Omura
joined. To a magnetically stirred solution of K3Fe(CN)6 (6.59 g,
20 mmol) and KOH (2.24 g, 40 mmol) in H2O (50 mL) in the
flask was added a N2-purged solution of 14 (1.310 g, 5 mmol) in
PhH (70 mL). The mixture was stirred for 40 min until the PhH
solution no longer contained 14 as suggested by TLC. The aqueous
layer was removed through the tube, and the deep-blue organic
layer was washed 5 times with N2-purged water (500 mL in total).
Each washing was removed through the tube. The third washing
was neutral. A N2-purged solution of an acid or aqueous acid (60
mmol) in MeOH (100 mL) was added to the stirred PhH solution.
The resulting homogeneous mixture was kept stirring at 25 °C for
the time shown in the table until its deep-blue color was totally
discharged (runs 4-6). In runs 1-3, after the stirring of the mixture
was carried out for 60 min, O2 was bubbled through the blue mixture
until the color was discharged. The mixture was washed with water,
dried (anhyd Na2SO4), and evaporated to give a residue.
Run 1: Comparison of the residue (1.382 g) with authentic
samples of 16 and 174c by 1H NMR spectroscopy and TLC
suggested that it consisted exclusively of the peroxides (100%).
Runs 2 and 4-6: Column chromatography of the residue gave
successively 14, 18a, and a mixture of 16 and 17.39 In run 4,
continued elution gave a mixture (28 mg) containing 18b and elution
with CH2Cl2 gave 19 (17 mg, 3%).
mL), and H2O (2.5 mL) was added at 25 °C a solution of 33 (824
mg, 4 mmol) in AcOH (15 mL) dropwise over a period of 5 min.
46
In run 1, the added acid was omitted. In runs 8 and 9, 70% HClO4
(1.38 mL, 16 mmol) and H2O (1.81 mL), and 70% HClO4 (2.76
mL, 32 mmol) and H2O (1.12 mL) were substituted for the added
acid and the H2O, respectively. The resulting mixture was kept
stirring for 5 min. The temperature of the reacting mixture rose to
33-38 °C (runs 2-9). The mixture was filtered into a flask
containing water. The filter cake was washed with CH2Cl2 into the
flask containing the filtrate. Extractive workup of the contents of
the flask with CH2Cl2 gave a residue.
1
Run 2: See the text for the H NMR spectrum of the residue.
Column chromatography of the residue gave successively 42 (527
mg, 65%), 39 (211 mg, 24%), and 40a (113 mg, 11%).
Compound 39: orange crystals from MeOH, identical with an
authentic sample;24 mp 67-68.5 °C (lit.47 mp 67-68 °C).
Compound 40a: colorless crystals from petroleum ether, identical
with an authentic sample;25 mp 90-91 °C (lit.48 mp 87-88 °C).
Compound 42: reddish brown crystals from PhH, identical with
an authentic sample;4c mp 248-250 °C (lit.49 mp 246 °C).
1
Run 1: The H NMR spectrum of the residue indicated that it
contained 36 principally and no or little 38. Recrystallization of
the residue from hexane provided 36 (158 mg) as colorless crystals,
identical with an authentic sample;7 mp 140-150 °C (lit.23 mp
140-150 °C). The filtrate from the recrystallization was evaporated
and the residue was chromatographed. Elution afforded 33 (112
mg, 14% recovery). Further elution provided 38 (486 mg): pale
yellow crystals from hexane, identical with an authentic sample;7
mp 187-189 °C (lit.49 mp 185 °C). Biphenol 38 isolated is assumed
to be an artifact formed from 36 during the chromatography.7 The
total yield of 36 thus is estimated to be 644 mg (79%). Further
elution gave successively 42 (49 mg, 6%), 39 (10 mg, 1%), and
40a (12 mg, 1%).
The reaction of 40a25 (1.056 g, 4 mmol) in place of 33 with
PbO2, CF3CO2H (2.38 mL, 32 mmol), AcOH, and H2O gave 39
(888 mg, 100%).
To a stirred homogeneous mixture of CF3CO2H (2.38 mL, 32
mmol), AcOH (30 mL), and H2O (2.5 mL) was added 3649 (103
mg, 0.25 mmol) in one portion at 25 °C, and the mixture was kept
stirring for 10 min. Pouring the reaction mixture into water and
extractive workup with CH2Cl2 afforded 38 (101 mg, 98% or
quantitative) alone. The reaction with CF3SO3H (2.82 mL, 32 mmol)
in place of CF3CO2H gave a similar result.
To a stirred mixture of PbO2 (2.39 g, 10 mmol), 70% HClO4
(2.76 mL, 32 mmol), H2O (1.12 mL), and AcOH (30 mL) was
added at 25 °C a pulverized solid of 42 (408 mg, 1 mmol) in one
portion, and the resulting mixture was kept stirring for 10 min.
Compound 42 was poorly soluble in the medium. The mixture was
worked up by a procedure similar to the general procedure described
above for the effect of acid on the oxidation of phenol 33 with
PbO2 in AcOH/H2O. Column chromatography of the residue
provided successively 42 (160 mg, 39% recovery) and 39 (155 mg,
35% or 58% based on reacted 42). The reaction using CF3CO2H
(2.38 mL, 32 mmol) and H2O (2.5 mL) in place of 70% HClO4
and the H2O gave recovery of 42 quantitatively. No 39 was
obtained. The reaction using more CF3CO2H (60 mmol) gave the
same result.
The reaction of 38 (410 mg, 1 mmol) in place of 42 with PbO2
and 70% HClO4 in AcOH/H2O gave 38 (84 mg, 20% recovery),
39 (181 mg, 41%), and 42 (95 mg, 23%). Compound 38 was not
sufficiently soluble in the reaction medium. The reaction using
CF3CO2H (2.38 mL, 32 mmol) and H2O (2.5 mL) in place of 70%
HClO4 and the H2O gave 38 (90 mg, 22% recovery) and 42 (320
Compound 18a: colorless crystals from MeOH; mp 56-57.5
°C (lit.40 mp 58-59 °C).
Compound 19: red crystals from hexane; mp 115-117 °C (lit.41
mp 113-114 °C).
Run 3: The residue was chromatographed on deactivated neutral
Al2O3 (Merck, activity grade III). Elution with petroleum ether gave
a colorless solid, which consisted exclusively of 14 (0.65 g, 108%),
18a (0.41 g, 61%), and 24 (69 mg, 10%) as analyzed by 1H NMR
spectroscopy as well as TLC.42 Compound 24 was synthesized
according to the reported method43 and used as an authentic sample
for the analysis. Further elution provided a mixture of 16 and 17
(112 mg, 8%). Elution with CH2Cl2 gave 18b (62 mg, 10%).
Compound 18b: colorless crystals from hexane; mp 82-124
°C (lit. mp 129-13044 and 80.9-82.1 °C45). Repeated recrystal-
lization did not reduce the mp range. Anal. Calcd for C18H30O2:
1
C, 77.65; H, 10.86. Found: C, 77.37; H, 10.96. The H NMR
spectrum was consistent with that reported for 18b.44
Duplication of each run gave essentially the identical results.
A solution of 2443 (371 mg, 1.25 mmol) in a mixture of MeOH
(50 mL) and PhH (35 mL) containing 36% HCl46 (2.55 mL, 30
mmol) was stirred at 25 °C for 60 min. The mixture was washed
with water, dried, and evaporated to give a residue (368 mg), which
consisted almost exclusively of recovery of 24 (99%) (1H NMR).
A trace amount of 18a was detectable by TLC.
Effect of Acid on Oxidation of Phenol 33 with PbO2 in AcOH/
H2O (Table 3): General Procedure. To a stirred mixture of PbO2
(Aldrich) (2.39 g, 10 mmol), an acid (16-60 mmol), AcOH (15
(39) Up to 1% of a mixture of 16 and 17 was obtained from runs 4-6.
They are compounds formed before the discontinuation of the reaction of
13; unintentional contamination of the contents of the flask by air could
not be totally avoided during the operation. The small amount of 13 lost
due to the undesired reaction is disregarded and not considered in calculating
the yields of the products as well as the recovery of 13. A small fraction of
the peroxides obtained from runs 1-3 may also be those which arose before
interrupting the reaction.
(40) Mu¨ller, E.; Ley, K.; Kiedaisch, W. Chem. Ber. 1954, 87, 1605.
(41) Ley, K.; Mu¨ller, E. Chem. Ber. 1956, 89, 1402.
(42) Compound 24 suffered decomposition upon chromatography on
SiO2.
(43) Pearson, D. E.; Venkataramu, S. D.; Childers, W. E., Jr. Synth.
Commun. 1979, 9, 5.
(44) Rieker, A.; Rundel, W.; Kessler, H. Z. Naturforsch. 1969, 24b, 547.
(45) Futamura, S.; Yamazaki, K.; Ohta, H.; Kamiya, Y. Bull. Chem. Soc.
Jpn. 1982, 55, 3852.
(46) One milliliter each of commercially available 36% HCl, 70% HClO4,
and 60% HNO3 were determined by titration to consist of HCl (11.8 mmol)
and H2O (0.76 mL), HClO4 (11.6 mmol) and H2O (0.50 mL), and HNO3
(13.5 mmol) and H2O (0.53 mL), respectively.
(47) Mu¨ller, E.; Ley, K. Chem. Ber. 1955, 88, 601.
(48) Mu¨ller, E.; Rieker, A.; Mayer, R.; Scheffler, K. Liebigs Ann. Chem.
1961, 645, 36.
(49) Kharasch, M. S.; Joshi, B. S. J. Org. Chem. 1957, 22, 1439.
866 J. Org. Chem., Vol. 73, No. 3, 2008