Beckmann rearrangement of oximes using doped silica gel complex

Article abstract of DOI:10.14233/ajchem.2015.17170

A new complex of perchloric acid absorbed on silica gel (doped silica gel) and dichloromethane was found to be very effective for converting ketoximes into their corresponding amides or lactams with excellent conversion via the Beckmann rearrangement. This method offers significant advantages such as efficiency and mild reaction conditions with shorter reaction time.

Full text of DOI:10.14233/ajchem.2015.17170

Asian Journal of Chemistry; Vol. 27, No. 4 (2015), 1209-1211
A
SIAN
J
OURNAL OF HEMISTRY
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http://dx.doi.org/10.14233/ajchem.2015.17170
Beckmann Rearrangement of Oximes Using Doped Silica Gel Complex
1
2
1
Y. UMANADH1,2,*, N. SRINIVASA REDDY , KHAGGA MUKKANTI and G. OMPRAKASH
1Pharma Zell R&D (India) Private Limited, Visakhapatnam-531 162, India
2Institute of Science & Technology, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad-500 072, India
*Corresponding author: E-mail: yepuri.umanath@gmail.com
Received: 5 February 2014;
Accepted: 10 May 2014;
Published online: 4 February 2015;
AJC-16758
A new complex of perchloric acid absorbed on silica gel (doped silica gel) and dichloromethane was found to be very effective for
converting ketoximes into their corresponding amides or lactams with excellent conversion via the Beckmann rearrangement. This method
offers significant advantages such as efficiency and mild reaction conditions with shorter reaction time.
Keywords: Doped silica gel/dichloromethane, Beckmann rearrangement, Ketoximes, Amides.
large amounts of basic neutralization agent has to be used,
which lead to the large amounts of byproducts. Therefore, it
is necessary to develop a green, simple and low-cost catalyst
system for Beckmann rearrangement of ketoxime.
Therefore, the development of a sulfate-free, green and
simple system for Beckmann rearrangement of ketoximes, has
been of interest to organic chemists. The search for improved
conditions for the rearrangement of ketoximes to the corres-
ponding amides essentially involves a search for an efficient mild
electrophilic reagent and herein we wish to report a simple and
efficient protocol for the Beckmann rearrangement using perchloric
acid adsorbed on silica gel and DCM complex (Scheme-I).
INTRODUCTION
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 C-C bond and the
formation of a C-N bond and represents a powerful method
particularly for manufacture ε-caprolactam in chemical
industry1-2.
The Beckmann rearrangement of oximes to lactams is a
very important commercial process for the production of raw
material of polyamides such as nylon-6 and nylon-123. Currently,
the Beckmann rearrangement is carried out using oleum as a
catalyst, which results in undesired sulfates as by-products
and requires a large amount of a strong acid such as sulfuric
acid4. Until now the mild conditions were related to the forma-
tion of activation of oxime derivatives followed by rearrange-
ment, for example, using chloral5, anhydrous oxalic acid6,
sulfamic acid7, chlorosulfonic acid8, cyanuric chloride/DMF9,
ethyl chloroformate/boron trifluoride etherate10, etc.Although
various protocols have been reported11, they have their own
drawbacks such as the use of toxic solvents, expensive reagents,
formation of undesired by products, prolonged reaction
timings, tedious workup procedures and low yields12.
Nevertheless, until now the occurrence of mild conditions
was only related to the use of rather toxic and expensive reagents
and homogeneous catalyst system. On the other hand, the
problem, which is almost common to homogeneous catalyst
system, is that it is very difficult to separate the product from
the resulting mixtures, in order to obtain a neat desired product
OH
O
R1 NH
HClO4 - SiO2
DCM, r.t.
N
R
R
R1
R & R1 = alkyl or aryl
Scheme-I: General scheme
The search for improved conditions for the Beckmann
reaction essentially involves a search for new electrophilic
reagents with the desired characteristics of mildness, etc. (The
reaction occurs under conditions of electrophilic activation of
the oxime hydroxyl group1) Generally, a variety of Brønsted
and strong Lewis acids have been employed as reagents, e.g.,
p-toluenesulphonic acid, SnCl4, PCl5, etc. However, mild Lewis
acids have hardly ever been reported to the best of our know-
ledge. It was of interest to investigate the possible use of
pivaloyal chloride in view of its ready availability and known
Lewis acidic properties.

1210 Umanadh et al.
Asian J. Chem.
N-(4-Methoxyphenyl)acetamide (7): m.p. 128-129 °C;
1H NMR (300 MHz, DMSO-d6): δ 8.52 (bs, 1H), 7.48 (d, 2H),
6.69 (d, 2H), 3.54 (s, 3H), 2.07 (s, 3H); 13C NMR: 169.3, 154.5,
133.1, 122.4, 122.2,113.9, 113.5, 53.8,22.7. MS (CI): m/z 166
[M·+ + 1] [ Found: C, 65.55; H, 6.65; N, 8.52, C9H11NO2 requires
C, 65.44; H, 6.71; N, 8.48].
EXPERIMENTAL
All the reagents used in this work were obtained from
commercial suppliers. Solvents were freshly distilled before
being used. Melting points were determined using a Buchi
melting point apparatus and are uncorrected. The progress of
the reaction was monitored by thin-layer chromatography
(TLC) performed on silica gel G (Merck) and spots were
exposed to iodine vapour or UV light. IR spectra were recorded
by using KBr disc on a Perkin-Elmer 240c analyzer. 1H NMR
spectra were recorded on Brucker DPX-400 at 400 MHz
(chemical shifts in d, ppm) and Mass spectra on an Agilent
LC-MS instrument giving only M+ values in Q + 1 mode.
General procedure for conversion of ketoximes to
acetamides with doped silica gel and DCM complex: To
the mixture of HClO4-SiO2 (doped silica gel) (1.3 mmol) and
DCM (5 mL) added the solution of ketoxime (0.1 g, 0.66 mmol)
in DCM (5 mL) at room temperature. The reaction was moni-
tored (TLC) until the complete disappearance of starting
material. Water (10 mL) was added and then the organic phase
was washed with 2.5 mL of a saturated solution of NaHCO3,
followed by 1 N HCl and brine. The organic layers were dried
over Na2SO4 and the solvent evaporated to yield acetamide.
N-(4-Hydroxyphenyl)acetamide (1): m.p. 167-168 °C;
1H NMR (300 MHz, DMSO-d6): δ 9.39 (bs, 1H), 8.92 (s, 1H),
7.55 (d, 2H), 6.95 (d, 2H), 2.04 (s, 3H); 13C NMR: 168.4, 153,
130.1, 121.7, 115.4, 24.2. MS (CI): m/z 152 [M·+ + 1] [ Found:
C, 63.98; H, 5.99; N, 9.03; C8H9NO2 requires C, 63.56; H,
6.00; N, 9.27].
N-(3-Hydroxyphenyl)acetamide (2): m.p. 147-149 °C;
1H NMR (300 MHz, DMSO-d6): δ 9.23 (bs, 1H), 8.94 (s, 1H),
7.33 (m, 1H), 7.05 (t, 1H), 6.89 (d, 1H), 6.54 (d, 1H), 2.08 (s,
3H); 13C NMR: 169.1, 157.5, 139.6, 129.3, 113, 110.7, 107.2,
24.2. MS (CI): m/z 152 [M·+ + 1] [ Found: C, 63.52; H, 6.17;
N, 9.09; C8H9NO2 requires C, 63.56; H, 6; N, 9.27.
N-(2-Hydroxyphenyl)acetamide (3): m.p. 208-209 °C;
1H NMR (300 MHz, DMSO-d6): δ 9.03 (bs, 1H), 8.69 (s, 1H),
7.48 (d, 1H), 7.02 (t, 2H), 6.85 (d, 1H), 2.24 (s, 3H); 13C NMR:
169.5, 147.5, 126.9, 125.6, 123.1, 121.2, 116.6, 22.8. MS (CI):
m/z 152 [M·+ + 1] [ Found: C, 63.27; H, 6.13; N, 9.11; C8H9NO2
requires C, 63.56; H, 6; N, 9.27].
1
N-(2-Nitrophenyl)acetamide (8): m.p. 92-94 °C; H
NMR (300 MHz, DMSO-d6): δ 9.94 (bs, 1H), 8.14 (d, 1H),
7.72 (d, 1H), 7.63 (t, 1H), 7.38 (t, 1H), 2.16 (s, 3H); 13C NMR:
169.1, 141.3, 135.6, 134.9, 126.5, 124.2, 121.4, 23.2. MS (CI):
m/z 181 [M·+ + 1] [Found: C, 53.29; H, 4.50; N, 15.62; C8H8N2O3
requires C, 53.33; H, 4.48; N, 15.55].
N-(3-Nitrophenyl)acetamide (9): m.p. 155-156 °C; 1H
NMR (300 MHz, DMSO-d6): δ 8.82 (bs, 1H), 8.20 (s, 1H),
8.04 (d, 1H), 7.94 (d, 1H), 7.52 (t, 1H), 2.09 (s, 3H); 13C NMR:
170.1, 148.3, 138.5, 128.9, 126.5, 116.2, 115.4, 22.7. MS (CI):
m/z 181 [M·+ + 1] [Found: C, 53.35; H, 4.49; N, 15.56, C8H8N2O3
requires C, 53.33; H, 4.48; N, 15.55].
3,4-Dihydro-2(1H)-quinolone (10): m.p. 165-166 °C; 1H
NMR (300 MHz, DMSO-d6): δ 8.82 (bs, 1H), 7.53 (d, 1H),
7.09 (d, 1H), 7.07 (t, 1H), 6.91 (t, 1H), 2.90 (t, 2H), 2.51 (t,
2H); 13C NMR: 170.1, 137.3, 131.5, 128.9, 126.5, 124.2, 121.4,
29.7, 26.3. MS (CI): m/z 148 [M·+ + 1] [Found: C,
73.39; H, 6.09; N, 9.66; C9H9NO requires C, 73.45; H, 6.16;
N, 9.52].
RESULTS AND DISCUSSION
Herein we wish to present our results for a very mild and
efficient conversion of ketoxime into corresponding amide.
In a typical experimental procedure doped silica gel and DCM
are mixed together to form a complex which is found to be
reactive, leading to Beckmann rearrangement when treated
with ketoximes. Classical Beckmann rearrangement generally
requires high reaction temperatures and strongly acidic and
dehydrating media13. But what we observed is that when we
use doped silica gel and DCM complex reaction proceeds in
room temperature without need of strong acids and dehydrating
conditions.
The doped silica gel complex14 added to stirring solution
of ketoxime in DCM at room temperature. Reaction was
monitored by TLC, water was added and then the organic phase
was washed with saturated solution of sodium carbonate
followed by 1 N HCl solution and brine. The corresponding
amides were recovered chemically pure in high yields.
To understand the scope and applicability of this reagent
for Beckmann rearrangement, various substrates were scanned
(Table-1) and observed that when electron releasing or with-
drawing group is in ortho or para position of aromatic ring
reaction proceeds for longer time (6-12 h).
A possible explanation for reaction mechanism is
discussed in Scheme-II. Addition of proton from perchloric
acid to oxime followed by removal of water. In the transition
state leading to the iminium ion (σ-complex), the methyl group
migrates to the nitrogen atom in a concerted reaction and the
hydroxyl group is expulsed. In the next step the electrophilic
carbon atom in the nitrilium ion is attacked by water and the
proton is donated back to perchloric acid. In the transition
state leading to the N-methyl acetimidic acid, the water oxygen
N-(4-Methylphenyl)acetamide (4): m.p. 148-150 °C; 1H
NMR (300 MHz, DMSO-d6): δ 9.03 (bs, 1H), 7.48 (d, 2H),
7.01 (d, 2H), 2.24 (s, 3H), 2.09 (s, 3H); 13C NMR: 169.5, 134.5,
133.1, 128.6, 128.2,121.2, 120.9, 23.8,22.6. MS (CI): m/z 150
[M·+ + 1] [Found: C, 72.55; H, 7.25; N, 9.54; C9H11NO requires
C, 72.46; H, 7.43; N, 9.39].
N-(4-Chlorophenyl)acetamide (5): m.p. 175-176 °C; 1H
NMR (300 MHz, DMSO-d6): δ 8.58 (bs, 1H), 7.48 (d, 2H),
7.12 (d, 2H), 2.09 (s, 3H); 13C NMR: 168.7, 134.5, 130.1,
128.6, 128.2,121.2, 120.9, 23.8. MS (CI): m/z 170 [M·+ + 1]
[Found: C, 56.72; H, 4.86; Cl, 20.88; N, 8.14, C8H8NOCl
requires C, 56.65; H, 4.75; Cl, 20.90; N, 8.26].
N-(4-Bromophenyl)acetamide (6): m.p. 165-168 °C; 1H
NMR (300 MHz, DMSO-d6): δ 8.68 (bs, 1H), 7.51 (d, 2H),
7.32 (d, 2H), 2.07 (s, 3H); 13C NMR: 169.7, 137.5, 131.7,
131.2, 123.4,123.2, 119.2, 23.8. MS (CI): m/z 215 [M·+ + 1]
[Found: C, 44.55; H, 3.81; Br, 37.12; N, 6.67, C8H8NOBr
requires C, 44.89; H, 3.77; Br, 37.33; N, 6.54].

Vol. 27, No. 4 (2015)
Beckmann Rearrangement of Oximes Using Doped Silica Gel Complex 1211
TABLE-1
CONVERSION OF KETOXIMES TO AMIDES
feature of this method is that use of perchloric acid adsorbed
silica gel/DCM as a mild, non-toxic and inexpensive reagent.
This method seems to be convenient with respect to other
existing reports and can be used as an alternative, which will
avoid tedious purifications or the use of toxic or expensive
reagents.
Reaction Conversion
time (h)
Entry
Oximes
N
Amides
(%)
O
OH
H N
1
12
98
OH
O H
O
H
R1
R1
N R
N R
N
N
OH
OH
HO
R1
O
H
HN
-H2O
N
H
N
2
3
6
98
90
R
R1
R
R
HO
HO
HO
O
HN
O
H2O
HO
11
R
O
HO
R1
R
N
H2O
N
-H
N
N
OH
HN
H
R1
R1
9
90
4
5
6
Scheme-II: Proposed mechanism
ACKNOWLEDGEMENTS
O
N
OH
HN
The authors are indebted to the authorities of Jawaharlal
Nehru Technological University, Hyderabad, India.
8
9
90
85
Cl
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Cl
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O
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HN
9
6
8
85
78
O2N
O2N
OH
H
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10
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isomerization step protonates the nitrogen atom leading to the
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Conclusion
In conclusion, a mild, general and efficient conversion of
oximes to corresponding amides has been developed. The key