Synthesis of N-alkylimidazolium salts and their utility as solvents in the Beckmann rearrangement

Article abstract of DOI:10.1016/j.tetlet.2007.10.051

Six different room temperature ionic liquids (RTILs) based on N-methyl or N-isopropyl imidazolium cations with counteranions, such as BF₄^-, PF₆^-, and OTf^-, have been synthesized by exchanging the counteranions of the corresponding N-methyl or N-isopropylimidazolium bromides using appropriate salts such as NH₄BF₄, KPF₆, and AgOTf. Catalytic amounts of these ionic liquids (ILs) have been used as the reaction medium for the Beckmann rearrangement of oximes to amides in the presence of PCl₅. A moderate to good conversion of oximes to amides in all the six ILs was observed.

Full text of DOI:10.1016/j.tetlet.2007.10.051

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Tetrahedron Letters 48 (2007) 9059–9062
Synthesis of N-alkylimidazolium salts and their utility
as solvents in the Beckmann rearrangement
Kandasamy Elango, Renganathan Srirambalaji and Ganapathi Anantharaman*
Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208 016, India
Received 5 July 2007; revised 4 October 2007; accepted 11 October 2007
Available online 14 October 2007
Abstract—Six different room temperature ionic liquids (RTILs) based on N-methyl or N-isopropyl imidazolium cations with count-
eranions, such as BF4ꢀ, PF6ꢀ, and OTfꢀ, have been synthesized by exchanging the counteranions of the corresponding N-methyl or
N-isopropylimidazolium bromides using appropriate salts such as NH4BF4, KPF6, and AgOTf. Catalytic amounts of these ionic
liquids (ILs) have been used as the reaction medium for the Beckmann rearrangement of oximes to amides in the presence of
PCl5. A moderate to good conversion of oximes to amides in all the six ILs was observed.
Ó 2007 Elsevier Ltd. All rights reserved.
The conversion of ketoximes to amides is known as the
Beckmann rearrangement and is an important method
for the synthesis of various N-substituted amides.
Amides, in general, are potential precursors for the syn-
thesis of various natural products as well as synthetic
intermediates for medicinal drugs and materials. For
instance, e-caprolactam, has been synthesized industri-
ally through Beckmann rearrangement of cyclohexa-
none oxime.1,2 In general, these reactions are carried
out in Brønsted acids, such as H2SO4 and SOCl2, at high
H
BF4
N
NH4BF4 ,CH2Cl2
3 h, RT, -NH4Br
H
1b, 2b
N
R
H
H
N
tBuBr
Toluene
Br
PF6
N
N
N
KPF6, CH2Cl2/CH3OH (5:1)
3 h, RT, -KBr
H
H
1c, 2c
1d, 2d
16 h, 80 °C
-C4H8
N
N
R
R
1a, 2a
R
R
H
N
R = Me (1a), iPr (2a)
OTf
AgOTf
H
CH2Cl2/CH3OH (5:1)
3 h, RT, -AgBr
N
Scheme 1. Synthesis of N-alkylimidazolium salts.
Keywords: N-Methylimidazolium bromide; N-Isopropylimidazolium bromide; Room temperature ionic liquids (RTILs); Anion exchange; Reaction
medium; Beckmann rearrangement; e-Caprolactam.
*
Corresponding author. Tel.: +91 512 2597517; fax: +91 512 2597436; e-mail: garaman@iitk.ac.in
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.10.051

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K. Elango et al. / Tetrahedron Letters 48 (2007) 9059–9062
temperatures (130 °C).3 However, a large amount of
NH4OH is necessary to neutralize the acid, which leads
to the formation of (NH4)2SO4 as a byproduct. Thus, to
avoid corrosion and generation of waste, an alternative,
mild route is required and hence Beckmann rearrange-
ments were studied both in organic liquids and in
vapor-phase media. Vapor-phase processes have been
carried out using solid catalysts such as metal oxides,
zeolites and clays at high temperatures close to 300 °C.
During these experiments a large amount of coke forma-
tion leading to deactivation of the catalysts was
observed.4 A few examples of solvent-free organo cata-
lyzed Beckmann rearrangements have been reported.5
Beckmann rearrangements in liquid-phase using cata-
lysts such as sulfamic acid, cyanuric chloride, lanthanide
triflate, BOP-Cl [bis(2-oxo-3-oxazolidinyl)phosphinic
chloride] and RuCl3 in organic solvents such as DMF
and acetonitrile, as well as in supercritical water, have
been carried out.6 An advantage of this method is that
a high conversion of oximes with very good selectivity
has been observed. Although several conversions of
oximes to the corresponding amides have been studied,
a mild and environmentally benign route for the conver-
sion of cyclohexanone oxime to e-caprolactam as well as
the separation of this product from the reaction mixture
is difficult to achieve.
Recently RTILs have been widely used as green solvents
for various organic syntheses.7 Deng et al. and others
have carried out the Beckmann rearrangements of
oximes to amides using Lewis acidic RTILs based on
N,N0-dialkylimidazolium salts or n-butylpyridinium tet-
rafluoroborate in the presence of PCl5, P2O5, or H3BO3
as catalyst, which showed high conversions and selecti-
vity, especially for e-caprolactam.8 However, the separa-
tion of e-caprolactam from the reaction mixture was
difficult due to its recombination with the Lewis acidic
RTILs.8d One of the advantages of imidazolium based
RTILs is the possibility of tuning the physical and chem-
ical properties with respect to the substituent on the
nitrogen centers of the imidazolium cations as well as
the counteranions. Recent studies have also indicated
that the solubility of the imidazolium salts in polar
solvents depends upon the nature of the counteranions,
which play an important role.9 The key would be to
design a suitable ionic liquid, which is soluble in water,
but immiscible with organic solvents, so that the organic
products can be extracted using organic solvents. Com-
pared to Lewis acidic ionic liquids, the solubility of
Brønsted acidic ionic liquids in water would be greater
and hence the latter would be the better choice of
solvent to separate the products from the reaction
mixtures. Recently, it has been demonstrated that
Brønsted acidic RTILs based on N-alkylimidazolium
salts have been successfully used as reaction media,
which promote reactions without the need of any addi-
tional catalyst and the final products were separated
using simple extraction. Examples include protection
of carbonyls as ketals/acetals, preparation of 2,4,5 tri-
arylimidazoles, esterification reactions, and the synthesis
of b-enaminones.10 Further, the use of a caprolactum-
based ionic liquid shows better conversion of cyclohex-
anone oxime and moderate to good isolated yields of

K. Elango et al. / Tetrahedron Letters 48 (2007) 9059–9062
9061
e-caprolactam were obtained. However, when the same
reaction was carried out using N-methylimidazolium
tetrafluoroborate as catalyst and solvent, the conversion
of the cyclohexanone oxime was only 44% with 33%
selectivity.8d
methanol, and ethanol (but not in n-butanol), and the
aprotic solvents, DMSO and DMF; however, they were
not soluble in the common organic solvents, toluene,
THF, CH2Cl2 and CHCl3. ILs 1a and 2a were soluble
in polar protic, aprotic solvents and also soluble in
CH2Cl2 and CHCl3.
We have synthesized an RTIL based on N-methylimida-
zolium bromide from N-methylimidazole and tert-butyl
bromide.11 Since we have been interested in studying the
utility of ILs as green solvents in various organic trans-
formations as well as in the synthesis of coordination
polymers; we have prepared six room temperature ionic
1
All the ILs (1b–1d and 2a–2d) were characterized by H
and 13C NMR and also by high resolution mass spec-
trometry (Table 1). In the H NMR, the 2-CH proton
1
falls in the range of 9.09–9.47 ppm. Moreover positive
ion ESI-MS+ gave the corresponding cationic
([MꢀX]+) peak for both N-methylimidazolium (1b–d)
and N-isopropylimidazolium (2a–d) salts. All the ILs,
except 1a and 2a, were used as reaction media in the
Beckmann rearrangement (Scheme 2).
liquids (RTILs) based on N-methyl or N-isopropylimi-
ꢀ
dazolium cations with counteranions, including BF4
,
PF6ꢀ, and OTf ꢀ. Herein we report the synthesis of N-
alkylimidazolium salts (1b–d and 2a–d; Scheme 1) and
their utility as reaction media in the Beckmann rear-
rangement in the presence of PCl5 as catalyst. The solu-
bility of ionic liquids 1b–d and 2b–d was very high in
polar protic/aprotic solvents but they were immiscible
with common organic solvents, which is indeed helpful,
especially when recovering the product from the reac-
tion mixture.
A
mixture of PCl5 (20 mmol %), ionic liquid
(20 mmol %) and oxime (2 mmol) was stirred for 3 h at
80 °C under an inert atmosphere.14 Then water
(10 mL) and CH2Cl2 (20 mL) were added. The organic
phase was separated and the aqueous phase was washed
with CH2Cl2 (x 3). The combined organic layers were
dried over anhydrous magnesium sulfate, and the sol-
vent was removed under vacuum. All the products were
characterized by 1H NMR spectroscopy. The yields
N-Alkylimidazolium salts are, in general, prepared by
mixing the N-alkylimidazole with the corresponding
protic acids.10e In contrast we have obtained N-methyl-
imidazolium bromide by the treatment of commercially
available N-methylimidazole with tert-butyl bromide at
elevated temperature. During the reaction, tert-butyl
bromide releases a molecule of HBr (with evolution of
isobutene gas), which further reacts with N-methylimid-
azole, to form N-methylimidazolium bromide (1a).12
Following the same method, we also prepared N-isopro-
pylimidazolium bromide (2a) starting from N-isopropyl-
imidazole. Treatment of 1a and 2a with salts such as
NH4BF4, KPF6, and AgOTf afforded the corresponding
N-alkylimidazolium salts containing different anions
(1b–d and 2b–d; Table 1).13 The ILs 1b–d and 2b–d
were soluble in polar protic solvents, including water,
1
were determined from the H NMR spectra, whereas
e-caprolactam was isolated and then crystallized
from EtOAc/pet ether (10:1), and its yield calculated
(Table 2).
From Table 2, it is evident that good yields of N-phenyl-
acetamide were obtained in all the ILs. However, the
rearrangement of dicyclopropyl ketoxime in ILs 1c
20% mmol RTIL
OXIME
AMIDE
20% PCl5, 80 °C and 3 h
Scheme 2. Beckmann rearrangement of oximes in ILs.
Table 2. Beckmann rearrangement of oximes in ILs 1b–d and 2b–d
Entry
Reactant
Producta
Yieldb (%)
1b
1c
1d
2b
2c
2d
O
NOH
1
80
74
69
85
83
71
Ph
Me
N
Me
Ph
H
NOH
O
2
3
31
65
43
54
66
56
N
H
O
NOH
65c
61c
42c
48c
78c
31c
NH
a Products were confirmed by 1H NMR.
b Yields are based on 1H NMR.
c Isolated yield.

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K. Elango et al. / Tetrahedron Letters 48 (2007) 9059–9062
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and 2c gave the best product yields compared to the
other ILs. The rearrangement of cyclohexanone oxime
was also carried out in all the ILs. The yield of e-capro-
lactam was high (78%) only when N-isopropylimidazoli-
um hexafluorophosphate (2c) was used. The isolation of
e-caprolactam was easier from 2c, which may be due to
the high solubility of this IL compared to e-caprolactam
in water. In the other cases, both the IL and e-
caprolactam were highly soluble in water, and hence
separation was difficult.
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In conclusion, an alternative method for the preparation
of N-isopropylimidazolium bromide has been reported.
The Beckmann rearrangement of three different ketoxi-
mes has been investigated using different ILs. The yields
were good for the rearrangement of acetophenone oxime
in all six ILs, whereas with dicyclopropyl ketoxime and
cyclohexanone oxime, good yields were obtained only
with N-isopropylimidazolium hexafluorophosphate.
Acknowledgements
The authors thank the Department of Chemistry and
the Indian Institute of Technology, Kanpur for infra-
structure and financial support.
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Supplementary data
9. Seddon, K. R.; Stark, A.; Torres, M. Pure Appl. Chem.
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ESI mass spectra for all ionic liquids are available. Sup-
plementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2007.10.051.
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tert-butyl bromide (6.85 g, 50 mmol) was added to a
toluene (100 mL) solution of N-isopropylimidazole
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80 °C for 16 h. The immiscible layers were separated by
decanting the toluene and the sticky product was washed
with hexane and dried under vacuum.
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General procedure for the synthesis of ILs (1b–d and 2b–d):
Ammonium tetrafluoroborate, potassium hexafluorophos-
phate, or silver triflate (15 mmol) was added to a solution
of 1a or 2a (15 mmol) in CH2Cl2 (25 mL)/CH3OH (5 mL).
The resulting mixture was stirred at room temperature for
3 h. The solution was cooled to ꢀ20 °C, filtered and the
volatiles were removed from the filtrate under vacuum to
afford the respective ionic liquids.
14. Prior to the Beckmann rearrangement, all the ionic liquids
were subjected to vacuum for half an hour to ensure
complete removal of water.