Ijaret 06 10_002

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International Journal of Advanced Research in Engineering and Technology
(IJARET)
Volume 6, Issue 10, Oct 2015, pp. 06-10, Article ID: IJARET_06_10_002
Available online at
http://www.iaeme.com/IJARET/issues.asp?JType=IJARET&VType=6&IType=10
ISSN Print: 0976-6480 and ISSN Online: 0976-6499
© IAEME Publication
___________________________________________________________________________
SYNTHESIS OF SPIROPYRROLIDINES AND
3-SPIROPYRROLIZIDINES USING THE
BAYLIS-BILLMAN ADDUCTS DERIVED
FROM DITROOLEFINS
Nagappan Sivakumar and Chendrasekaran Yogalakshmi
Department Chemistry, AMET University Chennai 603 112, India
ABSTRACT
We have successfully developed a novel protocol for the construction of
highly substituted 3-spiropyrrolidines and 3-spiropyrrolizidines using Baylis-
Hillman adducts derived from nitroolefins via 1, 3 dipolar cycloaddition
reaction.
Cite this Article: Nagappan Sivakumar and Chendrasekaran Yogalakshmi.
Synthesis of Spiropyrrolidines and 3-Spiropyrrolizidines Using The Baylis-
Billman Adducts Derived From Ditroolefins. International Journal of
Advanced Research in Engineering and Technology, 6(10), 2015, pp. 06-10.
http://www.iaeme.com/IJARET/issues.asp?JType=IJARET&VType=6&IType=10
INTRODUCTION
The Baylis–Hillman reaction is an atom economical, green and simple reaction which
provides densely functionalized molecules.1–4
As a result, Baylis–Hillman adducts
have become valuable sources for making cyclic frameworks, especially tricyclic
compounds containing heteroatoms.5–7
The abundance of oxygen- and nitrogen-
containing cyclic compounds in pharmaceuticals and agrochemicals continues to
ensure that they are important synthetic targets for organic chemists.8–10
Concerted
[3+2] cycloaddition of azomethine ylides is a powerful tool for the construction of
various types of complex polyheterocyclic frameworks.11–14
In recent years the
azomethine ylide has gained a vital place in the field of heterocyclic chemistry as it
serves as an important building block for the construction of nitrogen-containing five
membered heterocycles, which are often an integral part of many natural products and
bioactive molecules. The exploration of new methods towards the construction of
organic molecules from simple starting resources is an on-going contest for organic
chemists. The improvement of effective approaches for the synthesis of heterocyclic
compounds remains a very essential challenge for modern organic synthesis. In recent
periods, seven membered ring oxacycles1 have received increasing attention due to

2. Synthesis of Spiropyrrolidines and 3-Spiropyrrolizidines Using The Baylis-Billman Adducts
Derived From Ditroolefins
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their existence in natural products, biological activities, 15
and their use as natural
herbicides16
.
The spiropyrrolidines scaffold is found in a great number of scaffolds distributed
in number of biologically active natural products isolated predominantly from plant
resources. In addition, the 1, 3-dipolar cycloaddition reaction is one of the most
important and useful procedure for the construction of nitrogen / oxygen containing17
five membered heterocycles.
The 1, 3-dipolar cycloaddition reaction is one of the most important and useful
method for the preparation of five membered heterocycles. The reaction of
azomethine ylides with alkenes provides the pyrrolidine moiety which is present in
numerous natural products and biologically active molecules.18,19
Utilizing
azomethine ylide based [3+2] cycloaddition reaction, a variety of spiropyrrolidines
have been reported in the literature.20
In recent years the azomethine ylide has gained a
vital place in the field of heterocyclic chemistry as it serves as an important building
block for the construction of nitrogen containing five-membered heterocycles, which
are often an integral part of many natural products and bioactive molecules such as
tocopherol, (+) Haematoxyline, tocotrienols, martinelline etc.21-28
The Baylis-Hillman adducts and its derivatives are utilized as starting material for
various organic reactions which include several named reactions in organic chemistry.
For instance, recently the Baylis-Hillman adducts are utilized as dipolarophiles in
[3+2] cycloaddition chemistry to produce spiropyrrolidines
Literature survey reveals that spiropyrrolidines and spiropyrrolidizines
frameworks constitutes an important structural assembly owing to the presence of
these structural units in various molecules of historical importance.75
Hence the
development of new, simple and efficient methodologies for the synthesis of
spiropyrrolidines and spiropyrrolizidine frameworks represents an important endeavor
in the area of organic chemistry. We envisaged that Baylis-Hillman adduct (a) derived
from β-aryl nitroolefin would be a useful dipolarophile for the construction of
spiropyrrolidine and spiropyrrolizidine compounds via azomethine ylide based [3+2]
cycloaddition reaction. This new methodology is not only useful for the synthesis of
3-spiropyrrolidines and spiropyrrolizidines but also demonstrates the importance of
Baylis-Hillman adducts which are derived from nitroolefins. Infact in the Baylis-
Hillman chemistry, BH adducts derived from nitroolefins are not explored much.
To execute our idea we planned to synthesize various Baylis-Hillman adducts. we
first selected (2E,2'E,2''E)-3,3',3''-(4,4',4''-nitrilotris(benzene-4,1-diyl))tris(2-
nitroprop-2-en-1-ol) (2), a Baylis-Hillman adduct derived from nitrostyrene, as a
starting material for [3+2] cycloaddition reaction with dipoles generated from N-
methyl glycine and isatin. Best results were obtained when 2 was treated with isatin
and N-methyl glycine without any catalyst in acetonitrile solvent for 5 h at reflux
temperature, which successfully provided the desired 3-spiropyrrolidine compound 3
in very good yield (62%) after usual workup followed by column chromatography.
The compound 3 was characterized by IR, 1
H & 13
C NMR spectroscopy, mass
spectrometry and elemental analysis (Scheme 60).
The 1
H NMR spectrum of compound 3 showed a singlet for N-CH3 proton at δ
2.23 and triplet for benzylic proton at δ 4.69. The N-CH2 protons of pyrrolidine ring
appeared as two triplets at δ 3.56 and δ 4.07. The O-attached CH2 protons appeared
as multiplet in the region of δ 3.73-3.95. The NH proton of oxindole ring appeared at
δ 7.72. The aromatic protons appeared in the region of δ 6.85-7.59.

3. Nagappan Sivakumar and Chendrasekaran Yogalakshmi
http://www.iaeme.com/IJARET/index.asp 8 editor@iaeme.com
Scheme 1
CONCLUSION
Hence we have successfully developed a novel protocol for the construction of highly
substituted 3-spiropyrrolidines and 3-spiropyrrolizidines using Baylis-Hillman
adducts derived from nitroolefins via 1,3 dipolar cycloaddition reaction. All the
compounds were characterized by IR, 1
H NMR, 13
C NMR, mass spectral data and
elemental analyses.
Typical experimental procedure for the synthesis 3-spiropyrrolidines (3)
A mixture of (2E,2'E,2''E)-3,3',3''-(4,4',4''-nitrilotris(benzene-4,1-diyl))tris(2-
nitroprop-2-en-1-ol) 2 (2 mmol, 1.09g), isatin (2 mmol, 0.73g) and sarcosine (2 mmol,
0.52g) in acetonitrile (12 mL) was refluxed for 5h. After the completion of the
reaction as indicated by TLC, the reaction mixture was concentrated. Then the
resulting crude mass was diluted with water (10 mL) and extracted with ethyl acetate
(3 x 10 mL). The combined organic layers were washed with brine (2 x 10 mL) and
dried over anhydrous Na2SO4. The organic layer was concentrated and the residue
purified by column chromatography on silica gel (Acme 100-200 mesh), using ethyl
acetate: hexanes (2 : 8) to afford 3 as a colourless solid in 0.66g (62%) yield.
IR (KBr): 3487, 3229, 1727, 1544, 1326 cm1
1
H NMR (CDCl3, 300 MHz): δ 2.23 (s, 3H), 4.69 (dd, J = 2.8, 11.4Hz, 1H), 3.56
(t, J = 9.0Hz, 1H), 3.73-3.95 (m, 2H), 4.07 (t, J = 9.6 Hz, 1H), 4.95 (t, J = 9.0Hz, 1H),
6.85-7.59 (m, 9H), 7.72 (s, 1H). 13
C NMR (CDCl3, 75 MHz): δ 34.71, 49.43, 56.77,

4. Synthesis of Spiropyrrolidines and 3-Spiropyrrolizidines Using The Baylis-Billman Adducts
Derived From Ditroolefins
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65.27, 78.21, 106.05, 110.25, 124.38, 124.47, 125.26, 128.38, 128.73, 129.97, 131.48,
133.75, 142.55, 176.36.
MS: m/z = 1070 (M+).
Anal. Calcd for C57H54N10O12: C, 63.92; H, 5.08; N, 13.08; Found: C, 63.92; H,
5.08; N, 13.08.
ACKNOWLEDGMENTS
We thank AMET University for the financial support. We also thank University 0f
Madras for the NMR facility. Indian institute of Technology, Chennai for IR, and
Mass Spectra.
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