Oxidation of 2-methoxy-6-(1-methylethyl)naphthalene with oxygen

Article abstract of DOI:10.1007/s00706-011-0630-3

Aerobic oxidation of 2-methoxy-6-(1-methyl-ethyl)naphthalene to hydroperoxide, alcohol, and ketone, is reported. These compounds, particularly 2-acetyl-6-meth-oxynaphthalene, are important intermediates in naproxen synthesis. N-Hydroxyphthalimide is shown here to be an efficient catalyst for oxidation to the hydroperoxide, 2-methoxy-6-(1-hydroperoxy-1-methylethyl) naphthalene, with a yield of 87%. However, the ketone and alcohol were obtained with lower yields, with a maximum yield of 13% for the ketone and 27% for the alcohol, using N-hydroxyphthal-imide and Cu(II) acetylacetonate as a catalyst. The synthesis of the products 2-acetyl-6-methoxynaphthalene and 2-methoxy-6-(1-hydroxy-1-methylethyl)naphthalene via an initial oxidation step to the hydroperoxide followed by a hydroperoxide decomposition step is shown to be more efficient; the ketone and alcohol were obtained from 2-methoxy-6-(1-methylethyl)naphthalene with yields of 40 and 56%, respectively.

Full text of DOI:10.1007/s00706-011-0630-3

Monatsh Chem (2012) 143:295–301
DOI 10.1007/s00706-011-0630-3
ORIGINAL PAPER
Oxidation of 2-methoxy-6-(1-methylethyl)naphthalene
with oxygen
Beata Orli n´ ska
•
Zbigniew Stec Jan Zawadiak
•
Received: 5 May 2011 / Accepted: 19 August 2011 / Published online: 16 September 2011
Springer-Verlag 2011
ꢀ
Abstract Aerobic oxidation of 2-methoxy-6-(1-methyl-
ethyl)naphthalene to hydroperoxide, alcohol, and ketone, is
reported. These compounds, particularly 2-acetyl-6-meth-
oxynaphthalene, are important intermediates in naproxen
synthesis. N-Hydroxyphthalimide is shown here to be an
efficient catalyst for oxidation to the hydroperoxide, 2-
methoxy-6-(1-hydroperoxy-1-methylethyl)naphthalene,
with a yield of 87%. However, the ketone and alcohol were
obtained with lower yields, with a maximum yield of 13% for
the ketone and 27% for the alcohol, using N-hydroxyphthal-
imide and Cu(II) acetylacetonate as a catalyst. The syn-
thesis of the products 2-acetyl-6-methoxynaphthalene and
2-methoxy-6-(1-hydroperoxy-1-methylethyl)naphthalene
(2), the ketone 2-acetyl-6-methoxynaphthalene (3), and the
alcohol 2-methoxy-6-(1-hydroxy-1-methylethyl)naphtha-
lene (4), from which the relevant alkene compound
2-methoxy-6-(1-methylethenyl)naphthalene (5) can be
obtained (Scheme 1). These compounds, particularly the
ketone 3, are useful in the pharmaceutical industry as
intermediates in the synthesis of 2-(6-methoxy-2-naphthyl)-
propionic acid, the S enantiomer of which is the non-
steroidal anti-inflammatory drug naproxen [1–5].
The oxidation of 1 with oxygen has only been described
in a patent [5] as a step in the synthesis of 2-(6-methoxy-2-
naphthyl)propionic acid from 2,6-diisopropylnaphthalene.
It has previously been reported that an oxidation product
containing 15–25% hydroperoxide 2 can be obtained via
the oxidation of 1 in air at 80 ꢁC, using heptane as a sol-
vent, in the presence of a manganese catalyst and with
sodium carbonate and cumene hydroperoxide as initiator.
Previous data in the literature have shown that oxidation
of other representative isopropylaromatic hydrocarbons,
including cumene [6], 2,6-diisopropylnaphthalene [7–9],
2
-methoxy-6-(1-hydroxy-1-methylethyl)naphthalene via an
initial oxidation step to the hydroperoxide followed by a
hydroperoxide decomposition step is shown to be more effi-
cient; the ketone and alcohol were obtained from 2-methoxy-
6
-(1-methylethyl)naphthalene with yields of 40 and 56%,
respectively.
Keywords Oxidation ꢀ Homogeneous catalysis ꢀ
N-Hydroxyphthalimide ꢀ Transition metal compounds ꢀ
Naproxen
0
4,4 -diisopropylbiphenyl [8, 9], 1,3,5-triisopropylbenzene
[
10], and 1-methoxy-4-(1-methylethyl)benzene [11] in the
presence of N-hydroxyphthalimide (NHPI), results in the
generation of hydroperoxides with yields greater than 70%
and selectivities greater than 90%. In contrast, when a
catalyst composed of NHPI and transition metal salts was
used for the oxidation of isopropylaromatic hydrocarbons,
the respective alcohols and ketones were obtained rather
than the hydroperoxides [8, 12–15] because of the catalytic
effect of metal salts on hydroperoxide decomposition [16].
This paper investigates both the catalytic and non-cat-
alytic oxidation of 1 with oxygen. NHPI and NHPI in
combination with different metal salts were used as cata-
lysts. The purpose of this study was to determine the
Introduction
The oxidation products of 2-methoxy-6-(1-methyleth-
yl)naphthalene (1), similar to the oxidation products of other
isopropylaromatic hydrocarbons, are the hydroperoxide
B. Orli n´ ska (&) ꢀ Z. Stec ꢀ J. Zawadiak
Department of Organic Chemical Technology and
Petrochemistry, Silesian University of Technology,
Gliwice, Poland
e-mail: beata.orlinska@polsl.pl
123

2
96
B. Orli n´ ska et al.
Scheme 1
OOH
OH
O
O
O
O
O2
2
3
4
5
O
O
1
OH
O
O
Naproxen
-
2
3
to the oxidisability of cumene, 1.36 9 10 dm (mol s)
-1/2
potential use of the catalysts for the synthesis of hydro-
peroxide 2 or ketone 3 and alcohol 4, potential intermediate
products in naproxen synthesis. This paper also examines
the decomposition of hydroperoxide 2 to ketone 3 and
alcohol 4 in the presence of metal salts. Two methods for
the synthesis of ketone 3 and alcohol 4 were compared: (1)
a direct method via oxidation of 1 catalysed by NHPI/metal
salt systems and (2) a two-step method consisting of NHPI
catalysed oxidation of 1 to hydroperoxide 2 followed by its
decomposition.
[18].
To investigate whether 1 can be oxidised to the hydro-
peroxide with a high degree of conversion, long-term
oxidation studies were performed. The oxidation was done
in the presence of ACHN initiator, at 90, 100, and 110 ꢁC,
with tert-butylbenzene as a neutral solvent. The initiator
was added in an amount that ensures a uniform initiation
-
5
3
rate in each experiment (*0.5 9 10 mol/dm s). Fig-
ure 1 shows the course of oxidation and the final
conversions for 1, along with the selectivities for the
hydroperoxide 2.
Results and discussion
During the long-term oxidation of 1, the initial reaction
rate was relatively high, but gradually slowed down and
stopped. After approximately 8 h at a reaction temperature
of 90 ꢁC, the degree of conversion and selectivity were 24
and 90%, respectively; higher reaction temperatures
decreased both of these parameters.
Non-catalytic oxidation of 2-methoxy-6-(1-
methylethyl)naphthalene (1)
The non-catalytic oxidation of 1 was done to determine the
feasibility of synthesising hydroperoxide 2. First, the
The courses of the long-term oxidation reactions indi-
cate that the oxidation of 1 does not show an autocatalytic
characteristic. This confirms that compounds that inhibit
the process are formed during oxidation. This is particu-
larly evident at higher temperatures (at 110 ꢁC the process
is already completely inhibited, with a low conversion
degree). To achieve a higher conversion of 1, additional
amounts of initiator need to be added during the reaction.
‘
‘oxidisability’’ of 1 was determined. ‘‘Oxidisability’’ refers
the susceptibility of a hydrocarbon to free radical chain
0
t
.5
oxidation and is measured by the k /k quotient in the
p
following kinetic equation, which describes the rate of free
radical chain oxidation of hydrocarbons to hydroperoxides,
Eq. 1 [17]:
kp
1
=2
rox ¼ ri pffiffiffi cRH
the rate constant of the propagation reaction, k is the rate
ð1Þ
k
t
Catalytic oxidation of 2-methoxy-6-(1-
methylethyl)naphthalene (1)
where rox is the oxidation rate, r is the initiation rate, k is
p
i
t
constant of the termination reaction, and cRH is the
hydrocarbon concentration.
Because free-radical scavengers are formed during the
oxidation of 1, catalytic oxidation was attempted, using
catalysts that are known to increase the quantity of free
radicals in the reaction mixture. The following compounds
were used as catalysts:
To determine the oxidisability of 1, its initial oxidation
0
rate rox in the presence of the azo initiator 1,1 -azobis(1-
cyclohexanecarbonitrile) (ACHN) at 100 ꢁC was mea-
sured. Results can be found in Table 1.
These results show that the oxidisability of 1 at 100 ꢁC
, which is comparable
•
•
N-hydroxyphtalimide (NHPI),
Cu(II), Mn(II), and Co(II) acetylacetonates.
-
is high, 1.13 9 10 dm (mol s)
2
3
-1/2
1
23

Oxidation of 2-methoxy-6-(1-methylethyl)naphthalene
297
0
t
.5
Table 1 The ‘‘oxidisability’’ of k
p
/k
of 2-methoxy-6-(1-methylethyl)naphthalene (1)
-3
-3
-3 -1
s
-3 -1
s
0.5 3
t
/(dm /(mol s))
0.5
c
i
/mol dm
c
RH/mol dm
r
i
/mol dm
r
ox/mol dm
p
k /k
-
-
-
4
4
4
-5
-5
-5
-2
0
0
0
.0471
1.700
1.573
1.573
0.0516 9 10
0.1504 9 10
0.1325 9 10
4.291 9 10
7.016 9 10
6.471 9 10
1.11 9 10
1.15 9 10
1.13 9 10
-2
-2
.1371
.1208
3
2
cm solution of 1 in tert-butylbenzene; 100 ꢁC; c
i
is the initiator (ACHN) concentration; cRH is the concentration of 1; r
i
is the initiation rate;
r
ox is the initial oxidation rate
25
20
15
10
5
0
90
Conv.=24.4%
Sel.=90.5%
80
7
0
Conv.=17.7%
Sel.=88.6%
60
5
0
Conv.=11.8%
Sel.=87.7%
40
5
6
7
0°C
0°C
0°C
3
2
1
0
0
0
0
1
2
3
) 90°C
80°C
90°C
100°C
) 100°C
) 110°C
1
10°C
0
2
4
6
8
10
0
50
100
150
200
Time/h
Time/min
Fig. 1 Oxidation of 2-methoxy-6-(1-methylethyl)naphthalene (1) in
3
tert-butylbenzene (2 cm solution containing 3.33 mmol of 1) in the
Fig. 2 Oxidation of 2-methoxy-6-(1-methylethyl)naphthalene (1) in
3
PhCN (2 cm solution containing 3.4 mmol of 1) in the presence of
NHPI (0.17 mmol). Amounts of initiator used can be found in Table 2
presence of ACHN. Arrows indicate the addition of initiator. 1 90 ꢁC,
0
4
.34 mmol ACHN; 2 100 ꢁC, 2 9 0.083 mmol ACHN; 3 110 ꢁC,
9 0.026 mmol ACHN
Table 2 Oxidation of 2-methoxy-6-(1-methylethyl)naphthalene (1)
in the presence of NHPI
NHPI catalysed oxidation
a
Initiator /mmol
Temp./ꢁC
Time/min
Conv./%
Selectivity
of 2/%
Figure 2 and Table 2 outline the results for the oxidation of
1
for the temperature range between 50 and 110 ꢁC in the
50
60
70
80
90
100
110
3
2.45
2.45
0.61
0.17
0.91
0.24
0.074
180
170
165
115
120
75
67.1
91.5
75.9
68.9
64.4
45.6
40.2
98.0
95.5
96.0
94.0
90.7
89.9
81.2
0
presence of NHPI and azo initiators 2,2 -azobis(isobuty-
rylnitrile) (AIBN) or ACHN, with benzonitrile as the
solvent in order to solubilise the catalyst. Initiators were
added in quantities that ensure a constant initiation rate,
-
5
-5
-3 -1
ranging from 1.34 9 10 to 1.39 9 10 mol dm
s .
The results revealed that the NHPI catalysed oxidation
of 1 occurred at a much higher rate than the oxidation
reaction without the catalyst. Similar to the results found
for non-catalytic oxidation, the initial reaction rate was
high, but gradually slowed down until the reaction stopped.
The inhibition effect was particularly apparent at higher
temperatures.
45
2
cm solution of 1 (3.40 mmol) in PhCN, NHPI (0.17 mmol)
a
AIBN at 50–80 ꢁC and ACHN at 90–110 ꢁC
NHPI and transition metal salts catalysed oxidation
Compared to the non-catalytic oxidation of 1, the cata-
lytic oxidation reached higher conversions and hydro-
peroxide was formed with high selectivity as the main
product. The highest yield (87%) of hydroperoxide was
obtained at 60 ꢁC. At temperatures between 60 and 100 ꢁC,
the only by-product seen was the alcohol 4, but at 110 ꢁC,
the post-reaction mixture also contained minor quantities
of the ketone 3.
Further research was conducted to obtain ketone 3 and
alcohol 4 directly during the oxidation process of 1. It is
well known that transition metals catalyse the decomposi-
tion of hydroperoxides to alcohols and ketones [16].
Therefore, oxidation of 1 in the presence of NHPI and
Cu(II), Mn(II), and Co(II) acetylacetonates was examined.
Figures 3 and 4 outline the courses of the oxidation of 1 at
70 and 100 ꢁC.
123

2
98
B. Orli n´ ska et al.
6
5
4
3
2
1
0
0
0
0
0
0
0
Table 3 Oxidation of 2-methoxy-6-(1-methylethyl)naphthalene (1)
in the presence of NHPI and Cu(II), Co(II), or Mn(II) acetylacetonate
Catalyst
Temp./ꢁC Time/min Conv./% Selectivity/%
3 4
S /S
2
3
4
Cu(acac)
2
70
70
64
75
59.1
32.6
20.0
29.7
38.2
19.7
23.8
37.7 13.1 46.0 0.28
18.0 33.8 42.3 0.80
16.8 21.0 55.6 0.38
11.1 42.7 35.5 1.20
18.1 39.6 32.8 1.21
20.4 20.6 45.5 0.45
7.9 52.2 29.0 1.80
Mn(acac)
2
Co(acac)
Cu(acac)
Mn(acac)
2
70
50
2
100
100
100
110
55
Cu(II)
Mn(II)
Co(II)
2
60
Co(acac)
Cu(acac)
3
2
100
45
2
0
10
20
30
40
50
60
70
2
cm of solution of 1 (3.40 mmol) in PhCN, NHPI (0.17 mmol),
AIBN (0.61 mmol) at 70 ꢁC, ACHN (0.24 mmol) at 100 and 110 ꢁC,
Cu(acac) , Mn(acac) , or Co(acac)
(0.034 mmol) at 70 and 100 ꢁC,
or Cu(acac) (0.015 mmol) at 110 ꢁC
Time/min
2
2
2
Fig. 3 Oxidation of 2-methoxy-6-(1-methylethyl)naphthalene (1) in
3
2
PhCN (2 cm solution containing 3.4 mmol of 1) at 70 ꢁC in the
presence of NHPI (0.17 mmol), AIBN (0.61 mmol), and Cu(II),
Co(II), or Mn(II) acetylacetonate (0.034 mmol)
post-reaction mixture depends on the type of catalyst used
and the temperature of the process. The rise in temperature
led to an increase of the S /S ratio. This effect on the S /S
4
3
4
3
3
3
2
2
1
1
5
0
5
0
5
0
5
0
ratio was particularly observed when NHPI/Cu(II) acetyl-
acetonate was used as a catalyst. At 70 ꢁC the main reaction
product was the alcohol (S /S = 0.28), while at 110 ꢁC it
3
4
was the ketone (S /S = 1.8).
3
4
An examination of the oxidation reaction of 1 catalysed
by NHPI and transition metal salts showed that the use of
this method for the synthesis of the alcohol 4 and ketone 3
appears to be inefficient based on the low conversion and
complex composition of the post-reaction mixture. Because
Cu(II)
Mn(II)
Co(II)
1
can be oxidised with high efficiency to hydroperoxide,
further investigation focused on obtaining the ketone 3 and
alcohol 4 in a two-stage process that included NHPI-cata-
lysed oxidation of 1 to the hydroperoxide 2 followed by
catalytic decomposition.
0
20
40
60
80
100
120
Time/min
Fig. 4 Oxidation of 2-methoxy-6-(1-methylethyl)naphthalene (1) in
3
PhCN (2 cm solution containing 3.4 mmol of 1) at 100 ꢁC in the
Catalytic decomposition of 2-methoxy-6-(1-
hydroperoxy-1-methylethyl)naphthalene (2)
presence of NHPI (0.17 mmol), ACHN (0.24 mmol), and Cu(II),
Co(II), or Mn(II) acetylacetonate (0.034 mmol)
The results from the catalytic decomposition of hydroper-
oxide 2 at temperatures between 70 and 120 ꢁC are shown
in Table 4, along with the degree of conversion of hydro-
peroxide 2 and selectivities for the ketone 3 and alcohol 4.
The data show that hydroperoxide 2 is susceptible to a
rapid decomposition in the presence of Cu(II), Mn(II), and
Co(II) acetylacetonates, and after 1 to 2 h, the conversion
of 2 is *90–97%. The main reaction product was the
alcohol 4, with ketone 3 formed in smaller quantities. The
composition of the post-reaction mixture depends on
the reaction temperature and the type of catalyst. Similar to
the previous results with oxidation using NHPI and tran-
sition metal compounds, a rise in temperature led to an
increase in ketone content, with the largest effect of tem-
perature on ketone content occurring when copper catalyst
If the oxidation reaction of 1 is completed in the pres-
ence of NHPI and transition metal compounds, the reaction
rate is higher than in the presence of NHPI alone, but the
degree of conversion at the end of the reaction is lower.
Table 3 shows the reaction time until complete reaction
inhibition and the final conversion of 1 as well as the
selectivities for hydroperoxide 2, ketone 3, and alcohol 4.
The selectivity ratio of ketone 3 to alcohol 4 (S /S ) is also
3
4
included as an indicator of the direction of hydroperoxide
decomposition.
These results show that the hydroperoxide 2 only partially
decomposes in the presence of transition metal compounds
and that the reaction products were a mixture containing the
hydroperoxide, ketone, and alcohol. The composition of the
1
23

Oxidation of 2-methoxy-6-(1-methylethyl)naphthalene
299
Table 4 Catalytic decomposition of 2-methoxy-6-(1-hydroperoxy-1-
methylethyl)naphthalene (2) in the presence of Cu(II), Co(II), or
Mn(II) acetylacetonate
catalysed oxidation of 1 to hydroperoxide 2 followed by
catalytic decomposition is more efficient than the single-
stage oxidation reaction of 1 catalysed by NHPI and tran-
sition metal compounds; the ketone and alcohol were
obtained from 2-methoxy-6-(1-methylethyl)naphthalene
with yields of 40 and 56%, respectively.
Catalyst
Catalyst/mmol Temp./ꢁC Time/h Conv./% Selectivity/%
3 4
S /S
3
4
Cu(acac)
2
0.041
0.043
0.044
–
70
70
2.5
1.5
1.5
2
88.8
89.3
93.9
6.6
24.1
31.4
32.8
–
72.4
64.0
62.1
–
0.33
0.49
0.53
–
Mn(acac)
2
Co(acac)
–
2
70
Experimental
100
100
100
100
110
120
120
120
Cu(acac)
2
0.039
0.042
0.040
0.031
0.030
0.033
0.032
1
96.9
92.3
95.4
97.5
97.4
96.9
96.9
39.4
42.5
41.7
45.8
44.7
41.0
43.4
53.1
51.9
46.5
47.6
47.2
48.9
50.4
0.74
0.82
0.90
0.96
0.95
0.84
0.86
Mn(acac)
2
1
2,6-Diisopropylnaphthalene of greater than 99% purity
Co(acac)
Cu(acac)
Cu(acac)
2
1
with a melting point of 66.8 ꢁC was used. NHPI and
2
1
2-acetyl-6-methoxynaphthalene were purchased from
2
1
Sigma-Aldrich and from Alpha Aesar, respectively. Metal
salts and solvents were commercially available and used
without further purification.
Mn(acac)
2
1
Co(acac)
2
1
3
cm solution containing 15.2% of 2 (1.96 mmol)
3
1
13
H and C NMR spectra were recorded in CDCl on a
3
Varian Unity Inova-300 spectrometer. The melting points
were determined in capillary tubes using a SMP 3 (Stuart
Scientific) apparatus. Elemental analyses were performed
using a Perkin Elmer 2400 series II instrument, and the
results were found to be in good agreement with the cal-
culated values.
was used. The maximum selectivity (72.4%) of alcohol 4
was obtained at 70 ꢁC, with ketone 3 obtained at a maxi-
mum selectivity of *45% at 110–120 ꢁC in the presence
of Cu(acac)2.
A Waters Alliance 2690 HPLC equipped with an auto-
sampler, UV detector (Waters photodiode array), and a
Conclusion
˚
Nova-Pak Silica 60 A 4 lm column (150 9 3.9 mm;
Waters) was used. A mixture of hexane and 2-propanol at
We have shown that hydroperoxide 2 can be obtained in a
non-catalytic oxidation process of 1 with high selectivity
the ratio of 99:1 (v/v) was used as a mobile phase with a
3
flow rate of 1 cm /min. Ketone 3 and alcohol 4 were
(
*90%) but low yield (max. 22%) because of formation of
inhibitors during the reaction. NHPI has been shown to be an
efficient catalyst for oxidation of 1 to hydroperoxide 2.
Hydroperoxide 2 has been obtained with a yield and selec-
tivity of 87 and 95%, respectively, in the presence of NHPI at
a temperature of 60 ꢁC for 3 h.
detected at 239 and 227 nm, respectively. Calibration was
done according to the external standardisation method.
Kieselgel 60 (Merck 0.063–0.200 mm) was used for
column chromatography. TLC analyses were performed
using Merck’s plates coated with silica gel 60 F254.
The oxidation products of 1 obtained in the presence of
the catalyst NHPI and transition metal salts were a complex
mixture of unreacted hydrocarbon 1, hydroperoxide 2,
ketone 3, and alcohol 4. The ketone 3 and alcohol 4 were
obtained with a maximum yield of 13 and 27%, respec-
tively, when 1 was oxidised in the presence of NHPI and
Typical procedure for the oxidation reaction
in gasometric apparatus
The oxidations were performed in a gasometric apparatus
as described previously [19, 20]. Reagents were placed in a
3
thermostated 4 cm quartz flask connected to a thermo-
Cu(acac) at a temperature of 110 and 70 ꢁC, respectively.
2
This method for synthesis of the alcohol and ketone seems
to be inefficient judging by the low degree of conversion
and the complex composition of the post-reaction mixture.
Hydroperoxide 2 in the presence of transition metal
compounds decomposed at a high rate and degree of con-
version. The reaction products were the ketone 3 and
alcohol 4. A maximum alcohol yield of 64% and maximum
ketone yield of 45% were achieved via hydroperoxide
stated burette at 25 ꢁC. Oxygen was supplied into the flask
from a burette, and the pressure was kept constant at
1,013 mbar. The reaction was monitored by measuring the
oxygen uptake.
Determination of the oxidisability of 2-methoxy-6-
(1-methylethyl)naphthalene
3
A 2 cm solution of 2-methoxy-6-(1-methylethyl)naph-
decomposition catalysed by Cu(acac) at 70 and 120 ꢁC,
2
respectively.
thalene in tert-butylbenzene containing respective amounts
3
of the initiator ACHN was placed in the 4 cm flask of
The results from this study indicate that the two-stage
method of obtaining the ketone 3 and alcohol 4 from NHPI
gasometric apparatus. Oxidation reactions were conducted
123

3
00
B. Orli n´ ska et al.
at 100 ꢁC for 15–20, min and the initial oxidation rates
were determined by measuring the amount of chemisorbed
0
oxygen. The oxidisability (k /kt ) of 2-methoxy-6-(1-
.5
p
methylethyl)naphthalene was calculated using the equation
0
.5 0.5
kp/k = rox (1/ri cRH), where rox is the initial oxidation
k
rate, r the initiation rate, and c the hydrocarbon con-
i
RH
centration. The initiation rates were calculated as
r = 2ek c , where c is the initiator concentration, e the
i
d i
i
effectiveness coefficient (which was assumed to be 0.6 for
ACHN) [21], and k is the initiator decomposition rate
d
-
4
-1
constant (which was 9.41 9 10
00 ꢁC) [22].
s
for ACHN at
1
Scheme 2
initiator ACHN (2.2 g, added in three portions every 2 h)
Oxidation reaction of 2-methoxy-6-
1-methylethyl)naphthalene
for 6 h. The reaction product (O = 2.55%) was diluted
act
(
3
with 850 cm toluene, extracted three times using a 6%
3
solution of NaOH (3 9 120 cm ) to remove 2,6-bis(1-
Oxidations were completed in the gasometric apparatus, as
described above. 2-Methoxy-6-(1-methylethyl)naphtha-
lene, solvent (tert-butylbenzene or PhCN), and additives
hydroperoxy-1-methylethyl)naphthalene, washed with water
3
3 9 120 cm ), and dried over Na CO . A product (1,045 g)
(
2
3
containing 11.4% (0.49 mol) of 2-(1-hydroperoxy-1-
methylethyl)-6-(1-methylethyl)naphthalene was obtained.
(
initiator and catalyst) were placed in the flask and oxidised
at a temperature range of 50–110 ꢁC. The amount of oxygen
consumed was used to calculate the conversion of 1. For
product composition analysis, the amount of hydroperoxide
Step 2. Acid decomposition of 2-(1-hydroperoxy-1-
methylethyl)-6-(1-methylethyl)naphthalene
2 was determined iodometrically [23], and the amounts of
ketone 3 and alcohol 4 were determined via HPLC.
The product of 2,6-diisopropylnaphthalene oxidation
(
1,045 g) containing 11.4% 2-(1-hydroperoxy-1-methyl-
Decomposition reaction of 2-methoxy-6-
1-hydroperoxy-1-methylethyl)naphthalene
ethyl)-6-(1-methylethyl)naphthalene was dropped to a
3
solution of 2.93 cm H SO in 600 cm acetone at boiling
(
3
2
4
temperature. The resulting mixture was neutralised with an
excess of Na CO (177 g), and the Na SO /Na CO was
2
-Methoxy-6-(1-methylethyl)naphthalene (3.00 g, 14.98
3
2
3
2
4
2
3
mmol) dissolved in 5.8 cm PhCN was oxidised in a
bubble reactor at 60 ꢁC for 5 h using NHPI (0.75 mmol) as
a catalyst and AIBN (2.7 mmol) as an initiator. The reac-
tion product (9.15 g) containing 30.4% hydroperoxide 2
removed by filtration and the acetone by distillation.
-Hydroxy-6-(1-methylethyl)naphthalene was extracted
2
3
from the product using 418 cm 6% NaOH, and the
resulting alkaline aqueous phase was acidified using
3
08 cm 5% HCl. The 2-hydroxy-6-(1-methylethyl)naph-
(
12.0 mmol) and 0.4% alcohol 4 was diluted with PhCN in
5
3
a 1:1 weight ratio. Catalyst was added to 3 cm of this
solution containing 15.2% of hydroperoxide, and the
mixture was placed in an oil bath heated to an adequate
temperature. Every half hour the amount of hydroperoxide
thalene (83.63 g, 0.45 mol) was then collected by filtration
and used for O-alkylation in Step 3.
Step 3. O-Alkylation of 2-hydroxy-6-(1-
methylethyl)naphthalene
2
was determined iodometrically [23].
2
-Methoxy-6-(1-methylethyl)naphthalene (1)
-Methoxy-6-(1-methylethyl)naphthalene was obtained
2
O-Alkylation of 83.63 g 2-hydroxy-6-(1-methylethyl)naph-
3
thalene (0.45 mol) was performed in 101 cm methanol
according to the method described previously in a patent
5] with some additional modifications. The steps of the
3
(2.49 mol) in the presence of 20.3 cm H
[
2
SO
4
(0.36 mol) at
3
synthesis are presented in Scheme 2.
79–82 ꢁC for 6 h. After cooling to 60 ꢁC, 300 cm of 9%
NaOH solution (0.74 mol) was added, and the product was
stirred at this temperature for 15 min. Crude 2-methoxy-6-
Step 1. Oxidation of 2,6-diisopropylnaphthalene
(1-methylethyl)naphthalene was collected by filtration
2
,6-Diisopropylnaphthalene (370 g, 1.74 mol) was oxi-
(74.3 g, 0.37 mol, m.p. 62–65 ꢁC) and then crystallised
from 370 cm ethanol. 2-Methoxy-6-(1-methylethyl)naph-
3
dised with oxygen in a glass vessel supplied with a bubbler,
thermometer, reflux condenser, and heating jacket [24].
The reaction was done at 105 ꢁC in the presence of the
thalene (65.7 g, 0.33 mol) was obtained. M.p.: 63.5–65 ꢁC
([3] 60–61 ꢁC [5] 63.5–64.5 ꢁC).
1
23

Oxidation of 2-methoxy-6-(1-methylethyl)naphthalene
301
2
-Methoxy-6-(1-hydroperoxy-1-methylethyl)naphthalene
2, C H O )
obtained. The crude product (0.73 g) was purified by
column chromatography using first toluene and cyclohexane
(4:10 (v/v)), followed by elution with toluene and ethyl
acetate (10:0.25 (v/v)) and crystallisation from hexane to
give 0.35 g of 4. M.p.: 85–87 ꢁC ([25] 86–87 ꢁC).
(
1
4 16 3
2
-Methoxy-6-(1-methylethyl)naphthalene (3.00 g, 14.98
3
mmol) was dissolved in 5.8 cm PhCN and oxidised at
0 ꢁC with oxygen in a bubble reactor for 5 h using NHPI
0.75 mmol) as catalyst and AIBN (2.7 mmol) as initiator.
6
(
Acknowledgments We are grateful to the Ministry of Science and
Higher Education of Poland for financial support (grant no. N N209
The reaction product (9.15 g) containing 30.4% of hydro-
peroxide 2 (12.0 mmol) was diluted with 9.16 g methyl
isobutyl ketone, and the NHPI was extracted using 1%
1
53836).
3
3
NaOH (5 9 1 cm ). NaOH (40%, 1.25 cm ) was added
drop-wise for 1 h at 0 ꢁC to a solution of hydroperoxide 2,
and the resulting sodium salt of hydroperoxide 2 was
filtered off and washed with ether.
References
1. Harrington PJ, Lodewijk E (1997) Org Process Res Dev 1:72
3
2
3
. Sanchez AF (1976) US Patent 3,994,968
. Shishido K, Yamashita A, Hiroya K, Fukumoto K, Kametani T
Sodium salt of hydroperoxide 2 was added to 12 cm of
water, and the suspension was slowly neutralised using 5%
HCl at 0 ꢁC. (CAUTION! Hydroperoxide can decompose
violently in the presence of acid). The crude precipitate of
hydroperoxide 2 was filtered off, washed with water, and
dried under a vacuum. Crude hydroperoxide 2 (1.91 g) was
obtained with a yield of 52.9% and purity of 96.1%. Crude
hydroperoxide 2 (1 g) was crystallised from hexane to give
(
1990) J Chem Soc Perkin Trans 1:469
4
. Ishibashi H, Maeki M, Yagi J, Ohba M, Kanai T (1999) Tetra-
hedron 55:6075
5
6
7
8
. James DK, Komin AP, Siegman JR (1994) US Patent 5,286,902
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. Aoki Y, Sakaguchi S, Ishii Y (2004) Adv Synth Catal 346:199
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Paganelli R (2004) Org Process Res Dev 8:163
9
. Recupero F, Punta C (2007) Chem Rev 107:3800
0
1
.19 g of chromatographically pure hydroperoxide 2. M.p.:
1
10. Aoki Y, Hirai N, Sakaguchi S, Ishii Y (2005) Tetrahedron
1:10995
00–102 ꢁC; H NMR (300 MHz, CDCl ): d = 7.14–7.81
3
6
(
m, 7H, Ar, –OOH), 3.93 (s, 3H, –OCH ), 1.70 (s, 6H,
3
3
11. Orlinska B, Romanowska I (2011) Cent Eur J Chem 9:670
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Nishiyama Y (1995) J Org Chem 60:3934
1
–
1
8
CH ) ppm; C NMR (75.5 MHz, CDCl ): d = 157.9,
3
3
39.5, 133.9, 129.6, 127.2, 124.3, 124.0, 119.0, 105.5 (Ar),
1
3. Minisci F, Punta C, Recupero F (2006) J Mol Catal A: Chem
51:129
4.0 (C(CH ) ), 55.3 (OCH ), 26.0 (C(CH ) ) ppm.
3
3
2
3 2
2
1
1
1
4. Nakamura R, Obora Y, Ishii Y (2009) Tetrahedron 65:3577
5. Orlinska B (2010) Tetrahedron Lett 51:4100
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organic chemistry and biology. Taylor & Francis Group, Boca
Raton
2
-Methoxy-6-(1-hydroxy-1-methylethyl)naphthalene (4)
-Methoxy-6-(1-methylethyl)naphthalene was oxidised with
2
oxygen in a glass vessel fitted with a bubbler, a thermom-
eter, reflux condenser and heating jacket. 2-Methoxy-6-(1-
1
methylethyl)naphthalene (4.50 g, 22.47 mmol) dissolved in
3
8
.7 cm MeCN was oxidised at 60 ꢁC for 4.5 h using NHPI
1.14 mmol) as catalyst and AIBN (2.27 mmol) as initiator.
1
19. Emanuel NM, Denisov ET, Maizus ZK (1965) Cepnye Reakcii
8. Kulicki Z, Stec Z (1972) Chem Stos 16:317
(
_
Okislenija Uglewodorov v Zidkoj Faze. Izd Nauka, Moscow
20. Baj S, Chrobok A (2008) Int J Chem Kinet 40:287
The reaction product (12.23 g) containing 32.3% of hydro-
3
peroxide 2 (17.0 mmol) was diluted with 15 cm of ethanol
2
2
1. Russel GA (1975) J Am Chem Soc 79:3871
2. Overberger CG, Bitetch H, Finestone AB, Lilker J, Herber J
(1953) J Am Chem Soc 75:2078
and dropped to a solution of 3.56 g Na SO (28.24 mmol)
2
3
3
in 20 cm of H O for 0.5 h at 40 ꢁC. This mixture was then
2
2
2
2
3. Zawadiak J, Gilner D, Kulicki Z, Baj S (1993) Analyst 118:1081
4. Stec Z, Zawadiak J (1998) Pol J Appl Chem 42:237
5. Baliah V, Nadar PA (1971) Indian J Chem 9:1339
stirred at 40 ꢁC for 3 h to complete hydroperoxide decom-
position (the reaction was monitored by TLC analysis).
After cooling, the organic phase was separated, the solvent
was evaporated, and the crude product (3.97 g) was
123