A facile and efficient ultrasound-assisted stereospecific synthesis of novel bicyclo-cyclopropanes

Article abstract of DOI:10.1016/j.crci.2012.02.004

The regispecific synthesis of pyrazolines has been accomplished through the 1,3-dipolar cycloaddition of 2-diazopropane to pyridazine-3,6-dione derivatives. A convenient and inexpensive ultrasound-assisted preparation of bicyclo-cyclopropanes in a completely stereoselective manner in almost quantitative yields has been realized. The highly stereoselective extrusion of nitrogen suggests a concerted mechanism.

Full text of DOI:10.1016/j.crci.2012.02.004

C. R. Chimie 15 (2012) 409–413
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´
Full paper/Memoire
A facile and efficient ultrasound-assisted stereospecific synthesis of
novel bicyclo-cyclopropanes
*
Naoufel Ben hamadi , Moncef Msaddek
Laboratory of Synthesis heterocyclic and Natural Substances, Department of Chemistry, Faculty of Sciences of Monastir, Boulevard of Environment,
5000 Monastir, Tunisia
A R T I C L E I N F O
Article history:
A B S T R A C T
Received 20 October 2011
Accepted after revision 27 February 2012
The regispecific synthesis of pyrazolines has been accomplished through the 1,3-dipolar
Available online 3 April 2012
cycloaddition of 2-diazopropane to pyridazine-3,6-dione derivatives. A convenient and
inexpensive ultrasound-assisted preparation of bicyclo-cyclopropanes in a completely
Keywords:
stereoselective manner in almost quantitative yields has been realized. The highly
1,3-Dipolar Cycloaddition
stereoselective extrusion of nitrogen suggests a concerted mechanism.
ß 2012 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Pyrazolines
Regiochemistry
Ultrasound
Cyclopropanes
1. Introduction
antiviral properties [15]. Cyclopropane derivatives have
shown potent HIV antiviral activities as non-nucleoside
reverse transcriptase inhibitors [16]. Due to diversity of
cyclopropane containing compounds with biological activi-
ty, chemists have tried to find novel and facile methods for
synthesis of these compounds [17]. In this article, we
describe the results obtained for the regiospecific synthesis
of pyrazolines by 1,3-dipolar cycloaddition of 2-diazopro-
pane with pyridazine-3,6-dione derivatives. To the best of
our knowledge, there are no literature examples for
synthesis of cyclopropanes by ultrasonication. Herein, we
wish to report a facile sonochemical synthesis of cyclopro-
panes in EtOH.
Ultrasonic energy can clean or homogenize materials,
accelerate both physical and chemical reactions [1]. The
utilization of ultrasound energy in organic chemistry has
beenbetter known fromthe 1970s [2]. The useof ultrasound
in chemical reactions insolution provides specific activation
based on a physical phenomenon: acoustic cavitation [3].
Cavitation induces very high local temperatures and
pressure inside bubbles (cavities), leading to a turbulent
flow in the liquid and enhanced mass transfer [4].
Pyridazinone derivatives have been reported to possess a
wide variety of biological activities like antidiabetic [5],
anticancer [6] anti-AIDS, antihypertensive [7], antimicrobial
[8], fungicida [9], herbicida [10], antifeedant [11], antiplate-
let [12], analgesic, anti-inflammatory [13] and anticonvul-
sant activities [14]. The cyclopropane ring is a main
structural part in many synthetic and natural compounds
that exhibit a wide range of biological activities from
enzyme inhibition to antibiotic, herbicidal, antitumor, and
2. Results and discussion
2.1. Synthesis of pyrazolines
We have also investigated the cycloaddition reaction of
several pyridazine-3,6-diones 1a–d [18] with 2-diazopro-
pane 2 [19]. The 1,3-dipolar cycloaddition of 2-diazopro-
pane is, in each case, regiospecific. Unambiguous proofs for
the obtained cycloadducts regiochemistry arised from
their spectral data. However, regiochemical assignments of
* Corresponding author.
E-mail address: bh_naoufel@yahoo.fr (N. Ben hamadi).
1631-0748/$ – see front matter ß 2012 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.crci.2012.02.004

410
N. Ben hamadi, M. Msaddek / C. R. Chimie 15 (2012) 409–413
Table 1
Synthesis of pyrazolines via cycloaddition 1,3-dipolar.
O
O
Me
R
H
Me
R
H
Me
Me
N
N
N
N
N
Et2O, 0 °C
N
N
N
+
2
H
Me
Me
O
O
1a-d
3a-d
3a: R = Ph
1a: R = Ph
3b: R = p-C6H4-CH3
3c: R = p-C6H4-Cl
3d: R = Bn
1b: R = p-C6H4-CH3
1c: R = p-C6H4-Cl
1d: R = Bn
Entry
R
Yield (%)
13C NMR (CDCl3)
d
3a
3b
3c
3d
Ph
75
80
65
85
19.16 (CH3), 21.61 (CH3), 27.59 (CH3), 49.99 (C-3a), 93.47 (C-3), 97.21 (C-6a)
19.12 (CH3), 21.13 (CH3), 21.51 (CH3), 27.55 (CH3), 49.96 (C-3a), 93.45 (C-3), 97.17 (C-6a).
19.17 (CH3), 21.52 (CH3), 27.34 (CH3), 50.02 (C-3a), 93.43 (C-3), 97.01 (C-6a)
19.20 (CH3), 21.51 (CH3), 27.31 (CH3), 50.01 (C-3a), 50.72 (CH2Ar), 93.41 (C-3), 96.91 (C-6a)
p-C6H4-CH3
p-C6H4-Cl
Bn
all adduct were deduced from their 13C-NMR spectra.
Particularly the chemical shifts of C-6a (97.01–97.21 ppm)
are in excellent agreement with those usually obtained
when this quaternary carbon is attached to an oxygen
atom (Table 1) [20].
transfer [21] and allowing chemical reactions to occur. The
creation of the so-called hot spots in the reaction mixture
produces intense local temperatures and high pressures
generated inside the cavitation bubble and at its interfaces
when it collapses. In order to gauge the effect of different
irradiation frequencies, the model reaction was performed
under three different frequencies of 30, 40 and 50 kHz. The
cyclopropane 4a yield for these frequencies was 95, 80 and
65% respectively. It seems that the lower frequency of
ultrasound irradiation can improve the yield of cyclopro-
pane derivatives.
2.2. Formation of cyclopropanes
The photolysis of an ethereal solution of the pyrazolines
3a–d through pyrex with a high pressure mercury arc lamp
at 0–5 8C led to exclusive formation of bicyclo-cyclopro-
panes 4a–d.
Secondly, using the formation of 1,7,7-trimethyl-3-
phenyl-3,4-diazabicyclo[4.1.0]heptane-2,5-dione 4a as a
standard reaction, pyrazolines was sonicated under vari-
ous sets of conditions in order to obtain optimal irradiation
power conditions at a constant room temperature of
25 Æ 1 8C and constant frequency 30 kHz (Table 3). By
increasing the irradiation power from 100 to 200 W, the
reaction time of 4a decreased from 30 to 10 min and the yield
increased from 70 to 95%. The reaction time and yield of 4a
did not change from 200 to 250 W, therefore, 200 W of
ultrasonic irradiation was sufficient to push the reaction
forward. The best yield for 4a was obtained by ultrasonic
irradiation for 10 min at room temperature and 200 W.
Under stationary irradiations, pyrazolines 3a–d
afforded the corresponding cyclopropanes 4a–d with total
stereospecificity [22]. The stereochemistry of this ultra-
sonic product was determined from a NOESY spectrum.
The cis relation ship existing between the Me groups and
the proton H-6 in compounds 4a could be deduced from
observation of an NOE effect between H-6 and the methyl
protons (Fig. 1).
As shown in Table 2, pyrazoline derivatives 3a–d were
sonicated in EtOH in an ultrasonic cleaning bath afforded
gem-dimeylcyclopropanes 4a–d.
The results were summarized in Table 2. Firstly, it can
easily be seen that the irradiation of pyrazolines was
carried out in good yield in ethanol under ultrasound
irradiation (30 kHz, 150 W) within 15 min. The results
show that the method to obtain bicyclo-cyclopropanes 4a–
d under ultrasonic irradiation from pyrazoline derivatives
3a–d offers several significant advantages including faster
reaction rates, higher purity, and higher yields. In
comparison with conventional methods, the main advan-
tage of ultrasound application is the significant decrease in
the reaction times and milder experimental conditions.
Thus, while the conventional method requires 35–45 min,
ultrasonic irradiation affords the respective products in
only 15–20 min (Table 2). These results support the idea
that the energy provided by ultrasound significantly
accelerates these reactions. The difference in yields and
reaction times may be a consequence of the specific effects
of ultrasound, in particular, cavitation, a physical process
that creates, enlarges, and implodes gaseous and vaporous
cavities in an irradiated liquid, thus enhancing the mass
Whereas a diradical mechanistic pathway has been
proposed by several groups [23] to explain the highly
stereoselective evolution of pyrazolines under photolytic

N. Ben hamadi, M. Msaddek / C. R. Chimie 15 (2012) 409–413
411
Table 2
Synthesis of cyclopropanes under ultrasonication (25 8C, 30 kHz and 150 W).
O
O
Me
Me
R
H
R
H
Me
N
N
N
N
N
EtOH, 20 °C
N
)))))
Me
H
H
Me
Me
O
O
4a-d
4a: R = Ph
3a-d
3a: R = Ph
4b: R = p-C6H4-CH3
4c: R = p-C6H4-Cl
4d: R = Bn
3b: R = p-C6H4-CH3
3c: R = p-C6H4-Cl
3d: R: Bn
Entry
R
Reaction time (min)
Photolysis
Yield (%)
M.P. (8C)
Ultrasound
Photolysis
Ultrasound
4a
4b
4c
4d
Ph
45
40
35
45
15
20
15
20
35
45
40
50
95
90
85
75
112
143
127
129
p-C6H4-CH3
p-C6H4-Cl
Bn
Table 3
Influence of the reaction intensity.
Entry
R
Reaction time and yield
100 W
150 W
200 W
250 W
4a
4b
4c
4d
Ph
30 min/70%
30 min/65%
25 min/75%
25 min/60%
15 min/95%
20 min/90%
15 min/85%
20 min/75%
10 min/95%
15 min/90%
10 min/85%
10 min/75%
10 min/95%
15 min/90%
10 min/85%
10 min/75%
p-C6H4-CH3
p-C6H4-Cl
Bn
conditions, the course of the thermal decomposition of
pyrazolines into cyclopropanes still remains controversial.
Indeed, the hitherto reported stereochemical results from
thermal decomposition of 1-pyrazolines are quite divergent
and strongly dependent on the nature of the substituents at
the ring. Concerted [24] or diradical [25] mechanisms have
been postulated to explain the most usual pyrolytic
processes proceeding without stereoselectivity. Bearing in
mind the electron-withdrawing groups existing at the
pyrazoline rings reported herein, our stereochemical results
are consistent with the concerted thermal decomposition
´
proposed by Jose et al. [26] of pyrazoline derivatives, which
afford cyclopropanes by extrusion of nitrogen through a
polar transition state, where the degree of bond breaking of
the C(3a)-N bond is advanced over the bond breaking of the
C(7)-N bond (Fig. 2).
O
O
NOE
Me
Me
Ph
Me
δ
Ph
H
N
N
N
N
δ
N
N
Me
H
H
H
Me
Me
O
O
4a
Fig. 2. Proposed transition states for the concerted nitrogen extrusion
Fig. 1. NOE interaction between H-6 and the Me protons.
under ultrasonic conditions.

412
N. Ben hamadi, M. Msaddek / C. R. Chimie 15 (2012) 409–413
3. Conclusion
13C{1H}NMR (75 MHz, CDCl3)
d: 19.12 (CH3), 21.13 (CH3),
21.51 (CH3), 27.55 (CH3), 49.96 (C-3a), 93.45 (C-3), 97.17
(C-6a), 128.9-136.9 (Carom), 169.63, 170.21 (C-4,C-7).
6-(4-chlorophenyl)-3,3,7a-trimethyl-3a,5,6,7a-tetra-
hydro-3H-pyrazolo[3,4-d]pyridazine-4,7-dione 3c
Anal. Calcd. For C14H15ClN4O2: C, 54.82; H, 4.93;ÀN1 ,
In this article, a new methodology to obtain function-
alized bicycle-cyclopropanes under ultrasound irradiation
has been used. The present procedure under ultrasound
irradiation at room temperature significantly improved
conventional methods, giving way to obvious advantages
including simple operation, high yields, short reaction
times and decreased toxicity.
18.26%; Found: C, 54.73; H, 4.97; N, 18.38%; IR (KBr) ncm
;
1640 (N = N); 1690 (C = O); 1705 (C = O); 1H-NMR (300 MHz,
CDCl3) : 1.22 (s, 6H, CH3), 1.64 (s, 3H, CH3), 2.47 (s, 1H, 3a-
H), 6.34 (s, 1H, NH), 6.69 and 7.13 (d, 2H, Harom, J = 8.4 Hz);
13C{1H}NMR (75 MHz, CDCl3)
: 19.17 (CH3), 21.52 (CH3),
d
4. Experimental
d
27.34 (CH3), 50.02 (C-3a), 93.43 (C-3), 97.01 (C-6a), 118.13–
153.51 (Carom), 168.97, 171.08 (C-4,C-7).
4.1. Apparatus and analysis
6-benzyl-3,3,7a-trimethyl-3,3a,5,6-tetrahydro-7aH-
pyrazolo[3,4-d]pyridazine-4,7-dione 3d
IR spectra were recorded on a Perkin-Elmer IR-197
spectrometer. NMR spectra were obtained on a Bruker AC
300 spectrometer operating at 300 MHz for 1H and at
75.64 MHz for 13C. Melting points were determined on a
Buchi-510 capillary melting point apparatus. Coupling
constants are given in Hz. Elemental analyses were
Anal. Calcd. For C15H18N4O2: C, 62.92; H, 6.34; ÀN1 ,
19.57%; Found: C, 62.98; H, 6.26; N, 19.61%; IR (KBr) ncm
;
1640 (N = N); 1690 (C = O); 1700 (C = O); 1H-NMR
(300 MHz, CDCl3) : 1.21 (s, 6H, CH3), 1.62 (s, 3H, CH3),
2.48 (s, 1H, 3a-H), 5.12 (s, 2H, CH2Ar), 6.39 (s, 1H, NH),
7.26–7.35 (m, 5H, Harom); 13C{1H}NMR (75 MHz, CDCl3)
d
performed on
a
PERKIN-ELMER 240B microanalyzer.
d:
Ultrasonication was performed in a GEX750-5 C ultrasonic
processor equipped with a 3 mm wide and 140 mm long
probe that was immersed directly into the reaction
mixture. The operating frequency was 30–50 kHz and
the output power was 0–750 W through manual adjust-
ment. The temperature was controlled by a Buchi B-491
water bath at 25 Æ 1 8C. All reagents were of commercial
quality or purified by standard procedures.
19.20 (CH3), 21.51 (CH3), 27.31 (CH3), 50.01 (C-3a), 50.72
(CH2Ar), 93.41 (C-3), 96.91 (C-6a), 117.12–141.51 (Carom),
167.99, 170.88 (C-4,C-7).
4.2.2. General procedure for the irradiation of the pyrazolines
3a–d
4.2.2.1. Photolysis irradiation of pyrazolines 3a–d. All irra-
diationwerecarriedout usingsimilarconditions. Irradiation
ofanetherealsolutionofthepyrazolinesthroughpyrexwith
a high pressure mercury arc lamp (Philips HPK 125 W) at 0–
5 8C led to exclusive formation of gem-dimethylcyclopro-
panes. The derivative was dissolved in ether (pretreated by
stirring with solid [NaCO3], filtering and flushing with
argon) and irradiation at 5 8C for a total of 1 h or until the
starting materiel was consumed (TLC). After this period, the
solvent was removed in a vacuum without heating to give
brown oil, which was subjected to rapid silica filtration. The
recovered solid was subjected to a recrystallization treat-
ment from dichloromethane/light petroleum.
4.2. General procedure for trapping of 2-diazopropane 2 with
pyridazine-3,6-diones 1a–d
4.2.1. 1,3-dipolar cycloaddition of 2-diazopropane with
pyridazine-3,6-diones 1a–d
To a solution of pyridazine-3,6-diones 1a–d (1.0 mmol)
in diethyl ether, cooled at 0 8C, was added portionwise 2.6 M
ethereal solution of 2-diazopropane. The reaction was kept
at the same temperature during 1 h. the solvent was
removed in a vacuum without heating to give brown oil,
which was subjected to column chromatography (SiO2;
ethyl acetate/petroleum ether, 2:1) to afford compounds
3a–d.
4.2.2.2. Ultrasound irradiation of pyrazolines 3a–d. The
appropriate pyrazolines 3a–d (1 mmol) was dissolved in
ethanol (5 mL). The reaction was irradiated in the water
bath of the ultrasonic cleaner at 25 8C. The specific period
employed is listed in Table 1. The solvent was evaporated
under reduced pressure. The further purification was
accomplished by column chromatography on silica (200–
300 mesh, eluted with petroleum ether or a mixture of
petroleum ether and diethyl ether).
3,3,7a-trimethyl-6-phenyl-3a,5,6,7a-tetrahydro-3H-
pyrazolo[3,4-d]pyridazine-4,7-dione 3a
Anal. Calcd. For C14H16N4O2: C, 61.75; H, 5.92; ÀN1 ,
20.58%; Found: C, 62.00; H, 5.83; N, 20.50%; IR (KBr) ncm
;
1640 (N = N); 1690 (C = O); 1700 (C = O); 1H-NMR
(300 MHz, CDCl3) : 1.28 (s, 6H, CH3), 1.75 (s, 3H, CH3),
2.51 (s, 1H, 3a-H), 6.27 (s, 1H, NH), 6.55–7.20 (m, 5H,
arom); 13C{1H}NMR (75 MHz, CDCl3)
: 19.16 (CH3), 21.61
d
H
d
1,7,7-trimethyl-3-phenyl-3,4-diazabicyclo[4.1.0]hep-
tane-2,5-dione 4a
(CH3), 27.59 (CH3), 49.99 (C-3a), 93.47 (C-3), 97.21 (C-6a),
113.45–143.60 (Carom), 169.67, 170.38 (C-4,C-7).
3,3,7a-trimethyl-6-(4-methylphenyl)-3a,5,6,7a-tetra-
hydro-3H-pyrazolo[3,4-d]pyridazine-4,7-dione 3b
Anal. Calcd. For C15H18N4O2: C, 62.92; H, 6.34; ÀN1 ,
Anal. Calcd. For C14H16N2O2: C, 68.83; H, 6.60; ÀN1 ,
11.47%; Found: C, 68.80; H, 6.55; N, 11.41%; IR (KBr) ncm
;
:
1700 (C = O); 1710 (C = O); 1H-NMR (300 MHz, CDCl3)
d
1.24 (s, 3H, CH3), 1.28 (s, 3H, CH3), 1.55 (s, 3H, CH3), 2.16 (s,
1H, 6-H), 6.76–7.26 (m, 6H, Harom,NH); 13C{1H}NMR
19.57%; Found: C, 62.87; H, 6.24; N, 19.45%; IR (KBr) ncm
;
1645 (N = N); 1695 (C = O); 1700 (C = O); 1H-NMR
(300 MHz, CDCl3) : 1.25 (s, 6H, CH3), 1.25 (s, 6H, CH3),
(75 MHz, CDCl3)
d: 10.31 (CH3), 17.31 (CH3), 22.91
d
(CH3), 34.96 (C-7), 35.51 (C-6), 38.05 (C-1), 113.78–
145.63 (Carom), 172.48, 175.41 (C-2, C-5).
1.72 (s, 3H, CH3), 2.31 (s, 3H, CH3), 2.49 (s, 1H, 3a-H), 6.29
(s, 1H, NH), 6.85 and 7.08 (d, 4H, Harom, J = 8.1 Hz);

N. Ben hamadi, M. Msaddek / C. R. Chimie 15 (2012) 409–413
413
[6] (a) W. Malinka, A. Redzieka, O. Lozach, Fa´rmaco 59 (2004) 457;
1,7,7-trimethyl-3-(4-methylphenyl)-3,4-diazabicy-
clo[4.1.0]heptane-2,5-dione 4b
(b) P.G. Maria, V. Claudia, G. Carla, G. Nicoletta, B. Alessandro, D.P.
Vittorio, J. Med. Chem. 46 (2003) 1055.
Anal. Calcd. For C15H18N2O2: C, 69.74; H, 7.02; ÀN1 ,
[7] (a) S. Demirayak, A.C. Karaburun, R. Beis, Eur. J. Med. Chem. 39 (2004)
1089;
10.84%; Found: C, 69.69; H, 7.05; N, 10.76%; IR (KBr) ncm
;
:
(b) A.C. Karaburun, I. Kayagil, K. Erol, B. Sirmagul, S. Demirayak, Arch.
Pharm. Res. 27 (2004) 13.
1710 (C = O); 1705 (C = O); 1H-NMR (300 MHz, CDCl3)
d
1.22 (s, 3H, CH3), 1.27 (s, 3H, CH3), 1.59 (s, 3H, CH3), 2.14 (s,
1H, 6-H), 2.30 (s, 3H, CH3), 6.39 (s, 1H, NH), 6.85 and 7.08
[8] M. Sonmez, I. Borber, E. Akbas, Eur. J. Med. Chem. 41 (2006) 101.
[9] X.J. Zou, L.H. Lai, G.Y. Jin, Z.X. Zhany, J. Agric. Food. Chem. 50 (2002)
3757.
[10] H. Xu, X.M. Zou, Y.Q. Zhu, B. Liu, H.L. Tao, X.H. Hu, H.B. Sang, F.Z. Hu, Y.H.
Wang, .Z. Yang, Pest. Manag. Sci. 62 (2006) 522.
[11] S. Cao, N. Wei, C. Zhao, L. Li, Q. Huang, X. Qian, J. Agric. Food. Chem. 53
(2005) 3120.
[12] (a) S.C. Cherng, W.H. Huang, C.Y. Shiau, A.R. Lee, T.C. Chou, Eur. J.
Pharmacol. 532 (2006) 32;
(d, 4H, Harom, J = 8.1 Hz); 13C{1H}NMR (75 MHz, CDCl3)
d:
10.31 (CH3), 17.31 (CH3), 21.13 (CH3), 22.87 (CH3), 34.93
(C-7), 35.49 (C-6), 38.13 (C-1), 128.9–136.9 (Carom), 171.88,
174.62 (C-2, C-5).
3-(4-chlorophenyl)-1,7,7-trimethyl-3,4-diazabicy-
clo[4.1.0]heptane-2,5-dione 4c
(b) E. Stelo, M. Fraiz, M. Yamez, Y. Terrades, R. Laguna, E. Cano, F.
Rayina, Bioorg. Med. Chem. 10 (2002) 2873.
Anal. Calcd. For C14H15ClN2O2: C, 60.33; H, 5.42;ÀN1 ,
[13] (a) V.K. Chintakunta, Y. Aketta, M.S. Yedula, P.K. Mamnoor, P. Mishra,
S.R. Casturi, V.R. Rajagopalan, Eur. J. Med. Chem. 37 (2002) 339;
(b) B.S. Fumiss, A.J. Hanaford, P.W.G. Smith, A.R. Tatchell, 5th Edn,
Vogel’s textbook of practical organic chemistry, 695, Longeman Group
Ltd, London, 1989, 1015 p.;
10.05%; Found: C, 60.41; H, 5.39; N, 9.98%; IR (KBr) ncm
;
:
1690 (C = O); 1700 (C = O); 1H-NMR (300 MHz, CDCl3)
d
1.25 (s, 3H, CH3), 1.29 (s, 3H, CH3), 1.55 (s, 3H, CH3), 2.19 (s,
1H, 6-H), 6.57 (s, 1H, NH), 6.71 and 7.19 (d, 2H, Harom
J = 8.4 Hz) 13C{1H}NMR (75 MHz, CDCl3)
: 11.01 (CH3),
,
(c) M. Gokce, G. Bakir, M.F. Sachin, E. Kupeli, E. Yesilada, Arzneimittel-
Forschung 55 (2005) 318;
(d) M. Sukurolu, E.B. Caliskan, S. Unlu, M.F. Sahin, E. Kupeli, E. Yasilada,
E. Banogulu, Arch. Pharm. Res. 28 (2005) 509.
d
18.07 (CH3), 22.90 (CH3), 34.89 (C-7), 35.66 (C-6), 38.01 (C-
1), 117.21–152.43 (Carom), 171.36, 173.22 (C-2, C-5).
3-benzyl-1,7,7-trimethyl-3,4-diaza-bicyclo[4.1.0]hep-
tane-2,5-dione 4d
[14] (a) A. Hallot, R. Brodin, J. Merlier, J. Brochard, J.P. Chambon, K. Bizierek,
J. Med. Chem. 29 (1986) 369;
(b) A. Perio, J.P. Chambon, R. Calassi, M. Heaulme, K. Bizierek, J.
Pharmacol. Exp. Ther. 239 (1986) 542;
(c) R. Sivkumar, N. Anbalagan, V. GunaseKaran, J.T. Leonard, Biol.
Pharm. Bull. 26 (2003) 1407.
Anal. Calcd. For C15H18N2O2: C, 69.74; H, 7.02; ÀN1 ,
10.84%; Found: C, 69.61; H, 7.00; N, 10.73%; IR (KBr) ncm
;
:
1690 (C = O), 1705 (C = O); 1H-NMR (300 MHz, CDCl3)
d
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