Rapid, chemoselective and facile synthesis of azines by hydrazine/I2

Article abstract of DOI:10.1080/00397910701483837

We report the reaction of hydrazine hydrate with carbonyl compounds in the presence of molecular iodine at 0-10°C, which affords symmetrical azines in excellent yields in 1 to 4 min without any adverse effect on other substituents. The reactions are rapid and chemoselective, afford excellent yields, and have high-purity products. The workup procedure is environmentally benign and does not require solvent extraction. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701483837

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Rapid, Chemoselective and Facile Synthesis
of Azines by Hydrazine/I2
H. M. Nanjundaswamy a & M. A. Pasha b
a Chemical Examination Section , Public Health Institute , Bangalore, India
b Department of Studies in Chemistry , Central College Campus, Bangalore
University , Bangalore, India
Published online: 05 Oct 2007.
To cite this article: H. M. Nanjundaswamy & M. A. Pasha (2007) Rapid, Chemoselective and Facile Synthesis
of Azines by Hydrazine/I2 , Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 37:19, 3417-3420, DOI: 10.1080/00397910701483837
To link to this article: http://dx.doi.org/10.1080/00397910701483837
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Synthetic Communicationsw, 37: 3417–3420, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701483837
Rapid, Chemoselective and Facile Synthesis
of Azines by Hydrazine/I2
H. M. Nanjundaswamy
Chemical Examination Section, Public Health Institute, Bangalore, India
M. A. Pasha
Department of Studies in Chemistry, Central College Campus, Bangalore
University, Bangalore, India
Abstract: We report the reaction of hydrazine hydrate with carbonyl compounds in the
presence of molecular iodine at 0–108C, which affords symmetrical azines in excellent
yields in 1 to 4 min without any adverse effect on other substituents. The reactions are
rapid and chemoselective, afford excellent yields, and have high-purity products. The
workup procedure is environmentally benign and does not require solvent extraction.
Keywords: azines, carbonyl compounds, hydrazine hydrate, iodine
INTRODUCTION
In continuation of our research program on effective utilization of hydrazine
and its derivatives for organic transformations, recently we reported hydrazi-
nium formate as an efficient reagent for the generation of azines,[1a] which are
versatile intermediates in the construction of many heterocycles and in a
variety of chemical reactions.[1b] We also have been engaged in the search
for simple, nonhazardous methods for organic transformations using iodine
and reported some important and efficient transformations.[2]
We found that hydrazine hydrate in the presence of iodine is an exceedingly
efficient system for the rapid generation of azines at 0–108C as shown in
Received in India February 5, 2007
Address correspondence to M. A. Pasha, Department of Studies in Chemistry,
Central College Campus, Bangalore University, Bangalore 560 001, India. E-mail:
m_af_pasha@yahoo.co.in
3417

3418
H. M. Nanjundaswamy and M. A. Pasha
Scheme 1.
Table 1. Rapid generation of azines from carbonyl compounds by hydrazine hydrate/I2
Mp (8C)
Time
Yielda
(%)
Entry
R
X
(min)
Found
Reported
93[3a]
1
2
H
H
1
98
98
98
97
98
97
96
96
97
96
95
97
92
96
93
92–93
197–199
299–302
207–209
152–153
179–181
265–268
192–193
120–121
222–224
163–165
36
H
3-NO2
4-NO2
4-Cl
1
196–197[3b]
297–298[3b]
207[3c]
3
H
1
4
H
1
5
H
4-CH3
4-OMe
4-OH
3,4-OMe
H
1.5
1.5
1.5
1.5
3.5
2
153[3a]
6
H
179–180[3b]
268[3d]
7
H
8
H
193[3c]
9
CH3
CH3
Ph
121–122[3a]
222–223[3d]
164[3a]
10
11
12
13
14
15
4-OH
Ph
2
Cyclohexanone
Camphor
0.5
2
36[3c]
186–187
161–162
111–112
185–186[3e]
162[3b]
Cinnammaldehyde
Furfuraldehyde
1
1
110–111.5[3b]
Notes: Products were characterized by the comparison of TLC of melting point, IR,
and NMR spectra with those of authentic samples.
aIsolated yields.
CAUTION: Hydrazine hydrate is toxic and corrosive in nature, and the reaction of
hydrazine with iodine is very vigorous. Handle carefully.

Synthesis of Azines by Hydrazine/I2
3419
Scheme 1, and the results of the experiments are summarized in Table 1. There
was no adverse effect on many other substituents such as nitro, methyl,
methoxy, hydroxy, halogens, which proves the selectivity and exclusive conver-
sion of both aliphatic and aromatic carbonyls to the corresponding symmetrical
azines. The reactions have been carried out without solvent in the case of liquid
carbonyls; a solution of solid substrates dissolved in a minimum amount of
either THF or methanol can be employed. The reaction has been found to be
sensitive to the electronic and steric effects of the substituents. The electron-
donating (inductive and mesomeric) groups enhance the extent of reaction
period, whereas electron-withdrawing groups facilitate the reactions for the
complete conversion in less than 2 min. Carbonyl compounds generally
display strong absorption bands in the region between 1690 and 1750 cm21
of the IR spectra due to C55O, which cannot be observed in the products that
showed the strong absorption band between 1610 and 1650 cm21 due to the
C55N group. This clearly indicates the conversion of carbonyl compounds to
azines. This trend is noticed in all the azines prepared by our procedure.
EXPERIMENTAL
Melting points were obtained with a Bu¨chi B-540 apparatus. GC analyses
1
were performed on a Shimadzu GC-MS QP 5050A instrument. IR and H
NMR spectra were recorded on Nicolet 400D FT-IR and Bruker 400-MHz
spectrometers respectively.
CONCLUSION
In summary, we have developed a new methodology for the rapid generation of
symmetrical azines, which are useful compounds in organic synthesis whose
derivatives have been reported to possess a broad spectrum of biological
activity in excellent yields from carbonyls by hydrazine/I2. The workup
procedure is environmentally benign, which does not involve solvent extraction,
as the separated solid can be filtered and recrystallized to get the pure product.
Typical Procedure for the Rapid Generation of Benzalazine from
Benzaldehyde
Iodine (equal moles) in small portions was added to hydrazine hydrate in a
round-bottomed flask at 08C carefully with constant stirring. Benzaldehyde
(10.6 g, 0.1 mol) was added to this mixture (0.1 mol) in a 100-mL round-
bottomed flask while stirring at 0–108C. The yellow solid separated within
a minute, was filtered, and was recrystallized from ethanol to give 10.3 g of
benzalazine crystals (98%).

3420
H. M. Nanjundaswamy and M. A. Pasha
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