One-pot synthesis of phenols by hydroxylation of aromatics with hydroxylamine

Article abstract of DOI:10.1246/cl.2012.369

In this study, a new approach for one-pot synthesis of phenols is presented, i.e., benzene, ethylbenzene, and xylene were hydroxylated with hydroxylamine to give the corresponding phenols in good yield using molybdenum as a key catalyst.

Full text of DOI:10.1246/cl.2012.369

doi:10.1246/cl.2012.369
Published on the web March 24, 2012
369
One-pot Synthesis of Phenols by Hydroxylation of Aromatics with Hydroxylamine
Dongsheng Zhang,* Liya Gao, Wei Xue, Xinqiang Zhao, Shufang Wang, and Yanji Wang*
Key Laboratory of Green Chemical Technology and High Efficient Energy Saving of Hebei Province,
Hebei University of Technology, Tianjin 300130, P. R. China
(Received December 28, 2011; CL-111242; E-mail: zds1301@hebut.edu.cn, yjwang@hebut.edu.cn)
In this study, a new approach for one-pot synthesis of
phenols is presented, i.e., benzene, ethylbenzene, and xylene
were hydroxylated with hydroxylamine to give the correspond-
ing phenols in good yield using molybdenum as a key catalyst.
the reaction conditions in an open air system. First, several
acidic solvents were tried for hydroxylation of ethylbenzene. As
shown in Table 1, incorporation of water into HOAc-H2SO4
acidic medium is favorable to the hydroxylation. And H2O-
HOAc-H2SO4 medium with a volume ratio of 4:10:1 provides
high yield of ethylphenol.
Hydroxyaromatics including phenol, cresol, ethylphenol,
and xylenol are valuable intermediates for the production of
phenolic resins, plastics, pharmaceuticals, etc. These phenols
were originally extracted from coal tar and other natural sources.
To this day, several synthetic routes have been developed, such
as sulfonation or chlorination of the benzene ring, and the well-
known cumene/cymene process.1 However, these processes
suffer from some drawbacks such as multistep procedures and
harsh reaction conditions. Vapor-phase alkylation of phenol is
another way to produce cresols, ethylphenol, or xylenol.2
Additionally, synthesis of xylenol has been achieved by reaction
of methanol and cyclohexanone.3 The processes, however, use
relatively expensive starting materials and require high capital
costs for separation of products.
Table 2 shows the influence of reaction temperatures and
time on the hydroxylation. The yield of ethylphenol increases
first, passing through a maximum at 80 °C, and then decreases.
Among the reaction times, ethylphenol yield can be improved
by having longer reaction times. However, ethylphenol yield
increases slightly as the time exceeded 4 h. Hence, the ideal
reaction temperature and time are 80 °C and 4 h, respectively.
Next, various amounts of (NH4)6[Mo7O24]¢4H2O catalyst
and hydroxylamine were screened, and the results are summa-
Table 1. Effect of reaction medium on ethylbenzene hydrox-
ylationa
Product selectivity/%
Ethylphenolsc Othersd
XE
/%b
Solvent (mL:mL:mL)
HOAc-H2SO4 (12:3)
Fortunately, direct hydroxylation of aromatics has been
realized in recent years. It has attracted considerable attention for
its potential economic advantage and eco-efficiency.4 Currently
there are several approaches, involving catalytic oxidation of
36 4 (2:1:1) [1]
96
66
40
32
31
H2O-HOAc-H2SO4 (2:10:3) 14 34 (4:21:9) [5]
H2O-HOAc-H2SO4 (3:10:2) 12 60 (12:29:19) [7]
H2O-HOAc-H2SO4 (4:10:1) 13 68 (19:35:14) [9]
H2O-HOAc-H3PO4 (4:10:1) 10 69 (16:40:13) [7]
7
aromatics employing N2O,5 O2,6 and H2O2 as oxidant.
Recently, it was reported that cresols can be formed as by-
products in the reaction of direct amination of toluene with
hydroxylamine.8 In our previous work,9 cresols were success-
fully synthesized as the main product from toluene and
hydroxylamine catalyzed by (NH4)6[Mo7O24]¢4H2O.
Here, a question came to our mind. Could other aromatics
be hydroxylated with hydroxylamine to give the corresponding
phenols? Therefore, a variety of aromatics including benzene,
ethylbenzene and xylene, were examined by using molybdenum
(Mo) catalyst in this work. A schematic representation of the
one-pot reaction is given in Scheme 1.
Analytical grade (NH4)6[Mo7O24]¢4H2O and Na2[MoO4]¢
2H2O were obtained commercially and tested as homogeneous
catalysts. Supported Mo oxide catalyst was prepared by
impregnation,10 and the reactions were carried out separately
in open air and in closed systems.11
H2O-HCOOH-H2SO4
10 77 (18:37:22) [8]
(4:10:1)
23
aReaction conditions: 0.25 g (NH4)6[Mo7O24]¢4H2O catalyst,
10 mmol (NH2OH)2¢H2SO4, 20 mmol ethylbenzene, 15 mL
b
c
medium, 85 °C, 4 h. Ethylbenzene conversion. Numbers in
parenthesis and blanket show the ratio of o-, p-, and m-
ethylphenol and the yield of ethylphenol, respectively. dEthyl-
anilines.
Table 2. Effect of temperature and time on ethylbenzene
hydroxylationa
Product selectivity/%
Temperature Time XE
/°C
/h
/%
Ethylphenols
Ethylanilines
70
80
85
90
80
80
80
80
4
4
4
4
1
2
3
6
8
54 (18:21:15) [4]
46
26
32
40
50
32
30
23
13 74 (20:35:19) [10]
13 68 (19:35:14) [9]
13 60 (22:23:15) [8]
10 50 (14:25:11) [5]
11 68 (18:33:17) [7]
12 70 (20:34:16) [8]
14 77 (21:35:21) [11]
Initially, the reaction between ethylbenzene and hydroxyl-
amine sulfate was selected as a model reaction for optimizing
R2
+ NH2OH
R2
Mo catalyst , 70-90 °C
R1
R1
OH
H2O-HOAc-H2SO4 medium
aReaction conditions: 0.25 g (NH4)6[Mo7O24]¢4H2O catalyst,
10 mmol (NH2OH)2¢H2SO4, 20 mmol ethylbenzene, 15 mL
H2O-HOAc-H2SO4 medium (volume ratio is 4:10:1).
(R1 = H, CH3, C2H5; R2 = H, CH3)
Scheme 1. Schematic representation of the one-pot reaction.
Chem. Lett. 2012, 41, 369-371
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

370
Table 3. Effect of the amount of hydroxylamine and catalyst
on ethylbenzene hydroxylationa
Table 4. Hydroxylation of various aromatic compoundsa
Product selectivity/%
Xi
Aromatics
/%b
Product selectivity/%
Ethylphenols Ethylaniline
Hydroxylamine Catalyst XE
Anilinesc
Phenol derivatives
sulfate/g
/g
/%
OH
NH2
1.64
1.64
1.64
1.64
0.88
3.25
4.89
1.40b
1.64
1.64
1.64
0.10
0.25
0.55
1.00
0.25
0.25
0.25
0.25
10 59 (11:37:11) [6]
13 74 (20:35:19) [10]
14 83 (24:34:25) [12]
9 91 (24:33:34) [8]
4 76 (20:28:28) [3]
31 75 (20:38:17) [23]
40 80 (24:36:20) [32]
6 68 (16:39:13) [4]
41
26
17
9
24
25
20
32
17
41
29
51
16
55
45
CH3
OH
CH3
CH3
CH3
CH3
CH3
CH3
CH3
OH
NH2
23
59
18d
23d
30d
CH3
CH3
CH3
CH3
CH3
0.50c 15 83 (22:35:26) [13]
OH
CH3
CH3
18
17
OH
0.20d
0.25
8 59 (11:38:10) [5]
19e 71 (21:34:16) [14]
CH3
CH3
NH2
CH3
OH
10
9
58
aReaction conditions: (NH4)6[Mo7O24]¢4H2O catalyst, 15 mL
H2O-HOAc-H2SO4 medium (volume ratio is 4:10:1), 80 °C,
CH3
CH3
CH3
CH3
OH
NH2
b
c
d
4 h. NH2OH¢HCl. Na2[MoO4]¢2H2O catalyst. 15% MoO3/
CH3
CH3
e
70
Al2O3 catalyst. In closed system.
aReaction conditions: In closed system, 0.25 g (NH4)6[Mo7-
O24]¢4H2O catalyst, 10 mmol (NH2OH)2¢H2SO4, 20 mmol
aromatic compounds, 15 mL H2O-HOAc-H2SO4 medium
(volume ratio is 4:10:1), 80 °C (70 °C for benzene hydrox-
rized in Table 3. With increasing catalyst dosage, the selectivity
for ethylphenol increases steadily, whereas the conversion of
ethylbenzene increases first and then decreases. Better results
can be achieved at 0.25-0.55 g of catalyst. For the influence of
hydroxylamine, ethylphenol yield can be strongly improved by
increasing hydroxylamine dose. When 4.89 g of hydroxylamine
sulfate is added, ethylphenol yield increases up to 32% with
ethylbenzene conversion of 40%. In addition, hydroxylamine
hydrochloride was being substituted for hydroxylamine sulfate
in the present hydroxylation, and ethylphenol was also synthe-
sized with good selectivity. However, the conversion of ethyl-
benzene was only 6%. Hence hydroxylamine sulfate was chosen
for the rest of the experiments.
Furthermore, Na2[MoO4]¢2H2O and supported catalysts
15% MoO3/Al2O3 were tested for the hydroxylation. As shown
in Table 3, these Mo catalysts also exhibit good activity. It
means that the supported Mo oxide catalyst and dissolved Mo
species are equally effective, and the real active component may
be Mo species in the hydroxylation. To see the effect of the
absence of air, ethylbenzene hydroxylation was carried out in a
closed autoclave. Interestingly, ethylphenol yield was 14%,
which is higher than those (10%) in open air under the same
reaction conditions.
On the basis of the above results, benzene and xylene
isomers were examined in a closed system. Table 4 gives the
results. Benzene can also be hydroxylated with hydroxylamine
to give phenol, with the selectivity to phenol around 55%. In the
hydroxylation of xylene isomers, altogether six dimethylphenols
were obtained with good selectivity, corresponding to 2,3-
dimethylphenol, 2,4-dimethylphenol, 2,5-dimethylphenol, 2,6-
dimethylphenol, 3,4-dimethylphenol, and 3,5-dimethylphenol.
For o-xylene or m-xylene hydroxylation, the total selectivity of
dimethylphenols is around 80%.
It is not clear but we believe the reaction mechanisms of the
hydroxylations may be related to a radical mechanism. Take
ethylbenzene hydroxylation for example, the hydroxylation
gives a non-regiospecific mixture of o-, p-, and m-ethylphenols
as shown in Tables 1-3. This result is similar to former studies
b
c
ylation), 4 h. The conversion of aromatics. Aniline deriva-
d
tives. Besides dimethylaniline, trace amounts of tetramethyl-
biphenyl was also produced as by-products.
of toluene hydroxylation.9 If ethylbenzene hydroxylation pro-
gressed by an electrophilic mechanism, then o- and p-ethyl-
phenols would be predominant in the products. The unselective
product formation indicates the present hydroxylation may
occur through a radical mechanism. Further studies are now in
progress.
In conclusion, a new approach for one-pot synthesis of
phenol derivatives was described in this work. Benzene,
ethylbenzene, and xylene were hydroxylated with hydroxyl-
amine to give the corresponding phenols by using molybdenum
as a key catalyst.
This research was supported by National Natural Science
Foundation of China (Nos. 20876033, 21106029, and
21176056) and National Basic Research Program of China
(No. 2010CB234602).
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Chem. Lett. 2012, 41, 369-371
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/