Clean synthesis of azo compounds using Magtrieve in the ionic liquid [bmim][Br]

Article abstract of DOI:10.1007/s00706-008-0869-5

A series of azo compounds, N-aryl-2-phenyldiazenecarboxamides, and 4-substituted-1,2,4-triazoline-3,5-diones, were synthesized using Magtrieve, a magnetically retrievable and recyclable oxidant, in the ionic liquid [bmim][Br] under neutral condition. This procedure has several advantages, such as greenness, mild reactions, simple manipulation, and reusability of reagent and solvent.

Full text of DOI:10.1007/s00706-008-0869-5

Monatsh Chem 139, 909–912 (2008)
DOI 10.1007/s00706-008-0869-5
Printed in The Netherlands
Clean synthesis of azo compounds using MagtrieveTM in the ionic
liquid [bmim][Br]
Hui Wan1, Yanqing Peng2
1
Technological Center, Jinling Pharmaceutical Co. Ltd., Nanjing, China
2
Shanghai Key Laboratory of Chemical Biology, Institute of Pesticides and Pharmaceuticals,
East China University of Science and Technology, Shanghai, China
Received 29 November 2007; Accepted 10 December 2007; Published online 26 June 2008
# Springer-Verlag 2008
Abstract A series of azo compounds, N-aryl-2-phenyl-
diazenecarboxamides, and 4-substituted-1,2,4-triazo-
nitrogen oxides causes air pollution [4]. More re-
cently, a variety of reagents, such as NO2-DMF [5],
FeCl3 ꢀ 6H2O [6], Fe(NO3)3 ꢀ 6H2O [7], K3Fe(CN)6=
KOH [8], NO2-PEG [9], NaBrO3=H2SO4 [10], ac-
tive MnO2 [11], and NaNO2=Ac2O [12], have been
developed to convert hydrazine derivatives into the
corresponding azo compounds. However, these meth-
ods are deficient in some aspects, such as: non-re-
coverable reagents, tedious work-up, acidic or basic
media, complicated purification procedure, and so
on. Hence, there is still a strong need for the develop-
ment of new methods for azo compounds synthesis,
which employ safer oxidants and produce little waste.
The development of environmentally friendly tech-
nologies is the most challenging goal of contempo-
rary chemistry and chemical engineering. One of the
aims of green chemistry is to replace the environ-
mentally unacceptable solvents and=or reagents with
environmentally benign ones. Among the alternative
solvents, room-temperature ionic liquids [13] have
shown great promise as environmentally benign re-
action media because of their good solubility for a
wide range of organic, organometallic, and inorganic
compounds as well as their excellent chemical and
thermal stabilities. Further, as salts, they exhibit no de-
tectable vapor pressure under ambient conditions and
line-3,5-diones, were synthesized using MagtrieveTM
,
a magnetically retrievable and recyclable oxidant, in
the ionic liquid [bmim][Br] under neutral condition.
This procedure has several advantages, such as green-
ness, mild reactions, simple manipulation, and reus-
ability of reagent and solvent.
Keywords Azo compounds; Oxidations; Magtrieve; Ionic
liquids; Green chemistry.
Introduction
Azo compounds have caused great interest in organic
synthesis [1] and have been widely utilized as dyes,
analytical reagents, and as materials to store optics
information in laser disks [2]. Recently, many note-
worthy studies have shown that azo compounds
possess excellent photoelectric properties [3]. The
research of synthesizing azo compounds has re-
ceived much attention over the years. Fuming nitric
acid can be employed as a relatively economical
oxidant to convert substituted hydrazines to azo
compounds, but the evolution of large amounts of
Correspondence: Yanqing Peng, Shanghai Key Laboratory of
Chemical Biology, Institute of Pesticides and Pharmaceuti-
cals, East China University of Science and Technology,
Shanghai 200237, China. E-mail: yqpeng@ecust.edu.cn
are nonflammable. On the other hand, MagtrieveTM
,
a magnetically retrievable oxidant, has recently been
employed in a series of organic transformations, e.g.,

910
H. Wan, Y. Peng
Scheme 1
oxidation of alcohols [14], benzophenone hydrazone
[15], thiols [16], 1,4-dihydropyridines [17], depro-
tection=oxidation of protected alcohols [18] and
acetals [19], side chain oxidation of arenes [20], and
aromatization of imidazolines [21]. Here, we wish
to report the use of MagtrieveTM – [bmim][Br] as a
recoverable and regenerable system for the green
synthesis of azo compounds from corresponding
semicarbazides or carbazides (Scheme 1). To the
best of our knowledge, this is the first example using
such a reagent couple in organic synthesis.
procedure is very simple. MagtrieveTM oxidant was
retrieved by magnetic separation, while the product
was easily separated from ionic liquid by simple
extraction with a mixture of ethyl acetate and diethyl
ether. The remaining viscous ionic liquid was thor-
oughly washed with diethyl ether and reused in sub-
sequent reactions. It is worthy to note that after
several runs the recovered ionic liquid turned brown
even after repeating solvent washing. It could be de-
colored by the fluxing of its alcoholic solution with
activated charcoal, affording regenerated [bmim][Br]
as a pale yellow liquid after filtration and concentra-
tion. The reduced trivalent chromium oxyhydroxide
coating can be reconverted to CrO2 by heating in
air. Thus, the regeneration could be performed by
heating used MagtrieveTM in an oven at 350ꢁC for
2 h. The same batch of ionic liquid and regenerated
MagtrieveTM could be reused in successive four
runs, affording similar isolated yields of 2a (first
run: 93%, second run: 91%, third run: 89%, fourth
run: 90%, and fifth run: 92%).
Results and discussion
MagtrieveTM (trademark of E.I. Du Pont de Nemours
& Co. Inc.) is a superior heterogeneous oxidizer of
organic compounds which has been found more ef-
fective than activated MnO2 in many reactions. It is
tetravalent chromium dioxide (CrO2) whose reduced
form stays on the crystal surface. After reactions,
used MagtrieveTM could be recovered readily by a
magnet and regenerated by heating in air. In contrast
to traditional chromium reagents, it is a good choice
from the viewpoints of environmental protection and
cost-effectiveness.
At the beginning, the reaction conditions were
optimized using 1a as a model substrate. In our pro-
cedure, two ionic liquids, [bmim][Br], and [bmim]-
[BF4], were chosen as alternatives to traditionally
used chlorinated solvents or toluene. It was found
that there are no considerable differences in reaction
rates and yields either with [bmim][BF4] or with
[bmim][Br]. Hence, [bmim][Br] was chosen for fur-
ther investigations due to its cheapness and simplic-
ity of synthesis.
The scope and generality of this process were fur-
ther examined with respect to a range of substrates
under optimized conditions (Table 1). The reactions
proceeded smoothly at ambient temperature with
high selectivity, affording corresponding N-aryl-2-
phenyldiazenecarboxamides (2a–2e) and 4-substi-
tuted-1,2,4-triazoline-3,5-diones (2f–2h) in excellent
yields. The presence ofelectron-donating andelectron-
withdrawing groups on the aromatic ring of starting
materials does not make a difference in the oxidation.
By all appearances, this synthesis approach is opera-
tionally simple and safe to scale up due to the unique
properties of presented oxidant-solvent couple.
In conclusion, we found that MagtrieveTM
=
Having established the practicability of this pro-
cedure, attention was next focused on the regen-
eration and reuse of MagtrieveTM and [bmim][Br]
in above-mentioned model reaction. The separation
[bmim]Br can serve as an efficient system for the
transformation of substituted semicarbazides or car-
bazides into corresponding azo compounds. The
experimental procedure is quite simple, convenient,

Clean synthesis of azo compounds
911
Table 1 Clean synthesis of azo compounds with MagtrieveTM in [bmim][Br]
Entry
Substrate
Product
Time=
min
Yield=
%
mp=ꢁC
(lit.) [Ref.]
1
2
3
4
5
Ph–NHCONHNH–Ph
1a
4-Me–Ph–NHCONHNH–Ph
1b
3-Me–Ph–NHCONHNH–Ph
1c
4-Cl–Ph–NHCONHNH–Ph
1d
Ph–NHCON¼N–Ph
50
40
40
50
55
93
94
96
95
92
114–116
(112–114) [7]
105–107
(105–107) [7]
71–73
(67–69) [7]
142–143
(140–142) [11]
136–138
(132–134) [12]
2a
4-Me–Ph–NHCON¼N–Ph
2b
3-Me–Ph–NHCON¼N–Ph
2c
4-Cl–Ph–NHCON¼N–Ph
2d
ꢀ-Naph–NHCON¼N–Ph
ꢀ-Naph–NHCONHNH–Ph
1e
2e
6
7
8
90
80
90
94
91
96
175–178
(171–175) [24]
1f
2f
132–134
(132–135) [24]
1g
2g
45–46
(42–43) [24]
1h
2h
(see regeneration procedure described below). Removal of
solvents affords essentially pure product in good yields. If
necessary, the product could be further purified by recrystalli-
zation from ethanol using water as an anti-solvent at room
temperature.
and avoids tedious work-up procedures. The com-
bination of regenerable oxidant with recoverable
ionic liquids makes this procedure environmentally
benign, economic and user-friendly.
Regeneration of MagtrieveTM
Experimental
The recovered MagtrieveTM was washed thoroughly with 2ꢃ
20cm3 ethanol in order to remove organic compounds ad-
sorbed on the particles. Regeneration work-up was then per-
formed by heating the used oxidant in an oven at 350ꢁC for 2 h.
MagtrieveTM (98% as CrO2, specific surface area ꢂ30m2=g)
was purchased from Aldrich. The starting materials, substitut-
ed semicarbazides and urazoles, were prepared according to
standard method [22]. Ionic liquids were prepared by follow-
ing literature procedures [23]. All products are known com-
pounds; their physical and spectroscopic data were compared
with those reported in literatures and found to be identical.
Melting points were determined on a XR-6 microscopical ap-
paratus (made in Shanghai). IR spectra were recorded as KBr
pellets with a Perkin-Elmer 1600 spectrophotometer. 1H NMR
spectra were recorded on Bruker AC 80 spectrometer in
CDCl3 with TMS as an internal standard.
Acknowledgements
Financial support for this work from the National Basic
Research Program of China (2003CB114402), National Key
Technology R&D Program of China (2006BAE01A01-8), and
Shanghai Educational Committee are gratefully acknowledged.
References
General procedure for the synthesis of azo compounds
A mixture of 5 mmol substrate and 5 g MagtrieveTM in 30cm3
of [bmim][Br] was mechanically stirred at room temperature
and a colored heterogeneous suspension was obtained rapidly.
On completion of the reaction (monitored by TLC), a magnet
was held to the bottom of the reaction flask, and the superna-
tant liquid was then decanted into a separatory funnel. The
desired product was extracted from the ionic liquid media by
3ꢃ10 cm3 EtOAc:Et2O (1:1 v=v). The extracts were com-
bined with the alcoholic solution from MagtrieveTM washing
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