Synthesis and chemistry of new spiro-Δ1-pyrazoline

Article abstract of DOI:10.1002/jhet.827

In explorations of syntheses and chemistry of spiroheterocycles, we found that the reaction of 2-diazopropane with (E)-α-arylidenepyrrolin-2-one, (E)-α-arylidene-γ-butyrolactone, and (E)-arylidene-N-arylsuccinimide derivatives produced spiro-Δ¹

Full text of DOI:10.1002/jhet.827

March 2012
Synthesis and Chemistry of New Spiro-D1-Pyrazoline
Nesrine Louhichi, Amel Houas, Naoufel Ben Hamadi,* and Moncef Msaddek
267
Department of Chemistry, Faculty of Sciences of Monastir, Laboratory of Synthesis Heterocyclic
and Natural Substances, Boulevard of Environment, 5000 Monastir, Tunisia
*E-mail: bh_naoufel@yahoo.fr
Received October 24, 2010
DOI 10.1002/jhet.827
Published online 11 November 2011 in Wiley Online Library (wileyonlinelibrary.com).
In explorations of syntheses and chemistry of spiroheterocycles, we found that the reaction of 2-diaz-
opropane with (E)-a-arylidenepyrrolin-2-one, (E)-a-arylidene-c-butyrolactone, and (E)-arylidene-N-aryl-
succinimide derivatives produced spiro-D1-pyrazolines. The photolysis of D1-pyrazolines has led to
cyclopropanes. The structures of the obtained adducts have been assigned by means of spectroscopic
measurements.
J. Heterocyclic Chem., 49, 267 (2012).
INTRODUCTION
organic electroluminescence devices with a multilayer
structure and as fluorescence probes in some elaborated
chemosensors [14]. On the other hand, heterocycles con-
taining the cyclopropane ring also exhibit various phar-
macological activities [15]. Recently, much attention has
been focused on amino acids containing conformationally
constrained cyclopropane rings due to their important
biological activities. For example, b-cyclopropylalanine
is a potent antagonist to E. coli American Type Culture
Collection (ATCC) 9723 [16] and inhibits spore germi-
nation of Pyricularia oryzae Cav., the causative agent of
rice blast disease [17]. Pyrazolines are also synthetically
useful scaffolds in organic chemistry [18]. The reaction
of 1,3-dipolar cycloadditions (1,3-DCs) is a classical and
widely used method for the construction of pyrazolines
[19]. The general concept of 1,3-DCs was introduced by
Huisgen and co-workers in the early 1960. The work of
Huisgen stated the basis for the understanding of the
mechanism of concerted or stepwise cycloaddition reac-
tions [20]. In continuation to our work on the synthesis of
heterocycles via 1,3-DCs and evolution of cycloadducts
[21], we report that in the previous papers we have
In recent years, there has been an increasing interest in
the chemistry of heterocyclic compounds containing
nitrogen atom because of their biological significance.
Many of them show antibacterial [1], antidepressant [2],
anticonvulsant [3], antiparkinsonian [4], antitumor [5],
antimicrobial [6], and anti-inflammatory activities [7].
Pyrazolines present an interesting group of compounds,
many of which possess widespread pharmacological
properties such as analgesic, antipyretic, and antirheu-
matic activities [8]. These derivatives are also well
known for their pronounced anti-inflammatory properties
[9] and are used as potent antidiabetic agents [10]. In
addition, the pharmacological and antitumor activities of
many compounds containing pyrazoline rings have been
reviewed [11]. Recent progressive interest was directed
toward nanocrystal investigation of 1,3,5-triaryl-2-pyra-
zoline derivatives [12] due to their well-known fluores-
cence properties with high quantum yield useful as
whitening or brightening agents for textile fibre, plastic
and paper industries [13]. Many efforts have been also
directed toward use of this behavior for construction of
C
V
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268
N. Louhichi, A. Houas, N. B. Hamadi, and M. Msaddek
Vol 49
Scheme 1
Scheme 2
described the development of 1,3-DCs of 2-diazopropane.
These compounds are converted to cyclopropanes.
RESULTS AND DISCUSSION
the 1,3-DCs reaction of ethereal 2-diazopropane to a so-
lution of 3-methylene-N-phenylpyrrolidine-2,5-dione
derivatives 4 in dichloromethane at ꢀ78ꢁC leads to the
corresponding spiro-D1-pyrazolines 5 in good yield. Irra-
diation of an ethereal solution of the D1-pyrazolines 5
through Pyrex with a high-pressure mercury arc lamp
(Philips HPK 125 W) at 0–5ꢁC led to exclusive forma-
tion of gem-dimethylcyclopropanes [25] (Scheme 3). Its
spectroscopic data (NMR) fit perfectly with those of
product 6.
The starting materials 2 and 4 were prepared by con-
densation of pyrrolin-2-one, c-butyrolactone, and N-phe-
nylmaleimide, respectively, with aldehydes as described
in the literature [22]. Diazopropane 1 was prepared
according to the literature procedure and conserved at
ꢀ78ꢁC [23]. When a solution of hydrazone in CH2Cl2
containing 2.5 equiv. of triethylamine was added to a
ꢀ78ꢁC solution of chlorodimethylsulfonium chloride in
CH2Cl2, the color of the reaction immediately changed
to dark red (Scheme 1).
In summary, the reaction of 2-diazopropane with (E)-
a-arylidenepyrrolin-2-one, (E)-a-arylidene-c-butyrolac-
tone, and (E)-arylidene-N-arylsuccinimide derivatives is
regiospecific. Photolysis of the initially formed spiro-D1-
pyrazoline 5 afforded gem-dimethylcyclopropanes 6.
Addition of 2-diazopropane 1 to a solution of 2 in
dichloromethane at 0ꢁC until 2 was consumed followed
by warming to room temperature gave monoadducts
spiro-D1-pyrazolines 3 in good yield (Scheme 2). The
spiro adducts 3a–i were purified and characterized.
The 1,3-DCs of 2-diazopropane is, in each case,
regiospecific. The chemical shifts of C5 [13C-nuclear
magnetic resonance (NMR)] are in excellent agreement
with those usually obtained when this quaternary carbon
is attached to nitrogen atom [24]. In a similar manner,
EXPERIMENTAL
Generalities. Infrared spectra were recorded on Perkin-
Elmer IR-197 infrared spectrometer. Mass spectra were
Scheme 3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2012
Synthesis and Chemistry of New Spiro-D1-Pyrazoline
269
determined on a Nierjohnson MS80RF spectrometer. Melting
points were determined on a Buchi-510 capillary melting point
apparatus. Thin layer chromatography (TLC) was performed
on silica gel 254 plates (Merck) with UV (254 nm) visualisa-
tion whereas chromatographic separations were conducted on
silica gel Si-60-7734 Merck using water-Jacketed columns.
1H-NMR and 13C-NMR spectra were recorded at 300 and
75.47 MHz, respectively. Coupling constants are given in Hz.
Elemental analyses were performed on a Perkin-Elmer 240B
microanalyzer. Diethyl ether was freshly distilled over sodium
wire with a trace of benzophenone. Dichloromethane was dis-
tilled from calcium hydride.
General procedure for trapping of 2-diazopropane 1
with alkenes. A stirred solution of 2 and 4 (5 mmol) in dry
dichloromethane (150 mL) was cooled to ꢀ78ꢁC and treated
with an ethereal solution of 2-diazopropane. The mixture was
monitored by TLC, and the addition of 2-diazopropane was
ceased when no starting material was present. The mixture
was allowed to warm to room temperature for 3 h and concen-
trated to give the crude reaction product. Recrystallization
from ethanol.
CH3), 1.63 (s, 3H, CH3), 1.85 and 2.20 (m, 2H, H9), 3.05 and
3.65 (m, 2H, H8), 3.39 (s, 1H, H4), 4.38 and 4.42 (d, 2H, CH2,
J ¼ 16.5 Hz), 6.88–7.27 (m, 10H, Harom). 13C-NMR (CDCl3;
75.47 MHz) d: 24.3 and 28.8 (CH3), 29.0 (C9), 44.8 (C8), 48.0
(CH2), 53.1 (C4), 95.1 (C3), 101.4 (C5), 127.5–136.9 (Carom),
170.8 (C6). Anal. Calcd. For C21H23N3O: C, 75.65; H, 6.95;
N, 12.60%; Found: C, 75.34; H, 6.80; N, 12.55%.
7-Benzyl-4-tolyl-3,3-dimethyl-1,2,7-triazaspiro[4.4]non-1-ene-
6-one (3e). By the above method, (E)-N-benzyl-3-tolylidene-
pyrrolidin-2-one 2e (1.385 g, 5 mmol) gave white crystals
(1.179 g, 68%). mp 116–117ꢁC [ethanol]. IR: N¼¼N 1540,
C¼¼O 1680. 1H-NMR (CDCl3; 300 MHz) d: 1.53 (s, 3H,
CH3), 1.59 (s, 3H, CH3), 2.25 (s, 3H, CH3), 1.87 and 2.22 (m,
2H, H9), 3.06 and 3.58 (m, 2H, H8), 3.36 (s, 1H, H4), 4.37 and
4.41 (d, 2H, CH2, J ¼ 16.5 Hz), 6.98–7.68 (m, 9H, Harom).
13C-NMR (CDCl3; 75.47 MHz) d: 22.0, 24.3, and 27.7 (CH3),
29.0 (C9), 44.8 (C8), 48.1 (CH2), 53.2 (C4), 95.0 (C3), 101.4
(C5), 124.4–142.4 (Carom), 171.0 (C6). Anal. Calcd. For
C22H25N3O: C, 76.05; H, 7.25; N, 12.09%; Found: C, 76.43;
H, 7.40; N, 12.14%.
7-Benzyl-4-anisyl-3,3-dimethyl-1,2,7-triazaspiro[4.4]non-1-
ene-6-one (3f). By the above method, (E)-N-benzyl-3-anisyli-
denepyrrolidin-2-one 2f (1.46 g, 5 mmol) gave white crystals
(0.998 g, 55%). mp 113–114ꢁC [ethanol]. IR: N¼¼N 1535,
4-Phenyl-3,3-dimethyl-1,2,7-triazaspiro[4.4]non-1-ene-6-one
(3a). By the above method, (E)-3-benzylidenepyrrolidin-2-one
2a (0.865 g, 5 mmol) gave white crystals (0.972 g, 80%). mp
170–171ꢁC [ethanol]. IR: N¼¼N 1540, C¼¼O 1670 cmꢀ1
.
1H-
C¼¼O 1670 cmꢀ1. H-NMR (CDCl3; 300 MHz) d: 1.49 (s, 3H,
1
NMR (CDCl3; 300 MHz) d: 1.15 (s, 3H, CH3), 1.58 (s, 3H,
CH3), 2.00 and 2.28 (m, 2H, H9), 3.23 and 3.74 (m, 2H, H8),
3.30 (s, 1H, H4), 6.57 (s, 1H, NH), 6.89–7.25 (m, 5H, Harom).
13C-NMR (CDCl3; 75.47 MHz) d: 24.2 and 28.7 (CH3), 31.3
(C9), 40.3 (C8), 52.7 (C4), 94.9 (C5), 100.2 (C3), 127.5–136.8
(Carom), 173.9 (C6). Anal. Calcd. For C14H17N3O: C, 69.11; H,
7.04; N, 17.27%; Found: C, 69.14; H, 7.11; N, 17.05%.
CH3), 1.55 (s, 3H, CH3), 1.85 and 2.25 (m, 2H, H9), 3.03 and
3.49 (m, 2H, H8), 3.29 (s, 1H, H4), 3.88 (s, 3H, OCH3), 4.39
and 4.42 (d, 2H, CH2, J ¼ 16.5 Hz), 6.79–7.54 (m, 9H, Harom).
13C-NMR (CDCl3; 75.47 MHz) d: 24.4 and 28.0 (CH3), 29.2
(C9), 44.8 (C8), 47.9 (CH2), 54.0 (C4), 55.7 (OCH3), 95.0 (C3),
101.4 (C5), 126.4–159.0 (Carom), 170.8 (C6). Anal. Calcd. For
C22H25N3O2: C, 72.70; H, 6.93; N, 11.56%; Found: C, 72.71;
H, 6.78; N, 11.39%.
4-Tolyl-3,3-dimethyl-1,2,7-triazaspiro[4.4]non-1-ene-6-one
(3b). By the above method, (E)-3-tolylidenepyrrolidin-2-one
2b (0.935 g, 5 mmol) gave white crystals (0.617 g, 48%). mp
4-Phenyl-3,3-dimethyl-1,2-diaza-7-oxospiro[4.4]non-1-ene-
6-one (3g). By the above method, (E)-a-benzylidene-c-butyro-
lactone 2g (0.87 g, 5 mmol) gave white crystals (1.25 g, 61%).
160–161ꢁC [ethanol]. IR: N¼¼N 1540, C¼¼O 1670 cmꢀ1
.
1H-
NMR (CDCl3; 300 MHz) d: 1.21 (s, 3H, CH3), 1.63 (s, 3H,
CH3), 2.05 and 2.34 (m, 2H, H9), 2.32 (s, 3H, CH3), 3.28 and
3.79 (m, 2H, H8), 3.31 (s, 1H, H4), 6.72 (s, 1H, NH), 6.85 and
7.08 (d, 4H, Harom, J ¼ 8.1 Hz). 13C-NMR (CDCl3; 75.47
MHz) d: 21.0; 23.8 and 28.2 (CH3), 30.8 (C9), 40.0 (C8), 51.9
(C4), 94.3 (C5), 99.7 (C3), 128.9–136.9 (Carom), 173.7 (C6).
Anal. Calcd. For C15H19N3O: C, 70.01; H, 7.44; N, 16.33%;
Found: C, 70.03; H, 7.46; N, 16.40%.
mp 105–106ꢁC [ethanol]. IR: N¼¼N 1540, C¼¼O 1680 cmꢀ1
.
1H-NMR (CDCl3; 300 MHz) d: 1.18 (s, 3H, CH3), 1.58 (s,
3H, CH3), 2.15 (m, 1H, H9), 2.45 (m, 1H, H9), 3.31 (s, 1H,
H4), 4.35 (m, 1H, H8), 4.75 (m, 1H, H8), 6.84–7.27 (m, 5H,
Harom), 13C-NMR (CDCl3; 75.47 MHz) d: 24.1 and 28.8
(CH3), 32.6 (C9), 53.6 (C4), 67.2 (C8), 96.2 (C3), 99.2 (C5),
128.0–136.1 (Carom), 174.0 (C6). Anal. Calcd. For
C14H16N2O2: C, 68.83; H, 6.60; N, 11.47%; Found: C, 68.78;
H, 6.55; N, 11.41%.
4-Anisyl-3,3-dimethyl-1,2,7-triazaspiro[4.4]non-1-ene-6-one
(3c). By the above method, (E)-3-anisylidenepyrrolidin-2-one
2c (1.01 g, 5 mmol) gave white crystals (1.02 g, 75%). mp
4-Tolyl-3,3-dimethyl-1,2-diaza-7-oxospiro[4.4]non-1-ene-6-
one (3h). By the above method, (E)-a-tolylidene-c-butyrolac-
tone 2h (0.94 g, 5 mmol) gave white crystals (1.26 g, 65%).
110–111ꢁC [ethanol]. IR: N¼¼N 1535, C¼¼O 1675 cmꢀ1
.
1H-
NMR (CDCl3; 300 MHz) d: 1.21 (s, 3H, CH3), 1.63 (s, 3H,
CH3), 2.10 and 2.32 (m, 2H, H9), 3.29 and 3.81 (m, 2H, H8),
3.32 (s, 1H, H4), 3.79 (s, 3H, OCH3), 6.13 (s, 1H, NH), 6.81
and 6.87 (d, 4H, Harom, J ¼ 9 Hz), 13C-NMR (CDCl3; 75.47
MHz) d: 23.8 and 28.2 (CH3), 30.8 (C9), 39.8 (C8), 51.5 (C4),
55.2 (OCH3), 94.3 (C5), 99.5 (C3), 113.6–158.7 (Carom), 173.3
(C6). Anal. Calcd. For C15H19N3O2: C, 65.91; H, 7.01; N,
15.37%; Found:C, 69.99; H, 7.03; N, 15.42%.
mp 94–95ꢁC [ethanol]. IR: N¼¼N 1540, C¼¼O 1675 cmꢀ1
.
1H-NMR (CDCl3; 300 MHz) d: 1.08 (s, 3H, CH3), 1.74
(s, 3H, CH3), 2.04 (m, 1H, H9), 2.16 (s, 3H, CH3), 2.33
(m, 1H, H9), 3.18 (s, 1H, H4), 4.22 (m, 1H, H8), 4.64 (m,
1H, H8), 6.65; 6.94 (AA0BB0, Harom, JAA BB ¼ 8.1 Hz), 13C-
NMR (CDCl3; 75.47 MHz) d: 22.6, 27.3, 23.7, and 28.4
(CH3), 32.2 (C9), 53.0 (C4), 66.8 (C8), 95.6 (C3), 98.7 (C5),
129.2–137.4 (Carom), 173.7 (C6). Anal. Calcd. For
C15H18N2O2: C, 69.74; H, 7.02; N, 10.84%; Found: C, 69.63;
H, 6.92; N, 10.71%.
0
0
7-Benzyl-4-phenyl-3,3-dimethyl-1,2,7-triazaspiro[4.4]non-1-
ene-6-one (3d). By the above method, (E)-N-benzyl-3-benzyli-
denepyrrolidin-2-one 2d (1.31 g, 5 mmol) gave white crystals
(1.33 g, 80%). mp: 139–140ꢁC [ethanol]. IR: N¼¼N 1545,
4-Anisyl-3,3-dimethyl-1,2-diaza-7-oxospiro[4.4]non-1-ene-
6-one (3i). By the above method, (E)-a-anisylidene-c-butyro-
lactone 2i (1.02 g, 5 mmol) to give white crystals (0.894 g,
1
C¼¼O 1670 cmꢀ1. H-NMR (CDCl3; 300 MHz) d: 1.52 (s, 3H,
Journal of Heterocyclic Chemistry
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N. Louhichi, A. Houas, N. B. Hamadi, and M. Msaddek
Vol 49
49%). mp 64–65ꢁC [ethanol]. IR: N¼¼N 1535, C¼¼O 1670
REFERENCES AND NOTES
1
cmꢀ1. H-NMR (CDCl3; 300 MHz) d: 1.24 (s, 3H, CH3), 1.63
[1] (a) Lange, J. H. M.; Coolen, H. K. A. C.; vanStuivenberg,
H. H.; Dijksman, J. A. R.; Herremans, A. H. J.; Ronken, E.; Keizer,
H. G.; Tipker, K.; Mcreary, A. C.; Veerman, W.; Wals, H. C.; Stork,
B.; Verveer, P. C.; Denhartog, A. P.; deJong, N. M. J.; Adolfs, T. J.
P.; Hoogendoorn, J.; Kruse, C. G. J Med Chem 2004, 47, 627; (b) Chi-
menti, F.; Bolasco, A.; Manna, F.; Secci, D.; Chimenti, P.; Befani, O.;
Turini, P.; Giovannini, V.; Mondovi, B.; Cirilli, R.; La Torre, F. J
Med Chem 2004, 47, 2071; (c) Camacho, M. E.; Leon, J.; Entrena, A.;
Velasco, G.; Carrion, M. D.; Escames, G.; Vivo, A.; Acuna-Castro-
viejo, D.; Gallo, M. A.; Espinosa, A. J Med Chem 2004, 47, 5641; (d)
Rajendra Prasad, Y.; Lakshmana Rao, A.; Prasoona, L.; Murali, K.;
Ravi Kumar, P. Bioorg Med Chem Lett 2005, 15, 5030; (e) Cox, C.
D.; Torrent, M.; Breslin, M. J.; Mariano, B. J.; Whitman, D. B.; Cole-
man, P. J.; Buser, C. A.; Walsh, E. S.; Hamilton, K.; Schaber, M. D.;
Lobell, R. B.; Tao, W.; South, V. J.; Kohl, N. E.; Yan, Y.; Kuo, L. C.;
Prueksaritanont, T.; Slaughter, D. E.; Li, C.; Mahan, E.; Lu, B.; Hart-
man, G. D. Bioorg Med Chem Lett 2006, 16, 3175; (f) Goodell, J. R.;
Puig-Basagoiti, F.; Forshey, B. M.; Shi, P. Y.; Ferguson, D. M. J Med
Chem 2006, 49, 2127.
(s, 3H, CH3), 2.15 (m, 1H, H9), 2.41 (m, 1H, H9), 3.27 (s, 1H,
H4), 3.73 (s, 3H, OCH3), 4.33 (m, 1H, H8), 4.74 (m, 1H, H8),
6.74–7.2 (m, 4H, Harom), 13C-NMR (CDCl3; 75.47 MHz) d:
22.6 and 27.3 (CH3), 31.1 (C9), 51.5 (C4), 54. 2 (OCH3), 65.7
(C8), 94.5 (C3), 97.6 (C5), 112.8–157.9 (Carom), 172.7 (C6).
Anal. Calcd. For C15H18N2O3: C, 65.68; H, 6.61; N, 10.21%;
Found: C, 65.59; H, 6.56; N, 10.17%.
4-Furfuryl-3,3-dimethyl-7-phenyl-1,2,7-triazaspiro[4.4]non-
1-ene-6,8-one (5a). By the above method, furfurylidene-N-
phenylsuccinimide 4a (1.26 g, 5 mmol) to give a white ꢀcr1ystals
(0.807 g, 50%). mp 154–155ꢁC. IR: N¼¼N 1530 cm
.
1H-
NMR (CDCl3; 300 MHz) d: 1.28 (s, 3H, CH3), 1.67 (s, 3H,
CH3), 2.81 and 3.13 (d, 2H, H9, J ¼ 18.3 Hz), 3.77 (s, 1H,
H4), 6.91–7.39 (m, 8H, Harom). 13C-NMR (CDCl3; 75.47 MHz)
d: 22.9 and 25.9 (CH3), 36.2 (C9), 47.9 (C4), 94.1 (C3), 97.0
(C5), 127.6–133.0 (Carom), 172.1 and 174.5 (C6,8). Anal. Calcd.
For C18H17N3O3: C, 66.86; H, 5.30; N, 13.00%; Found: C,
66.80; H, 5.27; N, 13.09%.
[2] (a) Bilgin, A.; Palaska, E.; Sunal, R.; Gumusel, B. Pharmazie
1994, 49, 67; (b) Bilgin, A.; Palaska, E.; Sunal, R. Arzneimittel-for-
schung/Drug Res 1993, 43, 1041; (c) Bilgin, A.; Yesilada, A.; Palaska,
E.; Sunal, R. Arzneimittel-forschung/Drug Res 1992, 42, 1271.
[3] Gokhan, N.; Yesilada, A.; Ucar, G.; Erol, K.; Bilgin, A.
Arch Pham Med Chem 2003, 336, 362.
3,3-Dimethyl-7-phenyl-4-thiophenyl-1,2,7-triazaspiro[4.4]-
non-1-ene-6,8-one (5b). By the above method, (2-thiophe-
nyl)methylene-N-phenylsuccinimide 4b (1.34 g, 5 mmol) to
give white crystals (1.02 g, 60%). mp 173–174ꢁC. IR: N¼¼N
1
1540 cmꢀ1. H-NMR (CDCl3; 300 MHz) d: 1.35 (s, 3H, CH3),
1.74 (s, 3H, CH3), 2.93 and 3.16 (d, 2H, H9, J ¼ 18.3 Hz),
3.98 (s, 1H, H4), 6.87–7.54 (m, 8H, Harom). 13C-NMR (CDCl3;
75.47 MHz) d: 23.2 and 26.6 (CH3), 36.2 (C9), 48.8 (C4), 94.1
(C3), 96.4 (C5), 126.5–134.9 (Carom), 173.1 and 173.6 (C6,8).
Anal. Calcd. For C18H17N3O2S: C, 63.70; H, 5.05; N, 12.38%;
Found: C, 63.71; H, 5.08; N, 12.25%.
[4] Amr, A. E.; Hegab, M. I.; Ibrahim, A. A.; Abdalah, M. M.
Monatschefte fur Chemie 2003, 134, 1395.
[5] (a) Amr, A. E.; Abou-Ghalia, M. H. Amino Acids 2004, 26,
283; (b) Brana, M. F.; Castellano, J. M.; Mpran, M.; Perez de Vega,
M. J.; Gian, X. D.; Romerdahl, C. A.; Keihauer, G.; Eur Med Chem
1995, 30, 235.
General procedure for the irradiation of the spiro-D1-
pyrazolines (5a–b). All irradiations were carried out using
similar conditions. The derivative was dissolved in ether
[pretreated by stirring with solid (NaCO3), filtered and
flushed with argon] and irradiated at 5ꢁC for a total of 1 h
or until the starting material 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. Recrystallization from dichloromethane/light
petroleum.
2-Furfuryl-1,1-dimethyl-5-phenyl-5-azabicyclo[4.2]-4,6-dione
(6a). By the above method, pyrazoline 5a (1.61 g, 5 mmol) to
give a white solid (0.737 g, 50%). mp 180–181ꢁC. 1H-NMR
(CDCl3; 300 MHz) d: 1.21 (s, 3H, CH3), 1.63 (s, 3H, CH3),
2.66 and 2.80 (d, 2H, H7, J ¼ 19.2 Hz), 3.03 (s, 1H, H2),
6.97–7.33 (m, 8H, Harom), 13C-NMR (CDCl3; 75.47 MHz) d:
20.71 and 20.80 (CH3), 31.22 (C7), 31.85 (C1), 34.00 (C3),
40.23 (C2), 126.96–133.01 (Carom), 175.15 and 176.84 (C4,6).
Anal. Calcd. For C18H17NO3: C, 73.20; H, 5.80; N, 4.74%;
Found: C, 73.25; H, 5.76; N, 4.65%.
1,1-Dimethyl-5-phenyl-2-thiophenyl-5-azabicyclo[4.2]-4,6-
dione (6b). By the above method, pyrazoline 5b (1.69 g, 5
mmol) to give a white solid (1.24 g, 80%). mp 149–150ꢁC.
1H-NMR (CDCl3; 300 MHz) d: 1.22 (s, 3H, CH3), 1.52 (s,
3H, CH3), 2.64 and 2.73 (d, 2H, H7, J ¼ 19.2 Hz), 2.97 (s,
1H, H2), 6.79–7.44 (m, 8H, Harom). 13C-NMR (CDCl3; 75.47
MHz) d: 20.25 and 20.99 (CH3), 31.35 (C7), 31.41 (C1), 33.71
(C3), 40.11 (C2), 123.75–134.63 (Carom), 174.66 and 175.16
(C4,6). Anal. Calcd. For C18H17NO2S: C, 69.43; H, 5.50; N,
4.50%; Found: C, 69.40; H, 5.46; N, 4.39%.
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