Transient formation of hydrogen tetraoxide from hydrogen peroxide with bis(trifluoroacetoxyiodo)benzene: A chemical generator of singlet oxygen for organic synthesis

Article abstract of DOI:10.1055/s-2003-39889

Decomposition of hydrogen tetraoxide, produced by the reaction of hydrogen peroxide with bis(trifluoroacetoxyiodo) benzene, generates singlet molecular oxygen. Oxidation of typical organic substrates in an organic solvent through [4+2] cycloaddition and ene reactions have been camed out on a preparative scale.

Full text of DOI:10.1055/s-2003-39889

1180
LETTER
Transient Formation of Hydrogen Tetraoxide from Hydrogen Peroxide with
Bis(trifluoroacetoxyiodo)benzene: A Chemical Generator of Singlet Oxygen
For Organic Synthesis
T
ransient Formation of
u
H
ydrogen T
s
e
traoxidetafa Catir, Hamdullah Kilic*
Department of Chemistry, Ataturk University, 25240 Erzurum, Turkey
Fax +90(442)2360948; E-mail: hkilic@atauni.edu.tr
Received 31 March 2003
Dedicated to Professor Metin Balci on the occasion of his 55th birthday.
oxidation of organic compounds through [4+2] cycloaddi-
tion and ene reactions.
Abstract: Decomposition of hydrogen tetraoxide, produced by the
reaction of hydrogen peroxide with bis(trifluoroacetoxyiodo) ben-
zene, generates singlet molecular oxygen. Oxidation of typical or-
ganic substrates in an organic solvent through [4+2] cycloaddition
and ene reactions have been carried out on a preparative scale.
Treatment of PIFA with 35% hydrogen peroxide in THF
at 10 °C leads to the release of oxygen gas and produces
iodo-benzene. To prove the assumption that singlet oxy-
gen could be generated by the PIFA–H2O2 system an in-
ternal trap was added to the reaction mixture. a-Terpinene
1 was chosen as the internal trap because it reacts quickly
and selectively with singlet oxygen through a [4+2] cy-
cloaddition with negligible physical quenching. In view of
the product selectivity and discrimination between arom-
atization and peroxidation of a given substrate with this
present system a-terpinene 1 serves as a diagnostic tool.
The 1H NMR spectrum recorded after the oxidation of a-
terpinene 1 with PIFA–H2O2 proves the disappearance 1
and confirms the formation of ascaridole 29 and p-cymene
3. In view of the solvent effect, four different solvents
were selected for a screening of the product distribution:
THF, acetone, dichloromethane and carbon tetrachloride.
Table 1 presents the yields for the full conversion of 1 into
the endoperoxide 2 and p-cymene 3 in different solvents
after 2–3 h of reaction at 10 °C with PIFA–H2O2 system
(Table 1). We could establish that omission of PIFA or
hydrogen peroxide does not lead to the formation of 2,
providing that both components are essential for the for-
mation of singlet oxygen. Ascaridole 2 is stable under the
given reaction conditions, and no secondary reaction was
observed. However, control experiments have shown that
1 undergoes dehydrogenation with PIFA to give 3 quanti-
tatively in the absence of hydrogen peroxide.
Key words: hypervalent Iodine, hydrogen tetraoxide, singlet oxy-
gen, oxygenation, peroxide
Much work has been devoted to the chemistry and the bio-
chemistry of singlet oxygen (1O2) since the discovery, in
the 1960s, of its involvement in the photodynamic effect
in the photooxygenation of some polymers.1 In contrast to
ground state molecular oxygen, singlet oxygen has found
considerable synthetic utility since it undergoes selective
reactions with a variety of electron-rich molecules such as
olefins,2 conjugated dienes, polycyclic aromatic hydro-
carbons, phenols, sulfides, and heterocycles.3 This highly
reactive oxidant is usually generated by photosensitiza-
tion. However, due to the rather low stability of the dyes
(such as methylene blue, rose bengal) under photooxida-
tive conditions, there has been an intensive search for al-
ternative dark systems. These dark systems are based on
the conversion of hydrogen peroxide into water and sin-
glet oxygen.4 As an example, MoO42– is known to catalyze
the disproportionation of hydrogen peroxide into water
and singlet oxygen.5 In addition to those methods based
on disproportionation of hydrogen peroxide with metals,6
hydrogen polyoxides such as alkylsilyl hydrotrioxide
have been shown to be an excellent source of singlet oxy-
gen.7 Higher members of the hydrogen polyoxides, such
as hydrogen tetraoxide (H2O4), have been generated as in-
termediates via radical-radical coupling of perhydroxyl
radical (HOO·) on electrode surface and found to decom-
pose into hydrogen peroxide and singlet oxygen.8 Chemi-
cal evidence is presented herein that hydrogen tetraoxide
(H2O4) can be generated at 10 °C by the reaction of hydro-
gen peroxide with bis(trifluoroacetoxyiodo)benzene (PI-
FA) and that it decomposes to give singlet oxygen for
In all cases, 2.5 equivalent of PIFA relative to 1 is suffi-
cient to achieve the total oxidation of the starting materi-
al.10 The conversion of 1 is not dependent on the solvent
effect, but comparative studies have shown that moderate
yields of 2 are obtained in chlorinated solvents since the
formation of 3 is predominant (Table 1, entries 1 and 2).
This is probably due to the fact that chlorinated solvents
are not capable of dissolving sufficient quantities of H2O2
and, 1 undergoes partial dehydrogenation to give 3 before
addition of singlet oxygen. Results reported in Table 1
show that THF and acetone are the most efficient solvents
for formation of endoperoxide 2. Aromatization of the
substrate to give 3 is completely suppressed in THF
(Table 1, entry 4). To illustrate the potential of this meth-
Synlett 2003, No. 8, Print: 24 06 2003.
Art Id.1437-2096,E;2003,0,08,1180,1182,ftx,en;D07903ST.pdf.
© Georg Thieme Verlag Stuttgart · New York

LETTER
Transient Formation of Hydrogen Tetraoxide
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Table 1 Oxygenation of a-Terpinene (1) with Singlet Oxygen Gen- Four typical organic substrates including one conjugated
erated by the PIFA/H2O2 Systema
diene 4, two aromatic hydrocarbons 6, and 8, and one ole-
fin 9 were oxygenated by the PIFA–H2O2 system on pre-
parative scale. Oxygenation of 4 was carried out in THF
to afford 5 in a yield of 40% after chromatography
1
(Table 2, entry 1). The H and 13C NMR spectra were
identical with those obtained from photochemically pro-
duced material. Oxygenation of 6 (DBI) was carried out in
CH2Cl2 (Table 2, entry 2). The reaction was followed by
Entry
Solvent
Conversion Yield (2)
2:3b
loss of the intense color of the starting material. The yield
of pure 7 was 80% (after recrystallization). For the oxy-
genation of 9,10-diphenylanthracene (8) a slight excess of
PIFA and H2O2 was used for the completely conversion
(Table 2, entry 3). The endoperoxide 9 was purified by
means of column chromatography and characterized by
its 1H and 13C NMR spectra, shown to be identical with an
authentic sample. The oxygenations described above in-
clude [4+2] cycloaddition of singlet oxygen to the diene
unit of the given substrates. 2,3-Dimethyl-2-butene (9) is
highly reactive towards ene reaction with singlet oxygen.
Oxidation of 9 under the reaction condition gave 3-hydro-
peroxy-2,3-dimethyl-1-butene (10) which was reduced
with PPh3 to the corresponding alcohol and characterized
by GC(MS) (Table 2, entry 4).
(%)b
>99
>99
>99
>99
(%)c
1
2
3
4
CH2Cl2
CCl4
40
55:44
66:34
83:17
98:2
54
Acetone
THF
65
85
a Conditions: substrate (1 mmol), PIFA (2,5 mmol), 35% H2O2
(6 mmol), NaHCO3 (20 mmol) relative to 1.
b Conversions and product ratios were determined by 1H NMR
analysis of the crude reaction mixture.
c Isolated yields.
In view of the mechanistic explanation of this chemical
evidence for the generation of singlet oxygen we assume
PIFA reacts with H2O2 to give H2O4 as an intermediate
formed via radical-radical coupling of two surface HOO·
groups. H2O4 rapidly undergoes homolytic dissociation
to singlet oxygen and H2O2 (Scheme 1). An analogous
od in preparative organic synthesis and confirm chemical
evidence for the generation of singlet oxygen from the
PIFA–H2O2 system, a number of characteristic transfor-
mations of several substrates has been carried out at 0 °C
in THF or CH2CI2.
Table 2 Oxygenation of Various Substrates with Singlet Oxygen Generated by the PIFA–H2O2 Systema
Entry
1
Substrate
Solvent
THF
Stoichiometry
PIFA:H2O2:NaHCO3
Product
Yield (%)
40b
2.5:6:10
4
5
2
3
4
CH2Cl2
CH2Cl2
THF
2.5:6:10
80b
85b
30c
6
7
4:10:20
2.5:6:10
8
9
9
10
a Conditions: Complete substrate (1 mmol) consumption at 0 °C under atmospheric conditions.
b All products are known and gave satisfactory 1H and 13C NMR spectra. Yields were obtained after purification by simple column chromatog-
raphy (SiO2, hexane–diethyl ether).
c Product yield on substrate basis. Sample was taken and reduced with PPh3, then analyzed with GC-MS
Synlett 2003, No. 8, 1180–1182 ISSN 1234-567-89 © Thieme Stuttgart · New York

1182
M. Catir, H. Kilic
LETTER
(3) Wasserman, H. H.; Ives, J. L. Tetrahedron 1981, 37, 1825.
(4) Clennan, E. L. Tetrahedron 1991, 47, 1343.
(5) Aubry, J.-M.; Bouttemy, S. J. Am. Chem. Soc. 1997, 119,
5286.
(6) Pierlot, C.; Nardello, V.; Schrive, J.; Mabille, C.; Barbillat,
J.; Sombret, B.; Aubry, J.-M. J. Org. Chem. 2002, 67, 2418.
(7) Corey, E. J.; Mehrotra, M. M.; Khan, A. U. J. Am. Chem.
Soc. 1986, 108, 2472.
pathway has been proposed for alkylperoxy radicals
(2ROO· → ROOOOR →ROOR + O2).11
The above described experiments demonstrate the feasi-
bility of a new approach to the chemical generation of
singlet oxygen from the PIFA–H2O2 system which has
both practical and mechanistic implications.
(8) Sugimoto, H.; Sawyer, D. T.; Kanofsky, J. R. J. Am. Chem.
Soc. 1988, 110, 8707.
(9) Motoyoshiya, J.; Masunaga, T.; Harumoto, D.; Ishiguro, S.;
Narita, S.; Hayashi, S. Bull. Chem. Soc. Jpn. 1993, 66, 1166.
(10) General Procedure for Oxidation of a-terpinene(1) with
PIFA–H2O2 System:
To a solution of 1 (1 mmol)and 35% hydrogen peroxide (6
mmol) in 10 mL of solvent as given in Table 1 at 10 °C was
added NaHCO3 (10 mmol). Then, a freshly prepared
solution of PIFA (2.5 mmol relative to 1) in 15 mL of solvent
was added over 2–3 h. The suspension was filtered and
solvent removed under reduced pressure (5 °C/50 mbar).
The residue was extracted with CH2Cl2 (2 × 20 mL) and
washed with saturated NaHCO3 (10 mL), and with water (20
mL).The organic layer was dried over MgSO4 and the
solvent was removed at reduced pressure (5 °C/50 mbar).
The conversions and product ratios were determined by 1H
NMR analysis directly on the crude mixture in the presence
of dimethyl phthalate as internal standard. The products
were purified on a silica gel column (40 g) by eluting with
hexane–diethyl ether (95:5). First fractions gave iodo-
benzene. Further elution afforded ascaridole 2 as a colorless
oil.
Scheme 1 Decomposition Mechanism of PIFA with H2O2.
Acknowledgment
The authors are indebted to the Department of Chemistry (Ataturk
University) for the financial support of this work and the State
Planning Organization of Turkey (DPT) for purchasing a GC-MS
instrument (Ataturk University).
References
(1) (a) Frimer, A. A. Singlet Oxygen, Vol. I-IV; CRC Press:
Boca Raton, FL, 1985. (b) Ranby, B.; Rabek, J. F. Singlet
Oxygen; J. Wiley and Sons: NY, 1975.
(2) Perein, M.; Adam, W. Angew. Chem., Int. Ed. Engl. 1996,
35, 447.
(11) Milas, N. A.; Plesnicar, B. J. Am. Chem. Soc. 1968, 90, 4450.
Synlett 2003, No. 8, 1180–1182 ISSN 1234-567-89 © Thieme Stuttgart · New York