p-Toluenesulfonic acid mediated zinc chloride: highly effective catalyst for the Beckmann rearrangement

Article abstract of DOI:10.1016/j.tetlet.2007.07.171

PTSA-ZnCl₂ has been proved to be an excellent catalyst for liquid-phase Beckmann rearrangement of ketoximes in acetonitrile. The satisfactory yields of amides were obtained in the present of this catalyst system.

Full text of DOI:10.1016/j.tetlet.2007.07.171

Tetrahedron Letters 48 (2007) 7218–7221
p-Toluenesulfonic acid mediated zinc chloride:
highly effective catalyst for the Beckmann rearrangement
*
Lin-fei Xiao, Chun-gu Xia and Jing Chen
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics,
Chinese Academy of Sciences, Lanzhou 730000, PR China
Received 7 June 2007; revised 23 July 2007; accepted 26 July 2007
Available online 31 July 2007
2
Abstract—PTSA–ZnCl has been proved to be an excellent catalyst for liquid-phase Beckmann rearrangement of ketoximes in aceto-
nitrile. The satisfactory yields of amides were obtained in the present of this catalyst system.
Ó 2007 Elsevier Ltd. All rights reserved.
The conversion of ketoxime into corresponding amide,
known as the Beckmann rearrangement, is a common
method used in organic chemistry and is also a topic
of current interest. It accomplishes both the cleavage of
carbon–carbon bond and the formation of a carbon–
nitrogen bond, and represents a powerful method
particularly for manufacture of e-caprolactam in the
chemical industry. This reaction, however, generally
requires high reaction temperature and a large amount
of a strong Brønsted acid and dehydrating media,
causing large numbers of byproducts and serious corro-
expensive catalyst system for the Beckmann rearrange-
ment of ketoxime.
p-Toluenesulfonic acid (PTSA) is commercially avail-
able and is a very cheap chemical with stability.
Recently, it is shown that PTSA has the prospect to be
used as a substitute for conventional acidic catalytic
materials. Last year, it has been used as an efficient acid
1
6
catalyst for the synthesis of 4(3H)-quinazolinones, the
1
7
regiospecific nitration of phenols and the carbonyl-
1
8
ation of formaldehyde. Herein we wish to report our
preliminary results on the first highly effective p-toluene-
sulfonic acid (PTSA) mediated zinc chloride catalyzed
the Beckmann rearrangement of ketoxime to produce
corresponding amides without producing any waste
(Scheme 1).
1
sion problems. Although a great number of the vapor-
phase Beckmann rearrangement processes have been
reported, low selectivity for e-caprolactam and rapid
decay of activity generally resulted under very high reac-
2
tion temperatures. Liquid-phase catalytic Beckmann
rearrangement under mild condition, on the contrary,
3
can be obtained with high conversion and selectivity.
Initially, acetophenone oxime has been used as a sub-
On these basis, mild conditions were tried and several
interesting variants were developed, for example, using
ionic liquid at room temperature, trifluoromethanesulf-
strate to test the feasibility of PTSA/ZnBr used as a cat-
alyst for the Beckmann rearrangement. The results are
summarized in Table 1. Scarcely any reaction occurred
2
4
5
6
7
onic acid, chlorosulfonic acid, sulfamic acid, cyanuric
when PTSA and ZnBr were used as a sole catalyst
2
8
9
10
chloride, chloral, anhydrous oxalic acid, O-alkyl-
N,N-dimethylformamidium salt, ethyl chloroformate/
boron trifluoride etherate, P O , bis(2-oxo-3-oxazo-
lidinyl)phosphinic chloride and diethyl chlorophos-
phate. However, these methods currently suffer from
the use of toxic solvent, expensive reagents and low yields.
Therefore, it is necessary to develop a simple, clean and no
(Table 1, entries 1 and 2). While the reaction was con-
ducted with PTSA mediated zinc bromide, the 93% yield
of acetanilide was obtained (Table 1, entry 3). The only
by-product being confirmed is acetophenone, which is
derived from the deoximation of acetophenone oxime.
1
1
1
2
13
2
5
1
4
1
5
NOH
R2
O
PTSA-Lewis acid
R2
R1
R1
N
H
*
Corresponding author. Tel.: +86 931 496 8089; fax: +86 931 827
147; e-mail: cgxia@lzb.ac.cn
7
Scheme 1.
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.07.171

L. Xiao et al. / Tetrahedron Letters 48 (2007) 7218–7221
7219
a
Table 1. Effects of reaction conditions on the Beckmann rearrangement of acetophenone oxime
NOH
H
N
PTSA/Lewis acid
Solvent, reflux
O
e
Entry
Catalyst I
Catalyst II
Solvent
Reaction time [h]
Yield (%)
1
2
3
4
5
6
7
8
9
—
ZnBr
—
ZnBr
ZnBr
ZnBr
2
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeNO
Toluene
1,4-Dioxane
MeCN
MeCN
MeCN
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
2.0
3.0
4.0
—
—
93
68
41
93
67
51
—
82
—
—
51
98
99
75
90
95
PTSA
PTSA
Acetic acid
Benzoic acid
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
2
2
2
ZnCl
2
SnCl
FeCl
4
3
Zn(OAc)
2
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
ZnCl
ZnCl
ZnCl
ZnCl
ZnCl
ZnCl
ZnCl
ZnCl
ZnCl
2
2
2
2
2
2
2
2
2
2
b
c
d
MeCN
MeCN
MeCN
a
b
c
Reaction and conditions: catalyst I (0.10 mmol), catalyst II (0.10 mmol), acetophenone oxime (1.0 mmol), solvent 5 mL.
ZnCl
2
0.05 mmol.
0.12 mmol.
2
0.15 mmol.
ZnCl
2
d
e
ZnCl
GC yield.
The effects of the various organic acid on the Beckmann
rearrangement of acetophenone oxime were also investi-
gated (Table 1). When using acetic acid or benzoic acid
as a substitute, the yield of acetanilide is only 68% and
To explore the generality and scope of the Beckmann
rearrangement catalyzed by PTSA/ZnCl , respective
2
ketoximes as substrates were examined under reflux con-
dition in acetonitrile for 5 h (Table 2). The results
showed that excellent yields were obtained with aromatic
ketoximes (Table 2, entries 1–4) in this PTSA/ZnCl2
catalytic system. Cyclododecanone oxime was also very
reactive and converted to the corresponding amide in
93% of yield ( Table 2, entry 5), which was useful as a
staring material for nylons. When cyclohexanone oxime
was used as substrate, the e-caprolactam provided mod-
erate yield (Table 2, entry 6). Unfortunately, acetone
oxime was extremely unreactive to the corresponding
amide (Table 2, entry 7).
4
1%, respectively (Table 1, entries 4 and 5). This was
probably due to the different acidities of the various
organic acid.
Next, we examined the effect of the different Lewis acids
on the Beckmann rearrangement of acetophenone
oxime. From Table 1, it is clear that ZnCl and ZnBr
2
2
showed the best co-catalytic effects (Table 1, entries 3,
–9). ZnCl is chosen as the co-catalyst for the Beck-
6
2
mann rearrangement because it is much cheaper than
ZnBr and has satisfactory activity. At the same time,
2
the effect of the amount of ZnCl2 was investigated.
The results suggested that increasing the amount of
In summary, the Beckmann rearrangement of aromatic
ketoximes can be conducted with PTSA/ZnCl2 as a
catalyst under mild condition, excellent yield of corre-
sponding amides was obtained and the results strongly
depended on the nature of the solvents used. This
offers an attractive catalytic system for the Beckmann
rearrangement. Further studies are in progress in our
laboratories to clarify the catalytic mechanism and to
explore more versatile mediate catalytic system for the
Beckmann rearrangement.
ZnCl had a pronounced positive effect on the catalytic
2
activity (Table 1, entries 6, 13–15). However, the
enhancement of ZnCl beyond 0.12 mmol gave only a
2
slight increase in the yield of acetanilide.
In order to established the optimized reaction condi-
tions, we examined the effect of the solvent. Polar and
nucleophilic solvents, such as acetonitrile and nitrometh-
ane, were suitable for this catalyst (Table 1, entries 6 and
1
0). When using toluene and 1,4-dioxane as solvent, the
product of the Beckmann rearrangement was not found
Table 1, entries 11 and 12). It shows that solvent plays
General procedure: For each reaction, the oxime
(1.0 mmol), PTSA (0.1 mmol), ZnCl (0.12 mmol) and
2
(
acetonitrile (5.0 mL) were charged into 50 mL round
bottom flask equipped with a magnetic stirrer and con-
denser. The mixture was refluxed for 5.0 h and cooled to
room temperature. Qualitative analyses were conducted
with HP6890/5973 GC–MS and quantitative analyses
an important role in this reaction. The reaction time
effect was also investigated. It has shown that the
increase of the reaction time is propitious for the increas-
ing yield of acetanilide (Table 1, entries 16–18).

7220
L. Xiao et al. / Tetrahedron Letters 48 (2007) 7218–7221
a
Table 2. The effects of the different oxime on the Beckmann rearrangement
a
b
Entry
Substrate
NOH
Product
Yield (%)
H
N
1
97
92
97
90
O
NOH
H
2
3
4
N
O
H
NOH
N
MeO
O
MeO
NOH
H
N
O
O
5
NOH
93
NH
NOH
O
6
7
NH
40
—
O
NOH
N
H
a
Reaction and conditions: PTSA (0.10 mmol), ZnCl
Isolated yield.
2
(0.12 mmol), oxime (1.0 mmol), acetonitrile 5 mL, reaction time 5.0 h.
b
`
were conducted with Agilent 6820 equipped with FID
detector.
Fornasari, G.; Tosi, C.; TrifirO, F.; Vaccari, A.; Dumeig-
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Acknowledgement
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87, 83; (k) Palkovits, R.; Yang, C.; Olejnik, S.; Sch u¨ th, F.
This study was supported by the Natural Science
Founder of National (20625308).
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