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H. Heaney, A. J. Newbold / Tetrahedron Letters 42 (2001) 6607–6609
As expected, benzaldehyde was oxidised to benzoic acid
efficiently using either MMPP (81% yield) or UHP–ace-
tic anhydride (74%) and 3-methoxybenzaldehyde gave
3-methoxybenzoic acid in 71% yield using MMPP.
The yields reported for the oxidation of benzaldehyde
derivatives using aqueous hydrogen peroxide and
methyl-n-octylammonium bisulfate varied from excel-
lent (4-nitrobenzaldehyde to 4-nitrobenzoic acid 88%)
to poor (4-methoxybenzaldehyde to 4-methoxybenzoic
acid 6%).3 It is of interest to note that the epoxidation
of the a,b-unsaturated ketone isophorone proceeded in
good yield (68%) using UHP in methanol in the pres-
ence of 6 M aqueous sodium hydroxide.10 Similarly, we
found that pulegone and a-ionone gave the expected
epoxides in 50 and 61% yields, respectively. The epoxi-
dation of b-methyl-b-nitrostyrene provided interesting
results that varied with the concentration of the
aqueous sodium hydroxide used. When the reaction
was carried out using UHP in methanol and 2 M
aqueous sodium hydroxide the epoxide was obtained in
96% yield, while a reaction carried out in the presence
of 6 M aqueous sodium hydroxide resulted in the
formation of benzoic acid which was isolated in 73%
yield. The oxidation of aliphatic aldehydes to the corre-
sponding carboxylic acids using hydrogen peroxide in
aqueous sodium hydroxide solution has been reported
previously.15 We assumed that with an aromatic alde-
hyde, removal of a proton from the presumed interme-
diate would occur at a faster rate in the presence of
hydroxide ion than aryl group migration and that the
oxidation of methoxy-substituted benzaldehyde deriva-
tives would proceed efficiently to the related benzoic
acid derivatives using that protocol (Scheme 2). The
results of the oxidation of benzaldehyde and methoxy-
substituted derivatives are shown in Table 1.
(1)
provide good substrates for a comparison of the vari-
ous available methods. Thus, the oxidation of 4-
methoxybenzaldehyde using the system hydrogen
peroxide–boric acid–sulfuric acid gave 4-methoxyphe-
nol in 97% yield,11 and using m-chloroperoxybenzoic
acid in 92% yield.12 On the other hand, the oxidation of
4-methoxybenzaldehyde under two-phase conditions
using methyltrioctylammonium tetrakis(oxodiperoxo-
tungstato)phosphate gave the corresponding benzoic
acid in only 6% yield together with a low yield of
4-methoxyphenol.13 In our hands, 2-methoxybenzalde-
hyde gave 2-methoxyphenol in 81% yield using MMPP
and in 64% yield using UHP–acetic anhydride, the
phenol being isolated as a result of hydrolysis of the
formate ester during work-up.
Typical experimental procedures
2-Methoxybenzaldehyde (1.14 g, 8.4 mmol) was added
to a solution of MMPP (4.9 g, 10 mmol) in methanol
(60 mL) and the mixture was stirred at room tempera-
ture for 19 h. Addition of a slight excess of aqueous
potassium hydroxide followed by acidification after 1 h
and extraction into dichloromethane followed by dry-
ing (MgSO4), evaporation and distillation gave 2-
methoxyphenol (0.847 g, 81%) (bp 112°C at 20 mm,
lit.14 bp 106.5 at 24 mm); lH (CDCl3, 60 MHz) 3.85 (s,
3H), 5.83 (br. s, 1H), and 6.83 (m, 4H) ppm.
Typical experimental procedure
Acetic anhydride (2.05 g, 20 mmol) was added dropwise
to a stirred mixture of UHP (7.7 g, 82 mmol), 2-
methoxybenzaldehyde (1.30 g, 9.6 mmol) and disodium
Aqueous sodium hydroxide (3.1 mL, 6 M) was added
dropwise to a stirred solution of UHP (8.1 g, 87 mmol)
and 2-methoxybenzaldehyde (1.36 g, 10 mmol) in
methanol (40 mL) at room temperature. The mixture
was then heated at 65°C for 1 h, acidified with hydro-
hydrogenphosphate
(10.1
g,
75
mmol)
in
dichloromethane (30 mL) at 0°C. The mixture was then
stirred at room temperature for 22 h. Work-up as
above gave 2-methoxyphenol (0.768 g, 64%) (bp 149°C
at 40 mm, lit.14 bp 106.5 at 24 mm).
4-Methoxybenzaldehyde
gave
mixtures
of
4-
methoxyphenol (1) and 4-methoxybenzoic acid (2), the
reactions, shown in Eq. (1), with MMPP [(1) 40%; (2)
31%] and UHP–acetic anhydride [(1) 50%; (2) 16%].
Scheme 2.
Table 1. UHP–aq. NaOH oxidation of benzaldehyde and methoxybenzaldehydes to benzoic acid and derivatives
Aldehyde (mmol)
UHP (mmol)
Time (min)
% Yield of carboxylic acid
Benzaldehyde (11.5)
87
87
88
87
87
55
60
60
60
60
94
90
95
72
63
2-Methoxybenzaldehyde (10)
3-Methoxybenzaldehyde (12)
4-Methoxybenzaldehyde (11)
3,4-Dimethoxybenzaldehyde (11)