Ionic Liquid Promoted Rapid Synthesis of Aryl Hydrazones under Ambient Conditions

Article abstract of DOI:10.1081/SCC-120027236

Aryl hydrazones have been synthesized in excellent isolated yields (90-96%) in short reaction time (4 min) under ambient conditions in the absence of any added catalyst by the reaction of aryl hydrazines with carbonyl compounds in the ionic liquid 1,3-di-

Full text of DOI:10.1081/SCC-120027236

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Ionic Liquid Promoted Rapid Synthesis of Aryl
Hydrazones Under Ambient Conditions
S. A. Siddiqui a , R. N. Nadaf a , R. Rajagopal a , Thomas Daniel a , R. J. Lahoti a & K. V.
Srinivasan a
a Division of Organic Chemistry: Technology, National Chemical Laboratory, Dr. Homi
Bhabha Road, Pune, 411 008, India
Version of record first published: 16 Aug 2006.
To cite this article: S. A. Siddiqui , R. N. Nadaf , R. Rajagopal , Thomas Daniel , R. J. Lahoti & K. V. Srinivasan (2004):
Ionic Liquid Promoted Rapid Synthesis of Aryl Hydrazones Under Ambient Conditions, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 34:1, 41-48
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 1, pp. 41–48, 2004
Ionic Liquid Promoted Rapid Synthesis
of Aryl Hydrazones Under
Ambient Conditions
S. A. Siddiqui, R. N. Nadaf, R. Rajagopal, Thomas Daniel,
*
R. J. Lahoti, and K. V. Srinivasan
Division of Organic Chemistry: Technology, National Chemical
Laboratory, Pune, India
ABSTRACT
Aryl hydrazones have been synthesized in excellent isolated yields
(90–96%) in short reaction time (4 min) under ambient conditions in the
absence of any added catalyst by the reaction of aryl hydrazines with
carbonyl compounds in the ionic liquid 1,3-di-n-butyl imidazolium
bromide.
Key Words: Aryl hydrazones; Ionic liquid; Phenyl hydrazines;
Carbonyl compounds.
*
Correspondence: K. V. Srinivasan, Division of Organic Chemistry: Technology,
National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India;
Fax: þ91-20-5893614; E-mail: kvsri@dalton.ncl.res.in.
41
DOI: 10.1081/SCC-120027236
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

42
Siddiqui et al.
INTRODUCTION
Aryl hydrazones are important building blocks for the synthesis of a
variety of heterocyclic compounds such as indoles, pyrazolines, pyrazoles and
formazans.[1] Recent reports indicate the use of substituted hydrazones as
insecticides and acaricides,[2] non-linear optical materials,[3] in photoconduc-
tors,[4] stabilizers,[5] and as sensitivity enhancers.[6] They are also synthetic-
ally useful as protecting groups[7] and as metallation substrates.[8] Aryl
hydrazones have been most conveniently synthesized by the reaction of aryl
hydrazines with carbonyl compounds. The reaction has been performed in a
variety of solvents such as ethanol, acetic acid, dioxan, diglyme, DMF and
others with or without an acidic catalyst.[9–11]
In view of the importance of aryl hydrazones as described above and since
we were particularly interested in a rapid method for the preparation of 5-
substituted 1,3,3-trimethyl indoles from the corresponding aryl hydrazones,
we were evaluating methods using room temperature ionic liquid for
achieving the same. In recent times the use of room-temperature ionic liquids
(I.L.s) as solvents in organic synthetic processes has gained considerable
importance due to their solvating ability, negligible vapour pressure, easy
recyclability and reusability.[12–16] We have recently reported the ultrasound
promoted Heck and Suzuki reaction at ambient conditions in room temp-
erature ionic liquids.[17,18] We have also recently published our investigations
on the ionic liquid promoted synthesis of 1,5-benzodiazepines and bromoa-
renes respectively under ambient conditions.[19,20] In continuation, we wish to
report for the first time, a novel and rapid synthesis of aryl hydrazones under
ambient conditions in near quantitative yields from the corresponding phenyl
hydrazines and carbonyl compounds using the ionic liquid 1,3-di-n-butyl
imidazolium bromide [bbim]Br as a reaction medium, promoter and a catalyst.
RESULTS AND DISCUSSION
Phenyl hydrazine and para-substituted phenyl hydrazines (1) were reacted
with a variety of carbonyl compounds (2) (alkyl, aryl and heteroaryl) in room
temperature ionic liquid [bbim]Br (Sch. 1).
All the reactions proceed to completion in just 4 min at 288C in the I.L.
without the need for any catalyst. The respective aryl hydrazones could be
isolated in excellent yields in all the cases (Table 1). The hydrazones 3a–l are
1
known compounds and were well characterized by melting point, IR, H-
NMR and mass spectra.[21]
As is evident from Table 1, the methodology tolerates both electron
withdrawing and electron donating substiuents on the phenylhydrazines. The

Aryl Hydrazones
43
Scheme 1.
reactions wherein both 1 and 2 are liquids (Entries 2–4) when carried out neat
without the I.L. required 1.5 h for complete conversion under similar
conditions. Likewise, all the reactions when carried out in a molecular solvent
such as methanol under similar conditions required 1.5 h for complete
conversions. However, in both the cases, the addition of the I.L. even in
catalytic proportions (5 mol%) brought about the completion of reaction in
just 4 min as before giving rise to similar yields as recorded in Table 1. In all
the cases, the I.L. whether used as a reaction medium or a catalyst, could be
recovered and recycled at least three times without incurring any loss in
activity.
A typical reaction of 4-nitro phenyl hydrazine with 3-methyl-2-butanone
to afford aryl hydrazone 3e was carried out in other ionic liquids under similar
conditions for comparative study. The results are recorded in Table 2. It can be
seen that in imidazolium I.L.s the reaction was over in just 4 min. However, in
ethyl ammonium nitrate and N-butylpyridinium bromide as the I.L.s, the
reaction was comparatively sluggish requiring 1.5 h for complete conversion.
The significantly enhanced reaction rates for the synthesis of aryl
hydrazones in the imidazolium I.L.s both as reaction media and as a catalyst
respectively may be attributed to the inherent Bronsted and Lewis acidities of
the ring hydrogens H2, H4 and H5 of the imidazolium cation in the I.L.s.
Previous investigation by the same author[17–20] and study involving multi-
nuclear NMR spectroscopy and conductivity measurements for the
imidazolium ions correlating their acidity characteristics,[22–25] support the
above observations. Further work is in progress to enhance the acidities of
such I.L.s by incorporating weakly coordinating anions and study their
efficacy in promoting similar reactions.
In conclusion, we have developed a remarkably rapid synthesis of aryl
hydrazones in the solution phase under ambient conditions in near quantitative
yields using a room temperature ionic liquid viz. [bbim]Br as a reaction
medium, promoter and homogeneous catalyst. The high reaction rate coupled
with near quantitative yields makes this methodology a valuable tool to
generate dynamic combinatorial libraries of aryl hydrazones of importance.
The absence of a catalyst and recyclability of the non-volatile I.L. makes this
an environment friendly methodology amenable for scale up.

44
Siddiqui et al.
Table 1. Yield for arylhydrazones 3.
Entry
1
Hydrazone 3
R
R1
R2
Yielda %
3a
H
H
91
2
3
3b
3c
H
H
H
CH3
n-C5H11
Ph
92
93
4
3d
H
CH3
H
94
5
3e
NO2
96
6
7
3f
3g
NO2
NO2
H
CH3
n-C5H11
Ph
94
93
8
3h
3i
NO2
CH3
H
90
9
Cl
91
10
11
3j
3k
Cl
Cl
H
CH3
n-C5H11
Ph
92
91
12
13
3l
Cl
CH3
CH3
91
91
3mb
20, 30- (CH3)2
14
3nb
20, 30-(CH3)
H
93
2
aIsolated yields.
bNew compounds.
EXPERIMENTAL
Melting points are uncorrected. IR spectra were recorded on Mattson
Research Series FTIR spectrometer, mass spectra on Finnigan Mat-1020

Aryl Hydrazones
45
Table 2. Formation of 3e in other I.L.s.
Entry
I.L.
Time of completion Yielda %
1.
2.
3.
4.
[bbim]BF4
[bmim]BF4
Et ꢁNHu3NO3
4 min
4 min
1.5 h
1.5 h
96
95
96
96
aIsolated yield.
1
automated GC/MS spectrometer and H NMR spectra on Bruker-200 MHz
spectrometer.
All chemicals were of research grade and were used as obtained from
Aldrich or Fluka. The ionic liquids N-butylpyridinum bromide and
[bmim]BF4 were obtained from Acros Organics, Belgium and used as such.
Typical Procedures
Preparation of Ionic Liquid
The ionic liquids [bbim]Br and [bbim]BF4 were prepared as per the
method already reported by us.[26]
Preparation of Arylhydrazone 3h in I.L. as Reaction Medium
A mixture of 4-nitro phenyl hydrazine (3.2 mmol) and 3-methyl-2-
butanone (3.2 mmol) in [bbim]Br (3.2 mmol) was stirred at room temperature.
The completion of reaction was followed by TLC using 30% EtOAc in
petroleum ether as eluent. After completion (4 min), the reaction mixture was
diluted with water (25 mL) and extracted with EtOAc (2 ꢀ 15 mL). The
combined organic layer was separated, dried over anhydrous sodium sulphate
and the solvent evaporated under reduced pressure to afford the
arylhydrazone. The product, thus isolated, was pure (single spot on TLC). It
was subjected to further purification by chromatography through a column of
silica-gel using 20% EtOAc in petroleum ether as eluent and fully
characterized. The aqueous layer consisting of the I.L. was subjected to
distillation (808C at 10 mm Hg) for 2 h to remove water, leaving behind the
I.L. [bbim] Br (recovery 98%), which could be recycled. Similar procedure
was followed for all the aryl hydrazones.

46
Siddiqui et al.
Preparation of Arylhydrazone 3h Using Catalytic Amount of I.L.
A mixture of 4-nitro phenyl hydrazine (3.2 mmol) and pyrazole aldehyde
(3.2 mmol) in methanol (2 mL) and [bbim]Br (5 mole%) was stirred at room
temperature. The completion of reaction was followed by TLC using 30%
EtOAc in petroleum ether as eluent. After completion (4 min), the reaction
mixture worked up as described above.
Selected Data for the New Compounds 3m, 3n
3m. Pale yellow liquid, IR (cm1) 3275, 1659. 1H NMR (CDCl3). d1.2 (d,
6H, CH–(CH3)2), 1.6 (s, 3H, CH3), 2.35 (s, 3H, Ar–CH3), 2.35 (s, 3H, Ar–
CH3), 2.9 (m, 1H, CH), 7.1–8.2 (m, 3H, Ar–H). Mass (mz) 204 (M).
1
3n. M.p. 189C, IR (cm1) 3275, 1662. H NMR (CDCl3). d2.2 (s, 3H,
CH3), 2.35 (s, 3H, Ar–CH3), 2.35 (s, 3H, Ar–CH3), 3.9 (s, 1H, CH), 6.7–8.3
(m, 7H, Ar–H). Mass (mz) 320 (M).
ACKNOWLEDGMENT
Financial assistance from DST, New Delhi (Project, SR\S5\OC-23\2002)
is gratefully acknowledged.
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Received in India May 4, 2003