Dual nature of polyethylene glycol under microwave irradiation for the clean synthesis of oximes

Article abstract of DOI:10.1007/s00706-013-1101-9

Polyethylene glycol (PEG-400 and PEG-600) is an efficient, inexpensive, and recyclable homogeneous medium and catalyst (dual nature) for the clean synthesis of oximes (and aldoximes) under microwave irradiation in the absence of acid and base catalysts. Both aliphatic and aromatic aldehydes/ketones give satisfactory results under microwave irradiation within a short time. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-013-1101-9

Monatsh Chem (2014) 145:505–508
DOI 10.1007/s00706-013-1101-9
ORIGINAL PAPER
Dual nature of polyethylene glycol under microwave irradiation
for the clean synthesis of oximes
•
•
•
Papia Dutta Arup Kumar Dutta Parishmita Sarma
Ruli Borah
Received: 17 April 2013 / Accepted: 6 October 2013 / Published online: 5 November 2013
Ó Springer-Verlag Wien 2013
Abstract Polyethylene glycol (PEG-400 and PEG-600) is
an efficient, inexpensive, and recyclable homogeneous
medium and catalyst (dual nature) for the clean synthesis of
oximes (and aldoximes) under microwave irradiation in the
absence of acid and base catalysts. Both aliphatic and
aromatic aldehydes/ketones give satisfactory results under
microwave irradiation within a short time.
property can enable the precipitation of PEGs from reac-
tion mixtures in organic solvents for purification. The
combined use of microwaves (MW) with PEGs as reaction
media can accelerate organic reactions by the selective
absorption of microwave energy by polar molecules. The
short reaction time and selective product formation offered
by microwave-assisted synthesis are suited to meet the
increased demands of environmentally benign protocols.
The synthesis of oximes from aldehydes and ketones is a
valuable organic transformation. Oximation is an efficient
method for the characterization and purification of car-
bonyl compounds [6]. Oximes are more thermally stable
than the corresponding carbonyl compounds and may be
used as protecting groups, selective a-activating groups,
and intermediates for the preparation of amides [7], nitriles
[8], nitro compounds [9], and amines [10]. Oxime func-
tionality is also an important structural feature in several
biologically active compounds such as perillartine which is
about 2,000 times as sweet as sucrose [11]. A number of
methods [12–16] have been reported for the preparation of
oximes catalyzed by both acids and bases, such as formic
acid, pyridine/chloroform, ethanol/pyridine, and sulfuric
acids and sodium hydroxide with or without solvent. The
hazardous nature of these reagents results in many limita-
tions. Therefore, many new strategies have recently been
developed using solid acid catalysts [17] such as basic
alumina, silica gel, Amberlyst A-21 in ethanol, CaO,
Keywords Oximes Á PEG Á Microwave energy Á
Recyclable
Introduction
The development of protocols for synthetic organic trans-
formations with alternative reaction media to volatile
organic compounds (VOCs) remains an ever-challenging
objective [1, 2]. The unique solvent properties, higher
solubilizing power, and cation coordination ability of
polyethylene glycol (PEG) solutions make them useful as
green solvents and phase transfer catalysts in organic
synthesis [3]. PEGs are inexpensive, non-ionic, thermally
stable, non-toxic, and recoverable media by phase separa-
tion methods. Unlike VOCs, low molecular weight liquid
PEGs are non-volatile, biodegradable, and have low flam-
mability. PEG has been found to be stable to acid, base,
and high temperature [4, 5]. Both liquid and solid PEGs are
highly soluble in water. Lower PEGs can be used as sol-
vents in their own right with or without addition of water.
PEGs exhibit different solubility in organic solvents; this
2-
TiO2/SO4 without solvent, nanostructured pyrophosphate,
and ionic liquids under ultrasound irradiation.
In continuation of previous work [18], herein, we report
PEG-400 and PEG-600 as recyclable homogeneous reac-
tion media and catalysts for the preparation of oximes from
aldehydes and ketones with hydroxylamine hydrochloride
under microwave irradiation and thermal treatment without
use of acid and base catalysts (Scheme 1).
P. Dutta Á A. K. Dutta Á P. Sarma Á R. Borah (&)
Department of Chemical Sciences, Tezpur University,
Napaam, 784028 Tezpur, Assam, India
e-mail: ruli@tezu.ernet.in
123

506
P. Dutta et al.
Table 1 Optimization of the reaction with PEGs for the synthesis of
benzophenone oxime under microwave irradiation within 5 min at
different temperatures
Scheme 1
H
O
O
N
PE
G
·
+
NH H H l
2O
C
Entry MW
power/W PEG/cm3
Amount of Temp./°C Product yield/%a,b
MW
aryl,
R
R'
R
R'
PEG- PEG- PEG-
=
R R' Alkyl,
H
,
200
25
400
600
1
2
3
4
5
280
350
420
490
560
1
64
67
70
75
79
66
30
29
40
40
55
54
75
74
85
84
–
65
65
94
94
95
94
95
95
95
94
–
0.5
1
Results and discussion
30
40
45
50
–
0.5
1
Our efforts began with the synthesis of benzophenone
oxime from benzophenone (3 mmol) and hydroxylamine
hydrochloride (3 mmol) in PEG-200, 400, and 600 as
reaction media under microwave irradiation (Table 1).
From these results, PEG-600 was found to be the best
medium (Fig. 1) for the oxime synthesis.
0.5
1
0.5
1
0.5
0
The catalytic activity of polyethylene glycol for this
reaction was again investigated using 0.5 and 1 cm3 of
PEGs at different power levels of microwave energy. The
product yields increased with increasing microwave ener-
gies within the temperature range of 64–79 °C (Table 1);
these yields were the same in both 0.5 and 1 cm3 of PEG
(Table 1, entries 1–5). Increasing microwave power causes
more collisions between substrate molecules in the PEGs
via a dipolar ionization mechanism resulting in increasing
reaction temperature. Without PEG, no product formation
was observed even at higher power level (Table 1, entry 6).
All these observations indicate that the hydrophilic nature
of PEGs is the driving force for this reaction under
microwave irradiation wherein PEGs behave as both the
medium and catalyst.
6
a
560
Isolated yield
b
Using 3 mmol of benzophenone and 3 mmol of hydroxylamine
hydrochloride in PEGs
PEG200
PEG400
PEG600
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
After optimization of the reaction conditions with
3 mmol of ketone, 3 mmol of hydroxylamine hydrochlo-
ride, and 0.5 cm3 of PEG-600, we extended the above
synthesis to different aliphatic and aromatic keto com-
pounds using both thermal and microwave energies
(Table 2) for comparative studies. However no product
was obtained if the reaction was carried out by stirring at
room temperature (Table 2, entry 7). The reaction of ace-
tophenone did not give any product in the absence of
0.5 cm3 of PEG under microwave irradiation (280 W) for
5 min. The turnover frequencies (TOF) were determined
from GC analysis at the starting time for all reactions. The
thermal conditions gave lower TOF and less yields of
product at the same temperature than with microwave
irradiation (Table 2). We observed higher TOF for all
aliphatic keto compounds (Table 2, entries 1, 3, 5, 6) as
compared to aromatic keto compounds (Table 2, entries 2,
4) under microwave irradiation. All keto compounds yiel-
ded excellent results within 2–5 min reaction time
(Table 2). The results for the synthesis of aldoximes from
aliphatic and aromatic aldehydes using standard conditions
250
300
350
400
450
500
550
600
MW power /W
Fig. 1 Comparison of the yields of benzophenone oxime against
microwave power in 0.5 cm3 PEG
are included in Table 3. In the presence of strong electron-
donating groups, the aldehyde molecules were found to be
inactive (Table 3, entries 8, 9) at higher microwave ener-
gies. All other aldehyde molecules yielded good to
excellent results within 2–6 min at different microwave
energies (Table 3). The TOF also increased in the case of
4-nitrobenzaldehyde and 4-chlorobenzaldehyde with an
increase of the microwave power from 280 W to 350 W
(Table 3, entries 4, 7). The used PEG is recovered from the
aqueous solution by evaporation of water under reduced
pressure and used again for the next reaction cycle without
123

Dual nature of polyethylene glycol
507
Table 2 Synthesis of oximes in PEG-600 under microwave and thermal conditions
Entry Ketone
MW/W Temp./°C Product
m.p./°C (lit)a
Time/min
Product yield/%b,c,d
MW Thermal MW MW TOF
(% conversion)
Thermal Thermal TOF
(% conversion)
1
2
3
4
5
6
7
a
Cyclohexanone
280
280
280
350
280
60
60
42
67
70
44
25
87 (91)
2
5
2
5
3
3
–
30
90
91
88
94
95
85
–
165.2 (45.9)
65
50
65
70
60
50
NR
6.5 (1.8)
Acetophenone
Acetone
58 (59)
50
42.1 (11.7)
159.4 (44.3)
54 (15)
0
59 (60)
20
9.7 (2.7)
Benzophenone
Cyclopentanone
143 (144)
54 (55)
2 h
50
0
106.5 (29.6)
102.6 (28.5)
–
3.96 (1.1)
5.4 (1.5)
–
Ethyl methyl ketone 280
Liq. (-30)
30
Benzophenone
–
24 h
Literature data [19–22]
Isolated yield
b
c
Turnover frequency = (mmol of product/amount of PEG in cm3) h-1
d
Conversion calculated with GC analysis during the first minute
Table 3 Synthesis of
aldoximes in PEG-600 under
microwave irradiation
Entry Aldehydes
MW/ Temp./ Time/ Product m.p./ Product
°C (lit)a
TOFc
(% conversion)d
W
°C
min
yieldb/%
1
Benzaldehyde
280
350
280
350
560
280
350
60
70
70
75
65
62
66
60
56
65
75
76
78
80
65
50
70
2
3
5
2
5
6
2
5
5
5
2
2
2
2
2
2
3
Liq. (-35)
97 (98)
132 (133)
132 (133)
121 (122)
105 (107)
105 (107)
–
90
158.7 (44.1)
123.2 (34.2)
70.2 (19.5)
177.1 (49.2)
268 (74.5)
48.6 (13.5)
332.2 (92.3)
0
2
2-Nitrobenzaldehyde
4-Nitrobenzaldehyde
4-Nitrobenzaldehyde
3-Nitrobenzaldehyde
4-Chlorobenzaldehyde
4-Chlorobenzaldehyde
98
3
98
4
97
5
70
6
80
7
96
8
4-Hydroxybenzaldehyde 560
4-Methoxybenzaldehyde 560
NR
9
–
NR
0
10
11
12
13
14
15
16
17
4-Methylbenzaldehyde
Furaldehyde
Cinnamaldehyde
Butanal
490
490
490
350
350
280
280
350
78 (80)
71 (72)
137 (139)
- (29)
- (52)
–
75
77.4 (21.5)
243.3 (67.6)
153 (42.5)
169.2 (47)
173.5 (48.2)
–
97
85
a
Literature data [19–22]
94
b
Isolated yield
Pentanal
96
c
Turnover frequency = (mmol
of product/amount of PEG in
cm3) h-1
D-Glucose
Decomposed
Polymeric
Trace
Acrolein
–
–
2,2-Dimethyl-1,3-
dioxolane-4-
carbaldehyde
–
–
d
Conversion calculated with
GC analysis during the first
minute
loss of activity. The same recovered PEG is utilized for five
cycles of reactions for the preparation of benzophenone
oxime.
of oximes from carbonyl compounds and hydroxylamine
hydrochloride. This method offers a rapid and clean
alternative and reduces reaction times, thus fulfilling sev-
eral requirements of green chemistry.
Conclusion
Experimental
This work focuses on the dual nature of PEGs as an effi-
cient, inexpensive, and recyclable homogeneous medium
and catalyst under microwave irradiation for the synthesis
1H and 13C NMR spectra were recorded on a JEOL JNM
ECS-400 MHz FT-NMR spectrometer from solution in
123

508
P. Dutta et al.
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Acknowledgments The authors are thankful to Sophisticated
Instrument Facility, Tezpur University for analysis of various samples
for this work and also to CSIR, New Delhi, India for granting a
research Project No. 02(0067)/12/EMR-II to R.B.
123