Natural organic acids promoted Beckmann rearrangement: Green and expeditious synthesis of amides under solvent-free conditions

Article abstract of DOI:10.2478/s11696-013-0481-y

Naturally occurring organic acids are reported to be highly efficient promoters of the Beckmann rearrangement. Citric, oxalic, tartaric, malic, succinic, malonic, and fumaric acids efficiently promote the Beckmann rearrangement under solvent-free conditions and thermal and microwave irradiation. Tartaric acid was found to be the best promoter of the Beckmann rearrangement under conventional conditions as well as under microwave irradiation. Compared with conventional heating, microwave irradiation provides higher reaction rate and slightly higher yields.

Full text of DOI:10.2478/s11696-013-0481-y

Chemical Papers 68 (4) 575–578 (2014)
DOI: 10.2478/s11696-013-0481-y
SHORT COMMUNICATION
Natural organic acids promoted Beckmann rearrangement: Green
and expeditious synthesis of amides under solvent-free conditions
Sandeep Vasantrao Rohokale, Santosh Rajaram Kote,
Santosh Rangnath Deshmukh, Shankar Ramchandra Thopate*
Department of Chemistry, Ahmednagar College, Dr. John Barnabas Post Graduate School for Biological Studies,
Ahmednagar, Maharashtra, 414001, India
Received 1 April 2013; Revised 5 August 2013; Accepted 7 August 2013
Naturally occurring organic acids are reported to be highly efficient promoters of the Beckmann
rearrangement. Citric, oxalic, tartaric, malic, succinic, malonic, and fumaric acids efficiently promote
the Beckmann rearrangement under solvent-free conditions and thermal and microwave irradiation.
Tartaric acid was found to be the best promoter of the Beckmann rearrangement under conventional
conditions as well as under microwave irradiation. Compared with conventional heating, microwave
irradiation provides higher reaction rate and slightly higher yields.
ꢀ
c 2013 Institute of Chemistry, Slovak Academy of Sciences
Keywords: amides, Beckmann rearrangement, natural organic acids, oximes, solvent-free
Due to the growing concern over environmental
pollution, green chemistry has attracted an increasing
interest in recent years (Anastas & Williamson, 1998;
Matlack, 2001; Poliakoff & Anastas, 2001; DeSimone,
organic reactions generates toxic waste, also harmful
to the environment, and is another major source of
environmental pollution. The development of cheap,
naturally occurring, green acid catalyst could change
the traditional procedures into green ones, thus min-
imising chemical waste. Therefore, the use of naturally
occurring green acid catalysts under solvent-free con-
ditions would be a better solution to the environmen-
tal pollution.
A large number of organic acids with incredible
potential as green catalysts in synthetic organic trans-
formations exist in nature. These acids are nontoxic,
and readily and cheaply available. The biological and
pharmacological activities as well as the therapeutic,
cosmetic and nutritional potential of these acids and
their derivatives are well-known. However, despite the
fact that these acids are biodegradable and renewable
from nature, their synthetic potential as green cata-
lysts in organic reactions has been ignored to a large
extent, except for a few scattered reports in litera-
ture (Chandrasekhar & Gopalaiah, 2003; Suresh et al.,
2009; de Vasconcelos, 2012).
2
002). Intensive efforts have been focused on designing
and developing economical and environmentally be-
nign syntheses. Major environmental pollution is aris-
ing from the use of solvents since the amounts of sol-
vents used are usually much larger than the amounts
of reagents and products. Thus, the replacement of
conventional environmentally unfriendly organic sol-
vents, which are very volatile, harmful to the environ-
ment, and/or biologically incompatible, has attracted
many researchers. Ionic liquids and fluorinated sol-
vents have been used in organic synthesis, but their
use has its limits. Due to the toxicity of organic
solvents and the limitations of environmentally be-
nign solvents, the most promising approach is to per-
form organic reactions under solvent-free conditions.
Solvent-free reactions have received considerable at-
tention in recent years, not only due to ecological
and economical reasons, but also due to the simplicity
of reaction conditions, high yields and short reaction
times. The use of large quantities of acid catalysts in
As a part of an ongoing program related to the
development of a clean and eco-friendly acid catalyst,
*Corresponding author, e-mail: srthopate@gmail.com

5
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S. V. Rohokale et al./Chemical Papers 68 (4) 575–578 (2014)
Table 1. Screening of naturally occurring organic acid promoters of the Beckmann rearrangement of Ia under solvent-free
conditionsa
Conventional heating
Microwave heating
b
◦
Entry
Acid
Temperature / C
c
c
Time/min
Yield /%
Time/min
Yield /%
1
2
3
4
5
6
7
Citric
Fumaric
Malic
Malonic
Oxalic
Succinic
Tartaric
160
290
140
140
110
190
180
5
97
3
3
3
3
3
3
3
90
70
96
92
75
90
95
5
5
5
5
5
5
65
85
90
70
92
96
a) See Fig. 1; b) heating using a preheated oil bath or a microwave reactor; c) isolated yields.
we have reported citric acid as a highly efficient and
eco-friendly catalyst for the Beckmann rearrangement
under solvent-free conditions (Thopate et al., 2011).
This finding provoked us to evaluate the catalytic po-
tential of various naturally occurring organic acids in
the Beckmann rearrangement. For this purpose, ox-
alic, tartaric, malic, succinic, malonic, and fumaric
acids along with citric acid were selected as green cat-
alysts in the Beckmann rearrangement.
Beckmann rearrangement is a topic of current re-
search interest due to its effectiveness in the syn-
thesis of amides (Nubbemeyer, 2001; Abele & Luke-
vics, 2000). Several acids (Narasaka et al., 1993; Li et
al., 2005; Wang et al., 2004; Xiao et al., 2007), such
as trifluromethanesulfonic, chlorosulfonic, sulfamic, p-
toluenesulfonic, and anhydrous oxalic acid (Chan-
drasekhar & Gopalaiah, 2003), and heterogeneous cat-
alysts (Shiju et al., 2009; Zhao et al., 2008; Mitsudome
et al., 2012; You et al., 2008) have been employed in
this reaction. The effects of the acid strength of het-
erogeneous catalysts on the Beckmann rearrangement
have been addressed in literature (Shamzhy et al.,
Fig. 1. Beckmann rearrangement of ketoximes promoted by
naturally occurring organic acids. Reaction conditions:
i) for starting Ia (0.5 g): acid (1 mole eq), heating (110–
◦
2
90 C), solvent-free (see Table 1); ii) for starting Ia–
◦
Io (0.5 g): tartaric acid (1 mole eq), heating (180 C),
solvent-free (see Table 2).
Typically, the mixture of ketoxime I (0.5 g) and
acid (1.0 mole eq) was heated either in a preheated
oil bath at a given temperature (Table 1) for 5 min or
in a microwave reactor for 3 min. After the comple-
tion of the reaction (monitored by TLC), the reaction
mixture was allowed to cool to ambient temperature,
and water (10 mL) was added. The solid obtained on
stirring was filtered and washed with water. Crude
product was purified by recrystallisation using aque-
ous ethanol.
2
013). However, most of the reported methods suffer
from certain drawbacks such as the use of toxic/costly
solvents, expensive reagents, co-catalysts, production
of a considerable amount of by-products, long reac-
tion time, and low yields. Therefore, the development
of simple, inexpensive, highly efficient yet eco-friendly
catalysts for the Beckmann rearrangement is worth-
while. A simple and highly efficient protocol for the
Beckmann rearrangement using citric, oxalic, tartaric,
malic, succinic, malonic, and fumaric acids as green
promoters of the reaction under solvent-free condi-
tions using thermal and microwave irradiation is re-
ported herein.
Our initial efforts were focused on finding an ef-
ficient catalyst for the Beckmann rearrangement of
ketoximes. In order to screen the catalysts, the re-
arrangement of benzophenone oxime Ia (Fig. 1) was
taken as a model reaction. All the above mentioned
acids were tested for this rearrangement using solvent-
free conditions under thermal as well as microwave
irradiation (Table 1).
All the seven organic acids used were found to be
effective promoters of the Beckmann rearrangement
giving benzamide IIa (Fig. 1) in good to excellent
yields (Table 1). Citric, malonic, succinic, and tartaric
acids (Table 1, entries 1, 4, 6, and 7, respectively)
were found to be superior promoters in comparison
with fumaric, malic, and oxalic acids (Table 1, entries
2, 3, and 5, respectively). The reaction was found to
be faster and completed in 3 min under microwave
irradiation as compared to conventional heating (5
min) providing slightly better yields. It is evident (Ta-
ble 1) that tartaric acid gives the best results. Next,
the effect of the amount of tartaric acid on the Beck-
mann rearrangement of benzophenone oxime was in-
vestigated. It was found that one mole equivalent of
tartaric acid is essential for the completion of the reac-
tion. However, the use of less than one mole equivalent
of the acid resulted in low yield of the product along
with the recovery of the starting material. To check
the generality and scope of this reaction, various ke-

S. V. Rohokale et al./Chemical Papers 68 (4) 575–578 (2014)
Table 2. Tartaric acid promoted Beckmann rearrangement of ketoximesa
577
b
Yield /%
Entry
Compound
R
R1
C-heatingc
M-heatingd
1
2
3
4
5
6
7
8
9
IIa
IIb
IIc
IId
IIe
IIf
IIg
IIh
IIi
IIj
IIk
IIl
IIm
IIn
IIo
Phenyl
4-Methylphenyl
Phenyl
Phenyl
4-Methylphenyl
Methyl
96
91
89
87
86
95
93
88
91
90
95
88
72
76
65
95
94
91
89
90
96
95
90
94
91
92
91
75
80
72
Phenyl
Phenyl
Etthyl
n-Propyl
Methyl
Methyl
Methyl
Methyl
n-Propyl
Methyl
Methyl
Methyl
4-Methoxyphenyl
3-Methoxyphenyl
3-Hydroxyphenyl
4-Methylphenyl
4-Methoxyphenyl
Naphth-1-yl
Naphth-2-yl
Thiophen-2-yl
4-Bromophenyl
tert-Butyl
10
11
12
13
14
15
Methyl
Methyl
a) See Fig. 1; all products were identified spectroscopically and data were in accordance with those already reported (Thopate et
al., 2011); b) isolated yields; c) conventional heating – 5 min in a preheated oil bath; d) microwave heating – 3 min in a microwave
reactor.
toximes (Ia–Io, Fig. 1, Table 2) were subjected to the
convenient alternative to the reported reagents.
Beckmann rearrangement under the above conditions
using tartaric acid as a promoter at 180 C. Results
Acknowledgements. The authors thank Professor Mukund
G. Kulkarni (Department of Chemistry, University of Pune)
and Dr. R. J. Barnabas (Ahmednagar College, Ahmednagar)
for helpful discussions and suggestions. SRK thanks the Uni-
versity Grant Commission (UGC), New Delhi, for awarding a
fellowship.
◦
showed that the Beckmann rearrangement proceeded
smoothly under conventional heating within 5 min to
give the corresponding amides IIa–IIo (Fig. 1, Table 2)
in good to excellent yields. Microwave irradiation re-
quired less time and displayed comparable yields in
comparison with conventional heating. The synthetic
utility of this general reaction protocol was also exam-
ined in a larger scale. When benzophenone oxime Ia
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