Metalloporphyrin-catalyzed Oxidation of 2-Methylnaphthalene
J . Org. Chem., Vol. 62, No. 3, 1997 677
Potassium monopersulfate was the triple salt 2KHSO5‚
KHSO4‚K2SO4 (Curox) was a gift from Interox. The iron and
manganese derivatives of tetrasodium meso-tetra(p-sulfo-
natophenyl)porphyrin (TPPS),11 octasodium meso-tetrakis(3,5-
disulfonatomesityl)porphyrin (TMPS),26 tetrasodium meso-
tetrakis(2,6-dichloro-3-sulfonatophenyl)porphyrin (TDCPPS),27
meso-(4-(N-methylpyridiniumyl))porphyrin (TMPyP),28 meso-
tetrakis(4-(acetamidosulfonyl)phenyl)porphyrin (TPPSAc),29
and meso-tetrakis(3-(acetamidosulfonyl)mesityl)porphyrin (TMP-
SAc)29 were prepared in our laboratory according to published
syntheses (see Scheme 2 for structures). meso-Tetraphe-
nylporphyrin manganese complex was from Strem Chemicals.
H218O (98 atom %) was supplied by Eurisotop (Gif-sur-Yvette,
France).
Gen er a l P r oced u r e for t h e Ca t a lyt ic Oxid a t ion of
2-Meth yln a p h th a len e. Metalloporphyrin-catalyzed oxida-
tions of 2-methylnaphthalene were performed in a one-phase
solution constituted of acetonitrile and either distilled water
or a buffer solution, at room temperature (23 °C) and under
aerobic conditions, according to the same general procedure:
the reaction mixture (2 mL) contained 10 µmol of substrate
introduced as a 80 mM acetonitrile solution of 1 (or 2-methyl-
1-naphthol) with also trichlorobenzene as internal standart,
0.5 µmol (or lower concentration when mentioned) of catalyst
introduced as 20 mM solution in water, required amounts of
acetonitrile and 0.1 M buffer to obtain the desired ratio organic
phase/water, and at last 50 µmol of KHSO5 introduced as 0.67
M solution in water. Reactions at pH 4.0 and pH 5.0 were
performed in a 0.1 M acetate buffer, at pH 2.0 and 3.0 in a 0.1
M citrate-phosphate buffer30 and at pH 6.0 and 7.0 in a 0.1
M phosphate buffer. Catalytic oxidations were started by
addition of the monopersulfate solution (50 µmol correspond
to 15.4 mg of Curox).
explain why 2-methyl-1-naphthol was not an intermedi-
ate in the catalytic oxidation of 1, hydrolysis of the metal-
(III)-O-aromatic bond should be slower than the addition
of a second metal-oxo species at position 4, then giving
in several steps the intermediate D. The fact that yield
of quinones 2 + 3 decayed when the catalyst amount
decreased supports this hypothesis. The hydrolysis of
both metal-O-aromatic bonds present in D gives rise to
2-methylnaphthohydroquinone E, which is quickly oxi-
dized to quinone 2. We checked that a reference sample
of E was very quickly oxidized to the naphthoquinone 2
by KHSO5, even in the absence of catalyst. Such a
stepwise mechanism is in agreement with that one
proposed by Burka et al. for the hydroxylation of ha-
lobenzenes mediated by microsomal cytochrome P-450.21
Recent semiempirical molecular orbital calculations con-
firmed these mechanistic proposals.22
Although J erina et al. observed the formation of stable
intermediate epoxides in the cytochrome P-450-catalyzed
hydroxylation of naphthalene,23 recent studies on P-450-
mediated oxidation of benzene derivatives indicated that
the formation of arene oxides is not a general phenom-
enon in monooxygenase-catalyzed oxidation.24,25 At this
stage of the study, we can exclude the possibility of long-
life kinetic arene oxides as intermediates in the formation
of quinones 2 and 3 during the metalloporphyrin-
catalyzed oxidation of 2-methylnaphthalene.
Con clu sion
H218O Exp er im en ts. Reactions were carried out in H218O
(98 atom %) according to the following procedure. A mixture
of 12.5 µL of substrate (80 mM in CH3CN), 2.5 µL of
metalloporphyrin (20 mM in water), and 350 µL of 0.1 M
acetate buffer (pH 4 and 5) was taken to dryness using a
Speed-Vac. A 300 µL volume of H218O and 150 µL of CH3CN
were added to the residue. Reaction was started by addition
of 3.9 mg of KHSO5 in 50 µL of H218O. Control experiments
in order to check the exchange of oxygen between H218O and
naphthoquinone were carried out under the same conditions
by using 2 instead of 1 as initial substrate. Control experi-
ments in order to check the exchange of oxygen between H218O
and KHSO5 were carried out as follows: 350 µL of 0.1 M
acetate buffer (pH 5.0) or 0.25 M phosphate buffer (pH 7.0)
were taken to dryness, and 3.9 mg of KHSO5 (12.7 µmol) and
350 µL of H216O - H218O, 50/50, were added. A resulting
solution was stirred for 1 h at 20 °C. Then 1 mL of a CH2Cl2
solution containing the manganese complex of meso-tetra-
phenylporphyrin (76 nmol), 4-t-BuPy (1.59 µmol), styrene (6.35
µmol), and benzyldimethyltetradecylammonium chloride (318
nmol) was added. Ratios between reagents were the same as
those published in ref 19. After 30 min of additional stirring,
conversions of styrene and yields of epoxide were upper than
50%. The organic layer was separated, concentrated, and then
analyzed by GC-MS. More than 99% of the styrene oxide
contained light oxygen, indicating that no oxygen exchange
between KHSO5 and H218O occurred either at pH 5 or at pH 7
during the 1 h preincubation time or in the course of the
reaction.
The metalloporphyrin-catalyzed oxidation of 2-meth-
ylnaphthalene by potassium monopersulfate produced
mainly two naphthoquinones, 2-methyl-1,4-naphtho-
quinone (2) (menadione or vitamin K3) and 6-methyl-1,4-
naphthoquinone (3). In aqueous solution and at room
temperature in the presence of 5 mol % percent of the
water-soluble metalloporphyrins MnTPPS or FeTMPS,
2-methylnaphthalene was quantitatively oxidized to
quinones 2 and 3.
18O-labeling experiments suggest that, in an aqueous
solution, the metalloporphyrin-catalyzed oxidation of
2-methyl-naphthalene (1) to p-quinones involves two
consecutive oxygen transfers from an intermediate metal-
oxo entity in a cytochrome P-450-type oxygenation reac-
tion. The data show that the redox tautomerism mech-
anism previously described for metalloporphyrin-catalyzed
oxygenation reactions in aqueous medium15 is probably
involved and responsible for 30 to 55% indirect incorpo-
ration of 18O from water into the generated quinones.
Exp er im en ta l Section
Ch em ica ls. 2-Methylnaphthalene (1), 2-methyl-1,4-naph-
thoquinone (2), styrene, benzyldimethyltetradecylammonium
and 4-tert-butylpyridine were obtained from Aldrich. 2-Meth-
yl-1-naphthol from Aldrich was purified (precipitation by
addition of HCl from a 0.1 M NaOH aqueous solution) before
use in order to eliminate any trace of vitamin K3. 2-Methyl-
1,4-naphthohydroquinone, 2,3-epoxy-2-methyl-1,4-naphtho-
quinone and phthiocol were prepared according to ref 2.
Substrate conversion and yields of 2 and 3 were determined
by GC on a Intersmat IGC 120 FID gas chromatograph, using
(26) Hoffmann, P.; Labat, G.; Robert, A.; Meunier, B. Tetrahedron
Lett. 1990, 31, 1991.
(27) Turk, H.; Ford, W. T. J . Org. Chem. 1991, 56, 1253.
(28) Bernadou, J .; Pratviel, G.; Bennis, F.; Girardet, M; Meunier,
B. Biochemistry 1989, 28, 7268.
(29) Song, R.; Witvrouw, M.; Schols, D.; Robert, A.; Balzarini, J .;
De Clercq, E.; Bernadou, J .; Meunier, B. Antiviral Chem. Chemother.,
in press.
(30) Using Sorensen’s citrate buffer which contains HCl led to
variable amounts of chlorinated products on the aromatic ring. So we
recommend use of Mellvaine’s citric acid-phosphate buffer, deprived
of chloride anions, to avoid the formation of these side products.
(21) Burka, L. T.; Plucinski, T. M.; MacDonald, T. L. Proc. Natl.
Acad. Sci. U.S.A. 1983, 80, 6680.
(22) Rietjens, I. M. C. M.; Soffers, A. E. M. F.; Veeger, C.; Vervoort,
J . Biochemistry 1993, 32, 4801.
(23) J erina, D. M.; Daly, J . W.; Witkop, B.; Zaltzman-Nirenberg, P.;
Udenfriend, S. J . Am. Chem. Soc. 1968, 90, 6525.
(24) Vannelli, T.; Hooper, A. B. Biochemistry 1995, 34, 11743.
(25) Anzenbacher, P.; Niwa, T.; Tolbert, L. M.; Sirimanne, S. R.;
Guengerich, F. P. Biochemistry 1996, 35, 2512.