An expedient synthesis of pyrrolidinyl spirooxindole grafted 3-nitrochromanes through 1,3-dipolar cycloaddition reaction of azomethine ylides

Article abstract of DOI:10.1016/j.tetlet.2013.09.097

A facile one-pot synthesis of pyrrolidinyl-spirooxindole grafted 3-nitrochromanes has been accomplished by 1,3-dipolar cycloaddition (1,3-DC) reaction of 3-nitrochromenes with azomethine ylides generated in situ from isatin and secondary amino acids. The

Full text of DOI:10.1016/j.tetlet.2013.09.097

Accepted Manuscript
An expedient synthesis of pyrrolidinyl spirooxindole grafted 3-nitrochromanes
through 1,3-dipolar cycloaddition reaction of azomethine ylides
J. Naga Siva Rao, R. Raghunathan
PII:
S0040-4039(13)01662-6
DOI:
http://dx.doi.org/10.1016/j.tetlet.2013.09.097
TETL 43597
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
21 August 2013
17 September 2013
20 September 2013
Please cite this article as: Naga Siva Rao, J., Raghunathan, R., An expedient synthesis of pyrrolidinyl spirooxindole
grafted 3-nitrochromanes through 1,3-dipolar cycloaddition reaction of azomethine ylides, Tetrahedron Letters
(
2013), doi: http://dx.doi.org/10.1016/j.tetlet.2013.09.097
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

1
Graphical abstract
An expedient synthesis of pyrrolidinyl spirooxindole
Leave this area blank for abstract info.
grafted 3-nitrochromanes through 1,3-dipolar
cycloaddition reaction of azomethine ylides
J. Naga Siva Rao R. Raghunathan*

2
An expedient synthesis of pyrrolidinyl spirooxindole grafted
3
-nitrochromanes through 1,3-dipolar cycloaddition reaction
of azomethine ylides
J. Naga Siva Rao and R. Raghunathan*
Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai-600 025,
India.
Abstract:
A facile one-pot synthesis of pyrrolidinyl-spirooxindole grafted 3-nitrochromanes has
been accomplished by 1,3-dipolar cycloaddition (1,3-DC) reaction of 3-nitrochromenes with
azomethine ylides generated in situ from isatin and secondary amino acids. The regio- and
stereochemical outcome of the cycloaddition reaction was ascertained by X-ray crystallographic
analysis.
Keywords: 1,3-dipole, cycloaddition, azomethine ylide, pyrrolidinyl-spirooxindole,
3
-nitrochromenes.
The 1,3-dipolar cycloaddition reaction employing an azomethine ylide as a 1,3-dipole
1
has been used extensively to construct complex heterocycles from relatively simple precursors.
This type of cycloaddition simultaneously forms two carbon-carbon bonds to construct complex
2
ring systems with regio-and stereocontrol. Synthesis of polycyclic compounds incorporating
pyrrolidine and pyrrolizidine rings has been center of attraction for the past several decades since
3
it constitutes significant class of substances with highly pronounced biological activities. Among
the different synthetic strategies, The 1,3-dipolar cycloaddition of azomethine ylide is the most
4
convenient method for the construction of highly substituted pyrrolidine and pyrrolizine rings.
Corresponding author E-mail: ragharaghunathan@yahoo.com.(R.Raghunathan)
Phone: +91-44-22202811; Fax: +91-44-22300488

3
In recent years much attention has been focused on synthesis of 3,3’-pyrrolidinyl-
spirooxindole frame work as it forms core structure of numerous alkaloids with strong bioactivity
5
-7
such as horsifiline, spirotryprostatine A and B, pteropodine, isopteropodine etc. It is an
important structural motif which acts as potent non-peptide inhibitor of the p53–MDM2
8
interaction.
Chromane derivatives have received special attention in medicinal chemistry due to their
9
10
significant biological property and frequent occurrence in nature. Recently several studies have
11
12
demonstrated that benzopyranopyrrolidine derivatives S33084 and S33138 (Figure 1) act as
antagonists of the dopamine D3 receptor and potential antipsychotic medicaments, while
1
3
benzopyranopyrrolidine I is an antagonist of 5-HT receptors with respect to 5-HT . Similarly
2
C
2A
fiduxosin II is an α adrenoreceptor antagonist and shows an α /α1b selectivity for
1
1a
adrenoreceptors. It is suggested as a promising pharmaceutical agent for the treatment of benign
1
4
prostatic hyperplasia (Figure 1).
Figure 1
Encouraged by the reports on the structural features and biological activity of these
molecules, we plan to fuse structurally unique pyrrolidinyl-spirooxindole motifs with benzopyran
derivatives, with the expectation that this will lead to a new class of heterocycles with potential
biological activities. To the best of our knowledge, there is no report in the literature on the
synthesis of spirooxindole grafted 3-nitrochromanes through 1,3-dipolar cycloaddition reaction.
1
5
As part of our own interest in 1,3-dipolar cycloaddition of azomethine ylide herein we
report the facile synthesis of title compounds via [3+2] cycloaddition of 3-nitrochromenes with

4
azomethine ylides generated in situ from thermal decarboxylative condensation of isatin and
secondary aminoacids ( Figure 2) .
Figure 2
1
6
17
The 3-nitrochromenes containing 1-napthyl, ferrocenyl, N-methyl-3-indole, phenyl and 4-
methoxy phenyl at 2-position utilized for 1,3-dipolar cycloaddition were prepared by the
treatment of β-nitroalkenes with salicylaldehyde in the presence of DABCO under solvent-free
1
8
conditions in a single step by modification of the method reported by Yao (Scheme 1).
Scheme 1
Initially, we investigated the reaction of 2-napthyl-3-nitro chromene (3a) as dipolarophile
with azomethine ylide generated in situ from isatin and sarcosine in refluxing toluene under
Dean–Stark reaction conditions. [3+2] cycloaddition reaction occured smoothly to afford the
1
9
cycloadduct 6 in good yields (83%) with high regio- and stereoselectivity after 20 h (Scheme 2).
Scheme 2
The structure of the product was confirmed by spectroscopic analysis. A single product was
isolated and no trace of the other isomer was observed even after prolonged reaction time. The
1
crude H NMR spectra of the product confirmed the formation of single regio and stereoisomer.
1
The H NMR spectrum of compound 6 exhibited a characteristic singlet at δ 2.11corresponding to
N-methyl protons. The H proton of pyrrolidine ring attached to chromane core appeared as
a
singlet at δ 4.42, and H proton of chromane ring and NH proton of oxindole resonated as singlets
b
at δ 6.93 and δ 9.74,which clearly proved the incorporation of spiropyrrolidine oxindole ring in
2
-napthyl-3-nitrochromane. Furthermore the characteristic singlet at δ 4.42 corresponding to Ha
proton proved the formation of regio isomer 6. If the other regioisomer 6A had formed, the Ha
1
proton would have appeared as a multiplet in the H NMR spectrum. The amide carbonyl carbon

5
13
of oxindole showed characteristic peak at 176.9 ppm in C NMR spectrum. Further the N-methyl
carbon of pyrrolidine ring and carbons attached to H , H protons appeared at 34.2, 52.1 and 74.4
a
b
1
3
ppm respectively in C NMR spectrum. The pyrrolidine methylene carbon, resonated at 56.6
ppm, and was confirmed by DEPT-135 NMR spectroscopy. These observed chemical shift values
are in good agreement with the structure of the compound 6. The reaction was found to be highly
regioselective leading to the formation of only one product 6 (Figure 3, path A) and the formation
of the other possible regioisomer 6A (Figure 3, path B) was not observed. This may be due to the
high polarized charge of dipole and dipolarophile. The regio- and stereochemical outcome of the
cycloaddition reaction was clearly determined by single-crystal X-ray analysis of the cycloadduct
20
6
(Figure 4).
Figure 3
Figure 4
To optimize the reaction conditions, the reaction was carried out in different solvents such as
benzene, acetonitrile, methanol, DMF, and 1,4 dioxane. It was found that toluene was the best to
get the maximum yield of the products. To expand the scope of the reaction, we treated different
3
-nitrochromenes containing ferrocenyl, N-methyl-3-indole, phenyl and 4-methoxy phenyl at 2-
position with azomethine ylide generated in situ from isatin and sarcosine under optimized
reaction conditions. The reaction smoothly proceeded through [3+2] cycloaddition to give the
corresponding cycloaddition products in good yields (Table 1).
Table 1
Encouraged by these results, we further investigated similar type of reaction of structurally
diverse 3-nitrochromenes (3a-e) with different 1,3-dipoles generated in situ from decarboxylative

6
condensation of isatin and cyclic aminoacids such as proline and pipacolinic acid, under
optimized conditions. These reactions successfully led to the formation of desired cycloadducts in
good yields (Schemes 3).
Scheme 3
The results are summarized in Table 2. The cycloaddtion was found to be regioselective in all
1
cases. The H NMR spectrum of compound 12 showed a characteristic broad singlet at δ 7.39
corresponding to NH proton of isatin. The H proton of pyrrolizidine ring attached to chromane
a
core and H proton of chromane ring appeared as singlets at δ 4.89 and δ 5.25 respectively. The
b
characteristic singlet at δ 4.89 corresponding to H proton proved the formation of regioisomer 12.
a
If the other regioisomer had formed, the H should have appeared as doublet which we did not
a
1
observe in any of the cases. The H NMR spectra of the crude and column purified products
showed identical which confirm the stereoselective nature of the reaction.
2
1
The X-ray crystal structure analysis of compound 19 showed that the relative
stereochemistry (Figure 5) of the H proton and NO group in the vicinal positions is cis.
a
2
Similarly the phenyl group at 2-position of chromane and NO group in the vicinal positions also
2
have cis orientation.
Figure 5
In conclusion, we have demonstrated a simple and efficient protocol for the synthesis of
pyrrolidinyl-spirooxindole grafted 3-nitrochromanes through 1,3-dipolar cycloaddition
methodology. This multicomponent reaction offers high yield of the products, with simple
experimental procedure and formation of single regioisomer. The biological activities of the

7
synthesized compounds are currently under investigation, and further work in this direction is in
progress.
Acknowledgment
J.N thanks the Council of Scientific and Industrial Research (CSIR), New Delhi, India for the
award of Senior Research Fellowship (SRF). R.R. thanks UGC New Delhi for BSR Faculty
Fellowship. R.R and J.N thank DST, New Delhi for financial support and DST-FIST program for
the NMR facility. The authors wish to thank Professor D. Velmurugan and T. Srinivasan for
single crystal X-ray data.
Reference:
1
. Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and
Natural Products; Padwa, A.; Pearson, W. H., Eds.; John Wiley and Sons, Inc.: New
York, 2002.
2
. (a) Vedejs, E.; Piotrowski, D. W.; Tucci, F. C. J. Org. Chem. 2000, 65, 5498-5505;
(
b) Pandey, G.; Sahoo, A. K.; Bagul, T. D. Org. Lett. 2000, 2, 2299-2301; (c)Vedejs, E.;
Klapers, A.; Naidu, B. N.; Piotrowski, D. W.; Tucci, F. C. J. Am. Chem.Soc. 2000, 122,
401-5404; (d)Novikov, M. S.; Khlebnikov, A. F.; Besidina, O. V.; Kastikov, R. R.
5
Tetrahedron Lett. 2001, 42, 533-535.
3
. (a) The Alkaloids: Chemistry and Biology; Cordell, G. A.; Academic.: San Diego, 1998;
(b) Glassco, W.; Suchocki, J.; George, C.; Martin, B. R.; May, E. L. J. Med. Chem. 1993,
3
6, 3381-3385; (c) Nishimura, Y.; Kondo, S.; Umezawa, H. J. Org. Chem. 1985, 50,
210-5214; (d) Cui, C.-B.; Kakeya, H.; Osada, H. Tetrahedron 1996, 52, 12651-12666;
5
(d) Snider, B. B.; Ahn, Y.; Foxman, B. M. Tetrahedron Lett. 1999, 40, 3339-3342; (e)

8
Nieman, J. A.; Ennis, M. D. Org. Lett. 2000, 2, 1395-1397; (f) Angle, S. R.; Bensa, D.;
Belanger, D. S. J. Org. Chem. 2007, 72, 5592-5597.
4
. (a) Gothelf, K. V.; Jørgensen, K. A. Chem. Rev.1998, 98, 863-909; (b) Pandey, G.;
Banerjee, P.; Smita, R. G. Chem. Rev. 2006, 106, 4484-4517; (c) Pearson, W. H.; Stoy, P.;
Mi, Y. J. Org. Chem. 2004, 69, 1919 – 1939; (d) Alcaide, B.; Almendros, P.; Alonso, J.
M.; Aly, M. F. J. Org. Chem. 2001, 66, 1351 – 1358; (e) Ghandi, M.; Taheri, A.; Abbasi,
A. Tetrahedron.2010, 66, 6744-6748; (f) Alimohammadi, K.; Sarrafi , Y.; Tajbakhsh, M.;
Yeganegi, S.; Hamzehloueian, M. Tetrahedron 2011, 67, 1589-1597; (g) Moshkin, V. S.;
Sosnovskikh, V. Y.; Röschenthaler, G.-V. Tetrahedron Lett. 2012, 53, 3568-3572; (h) Deb
Barman, P.; Sanyal, I.; Mandal, S. B.; Banerjee, A. K. Synthesis 2011, 21, 3563–3568.
. (a) Galliford, C. V.; Scheidt. K. A. Angew. Chem. Int. Ed. 2007, 46, 8748-8758. (b) Marti,
C.; Carreira, E. M.; Eur. J. Org. Chem. 2003, 2209-2219.
5
6
. (a) Lizos, D.; Tripoli, R.; Murphy, J. A. Chem. Commun. 2001, 2732-2733. (b) Cochard,
F.; Laronze, M.; Prost, E.; Nuzillard, J.-M.; Auge, F.; Petermann, C.; Sigaut, P.; Sapi, J.;
Laronze, J.-Y. Eur. J. Org. Chem. 2002, 3481-3490. (c) Lizos, D. E.; Murphy, J. A. Org.
Biomol. Chem. 2003, 1, 117-122.
7
. (a) Usui, T.; Kondoh, M.; Cui, C.-B.; Mayumi, T.; Osada, H. Biochem. J. 1998, 333, 543-
5
48; (b) Edmondson, S.; Danishefsky, S. J.; Sepp-lorenzinol, L.; Rosen, N. J. Am. Chem.
Soc. 1999, 121, 2147-2155; (c) Kang, T. H.; Matsumoto, K.; Murakami, Y.; Takayama,
H.; Kitajima, M.; Aimi, N.; Watanabe, H. Eur. J. Pharmacol. 2002, 444, 39-45; (d) Hecht,
J. Ma, S. M. Chem. Commun. 2004, 1190-1191.
8
. (a) Ding, K.; Lu, Y.; Nikolovska-Coleska, Z.; Qiu, S.; Ding Y.; Gao, W.; Stuckey, J.;
Krajewski, K.; Roller, P. P., Tomita, Y.; Parrish, D. A.; Deschamps, J. R.; Wang, S. J. Am.

9
Chem. Soc. 2005, 127, 10130-10131; (b) Ding, K.; Lu, Y.; Nikolovska-Coleska, Z.;
Wang, G.; Qiu, S.; Shangary, S.; Gao, W.; Qin, D.; Stuckey, J.; Krajewski, K.; Roller, P.
P.; Wang, S. J. Med. Chem. 2006, 49, 3432-3435.
9
. (a) Schmidt, R. G.; Bayburt, E. K; Latshaw, S. P.; Koenig, J. R.; Daanen, J. F.; McDonald,
H. A.; Bianchi, B. R.; Zhong, C.; Joshi, S.; Honore, P.; Marsh, K. C.; Lee, C. H.;
Faltynek, C. R.; Gomtsyan, A. Bioorg. Med. Chem. Lett. 2011, 21, 1338-1341; (b)
Dubuffet, T.; Newman-Tancredi, A.; Cussac, D.; Audinot, V.; Loutz, A.; Millan, M. J.;
Lavielle, G. Bioorg. Med. Chem. Lett. 1999, 9, 2059-2064.
1
1
0. Ellis, G. P. Chemistry of Heterocyclic Compounds; Wiley: New York, 1997, Vol. 31.
1. (a) Cussac, D.; Newman-Tancredi, A.; Sezgin, L.; Millan, M. J. Eur. J. Pharmacol. 2000,
3
94, 47–50; (b) Millan, M. J.; Gobert, A.; Newman-Tancredi, A.; Lejeune, F.; Cussac, D.;
Rivet, J.-M.; Audinot, V.; Dubuffet, T.; Lavielle, G. J. Pharmacol. Exp. Ther. 2000, 293,
048–1062.
1
1
1
1
2. Millan, M. J.; la Cour, C. M.; Novi, F.; Maggio, R.; Audinot, V.; Newman-Tancredi, A.;
Cussac, D.; Pasteau, V.; Boutin, J.-A.; Dubuffet, T.; Lavielle, G.; J. Pharmacol.Exp. Ther.
2
008, 324, 587–599.
3. (a) Lavielle, G.; Dubuffet, T.; Millan, M. J.; Newman-Tancredi, A. US Patent. 5663191,
997; (b) Meyer, M. D.; Altenbach, R. J.; Basha, F. Z.;Carroll, W. A.; Drizin, I.; Kerwin,
1
J. F.; Wendt, M. D.; Haight, A. R.; Zhang, W. US Patent. 6046207, 2000.
4. Haight, A. R.; Bailey, A. E.; Baker, W. S.; Cain, M. H.; Copp, R. R.; DeMattei, J. A.;
Ford, K. L.; Henry, R. F.; Hsu, M. C.; Keyes, R. F.; King, S. A.; McLaughlin, M. A.;
Melcher, L. M.; Nadler, W. R.; Oliver, P. A.; Parekh, S. I.; Patel, H. H.; Seif, L. S.;

1
0
Staeger, M. A.; Wayne, G. S.; Wittenberger, S. J.; Zhang, W. Org. Process Res. Dev.
004, 8, 897-902.
2
1
5. (a) Rajesh, R.; Raghunathan, R. Eur. J. Org. Chem. 2013, 2597–2607; (b) Saravanan, P.;
Pushparaj, S.; Raghunathan, R. Tetrahedron Lett. 2013, 54, 3449–3452; (c) Naga Siva
Rao, J.; Raghunathan, R. Tetrahedron Lett. 2012, 53, 854–858; (d) Sirisha, N.;
Raghunathan, R. Tetrahedron Lett. 2010, 51, 2515-2518; (e) Prasanna, R.;
Purushothaman, S.; Raghunathan, R. Tetrahedron Lett. 2010, 51, 4538-4542; (f)
Purushothaman, S.; Prasanna, R.; Niranjana, P.; Raghunathan, R.; Nagaraj, S.;Rengasamy,
R. Bioorg. Med. Chem. Lett. 2010, 20, 7288–7291.
1
6. To a solution of salicylaldehyde (2 equiv) and (E)-(2-nitrovinyl) ferrocene (1 equiv) was
added 1,4 diazabicyclo[2.2.2]octane (DABCO) (0.5 equiv) respectively. In the absence of
solvent the reaction mixture was stirred at 90°C for 2h. After completion of the reaction as
indicated by TLC, the crude product was extracted with ethylacetate. The organic layer
was dried with anhydrous sodium sulphate and concentrated in vacuo. Then the crude
product was purified by column chromatography using hexane/EtOAc (9:1) as eluent.
1
7. To a solution of salicylaldehyde (2 equiv) and (E)-1-methyl-3-(2-nitrovinyl)-1H-indole (1
equiv) was added 1,4 diazabicyclo[2.2.2]octane (DABCO) (0.5 equiv). In the absence of
solvent the reaction mixture was stirred at 90 °C for 5h. After completion of the reaction
as indicated by TLC, the crude product was extracted with ethylacetate. The organic layer
was dried with anhydrous sodium sulphate and concentrated in vacuo. Then the crude
product was purified by column chromatography using hexane/EtOAc (7:3) as eluent.

1
1
1
1
8. (a) Yan, M.-C.; Jang, Y.-J.; Yao, C.-F. Tetrahedron Lett. 2001, 42, 2717-2720; (b) Yan,
M.-C.; Jang, Y.-J.; Kuo, W.-Y.; Tu, Z.; Shen, K.-H.; Cuo, T.-S.; Ueng, C.-H.; Yao, C.-F.
Heterocycles. 2002, 57, 1033-1048.
9. General Procedure for synthesis of pyrrolidinyl-spirooxindole fused 3-
nitrochromanes: To a solution of isatin (1.0 mmol) and cyclic or acyclic secondary
amino acid (1.5 mmol) in dry toluene, were added 3-nitrochromenes (3a-e) under nitrogen
atmosphere. The solution was refluxed for 24 h in Dean-Stark apparatus to give the
cycloadducts. After completion of the reaction as indicated by TLC, the solvent was
evaporated under reduced pressure. The crude product obtained was purified by column
chromatography using hexane/EtOAc (8:2) as eluent.
Spectroscopic Data for Selected Compounds
Compound 6: White solid, (83%), Mp: 280-282 ˚C, IR (KBr): 1728, 1619, 3410, 1321,
-
1 1
1
4
2
7
529 cm . H NMR (300 MHz, CDCl + DMSO-d ): δ 2.11 (s, 3H), 3.83-3.95 (m, 2H),
3 6
.42 (s, 1H), 6.44 (d, J = 7.8 Hz, 1H), 6.73 (t, J = 7.5 Hz, 1H), 6.93 (s,1H), 6.95-6.98 (m,
H), 7.09-7.18 (m, 2H), 7.32-7.42 (m, 2H), 7.49-7.54 (m, 2H), 7.57-7.63 (m, 2H), 7.89-
1
3
.93 (m, 2H), 8.66 (d, J = 8.4 Hz, 1H), 9.74 (s, 1H). C NMR (75MHz, CDCl + DMSO-
3
d6): δ 34.2, 52.1, 56.6, 74.4, 76.6, 95.8, 110.2, 117.4, 118.9, 121.8, 122.9, 123.0, 124.0,
1
1
8
25.0,125.1, 125.5, 126.1, 126.5, 127.8, 128.0, 128.6, 129.5, 129.9, 130.6, 131.2, 133.4,
42.3, 154.6, 176.9. m/z: 477.52. Anal. Calc. For C H N O : C, 72.94; H, 4.85; N,
29
23
3
4
.80%. Found: C, 72.98; H, 4.81; N, 8.85%.
Compound 12: Brown solid, (84%), Mp: 180-182˚C, IR (KBr):1734, 1618, 3410, 1325,
-1
1
1
547 cm . H NMR (300 MHz, CDCl ): δ 1.02-1.21 (m, 2H), 1.77-2.03 (m, 2H), 2.24-
3

1
2
2
4
6
1
6
1
.31 (m, 1H), 2.76-2.82 (m, 1H), 4.18-4.18 (m, 1H), 4.24-4.26 (m, 1H), 4.28 (s, 5H), 4.56-
.57 (m, 1H), 4.67-4.72 (m, 2H), 4.89 (s, 1H), 5.25 (s, 1H), 6.44 (d, J = 7.5 Hz, 1H), 6.75-
.80 (m, 2H), 7.08 (d, J = 7.2 Hz, 1H), 7.15 (t, J = 7.8 Hz, 1H), 7.28-7.33 (m, 1H), 7.39 (s,
1
3
H), 7.63 (d, J = 7.5 Hz, 1H). C NMR (75MHz, CDCl ): δ 24.2, 26.2, 42.8, 62.0, 67.7,
3
7.9, 68.10, 69.1, 69.3, 69.8, 71.9, 77.2, 83.6, 97.8, 109.6, 117.3, 122.7, 122.7, 123.1,
25.3, 126.5, 128.7, 129.0, 129.6, 141.1, 155.8, 176.5. m/z: 561.93. Anal. Calc. For
C H FeN O : C, 66.32; H, 4.85; N, 7.48%. Found: C, 66.39; H, 4.91; N, 7.53%.
31
27
3
4
Compound 19: White solid, (87%), Mp: 250-252 ˚C, IR (KBr): 1705, 1620, 3441, 1327,
-
1
1
1
1
1
1
4
543 cm . H NMR (300 MHz, CDCl ):  0.96-1.08 (m, 1H), 1.19-1.39 (m, 2H), 1.50-
3
.53 (m, 1H), 1.63-1.66 (m, 1H), 1.74-1.77 (m, 1H), 2.23-2.24 (m, 1H), 2.52-2.56 (m,
H), 4.14-4.18 (m, 1H), 4.93 (s, 1H), 5.88 (s, 1H), 6.41 (d, J = 7.8Hz, 1H), 6.65-6.70 (m,
H), 6.85 (t, J = 8.1 Hz, 1H), 7.03 (t, J = 7.3Hz, 1H), 7.20-7.25 (m, 1H), 7.35-7.39 (m,
1
3
H), 7.45-7.48 (m, 2H), 7.59 (d, J = 7.2 Hz, 1H), 7.66 (s, 1H). C NMR (75 MHz,
CDCl ):  24.2, 24.8, 28.8, 46.3, 50.4, 64.3, 75.2, 80.0, 98.1, 109.8, 117.8, 120.2, 122.3,
3
1
23.8, 124.9, 126.2, 127.7, 127.9, 128.4, 128.6, 128.9, 130.0, 135.8, 141.5, 154.5, 177.1.
m/z: 468.20. Anal. Calc. For C H N O : C, 71.93; H, 5.39; N, 8.99%. Found: C, 71.98;
2
8
25
3
4
H, 5.33; N, 8.94%.
2
2
0. Karthiga Devi, S.; Srinivasan,T.; Naga Siva Rao, J.; Raghunathan, R.; Velmurugan, D.
Acta Crystallogr., Sect. E. 2013, 69, o1045-o1046.
1. Karthiga Devi, S.; Srinivasan,T.; Naga Siva Rao, J.; Raghunathan, R.; Velmurugan, D.
Acta Crystallogr., Sect. E. 2013, 69, o993.

1
3
Figure 1 Biologically active benzopyranopyrrolidines
Figure 2 Synthetic plan for synthesis of spirooxindoles fused benzopyrans

1
4
Scheme 1 Synthesis of 3-nitrochromene derivatives
Scheme 2 Synthesis of spiropyrrolidine oxindole fused 3-nitrochromanes
Figure 3: The possible regio chemical mode of approach of azomethine ylide to the dipolarophile

1
5
Figure 4: ORTEP diagram of compound 6

1
6
Table 1: Synthesis of spiropyrrolidine oxindole fused 3-nitrochromanes
a
b
c
Completion of the reaction based upon TLC analysis.
The products were characterized by IR, NMR, MS and elemental analysis.
Isolated yield after purification.

1
7
Scheme 3 Synthesis of spiropyrrolizidine/spiroindolizidine oxindole fused 3-nitrochromanes
Figure 5: ORTEP diagram of compound 19

1
8
Table 2: Syntheis of spiro pyrrolizidine/spiro indolizidine oxindole fused 3-nitrochromanes
a
b
c
Completion of the reaction based upon TLC analysis.
The products were characterized by IR, NMR, MS and elemental analysis.
Isolated yield after purification.