Novel de-acylative ring opening of 3-acetyl and 3-bromo acetyl coumarins

Article abstract of DOI:10.2174/157017812802850294

Reaction of 3-acetyl and 3-bromoacetyl coumarins with hydrazine hydrate has resulted in the ring opening of the coumarin moiety. The reaction was attempted with a view to obtain some new pyridazinones and pyrazolones. The reaction did not proceed via the expected pathway instead led to the formation of salicyl azines, the structure of which has been confirmed by single crystal X-ray studies.

Full text of DOI:10.2174/157017812802850294

594
Letters in Organic Chemistry, 2012, 9, 594-597
Novel De-Acylative Ring Opening of 3-Acetyl and 3-Bromo Acetyl
Coumarins
Naazneen B. Yaragattia, Manohar V. Kulkarnia,*, Gudibande N. A. Kumarb and Tayur N. Gururowc
aPost Graduate Department of Studies in Chemistry, Karnatak University Dharwad 580 003, Karnataka, India
bDepartment of Physics, M. S. Ramaiah Institute of Technology, Bangalore 560 054, Karnataka, India
cDepartment of S.S.C.U, Indian Institute of Science, Bangalore 560 012, Karnataka, India
Received January 09, 2012: Revised April 26, 2012: Accepted May 23, 2012
Abstract: Reaction of 3-acetyl and 3-bromoacetyl coumarins with hydrazine hydrate has resulted in the ring opening of
the coumarin moiety. The reaction was attempted with a view to obtain some new pyridazinones and pyrazolones. The re-
action did not proceed via the expected pathway instead led to the formation of salicyl azines, the structure of which has
been confirmed by single crystal X-ray studies.
Keywords: 3-Acetylcoumarins, 3-bromoacetyl coumarins, 4-bromomethyl coumarins, de-acylation, ring opening.
INTRODUCTION
later being D2O exchangeable. The mass spectrum EI
showed the molecular ion peak at 240 (ESI 241) Table No.
1. The lesser number of protons in the H NMR and high
Reactions of coumarins with hydrazine hydrate have
been of considerable interest since they lead to the formation
of pyrazolones [1, 2] by a SNRORC pathway. This behavior
of the pyranone part has also been exploited to synthesize
pyrimidinones using nucleophiles like amidines and thiourea
[3]. Reaction of 5-formyl 3-imidazothiadiazolyl coumarins
with hydrazine hydrate has led to diazepines by an in-
tramolecular amidation [4]. Recently, we have shown that
the reaction of 4-bromomethyl coumarins with hydrazines
facilitates introduction of aryl moieties at C-5 and N2-C5
positions in pyridazinones [5, 6]. In the light of these obser-
vations, the reaction of 3-bromoacetyl coumarins [7] with
excess of hydrazine hydrate in refluxing ethanol was at-
tempted with a view to obtain some new pyridazinones, the
formation of which was envisaged in terms of an initial nu-
cleophilic substitution followed by an intramolecular amida-
tion. Similarly the reaction of 3-acetyl coumarins with hy-
drazine hydrate was attempted with a view to obtain pyra-
zolones from an initial nucleophilic addition followed by an
intramolecular amidation leading to the opening of the lac-
tone, Scheme 1.
1
molecular weight hinted at a symmetrical structure. At this
stage of investigation we attempted the reaction of 3-acetyl
coumarin with excess of hydrazine hydrate and to our sur-
prise the product was identical in all respects (analytical and
spectral) from the one obtained from 3-bromo acetyl cou-
marin. Absence of the CH3 protons in the 1H NMR and both
the carbonyls in the IR spectrum led us to think in terms of a
ring opening accompanied by deacylation. A survey of lit-
erature indicated one report on deacylation in the reaction of
3-carbethoxy coumarins with potassium cyanide leading to
the formation of 3-cyano coumarins [8] X-ray analysis of the
product indicated that the product obtained in the reaction
was salicyl azine Fig. (1). Further identity was established by
the reported independent route using salal and hydrazine
hydrate [9] (Scheme 2). A plausible mechanistic pathway for
the formation of azines is indicated in Scheme 3.
It is also pertinent to mention an earlier report on the re-
action of dihydro 7,8-b- furo coumarins and 3-acetyl cou-
marins proposing the formation of the presently obtained
compounds favouring an attack at the C4-carbon [10] which
is based only on the infra red spectroscopic studies and not
supported by an independent synthetic route. To investigate
a probable formation of 3-methyl-5-pyrazolone in this reac-
tion we have synthesized this compound from ethyl acetate
and hydrazine hydrate [11] and found that it exhibited two
bands at 221 and 242 nm. However, the repeated work up of
reaction mixture and ether extract did not show these bands
in the UV spectrum. Instead three bands around 354, 289,
257 nm characteristic of azines were observed. It is likely
that excess of hydrazine hydrate would generate an addition
intermediate by the Michael addition and ring opening. Such
intermediates have been proposed earlier by Morita et al. [2]
RESULTS AND DISCUSSION
The product obtained in the reaction of 3-bromo acetyl
coumarin 2 with hydrazine hydrate in ethanol was a yellow
crystalline compound with no IR bands in the region of
1650-1740 cm-1. Further, the H NMR showed no up field
1
protons indicating the absence of methylene protons. The
1H-NMR indicated protons in the aromatic region 6.9-7.3
ppm and two downfield signals at 8.6 and 11.3 ppm with the
* Address correspondence to these authors at the Post Graduate Department
of Studies in Chemistry, Karnatak University Dharwad 580 003, Karnataka,
India;
Tel:
91
836
2215286;
Fax:
91
836
2747884;
E-mail: manohar274@gmail.com
1875-6255/12 $58.00+.00
© 2012 Bentham Science Publishers

Novel De-Acylative Ring Opening
Letters in Organic Chemistry, 2012, Vol. 9, No. 8 595
O
H
OH
O
O
hydrazine hydrate (99 %)
alcohol, reflux
CH2
NH
CH2Br
R
R
O
N
O
H
2
Expected, not obtained
O
O
OH
H
CH3
hydrazine hydrate (99 %)
alcohol, reflux
CH3
N
R
R
NH
O
O
1
Expected, not obtained
R= H, 6-Cl, 6-Br, 5,6-benzo
Scheme 1. Expected Products in the Reaction of 3-acetyl and 3-bromoacetyl Coumarins with Hydrazine Hydrate.
HO
H
N
H2N
H2N
O
O
O
NH
OH
O
NH
O
H
H
X
X
H
X
H
NH2-NH2
N
H
O
O
O
NH
H2N
OH
1/2
II
3
I
Fig. (1). ORTEP diagram of salicyl azine 3a.
with proton and carbon resonances at 300 and 75 MHz, re-
spectively. Mass spectral data (ESI) was recorded on HCT
Ultra ETD II. Bruker Daltonics, Germany Mass Spectrome-
ter.
and more recently in the reaction of malonyl hydrazide with
3-acetyl coumarin [12]. This 3,4-dihydro coumarin interme-
diate can undergo a C3-C4 cleavage which triggers an N-N-
cleavage. Further, the attack of NH2 on either of the carbon-
yls would lead to low molecular weight hydrazinated com-
pounds.
General Procedure for the Synthesis of Salicyl Azines
Salicyl azines obtained probably in a multistep mechanis-
tic transformation from the reaction of both 3-acetyl and 3-
bromo acetyl coumarins have been characterized and con-
firmed by the reported synthesis also. This forms an un-
precedented case of a deacylation and ring opening of cou-
marins.
3-acetyl coumarin/3-bromo acetyl coumarins (0.005 mol)
were taken in round bottom flask in 30 mL of absolute alco-
hol. Hydrazine hydrate 99 % (0.025 mol) was added drop
wise with stirring at room temperature and further was re-
fluxed for 8-10 h on water bath. The reaction on completion
as monitored on TLC, alcohol concentrated and reaction
mixture was cooled and poured into ice cold water, separated
solid was filtered off (pH =7). It was washed with ethanol,
dried and recrystallized from ethanol to yield crystalline sol-
ids.
EXPERIMENTAL
Materials and Instruments
All chemicals were obtained from commercial suppliers
and were used without further purification unless otherwise
stated. TLC analyses were performed on commercial Kiesel-
gel 60 F254 silica gel plates. IR spectra were recorded on a
Bruker EQUINOX 55 FTIR. NMR spectra were obtained on
Bruker Spectrometer using DMSO and CDCl3 as solvent,
Salicylaldehyde Azine (3a)
Yield: 0.9 g (75 %). M.p 214 C. FT- IR (KBr, cm-1)
o
1
CH= N-1620. H NMR (300 MHz, DMSO) ꢀ: 11.32 (s, 1H,
OH), 8.64 (s, 1H, CH= N), 6.95 (d, J = 8.4 Hz, 1H, C3- H),

596 Letters in Organic Chemistry, 2012, Vol. 9, No. 8
Yaragatti et al.
O
R
OH
CH3
NH2-NH2.H2O
+
R
2
CHO
O
O
1
hydrazine hydrate (99 %)
alcohol, reflux, 8-10 h
alcohol, reflux
H
C
H
C
N
N
R
R
OH
HO
3
hydrazine hydrate (99 %)
alcohol, reflux, 8-10 h
O
O
CH2Br
R
O
2
R= H, 6-Cl, 6-Br, 5,6-benzo
Scheme 2. Formation of salicyl azines 3 from 3-acetyl and 3-bromo acetyl coumarins.
Table 1. Salicyl Azines Synthesized from 3-acetyl/3-bromo Acetyl Coumarins.
Entry
R
Compound
Yield (%)
Mass (m/z)
1
2
3
4
H
6-Cl
3a
3b
3c
3e
75
79
80
70
241
308, 310
396, 398
340
6-Br
5,6-benzo
HO
H
H2N
H2N
O
O
NH
OH
NH
O
O
H
H
N
X
X
H
H X
NH2-NH2
N
H
O
O
O
O
NH
H2N
OH
II
1/2
3
I
Scheme 3. Plausible Mechanism for the formation of Salicyl azines.
6.90 (t, J = 7.5 Hz, C5-H), 7.33 (d, J = 8.4 Hz), 7.30 (t, J =
7.8 Hz). 13C NMR (75 MHz, DMSO) ꢀ: 163, 160, 134, 133,
121,120,119. MS (ESI+) m/ z = 241(M+H). Anal. calc. for
C14H12N2O2: C, 69.99; H, 5.03; N,11.66. Found C, 69.83; H,
5.22; N, 11.02.

Novel De-Acylative Ring Opening
Letters in Organic Chemistry, 2012, Vol. 9, No. 8 597
5-Chloro-salicylaldehyde Azine (3b)
in science for meritorious students. The authors thank Uni-
versity Scientific Instrumentation Center (USIC), Karnatak
University Dharwad, IISc, Bangalore for spectral and ana-
lytical data.
o
Yield: 2.43 g (79 %). M.p 256 C. FT- IR (KBr, cm-1)
1
CH= N-1626. H NMR (300 MHz, CDCl3) ꢀ: 11.26 (s, 1H,
OH), 8.65 (s, 1H, CH=N), 7.34-6.98 (m, 3H). Mass GCMS
(EI) m/ z = 308 (M), 310 (M+2). Anal. calc. for
C14H10Cl2N2O2: C, 54.39; H, 3.26; N, 9.06. Found C, 54.12;
H, 3.44; N, 9.72.
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CONFLICT OF INTEREST
The author(s) confirm that this article content has no con-
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ACKNOWLEDGEMENTS
Dr. N. B. Yaragatti is grateful to UGC (New Delhi) for
the financial assistance in the form of Research Fellowship