A mild and efficient catalyst for the Beckmann rearrangement, BOP-Cl

Article abstract of DOI:10.1016/j.tetlet.2006.05.029

BOP-Cl (bis(2-oxo-3-oxazolidinyl)phosphinic chloride) was found to be very active as the first organophosphorus catalyst (1-5 mol % loading) for the Beckmann rearrangement of various ketoximes to the corresponding amides in anhydrous acetonitrile at refluxing temperature.

Full text of DOI:10.1016/j.tetlet.2006.05.029

Tetrahedron Letters 47 (2006) 4861–4863
A mild and efficient catalyst for the Beckmann
rearrangement, BOP-Cl
*
*
Minze Zhu, Chuantao Cha, Wei-Ping Deng and Xiao-Xin Shi
School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China
Received 23 March 2006; revised 4 May 2006; accepted 8 May 2006
Abstract—BOP-Cl (bis(2-oxo-3-oxazolidinyl)phosphinic chloride) was found to be very active as the first organophosphorus cata-
lyst (1–5 mol % loading) for the Beckmann rearrangement of various ketoximes to the corresponding amides in anhydrous aceto-
nitrile at refluxing temperature.
Ó 2006 Elsevier Ltd. All rights reserved.
The Beckmann rearrangement (BKR) is an important
reaction for transformation of ketoxime into amide,
which has been successfully utilized to produce x-capro-
none oxime in ionic liquid or DMF, further studies on
new catalyst still need to be done since they are all cor-
rosive and not easy to handle. Furthermore the mecha-
nism of these two catalysts in the BKR is still not clear,
although PCl5 and P O may act as dehydration
1
–3
lactam and laurolactam in industry. However, it often
suffers from the co-production of large amount of unde-
sired ammonium sulfate and suffers from serious corro-
sion problems in conventional liquid-phase industrial
process. To solve the problems, catalytic version of the
Beckmann rearrangement have been mainly focused
2
5
reagents according to the classical BKR mechanism.
1
1
BOP-Cl (6) is a well known excellent dehydration
reagent in peptide synthesis, which is more stable, less
corrosive and easy to handle. Initially we would like to
know if BOP-Cl could also act as an effective dehydra-
tion reagent in the Beckmann rearrangement. To our
delight, it did catalyze the BKR of acetophone oxime
to N-acetyl aniline very well (10 mol % of 6, 99% yield).
Interestingly, according to the classical BKR mechanism
and dehydration pathway of BOP-Cl, a maximum 10%
of conversion should be obtained by using 10 mol % of
BOP-Cl. The mechanism therefore needed to be
addressed.
3
g–m
on vapor-phase processes
by developing solid cata-
lyst such as metal oxides, clays, and zeolites, which often
suffer from high reaction temperature and decay of
4
activity of catalyst. In liquid-phase, Deng’s group have
developed a series of catalysts such as PCl , chlorosulf-
5
onic acid, and ionic supported sulfonyl chloride. Other
5
6
catalysts such as sulfamic acid, lanthanide triflate,
7
and RuCl3 have also been reported. However, few re-
ports focus on small organomolecule catalyzed BKR.
Recently, Yamamoto and Ishihara’s group reported
8
9
that cyanuric chloride is a mild and active catalyst for
the BKR. Herein, we would like to report our prelimin-
ary results on the first highly effective organophospho
BOP-Cl (6) catalyzed Beckmann rearrangement of keto-
xime to amide.
Recently, Yamamoto and Ishihara proposed a novel
BKR mechanism for the cyanuric chloride catalyzed
BKR. On the basis of this mechanism, we propose here
9
a similar mechanism (Scheme 1) for BOP-Cl catalytic
Beckmann rearrangement, which accounts for the excel-
lent catalytic behavior of BOP-Cl. If this is true, de-
crease of the BOP-Cl loading to 5 mol % would also
catalyze this rearrangement efficiently. As expected, N-
acetyl aniline was obtained in 94% of yield within 1 h.
Then a series of phosphinic chloride catalysts were
tested, however only moderate catalytic activity was
found. These were probably less active than BOP-Cl
due to an undetermined electronic effect on the
phosphorous center caused by different substituents on
Although PCl54a and P O
10
have been reported to be
2
5
good catalysts (normally 10–20 mol % loading is re-
quired) for the Beckmann rearrangement of cyclohexa-
*
Corresponding authors. Tel./fax: +86 021 64252431 (W.-P.D.); tel./
fax: +86 021 64252052 (X.-X.S.); e-mail addresses: weiping_deng@
ecust.edu.cn; xxshi@ecust.edu.cn
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.05.029

4862
M. Zhu et al. / Tetrahedron Letters 47 (2006) 4861–4863
Table 2. Influences of Lewis acids and water on the BOP-Cl catalyzed
OH
R2
N
a
Beckmann rearrangement of acetophenone
OH
Ph
O
H
R1
N
N
BOP-Cl
Cat. BOP-Cl
HCl
Ph
MeCN, reflux, 1h
1
2
-
R1
OBOP
N
N
b
c
Entry BOP-Cl (mol %) Additive (%) (mol %) Yield (%)
BOPO
R2
R1
R2
1
2
3
4
5
6
7
8
9
5
5
2
2
2
2
2
5
5
No
94
99
92
40
56
85
73
55
5
H+
ZnCl
ZnCl
No
InCl
In(OTf)
Sc(OTf)
2
(2)
(2)
2
N
R1
R2
O
3
(2)
N
O
O
3
(2)
(2)
O
P
H
3
N
H
H
2
O (33)
O (100)
O
R2
O
OH
R1
N
2
NH
R2
O
N
a
b
c
Complex A
R1
2 mmol of acetophenone oxime was used for BKR in anhydrous
MeCN (4 mL).
Lewis acids were dissolved in anhydrous MeCN to make 1 M solu-
tion, which were then added into reaction mixture via syringe.
Isolated yield.
O
R1
R2
Scheme 1. Proposed mechanism for BOP-Cl catalyzed BKR.
the phosphorous atom. Solvent effects were also
investigated and the results summarized in Table 1. Polar
solvent acetonitrile gave the best result (Table 1, entries
0.33 equiv of water and 1 equiv of water (based on
oxime) were added to reaction system respectively in
the presence of 5 mol % of BOP-Cl, N-acetyl aniline
was obtained in 55% and 5% of yield, respectively
(entries 8 and 9).
4
and 5).
It has been reported that Lewis acids such as ZnCl are
2
good co-catalysts for cyanuric chloride catalyzed BKR,
9
which is not active in the absence of cyanuric chloride.
Next we examined the generality of the BOP-Cl
In order to understand whether this Lewis acid effect
works similarly in our BOP-Cl system, a series of Lewis
acids were investigated. A similar Lewis acid effect was
(2 mol %) catalyzed BKR with ZnCl (2 mol %) as co-
2
catalyst in anhydrous acetonitrile (Table 3). The Beck-
mann rearrangement of various ketoximes proceeded
smoothly with complete reaction within 1 h to give the
corresponding amides in good to excellent yield in most
cases. Interestingly, 1 mol % BOP-Cl in the absence of
found. From Table 2, it is clear that ZnCl showed the
2
best co-catalytic effect, and BOP-Cl could be further de-
creased to 2 mol % by using 2 mol % of ZnCl as co-cat-
2
alyst to maintain the catalytic activity. In the course of
our study, we also noticed that using anhydrous solvent
is the key to achieving high catalytic activity. When
ZnCl was extremely active in the rearrangement of ben-
2
zophenone to the corresponding amide (entry 1). Cyclo-
dodecanone oxime was also very reactive and
converted to the corresponding laurolactam in 99% of
yield (entry 9), which is a very useful monomer material
Table 1. Phosphinic chlorides (5 mol %) catalyzed Beckmann rear-
a
rangement of acetophenone oxime
OH
Ph
O
H
Phosphinic Chlorides
mol%
a
N
N
2
Table 3. Scope of BOP-Cl/ZnCl catalyzed Beckmann rearrangement
5
Ph
Solvent, reflux, 1h
OH
R1
O
H
1
2
N
BOP-Cl(2mol%)/ZnCl (2mol%)
2
N
O
O
P
O
P
O
P
PhO
Cl
O
O
R1
R2
P
MeCN, reflux, 1h
O
R2
Cl
Cl
Ph
Cl
PhO
Cl
Cl
Cl
N
N
1
2
c
O
Entry
R
R
Yield (%)
3
4
5
6
b
1
Ph
Ph
Ph
99
92
97
96
95
99
97
95
99
<5
c
Entry
Catalyst
Solvent
Yield (%)
2
3
4
5
6
7
8
9
Me
Me
Me
Me
Me
Et
1
2
3
4
3
4
5
6
6
6
6
6
MeCN
MeCN
MeCN
MeCN
MeCN
THF
55
50
48
94
99
50
5
p-(Me)C
o-(MeO)C
m-(MeO)C
p-(MeO)C H
6 4
Ph
CH
(CH
(CH
6
H
4
6
H
4
6
H
4
b
5
6
7
8
3
(CH
2
)
7
Me
Toluene
Dioxane
2
)
)
11
5
5
10
2
a
a
2
mmol of acetophenone oxime was used for the BKR in anhydrous
2 mmol of ketoximes were used for the Beckmann rearrangement in
anhydrous MeCN (4 mL) in the presence of BOP-Cl (2 mol %) and
ZnCl (2 mol %).
2
solvent (4 mL) and in the presence of 5 mol % of catalysts at refluxing
temperature.
1
b
c
b
c
0 mol % of catalyst BOP-Cl was used.
Only 1 mol % of BOP-Cl was used in the absence of ZnCl
Isolated yield.
2
.
Isolated yield.

M. Zhu et al. / Tetrahedron Letters 47 (2006) 4861–4863
4863
for nylons.12 However, cyclohexanone oxime was extre-
2003, 58, 935; (f) Fern a´ ndez, A. B.; Boronat, M.; Blasco,
T.; Corna, A. Angew. Chem., Int. Ed. 2005, 44, 2370; For
vapor-phase Beckmann rearrangement, see: (g) Kim, S. J.;
Jung, K. D.; Joo, O. S.; Kim, E. J.; Kang, T. B. Appl.
Catal. A: Gen. 2004, 266, 173; (h) Dongare, M. K.;
Bhagwat, V. V.; Ramana, C. V.; Gurjar, M. K. Tetra-
hedron Lett. 2004, 45, 4759; (i) Mao, D.; Chen, Q.; Lu, G.
Appl. Catal. A: Gen. 2003, 244, 273; (j) Maheswari, R.;
Sivakumar, K.; Sankarasubbier, T.; Narayanan, S. Appl.
Catal. A: Gen. 2003, 248, 291; (k) Dahlhoff, G.; Barsnick,
U.; H o¨ lderich, W. F. Appl. Catal. A: Gen. 2001, 210, 83; (l)
Singh, P. S.; Bandyopadhayay, R.; Hegde, S. G.; Rao, B.
S. Appl. Catal. 1996, 136, 249; (m) Raja, R.; Sankar, G.;
Thomas, J. M. J. Am. Chem. Soc. 2001, 123, 8153.
mely unreactive to BOP-Cl (entry 10), which behaved
similarly to cyanuric chloride.9
In summary, we have developed the first generation of
organophosphinic chloride, commercially available
BOP-Cl (5 mol %) or BOP-Cl (2 mol %)/ZnCl2
(
2 mol %) system,13 as highly effective catalyst for the
Beckmann rearrangement of ketoximes to correspond-
ing amides. This finding will broaden the scope of cata-
lytic Beckmann rearrangement. Further modifications
of substituents on the phosphorous center will be pur-
sued in an effort to increase catalyst performance. Fur-
ther studies are in progress in our laboratories to
clarify the catalytic mechanism and to explore more
versatile catalysts for the Beckmann rearrangement of
various ketoximes to corresponding amides.
4
. (a) Peng, J.; Deng, Y. Tetrahedron Lett. 2001, 42, 403; (b)
Gui, J.; Deng, Y.; Hu, Z.; Sun, Z. Tetrahedron Lett. 2004,
4
5, 2681; (c) Li, D.; Shi, F.; Guo, S.; Deng, Y. Tetrahedron
Lett. 2005, 46, 671.
. Wang, B.; Gu, Y.; Luo, Y. C.; Yang, T.; Yang, L.; Suo, J.
Tetrahedron Lett. 2004, 45, 3369.
5
6
. De, S. K. J. Chem. Res. 2004, 131.
Acknowledgements
7. De, S. K. Synth. Commun. 2004, 34, 3431.
8
. (a) Chandrasekhar, S.; Gopalaiah, K. Tetrahedron Lett.
003, 44, 755; (b) Chandrasekhar, S.; Gopalaiah, K.
2
The authors would like to thank a start-up fund from
East China University of Science and Technology.
Tetrahedron Lett. 2003, 44, 7437.
9
. Furuya, Y.; Ishihara, K.; Yamamoto, H. J. Am. Chem.
Soc. 2005, 127, 11240.
1
0. Ren, R. X.; Zueva, L. D.; Ou, W. Tetrahedron Lett. 2001,
42, 8441.
References and notes
1
1. Van der Auwera, C.; Anteunis, M. J. O. Bull. Soc. Chim.
Belg. 1986, 95, 203–205.
1
. For reviews, see: (a) Gawly, R. E. Org. React. 1988, 35, 1,
and references cited therein; (b) Smith, M. B.; March, J. In
Advanced Organic Chemistry, 5th ed.; John Wiley & Sons:
New York, 2001; p 1415, and references cited therein.
. (a) Dalhhoff, G.; Niederer, J. P. M.; H o¨ lderich, W. F.
Catal. Rev.-Sci. Eng. 2001, 43, 381–441; (b) Tatsumi, T. In
Fine Chemicals through Heterogeneous Catalysis; Sheldon,
R. A., van Bekkum, H., Eds.; Wiley-VCH, 2001; p 185; (c)
Li, W. C.; Lu, A. H.; Palkovits, R.; Schmidt, W.;
Spliethoff, B.; Schuth, F. J. Am. Chem. Soc. 2005, 127,
12. Phang, Y.; Liu, T.; Mohamed, A.; Pramoda, K. P.; Chen,
L.; Shen, L.; Chow, S. Y.; Lu, X.; Hu, X. Polym. Int. 2005,
54, 456.
2
13. General procedure for the BOP-Cl catalyzed Beckmann
rearrangement reaction: A solution of ketoxime (2 mmol),
1–5 mol % of BOP-Cl 6 and/or 2 mol % Lewis acid in
4 mL of dry MeCN was refluxed under a nitrogen
atmosphere. After completion of the reaction as moni-
tored by TLC, the reaction was quenched with saturated
aqueous sodium hydrogen carbonate. The organic layer
was extracted with ethyl acetate, dried over anhydrous
sodium sulfate, and concentrated in vacuo. The resulting
crude product was purified by column chromatography on
silica gel to give the corresponding amide in high yield.
1
2595.
3
. For selected examples of catalytic Beckmann rearrange-
ment, see: (a) Narasaka, K.; Kusama, H.; Yamashita, Y.;
Sato, H. Chem. Lett. 1993, 489; (b) Ichihashi, H.;
Kitamura, M. Catal. Today 2002, 73, 23; (c) Yadav, J.
S.; Reddy, B. V. S.; Madhavi, A. V.; Ganesh, Y. S. S. J.
Chem. Res. (S) 2002, 236; (d) Srinvas, K. V. N. S.; Reddy,
E. B.; Das, B. Synlett 2002, 625; (e) Ikushima, Y.; Sato,
O.; Sato, M.; Hatakeda, K.; Arai, M. Chem. Eng. Sci.
1
0 1
Typical example: Acetanilide (Table 1, entry 1) 2.
H
NMR (500 MHz, CDCl ): d 2.17 (s, 3H), 7.10 (t,
3
J = 7.4 Hz, 1H), 7.30–7.35 (m, 3H), 7.50 (d, J = 8.0 Hz,
2H).