Selective protection of carbonyl compounds as azines and their facile regeneration

Article abstract of DOI:10.1080/00397910600908835

Carbonyl compounds with freshly prepared hydrazinium formate successfully yielded the corresponding azines in excellent yields. In turn, azines were deprotected to the corresponding carbonyls using triethylammonium chlorochromate chemoselectively. Copyright Taylor & Francis Group, LLC.

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Selective Protection of Carbonyl Compounds
as Azines and Their Facile Regeneration
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: 24 Nov 2006.
To cite this article: H. M. Nanjundaswamy & M. A. Pasha (2006) Selective Protection of Carbonyl Compounds
as Azines and Their Facile Regeneration, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 36:21, 3161-3165
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Synthetic Communicationsw, 36: 3161–3165, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600908835
Selective Protection of Carbonyl
Compounds as Azines and Their Facile
Regeneration
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: Carbonyl compounds with freshly prepared hydrazinium formate successfully
yielded the corresponding azines in excellent yields. In turn, azines were deprotected to
the corresponding carbonyls using triethylammonium chlorochromate chemoselectively.
Keywords: Carbonyl compounds, protection, hydrazinium formate, azines, deprotection
INTRODUCTION
Carbonyl compounds occupy a central position in organic syntheses. The
selective protection of the carbonyl group and its subsequent regeneration is
an important transformation in synthetic organic chemistry. On the other
hand, azines have generated attention because of their ability to be used in
a variety of chemical reactions, such as 1,3-dipolar cycloadditions with dieno-
philes and 3 þ 2 cycloadditions[1] in the construction of five-membered rings,
which parallels the Diels–Alder reaction in construction of six-membered
rings.
Received in India April 24, 2006
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
3161

3162
H. M. Nanjundaswamy and M. A. Pasha
Methods have been developed for the preparation of these compounds
under various conditions,[2] but none of them are simple and most require
elevated temperature, complex catalysts, and unstable starting materials.
Hussein et al. have reported the synthesis of azines under microwave
irradiation but the chemistry community fails to obtain gram-scale prep-
aration.[3] In this communication, we show that hydrazinium formate is an
efficient reagent for the generation of azines without any catalyst, without
solvent if the substrate is liquid or with a minimum amount of methanol to
dissolve the solid substrates as shown in Scheme 1. The results of the exper-
iments are summarized in Table 1.
An effort was made to get unsymmetrical azines by performing the
reaction with 1 equiv of hydrazinum formate in combination with different
aldehydes and ketones, but recovered symmetrical aldazines left the ketones
unaffected, which proves the selectivity and exclusive conversion of
aldehydes despite the presence of ketones. The reaction has been found to
be sensitive to the electronic and steric effects of the substituents. The
electron-donating (inductive and mesomeric) groups seem to enhance the
extent of reaction period whereas electron-withdrawing groups facilitate it
in less than 50 s Carbonyl compounds generally display strong absorption
bands in the region between 1690 and 1750 cm21 of the IR spectra, due to
C55O. This cannot be observed in the products that showed the strong absorp-
tion band between 1610 and 1650 cm21, due to the C55N group, which clearly
indicates the conversion of carbonyl compounds to azines. This trend is
noticed in all the azines prepared by our procedure.
Although many methods have been developed for the oxidative cleavage
of oximes, hydrazones, and semicarbazones to the corresponding carbonyl
compounds, little attention has been paid to the cleavage of the carbon–
nitrogen double bonds of azines. After successfully generating very stable
azines, we have succeeded to develop a method for the facile regeneration
Scheme 1.

Protection of Carbonyl Compounds
3163
Table 1. Rapid generation of azines from carbonyl compounds with stirring at 258C
Mp 8C
Time
(S)
Yielda
(%)
Entry
R
X
Found
Reported
1
2
H
H
H
H
H
H
H
H
H
30
30
98
98
98
98
98
98
98
97
97
97
97
98
97
98
97
93
93[4]
196–197[5]
297–298[5]
207[2b]
3-NO2
4-NO2
4-Cl
196–198
300–303
208–210
154–155
177–179
266–269
192–193
121–122
222–224
161–162
35
3
30
30
4
5
4-CH3
4-OMe
4-OH
3,4-OMe
H
50
50
153[4]
6
179–180[5]
268[5]
7
50
50
8
193[2b]
9
CH3
CH3
Ph
180
240
300
40
121–122[4]
222–223[6]
164[4]
10
11
12
13
14
15
4-OH
Ph
Cyclohexanone
Camphor
36[2b]
300
50
185–186
161–162
110–112
185–186[3]
162[5]
Cinnammaldehyde
Furfuraldehyde
50
110–111.5[5]
Notes: CAUTION: Hydrazine hydrate is toxic and corrosive in nature handle
carefully. Products were characterized by the comparison with TLC, melting point,
IR, and NMR spectra of authentic samples.
aIsolated yields.
of carbonyls using triethylammonium chlorochromate as shown in Scheme 2,
and the results are summarized in Table 2.
EXPERIMENTAL
Melting points were obtained with Bu¨chi B-540 apparatus. Gas chromato-
graphy (GC) analyses were performed on a Shimadzu GC-MS QP 5050A
1
instrument. IR and H NMR spectra were recorded on Nicolet 400D FT-IR
and Bruker 400-MHz spectrometer respectively. Elemental analysis was
performed on Thermo Finnigan Flash EA 1112 CHNS analyzer.
Scheme 2.

Table 2. Regeneration of carbonyl compounds from azines by triethylammonium chlorochromate with stirring at 258C
Time
(h)
Yield
(%)
Entry
Substrate
Producta
Benzaldehyde
1
2
Benzalazine
1
88
82
86
84
85
86
82
83
89
79
86
88
78
85
82
3,30-Dinitrobenzalazine
4,40-Dinitrobenzalazine
4,40-Dichlorobenzalazine
4,40-Dimethylbenzalazine
4,40-Dimethoxybenzalazine
4,40-Dihydrobenzalazine
3,30, 4,40-Methoxybenzalazine
Acetophenone azine
3-Nitrobenzaldehyde
4-Nitrobenzaldehyde
4-Chlorobenzaldehyde
4-Methylbenzaldehyde
4-Methoxybenzaldehyde
4-Hydroxybenzaldehyde
3,4-Dimethoxybenzaldehyde
Acetophenone
1
3
1
4
1
5
1
6
1
7
1
8
1
9
1.2
1.2
1.2
1
10
11
12
13
14
15
4,40-Dihydroxyacetophenone azine
4-Hydroxyacetophenone
Benzophenone
Cyclohexanone
Benzophenone azine
Cyclohexanone azine
Camphor azine
Cinnammaldazine
Camphor
Cinnammaldehyde
Furfuraldehyde
1.2
1
Furfuraldazine
1
aProducts were characterized by their physical constants, comparison with authentic samples, and IR and NMR
spectroscopy.

Protection of Carbonyl Compounds
3165
Typical Procedure for the Rapid Preparation of Benzalazine
Hydrazinium monoformate was prepared by carefully neutralizing equal
quantities of hydrazine hydrate (99–100%) and formic acid (85%) below
08C, with constant stirring. To this neutral solution (15 mL) in a 500-mL
round-bottomed flask, 0.1 mol of benzaldehyde (10.6 g) was added while
stirring at 258C. An exothermic reaction affords the yellow solid in 30 s,
which was filtered and recrystallized from ethanol to get 10.2 g of benzalazine
crystals (ꢀ98%).
Typical Experimental Procedure for the Regeneration of
3-Nitrobezaldehyde from 3,30-Dinitrobenzalazine
3,30-Dinitrobenzalazine (1.49 g, 5 mmol) is added to a rapidly stirred solution
of triethylammonium chlorochromate (4 g) in dichloroethane (20 mL). The
resultant dark mixture is stirred for 1 h, and the reaction mixture quenched
by ether (25 mL) and filtered through a bed of celite. Removal of solvent
and silica-gel chromatography gave 3-nitrobenzaldehyde (1.23 g, 82%), mp:
42–438C. IR (KBr): 3050 (m), 2950 (m), 2760 (m), 1685 (s), 1610 (m),
1
1570 (m), 1360 (m), 828 (m), 760 (m) cm21; H NMR (d): 9.7 (s, 2H),
8.0–8.4 (m, 8H). MS (m/z): 151 (Mþ).
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