Quinone Hemiacetal from Protocatechuic Acid
1579
in 2 (
d
C 181.2 and 133.3, respectively). More noticea-
to yield a mixture of protocatechuquinone methyl es-
ble was that H-5 (
d
H 6.10) of 3, which resonated in a
ter (5, H-5, dH 6.43; H-2, dH 6.93; H-6, dH 7.51) and
higher ˆeld than that of 2 (dH 6.43), showed charac-
its methyl hemiacetal (6, H-5, dH 6.11; H-6, dH 7.42),
teristic HMBC correlation peaks with a considerably
which could be identiˆed by the similar NMR spectra
to those of the reaction mixture with 1, although H-2
of the latter was buried under strong peaks of 2,2-
diphenyl-1-picrylhydrazine produced by the reduc-
tion of DPPH radical. However, the peak areas of
the product derived from 4 were less than half of
those from 1. The smaller amounts of quinone and
acetal produced from 4 might re‰ect rapid progress
of a further oxidation reaction by consuming those
intermediates, which resulted in the stronger radical
scavenging activity of the ester than of the acid.1,2)
The reaction beyond the quinone or its equivalent
acetal proceeding with DPPH radical in alcoholic
solvents is still unclear, although the ester residue and
an alcoholic solvent seem to be necessary for a rapid
reaction. The tendency to form hydrates from qui-
nones has been reported in the oxidation products of
polyphenols.4,5) In the case of 1, signals for the qui-
none hydrate, which was tentatively identiˆed by its
spectral similarity to 3, were detected in the reaction
high ˆeld carbon of dC 89.5, while corresponding H-6
of 2 was correlated with a quinone carbonyl at dC
182.3, as well as with a quaternary carbon ( C 128.6).
d
These diŠerences between 2 and 3 suggest 3 to have
been a 3-acetal derivative of 2. In order to conˆrm
the structure of 3, protocatechuquinone 3- and 4-
dimethyl acetals were prepared by (diacetoxy)io-
dobenzene (DAIB) oxidation of vanillic (7) and
isovanillic (9) acids, respectively, in methanol-d4
3)
.
The quinone acetals produced in the reaction mixture
were directly analyzed by NMR, since they were not
su‹ciently stable to isolate from the solutions. As a
result, the signals of 3 were found to be similar to
those of the 3-acetal (8) derived from 7, but distinctly
diŠerent from those of the 4-acetal (10) from 9,
which indicates 3 having an acetal position at C-3
rather than C-4 as indicated in the HMBC results.
However, the 1H- and 13C-NMR data for 3 and those
for the protocatechuquinone 3-dimethyl acetal (8)
seemed slightly but signiˆcantly diŠerent (Table 1),
suggesting the possibility that 3 might have been a
methyl hemiacetal at C-3 instead of the dimethyl
acetal. Discrimination between the methyl hemiacetal
and dimethyl acetal was problematic in the in situ
NMR analyses, since methoxyl signals introduced
from the solvent were completely deuterated and thus
invisible in the 1H-NMR spectrum. Protocatechuqui-
none 3-methyl hemiacetal was therefore prepared for
a comparison by the DAIB oxidation of 1 in
with DPPH radical when using acetone-d6-deuterium
oxide (4:1) as a solvent. Hence, this quinone-acetal or
hydrate equilibrium could occur during polyphenol
oxidation in an aqueous biological system, although
the contribution of the hemiacetal produced from the
quinone to the overall radical scavenging reaction
remains unknown.
References
1) Kawabata, J., Okamoto, Y., Kodama, A., Makimoto,
T., and Kasai, T., Oxidative dimers produced from
protocatechuic and gallic esters in the DPPH radical
methanol-d4 as already described. The resulting reac-
tion mixture only showed the characteristic signals of
3-acetal, those of 4-acetal not being detected in the
NMR spectra. The NMR signals from the 3-acetal
(3a) derived from the hypervalent iodinane oxidation
of 1 were slightly diŠerent from those of the dimethyl
acetal (8) derived from 7 and were superimposable on
those of 3, which appeared during the reaction of 1
with DPPH radical. Thus, the structure of 3 was
concluded to be protocatechuquinone 3-methyl
hemiacetal. The preference for the formation of 3-
hemiacetal formation over 4-hemiacetal from 2 could
have been due to the lower electron density of 3-CO
conjugated with the pendant carboxyl group than
that of 4-CO.
scavenging reaction. J. Agric. Food Chem.
5468–5471 (2002).
, 50,
2) Kimura, T., Yamamoto, S., Ogawa, I., Miura, H.,
and Hasegawa, M., Antioxidant ability of chicolic acid
and its analogous compounds. Nippon Kagaku Kaishi
(in Japanese), 739–750 (1999), [C.A., 132, 222322
(2000)].
3) Liao, C.-C., Chu, C.-S., Lee, T.-H., Rao, P. D., Ko,
S., Song, L.-D., and Shiao, H.-C., Generation, stabil-
ity, dimerization, and Diels-Alder reactions of masked
o
-benzoquinones. Synthesis of substituted bicy-
clo[2.2.2]octanones from 2-methoxyphenols. J. Org.
Chem., 64, 4102–4110 (1999).
4) Okuda, T., Yoshida, T., and Hatano, T., Constituents
of Geranium thunbergii Sieb. et Zucc. Part 12.
Hydrated stereostructure and equilibration of ger-
aniin. J. Chem. Soc. Perkin 1, 9–14 (1982).
5) Feldman, K. S., Quideau, S., and Appel, H. M.,
Galloyl-derived orthoquinones as reactive partners in
nucleophilic additions and Diels-Alder dimerizations:
a novel route to dehydrodigalloyl linker unit of
agrimoniin-type ellagitannins. J. Org. Chem., 61,
6656–6665 (1996).
In the reaction of protocatechuic acid and DPPH
radical, protocatechuquinone (2) produced was thus
rapidly equilibrated with its methyl hemiacetal (3) in
a molar ratio of ca. 3:2 after 8 min and the mixture
remaining unchanged after 60 min. The hemiacetal
form seems to have been rather stable by the forma-
tion of an intramolecular hydrogen bond between
3-OH and 4-CO. In the case of methyl protocatechu-
ate (4), the same reaction as that of the acid occurred
Saito, Shizuka
