Research on the synthesis of aromatic hydrazone in ionic liquids

Article abstract of DOI:10.1080/00397911.2010.517612

Aromatic hydrazones are important intermediates for pesticides cibenzoline and cefxime. The methodology of synthesis of aromatic hydrazone from aromatic ketone and hydrazine hydrate in ionic liquid, was described and various aromatic hydrazones were prepared by the reaction of aromatic ketone with hydrazine hydrate in ionic 1iquid at 100C with good yields. The ionic liquids could be recycled and reused after the reaction. The influences of the various ionic liquids on the reaction are discussed. The product structure was characterized by infrared, mass spectrometry, NMR spectra, and elemental analysis. Copyright

Full text of DOI:10.1080/00397911.2010.517612

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Research on the Synthesis of Aromatic
Hydrazone in Ionic Liquids
Haibin Wang a , Li Sun a , Xiaonian Li a , Jiangli Duan a & Wen Pei a
a College of Chemical Engineering and Materials , Zhejiang
University of Technology , Hangzhou , China
Published online: 27 Jul 2011.
To cite this article: Haibin Wang , Li Sun , Xiaonian Li , Jiangli Duan & Wen Pei (2011) Research on
the Synthesis of Aromatic Hydrazone in Ionic Liquids, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 41:21, 3223-3227, DOI:
10.1080/00397911.2010.517612
To link to this article: http://dx.doi.org/10.1080/00397911.2010.517612
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Synthetic Communications1, 41: 3223–3227, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.517612
RESEARCH ON THE SYNTHESIS OF AROMATIC
HYDRAZONE IN IONIC LIQUIDS
Haibin Wang, Li Sun, Xiaonian Li, Jiangli Duan, and Wen Pei
College of Chemical Engineering and Materials, Zhejiang University of
Technology, Hangzhou, China
GRAPHICAL ABSTRACT
Abstract Aromatic hydrazones are important intermediates for pesticides cibenzoline and
cefxime. The methodology of synthesis of aromatic hydrazone from aromatic ketone and
hydrazine hydrate in ionic liquid, was described and various aromatic hydrazones were pre-
pared by the reaction of aromatic ketone with hydrazine hydrate in ionic 1iquid at 100 ꢀC
with good yields. The ionic liquids could be recycled and reused after the reaction. The influ-
ences of the various ionic liquids on the reaction are discussed. The product structure was
characterized by infrared, mass spectrometry, NMR spectra, and elemental analysis.
Keywords Aromatic hydrazone; ionic liquids; synthesis
INTRODUCTION
Aromatic hydrazone derivatives have been claimed to possess interesting
bioactivity such as antibacterial, antifungal, anticonvulsant, antimalarial, analgesic,
and anticancer activities.[1,2] The mechanism of DNA cleavage by this type of
compound is of biochemical and pharmaceutical interest.[3] Therefore, the study of
aromatic hydrazone derivatives has important applications.
Our recent interest has been in the area of clean synthesis using ionic liquids as
a green recyclable alternative to classical molecular solvents.[4,5] As a part of pro-
gram to investigate the range of organic reaction possible in ionic liquids, to the best
of our knowledge, since 1944 there has been a series of studies on the synthesis of
aromatic hydrazone,[6] but no report describing the process for preparing aromatic
Received October 15, 2009.
Address correspondence to Wen Pei, College of Chemical Engineering and Materials, Zhejiang
University of Technology, Hangzhou, 310014, China. E-mail: peiwen58@zjut.edu.cn
3223

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H. WANG ET AL.
hydrazone derivatives using ionic liquids as reaction media. Therefore, we employed
various aromatic ketones as our starting materials to investigate the synthesis of aro-
matic hydrazone derivatives in ionic liquid media and discuss the influences of the
various solvents on the reactions.
RESULTS AND DISCUSSION
First, benzophenone 2a (R1 ¼ H, R2 ¼ H) was used as model substrate to react
with hydrazine hydrate in various solvents (Scheme 1, Table 1). The reaction results
demonstrated that ionic liquids do work very well and gave the desired product 2a in
a good yield of 95.2% when 1a was treated with 3 equiv. of hydrazine hydrate in
[Bmim]BF4 at 100 ꢀC (entry 1). We also found that the reaction proceeded better
in ionic liquid [Bmim]BF4 than [Bmim]PF6 (entry 2) or [Bmim]CH3COO (entry 3).
Furthermore, we investigated this reaction used recycled ionic liquid five times
and found the same result was obtained (entry 4).
Next, a series of aromatic ketone 1 reacted with hydrazine hydrate to give
aromatic hydrazones 2, new compounds, in the one-pot synthesis at 100ꢀC in
[Bmim]BF4 according to this experimental procedure (Scheme 2, Table 2). In addition,
Scheme 1.
Table 1. Synthesis of hydrazone 2a in various solvents
Entry
Solvent
Yields (%)a
1
[Bmim]BF4
[Bmim]PF6
95.2
93.4
91.2
95
2
3
4b
[Bmim]CH3COO
[Bmim]BF4
aIsolated yields.
bUsed recycled ionic liquid.
Scheme 2.

SYNTHESIS OF AROMATIC HYDRAZONE
3225
Table 2. Reactions of different substratesa
Compound
R1
R2
Yields (%)b
2a
2b
2c
2d
2e
2f
4-H
4-Cl
4-H
95.2
92.9
90.0
88.8
83.7
81.5
79.3
4-NO2
4-NO2
4-NO2
4-NO2
4-NH2
4-NH2
4-Br
4-CH(CH3)2
2,4-Cl2
4-Cl
2g
4-Br
aAll reactions were in ionic liquid [Bmim]BF4.
bIsolated yields.
we found that better results were obtained used aromatic hydrazone with electron-
withdrawing groups 2b, 2c, 2d, and 2e than with electron-donating groups 2f and 2g.
In conclusion, we have successfully developed a green synthetic procedure for
preparing aromatic hydrazone derivatives in ionic liquid as reaction media. It is
possible to apply this green synthetic method to industrialization.
EXPERIMENTAL
Melting points were uncorrected. 1H NMR spectra were obtained on a Bruker
AC 400 (400-MHz) instrument in CDCl3 using tetramethylsilane (TMS) as internal
standard. Infrared (IR) spectra were taken with a Bruker Victor 22 spectrometer.
Mass spectra were obtained on a HP 5989B mass spectrometer. Ionic liquids and
aromatic ketone were prepared according to the literature method.[7,8]
General Procedure
A three-necked, round-bottomed flask containing a stirring bar was charged
with aromatic ketones (1.0 mmol), hydrazine hydrate (2.0 mmol), and ionic liquid
(5 mL) at 100 ꢀC using thin-layer chromatography (TLC) to monitor the reaction
for about 4 h. After being cooled, the mixture was extracted with CH2Cl2(3 ꢁ 20 mL)
) or toluene (3 ꢁ 20 mL), and then the organic layers were combined, washed with
water, dried with MgSO4, filtered, and concentrated in vacuo. The product was pur-
ified by flash chromatography on silica gel using ethyl acetate and hexane (10=90 to
1
30=70) as eluant. The structure of the compound was confirmed by H NMR, MS,
and elemental analysis. The physical and spectra data of the compounds are as follows.
Benzophenone Hydrazone 2a [5350-57-2]
Mp 97–98 ꢀC; MS (70 eV) m=z (%): 196 (Mþ, 100), 180 (21).
4-Chloro-4’-nitrobenzophenone Hydrazone 2b
Mp 116–118 ꢀC; 1H NMR (CDCl3, 400 MHz) d: 8.14 (d, J ¼ 8 Hz, 2H),
7.51–7.60 (m, 4H), 7.23–7.32 (m, 2H), 5.72 (s, 2H); IR (KBr, cmꢂ1): 3432, 3388,

3226
H. WANG ET AL.
3289, 1633, 1594, 1562, 1513, 1342, 1090, 857, 829, 757, 696; MS (70 eV) m=z (%):
275 (Mþ, 100), 228 (23), 163 (16). Anal. calcd. for C13H10ClN3O2: C, 56.73; H,
3.64. Found: C, 56.7; H, 3.66.
4-Bromo-4’-nitrobenzophenone Hydrazone 2c
Mp 72–73 ꢀC; 1H NMR (DMSO-d6, 400 MHz) d: 8.11–8.15 (m, 2H), 7.76–7.79
(m, 2H), 7.46–7.56 (m, 2H), 7.20–7.24 (m, 2H), 7.06 (s, 2H); IR (KBr, cmꢂ1): 3425,
3289, 1589, 1555, 1503, 1337, 1070, 854, 824, 757, 698; MS (70 eV) m=z (%): 320 (Mþ,
100), 193(24), 177 (25), 163 (54). Anal. calcd. for C13H10BrN3O2: C, 48.75; H, 3.13.
Found: C, 48.77; H, 3.16.
4-Isopropyl-4’-nitrobenzophenone Hydrazone 2d
Mp 116–118 ꢀC; 1H NMR (DMSO-d6, 400 MHz) d: 8.37 (d, J ¼ 8 Hz, 2H), 8.14
(d, J ¼ 8 Hz, 2H), 7.46–7.53 (m, 2H), 7.19 (d, J ¼ 28 Hz, 2H), 6.87 (s, 2H), 2.95–3.01
(m, 1H), 1.22 (d, J ¼ 7.6 Hz, 6H); IR (KBr, cmꢂ1): 3446, 3300, 2962, 1598, 1555,
1514, 1407, 1384, 1337, 1048, 946, 836; MS (70 eV) m=z (%): 283 (Mþ, 100), 268
(95). Anal. calcd. for C16H17N3O2: C, 67.84; H, 6.01. Found: C, 67.87; H, 6.03.
2,4-Dichloro-4’-nitrobenzophenone Hydrazone 2e
1
Mp 172–174 ꢀC; H NMR (CDCl3, 400 MHz) d: 8.15 (d, J ¼ 9.2 Hz, 2H), 7.64
(d, J ¼ 1.6 Hz, 1H), 7.56 (d, J ¼ 9.2 Hz, 2H), 7.48 (d, J ¼ 9.2 Hz, 1H), 7.21–7.19 (d,
J ¼ 8 Hz, 1H), 5.74 (s, 2 H); MS (70 eV) m=z (%): 309 (Mþ, 100). Anal. calcd. for
C13H9Cl2N3O2: C, 50.49; H, 2.91. Found: C, 50.47; H, 2.93.
4-Chloro-4’-aminobenzophenone Hydrazone 2f
Mp 125–127 ꢀC; 1H NMR (DMSO-d6, 400 MHz) d: 6.59–7.50 (m, 8H), 5.48 (s,
2H), 3.87 (s, 2H); IR (KBr, cmꢂ1): 3424, 3332, 1621, 1512, 1487, 1384, 1329, 1278,
1164, 1090, 1012, 956, 832; MS (70 eV) m=z (%): 245 (Mþ, 100). Anal. calcd. for
C13H12ClN3: C, 63.67; H, 4.90. Found: C, 63.69; H, 4.93.
4-Bromo-4’-aminobenzophenone Hydrazone 2g
1
Mp 89–91 ꢀC; H NMR (DMSO-d6, 400 MHz) d: 6.58–7.66 (m, 8H), 5.49 (s,
2H), 3.86 (s, 2H); IR (KBr, cmꢂ1): 3456, 3424, 3335, 1623, 1513, 1483, 1384, 1338,
1279, 1164, 1070, 1008, 956, 831; MS (70 eV) m=z (%): 290 (Mþ, 100), 273 (10),
199 (20), 93 (48). Anal. calcd. for C13H12BrN3: C, 53.79; H, 4.14. Found: C,
53.78; H, 4.13.
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SYNTHESIS OF AROMATIC HYDRAZONE
3227
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