Cyclopropenium ion catalysed Beckmann rearrangement

Article abstract of DOI:10.1039/c0cc00815j

1-Chloro-2,3-diphenylcyclopropenium ion was found to be a very efficient organocatalyst (3 mol% loading) for liquid phase Beckmann rearrangement of various ketoximes to the corresponding amides/lactams within 2 h in acetonitrile at reflux temperature. This is the first example of the application of the cyclopropenium ion as a catalyst, which opens up a new aspect of the synthetic utility of aromatic cation based catalysis.

Full text of DOI:10.1039/c0cc00815j

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Cyclopropenium ion catalysed Beckmann rearrangementw
Vishnu P. Srivastava, Rajesh Patel, Garima and Lal Dhar S. Yadav*
Received 7th April 2010, Accepted 8th June 2010
DOI: 10.1039/c0cc00815j
1
-Chloro-2,3-diphenylcyclopropenium ion was found to be a very
efficient organocatalyst (3 mol% loading) for liquid phase
Beckmann rearrangement of various ketoximes to the corres-
ponding amides/lactams within 2 h in acetonitrile at reflux
temperature. This is the first example of the application of the
cyclopropenium ion as a catalyst, which opens up a new aspect of
the synthetic utility of aromatic cation based catalysis.
¨
The cyclopropenium ion is the smallest member of the Huckel
aromatic systems (aromatic cations), the first example of
which was, triphenylcyclopropenylium perchlorate, prepared
1
by Breslow in 1957. Extensive subsequent investigations have
Scheme 1 Cyclopropenium ion catalysed Beckmann rearrangement.
been carried out by Breslow and others that revealed much
about the unusual properties of this remarkable class of
2
molecules. Despite the apparent molecular strain inherent in
5
their corresponding oximes since its discovery in 1886.
6
After Chandrasekhar and Gopalaiah reports focused on
such a small ring with two p-electrons delocalized over
three 2p orbitals, this type of cation is now known to have
considerable thermodynamic stability, possessing the dual
properties of aromatic stability and ionic charge. Thus, such
aromatic cations readily combine with an anion or a Lewis
basic heteroatom causing reversible generation of the corres-
ponding neutral carbocycles species (Fig. 1).
small organic molecule (oxalic acid and chloral) catalysed
BKR, organocatalytic liquid phase processes have attracted
researchers’ attention for their efficiency in catalytic activity
and easy handling during the rearrangement, and several
organocatalysts, especially phosphorus or sulfur based, have
7
been employed in organocatalytic liquid phase BKR. We
have also reported an organocatalytic green procedure for
The literature reports that aromatic cations are stable in
aqueous solution and they undergo reversible hydrolysis even
3
up to pH 10. These interesting characteristics of aromatic
BKR using bromodimethylsulfonium bromide (BDMS) in
8
ionic liquid [bmim]PF .
6
In this continuation, attracted by the unique reactivity
2a
profile of the cyclopropenium ion and knowing the fact that
cations make them suitable as a promoter for reactions involving
dehydration or activation of a Lewis basic heteroatom.
Very recently, Lambert et al. have implemented a novel
strategy for conversion of alcohols and carboxylic acids to
alkyl halides and acyl halides, respectively, based on aromatic
liquid phase BKR usually proceeds under the conditions of
electrophilic activation of the oxime hydroxyl group, we
reasoned that cyclopropenium ion might be a well suited
electrophilic species for activation of the oxime hydroxyl
group facilitating the transformation of ketoximes into amides/
lactams. This envisaged protocol employing a cyclopropenium
ion as a catalyst, instead of typically used sulfur- or phosphorus-
based catalysts, would be a significant advance in organo-
catalytic liquid phase BKR. A preliminary examination of
feasibility of cyclopropenium ion catalysed BKR and to screen
the optimal catalytic system using 4-methoxyacetophenone
oxime as a model substrate in various conditions is compiled
in Table 1. To our amazement, we observed a rapid and
selective conversion (up to 96%) of 4-methoxyacetophenone
oxime to N-(4-methoxyphenyl)acetamide using a catalytic
4
cation activation. Herein, we report the first example of
cyclopropenium ion catalysis illustrating its organocatalytic
utility in Beckmann rearrangement using 3,3-dichloro-1,2-
diphenylcyclopropene as the precursor of the cyclopropenium
ion (Scheme 1).z
The Beckmann rearrangement (BKR) has become a
powerful tool in the syntheses of amides and lactams from
9
amount (5 mol%) of 3,3-dichloro-1,2-diphenylcyclopropene
2
in acetonitrile (CH CN) at reflux temperature (Table 1, entry 2).
3
As evident from Table 1, use of ZnCl as a cocatalyst further
2
Fig. 1 Cyclopropenium ion.
enhances the catalytic activity of 2, thus BKR proceeds well
with excellent conversion and selectivity (up to 100%) using
Department of Chemistry, University of Allahabad-211 002,
Allahabad, India. E-mail: ldsyadav@hotmail.com;
Fax: +91 5322460533; Tel: +91 5322500652
w Electronic supplementary information (ESI) available: Characteri-
sation data for all compounds. See DOI: 10.1039/c0cc00815j
3 mol% of each 2 and ZnCl
other Lewis acids as cocatalysts, namely, InCl
MgCl , and CuCl did not show any significant superiority
over ZnCl
(Table 1, entry 5). The use of
2
3
, FeCl , SnCl ,
3
4
2
2
2
(Table 1, entries 15–19).
5
808 | Chem. Commun., 2010, 46, 5808–5810
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Table 1 Optimisation of conditions for cyclopropenium ion catalysed
Beckmann rearrangement of 4-methoxyacetophenone oxime
Table 2 Generality and scope of cyclopropenium ion catalysed
Beckmann rearrangement
a
a
Cocatalyst
2 (mol%) (mol%)
Conv. Select.
b c
Entry Solvent
T (1C) (%) (%)
Yield
(%)
1
2
b
Entry
R
R
Time (h)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
CH
CH
CH
CH
CH
CH
CH
3
3
3
3
3
3
3
CN
CN
CN
CN
CN
CN
NO
(10)
(5)
(3)
(3)
(3)
—
(3)
(3)
(3)
—
—
—
—
—
—
Reflux 96
Reflux 96
Reflux 90
99
99
99
99
99
—
99
—
47
—
—
60
20
50
80
96
70
68
80
80
—
1
2
3
4
5
6
7
8
Ph
2-(MeO)C H
6
3-(MeO)C H
6
4-(MeO)C H
2-(Cl)C H
6
Ph
2-Naphthyl
Ph
4-(F)C H
4-(MeO)C H
6
PhCH2
i-Pr
Me
Me
Me
Me
Me
Et
Me
Ph
Ph
Ph
2
1
1
1
2
1.5
2
1.5
2
1
2
2
2
2
2
2
2
98
98
94
99
96
94
95
94
6
4
4
4
ZnCl
ZnCl
ZnCl
ZnCl
ZnCl
ZnCl
ZnCl
ZnCl
ZnCl
HCld
HCl +ZnCl
InCl
FeCl
SnCl
2
2
2
2
2
2
2
2
2
(5) Reflux 100
(3) Reflux 100
(3) Reflux —
4
2
(3) 82
92
THF
DCE
(3) Reflux 40
(3) Reflux 60
c
0
1
2
3
4
5
6
7
8
9
0
1
1,4-dioxane (3)
(3) 82
(3) 82
45
30
9
86
89
6
4
d
Toluene
Acetone
(3)
(3)
—
10
11
12
13
14
15
16
17
4
(3) Reflux 20
(3) Reflux 10
(3) Reflux 30
(3) Reflux 94
(3) Reflux 80
(3) Reflux 20
(3) Reflux 40
(3) Reflux 30
PhCH2
i-Pr
Me
91
94
96
94
96
29
18
d
CH
CH
CH
CH
CH
CH
CH
3
3
3
3
3
3
3
CN
CN
CN
CN
CN
CN
CN
e
—
2
C H
8
17
(3)
(3)
(3)
(3)
(3)
(3)
(3)
3
(CH2)11
(CH2)9
(CH2)7
(CH2)5
3
4
MgCl
CuCl
—
2
2
a
Ketoximes 1 (1 mmol) were used for BKR in anhydrous CH
3 mL) in the presence 3,3-dichloro-1,2-diphenyl cyclopropene 2
3
CN
[bmim]PF
[bmim]BF
6
—
—
82
82
20
—
(
(
4
—
b
c
2
3 mol%) and ZnCl (3 mol%). Isolated yield. Syn/anti isomeric
a
Reaction conditions: 165 mg (1 mmol) 4-methoxyacetophenone
b
oxime, solvent (3 mL). Conversion (%) of 4-methoxyacetophenone
c
oxime as determined by GC analysis. Selectivity for 4-methoxy-
mixture of oxime in the ratio of 0.8 : 1.0 was used: N-(4-fluoro-
phenyl)benzamide and 4-fluoro-N-phenylbenzamide were obtained
d
in the ratio of 0.8 : 1.0. Syn/anti isomeric mixture of oxime in the
ratio of 1.0 : 0.7 was used: N-(4-methoxyphenyl)benzamide and
d
e
acetanilide. 4 M HCl solution in 1,4-dioxane was used. Mol% of
each cocatalyst.
4
1
-methoxy-N- phenylbenzamide were obtained in the ratio of
.0 : 0.7.
A competitive rearrangement experiment of 4-methoxy-
acetophenone oxime using 3 mol% HCl solely or in combina-
7
a
conformity with cyanuric chloride catalysed BKR (Table 2,
entries 16 and 17).
2
tion with ZnCl (3 mol%) gave unsatisfactory results ruling
out the possibility of a potential acid HCl (generated in situ by
the reaction of 3,3-dichloro-1,2-diphenylcyclopropene 2 with
ketoxime 1) catalysed pathway (Table 1, entries 13 and 14),
supporting the notion that the cyclopropenium intermediate is
in fact responsible for activation. The solvent effects on the
transformation were also studied (Table 1, entries 5 and 7–12).
Polar and nucleophilic solvents such as CH CN and CH NO
Based on the hypothesis for new generation organocatalytic
7a
BKR by Ishihara and co-workers, a plausible catalytic cycle
for the present cyclopropenium ion catalysed BKR is outlined
in Scheme 2. Under the present reaction conditions, the
formation of a 2,3-diphenylcyclopropenone 4 or immidoyl
chloride 5 is not observed (Scheme 2) and the reaction works
well with a catalytic amount (3 mol%) of the pre-catalyst
(3,3-dichloro-1,2-diphenylcyclopropene 2). This supports the
proposed catalytic cycle.
3
3
2
(
Table 1, entries 5 and 7) were suitable for this catalysis. In
7
b,8
light of earlier reports,
we have also performed the
cyclopropenium ion catalysed BKR in ionic liquids bmim[BF
4
]
In conclusion, we have developed a new organocatalytic
system for the transformation of ketoximes to amides/lactams
based on a novel paradigm for activation of oxime hydroxyl
group by making use of a simple, sterically and electronically
tunable carbon moiety 3,3-dichloro-1,2-diphenylcyclopropene
as organocatalyst instead of the phosphorus- or sulfur-based
catalysts typically used for such purposes. The present work
opens up a new aspect of the synthetic utility of aromatic
cation based catalysis.
and bmim[PF ] without using any cocatalyst. However,
6
it gave unsatisfactory results (Table 1, entries 20 and 21). To
explore the generality and scope of cyclopropenium ion
catalysed BKR, various ketoximes were examined as sub-
strates under reflux conditions in acetonitrile (Table 2). It is
obvious that excellent yields (86–99%) were obtained for both
aromatic as well as aliphatic ketoximes under the present
catalytic system within 2 h. Large cycloalkanone oximes
were also very reactive and were transformed to the corres-
ponding lactams, which were useful as starting materials for
We sincerely thank SAIF, Punjab University, Chandigarh,
for providing microanalyses and spectra. R. P. and Garima are
grateful to the CSIR, New Delhi, for the award of a Junior
Research Fellowship.
1
0
nylons. Unfortunately, cyclooctanone and cyclohexanone
oximes gave the desired lactams in poor yields showing
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Scheme 2 A plausible catalytic cycle for cyclopropenium ion catalysed Beckmann rearrangement.
Notes and references
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4
z General procedure: to a solution of ketoxime 1 (1 mmol) in dry
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acetonitrile (3 mL), 3,3-dichloro-1,2-diphenylcyclopropene 2 (3 mol%)
2
and ZnCl (3 mol%) were added at rt and the reaction mixture was
heated at reflux under a nitrogen atmosphere for 1–2 h (Table 2). After
completion of the reaction as indicated by TLC, the mixture was
quenched with saturated aqueous sodium hydrogen carbonate (10 mL)
and extracted with ethyl acetate (3 ꢁ 10 mL). The organic phase was
dried over anhydrous magnesium sulfate and concentrated in vacuo to
yield the crude product, which was purified by silica gel column
chromatography (EtOAc–hexane) to give the corresponding amide.
The structure of the products was confirmed by comparison of their
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