Preparation of Hydroperoxides by N-Hydroxyphthalimide-Catalyzed Aerobic Oxidation of Alkylbenzenes and Hydroaromatic Compounds and Its Application

Article abstract of DOI:10.1002/1615-4169(20011231)343:8<809::AID-ADSC809>3.0.CO;2-1

An efficient approach to phenols and aldehydes through the formation of hydroperoxides from alkylbenzenes was successfully achieved by aerobic oxidation using N-hydroxyphthalimide (NHPI) as a catalyst. The oxidation of various alkylbenzenes with dioxygen by NHPI followed by treatment with a Lewis acid or triphenylphosphine led to phenols or aldehydes, respectively, in good yields. For example, the aerobic oxidation of cumene in the presence of a catalytic amount of NHPI at 75°C and subsequent treatment with H₂SO₄ gave phenol in 77% yield. 1,4-Dihydroxybenzene (61%) and 4-isopropylphenol (33%) were obtained from 1,4-diisopropylbenzene. On the other hand, dibenzyl ether was converted into phenol or benzaldehyde upon treatment of the resulting hydroperoxide with InCl₃ or PPh₃, respectively.

Full text of DOI:10.1002/1615-4169(20011231)343:8<809::AID-ADSC809>3.0.CO;2-1

FULL PAPER
Preparation of Hydroperoxides by N-Hydroxyphthalimide-
Catalyzed Aerobic Oxidation of Alkylbenzenes and
Hydroaromatic Compounds and Its Application
Osamu Fukuda, Satoshi Sakaguchi, Yasutaka Ishii*
Department of Applied Chemistry, Faculty of Engineering, Kansai University, Suita, Osaka 564±8680, Japan
Fax: (+81) 6-6339-4026, e-mail: ishii@ipcku.kansai-u.ac.jp
Received: July 18, 2001; Accepted September 21, 2001
Abstract: An efficient approach to phenols and alde- subsequent treatment with H2SO4 gave phenol in
hydes through the formation of hydroperoxides 77% yield. 1,4-Dihydroxybenzene (61%) and 4-iso-
from alkylbenzenes was successfully achieved by propylphenol (33%) were obtained from 1,4-diiso-
aerobic oxidation using N-hydroxyphthalimide propylbenzene. On the other hand, dibenzyl ether
(NHPI) as a catalyst. The oxidation of various alkyl- was converted into phenol or benzaldehyde upon
benzenes with dioxygen by NHPI followed by treat- treatment of the resulting hydroperoxide with InCl3
ment with a Lewis acid or triphenylphosphine led or PPh3, respectively.
to phenols or aldehydes, respectively, in good yields.
For example, the aerobic oxidation of cumene in the
Keywords: homogeneous catalysis; oxidations, per-
presence of a catalytic amount of NHPI at 75 °C and
oxides; radicals
difficult to obtain selectively in higher conversion un-
der mild conditions by the conventional aerobic oxi-
dation of hydrocarbons. Now we have found that alkyl
hydroperoxides are easily prepared in high yields by
aerobic oxidation of alkylbenzenes assisted by NHPI.
In this paper, we wish to report on the preparation of
alkyl hydroperoxides by the NHPI-catalyzed aerobic
oxidation of alkylbenzenes and hydroaromatic com-
pounds and their application to useful compounds
like phenols (Scheme 1).
Introduction
Hydroperoxides are used not only as oxidizing agents
of olefins but also as important precursors for the
synthesis of phenols. For instance, ꢀ-hydroperoxy-
ethylbenzene obtained by aerobic oxidation of ethyl-
benzene is used as an active oxygen carrier in the
epoxidation of propylene which is known as the Hal-
con process.[1] The cumene-phenol process (Hock
process) based on the decomposition of cumene hy-
droperoxide with sulfuric acid to phenol and acetone
is the current method for phenol synthesis used
worldwide.[2]
Recently, we have shown that phthalimide N-oxyl
(PINO), generated from N-hydroxyphthalimide
(NHPI) and dioxygen assisted by a Co(II) species,
smoothly abstracts a hydrogen atom from hydrocar-
bons to generate alkyl radicals which are readily
trapped by O2 to give oxygenated products such as al-
cohols, ketones and carboxylic acids through the re-
dox decomposition of the resulting alkyl hydroperox-
ides by a Co ion.[3] It is well known that transition
metal ions such as iron, copper and cobalt catalyze
the redox decomposition of alkyl hydroperoxides.[4]
In the conventional autoxidation of alkanes, the de-
composition of alkyl hydroperoxides formed in the
reaction course leads to alkylhydroperoxy and/or
alkoxy radicals which promote the radical-chain pro-
cess. Therefore, the alkyl hydroperoxides are usually
Scheme 1. Strategy for synthesis of phenol and aldehydes.
Adv. Synth. Catal. 2001, 343, No. 8
Ó WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2001
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809

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Results and Discussion
Initially, the aerobic oxidation of cumene (1) was ex-
amined under several reaction conditions (Table 1,
Equation 1). The oxidation of 1 in the presence of
NHPI (10 mol %) in CH3CN under O2 (1 atm) at 75 °C
for 20 h followed by treatment with excess PPh3
formed 2-phenyl-2-propanol (2) in 77% yield and tri-
phenylphosphine oxide (77%) (Run 1). GC analysis of
the same reaction mixture before the treatment with
PPh3 showed the formation of 2 (8%) at 90% conver-
sion of 1 (Run 2). The resulting cumene hydroperox-
ide could not be detected by the GC measurements.
From Runs 1 and 2, it was found that cumene hydro-
peroxide reacts easily with PPh3 to yield 2 and triphe-
nylphosphine oxide. When AIBN was added as an in-
itiator, 2 was obtained in 75% yield at 76% conversion
within 8 h (Run 3). The reaction by AIBN alone with-
out NHPI under these conditions resulted in a signifi-
cant decrease in the conversion of 1 (Run 4).
Figure 1. Time-dependence curves for the aerobic oxida-
tion of 1 by NHPI (10 mol %) or NHPI (10 mol %)/AIBN
(3 mol %) in CH3CN under O2 (1 atm) at 75 °C.
lowed by treatment with sulfuric acid or InCl3 (Equa-
tion 2). The oxidation of 1 with O2 (1 atm) in the
presence of NHPI (10 mol %) in CH3CN at 75 °C fol-
lowed by treatment with 0.15 M H2SO4 solution in
CH3CN afforded 3 in 73% yield (Method A) (Run 1).
Similarly, treatment of the reaction mixture with
InCl3 (10 mol %) in CH3CN (1 mL) at 25 °C (Meth-
od B) gave 3 in almost the same yield (71%) as that
with H2SO4 (Run 2). The reaction in acetic acid re-
sulted in low conversion of 1. This is believed to be
due to the fact that a part of the cumene hydroperox-
ide formed is decomposed by acetic acid to give phe-
nol 3 which serves as a radical inhibitor (Run 3).[5]
ꢀ1†
Table 1. Oxidation of 1 with O2 by NHPI.[a]
Run
Initiator
Time (h) Conversion (%) Yield of 2 (%)
1
±
±
20
20
8
90
90
76
7
77
8
75
6
2[b]
3
AIBN
AIBN
4[c]
8
[a] Cumene (1) (3 mmol) was allowed to react with O2
(1 atm) in the presence of NHPI (10 mol %) and initiator
(3 mol %) in CH3CN (5 mL) at 75 °C, followed by treat-
ment with excess of PPh3.
ꢀ2†
[b] No treatment with PPh3.
[c] Without NHPI.
Figure 1 shows time-dependence curves for the
aerobic oxidation of 1 by the NHPI and the NHPI/AIBN
systems. The oxidation of 1 by NHPI seems to proceed
via two stages. It was found that the oxidation takes
place very fast at the early stage of the reaction by
both catalytic systems. This shows that the rapid radi-
cal chain transfer reaction can take place at the initial
stage. The reaction at the later stage may be induced
by radicals generated by decomposition of the result-
ing cumene hydroperoxide. The oxidation by the
NHPI/AIBN system progressed faster than that by
NHPI alone at the initial stage of the reaction, prob-
ably because the generation of PINO from NHPI was
promoted by AIBN.
Table 2. Oxidation of 1 with O2 by NHPI followed by treat-
ment with acids.[a]
Run Solvent (mL)
Method[b] Conversion (%) Yield (%) of 3
1
2
3
CH3CN (5)
CH3CN (5)
AcOH (5)
A
B
A
A
A
90
90
10
78
85
73
71
10
68
77
4[c,d] CH3CN (5)
5[c,e] CH3CN (3)
[a] 1 (3 mmol) was allowed to react with O2 (1 atm) in the
presence of NHPI (10 mol %) in solvent at 75 °C for 20 h,
followed by addition of various acids.
[b] A: 0.15 M H2SO4 in CH3CN (2 mL), 75 °C, 4 h. B: InCl3
(10 mol %) in CH3CN (1 mL), 25 °C, 6 h.
[c] AIBN (3 mol %) was added.
[d] Aerobic oxidation step was carried out for 8 h.
[e] Aerobic oxidation step was carried out for 6 h.
Table 2 shows the result for the conversion of cu-
mene 1 to phenol 3 by the aerobic oxidation of 1 fol-
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The addition of a small amount of AIBN shortened the treating with InCl3, the yields of 8 and 7 were slightly
reaction time in the aerobic oxidation step and in- decreased (Run 3). 1,4-Diisopropylbenzene (9) af-
creased the selectivity of 3 (Run 4). In addition, when forded 1,4-dihydroquinone (11) and 4-isopropylphe-
a smaller amount of CH3CN was used, the yield of 3 nol (10) in 61% and 33% yields, respectively (Run 4).
was slightly improved (Run 5).
The oxidation of isochroman (12) led to 2-(2-hydroxy-
On the basis of these results, the oxidation of sev- phenyl)ethyl formate (13) (63%) as a main product
eral alkylbenzenes with O2 in the presence of a cata- along with 1-hydroxyisochroman (14) and 1-isochro-
lytic amount of NHPI and AIBN, followed by treatment manone (15) (Run 5). These results suggest that the
with H2SO4 or InCl3 was examined (Table 3).
resulting alkyl hydroperoxide is decomposed by
H2SO4 in the same fashion as 1. Dibenzyl ether (16)
gave benzaldehyde (17) together with rearranged
product 3 and benzyl alcohol (18) as well as benzyl
formate (19) (Run 6). In addition, tetrahydrofuran
(20) yielded butyrolactone (21) (50%) and hydrogen
peroxide (22) (30%) as major products, although the
reaction of 12 afforded the rearranged compound 13
as a main product (Run 7).
Table 3. Oxidation of various substrates with O2 by NHPI
followed by treatment with acids.[a]
Run Substrate Con-
version
(%)
Method[b]
Product
(Yield [%])
As mentioned above, since alkyl hydroperoxides
readily react with PPh3 to yield the corresponding al-
cohols, we next examined the preparation of alde-
hyde derivatives from alkyl hydroperoxides derived
from ethers.
Table 4. Oxidation of various substrates with O2 by NHPI fol-
lowed by treatment with PPh3.[a]
Run Substrate
Conversion (%)
Product (Yield [%])
[a] Substrate (3 mmol) was allowed to react with O2 (1 atm)
in the presence of NHPI (10 mol %) and AIBN (3 mol %)
in CH3CN (3 mL) at 75 °C, followed by treatment with ex-
cess of PPh3.
Table 4 summarizes the result for the oxidation of
benzylic ethers followed by treatment with PPh3. The
reaction of 12 in the presence of NHPI (10 mol %) and
AIBN (3 mol %) in CH3CN (3 mL) at 75 °C for 8 h, fol-
lowed by treatment with excess PPh3 provided 14 in
62% yield and 15 in 13% yield (Run 1). The reaction
of 16 gave selectively 17 as a main product (Run 2),
in contrast to the treatment with acids where various
products were formed (Table 3, Run 6). The oxidation
of phthalane (23) afforded 1-hydroxyphthalane (24)
[a] Substrate (3 mmol) was allowed to react with O2 (1 atm)
in the presence of NHPI (10 mol %) and AIBN (3 mol %)
in CH3CN (3 mL) at 75 °C for 20 h, followed the addition
of various acids.
[b] See Table 2, footnote [b].
[c] The aerobic oxidation was carried out at 65 °C.
[d] Treatment with 0.15 M H2SO4 at 60 °C.
The oxidation of p-cymene (4) took place selec- (29%), phthalimide (25) (14%), phthalaldehyde (26)
tively at the isopropyl position to afford p-cresol 5 in (34%) and a small amount of phthalic anhydride (27)
47% yield after treatment with InCl3 (Run 1). Simi- (Run 3).
larly, the oxidation of 1,3-diisopropylbenzene (6) fol-
Mechanistically, the aerobic oxidation of ethers by
lowed by treatment with H2SO4 yielded resorcinol (8) the NHPI catalyst is rationally explained by Scheme 2.
(56%) and 3-isopropylphenol (7) (16%) (Run 2). By A hydroperoxide (C) formed by the oxidation of an
Adv. Synth. Catal. 2001, 343, 809±813
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asc.wiley-vch.de
0.2 mm  25 m capillary column (OV-17). Mass spectra were
determined at an ionizing voltage of 70 eV. All starting mate-
rials, catalysts, and initiators were purchased from commer-
cial sources and used without further treatment. The yields
of products were estimated from the peak areas based on the
internal standard technique.
ether reacts with PPh3 to lead to aldehyde and alcohol
through the formation of a hemiacetal (D). On the
other hand, the treatment of hydroperoxide C with
acid gives rise to a formate and an aldehyde as prod-
ucts. It seems likely that the attack of a proton to the
hydroperoxide C occurs via two different pathways
to form two pairs of products, i.e., alcohol and for-
mate from the path a, and aldehyde and H2O2 from
path b. The rearrangement of the R1 group of the C
to the oxygen part followed by the attack of H2O to a
carbocation formed gave alcohol and formate
(path a), while the addition of a proton to alcoholic
oxygen and subsequent removal of alcohol from an
intermediate G followed by addition of H2O gave a ꢀ-
hydroxyhydroperoxide (I) which eventually trans-
formed to aldehyde and H2O2 (path b).
General Procedure for the Oxidation of Various
Substrates to the Phenol Derivatives
An acetonitrile (3 mL) solution of substrate (3 mmol), NHPI
(10 mol %), and AIBN (3 mol %) was placed in a two-necked
flask equipped with a balloon filled with O2. Caution: A bal-
loon filled with oxygen can be hazardous, even with a small-
scale reaction. The mixture was stirred at 75 °C for 20 h. The
reaction mixture was treated with various acidic solutions
[0.15 M H2SO4 in CH3CN (2 mL) or InCl3 (10 mol %) in
CH3CN (1 mL)] at 75 °C or 25 °C for 6 h, respectively. Re-
moval of the solvent under reduced pressure afforded a
cloudy solution, which was purified by column chromato-
graphy on silica gel (n-hexane/AcOEt = 3/2) to give the cor-
responding product. The products were characterized by 1H
and 13C NMR, IR, and GC-MS, respectively.
Procedure for the Oxidation of Various Substrates
to Aldehyde Derivatives
To the solution of substrate (3 mmol) in acetonitrile (3 mL)
in a two-necked flask were added NHPI (10 mol %) and
AIBN (3 mol %), and the flask was equipped with a balloon
filled with O2. Caution: A balloon filled with oxygen can be
hazardous, even with a small-scale reaction. The solution
was stirred at 75 °C for 20 h. The reaction mixture was treat-
ed with an excess amount of PPh3. The work-up was per-
formed by the same method as described above. All products
except for 13[6]and 24[7] were commercially available, and
were identified through comparison of the isolated product
with an authentic sample.
Acknowledgements
Scheme 2. A possible reaction path for aerobic oxidation of
ethers catalyzed by NHPI followed by treatment with PPh3
or acid.
This work was partially supported by Daicel Chemical Indus-
tries Ltd. and
a Grant-in-Aid for Scientific Research
(No. 13853008) from Japan Society for the Promotion of
Science (JSPS).
In conclusion, we have achieved the selective pro-
duction of alkyl hydroperoxides in high yields by
aerobic oxidation of alkylbenzenes by NHPI under
mild conditions, and demonstrate its potential appli-
cation to organic synthesis.
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