Study of Regiochemical Trends During the Synthesis of Furan and 5-(p-chlorophenyl)Furan Containing Novel Spiropyrrolidine Library Through 1,3-dipolar Cycloaddition Reactions

Article abstract of DOI:10.1002/jhet.2499

A new class of functionalized furan and 5-(p-chlorophenyl)furan containing spiropyrrolidines has been synthesized in moderate to excellent yields by the one-pot, three-component 1,3-dipolar cycloaddition reaction of in situ generated azomethine ylides with various furan/aryl furan-substituted chalcones as dipolarophiles. The effect of electron deficient substituents at the fifth position of the furan ring in the chalcone on the regiochemistry of the cycloaddition formed was studied. The structures of the newly synthesized cycloaddicts were proved by analytical and spectral data.

Full text of DOI:10.1002/jhet.2499

Month 2015
Study of Regiochemical Trends During the Synthesis of Furan and
5-(p-chlorophenyl)Furan Containing Novel Spiropyrrolidine Library
Through 1,3-dipolar Cycloaddition Reactions
*
Sahana Mallya, Balakrishna Kalluraya, and H. S. Vidyashree Jois
Department of Studies in Chemistry, Mangalore University, Mangalagangothri 574 199, Karnataka, India
*
E-mail: bkalluraya@gmail.com
Additional Supporting Information may be found in the online version of this article.
Received April 23, 2015
DOI 10.1002/jhet.2499
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
A new class of functionalized furan and 5-(p-chlorophenyl)furan containing spiropyrrolidines has been
synthesized in moderate to excellent yields by the one-pot, three-component 1,3-dipolar cycloaddition reac-
tion of in situ generated azomethine ylides with various furan/aryl furan-substituted chalcones as
dipolarophiles. The effect of electron deficient substituents at the fifth position of the furan ring in the
chalcone on the regiochemistry of the cycloaddition formed was studied. The structures of the newly synthe-
sized cycloaddicts were proved by analytical and spectral data.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
significantly affected the regioselectivity of the 1,3-dipolar
cycloaddition, which allowed the formation of (3′R,4′R)-
4′-(4-substituted benzoyl)-1′-methyl-3′-(5-nitro-2-furfuryl)
spiro[indene-2,2′-pyrrolidine]-1,3-dione in good regioselec-
tivity. Our continued interest in further exploring the effect
of electron withdrawing groups on the regioselectivity trends
prompted us to study the mode of addition during the 1,3-
dipolar cycloaddition of azomethine ylides to unsubstituted
furfuryl chalcones and aryl furfuryl chalcones. Moreover,
as we envisioned that the strong electron-withdrawing nature
of substituents like nitro group on the furan ring effectively
tunes the regioselectivity of a 1,3-dipolar cycloaddition of
azomethine ylide in our previous work [12], herein, we
reported the regioselectivity trends observed during the one-
pot, three-component 1,3-dipolar cycloaddition of azomethine
ylides, generated in situ from ninhydrin and sarcosine, with
α,β-unsaturated enones having furyl moiety and aryl furyl
moiety, with weaker electron withdrawing p-chlorophenyl
substituent at the fifth position of the furan ring.
Spiropyrrolidine ring systems form the core structure of
numerous natural products and alkaloids and are also ele-
gant precursors in organic synthesis due to their significant
pharmacological and biological activities [1–9]. A number
of strategies have been devised to provide access to the
synthesis of spiropyrrolidine core. The 1,3-dipolar cyclo-
addition of azomethine ylides with olefinic dipolarophiles
offers an excellent route for the construction of nitrogen
containing five membered substituted pyrrolidine deriva-
tives [10]. Although highly substituted spiropyrrolidines
are known [10], there seems to be a very sparse report on
the study of substituent effect on the regioselectivity of
spiropyrrolidines [11,12]. The regiochemistry and stereo-
chemistry of spiropyrrolidine formed by 1,3-dipolar cycload-
dition may be controlled either by choosing the appropriate
dipole and dipolarophile or by controlling the reaction using
a catalyst. The steric and electronic effects are two major
factors that can influence the selectivity of these reactions.
Our group had recently reported a novel regioselectivity
trend during the reaction of 1-(substituted benzyl)-3-(5-
nitrofuryl) prop-2-en-1-one were employed as dipolarophiles
to react with azomethine ylides [12]. The presence of strong
electron withdrawing nitro substituents on the substrates
RESULT AND DISCUSSION
As described in Scheme 1, the 1,3-dipole generated in
situ from decarboxylative cyclocondensation of ninhydrin
© 2015 HeteroCorporation

S. Mallya, B. Kalluraya, and H. S. V. Jois
Vol 000
Scheme 1. Synthesis of aryl furan containing spiropyrrolidines.
obtained with a modest yield and a poor regioisomeric
ratio.
It is interesting to note that in the case of electron-
withdrawing aryl substituents on the fifth position of furan
ring in the chalcone, unusual cycloadduct is formed easily
with regioselectivity. A plausible mechanism for the regio-
selectivity in this transformation can be proposed as the
presence of electron-withdrawing p-chlorophenyl attached
to the fifth position of furfuryl ring of the chalcone generates
the electron-deficient α-carbon of aryl furfuryl chalcone
(Fig. 1), which adds up with the nucleophilic carbon center
of azomethine ylides generated from the reaction of ninhy-
drin with sarcosine during the cycloaddition, leading to sin-
gle regioisomer. In the case of furfuryl chalcones, due to
the absence of electron withdrawing group, there was no
polarity in the alkenyl bond of chalcone (Fig. 1). Thus,
the nucleophilic center of the azomethine ylide adds to α
as well as β carbon of the olefinic portion of furfuryl
chalcone. Even when efforts were given to study the reac-
tion of 5-methyl furyl chalcones with azomethine ylides,
a pair of regioisomers were obtained as product. The
regioseparation was not observed in cases of electron do-
nating groups.
Thus, it can be summarized that the presence of electron-
withdrawing groups significantly changed the regiochemistry
and yield of this reaction, whereas removal of electron with-
drawing group makes the reaction to loose regiospecificity.
More importantly, the regioselectivity of the 1,3-dipolar cy-
cloaddition of azomethine ylide can be changed by the pres-
ence of electron withdrawing groups in the dipolarophiles,
which lead to the formation of spirooxindoles with novel
regiochemical trends.
1 and sarcosine 2 reacted readily with the aryl furan con-
taining chalcones 3a-j as dipolarophiles under refluxing
conditions in absolute ethanol medium to give only one
regioisomer as cycloadducts 4a-j in high yield, in which
the benzoyl group was connected to C-4 of the newly con-
structed pyrrolidine, thus showing that when strong
electron-withdrawing nitro group was replaced by weaker
electron-withdrawing group such as p-chlorophenyl, we
were still able to reproduce the regiochemical trends simi-
lar to those of nitrofuran [12]. But in the case of cycloaddi-
tion of azomethine ylides to furfuryl chalcone derivatives,
6a-e (Scheme 2), a pair of regioisomers 7a-e and 8a-e were
Scheme 2. Synthesis of furan containing spiropyrrolidines.
The structures of newly synthesized spiropyrrolidines
1
were elucidated using H NMR, 13C NMR, HMBC, mass
spectra, and elemental analysis data. The analytical and
spectral data are in consistency with the proposed structure.
Thus, in the IR spectrum of 4a, the three carbonyl absorp-
tion bands of furfuryl containing spiropyrrolidine moiety
were observed at 1638, 1680, and 1741cmÀ1, respectively,
thus providing proof for the formation of spiropyrrolidines.
1H NMR (400MHz, CDCl3) spectrum of compound 4a
shows a doublet at δ=4.66ppm for proton Ha, a multiplet
Figure 1. Mechanism for the formation of polarity in the chalcones.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Effect of substituent on the regiochemical trends during dipolar addition reaction
at δ =4.72ppm for proton Hb, a doublet of doublet at
δ=3.44ppm for proton Hc, and a doublet of doublet at
3.86ppm for proton Hd of spiropyrrolidine, respectively. The
aromatic protons came into resonance at δ=6.80–8.02ppm
as multiplet, the protons of aryl furfuryl ring appeared at
δ= 5.99 and 6.19 ppm respectively as two doublets, and
N-CH3 protons of spioropyrrolidine ring appeared at
δ= 2.61ppm as a singlet. Similarly, the 13C NMR spectrum
of 4a shows the peak at δ= 78.41 ppm due to spirocarbon,
whereas two C=O carbons of ninhydrin ring appeared at
200.04 and 202.25 ppm, while C=O carbon of benzoyl
group appears at δ =195.59ppm.
The regiochemistry of the product was established from
the HMBC data of 4a; the benzoyl C=O group at
δ= 195.59 ppm correlates with all the four protons attached
to the pyrrolidine ring (Ha, Hb, Hc, and Hd) protons, show-
ing that the correct regiochemistry of the product is as
shown previously. If the other possible regioisomer had
formed, a long-range coupling between the benzoyl C=O
group and Hc would not have been observed.
Furthermore, the support for the formation of the
spiropyrrolidines has been obtained by mass spectral studies.
All the compounds showed the molecular ion peak (M+ +1)
there by indicating the stability of spiropyrrolidines. In the
mass spectrum of compound 4f, the molecular ion (M+ +1)
peak was observed at m/z 526.2:528.2 at 3:1 ratio, which is in
agreement with the molecular formula (M. F.: C31H24ClNO5)
and confirms the formation of the product 4f.
In the IR spectrum of compound 7d, the carbonyl ab-
sorption bands were observed in the range of 1699, 1709,
and 1741 cm-1, respectively, whereas in the IR spectrum
of compound 8d, the carbonyl absorption bands were ob-
served in the range of 1684, 1701, and 1733cm-1, respec-
tively, thus showing the formation of regioisomeric
cycloadducts.
a singlet; and methyl group of benzoyl substituent is found
at δ= 2.33 ppm as singlet.
The 13C NMR spectrum of 7d showed a peak at
δ= 77.06 ppm due to spirocarbon, whereas the two C=O
of ninhydrin ring appear at δ= 202.87 and 200.39 ppm,
while C=O of benzoyl group appears at δ= 196.15 ppm.
The 13C NMR spectrum of 8d showed a peak at
δ= 77.39 ppm due to spirocarbon, whereas the two C=O
of ninhydrin ring appears at δ= 200.35 and 202.83 ppm,
while C=O of benzoyl group appears at δ= 196.35 ppm.
As indicated in the HMBC data of 8d, the benzoyl C=O
group at δ= 196.35 ppm correlates with all the four protons
attached to the pyrrolidine ring (Ha, Hb, Hc, and Hd) pro-
tons, showing that the correct regiochemistry of the prod-
uct is as shown in structure. Similarly, as indicated in the
HMBC data of 7d, the benzoyl C=O group at δ =196.15ppm
correlates with only two protons of pyrrolidine ring
(Ha and Hb), and a long-range coupling between the ben-
zoyl C=O group and Hc would not have been observed,
showing that the correct regiochemistry of the product is
as shown in structure.
The mass spectrum of the compound 7d shows the mo-
lecular ion (M+ +1) peak at m/z 464.1 and 466.1 [M+ +1]
(1:1 ratio), which is in agreement with the molecular for-
mula there by confirming the formation of the product
7d. Similarly, the mass spectrum of the compound 8d
shows the molecular ion (M++1) peak at m/z 464.8 and
467.2 [M+ + 1] (1:1 ratio), which is in agreement with the
molecular formula that confirms the formation of the prod-
uct 8d. Here, although compounds had same molecular
formula, their formula weight did differ, providing a hint
for the formation of isomers.
During the cycloaddition reaction of ninhydrin, sarcosine,
and aryl furfuryl chalcone, only a single regioisomer was
formed, whereas a pair of regioisomers was obtained in
poor regioselectivities when the cycloaddition of ninhydrin,
sarcosine, and furfuryl chalcone derivatives were carried
out, in which the benzoyl group was connected to the C-4
of the newly constructed pyrrolidine in one regioisomer,
whereas the benzoyl group was connected to the C-3 of the
newly constructed pyrrolidine in another regioisomer. It
was found that the presence of electron-withdrawing groups
can significantly changed the regiochemistry and yield of
this reaction in the previous cases, whereas the absence of
electron-withdrawing group in furfuryl chalcones resulted
in a pair of regioisomers. More importantly, the regioselec-
tivity of the 1,3-dipolar cycloaddition of azomethine ylide
was changed by the presence of electron withdrawing
groups, which led to the formation of spirooxindoles with
novel regiochemical trends.
1H NMR (400 Hz, CDCl3) spectrum of compound 7a
shows a doublet at δ= 4.66 ppm for Ha, a multiplet at
δ= 4.74–4.82 ppm for Hb, a doublet of doublet at δ= 3.43
and 3.87 ppm for Hc and Hd, respectively. The aromatic
protons appeared around δ = 7.26–7.98ppm as multiplet,
the α and γ protons of furyl ring appeared at δ= 5.89 and
6.92ppm as doublets and β proton appeared at 5.93 ppm
respectively as a doublet of doublet and N-CH3 protons
of spioropyrrolidine ring appeared at δ= 2.33ppm as sin-
glet and methyl group of benzoyl substituent is found at
δ= 2.41ppm as singlet.
1
Further H NMR (400 MHz, CDCl3) spectrum of com-
pound 8a showed a doublet at δ= 4.55 ppm for Ha, a mul-
tiplet at δ =4.68 ppm for Hb, a doublet of doublet at
δ= 3.36 and 3.78ppm for Hc and Hd, respectively. The ar-
omatic protons appeared around δ= 7.18–7.90 ppm as mul-
tiplet; the protons of furyl ring appeared at δ= 5.80 ppm(d),
5.86ppm(dd), and 6.84 ppm(d), respectively; N-CH3 pro-
tons of spioropyrrolidine ring appeared at δ = 2.25ppm as
In summary, we have successfully synthesized a new class
of functionalised aryl furan containing spiropyrrolidines 4a-j
and furan containing spiropyrrolidines 7a-e and 8a-e contain-
ing furan moiety by one-pot, three-component 1,3-dipolar
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. Mallya, B. Kalluraya, and H. S. V. Jois
Vol 000
cycloaddition of in situ generated azomethine ylides with
chalcones. It was found that the presence of electron with-
drawing groups can significantly changed the regiochemistry
and yield of this reaction in the previous case of nitrofuran
and aryl furan, whereas the absence of electron withdrawing
group in furfuryl chalcones resulted in a pair of regioisomers.
arylfuryl-3H, 3.2Hz), 6.19 (d, 1H, arylfuryl-4H, 3.2Hz),
6.80–8.02 (m, 12H ,Ar-H); 13C NMR (100MHz, CDCl3):
δ 35.57, 38.94, 47.55, 47.09, 55.41, 57.25, 76.87, 78.41,
78.74, 79.07, 106.44, 109.59, 113.96, 122.11, 122.75,
124.27, 128.17, 128.40, 128.46, 130.70, 131.75, 136.45,
140.07, 141.18, 149.97, 151.09, 163.51, 195.59, 200.04,
202.25; ms: m/z 574.6 (M+ +1). Anal. Calcd. for
C30H21BrClNO4: C, 62.68; H, 3.68; N, 2.44. Found: C,
MATERIALS AND METHODS
62.70; H, 3.70; N, 2.40.
4′-(benzoyl)-1′-methyl-3′-(5-(p-chlorophenyl)-2-furyl) spiro
[indene-2,2′-pyrrolidine]-1,3-dione (4b). Orange crystalline
The melting points of the newly synthesized compounds
were determined in open capillaries and are uncorrected.
IR spectra were obtained in KBr discs on a Shimadzu-
(78%), mp 125–127°C; IR (KBr): 1641 (C=O), 1681
(C=O), 1740 (C=O) cmÀ1; H NMR (400 MHz, CDCl3):
1
1
8400 FTIR spectrophotometer (Kyoto, Japan), H NMR
δ 4.69 (d, 1H, Ha, J = 10.0Hz), 4.73 (m, 1H, Hb), 3.39
(dd, 1H, Hc, J= 5.9 Hz, J = 8.9 Hz), 3.82 (dd, 1H, Hd,
J = 9.1 Hz, J= 10.6Hz), 2.73 (s, 3H, N-CH3), 5.72 (d, 1H,
aryl furfuryl α-H, J=3.2Hz) 6.03 (d, 1H, aryl furfuryl β-H,
J=3.3Hz), 6.92–8.01 (m, 13H ,Ar-H); 13C NMR (100MHz,
CDCl3): δ 37.24, 47.62, 56.41, 76.72 (spirocarbon), 104.36,
106.52, 111.31, 117.54, 120.13, 121.89, 123.56, 125.91,
126.72, 127.23,, 128.93, 129.62, 129.98, 130.31, 131.12,
133.54, 136.98, 138.20, 139.84, 141.63, 144.52, 150.62,
152.39, 153.27, 156.93, 196.38, 199.97, 201.89; ms: m/z
496.5:498.6 (3:1) (M+ +1). Anal. Calcd. for C30H22ClNO4:
spectra were recorded on Bruker spectrometer (400MHz)
(Billerica, MA, USA) in CDCl3 using TMS as an internal
standard, and 13C NMR spectra were recorded on Bruker
spectrometer (100 MHz) in CDCl3 as solvent. All the
chemical shift values are expressed in δ scale downfield
from TMS, and proton signals are indicated as s= singlet,
d = doublet, dd= doublet of doublet, t= triplet, q = quartlet,
and m= multiplet. Mass spectra were recorded on Waters
Micromass Q-Tof Micro mass spectrometer (Milford, MA,
USA). Elemental analyses were carried out on Elementar
Vario-EL-Elementar III model analyzer. The purity of the
compounds was confirmed by TLC using silica gel plates
(Merck, Kenilworth, NJ, USA) using hexane:ethyl acetate
(6:4) as mobile phase.
The required dipolarophiles, 1-aryl-3-[5-(p-chlorophenyl)
furfuryl] propenones 3a-j/1-aryl-3-furyl propenones 6a-e,
were prepared according to literature procedure by base-
catalyzed Claisen–Schmidt condensation of 5-(p-chlorophenyl)
furfuraldehyde13/furfuraldehyde with substituted acetophe-
nones [13].
C, 72.65; H, 4.47; N, 2.82. Found: C, 72.60; H, 4.50; N, 2.80.
4′-(4-chlorobenzoyl)-1′-methyl-3′-(5-(p-chlorophenyl)-2-furyl)
spiro[indene-2,2′-pyrrolidine]-1,3-dione (4c). Yellowish brown
crystalline (80%), mp 120–122°C; IR (KBr): 1643 (C=O),
1687 (C=O), 1742 (C=O) cmÀ1 1H NMR (400MHz,
;
CDCl3): δ 4.72 (d, 1H, Ha, J=9.92Hz), 4.81 (m, 1H, Hb),
3.47 (dd, 1H, Hc, J=5.6Hz, J=8.8Hz), 3.87 (dd, 1H, Hd,
J=8.9Hz, J=10.5Hz), 2.26 (s, 3H, N-CH3), 6.01 (d, 1H,
aryl furfuryl 3H, J=3.1Hz), 6.25 (d, 1H, aryl furfuryl β-H,
J=3.5Hz), 7.01–8.28 (m, 12H ,Ar-H); 13C NMR (100
MHz, CDCl3): δ 35.62, 44.56, 49.71, 54.65, 76.81
(spirocarbon), 104.81, 107.84, 109.63, 111.42, 115.79,
120.53, 123.74, 123.98, 125.97, 127.86, 128.35, 129.37,
131.62, 132.21, 132.43, 132.75, 133.68, 135.93, 136.29,
139.68, 140.71, 147.45, 149.76, 151.68, 154.32, 187.68,
195.98, 200.03, 202.31; ms: m/z 530.3:532.2:534.4 (1:2:1)
(M+ +1). Anal. Calcd. for C30H21Cl2NO4: C, 67.93; H,
General procedure for the synthesis of spiropyrrolidines
4a-j. A mixture of chalcone 3a-j (1m mol), ninhydrin
(1mmol), and sarcosine (1.1mmol) was refluxed in
ethanol (10mL) at 100–120°C until the disappearance of
the starting materials (5–6h) as evidenced by the TLC.
After the completion of reaction, the reaction mixture was
concentrated in vacuum, and the resulting crude mass was
diluted with water (30mL) and extracted with ethyl acetate
(3× 15mL) and dried over anhydrous, Na2SO4. The organic
layers were concentrated and purified by flash chromatography
(SiO2) with progressive increase in polarity (hexane:ethyl
acetate as eluent from 95:5 to 60:40). The pure products
4a-j thus obtained were recrystallized from ethanol:DMF
3.99; N, 2.64. Found: C, 67.90; H, 4.00; N, 2.60.
4′-(4-methylbenzoyl)-1′-methyl-3′-(5-(p-chlorophenyl)-2-furyl)
spiro[indene-2,2′-pyrrolidine]-1,3-dione (4d).
Dark brown
amorphous (75%), mp 180–184°C; IR (KBr): 1642 (C=O),
1689 (C=O), 1744 (C=O) cmÀ1 1H NMR (400MHz,
;
CDCl3): δ 4.47 (d, 1H, Ha, J=10.0Hz), 4.58 (m, 1H, Hb),
3.21 (dd, 1H, Hc, J=5.8Hz, J=8.7Hz), 3.79 (dd, 1H, Hd,
J= 8.9 Hz, J= 10.5Hz), 2.71 (s, 3H, N-CH3), 3.28(s, 3H,
CH3), 6.14 (d, 1H, aryl furfuryl α-H, J=3.2Hz), 6.48 (d, 1H,
(2:1).
4′-(4-bromobenzoyl)-1′-methyl-3′-(5-(p-chlorophenyl)-2-furyl)
spiro[indene-2,2′-pyrrolidine]-1,3-dione (4a). Brownish yellow
aryl furfuryl β-H, J= 3.4 Hz), 7.08–8.17 (m, 12H ,Ar-H); 13
C
amorphous (79%), mp 170–172°C; IR (KBr): 1638 (C=O),
1680 (C=O), 1741 (C=O) cmÀ1 1H NMR (400MHz,
;
NMR (100MHz, CDCl3): δ 35.86, 41.97, 47.53, 56.89,
76.73 (spirocarbon), 103.95, 106.38, 107.91, 112.35, 115.68,
118.74, 121.58, 123.46, 125.43, 126.58, 128.93, 129.17,
129.37, 130.35, 131.43, 133.58, 134.81, 135.79, 136.38,
CDCl3): δ 4.66 (d, 1H, Ha, J=9.7Hz), 4.72 (m, 1H, Hb),
3.44 (dd, 1H, Hc, J=6.1Hz, J=9.0Hz), 3.86 (dd, 1H, Hd,
J=9.9Hz, J=10.8), 2.61 (s, 3H, N-CH3), 5.99 (d, 1H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Effect of substituent on the regiochemical trends during dipolar addition reaction
4′-(2-chlorobenzoyl)-1′-methyl-3′-(5-(p-chlorophenyl)-2-furyl)
spiro[indene-2,2′-pyrrolidine]-1,3-dione (4h).
139.68, 144.56, 148.39, 152.36, 153.89, 155.76, 196.47,
200.08, 202.76; ms: m/z 510.4:512.3 (3:1) (M+ +1). Anal.
Calcd. for C31H24ClNO4: C, 73.01; H, 4.74; N, 2.75. Found:
Dark yellow
crystalline (82%), mp 201–203°C; IR (KBr): 1644 (C=O),
1685 (C=O), 1742 (C=O) cmÀ1 1H NMR (400MHz,
;
C, 73.10; H, 4.80; N, 2.70.
CDCl3): δ 4.67 (d, 1H, Ha, J=10.0Hz), 4.89 (m, 1H, Hb),
3.43 (dd, 1H, Hc, J=5.7Hz, J=9.1Hz), 3.68 (dd, 1H, Hd,
J=9.1Hz, J=10.7Hz), 2.36 (s, 3H, N-CH3), 5.76 (d, 1H,
aryl furfuryl α-H, J=3.2Hz), 6.08 (d, 1H, aryl furfuryl β-H,
J=3.3Hz), 7.10–8.12 (m, 12H, Ar-H); 13C NMR
(100MHz, CDCl3): δ 37.46, 41.53, 47.61, 55.18, 76.68
(spirocarbon), 104.78, 106.37, 107.57, 111.56, 113.59,
117.89, 119.57, 121.75, 124.46, 126.73, 127.79, 128.85,
129.56, 130.32, 132.27, 134.78, 140.48, 142.56, 144.45,
146.76, 147.07, 148.87, 149.91, 195.98, 200.13, 202.61;
ms: m/z 530.3:532.2:534.4 (1:2:1) (M+ +1). Anal. Calcd.
for C30H21Cl2NO4: C, 67.93; H, 3.99; N, 2.64. Found: C,
4′-(4-hydroxybenzoyl)-1′-methyl-3′-(5-(p-chlorophenyl)-2-furyl)
spiro[indene-2,2′-pyrrolidine]-1,3-dione (4e). Yellowish brown
crystalline (72%), mp 203–204°C; IR (KBr): 1640 (C=O),
1687 (C=O), 1742 (C=O) cmÀ1 1H NMR (400 MHz,
;
CDCl3): δ 4.64 (d, 1H, Ha, J= 9.8 Hz), 4.69 (m, 1H, Hb),
3.39 (dd, 1H, Hc, J= 5.6Hz, J= 8.9 Hz), 3.85 (dd, 1H, Hd,
J =9.0Hz, J= 10.5 Hz), 2.78 (s, 3H, N-CH3), 6.08 (d, 1H,
aryl furfuryl α-H, J =3.1Hz), 6.57 (d, 1H, aryl furfuryl β-H,
J = 3.3 Hz), 6.81(s, br, 1H, Ar-OH), 7.04–7.90 (m, 12H ,Ar-H);
13C NMR (100MHz, CDCl3): δ 37.69, 41.82, 47.63, 53.68,
77.21 (spirocarbon), 103.27, 105.68, 107.89, 109.37,
112.37, 117.93, 120.29, 121.58, 123.76, 126.39, 128.46,
129.37, 131.48, 131.52, 136.47, 136.67, 137.75, 137.89,
137.95, 140.37, 141.38, 147.68, 150.37, 151.81, 154.88,
156.74, 196.11, 200.82, 202.32; ms: m/z 512.6:514.5 (3:1)
(M+ +1). Anal. Calcd. for C30H22ClNO5: C, 70.38; H, 4.33;
67.90; H, 4.00; N, 2.60.
4′-(3-bromobenzoyl)-1′-methyl-3′-(5-(p-chlorophenyl)-2-furyl)
spiro[indene-2,2′-pyrrolidine]-1,3-dione (4i). Yellowish brown
amorphous (78%), mp 126–128°C; IR (KBr): 1638 (C=O),
1686 (C=O), 1740 (C=O) cmÀ1 1H NMR (400MHz,
;
N, 2.74. Found: C, 70.40; H, 4.30; N, 2.80.
CDCl3): δ 4.61 (d, 1H, Ha, J=9.8Hz), 4.74 (m, 1H, Hb),
3.42 (dd, 1H, Hc, J=5.8Hz, J=8.9Hz), 3.85 (dd, 1H, Hd,
J=9.1Hz, J=10.6Hz), 2.39 (s, 3H, N-CH3), 5.83 (d, 1H,
aryl furfuryl α-H, J=3.1Hz), 6.06 (d, 1H, aryl furfuryl β-H,
J=3.3Hz), 7.20–8.10 (m, 12H, Ar-H); 13C NMR
(100MHz, CDCl3): δ 35.76, 38.87, 41.18, 55.78, 76.68
(spirocarbon), 104.67, 107.78, 109.95, 114.43, 117.89,
121.36, 122.37, 123.65, 125.83, 127.62, 128.37, 129.53,
129.37, 130.15, 132.56, 132.78, 133.54, 135.78, 136.39,
141.43, 141.57, 145.57, 150.38, 151.78, 153.57, 157.86,
196.47, 200.39, 202.76; ms: m/z 574.7 (M+ +1). Anal.
Calcd. for C30H21BrClNO4: C, 62.68; H, 3.68; N, 2.44.
4′-(4-methoxybenzoyl)-1′-methyl-3′-(5-(p-chlorophenyl)-2-furyl)
spiro[indene-2,2′-pyrrolidine]-1,3-dione (4f). Yellow amorphous
(81%), mp 198–199°C; IR (KBr): 1643 (C=O), 1689 (C=O),
1
1743 (C=O) cmÀ1; H NMR (400MHz, CDCl3): δ 4.50 (d,
1H, Ha, J = 9.92Hz), 4.67 (m, 1H, Hb), 3.25 (dd, 1H, Hc,
J=5.84 Hz, J= 8.88Hz), 3.82 (dd, 1H, Hd, J=9.32Hz,
J=10.72Hz), 2.22 (s, 3H, N-CH3), 3.89(s, 3H, OCH3), 6.12
(d, 1H, aryl furfuryl α-H, J=3.12Hz), 6.49 (d, 1H, aryl
furfuryl β-H, J=3.40Hz), 7.04–8.20 (m, 12H ,Ar-H); 13C
NMR (100MHz, CDCl3): δ 36.19, 40.97, 48.51, 57.23,
76.77 (spirocarbon), 105.78, 108.73, 110.24, 118.22, 119.29,
122.41, 124.49, 125.68, 127.81, 129.11, 129.92, 130.00,
130.72, 131.88, 132.81, 134.42, 136.00, 136.92, 140.72,
141.69, 149.28, 151.18, 152.18, 155.39, 188.47, 196.19,
200.28, 202.92; ms: m/z 526.2:528.2 (3:1) (M+ +1). Anal.
Calcd. for C31H24ClNO5: C, 70.79; H, 4.60; N, 2.66. Found:
Found: C, 62.70; H, 3.70; N, 2.40.
4′-(3-hydroxybenzoyl)-1′-methyl-3′-(5-(p-chlorophenyl)-2-furyl)
spiro[indene-2,2′-pyrrolidine]-1,3-dione (4j).
Brown crystals
(81%), mp 123–126°C; IR (KBr): 1639 (C=O), 1682
1
(C=O), 1741(C=O) cmÀ1; H NMR (400 MHz, CDCl3): δ
C, 70.80; H, 4.60; N, 2.70.
4.58 (d, 1H, Ha, J =9.8Hz), 4.76 (m, 1H, Hb), 3.36 (dd, 1H,
Hc, J = 5.8 Hz, J= 8.9Hz), 3.78 (dd, 1H, Hd, J=9.2Hz,
J = 10.4 Hz), 2.37 (s, 3H, N-CH3), 5.84 (d, 1H, aryl furfuryl
α-H, J = 3.2 Hz), 6.15 (d, 1H, aryl furfuryl β-H, J =3.3 Hz),
7.01–8.03 (m, 12H ,Ar-H); 13C NMR (100MHz, CDCl3): δ
37.68, 40.37, 47.58, 49.38, 57.68, 76.69 (spirocarbon),
104.65, 1 07.54, 109.68, 114.67, 116.37, 121.38, 123.37,
124.57, 127.38, 128.89, 129.39, 129.98, 130.56, 131.23,
132.12, 132.34, 134.39, 136.37, 135.78, 141.16,149.03,
150.95, 151.27, 153.05, 196.27, 200.01, 202.17; ms: m/z
512.3:514.2 (3:1) (M+ +1). Anal. Calcd. for C30H22ClNO5:
C, 70.38; H, 4.33; N, 2.74. Found: C, 70.40; H, 4.30; N, 2.80.
4′-(4-fluorobenzoyl)-1′-methyl-3′-(5-(p-chlorophenyl)-2-furyl)
spiro[indene-2,2′-pyrrolidine]-1,3-dione (4g). Reddish brown
crystalline (73%), mp 203–204°C; IR (KBr): 1641 (C=O),
1687 (C=O), 1739 (C=O) cmÀ1 1H NMR (400MHz,
;
CDCl3): δ 4.74 (d, 1H, Ha, J=9.92Hz), 4.82 (m, 1H, Hb),
3.52 (dd, 1H, Hc, J=5.9Hz, J=9.0Hz), 3.89 (dd, 1H, Hd,
J=9.3Hz, J=10.8Hz), 2.36 (s, 3H, N-CH3), 5.76 (d, 1H,
aryl furfuryl α-H, J = 3.3 Hz), 6.07 (d, 1H, aryl furfuryl β-H,
J=3.5Hz), 7.01–7.90 (m, 12H ,Ar-H); 13C NMR
(100MHz, CDCl3): δ 38.67, 41.86, 47.69, 56.36, 76.86
(spirocarbon), 105.58, 107.83, 109.73, 110.85, 117.89,
118.37, 121.69, 123.73, 125.41, 126.95, 127.68, 128.59,
129.36, 130.19, 131.58, 131.75, 132.36, 133.39, 135.89,
136.43, 141.32, 141.67, 147.56, 150.65, 151.79, 154.69,
162.32, 196.15, 200.03, 202.43; ms: m/z 514.3:516.2 (3:1)
(M+ +1). Anal. Calcd. for C30H21FClNO4: C, 70.11; H,
4.12; N, 2.73. Found: C, 70.10; H, 4.10; N, 2.70.
General procedure for the synthesis of spiropyrrolidines
7a-e and 8a-e.
A mixture of chalcone 6a-e (1 m mol),
ninhydrin (1m mol), and sarcosine (1.1 mmol) was refluxed
in ethanol (10mL) at 100–120°C until the disappearance of
the starting materials (6–8h) as evidenced by the TLC. After
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. Mallya, B. Kalluraya, and H. S. V. Jois
Vol 000
the completion of reaction, the reaction mixture was
concentrated in vacuo, and the resulting crude mass was
diluted with water (30 mL) and extracted with ethyl
acetate (3 × 15mL) and dried over anhy, Na2SO4. The
organic layers were concentrated and purified by flash
chromatography (SiO2) with progressive increase in polarity
(hexane:ethyl acetate as eluent from 95:5 to 70:30). The
separated regioisomers 7a-e and 8a-e were recrystallised
(3:1) (M+ +1). Anal. Calcd. for C24H18ClNO4: C, 68.66;
H, 4.32; N, 3.34. Found: C, 68.60; H, 4.30; N, 3.30.
3′-(4-bromobenzoyl)-1′-methyl-4′-(2-furyl) spiro[indene-2,2′-
pyrrolidine]-1,3-dione (7d). Yellowish crystalline (43%),
mp 204–205°C; IR (KBr): 1699 (C=O), 1709 (C=O),
1
1741 (C=O) cmÀ1; H NMR (400MHz, CDCl3): δ 4.50
(d, 1H, Ha, J= 10.1Hz), 4.64–4.70 (m, 1H, Hb), 3.35 (dd,
1H, Hc, J =15.08 Hz, J = 8.36Hz), 3.75 (dd, 1H, Hd,
J = 10.0Hz, J= 9.6 Hz), 2.25 (s, 3H, N-CH3), 5.80 (d, 1H,
furyl α-H, J= 3.7 Hz), 5.86 (dd, 1H, furyl β-H, J =1.3 Hz,
J = 3.7 Hz), 6.87 (d, 1H, furyl γ-H, J= 1.6 Hz), 7.20–7.90
(m, 8H ,Ar-H); 13C NMR (100MHz, CDCl3): δ 36.20,
48.22, 48.50, 57.15, 76.74, 77.06, 77.37, 78.03, 108.25,
110.16, 122.43, 123.11, 129.93, 129.08, 134.53, 135.97,
136.22, 139.95, 140.77, 141.77, 142.15, 149.16, 196.15,
200.39, 202.87; ms: m/z 464.1:466.1 (1:1) (M+ + 1). Anal.
Calcd. for C24H18BrNO4: C, 62.08; H, 3.91; N, 3.02.
from ethanol:DMF (2:1) to give the products.
3′-(4-methylbenzoyl)-1′-methyl-4′-(2-furyl) spiro[indene-2,2′-
pyrrolidine]-1,3-dione (7a).
Creamish yellow amorphous
(32%), mp 208–209°C; IR (KBr): 1701 (C=O), 1707
1
(C=O), 1741 (C=O) cmÀ1; H NMR (400MHz, CDCl3): δ
4.66 (d, 1H, Ha, J=10.2Hz), 4.78 (m, 1H, Hb), 3.43 (dd,
1H, Hc, J=6.5Hz, J=8.9Hz), 3.87 (dd, 1H, Hd, J=9.1Hz,
J=10.6Hz), 2.33 (s, 3H, N-CH3), 2.41(s, 3H, CH3), 5.89
(d, 1H, furyl α-H, J=3.16Hz), 5.93 (dd, 1H, furyl β-H,
J=1.8Hz, J=5.0Hz), 6.92 (d, 1H, furyl γ-H, J=1.56Hz),
7.26–7.98 (m, 8H ,Ar-H); 13C NMR (100MHz, CDCl3): δ
30.87, 36.58, 48.63, 48.92, 55.79, 76.98, 77.07, 77.18,
77.52, 104.38, 105.98, 108.37, 117.45, 120.54, 127.61,
128.09, 131.12, 133.25, 135.49, 136.94, 138.87, 140.38,
140.08, 143.35, 193.38, 199.55, 201.07; ms: m/z 400.3
(M+ +1). Anal. Calcd. for C25H21NO4: C, 75.17; H, 5.30;
Found: C, 62.10; H, 3.90; N, 3.00.
3′-(4-methoxybenzoyl)-1′-methyl-4′-(2-furyl) spiro[indene-2,2′-
pyrrolidine]-1,3-dione (7e). Golden yellow crystalline (34%),
mp 204–205°C; IR (KBr): 1697 (C=O), 1708 (C=O), 1740
1
(C=O) cmÀ1; H NMR (400MHz, CDCl3): δ 4.58 (d, 1H,
Ha, J=10.1Hz), 4.68 (m, 1H, Hb), 3.28 (dd, 1H, Hc,
J=6.8Hz, J=9.0Hz), 3.65 (dd, 1H, Hd, J=9.0Hz,
J=10.6Hz), 2.36 (s, 3H, N-CH3), 3.97(s, 3H, OCH3), 5.77
(d, 1H, furyl α-H, J =3.6Hz), 5.89 (dd, 1H, furyl β-H,
J=1.7Hz, J= 5.1Hz), 6.75 (d, 1H, furyl γ-H, J=1.7Hz),
7.17–7.95 (m, 8H, Ar-H); 7d (Fig. 3.2.9): 13C NMR
(100MHz, CDCl3): δ 30.98, 35.98, 47.62, 48.38, 56.98,
76.89, 77.13, 77.45, 77.91, 107.93, 108.98, 109.76, 121.13,
123.08, 127.73, 128.81, 133.39, 136.04, 136.51, 138.89,
141.13, 141.34, 142.12, 146.65, 196.06, 200.03, 202.17;
ms: m/z 416.3 (M+ +1). Anal. Calcd. for C25H21NO5: C,
N, 3.51. Found: C, 75.10; H, 5.30; N, 3.60.
3′-(benzoyl)-1′-methyl-4′-(2-furyl) spiro[indene-2,2′-pyrrolidine]-
1,3-dione (7b). Golden yellow crystalline (29%), mp 201–
203°C; IR (KBr): 1698 (C=O), 1707 (C=O), 1743 (C=O)
1
cmÀ1; H NMR (400 MHz, CDCl3): δ 4.63 (d, 1H, Ha,
J = 10.1 Hz), 4.78 (m, 1H, Hb), 3.42 (dd, 1H, Hc,
J = 6.6 Hz, J = 9.0 Hz), 3.83 (dd, 1H, Hd, J = 9.2 Hz,
J = 10.7 Hz), 2.31 (s, 3H, N-CH3), 5.85 (d, 1H, furyl α-H,
J = 3.2 Hz), 5.93 (dd, 1H, furyl β-H, J = 1.8 Hz,
J = 4.9 Hz), 6.83 (d, 1H, furyl γ-H, J = 1.6 Hz), 7.03–7.86
(m, 9H ,Ar-H); 13C NMR (100 MHz, CDCl3): δ 35.87,
49.01, 49.65, 57.61, 76.82, 77.12, 77.23, 77.98, 105.96,
107.94, 109.68, 118.97, 121.35, 128.74, 129.16, 133.68,
135.07, 136.11, 138.87, 140.88, 141.54, 142.07, 149.16,
195.93, 200.08, 202.25; ms: m/z 386.3 (M+ + 1). Anal.
72.28; H, 5.10; N, 3.37. Found: C, 72.30; H, 5.20; N, 3.40.
4′-(4-methylbenzoyl)-1′-methyl-3′-(2-furyl) spiro[indene-2,2′-
pyrrolidine]-1,3-dione (8a).
Yellowish brown crystalline
(68%), mp 178-179°C; IR (KBr): 1683 (C=O), 1702 (C=O),
1
1735 (C=O) cmÀ1; H NMR (400 MHz, CDCl3): δ 4.55 (d,
1H, Ha, J=10.2Hz), 4.68 (m, 1H, Hb), 3.36 (dd, 1H, Hc,
J = 6.6 Hz, J =8.9 Hz), 3.78 (dd, 1H, Hd, J=9.0Hz, J=10.7Hz),
2.25 (s, 3H, N-CH3), 2.33 (s, 3H, CH3), 5.80 (d, 1H, furyl α-H,
J=3.2Hz), 5.86 (dd, 1H, furyl β-H, J=1.8Hz, J=5.1Hz), 6.84
(d, 1H, furyl γ-H, J =1.7 Hz), 7.18–7.90 (m, 8H, Ar-H); 13C
NMR (100MHz, CDCl3): δ 21.65, 29.68, 30.20, 31.43, 36.22,
48.10, 48.51, 57.48, 77.06, 108.06, 110.08, 122.38,
123.06, 128.66, 129.42, 133.79, 135.88, 136.11, 140.81,
141.81, 142.01, 144.33, 149.53, 196.76, 200.57, 202.95;
ms: m/z 400.2 (M+ +1). Anal. Calcd. for C25H21NO5: C,
Calcd. C24H19NO4: C, 74.79; H, 4.97; N, 3.63. Found:
C, 74.80; H, 5.00; N, 3.70.
3′-(4-chlorobenzoyl)-1′-methyl-4′-(2-furyl) spiro[indene-2,2′-
pyrrolidine]-1,3-dione (7c).
Creamish yellow crystalline
(38%), mp 196–197°C; IR (KBr): 1700 (C=O), 1708
1
(C=O), 1742 (C=O) cmÀ1; H NMR (400 MHz, CDCl3):
δ 4.38 (d, 1H, Ha, J =10.2 Hz), 4.59 (m, 1H, Hb), 3.25
(dd, 1H, Hc, J= 6.7 Hz, J =8.9 Hz), 3.68 (dd, 1H, Hd,
J =9.0Hz, J = 10.5Hz), 2.13 (s, 3H, N-CH3), 5.69 (d, 1H,
furyl α-H, J= 3.1 Hz), 5.75 (dd, 1H, furyl β-H, J= 1.9 Hz,
J =4.8Hz), 6.68 (d, 1H, furyl γ-H, J= 1.7 Hz), 7.15–7.98
(m, 8H ,Ar-H); 13C NMR (100 MHz, CDCl3): δ 37.34,
41.56, 47.53, 48.39, 55.48, 74.38, 75.91, 76.32, 75.49,
107.51, 107.83, 109.87, 115.53, 119.80, 124.56, 128.96,
131.79, 133.25, 136.58, 138.86, 139.97, 142.23, 142.39,
148.71, 195.98, 200.09, 202.63; ms: m/z 420.2:422.1
75.17; H, 5.30; N, 3.51. Found: C, 75.20; H, 5.20; N, 3.50.
4′-(benzoyl)-1′-methyl-3′-(2-furyl) spiro[indene-2,2′-pyrrolidine]-
1,3-dione (8b). Brownish crystals (71%), mp 165–167°C; IR
1
(KBr): 1683 (C=O), 1702 (C=O), 1734 (C=O) cmÀ1; H
NMR (400MHz, CDCl3): δ 4.63 (d, 1H, Ha, J= 10.2 Hz),
4.78 (m, 1H, Hb), 3.47 (dd, 1H, Hc, J=6.5Hz, J=8.9Hz),
3.77 (dd, 1H, Hd, J=9.0Hz, J=10.5Hz), 2.28 (s, 3H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Effect of substituent on the regiochemical trends during dipolar addition reaction
N-CH3), 5.79 (d, 1H, furyl α-H, J =3.3 Hz), 5.99 (dd, 1H,
furyl β-H, J =1.8 Hz, J =3.3 Hz), 6.86 (d, 1H, furyl γ-H,
J=1.3Hz), 7.15–8.03 (m, 9H ,Ar-H); 13C NMR (100 MHz,
CDCl3): δ 37.21, 48.01, 48.17, 56.38, 76.77, 77.05, 77.34,
78.07, 106.59, 108.67, 110.56, 121.67, 122.56, 127.39,
129.08, 131.36, 134.08, 135.39, 136.08, 140.05, 141.48,
141.97, 148.87, 196.08, 200.14, 202.49; ms: m/z 386.6
(M+ +1). Anal. Calcd. for C24H19NO4: C, 74.79; H, 4.97; N,
(M+ +1). Anal. Calcd. for C25H21NO5: C, 72.28; H, 5.10;
N, 3.37. Found: C, 72.30; H, 5.10; N, 3.40.
CONCLUSION
In summary, we studied the effect of the presence of
electron–withdrawing groups on the regiochemical trends
during the 1,3-dipolar cycloaddition reaction of azomethine
ylides with propenones carrying furan/5-aryl-substituted
furan to give the novel series of spiropyrrolidines in good to
excellent yields. It was observed that the regioselectivity
can be conveniently tuned and reversed by the presence of
electron-withdrawing groups attached to the furan ring,
which provides a facile approach to access a wide range of
spiropyrrolidine ring systems with novel substitution patterns.
3.63. Found: C, 74.80; H, 5.00; N, 3.60.
4′-(4-chlorobenzoyl)-1′-methyl-3′-(2-furyl) spiro[indene-2,2′-
pyrrolidine]-1,3-dione (8c). Yellowish brown powder (62%),
mp 169–170°C; IR (KBr): 1682 (C=O), 1700 (C=O), 1731
1
(C=O) cmÀ1; H NMR (400MHz, CDCl3): δ 4.51 (d, 1H,
Ha, J=10.1Hz), 4.69 (m, 1H, Hb), 3.42 (dd, 1H, Hc,
J= 6.5 Hz, J= 8.9Hz), 3.79 (dd, 1H, Hd, J=9.0Hz,
J= 10.7 Hz), 2.27 (s, 3H, N-CH3), 5.83 (d, 1H, furyl α-H,
J= 3.3 Hz), 5.97 (dd, 1H, furyl β-H, J=1.7Hz, J=3.2Hz),
6.95 (d, 1H, furyl γ-H, J=1.4Hz), 7.32–8.56 (m, 8H ,Ar-H);
13C NMR (100 MHz, CDCl3): δ 37.56, 40.39, 47.64, 56.84,
76.89, 77.04, 77.31, 77.89, 107.84, 109.96, 120.49, 122.67,
127.58, 130.19, 131.93, 134.37, 135.15, 136.85, 140.09,
141.73, 141.98, 148.89, 196.08, 200.18, 202.45; ms:
m/z 420.1:422.3 (3:1) (M+ +1). Anal. Calcd. for
C24H18ClNO4: C, 68.66; H, 4.32; N, 3.34. Found: C, 68.70;
Acknowledgments. The authors are thankful to the Head, SAIF,
Panjab University, Chandigarh, for spectral and elemental analysis.
S. Mallya is also thankful to University Grants Commission, New
Delhi, for Senior Research Fellowship.
REFERENCES AND NOTES
[1] Hanessian, S.; McNaughton-Smith, G.; Lombart, H. G.;
Lubell, W. D. Tetrahedron 1997, 53.
[2] (a) O’Hagan, D. Nat Prod Rep 2000, 17; (b) Hilton, S. T.;
Ho, T. C.; Pjevaljcic, G.; Jones, K. Org Lett 2000, 2; (c) Ban, Y.;
Taga, N.; Oishi, T. Tetrahedron Lett 1974, 15; (d) Early, W. G.; Oh, T.;
Overman, L. E. Tetrahedron Lett 1988, 27.
[3] (a) Raj, A. A.; Raghunathan, R.; Kumari, M. R. S.; Raman, N.
Bioorg Med Chem 2003, 11; (b) Wei, A. C.; Ali, M. A.; Yoon, Y. K.;
Ismail, R.; Choon, T. S.; Kumar, R. S.; Arumugam, N.; Almansour, A. I.;
Osman, H. Bioorg Med Chem Lett 2012, 22; (c) Ghandi, M.; Yari, A.;
Rezaei, T.; Jamal, S.; Taheri, A. Tetrahedron Lett 2009, 50;
(d) Jayashankaran, J.; Durga, R.; Raghunathan, R. ARKIVOC 2005, 11;
(e) Obniska, J.; Zeic, A.; Zagorska, A. Acta Pol Pharm 2002, 59.
[4] Cordell, G. A., Ed. The Alkaloids: Chemistry and Biology;
Academic Press: San Diego, 1998 Vol. 50.
[5] Cui, C. B.; Kakeya, H.; Osada, H. Tetrahedron 1996, 52.
[6] James, M. N. G.; Williams, G. J. B. Can J Chem 1972, 50.
[7] Jossang, A.; Jossang, P.; Hadi, H. A.; Sevenet, T.; Bodo, B.
J Org Chem 1991, 56.
[8] (a) Abou-Gharbia, M. A.; Doukas, P. H. Heterocycles 1979, 12;
(b) Kornet, M. J.; Thio, A. P. J Med Chem 1976, 19; (c) Rosenmond, P.;
Hosseini-Merescht, M.; Bub, C. Liebigs Ann Chem 1994.
[9] (a) Kang, T. H.; Matsumoto, K.; Todha, M.; Murakami, Y.;
Takayama, H.; Kitajima, M.; Aimi, N.; Watanabe, H. Eur J Pharmacol 2002,
444; (b) Dideberg, O.; Lamotte-Brasseur, J.; Dupont, L.; Campsteyn, H.;
Vermeire, M.; Angenot, L. Acta Crystallogr Sect B 1977, 33.
[10] (a) Harwood, L. M.; Vickers, R. J. In Synthetic Applications of
1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural
Products; Padwa, APearson, H. P. Ed. Ed.; John Wiley & Sons, Inc.:
New York, 2002, pp 169; (b) Prasad, T. A. A.; Vithiya, B. S. M.;
Ignacimuthu, S. D. Pharma Chemica 2011, 3; (c) Thangamani, A. Eur J
Med Chem 2010, 45; (d) Llamas, T.; Arrayas, R. G.; Carretero, J. C.
Org Lett 2006, 8.
H, 4.30; N, 3.40.
4′-(4-bromobenzoyl)-1′-methyl-3′-(2-furyl) spiro[indene-2,2′-
pyrrolidine]-1,3-dione (8d). Brown crystalline (57%), mp
181–182°C; IR (KBr): 1684 (C=O), 1701 (C=O), 1733
(C=O) cmÀ1; 1H NMR (400 MHz, CDCl3): δ 4.58 (d, 1H,
Ha, J= 10.2 Hz), 4.74 (m, 1H, Hb), 3.44 (dd, 1H, Hc,
J =6.4Hz, J= 8.9 Hz), 3.86 (dd, 1H, Hd, J= 9.1 Hz,
J =10.6 Hz), 2.33 (s, 3H, N-CH3), 5.88 (d, 1H, furyl α-H,
J =3.2Hz), 5.95 (dd, 1H, furyl β-H, J= 1.8 Hz, J= 3.1 Hz),
6.95 (d, 1H, furyl γ-H, J=1.1Hz), 7.28–7.98 (m, 8H, Ar-H);
13C NMR (100 MHz, CDCl3): δ 36.18, 48.21, 48.49, 57.13,
76.75, 77.07, 77.39, 78.01, 108.23, 110.16, 122.42, 123.09,
128.69, 130.01, 132.06, 134.95, 135.96, 136.21, 140.78,
141.77, 142.13, 149.17, 196.35, 200.35, 202.83; ms:
m/z 464.8:467.2 (1:1) (M+ +1). Anal. Calcd. for
C24H18BrNO4: C, 62.08; H, 3.91; N, 3.02. Found: C, 62.10;
H, 3.90; N, 3.00.
4′-(4-methoxybenzoyl)-1′-methyl-3′-(2-furyl) spiro[indene-2,2′-
pyrrolidine]-1,3-dione (8e). Creamish yellow crystals (66%),
mp 164–165°C; IR (KBr): 1685 (C=O), 1702 (C=O), 1732
1
(C=O) cmÀ1; H NMR (400MHz, CDCl3): δ 4.51 (d, 1H,
Ha, J=10.1Hz), 4.72 (m, 1H, Hb), 3.40 (dd, 1H, Hc,
J=6.3Hz, J=9.0Hz), 3.85 (dd, 1H, Hd, J=9.1Hz,
J =10.5Hz), 2.27 (s, 3H, N-CH3), 3.91 (s, 3H, OCH3), 5.83
(d, 1H, furyl α-H, J=3.3Hz), 5.94 (dd, 1H, furyl β-H,
J=1.5Hz, J=3.2 Hz), 6.96 (d, 1H, furyl γ-H, J = 1.4 Hz),
7.15–8.02 (m, 8H, Ar-H); 13C NMR (100MHz, CDCl3): δ
35.48, 38.89, 40.36, 47.58, 47.91, 56.35, 76.89, 77.04,
77.35, 78.04, 107.58, 111.37, 121.53, 122.97, 127.87,
129.56, 131.71, 134.85, 135.09, 135.98, 140.51, 142.39,
142.70, 148.95, 196.29, 200.41, 202.76; ms: m/z 416.5
[11] Sureshbabu, A. R.; Raghunathan, R.; Satiskumar, B. K.
Tetrahedron Lett 2009, 50.
[12] Mallya, S.; Kalluraya, B.; Girisha, K. S. J Het Chem
(published online), DOI: 10.1002/jhet.2092
[13] (a) Devi, K. V.; Kranthi, G.; Kumar, B. K.; Ramakrishna, C. H.;
Gupta, P. R.; Kumar, C. S. J Pharma Res 2011, 4; (b) Drake, N. L.;
Gilbert, H. W. J Am Chem Soc 1930, 52.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet