Liquid-phase oxidation of 1-isopropyl- and 1-ethyl-4-methoxybenzenes with oxygen to hydroperoxides

Article abstract of DOI:10.1002/kin.10108

A study was carried out on the kinetics of free-radical chain oxidation of 1-isopropyl-4-methoxybenzene (1a) and 1-ethyl-4-methoxybenzene (1b) with oxygen in the liquid phase to yield 1-methyl-1-(4-methoxyphenyl)ethyl hydroperoxide (2a) and 1-(4-methoxyphenyl)ethyl hydroperoxide (2b). The oxidizability of 1a and 1b was studied over the temperature range 50-100°C. Long-term oxidations of 1a and 1b to the corresponding hydroperoxides were carried out and the properties and thermal stability of 2a were established.

Full text of DOI:10.1002/kin.10108

Liquid-Phase Oxidation
of 1-Isopropyl- and 1-Ethyl-
4-methoxybenzenes with
Oxygen to Hydroperoxides
´
JAN ZAWADIAK, ZBIGNIEW STEC, BARTLꢀ OMIEJ JAKUBOWSKI, BEATA ORLINSKA
Institute of Organic Chemistry and Technology, Silesian University of Technology, Gliwice, Poland
Received 22 April 2002; accepted 22 October 2002
DOI 10.1002/kin.10108
ABSTRACT: A study was carried out on the kinetics of free-radical chain oxidation of 1-isopropyl-
4-methoxybenzene (1a) and 1-ethyl-4-methoxybenzene (1b) with oxygen in the liquid phase
to yield 1-methyl-1-(4-methoxyphenyl)ethyl hydroperoxide (2a) and 1-(4-methoxyphenyl)ethyl
hydroperoxide (2b). The oxidizability of 1a and 1b was studied over the temperature range 50–
100◦C. Long-term oxidations of 1a and 1b to the corresponding hydroperoxides were carried
out and the properties and thermal stability of 2a were established. ꢀ 2002 Wiley Periodicals,
C
Inc. Int J Chem Kinet 35: 89–94, 2003
These compounds, and also 1-hydroxy-4-methoxy-
benzene which is prepared by acidic decomposition of
2a, can be used as raw materials to make fragrants,
pharmaceuticals, and plant pesticides.
Oxidation of arylalkyl compounds to hydroperox-
ides with oxygen proceeds via a free-radical chain
mechanism described by the following scheme [1–3]:
INTRODUCTION
1-Methyl-1-(4-methoxyphenyl)ethyl hydroperoxide
(2a) and 1-(4-methoxyphenyl)ethyl hydroperoxide
(2b) are the primary products of the oxidation of
1-isopropyl-4-methoxybenzene (1a) and 1-ethyl-4-
methoxybenzene (1b). On further transformations,
these hydroperoxides can yield corresponding
alcohols and ketone.
Initiation
·
R1
initiator → radical → R
{1}
R1
R1
O
OOH
OH
Propagation
O2
k0
·
·
R + O2 → RO2
{2}
{3}
kp
·
·
OCH3
OCH3
OCH3
OCH3
RO2 + RH → RO2H + R
1
2
3
4
Termination
1 - 3
kt
·
·
RO2 + RO2 → nonradical product
{4}
a R1 = CH3
b R1 = H
For this scheme the rate of oxidation is given by the
following equation:
Correspondence to: Jan Zawadiak; e-mail: janzaw@zeus.polsl.
gliwice.pl.
Contract grant sponsor: Ru¨tgers Kureha Solvents GmbH,
Duisburg, Germany.
2002 Wiley Periodicals, Inc.
kp
rox = ri0.5
√
CRH
(1)
kt
c
ꢀ

90
ZAWADIAK ET AL.
whererox is the rate of oxidation,ri the rate of initiation,
kp the propagation reaction rate constant, kt the termi-
nation reaction rate constant, and CRH the hydrocarbon
(4) in 20–25, 13–17, 80, and 80% yields, respectively.
1-(4-Methoxyphenyl)ethanol (3b) has been prepared
with N-hydroxyphthalimide [12] or Mn(salen) [13] as
catalysts in 7 and 22% yields, respectively.
concentration.
√
The value of kp/ kt, which is termed the oxidiz-
ability, is a measure of reactivity of hydrocarbons in
the free-radical, chain oxidation process. The combi-
nation with the Arrhenius equation allows to transform
Eq. (1) into the following form:
This study is concerned with the kinetics of liquid-
phase oxidation of 1a and 2a with molecular oxygen.
Initial oxidation rates were determined in the presence
of azo initiators at temperatures of 50–110◦C. Under
these conditions, the hydroperoxide is produced in only
slight amounts and this fact allows to ignore the effect
of the hydroperoxide and of the products of its decom-
position on the kinetics of the oxidation reaction.
Attempts were also undertaken to carry out long-
term oxidations of 1a and 2a, which allowed to
establish the conditions allowing to prepare the hy-
droperoxides in high yields. The reaction mixture con-
tained hydroperoxides that partially underwent free-
radical decomposition. Obtained radicals initiated new
kinetic chains which made oxidation reaction to be au-
tocatalytic. From the other side hydroperoxides could
also undergo acid decomposition to hydroxyaromatic
compounds (under the influence of small amount of
HCOOH formed in the process). Hydroxyaromatic
compounds are known to be strong inhibitors of free-
radical chain process. Traces of such compounds de-
crease the oxidation rate or even discontinues the
process.
−0.5E
e E
t CRH
(2)
p
kp∞
kt∞
rox = ri0.5
√
RT
where kp∞, kt∞ are preexponential factors, Ep the en-
ergy of activation of the propagation reaction, and Et
the energy of activation of the termination reaction.
The oxidation of alkylaromatic compounds to hy-
droperoxides is well known [3], but the literature on
oxidation of 1a is fairly scarce. Russell and Williamson
[4] and Howard and Ingold [5] have studied the oxidiz-
ability of this hydrocarbon at 60 and 30◦C. Their data
show this hydrocarbon in the reaction of oxidation to
be 1.3 and 1.5 times as reactive as is cumene at those
temperatures. Compound 2a has been prepared by oxi-
dizing2-(4-methoxyphenyl)propan-2-ol(3a)with30%
hydrogen peroxide in acetone as solvent in the presence
of sulfuric acid [6]. The hydroperoxide has been found
to be unstable.
The literature on oxidation of 1b is fairly ample.
Opeida [7] has studied the kinetics of oxidation of this
hydrocarbon and determined its oxidizability at 75◦C.
At that temperature the hydrocarbon is about 2.7 times
as oxidizable as is ethylbenzene. In only one case, viz.,
in a noncatalyzed oxidation carried out at 120◦C, a
solution was obtained of 2b at a concentration of 0.3–
0.6 mol/l [8]. All other oxidations were carried out
in the presence of catalysts and the products of the
reaction were an alcohol and a ketone. Rhodium [9],
rhutenium [10], cobalt [10], and cerium catalysts [11]
have allowed to prepare 1-(4-methoxyphenyl)ethanone
RESULTS AND DISCUSSION
The kinetics of oxidation of 1a and 1b with oxygen was
studied in the presence of 2,2ꢁ-azo-bis(isobutyronitrile)
(AIBN) and 1,1ꢁ-azo-bis(cyanocyclohexane) (ACHN).
Tables I and II list the oxidation rates of 1a and 1b
(rox) in the presence of the azo initiators used at a con-
centration of Ci and the initiation rates (ri) as also the
√
oxidizabilities kp/ kt of 1a and 1b. For comparison the
√
reported oxidizabilities kp/ kt of cumene [14,15] and
ethylbenzene [19,20] are given.
Table I Oxidation of 1a (6.29 mol/dm3) with Molecular Oxygen in the Presence of Azo Initiators
No. T (◦C) Ci (mol/dm3) ria (10−7 mol/(dm3 s)) rox (10−5 mol/(dm3 s)) kp/kt1/2 (10−3 (dm3/(mol s))1/2) kp/kt1/2 (10−3 b
)
1
2
3
4
5
6
50
60
70
80
100
110
0.2073c
0.0457c
0.0866c
0.0223c
0.0080d
0.0039d
5.57
5.22
41.10
36.26
9.02
1.33
2.01
7.53
8.92
5.86
10.32
3.7 0.4
4.7 0.2
6.0 0.2
7.6 0.3
9.5 0.3
13.7 0.3
–
4.22
5.70
7.65
13.6
17.2
15.33
a ri calculated from equation ri = 2ekdCi with 0.6 taken for e (efficiency of initiation) [16].
b Cumene [14,15].
c AIBN; kd = 1.6 × 1015 × e−30,800/RT [17].
d ACHN; kd = 5.24 × 1016 × e−35,400/RT [18].

LIQUID-PHASE OXIDATION OF 1-ISOPROPYL- AND 1-ETHYL-4-METHOXYBENZENES
91
Table II Oxidation of 1b (7.03 mol/dm3) with Molecular Oxygen in the Presence of Azo Initiators
No. T (◦C) Ci (mol/dm3) ri (10−7 mol/dm3 s) rox (10−5 mol/dm3 s) kp/k1/2 (10−3 (dm3/(mol s))1/2
) )
kp/k1/2 (10−3 a
t
t
1
2
3
4
5
6
50
60
70
80
100
110
0.2104b
0.0451b
0.0927b
0.0232b
0.0100c
0.0074c
5.68
5.15
41.93
37.67
11.33
28.96
0.44
0.89
3.30
3.78
4.02
9.37
0.8 0.3
1.6 0.2
2.2 0.1
2.7 0.2
5.4 0.1
7.7 0.1
0.41
0.60
0.81
1.17
2.54d
3.03e
a Ethylbenzene [19,20].
b AIBN as initiator.
c ACHN as initiator.
d Temperature 97.6◦C [21].
e Temperature 104.3◦C [21].
The −log(oxidizabilities) of 1a, 1b, cumene, and
In the long-term oxidations of 1a and 1b, partial
decomposition of the resulting hydroperoxides yields
inhibitors, which reduce the rate of the reaction and
can even cause a complete discontinuation of the
reaction.
In order to check whether it is possible to oxi-
dize 1a and 1b to the corresponding hydroperoxides
at high conversion degrees, experiments were made in-
volving long-term oxidations of the two compounds
at temperatures of 60, 70, 80, 100, and 110◦C. To
achieve higher hydroperoxide contents, the initiator
had to be added several times during the process. The
amount of the oxygen consumed was used to calcu-
late the degree of conversion (α) of the reactant. A
representative course of the oxidation is presented in
Fig. 2.
ethylbenzene are presented graphically in Fig. 1 in re-
lation to reciprocal absolute temperature.
The presented data show that at temperatures lower
than 74◦C, the oxidizability of 1a is higher than that of
cumene. At temperatures higher than 74◦C, the reverse
is true. This fact can be explained by the stronger effect
of temperature on the oxidation of cumene, resulting
from the different overall energies of activation (Ep −
0.5Et) of cumene and 1a, 28 1 kJ/mol [14] and 22
2 kJ/mol, respectively.
The oxidizability of 1b is 2–3 times as high as that of
ethylbenzene. The oxidation of 1b is affected by tem-
perature nearly as intensely as is that of ethylbenzene;
the total energies of activation are 33 3 kJ/mol and
35.2 kJ/mol [19], respectively.
3,4
3,2
ethylbenzene
1b
3
2,8
2,6
cumene
2,4
2,2
2
1a
74°
1,8
1,6
1,4
2,5
2,6
2,7
2,8
2,9
3
3,1
3,2
1/T*103 [1/K]
Figure 1 −Log(oxidizability) of 1a, 1b, cumene, and ethylbenzene versus reciprocal absolute temperature.

92
ZAWADIAK ET AL.
6
5
4
3
2
1
0
140
120
100
80
60
40
20
0
0,0497g
I
c
2a=29%
=26%
c2a=36%
=34%
α
α
II
0.0525g
0.023g
0.0073g
0.0132g
0.0284g
0
2
4
6
8
1 0
1 2
1 4
time [h]
Figure 2 The oxidation course of 1a (2 ml, 12.58 mmol) with molecular oxygen (760 mm Hg, 25◦C) at temperatures of 70◦C
(I) and 80◦C (II) in the presence of AIBN (amounts of AIBN added are given in the figure).
TablesIIIandIVlistthemaximumconcentrationsof
the hydroperoxides attained in the experimental range
of temperatures.
In the case of oxidation of 1b, the maximum
2b concentrations were lower, 17.6–13.9%, within
the temperature range examined. The lower maxi-
mum hydroperoxide concentration is the result of
the much lower stabilities of secondary alkylaromatic
hydroperoxides.
The long-term oxidation of 1a over the temperature
range of 60–110◦C revealed no autocatalytic effects
to occur in the reaction of oxidation; on the contrary,
the rate of the reaction fell as the process was contin-
ued. After the reaction discontinued, addition of an-
other portion of the initiator revived the reaction. The
long-term oxidation of 1b followed a similar course.
This fact can be taken to prove that the decomposition
of the hydroperoxides yields compounds that inhibit
the free-radical oxidation of the hydrocarbons.
When 1a was oxidized at 60◦C for 18 h, the prod-
uct contained 39.6% of 2a (selectivity ca. 94%). At
higher temperatures, the oxidation was seen to become
inhibited and the contents of the hydroperoxide were
lower.
EXPERIMENTAL
Compounds 1a and 1b (Lancaster Synthesis), each
>98% pure, were additionally purified by distillation
over sodium in an atmosphere of nitrogen [b.p. 78–
20
79◦C/9 mm Hg, nD = 1.5034 (1.5033 [22]); and
20
34–37◦C/2 mm Hg, nD = 1.5080 (1.5092 [23]),
resp.].
The hydroperoxide in the oxidate was deter-
mined by iodometry [24]. Qualitatively, the oxidate
was analyzed by TLC [Kieselgel 60F254 plates, gel
Table III Long-Term Oxidation of 1a in the Presence
of Azo Initiators
Table IV Long-Term Oxidation of 1b in the Presence
of Azo Initiators
No. T (◦C) minitiator (g) Time (h) C2a (%) α (%)
No. T (◦C) minitiator (g) Time (h) C2b (%) α (%)
1
2
3
4
5
60
70
80
100
110
0.4337a
0.1306a
0.0435a
0.0354b
0.0352b
17.8
11.5
7.0
5.2
3.7
39.6
36.5
28.7
16.6
13.3
40
34
26
15
13
1
2
3
4
70
80
100
110
0.1196a
0.0448a
0.0344b
0.0325b
13.4
8.6
8.7
17.6
16.3
15.0
13.9
17
14
13
13
4.8
a AIBN added in three portions.
b ACHN added in three portions.
a AIBN added in three portions.
b ACHN added in three portions.

LIQUID-PHASE OXIDATION OF 1-ISOPROPYL- AND 1-ETHYL-4-METHOXYBENZENES
93
layer 0.2 mm thick; carbon tetrachloride–chloroform–
benzene–methanol (10:5:5:1.2 v/v) as the developing
liquid for 1a oxidation products]; the Rf values for 2a,
4, 3a, and 1a: 0.35, 0.58, 0.53, and 0.65, resp.; hexane–
ethyl ether (1:2 v/v) as the developing liquid for 2b; the
Rf values for 2b, 4, 3b, and 1b: 0.47, 0.36, 0.27, and
0.64, resp.
The initial oxidation rates were measured, and the
long-term oxidation experiments were carried out, in
thegasometricapparatusdescribedelsewhere[14]. The
oxidation was carried out in a thermostatted, 4-cm3
quartz flask connected with a thermostatted burette.
Oxygen was supplied into the flask from a burette in
which the pressure was kept constant. The reaction was
monitored by measuring the oxygen uptake. The ini-
tial oxidation rates were determined five times at each
temperature.
From the 1a oxidate, 2a was isolated via the sodium
salt. To 24 g of a 9% 2a (0.0119 mol) solution, 1.25
ml of 25% NaOH (0.04 mol) was added dropwise at a
temperature kept below 4◦C. The resulting white pre-
cipitate was collected by filtration and washed three
times with Et2O to collect 0.80 g sodium salt of 2a.
The salt was resuspended in 15 ml H2O and saturated
with gaseous carbon dioxide to yield 0.11 g 2a. The hy-
droperoxide was purified by TLC (horizontal chamber
DS-L; Kieselgel 60F254 plates, gel layer 0.2 mm thick;
dichloromethane–acetone (20:1 v/v) as the developing
liquid) to yield 0.02 g of chromatographically pure 2a.
Larger amounts of the hydroperoxide were pre-
pared by oxidation of 3a (10 g, 0.06 mol) in ben-
zene (100 ml) with 50% hydrogen peroxide (0.6 mol,
24.2 ml) at a temperature of 40◦C in the presence
of H2SO4 (2.6 × 10−4 mol, 0.023 ml). Compound 2a
was isolated from the reaction as a sodium salt which
was saturated with gaseous carbon dioxide. The hy-
droperoxide was purified twice via the sodium salt to
yield 1.9 g (0.01 mol) 2a, 97% pure (as determined
1
by iodometry). H NMR (CDCl3/TMS) δ = 1.60 (s,
6H, Ar C(CH3)2C O O , 3.81 (s, 3H, CH3OPh),
6.91 (d, J = 9 Hz, 2H, H-2, H-6), 7.40 (d, J = 9 Hz,
2H, H-3, H-5), 7.43 (s, 1H, C O OH), 13C NMR
(CDCl3) δ = 158.8, 136.4, 126.8, 113.8 (C ar), 83.6
( C(CH3)2 ), 55.3 ( OCH3), 26.0 ( CH3) (a Var-
ian Unity Inova 300 spectrometer was used). Calcd
for C10H14O3: C, 65.91; H, 7,74. Found: C, 65.57;
H, 7.34 (Perkin-Elmer 2400 Ser. II microanalysis was
used).
In view of the reported low thermal stability of 2a
[6], a study was carried out to compare the stabili-
ties of 2a and cumyl hydroperoxide cumene by the
DSC method (Fig. 3). The stability of 2a is seen to be
lower than that of cumene. The temperatures at which
the decomposition rates of the two hydroperoxides at-
tain maximum are 150.61 and 176.23◦C, respectively.
However, our experience has shown that carefully pu-
rified 2a can be stored for several weeks at 0◦C with
no visible signs of decomposition.
Figure 3 The DSC thermograms for 2a and cumene hydroperoxide. Rate of heating 10◦C/min.

94
ZAWADIAK ET AL.
4. Russell, G.; Williamson, R. J Am Chem Soc 1964, 86,
2357.
CONCLUSIONS
5. Howard, J.; Ingold, K. Can J Chem 1968, 46(6), 1017.
6. Choe, S.; Tsutsumi, S. Nippon Kagaku Zasshi 1960, 81,
582; Chem Abstr 1962, 56, 397e.
Compounds 1a and 1b are apt to become oxidized in
free-radical chain oxidation processes. The oxidizabil-
ity of the former is comparable with that of cumene.
The oxidizability of the latter is about 2–3 times as high
as that of ethylbenzene.
Long-term oxidation of 1a at lower temperatures
carried out in the presence of azo initiators has yielded
product with high concentration of 2a (ca. 40%). The
long-term oxidation of 1b has afforded products with
lower maximum concentrations of 2b (ca. 18%).
Compounds 2a and 2b are the precursors of the
inhibitors formed as a result of their decomposition.
These inhibitors reduce the rate of the oxidation reac-
tion so that the initiator has to be continuously added to
reinitiate the reaction and to allow the hydroperoxides
to be prepared in higher yields.
7. Opeida, I. A. Zh Org Khim 1988, 24(3), 572.
8. Efimova, I. B. Ukr Khim Zh 1988, 54, 756.
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Nauka: Moscow, 1965
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