An efficient one pot synthesis of new indanopyrazoline and indanopyrazole derivatives

Article abstract of DOI:10.2174/157017811795371421

Synthesis of a series of novel fused pyrazolines and pyrazoles has been accomplished in good yields by regioand diastereoselective 1,3-dipolar cycloaddition of enamines of indan-1-one 1a-c towards C-aryl-N- phenylnitrilimines 2df. The structure of the cycloadducts was elucidated by 1D and 2D NMR studies.

Full text of DOI:10.2174/157017811795371421

268
Letters in Organic Chemistry, 2011, 8, 268-273
An Efficient One Pot Synthesis of New Indanopyrazoline and
Indanopyrazole Derivatives
Hanene Jelizia, Mohamed M. Rammaha, Moheddine Askria, Mohamed El Baker Rammah*,a,
Kabula Ciamalab and Karin Monnier-Jobé*,b
aLaboratoire de Chimie Organique Heterocyclique/LPCI, Département de Chimie, Faculty of Science of Monastir, 5000
Monastir, Tunisia
bInstitut UTINAM - UMR CNRS 6213- Equipe Matériaux et Surfaces Structurés - University of Franche-Comté,
Besançon, France
Received September 16, 2010: Revised October 29, 2010: Accepted January 06, 2011
Abstract: Synthesis of a series of novel fused pyrazolines and pyrazoles has been accomplished in good yields by regio-
and diastereoselective 1,3-dipolar cycloaddition of enamines of indan-1-one 1a-c towards C-aryl-N-phenylnitrilimines 2d-
f. The structure of the cycloadducts was elucidated by 1D and 2D NMR studies.
Keywords: 1-Aminoindenes, C-aryl-N-phenylnitrilimines, [3+2] Cycloaddition, pyrazole, pyrazoline, regiochemistry.
INTRODUCTION
Pyrazoles can be easily prepared from nitrilimines and
dipolarophiles bearing a carbon-carbon double or triple
bonds in a two-step reaction, the subsequent oxidative
heteroaromatization of pyrazolines requires drastic reaction
conditions.
Pyrazolines and pyrazoles represent important nitrogen-
containing five membered heterocyclic compounds and
various methods have been worked out for their synthesis [1-
4]. Derivatives of pyrazolines and pyrazoles have played a
crucial role in the history of heterocyclic chemistry and have
been used extensively as important pharmacophores and
synthons in the field of organic chemistry and drug design.
Since several years, we have focused our research on the
reactivity of dipolarophiles bearing an exo- and endocyclic
carbon-carbon double bond towards several 1,3-dipole such
as nitrile oxides [33], diazoalkanes [34] and
diarylnitrilimines [35].
Several pyrazoline derivatives have been found to
process considerable activity such as antifungal [5],
antidepressant [6-9] anticonvulsant [8, 9], anti-inflammatory
[10], antibacterial [11] and anti-tumor [12] properties.
Moreover, many selectively fluoro-substituted organic
compounds show peculiar pharmacological and agroche-
mical properties [13-18].
In continuation of our work in the area of cycloaddition
reactions, we report herein on the efficient synthesis of series
of novel fused pyrazolines and pyrazoles by regio- and
stereoselective 1,3-dipolar cycloaddition of enamines of
indan-1-one 1a-c towards C-aryl-N-phenylnitrilimines 2d-f.
2-pyrazoline seems to be one the most frequently studied
derivatives among all pyrazoline-type compounds. Pyrazoles
are extensively used in the field of medicine and
agrochemistry. A number of pyrazole derivatives have been
reported to process interesting biological activities like anti-
inflammatory, antimicrobial, antiprotozoal and cerebro-
protective [19-22].
In our previous work, we have reported the 1,3-dipolar
cycloaddition of diphenylnitrilimine with enamines of 1-
tetralone at benzene reflux [36]. Under these conditions, only
the pyrazoles were isolated, resulting from the loss of the
amino group in the acidic reaction medium from the
intermediate pyrazolines. In a preliminary note, some
members of our group have already reported the reaction of
C-p-anisyl-N-phenylnitrilimine towards 3,3-dimethylindan-
1-one at benzene reflux [37]. For the first time, we have now
succeeded to isolate and to characterize the pyrazolines 3
bearing a cyclic amino-substituent. The later were obtained
as the major products from reaction conducted in toluene at
60° C instead of refluxing benzene, implementing the [3+2]
cycloaddition of C-aryl-N-phenylnitrilimines towards
enamines of indan-1-one.
Several methods are employed for the synthesis of
pyrazolines, including the condensation of chalcones with
hydrazine, hydrazine derivatives [23-27] and thiosemi-
carbazide [28] under acidic [23, 24] or basic [28] conditions,
and the cycloaddition of nitrilimines with carbon-carbon
double bonds of a suitable dipolarophile [29-32].
*Address correspondence to these authors at the Laboratoire de Chimie
Organique Heterocyclique/LPCI, Département de Chimie, Faculty of
Science of Monastir, 5000 Monastir, Tunisia; Tel: + [216] 73501968;
E-mail: mohamedelbaker.rammah@fsm.rnu.tn
The results reported herein were aimed at the preparation
of some new pyrazolines and pyrazoles derivatives with
anticipated biological activities.
Institut UTINAM - UMR CNRS 6213- Equipe Matériaux et Surfaces
Structurés - University of Franche-Comté, Besançon, France; Tel: + [33] 3
81 66 62 69; E-mail: karin.monnier-jobe@univ-fcomte.fr
1570-1786/11 $58.00+.00
© 2011 Bentham Science Publishers Ltd.

New Indanopyrazoline and Indanopyrazole Derivatives
Letters in Organic Chemistry, 2011, Vol. 8, No. 4
269
RESULTS AND DISCUSSION
cycloadducts 3 and pyrazoles 4 for an X-ray analysis. The
assigned structures 3ad-cf and are, however,
4
In order to evaluate the effect of an electron-donating
group on the double bond, the cycloaddition of C-aryl-N-
phenylnitrilimine 2d-f (generated in situ by the
dehydrochlorination of hydrazonoyl chlorides with
triethylamine) with various enamines of indan-1-one 1a-c
was carried out at 60°C in toluene (Scheme 1). This choice
was based on previous results [36, 37] which show that a
secondary amino group is very essential leaving group in
[3+2] cycloaddition. The reaction leads to a mixture of two
products, the 4H-3a,8b-dihydro-indeno[2,3-d]pyrazolines
3ad-cf (45-60 %) and the derivatives 4H-indeno[2, 3-
d]pyrazoles 4 (30-38 %, see Table 1).
unambiguously supported by analytical and spectroscopic
data (IR, 1H, 13C NMR, see experimental part).
The 1,3 dipolar cycloaddition of C-aryl-N-
phenylnitrilimines is in each case 100% regioselective. The
1
regioselectivity of the adducts 3ad-cf was accessed by H
and 13C NMR spectroscopy. The 13C NMR studies gave a
singlet for the quaternary carbon C-8b at 96 ppm. On the
other side, a doublet was observed for the tertiary carbon C-
1
3a at around 44.33-49.93 ppm (CDCl3/TMS). The H NMR
spectra (300 MHz) exhibit a doublet of doublets between 3.8
ppm and 4 ppm attributed to the 3a-H proton. Note that in
the case of the reverse regioisomers 3’, one should observe a
chemical shift value higher than 4.9 ppm for the 3a-H proton
[36, 38]. The 1,3-dipole can be oriented by a secondary
These
products
were
isolated
by
column
chromatography, using hexane/ ethyl acetate as an eluent.
Unfortunately, we failed in obtaining suitable crystals of
N
d : R=H
C
N NH
e : R=CH3
f : R=OCH3
+
cl
1a-c
2d-f
a : N-pyrrolidinyl
b : morpholino
c: N-piperidinyl
N
Toluène reflux
Et3N
1
N
N
N
2
3
1
+
N
N
2
3
N
N
N
8b
3a
8b
3a
4
4
H
H
H
H
R
R
3ad-cf
Scheme 1. Reactions of amino-indenes 1a-c with C-aryl-N-phenylnitrilimines 2d-f.
Table 1. Yields of 4H-3a,8b-dihydro-indeno[2, 3-d]pyrazoline 3ad-cf and 4H-indeno[2, 3-d]pyrazoles 4df
R
4d-f
3'ad-cf
Entry
Dipolarophiles
Dipoles
Pyrazolinesa
Yieldb(%)
Pyrazoles
Yield(%)
a
a
a
b
b
b
c
c
c
d
e
f
3ad
3ae
3af
3bd
3be
3bf
3cd
3ce
3cf
54
50
60
45
50
55
51
50
55
4d
4e
4f
37
34
35
35
36
31
38
34
30
1
d
e
f
4d
4e
4f
2
3
d
e
f
4d
4e
4f
aReaction in toluene at 60°C during 3 days.

270 Letters in Organic Chemistry, 2011, Vol. 8, No. 4
Jelizi et al.
amino group fixed on the C-atom of the dipolarophilic
double bond. In any case, the terminal nitrogen atom of the
dipole is linked with the C-atom bearing the amino group.
The chemical shifts of their 3a-H proton corresponded to
those of 3a-H of the related pyrazolines derivatives obtained
in our previous work from C-p-anisyl-N-phenylnitrilimine
towards 3,3-dimethylindan-1-one [37]
This result can be explained by the presence of an excess of
hydrogen chloride, liberated from C-aryl-N-phenylbenzohy-
drazidochloride; which promotes then the elimination of
amino group.
In order to verify, whether product 4 stems from 3, we
first refluxed compound 3 in a EtOH/HCl 12 M mixture
(10:1) (Scheme 2). The physical characteristics, IR and
NMR spectroscopic data of the isolated products 4d-f were
identical to those of compounds 4 generated initially in the in
situ one-pot reaction. It is interesting to note that
independent of the nature of the amino group of the
enamines, cycloaddition leads to the same result. The
reactions were carried out with pyrolydinyl, morpholino and
piperidinyl groups.
Further confirmation for the proposed regiochemistry is
provided from the HMBC spectra, which show two
correlations between 4-H, 4’-H with C-3 at 160 ppm and 4-
H, 4’H with C-3’ at 139 ppm: (Fig. 1). This excludes the
presence of the inverse regioisomer 3’, in which the last
5
correlations should be absent (4-H and 4’-H present a J
coupling constant with C-3’).
MATERIALS AND METHODS
O
B
Reactions were carried out under an atmosphere of dry
N2. Solvents were purified by standard methods and freshly
distilled under nitrogen and dried before use. Melting points
were determined on a Kofler bank. Only structurally
significant bands are reported. NMR spectra were recorded
on a Bruker-Spectrospin AC 300 spectrometer operating at
300 MHz for 1H and 75.5 MHz for 13C. Chemical shifts were
measured relative to TMS in CDCl3 as a solvent. Materials:
thin-layer chromatography (TLC): TLC plates (Merck, silica
gel 60 F254 0.2 mm 200ꢀ200 nm).
N
H
N
A
N
1
2
3
3a
3'
4
3J
H
OCH3
4J
Fig. (1). selected HMBC correlations of 3bf.
The enamines of indan-1-one 1a-c were prepared by
reacting given secondary amine with indanone, often in the
presence of an acid catalyst according to reported methods
[42-44].
For all pyrazolines 3 the chemical shifts of each
hydrogen atom attached on a sp3 carbon atom, have been
unambiguously attributed according to the observations
made in previous reports [39-41]. Indeed, it was clearly
established that the values of cis coupling constants were
always larger than that of the trans coupling constants.
Furthermore, the J value of 4.2 Hz suggests that the protons
at 3.35 ppm (4’-H), are in trans relationship with that at 3.80
ppm (3a-H). The doublets of doublets at 3.62- 3.75 ppm are
assigned to 4-H in cis relationship with 3a-H due to the J
values of 7.8 or 9.3 Hz. In addition, it has been shown that
the difference in chemical shifts of the two C-4 protons, with
J coupling constants of 12.9 - 13.8 Hz in gem-position can
be used to establish the relative stereochemistry of the C-3a
and C-4.
The C-aryl-N-phenylnitrilimines were prepared in situ
from the respective hydrazonoyl chlorides 2d-f by reaction
with triethylamine according to ref [45, 46].
General Procedure for the Preparation of the
Cycloadducts 3ad-cf and 4d-f
A magnetically stirred solution of dipolarophiles 1a-c
and C-aryl-N-phenylnitrilimines 2d-f in dry toluene, was
kept at 60°C for 3 days. The solvent was then evaporated
under reduced pressure and the residue was purified by
column chromatography on silica gel with hexane/ethyl
acetate mixture (80/20) as eluent to afford compounds 3ad-
cf and 4d-f.
The acid-catalyzed transformation of compound 3
produces more stable heteroaromatic pyrazoles derivatives 4.
HCl
N
EtOH
N
N
N
N
N
-
N
N
NH
H
H
R
R
R
4d-f
3ad-cf
d : R=H
e : R=CH3
f : R=OCH3
Scheme 2. Formation of pyrazoles 4d-f by elimination of amino group.

New Indanopyrazoline and Indanopyrazole Derivatives
Letters in Organic Chemistry, 2011, Vol. 8, No. 4
271
1,3-diphenyl-8b-pyrolydinyl-4H-3a,8b-dihydro-indeno[2,3-
d]pyrazoline (3ad)
3-(4-methoxyphenyl)-8b-morpholino-1-phenyl-4H-3a,8b-
dihydro-indeno[2,3-d]pyrazoline (3bf)
Yield (55%); dark yellow needles; Mp 192°C; IR (KBr):
Yield (54%); green needles; Mp 172 °C; IR (KBr): ꢀ
1
ꢀ 1595, 1250 cm-1; H NMR (CDCl3): ꢁ 2.63-2.65 (m, 4H);
1
1583, 1248 cm-1; H NMR (CDCl3) :ꢁ 1.10-1.15 (m, 4H);
3.05-3.10 (m, 4H); 3.40 (dd, 1H, J=4.2Hz, J=13.8Hz); 3.75
(dd, 1H, J=7.8Hz, J=13.8Hz); 3.82 (s, OCH3); 3.80 (dd, 1H
J=4.2Hz, J=7.8Hz); 6.95-7.90 (m, aromatic H) ppm; 13C
NMR (CDCl3): 30.08 (C-4); 45.27 (C-3a); 47.33 (N-C);
55.65 (OCH3); 66.97 (O-C); 96 (C-8b); 113.19-167.93
(aromatic C). Anal. Calcd. for C27H27N3O2: C 76.21%, H
6.40%, N 9.87%. Found: C 76.40%, H 6.41%, N 9.85%.
3.36 (dd, 1H, J=4.2Hz, J=12.9Hz); 3.5-3.61 (m, 4H); 3.72
(dd, 1H, J=9.3Hz, J=12.9Hz); 3.79 (dd, 1H, J=4.2Hz,
J=9.3Hz); 6.88-7.83 (m, aromatic H) ppm; 13C NMR
(CDCl3) : ꢁ 24.28 (CA) ; 30.14 (C-4); 47.52 (N-C); 49.52 (C-
3a); 96 (C-8b) ;158.71(C-3); 112.77-166.50 (aromatic C).
Anal. Calcd. for C26H25N3 : C 82.29%, H 6.64%, N 11.07%.
Found: C 82.41%, H 6.48%, N 10.98.
1,3-diphenyl-8b-piperidinyl-4H-3a,8b-dihydro-indeno[2,3-
d]pyrazoline (3cd)
3-(4-methylphenyl)-1-phenyl-8b-pyrolydinyl-4H-3a,8b-
dihydro-indeno[2,3-d]pyrazoline (3ae)
Yield (51%); green solid; Mp 176°C; IR (KBr): ꢀ 1590,
Yield (50%); green needles; Mp 168 °C; IR (KBr): ꢀ
1
1248 cm-1; H NMR (CDCl3): ꢁ 1.55 (m, 2H); 1.56 (m,4H);
1
1588, 1250 cm-1; H NMR (CDCl3): ꢁ 1.09-1.16 (m, 4H);
2.30-2.60 (m, 4H); 3.32 (dd, 1H, J=4.2Hz, J=13.8Hz); 3.68
(dd, 1H, J=9.3Hz, J=13.8Hz); 3.80 (dd, 1H, J=4.2Hz,
J=7.8Hz); 6.70-7.80 (m, aromatic H) ppm; 13C NMR
(CDCl3): ꢁ 24.83 (CB); 25.78 (CA); 30.19 (C-4); 47.43 (N-
C); 47.88 (C-3a); 96 (C-8b); 112.82-167.40 (aromatic C).
Anal. Calcd. for C27H27N3: C 82. 41%, H 6.92%, N 10.68%.
Found: C 82.24%, H 6.95%, N 10.73%.
2.41 (s, CH3); 3.35 (dd, 1H, J=4.2Hz, J=12.9) ; 3.55-3.59
(m, 4H); 3.62 (dd, 1H, J=9.3Hz, J=12.9Hz); 3.81(dd, 1H,
J=4.2Hz, J=9.3Hz); 6.89-7.84 (m, aromatic H) ppm; 13C
NMR (CDCl3): ꢁ 21.39 (CH3); 24.63 (CA); 30.18 (C-4);
47.85 (N-C); 49.93 (C-3a); 96(C-8b); 159.02 (C-3) ;113.62-
167.40 (aromatic C). Anal. Calcd. for C27H27N3: C 82.41%,
H 6.92%, N 10.68%. Found: C 82.18%, H 6.84%, N 10.79.
3-(4-methylphenyl)-1-phenyl-8b-piperidinyl-4H-3a,8b-
dihydro-indeno[2,3-d]pyrazoline (3ce)
3-(4-methoxyphenyl)-1-phenyl-8b-pyrolydinyl-4H-3a,8b-
dihydro-indeno[2,3-d]pyrazoline (3af)
Yield (50%); green needles; Mp 165°C; IR (KBr): ꢀ
1
1600, 1250 cm-1; H NMR (CDCl3): ꢁ 1.41 (m, 2H); 1.68
Yield (60%); green solid; Mp 198 °C; IR (KBr): ꢀ 1595,
1
1254 cm-1; H NMR (CDCl3): ꢁ 1.13-1.16 (m, 4H); 2.41 (s,
(m, 4H); 2.40-2.60 (m, 4H); 2.4 (s, CH3) ; 3.35 (dd, 1H,
J=4.2Hz, J=13.8Hz); 3.75 (dd, 1H, J=9.3Hz, J=13.8Hz);
3.80(dd, 1H J=4.2Hz, J=9.3Hz); 6.68-8.1 (m, aromatic H)
ppm; 13C NMR (CDCl3): ꢁ 21.85 (CH3); 25.05 (CB); 25.94
(CA); 30.35 (C-4);45.01 (C-3a); 47.91 (N-C); 96 (C-
8b); 112.82-167.40 (aromatic C). Anal. Calcd. for C28H29N3:
C 82.52%, H 7.17%, N 10.31%. Found: C 82.29%, H 7.21%,
N 10.27%.
CH3); 3.36 (dd, 1H, J=4.2Hz, J=12.9Hz); 3.50-3.61 (m, 4H);
3.69 (dd, 1H, J=9.3Hz, J=12.9Hz); 3.81(dd, 1H, J=4.2Hz,
J=9.3Hz); 3.77 (s,OCH3) 6.89-7.83 (m, aromatic H) ppm;
13C NMR (CDCl3): ꢁ 24.43(CA); 30.44 (C-4); 47.43 (N-C);
49.49( C-3a); 55.70 (OCH3); 96 (C-8b); 161.78 (C-3);
114.62-166.40 (aromatic C). Anal. Calcd. for C27H27N3O: C
79.19%, H 6.65%, N 10.26%. Found: C 79.40%, H 6.47%, N
10.03%.
3-(4-methoxyphenyl)-1-phenyl-8b-piperidinyl-4H-3a,8b-
dihydro-indeno[2,3-d]pyrazoline (3cf)
1,3-diphenyl-8b-morpholino-4H-3a,8b-dihydro-indeno[2,3-
d]pyrazoline (3bd)
Yield (55%); green needles; Mp 190 °C; IR (KBr): ꢀ
1
1610, 1249 cm-1; H NMR (CDCl3): ꢁ 1.40 (m, 2H); 1.57
Yield (45 %); Light yellow needles; Mp 175 °C; IR
1
(KBr): ꢀ 1588, 1250 cm-1; H NMR (CDCl3): ꢀ 2.1-2.4 (m,
(m, 4H); 2.30-2.60 (m, 4H); 3.34 (dd, 1H, J=4.2Hz,
J=13.8Hz); 3.65 (dd, 1H, J=9.3Hz, J=13.8Hz); 3.80 (dd, 1H,
J=4.2Hz, J=9.3Hz); 3.82 (s, OCH3); 6.81-7.82 (m, aromatic
H) ppm; 13C NMR (CDCl3): ꢁ 25.08 (CB); 25.98 (CA); 30.28
(C-4); 46.91(N-C); 47.91(C-3a); 55.78 (OCH3); 96 (C-8b);
113.62-165.46 (aromatic C). Anal. Calcd. for C28H29N3O:
C79.40%, H 6.90%, N 9.92%. Found: C 79.31%, H 6.99%,
N 9.89%.
4H); 3.25-3.6 (m,4H); 3.36 (dd, 1H, J=4.2Hz, J=13.8Hz);
3.65 (dd, 1H, J=7.8Hz, J=13.8Hz); 3.80 (dd, 1H, J=4.2Hz,
J=7.8Hz) 6.69- 7.49 (m, aromatic H) ppm; NMR (CDCl3): ꢁ
30.54 (C-4); 44.33 (C-3a); 46.86 (N-C); 66.62 (O-C); 96 (C-
8b); 113.22-168.34 (aromatic C). Anal. Calcd. for
C26H25N3O: C 78.96%, H 6.37%, N 10.26%. Found: C
78.77%, H 6.25%, N 10.35%.
1,3-diphenyl-4H-indeno[2, 3-d]pyrazole (4d)
3-(4-methylphenyl)-8b-morpholino-1-phenyl-4H-3a,8b-
dihydro-indeno[2,3-d]pyrazoline (3be)
Yield (37 %); green needles; Mp 170 °C; IR (KBr): ꢀ
1
1595, 1248 cm-1; H NMR (CDCl3): ꢁ 3.74 (s, H4); 6.72-
Yield (50 %); yellow needles ; Mp 18 0 °C; IR (KBr): ꢀ
7.90 (m, aromatic H) ppm; 13C NMR (CDCl3): ꢁ 30.15 (C-
4); 112-149 (aromatic C). Anal. Calcd for C22H16N2: C
85.69%, H 5.23%, N 9.08%. Found: C 85.97%, H 5.01%, N
9.13%.
1
1610, 1248 cm-1; H NMR (CDCl3): ꢁ 1.88-2.36 (m, 4H);
2.40 (s, CH3); 3.35 (dd, 1H, J=4.2Hz, J=13.8Hz); 3.65-3.72
(m, 4H); 3.69 (dd, 1H, J=7.8Hz, J=13.8Hz); 3.88 (dd, 1H,
J=4.2Hz, J=7.8Hz); 6.68-8.13 (m, aromatic H) ppm; 13C
NMR (CDCl3): ꢁ 21.81 (CH3); 30.56 (C-4); 44.33 (C-3a);
46.86 (N-C); 66.62 (O-C); 96 (C-8b); 112.88-167.99
(aromatic C). Anal. Calcd. for C27H27N3O: C 79.96%, H
6.65%, N 10.26%. Found: C 80.15%, H 6.48%, N 10.19%.
3-(4-methylphenyl)-1-phenyl-4H-indeno[2,
(4e)
3-d]pyrazole
Yield (34 %); yellow needles; Mp 180°C; IR (KBr): ꢀ
1600, 1237 cm-1; 1H NMR (CDCl3): ꢁ 2.45 (s, CH3); 3.88 (s,

272 Letters in Organic Chemistry, 2011, Vol. 8, No. 4
Jelizi et al.
H4); 7.26-7.90 (m, aromatic H) ppm; 13C NMR (CDCl3): ꢀ
21.45 (CH3); ꢀ 30.20 (C-4); 119.51-149.38 (aromatic C).
Anal. Calcd. for C23H18N2: C 85.68%, H 5.63%, N 8.69%.
Found: C 85.19%, H 5.69%, N 8.71%.
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Yield (35 %); yellow needles; Mp 191 °C; IR (KBr): ꢁ
1
1620, 1250 cm-1; H NMR (CDCl3): ꢀ 3.79 (s, OCH3); 3.76
(s, H4); 6.91-7.85 (m, aromatic H) ppm; 13C NMR (CDCl3):
ꢀ 30.08 (C-4); ꢀ 55.72 (OCH3); 114.51-159.88 (aromatic C).
Anal. Calcd. for C23H18N2O: C 81.63%, H 5.36%, N 8.28%.
Found: C 81.86%, H 5.34%, N 8.33%.
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CONCLUSION
In conclusion, we have shown that cycloaddition reaction
of enamines of indan-1-one 1a-c with C-aryl-N-
phenylnitrilimines 2d-f leads regioselectively and
respectively to a mixture of the 4H-3a,8b-dihydro-indeno[2,
3-d]pyrazoline 3ad-cf and 4H-indeno[2, 3-d]pyrazoles 4d-f.
naphthyridine-3-carboxylic acids, including enoxacin,
a new
antibacterial agent. J. Med. Chem., 1984, 27, 292-301.
The great interest in C-aryl-N-phenylnitrilimines
reactions on enamines of indan-1-one lies in the fact that it is
possible to obtain in high regioselectivity and directly the
pyrazolines derivatives. Independently, the conversion of the
pyrazolines 3 in acidic medium leads to the same pyrazole 4
as those formed in situ in the one-pot reaction.
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