Formation of 6-formyl-7-hydroxy-8-methoxycoumarin and 5,8-dioxopsoralen by reaction of 8-methoxypsoralen with H2O2 and potassium superoxide (KO2) catalyzed by halogenated or perhalogenated 5,10,15,20-tetraarylporphyrinatoiron(III) chlorides

Article abstract of DOI:10.1248/cpb.49.1232

The oxidation of 8-methoxypsoralen (2) with hydrogen peroxide and potassium superoxide catalyzed by 5,10,15,20-(2,4,6-trimethylphenyl)porphyrinatoiron(III) chlorides [Me₁₂-TPPFe(III)Cl] (1a) and 5,10,15,20-(2,6-dichlorophenyl)porphyrinatoiron(III) chlorides [Cl₈TPPFe(III)Cl] (1b) in dichloromethane gives 6-formyl-7-hydroxy-8-methoxycoumarin (3) in moderate yields, whereas the oxidation of (2) with H₂O₂ catalyzed by 5,10,15,20-(2,6-dichlorophenyl)-β-octahaloporphyrinatoiron(III) chlorides [Cl₈βX₈TPPFe(III)Cl] (X=Cl, Br) (1c, 1d) gives specifically 5,8-dioxopsoralen (4) in moderate yields.

Full text of DOI:10.1248/cpb.49.1232

1
232
Communications to the Editor
Chem. Pharm. Bull. 49(9) 1232—1233 (2001)
Vol. 49, No. 9
Similarly the reaction of H O with 2 in presence of
Formation of 6-Formyl-7-hydroxy-
2
2
5
,10,15,20-(2,6-dichlorophenyl)porphyrinatoiron(III) chlorides
8
5
8
-methoxycoumarin and
,8-Dioxopsoralen by Reaction of
-Methoxypsoralen with
[
Cl TPPFe(III)Cl] (1b) gave 3 in 29.5% yield. Further the re-
8
action of KO with 2 in presence of 1a gave 3 in 21% yield.
2
Moreover 3 can be obtained by the photooxidation of 2 with
1
15)
O in 1.4% yield. Therefore H O /TAPFe(III)Cl is the bet-
2
2
2
H O and Potassium Superoxide (KO )
2
2
2
ter system for the preparation of 3 from 2.
The reaction of H O with 2 in presence of 5,10,15,20-
Catalyzed by Halogenated or
Perhalogenated 5,10,15,20-
Tetraarylporphyrinatoiron(III)
Chlorides
2
2
(
2,6-dichlorophenyl)-b-octahaloporphyrinatoiron(III) chlo-
rides [Cl bX TPPFe(III)Cl] (XϭCl, Br) (1c, 1d) gave 5,8-
dioxopsoralen (4) in 8.0% and 9.5% yield respectively (Chart
8
8
1
). Similarly the reaction of 2 with KO /MeOH catalyzed by
2
1
c gave 4 in 2.0% yield. The formation of psoraleneqiunone
1
(4) is confirmed by IR, H-NMR, EI-MS and other spectro-
Shive M. S. CHAUHAN,* Bishwabhusan SAHOO,
Prabhu P. MOHAPATRA, Bhanu KALRA, and
Anju GULATI
1
6)
scopic data.
The reaction of iron(III)porphyrins (1a, 1b) and H O
2
2
forms hydroperoxoiron(III)porphyrin species initially and
Department of Chemistry, University of Delhi, Delhi 110 007, India. iron(IV)porphyrin oxo radical cation species subsequently
Received May 7, 2001; accepted June 29, 2001
which may epoxidise the electron rich 4Ј,5Ј double bond of
2
. The electrocyclic ring opening of 2 and subsquent decom-
The oxidation of 8-methoxypsoralen (2) with hydrogen perox-
ide and potassium superoxide catalyzed by 5,10,15,20-(2,4,6-
position in presence of water is responsible for the formation
of 3. The formation of hydroperoxoiron(III) and iron(IV)-
porphyrin-oxo complexes by the reaction of H O or KO and
synthetic iron(III)porphyrins and their application in the oxi-
dation of different organic substrates have been reported.
Although the oxidation of different methoxybenzenes to
17)
trimethylphenyl)porphyrinatoiron(III)
chlorides
[Me -
12
2
2
2
TPPFe(III)Cl] (1a) and 5,10,15,20-(2,6-dichlorophenyl)porphyri-
natoiron(III) chlorides [Cl TPPFe(III)Cl] (1b) in dichloromethane
8
18,19)
gives 6-formyl-7-hydroxy-8-methoxycoumarin (3) in moderate
yields, whereas the oxidation of (2) with H O2 catalyzed by
2
5
,10,15,20-(2,6-dichlorophenyl)-b-octahaloporphyrinatoiron(III) quinones have been reported by the reaction with monooxy-
20)
chlorides [Cl bX TPPFe(III)Cl] (X؍Cl, Br) (1c, 1d) gives gen donors and metalloporphyrins, but the reaction with 2
8
8
specifically 5,8-dioxopsoralen (4) in moderate yields.
with H O or KO in presence of 1a and 1b does not give the
2 2 2
quinone 4.
Key words 8-methoxypsoralen; H O and KO ; halogenated and per-
2
2
2
halogenated iron(III)porphyrins; 5,8-dioxopsoralen; 6-formyl-7-hydroxy-8-
methoxycoumarin
The eight chlorine atoms bonded to the ortho phenyl
groups change the redox potential of the Fe(III)/Fe(II) couple
of Cl TPPFe(III)Cl (1b) (E ϭϪ0.34) by only 50 mV com-
8
1/2
The 8-methoxypsoralen (2) is an important photodynamic pared to TPPFe(III)Cl (E ϭϪ0.39), the additional eight
1
/2
agent, used in the treatment of vitiligo, psorisis and other de- chlorine on the porphyrin ring in Cl bCl TPPFe(III)Cl (1b)
8
8
1
)
seases. The 8-methoxypsoralen are metabolized by different (E ϭϩ0.10) move the potential by more than 600 mV com-
isoforms of cytochrome P450 in man, dog, rat and in- pared to TPPFe(III)Cl. Therefore the electron deficient iron–
sects. Formation of different metabolic products in man in- oxo porphyrin complexes having high positive redox poten-
dicate that specific product has formed by specific isoform of tials are much better electron acceptors than the correspond-
cytochrome P450 enzyme systems. The selected drugs have ing species derived from simple TPPFe(III) complexes and
been oxidized with different monooxygen donors catalyzed they are more efficient oxidants for hydroxylation for aro-
1
/2
2
)
3)
4)
5
)
6
—10)
by metalloporphyrins in different conditions.
Aqueous matic and aliphatic hydrocarbons. Therefore 1c and H O
hydrogen peroxide is an ideal oxidant and it has been used in system preferentially hydroxylates the position 5 of 2 which
2 2
1
1,12)
the environment-consious chemical process.
tion of hydrogen peroxide and potasium superoxide with
,10,15,20-tetraarylporphyrinatoiron(III) chlorides form, high
The reac-
5
valent oxo-iron(IV)porphyrin radical cation and related
species which mimic the different reaction of cytochrome
1
3)
P450 enzyme system. We report the biomimetic oxidation
of 8-methoxypsoralen (2) with hydrogen peroxide (H O )
2
2
and potassium superoxide (KO ) catalyzed by different halo-
2
genated and perhalogenated iron(III) porphyrins to under-
stand the molecular mechanism of different isoforms of cy-
tochrome P450 in different reaction conditions.
The reaction of hydrogen peroxide (0.05 mmol) with 8-
methoxypsoralen (2) catalyzed by 5,10,15,20-(2,4,6-
trimethylphenyl)porphyrinatoiron(III) chlorides [Me TPPFe-
1
2
(
6
(
III)Cl] (1a) (0.005 mmol) in dichloromethane (10 ml) gave
-formyl-7-hydroxy-8-methoxycoumarin (3) in 25.5% yield
Chart 1) and confirmed by different spectroscopic data.
Chart 1. Oxidation of 8-Methoxypsoralen (2) with Hydrogen Peroxide
H O ) Catalyzed by Me TPPFe(III)Cl (1a), Cl TPPFe(III)Cl (1b) and
(
2
2
12
8
1
4)
Cl b-X TPPFe(III)Cl (XϭCl, Br) (1c, 1d) in Dichloromethane
8 8
∗
To whom correspondence should be addressed.
© 2001 Pharmaceutical Society of Japan

September 2001
1233
2
0)
on ipso substitution at position 8 of 2 and subsequent elim- 11) Sato K., Aoki M., Noyori R., Science, 281, 1646—1647 (1998).
1
2) Sato K., Aoki M., Takagi J., Noyori R., J. Am. Chem. Soc., 119,
2386—12387 (1997).
3) Chauhan S. M. S., Kalra B., Mohapatra P. P., J. Mol. Cat. A: Chem.,
37, 85—92 (1999).
ination of methanol leading to formation of 4. The high se-
lectivity of reactive intermediates formed by reaction of hy-
drogen peroxide with iron(III)porphyrins (1a, 1b) for epoxi-
1
1
1
17)
dation of olefins and perhalogenated iron(III)porphyrins (1c, 14) 6-Formyl-7-hydroxy-8-methoxycoumarin (3), mp 193 °C (lit. mp
194—195 °C); UV (CHCl
61 (0.75) and 421 (0.6) nm; IR (KBr) nmax: 1727, 1659, 1622 cm
1
d) for hydroxylation of hydrocarbons may be used in the se-
, lmax, rel. abs.): 277 (1.5), 310 (sh, 0.8),
3
Ϫ1
3
;
lective oxidation of organic substrates in different reaction
conditions.
1
H-NMR (CDCl ) d ppm: 11.30 (s, 1H, 7-OH), 9.89 (s, 1H, 6-CHO),
.64 (d, 1H, H-3), 7.45 (s, 1H, H-5), 6.32 (d, 1H, H-4), 4.30 (s, 3H,
3
7
–
(
4
1
3
OCH3); C-NMR (CDCl ) d ppm: 195 (CHO), 159.3 (C-2), 157.5
3
Acknowledgements This work is financially supported by Department
of Science and Technology (DST) and Council of Scientific and Industrial
Research (CSIR), New Delhi, India.
C-7), 152.7 (C-6), 143.2 (C-4), 135.7 (C-8), 128.3 (C-4), 118.8 (C-
ϩ
a), 114.9 (C-3), 113.3 (C-5), 61.8 (OCH ); EI-MS m/z: 220 (M ),
3
ϩ ϩ
2
05 (M ϪCH ), 192 (M ϪCO), 177 (205ϪCO), 164 (192ϪCO), 149
3
(
177ϪCO).
References and Notes
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