Reversible 1,4-cycloaddition of singlet oxygen to N-substituted 2-pyridones: 1,4-Endoperoxide as a versatile chemical source of singlet oxygen

Article abstract of DOI:10.1039/b414845b

N-substituted pyridones (1) easily undergo singlet oxygenation to give exclusively the corresponding endoperoxides (2), which decompose to give pyridones again while liberating ¹O₂ in high yield.

Full text of DOI:10.1039/b414845b

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Reversible 1,4-cycloaddition of singlet oxygen to N-substituted
2-pyridones: 1,4-endoperoxide as a versatile chemical source of singlet
oxygen{
Masakatsu Matsumoto,* Masayo Yamada and Nobuko Watanabe
Received (in Cambridge, UK) 27th September 2004, Accepted 22nd October 2004
First published as an Advance Article on the web 2nd December 2004
DOI: 10.1039/b414845b
(2a) was produced exclusively. Chromatographic purification
(silica gel/hexane–dichloromethane) was attained easily to give
peroxide (2a) as colorless leaflets (mp 67.0–68.0 uC, dec.), the
N-substituted pyridones (1) easily undergo singlet oxygenation
to give exclusively the corresponding endoperoxides (2), which
decompose to give pyridones again while liberating 1O2 in high
yield.
1
structure of which was determined by H-NMR, 13C-NMR, IR,
and mass spectral analysis.{ The other pyridones (1b–1e) gave also
exclusively the corresponding 1,4-endoperoxides (2b–2e) on similar
singlet oxygenation.
a-Pyranones are known to undergo 1,4-cycloaddition with singlet
oxygen (1O2),1–3 to afford 1,4-endoperoxides, which decompose
thermally into 1,2-diacylethylenes while extruding CO2 (Scheme 1).
All endoperoxides (2a–2e) synthesized here were stable enough
for handling at room temperature and storing for . 1 year in a
freezer though they decomposed into the corresponding pyridones
(1a–1e) exclusively in a solvent such as CDCl3 at 40 uC with half-
life of 2–6 h. When the thermolysis of 2a–2e was carried out in the
presence of typical substrates, namely, dihydrofuran (3) for 1,2-
1
We report here that a) O2 adds also to nitrogen-analogues of
a-pyranone, namely, N-substituted pyridones (1) to give 1,4-
endoperoxides (2) exclusively, b) the thus-obtained peroxides (2)
liberate 1O2 in high yield, differing from the case of 1,4-
endoperoxides of a-pyranones, and c) the peroxides (2) are a
1
1
addition of O2,4 isobenzofuran (4) for 1,4-addition of O2,5 and
2,3-dimethylbut-2-ene (5) for ‘‘ene’’ reaction of 1O2,6 dioxetane
(6),§ diketone (7), and hydroperoxide (8) were produced,
respectively. These results showed that the retro-1,4-cycloaddition
1
promising chemical O2 source with characteristics different from
those of 1,4-endoperoxides of substituted polynuclear aromatics.
Commercially available 2-hydroxypyridine and its 4-methyl-
analogue were easily alkylated with benzyl bromide, 4-bromo-
methylbiphenyl, and t-butyl bromoacetate to give the
corresponding N-substituted 2-pyridones (1a–1e) in high yields.
When a solution of N-benzyl-2-pyridone (1a) (250 mg) in
dichloromethane (10 mL) was irradiated with a Na-lamp (940 W)
together with a catalytic amount of tetraphenylporphine (TPP)
under an oxygen atmosphere at 278 uC for 2 h, 1,4-endoperoxide
1
proceeded to liberate O2.
Thus, we attempted to estimate the efficiency of 1O2 generation
by means of a trapping experiment of 1O2 with an olefin (5) for the
thermolysis of endoperoxides (2a–2e). First of all, we examined
whether the re-combination of 1O2 with pyridones, formed during
the thermolysis of 2a, could be prevented substantially by the use
of a highly reactive olefin (5). Sensitized photooxygenation of a
mixture of 1a (1.5 6 1022 M) and an equimolar amount of 5 in
CDCl3 at 30–40 uC was confirmed to give exclusively a
hydroperoxide (8) without formation of 2a even after ca. 40%
conversion of 5.
A solution of endoperoxide (2a) (1.5 6 1022 M) and an olefin
(5) (7.5 6 1022 M) in CDCl3 was heated, and the time-course of
the formation of 8 and 1a and of the decrease of 2a was followed
by means of 1H-NMR at 30, 40, and 50 uC." Similar kinetic
experiments were carried out for thermolysis of the other
endoperoxides (2b–2e). All endoperoxides (2a–2e) were found to
decompose into the corresponding 2-pyridones (1a–1e) by first-
order kinetics and to afford 1O2 in high yields even at high
conversion (y80%). These results are summarized in Table 1
together with activation parameters for the thermolysis, which
were estimated from the Arrhenius plots.
1
Reversible 1,4-cycloaddition of O2 to a conjugate system has
been recognized as one rather characteristic feature for polynuclear
aromatic hydrocarbons.7 In fact, endoperoxides of 9,10-diphenyl-
anthracenes and 1,4-dialkylnaphthalenes are well known to
Scheme 1
1
generate O2 in yields from 30 to 95% on heating.8,9 Turro and
{ Electronic supplementary information (ESI) available: experimental
section. See http://www.rsc.org/suppdata/cc/b4/b414845b/
*matsumo-chem@kanagawa-u.ac.jp
his co-workers have found for the thermolysis of these endoper-
oxides that a) DS{ values range from positive to slightly negative,
This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 483–485 | 483

View Article Online
Table 1 Activation parameters and efficiency of 1O2 generation for
thermolysis of N-substituted 2-pyridone endoperoxides (2a–2e) in
CDCl3
1O2/%
DG{/
DH{/
DS{/
kcal mol21 kcal mol21 cal K21 mol21
Aa
Bb
2a
2b
2c
2d
2e
a
24.3
24.1
24.7
24.6
25.2
22.8
23.0
23.2
24.1
25.2
25.3
23.7
25.0
21.4
0.1
96 ¡ 1 81 ¡ 1
96 ¡ 1 73 ¡ 1
97 ¡ 1 84 ¡ 4
89 ¡ 2 74 ¡ 6
84 ¡ 1 82 ¡ 1
b
Mean of 1O2 yields for , 20% conversion of 2 at 40 uC. Mean of
1O2 yields at 30, 40, and 50 uC. 1O2 yield at each temperature was
estimated from the data at five points for 30–80% conversion of 2.
Scheme 2
Chemical 1O2 sources which are less complicated mechanistically
are quite useful for 1O2 reactions of biological substrates,
mechanistic investigations of 1O2 reactions with organic substrates,
and as an essential chemical species for COIL (chemical oxygen–
iodine laser).10 As described earlier, the present endoperoxides (2)
and 2) positive DS{ values correlate with the relatively low yields of
1O2, and slightly negative or near zero DS{ values correlate with
the high yields of 1O2.8,9 They have also suggested that these
tendencies can be interpreted in terms of a diradical mechanism
1
would be useful as a new chemical source of O2. Comparing 2
1
with 1,4-endoperoxides of alkylnaphthalene derivatives11,12 as
chemical 1O2 sources, one advantageous feature of 2 probably lies
in the easy preparation and modification of their precursors,
namely, N-substituted 2-pyridones (1), since the synthesis of most
substituted naphthalenes is unexpectedly burdensome. A good
example is the preparation of a polymer-supported 1O2 generator.
Functionalized polymer represented by Merrifield’s resin is often
used in a wide variety of reactions in the solid phase. 2-Pyridone
was easily joined to Merrifield’s resinI to give 1f by means of
nucleophilic substitution similar to the synthesis of 1a–1e. The
thus-prepared pyridone supported on polymer (1f) was also easily
converted into the corresponding endoperoxide (2f) by sensitized
photooxygenation similar to the case of 1a–1e except that a
suspension of the substrate was used (Scheme 2).** When
endoperoxide supported on Merrifield’s resin (2f) was heated with
olefin (5) at 40 uC for 1 h, 1O2 was estimated to be liberated in 85%
yield based on produced hydroperoxide (8) and the consumed
endoperoxide.
which leads to a low yield of O2 and a concerted mechanism
1
which leads to high yields of O2, respectively.
DS{ values ranged from slightly positive to negative for
endoperoxides of pyridones (2a–2e). Furthermore, column A in
Table 1 shows that the liberation of 1O2 occurred nearly
quantitatively for most cases of thermolysis of 2 at low conversion
of 2 (, 20%). These relationships between the yield of 1O2 and the
DS{ value are illustrated in Fig. 1. One would realize from Fig. 1
that endoperoxides of pyridones (2) (squares) belong to the same
class which includes endoperoxides of polynuclear aromatics for
the mechanism of 1O2 liberation. On the other hand, the efficiency
1
of O2 generation decreased considerably at high conversion of 2
1
except 2e (y80%), though the absolute yields of O2 stayed at a
high level. When the thermolysis of 2a was carried out in the
1
presence of an equimolar amount of 2-pyridone (1a), O2 yield
decreased to ca. 80% at low conversion of 2a. Thus, the decrease of
1O2 yields is likely to be attributable to the fact that 2-pyridone (1)
produced during the thermolysis of 2 quenches 1O2 physically,
though detailed experiments would be required to confirm such a
conclusion.
In conclusion, we have shown here that N-substituted pyridones
(1) easily undergo singlet oxygenation to give exclusively the
corresponding endoperoxides (2), which decompose to give
pyridones again while liberating 1O2 in high yields.
Endoperoxides (2) have been shown to be a new type of chemical
1O2 source, preparation and structural modification of which are
1
very easy and the efficiency of O2 liberation from which is high.
1
Finally, it should be noted that a water-soluble and neutral O2
generator, such as an amide derivative (2g), was also obtained.
Masakatsu Matsumoto,* Masayo Yamada and Nobuko Watanabe
Department of Materials Science, Kanagawa University, Tsuchiya,
Hiratsuka, Kanagawa, 259-1293, Japan.
E-mail: matsumo-chem@kanagawa-u.ac.jp
Notes and references
{ Selected data for 2a: 1H-NMR (400 MHz, CDCl3): dH 4.42 (d,
J 5 15.3 Hz, 1H), 4.87 (d, J 5 15.3 Hz, 1H), 5.08 (ddd, J 5 5.8, 2.1,
0.6 Hz, 1H), 5.53 (ddd, J 5 5.2, 2.1, 0.6 Hz, 1H), 6.71 (ddd, J 5 7.8, 5.2,
2.1 Hz, 1H), 6.76 (ddd, J 5 7.8, 5.8, 2.1 Hz, 1H), 7.19–7.24 (m, 2H), 7.28–
7.39 (m, 3H) ppm; 13C-NMR (100 MHz, CDCl3): dC 46.9, 78.0, 83.2, 127.8,
127.9, 128.6, 128.8, 134.2, 135.1, 167.9 ppm; IR (KBr): 3089, 3031, 2932,
1691, 1426, 1350, 1158 cm21; Mass (EI, %): 217 (M+, 25), 201 (70), 185
(76), 184 (34), 106 (34), 91 (100), 65 (20).
Fig. 1 Relationship between 1O2 yield and activation entropy for
thermolysis of endoperoxides of polynuclear aromatics and pyridone
endoperoxides (2).
484 | Chem. Commun., 2005, 483–485
This journal is ß The Royal Society of Chemistry 2005

View Article Online
§ When an endoperoxide (2) (1.5 6 1022 M) and a dihydrofuran (3) (3.0 6
1023 M) were heated in CDCl3 for 2 h, a dioxetane (6) was produced in 12–
56% yield.
" The reaction was carried out in an NMR sample tube without stirring.
I As Merrifield’s resin, 1% cross-linked polystyrene (200–400 mesh,
1.2 mmol Cl2/g) was used. The 2-pyridone unit was estimated to be
supported nearly quantitatively on the polymer from the difference between
the pyridone used initially and that recovered.
5 A. J. Bloodworth and H. J. Eggelte, ‘Endoperoxides’, in Singlet Oxygen,
ed. A. A. Frimer, Vol. II, CRC Press, Boca Raton, 1985, pp. 93–203.
6 (a) K. Gollnick and H. J. Kuhn, ‘Ene-reactions with Singlet Oxygen’, in
Singlet Oxygen, ed. H. H. Wasserman and R. W. Murray, Academic
Press, New York, 1979, pp. 287–427; (b) A. A. Frimer and
L. M. Stephenson, ‘The Singlet Oxygen ‘‘Ene’’ Reaction’, in Singlet
Oxygen, ed. A. A. Frimer, Vol. II, CRC Press, Boca Raton, 1985,
pp. 67–92.
7 E. L. Clennan and C. S. J. Foote, ‘Endoperoxides’, in Organic
Peroxides, ed. W. Ando, Wiley, New York, 1992, pp. 255–318.
8 N. J. Turro, M.-F. Chow and J. Rigaudy, J. Am. Chem. Soc., 1977, 101,
1300–1301.
9 N. J. Turro, M.-F. Chow and J. Rigaudy, J. Am. Chem. Soc., 1979, 103,
7218–7224.
** Completion of singlet oxygenation was checked by monitoring the
increase of the CLO peak (1710 cm21) due to endoperoxide of pyridone
and disappearance of the CLO peak (1661 cm21) due to N-substituted
2-pyridone for the IR spectrum.
1 W. Adam and I. Erden, Angew. Chem., 1978, 90, 223.
2 (a) J. P. Smith and G. B. Schuster, J. Am. Chem. Soc., 1978, 100, 2564;
(b) J. P. Smith, A. K. Schrock and G. B. Schuster, J. Am. Chem. Soc.,
1982, 104, 1041.
3 W. Adam and I. Erden, J. Am. Chem. Soc., 1979, 101, 5692–5696.
4 (a) M. Matsumoto, H. Murakami and N. Watanabe, Chem. Commun.,
1998, 2319–2320; (b) M. Matsumoto, J. Photochem. Photobiol. C, 2004,
5, 27–53.
10 For example, F. Wani, M. Endo and T. Fujioka, Appl. Phys. Lett.,
1999, 75, 20, 3081–3083.
11 (a) I. Saito, T. Matsuura and K. Inoue, J. Am. Chem. Soc., 1981, 103,
188; (b) I. Saito, T. Matsuura and K. Inoue, J. Am. Chem. Soc., 1983,
105, 3200; (c) K. Inoue, T. Matsuura and I. Saito, J. Photochem., 1984,
25, 511.
12 I. Saito, R. Nagata and T. Matsuura, J. Am. Chem. Soc., 1985, 107,
6329–6334.
This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 483–485 | 485