration to give 12a +‚BF4 or 12b+‚BF4-, respectively
(12a +‚BF4-, 217 mg, 90%; 12b+‚BF4-, 234 mg, 97%).
Gen er a l P r oced u r e for th e Oxid a tion of Alcoh ols in
th e P r esen ce of 12a +‚BF 4 a n d 12b+‚BF 4-. A CH3CN (16
-
mL) solution of salt 12a +‚BF4- or 12b+‚BF4- (0.005 mmol), an
alcohol (2.5 mmol, 500 equiv), and K2CO3 (138 mg, 1 mmol) in
a Pyrex tube was irradiated by RPR-100, 350-nm lamps under
aerobic conditions for 16 h. The reaction mixture was concen-
trated in vacuo and diluted with Et2O and filtered. The filtrate
was treated with a saturated solution of 2,4-dinitrophenylhy-
drazine in 6% HCl to give 2,4-dinitrophenylhydrazone. The
results are summarized in Table 2.
+
taken as the pKR value.
Cyclic Volta m m etr y of Ca tion s 12a + a n d 12b+. The
reduction potential of 12a + and 12b+ was determined by using
a 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 a CH3CN solution (4 mL) of cations 12a + and 12b+
(0.5 mmol dm-3) and Bu4NClO4 (0.1 mol dm-3) to deaerate it.
The measurements were made at a scan rate of 0.1 V s-1 and
the voltammograms were recorded on a WX-1000-UM-019
(Graphtec Co) X-Y recorder. Immediately after the measure-
ments, ferrocene (0.1 mmol) (E1/2 ) +0.083) was added as the
internal standard, and the observed peak potential was
corrected with reference to this standard. The cations 12a +
and 12b+ exhibited a reduction wave, and they are sum-
marized in Table 1.
Gen er a l P r oced u r e for th e Oxid a tion of Am in es in th e
P r esen ce 12a +‚BF 4 a n d 12b+‚BF 4-. A CH3CN (16 mL)
-
solution of salt 12a +‚BF4 and 12b+‚BF4 (0.005 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 filtrate was treated with
a
saturated solution of 2,4-dinitrophenylhydrazine in 6% HCl
to give 2,4-dinitrophenylhydrazone. The results are sum-
marized in Table 2.
Ack n ow led gm en t. Financial support from a Wase-
da University Grant for Special Research Project and
J . Org. Chem, Vol. 69, No. 14, 2004 4739

Naya et al.
values and cyclic voltammetry of 12a +‚BF4 and 12b+‚BF4
;
-
-
21COE “Practical Nano-chemistry” from MEXT, J apan,
is gratefully acknowledged. We thank the Materials
Characterization Central Laboratory, Waseda Univer-
sity, for technical assistance with the spectral data,
elemental analyses, and X-ray analyses.
UV-vis spectra of 12a +‚BF4 and 12b+‚BF4 and reference
compound 4a +‚BF4-. Analytical and spectroscopic data of 8,
11, 12a +‚BF4-, 12b+‚BF4-, 18a ,b, 19a , and 21a ,b; and NMR
data of 8, 11, 12a +‚BF4-, 12b+‚BF4-, 18a ,b, 19a , and 21a ,b.
This material is available free of charge via the Internet at
http://pubs.acs.org.
-
-
Su p p or tin g In for m a tion Ava ila ble: Detailed descrip-
tions of the X-ray crystal analyses and calculated data for
-
-
12a +‚BF4 and 12b+‚BF4 as well as determination of pKR
J O049668C
+
4740 J . Org. Chem., Vol. 69, No. 14, 2004