Synthesis of highly substituted 2,3-dihydro-1H-pyrrole derivatives via a tandem regioselective addition of nitrones to 1,3-enynes with subsequent rearrangement

Article abstract of DOI:10.1021/jo702610j

(Chemical Equation Presented) A novel method for the synthesis of 1,3-enynes is described through oxidative cyclization of the semicarbazones of Michael adducts having potential nitrile functionality. Reaction of these 1,3-enynes with diaryl nitrones has yielded a diastereomeric mixture of highly substituted 2,3-dihydro-1H-pyrrole derivatives via a tandem regioselective addition with subsequent rearrangement.

Full text of DOI:10.1021/jo702610j

Synthesis of Highly Substituted 2,3-Dihydro-1H-pyrrole Derivatives
via a Tandem Regioselective Addition of Nitrones to 1,3-Enynes
with Subsequent Rearrangement
Sivaperuman Saravanan, Ismail Abulkalam Azath, and Shanmugam Muthusubramanian*
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj UniVersity,
Madurai 625 021, India
muthumanian2001@yahoo.com
ReceiVed December 6, 2007
A novel method for the synthesis of 1,3-enynes is described through oxidative cyclization of the
semicarbazones of Michael adducts having potential nitrile functionality. Reaction of these 1,3-enynes
with diaryl nitrones has yielded a diastereomeric mixture of highly substituted 2,3-dihydro-1H-pyrrole
derivatives via a tandem regioselective addition with subsequent rearrangement.
Introduction
boration of alkynes.4 Synthesis of 1,3-enynes through alk-1-
enyldialkylborane,5 alkenyl nonaflates,6 phosphorane,7 and
partial catalytic hydrogenation8 have also been reported. Herein,
we report a novel method for the synthesis of tetrasubstituted
1,3-enynes through oxidative cyclization of the semicarbazones
of Michael adducts and their subsequent reactivity toward diaryl
nitrones yielding highly substituted pyrrole derivatives. Syn-
theses of highly substituted pyrroles via transition-metal-
catalyzed multicomponent coupling have been reported re-
cently.9 Highly substituted pyrrole derivatives have also been
prepared by the cycloaddition of alkene with azalactones and
oxazolones.10
1,3-Enyne functionality can be found in many naturally
occurring and biologically active compounds. The most potent
antifungal agent possessing this substructure is terbinafine
(commonly known as Lamisil), which is used to treat fungal
infections of the toe and finger nails. It inhibits ergosterol
synthesis by inhibiting squalene epoxidase, an enzyme that is
involved in the fungal cell wall synthesis.1 Although the
palladium(0)-catalyzed Sonogashira coupling2 of terminal alkynes
with aryl or vinyl halides is one of the most widely employed
methods for the synthesis of conjugated enynes, the other
commonly utilized methodologies to access 1,3-enynes are
copper(I)-catalyzed coupling3 and nickel-catalyzed alkynyl
Results and Discussion
(1) (a) Ryder, N. S. Br. J. Dermatol. 1992, 126, 2. (b) Darkes, M. J. M;
Scott, L. J.; Goa, K. L. Am. J. Clinic. Dermatol. 2003, 4, 39.
(2) Clayden, J.; Greeves, N.: Warren, S.; Wothers, P. Organic Chemistry,
1st ed.; Oxford University Press: New York, 2001; p 1330.
(3) (a) Bates, C. G.; Saejweng, P.; Venkataraman, D. Org. Lett. 2004,
6, 1441. (b) Lemay, A. B.; Vulic, K. S.; Ogilivie, W. W. J. Org. Chem.
2006, 71, 3615.
(4) Suginome, M.; Shirakura, M.; Yamamoto, A. J. Am. Chem. Soc. 2006,
128, 14438.
(5) Hoshi, M.; Kawamura, N.; Shirakawa, K. Synthesis 2006, 6, 1961.
(6) Lyapkalo, I. M.; Vogel, M. A. K. Angew. Chem., Int. Ed. 2006, 45,
4019.
The synthetic approach started by modifying the reported
procedure11 for the Michael addition of ethyl cyanoacetate (2)
(7) Kartholuvhu, M. S.; Fuchs, P. L. J. Am. Chem. Soc. 2004, 126, 14314.
(8) Passarella, D.; Giardini, A.; Martinelli, M.; Silvani, A. J. Chem. Soc.,
Perkin Trans. 1 2001, 2, 127.
(9) (a) Binder, J. T.; Kirsch, S. F. Org. Lett. 2006, 8, 2151. (b) Dhawan,
R.; Arndtsen, B. A. J. Am. Chem. Soc. 2004, 126, 468. (c) Galliford, C. V.;
Beenen, M. A.; Nguyen, S. T.; Scheidt, K. A. Org. Lett. 2003, 5, 3487.
(10) (a) Yebdri, O.; Henri-Rousseau, O.; Texier, F. Tetrahedron Lett.
1983, 24, 369. (b) Yebdri, O.; Texier, F. Bull. Soc. Chim. Fr. 1983, 195.
10.1021/jo702610j CCC: $40.75 © 2008 American Chemical Society
Published on Web 02/22/2008
J. Org. Chem. 2008, 73, 2323-2329
2323

Saravanan et al.
SCHEME 1. Formation of Enyne and Oxidized Selenadiazole
to substituted benzylidene acetophenones (1) in the presence
of an equimolar amount of potassium carbonate without any
solvent at room temperature. It is also reported that the formation
of cyclized products is quite common by the Michael addition
of ethyl cyanoacetate with two molecules of benzylidene
acetophenone followed by aldol condensation.12 The members
of the diastereomeric mixture of the Michael adduct have close
Rf values, and hence, it is difficult to isolate the individual
diastereomers (Scheme 1).
Without isolating the individual diastereomers, the ketones
3 were converted to their semicarbazones 4 by conventional
methods.13 Quantitative conversion has been effected, and the
diastereomeric pair has been obtained in the same ratio. It is to
be noted that, of the two possible semicarbazone geometrical
isomers, only one isomer has been obtained in all of the cases,
probably the one in which the phenyl group and the NHCONH2
are trans to each other. In these cases too, it is difficult to
separate the diastereomers by column chromatography as they
have close Rf values (Scheme 1).
Synthesis of 1,2,3-selenadiazoles is of recent interest as they
are not only versatile intermediates for the preparation of alkynes
and other selenium compounds14 but also have attracted much
attention for their biological characteristics like antifungal,
antibacterial, antimicrobial, and insecticidal activities.15 The
semicarbazones 4 were then subjected to selenium dioxide
treatment in THF to achieve the oxidative ring closure. Thus,
when 4a was subjected to selenium dioxide in THF, three
products were formed as evident from TLC. These three
fractions (5a, 6a, 7a) have been separated by column chroma-
tography. The overall yield of these three products is 64%, and
the ratio of 5a/6a/7a is 48:27:25, as evident from the 1H NMR
spectrum of the crude mixture. The column-separated 5a, 6a/
and 7a have been analyzed for structure by spectral techniques.
Thus, 5a is an inseparable mixture of two diastereomeric forms
of ethyl 2-cyano-3-phenyl-3-(4-phenyl-1,2,3-selenadiazol-5-yl)-
propanoate in the ratio 1:0.8, 6a is ethyl 2-cyano-3-phenyl-3-
(4-phenyl-1,2,3-selenadiazol-5-yl)-2-propenoate, and 7a is the
mixture of geometrical isomers of ethyl 2-cyano-3,5-diphenyl-
2-penten-4-ynoate in a ratio of 5:1. The formation of the
(11) Paul, S.; Gupta, M.; Singh, P. P.; Gupta, R. Synth. Commun. 2005,
35, 325.
(12) Al-Arab, M. M.; Ghanem, B. S. Tetrahedron 1989, 45, 6545.
(13) Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.; Tatchell, A. R.
In Vogel’s Textbook of Practical Organic Chemistry, 5th ed., InVestigations
and Characterization of Organic Compounds; Longman: Harlow, England,
1989.
(14) Al-Smadi, M.; Ratrout, S. J. Heterocycl. Chem. 2004, 41, 887.
(15) (a) Faria, C.; Prizza, M.; Gramba, A.; Pifferri, G. I. Eur. J. Med.
Chem. Chem. Ther. 1979, 14, 27. (b) Lalezari, I.; Shafiee, A.; Khorrami,
J.; Soltani, A. J. Pharm. Sci. 1978, 67, 1336. (c) Kandeel, M. M.; El-Meligie,
S.; Omar, R. H.; Roshdy, S. A.; Youssef, K. M. Chem., J. Pharm. Sci.
1994, 3, 197.
2324 J. Org. Chem., Vol. 73, No. 6, 2008

Synthesis of Highly Substituted 2,3-Dihydro-1H-pyrrole DeriVatiVes
TABLE 1. Reaction of Semicarbazone 4 with Selenium Dioxide in
Acetic Acid
SCHEME 2. Selective Formation of Enyne
entry product yield (%) mp (°C) product yield (%) mp (°C)
1
2
3
4
6a
6b
6c
6d
36
31
34
32
125
127
138
viscous
liquid
7a
7b
7c
7d
28
25
22
23
121
116
107
viscous
liquid
unexpected products, viz. 6a and 7a, can be rationalized
considering the oxidation of the side chain by excess selenium
dioxide and thermal decomposition of the alkene-substituted
selenadiazole molecule. It is to be noted that such a dehydro-
genation and elimination have not been observed in related
reactions.16
The unexpected products 6 and 7 are ideally suited for the
construction of heterocyclic compounds by cycloaddition strate-
gies. Hence, the reaction of semicarbazone 4 with selenium
dioxide was carried out in acetic acid with a 1:10 ratio of
substrate and oxidizing agent to give compounds 6 and 7,
allowing 5 to react completely. The yields and melting points
of the products are summarized in Table 1. An earnest attempt
is made here to assign the correct stereochemistry of the major
and minor isomers of 6 and 7 with the NMR data, and the
following discussion offers a rationale for the formation of the
major and minor isomers in the observed ratio.
In the E isomer of 6d, the carbethoxy group and the aryl
ring are cis to each other. Due to deshielding anisotropy of the
aryl ring, the ethyl hydrogens are deshielded and, due to the
deshielding effect of the carbonyl group, the aryl hydrogens of
the p-methoxyphenyl ring are deshielded. The minor isomer of
6d has its methylene hydrogens, methyl hydrogens, and p-
methoxyphenyl hydrogens signals appearing at 4.4, 1.4, 7.8, and
7.0 ppm, respectively. The major isomer of 6d has its methylene
hydrogens, methyl hydrogens, and aromatic hydrogens signals
appearing at 4.05, 1.12, 7.70, and 6.85 ppm, respectively. Hence,
the major isomer has a Z configuration and the minor isomer
has an E configuration. The E and Z isomers are in a ratio of
1:3 in 6d. The structure of compound 6b is unambiguously
confirmed by single-crystal X-ray analysis (ORTEP 1, see the
Supporting Information for more details).
Based on the same arguments, the stereochemistry for the
major and minor isomers of 7d can be assigned. The major
isomer of 7d has its methylene hydrogens, methyl hydrogens,
and aromatic hydrogens at 4.40, 1.42, 7.85, and 7.00 ppm,
respectively. The minor isomer has its methylene hydrogens,
methyl hydrogens and aromatic hydrogens appearing at 4.25,
1.28, 7.50, and 6.94 ppm, respectively. It can be noticed that
the isomer with deshielded hydrogens, which is supposed to be
the E isomer, is the major isomer here and the isomer
corresponding to the shielded hydrogens, the Z isomer, is the
minor one. The E and Z isomers are in the ratio 2:1.
The observed ratio of and E and Z isomers in 6d and 7d
helps us to understand the course of the reaction. Selenium
dioxide reacts initially with the R-methylene end of semicar-
bazone 4 to give selenadiazole 5. In the presence of excess
selenium dioxide, 5 is very reactive and gets further oxidized
at the side chain to give an equal amount of the geometrical
isomers of 6. The E form of 6 seems to be more vulnerable to
thermolysis eliminating nitrogen and selenium to give the enyne
than the other isomer. Hence, in the final reaction mixture
consisting of 6 and 7, the E-isomer dominates in 7 and Z-isomer
dominates in 6 (Scheme 2). However, the reason for the
preferential thermolysis of E form of 6 is not well understood.
It is well-known that 1,3-enynes behave as four electron
donors in various intramolecular and intermolecular [4 + 2]
cycloaddition reactions, which has found substantial application
in experimental synthesis as an efficient and general route for
ring construction of aromatic and dihydroaromatic compounds.
The proposed mechanism of this reaction involves the formation
of a six-membered allene (1,2,4-cyclohexatriene) and its deriva-
tives.17 An inspection of the pertinent literature on the reactivity
of 1,3-enynes revealed that the 1,3-diploar addition of diazoal-
kane, chlorobenzylidene-N-phenylhydrazine, R,N-diphenylni-
trone, benzonitrile N-oxide 1,3-diphenylnitriloamine with various
substituted enynes takes place at the double bond, not at the
triple bond, leading to pyrazoline and isoxazolidine derivatives.18
As 7a-d are good dipolorophiles, we effected the cycloaddition
with nitrones (8) viz., R-(4-chlorophenyl)-N-phenyl nitrone (8a)
and R-(4-methoxyphenyl)-N-phenyl nitrone (8b) expecting 1,3-
dipolar addition to take place leading to isoxazoline derivatives.
However, the reaction proceeds smoothly, giving two isomeric
products (9 and 10) in good yield in an almost equal ratio
(Scheme 3). The Rf values of 9 and 10 are closer, but they have
been successfully separated by column chromatography, and
the structures of the products are deduced by two-dimensional
NMR connectivity analysis to be isomeric pyrrole derivatives.
(17) (a) Dunetz, J. R.; Danheiser, R. L. J. Am. Chem. Soc. 2005, 127,
5766. (b) Hayes, M. E.; Shinokubo, H.; Danheiser, R. L. Org. Lett. 2005,
7, 3917. (c) Danheiser, R. L.; Gould, A. E.; Pradilla, R. F.; Helgason, A.
L. J. Org. Chem. 1994, 59, 5514. (d) Gevorgyan, V.; Takeda, A.; Yamamoto,
Y. J. Am. Chem. Soc. 1997, 119, 11313. (e) Gevorgyan, V.; Takeda, A.;
Homma, M.; Sadayori, N.; Radhakrishnan, U.; Yamamoto, Y. J. Am. Chem.
Soc. 1999, 121, 6391. (f) Prassarella, D.; Giardini, A.; Martinelli, M.; Silvani,
A. J. Chem. Soc., Perkin Trans. 1 2001, 2, 127.
(18) (a) Yoshimatsu, M.; Kawahigashi, M.; Honda, E.; Kataoka, T. J.
Chem. Soc., Perkin Trans. 1 1997, 5, 695. (b) Kuznetsov, M. A.; Kuchuk,
I. D.; Gindin, V. A. Zh. Obshch. Khim. 1993, 63, 1627. (c) Himbert, G. J.
Chem. Res., Synop. 1979, 3, 88. (d) Chistokletov, V. N.; Petrov, A. A. Zh.
Obshch. Khim. 1962, 32, 238. (e) Chistokletov, V. N.; Vagina, L. K.; Petrov,
A. A. Zh. Org. Khim. 1965, 1, 369. (f) Chistokletov, V. N.; petrov, A. A.
Zh. Obshch. Khim. 1963, 33, 3558. (g) Kolokoltseva, I. G.; Chistokletov,
V. N.; Stadnichuk, M. D.; Petrov, A. A. Zh. Obshch. Khim. 1968, 38, 1820.
(16) (a) Saravanan, S.; Muthusubramanian, S. Phosphorus Sulfur Silicon
Relat. Elem. 2004, 179, 2411. (b) Saravanan, S.; Nithya, A.; Muthusubra-
manian, S. J. Heterocycl. Chem. 2006, 43, 149. (c) Saravanan, S.;
Athimoolam, S.; Muthusubramanian, S. ARKIVOC 2007, 1, 22.
J. Org. Chem, Vol. 73, No. 6, 2008 2325

Saravanan et al.
SCHEME 4. Mechanism for the Formation of 9 and 10
SCHEME 3. Reaction of Enyne 7 with Dipole 8
SCHEME 5. Reaction of Selenadiazole 6 with Dipole 8
TABLE 2. Reaction of 1,3-Enyne 7 with Nitrone 8
entry
product
yield (%)
product
yield (%)
1
2
3
4
5
6
7
8
9a
9b
9c
9d
9e
9f
43
34
40
36
35
33
46
28
10a
10b
10c
10d
10e
10f
38
27
29
28
29
27
36
24
9g
9h
10g
10h
The fact that the expected cycloadducts were not formed has
been inferred by the presence of carbonyl carbon signals beyond
190.0 ppm shown in the 13C NMR spectra of both the products.
1
Compounds 9 and 10 have a close H NMR spectral pattern
and this is due to the anisotropy of the ester carbonyl in the
former, as supported by the crystal structure.
with small chemical shift differences due to the ortho hydrogens
of benzoyl ring, methine, methylene, and methyl hydrogens. In
the 13C NMR spectra, the remarkable difference is that the
methine carbon appears at 77.2 ppm in 9a but at 75.5 ppm in
10a. Obviously, these two compounds are stereoisomers arising
due to a change in the orientation of the cyano and the
carbethoxy groups with respect to the hydrogen and aryl group
in the nearby carbon. However, the spectral data are not very
helpful in distinguishing 9 and 10, preventing the correct
stereochemical assignment for 9 and 10.
The formation of the product can be explained by considering
the dipolar addition of the nitrone moiety with enyne, not in a
[4 + 2] fashion but in a [3 + 4] fashion. Obviously, this reaction
may not be concerted because a [3 + 4] reaction is not thermally
allowed and hence stepwise. A very unstable seven membered
allene type intermediate can be proposed which subsequently
undergoes rearrangement as shown in the following scheme
(Scheme 4).
This type of strained cyclic allene intermediate has already
been proposed.19 An attempted cycloaddition of 6 instead of 7
with R-N-diarylnitrone has also been made. Here again, it is
found that compounds 9 and 10 are formed in the same ratio.
Elimination of nitrogen and selenium would have occurred in
6 prior to the cycloaddition and hence the reaction is very similar
to that of 7 with nitrone (Scheme 5).
The reaction has been carried out with differently substituted
enynes, and the results are summarized in Table 2. Fortunately,
it was possible to grow a single crystal of 9g to assign the
structure unambiguously. It is clear from the crystal structure
that compounds 9 are those diasteroisomers in which the aryl
group at the C-2 position of the pyrrole and the cyano group at
C-3 position are trans to each other, and hence, these two groups
must have a cis relationship in 10. From the crystal structure
(ORTEP 2, see the Supporting Information for more details), it
is clear that the methylene and methyl hydrogens of carbethoxy
group at C-3 of 9 are in the shielding region of the aryl ring at
the C-2 position, which is very much evident from the 1H NMR
data. For 9g, the methyl and methylene hydrogens appear at
0.96 and 3.89 ppm, respectively, while for 10g, these hydrogens
appear at 1.24 and 4.32 ppm, respectively. The ortho hydrogens
of the aroyl ring at C-5 are deshielded in 9g compared to 10g,
Conclusion
In summary, a novel method for the synthesis of 1,3-enynes
is described starting from readily available precursors. Reaction
(19) (a) Butz, L. W.; Geddis, A. M.; Butz, E. W. J.; Davis, R. E. J. Org.
Chem. 1940, 5, 379. (b) Dykstra, H. B. J. Am. Chem. Soc. 1934, 56, 1625.
(c) Roser, J.; Eberbach, W. Tetrahedron Lett. 1984, 25, 2455. (d) Hoffmann,
H. M. R.; Krumwiede, D.; Mucha, B.; Oehlerking, H. H.; Prahst, G. W.
Tetrahedron 1993, 49, 8999.
2326 J. Org. Chem., Vol. 73, No. 6, 2008

Synthesis of Highly Substituted 2,3-Dihydro-1H-pyrrole DeriVatiVes
According to the typical procedure, semicarbazone 4c was treated
with selenium dioxide in acetic acid to give 34% of 6c and 22% of
7c.
of these 1,3-enynes with diaryl nitrones has been shown to give
a diastereomeric mixture of highly substituted 2,3-dihydro-1H-
pyrrole derivatives via a tandem regioselective addition with
subsequent rearrangement.
Ethyl 3-(4-chlorophenyl)-3-[4-(4-chlorophenyl)-1,2,3-selena-
diazol-5-yl]-2-cyano-2-propenoate (6c): mp ) 138 °C; IR (cm-1
)
2215, 1739, 1587, 1253; 1H NMR (300 MHz, CDCl3) δ 1.15 (t, J
) 6.9 Hz, 3H), 4.09 (q, J ) 6.9 Hz, 2H), 7.35-7.45 (m, 6H), 7.62
(d, J ) 8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 13.7, 63.1,
107.7, 115.2, 129.0, 129.3, 129.4, 130.0, 130.5, 133.8, 135.7, 138.9,
153.4, 158.0, 158.2, 160.6. Anal. Calcd for C20H13Cl2N3O2Se: C,
50.34; H, 2.75; N, 8.81. Found: C, 50.33; H, 2.75; N, 8.82.
Experimental Section
Typical Procedure for the Reaction of Semicarbazone (4) with
Selenium Dioxide. A solution of semicarbazone 4 (0.005 mol) and
powdered selenium dioxide (0.05 mol) in THF/acetic acid (15 mL)
was gently heated on a water bath for 2 h. The selenium deposited
on cooling was removed by filtration, and the filtrate was poured
into crushed ice, extracted with chloroform, and purified by column
chromatography using silica gel (60-120 mesh) with 97:3 petro-
leum ether/ethyl acetate as eluent to give an acetylene derivative
(7) and the selenadiazoles (5 and 6), which were recrystallized from
ethyl alcohol.
Ethyl 3,5-bis(4-chlorophenyl)-2-cyano-2-penten-4-ynoate (7c):
1
mp ) 107 °C; IR (cm-1) 2192, 1724, 1535, 1243; H NMR (300
MHz, CDCl3) δ 1.41 (t, J ) 7.2 Hz, 3H), 4.40 (q, J ) 7.2 Hz,
2H), 7.37 (d, J ) 9.0 Hz, 2H), 7.47 (d, J ) 8.7 Hz, 2H), 7.53 (d,
J ) 8.7 Hz, 2H), 7.74 (d, J ) 9.0 Hz, 2H); 13C NMR (75 MHz,
CDCl3) δ 14.1, 62.5, 89.1, 109.0, 112.5, 114.6, 119.8, 129.1, 129.2,
129.8, 133.8, 134.2, 137.2, 137.8, 147.7, 161.0. Anal. Calcd for
C20H13Cl2NO2: C, 64.88; H, 3.54; N, 3.78. Found: C, 64.91; H,
3.54; N, 3.79.
According to the typical procedure, semicarbazone 4a was treated
with selenium dioxide in THF to get 38% of 5a, 14% of 6a, and
13% of 7a.
According to the typical procedure, semicarbazone 4d was treated
with selenium dioxide in acetic acid to give 32% of 6d and 23%
of 7d.
Ethyl 2-cyano-3-phenyl-3-(4-phenyl-1,2,3-selenadiazol-5-yl)-
propanoate (5a): viscous liquid; IR (cm-1) 2250, 1749, 1604, 1025;
1H NMR (300 MHz, CDCl3) δ 1.02 (t, J ) 7.2 Hz, 3H), 1.07 (t, J
) 7.2 Hz, 3H), 3.95-4.10 (m, 5H), 4.13 (d, J ) 6.6 Hz, 1H), 5.27
(d, J ) 7.5 Hz, 1H), 5.35 (d, J ) 6.3 Hz, 1H), 7.26 (d, J ) 7.5 Hz,
2H), 7.33-7.38 (m, 8H), 7.50-7.56 (m, 10H); 13C NMR (75 MHz,
CDCl3) δ 13.5, 13.6, 46.0, 46.1, 46.7, 47.5, 63.2, 63.3, 114.4, 114.7,
127.6, 127.8, 128.6, 128.8, 128.9, 129.0, 129.2, 129.3, 129.4,*
129.6, 129.7, 131.0, 131.2, 136.8, 137.1, 156.1, 158.6, 160.2, 161.8,
163.3, 163.5. *One carbon has merged with another.
Ethyl 3-[4-(4-chlorophenyl)-1,2,3-selenadiazol-5-yl]-2-cyano-
3-(4-methoxyphenyl)-2-propenoate (6d): viscous liquid; IR (cm-1
)
1
2188, 1729, 1577, 1336; H NMR (300 MHz, CDCl3) δ (major
isomer alone) 1.12 (t, J ) 7.2 Hz, 3H), 3.83 (s, 3H), 4.05 (q, J )
7.2 Hz, 2H), 6.85 (d, J ) 9.0 Hz, 2H), 7.38 (d, J ) 8.7 Hz, 2H),
7.48 (d, J ) 9 Hz, 2H), 7.70 (d, J ) 8.7 Hz, 2H); 13C NMR (75
MHz, CDCl3) δ 13.7, 55.5, 62.6, 104.3, 114.4, 116.2, 127.7, 128.5,
129.3, 131.0, 133.6, 135.4, 154.6, 157.9, 158.7, 161.2, 163.2.
Ethyl 2-cyano-3-phenyl-3-(4-phenyl-1,2,3-selenadiazol-5-yl)-
2-propenoate (6a): mp ) 125 °C; IR (cm-1) 2219, 1727, 1255,
1122; 1H NMR (300 MHz, CDCl3) δ (major isomer alone) 1.11 (t,
J ) 7.2 Hz, 3H), 4.05 (q, J ) 7.2 Hz, 2H), 7.38-7.49 (m, 8H),
7.69 (dd, J ) 9.0, 3.3 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ
13.7, 62.9, 107.3, 115.6, 128.8, 128.9, 129.0, 129.2, 129.5, 130.7,
132.4, 136.1, 153.8, 159.4, 159.8, 160.9. Anal. Calcd for C20H15N3O2-
Se: C, 58.83; H, 3.70; N, 10.29. Found: C, 58.85; H, 3.71; N,
10.31.
Ethyl 5-(4-chlorophenyl)-2-cyano-3-(4-methoxyphenyl)-2-
penten-4-ynoate (7d): viscous liquid; IR (cm-1) 2188, 1735, 1507,
1336; 1H NMR (300 MHz, CDCl3) δ (major isomer alone) 1.42 (t,
J ) 6.9 Hz, 3H), 3.88 (s, 3H), 4.40 (q, J ) 6.9 Hz, 2H), 7.00 (d,
J ) 8.7 Hz, 2H), 7.38 (d, J ) 8.7 Hz, 2H), 7.54 (d, J ) 8.7 Hz,
2H), 7.85 (d, J ) 8.7 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 14.2,
55.5, 62.2, 89.4, 106.4, 111.3, 114.1, 116.9, 120.1, 128.0, 129.1,
131.1, 133.7, 136.9, 148.5, 162.4.
Typical Procedure for the Reaction of Ethyl 2-Cyano-3,5-
diaryl-2-penten-4-ynoate (7) with R-Aryl-N-phenylnitrone (8).
A solution of ethyl 2-cyano-3,5-diaryl-2-penten-4-ynoate 7 (0.0005
mol) and R-(4-chlorophenyl)-N-phenylnitrone 8a/(4-methoxyphe-
nyl)-N-phenylnitrone 8b (0.0006 mol) in toluene (20 mL) was
refluxed for 2-3 h. After completion of the reaction, the solvent
was evaporated under reduced pressure and the products 9 and 10
were separated by column chromatography using silica gel (60-
120 mesh) with 97:3 petroleum ether/ethyl acetate as eluent.
Ethyl 5-benzoyl-3-cyano-2-(4-chlorophenyl)-1,4-diphenyl-2,3-
dihydro-1H-pyrrole-3-carboxylate (9a) was obtained by following
the typical procedure with 7a and 8a. (yield ) 43%; viscous
liquid): IR (cm-1) 2225, 1743, 1671; 1H NMR (300 MHz, CDCl3)
δ 0.94 (t, J ) 7.2 Hz, 3H), 3.85 (q, J ) 7.2 Hz, 2H), 5.74 (s, 1H),
6.87 (d, J ) 7.8 Hz, 2H), 7.00-7.70 (m, 15H), 8.15 (d, J ) 7.8
Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 13.4, 61.3, 63.2, 77.2,
114.4, 117.9, 124.2, 125.9, 127.2, 128.5, 128.6, 128.8, 129.1, 129.5,
129.6, 129.7, 131.0, 132.0, 134.2, 135.2, 135.4, 141.7, 148.0, 164.4,
190.1.
Ethyl 5-benzoyl-3-cyano-2-(4-chlorophenyl)-1,4-diphenyl-2,3-
dihydro-1H-pyrrole-3-carboxylate (10a) was obtained by fol-
lowing the typical procedure with 7a and 8a (yield ) 38%; viscous
liquid): IR (cm-1) 2242, 1743, 1668; 1H NMR (300 MHz, CDCl3)
δ 1.21 (t, J ) 7.2 Hz, 3H), 4.33 (q, J ) 7.2 Hz, 2H), 5.70 (s, 1H),
6.83 (d, J ) 7.2 Hz, 2H), 7.00-7.70 (m, 15H), 7.98 (d, J ) 7.8
Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 13.9, 62.7, 64.0, 75.5,
114.6, 115.7, 123.0, 125.9, 128.0, 128.4, 128.5, 128.7, 129.2, 129.3,
129.5, 129.6, 130.8, 133.1, 134.2, 135.4, 135.7, 141.7, 146.8, 166.9,
190.1.
Ethyl 2-cyano-3,5-diphenyl-2-penten-4-ynoate (7a): mp )
1
121 °C; IR (cm-1) 2185, 1724, 1246, 1130; H NMR (300 MHz,
CDCl3) δ (major isomer alone) 1.40 (t, J ) 7.2 Hz, 3H), 4.41 (q,
J ) 7.2 Hz, 2H), 7.39-7.52 (m, 6H), 7.60 (dd, J ) 8.1, 1.8 Hz,
2H), 7.81 (dd, J ) 7.8, 1.8 Hz, 2H); 13C NMR (75 MHz, CDCl3)
δ 14.2, 16.3, 88.7, 108.6, 113.8, 116.3, 121.6, 128.6, 128.7, 128.8,
130.7, 131.4, 132.6, 136.1, 149.5, 161.4. Anal. Calcd for C20H15-
NO2: C, 79.72; H, 5.02; N, 4.65. Found: C, 79.75; H, 5.03; N,
4.65.
According to the typical procedure, semicarbazone 4b was treated
with selenium dioxide in acetic acid to give 31% of 6b and 25%
of 7b.
Ethyl 3-(4-chlorophenyl)-2-cyano-3-(4-phenyl-1,2,3-selenadia-
zol-5-yl)-2-propenoate (6b): mp ) 127 °C; IR (cm-1) 2217, 1733,
1
1629, 1251; H NMR (300 MHz, CDCl3) δ 1.12 (t, J ) 7.2 Hz,
3H), 4.07 (q, J ) 7.2 Hz, 2H), 7.35-7.45 (m, 7H), 7.66 (dd, J )
7.8, 1.8 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 13.7, 63.0, 107.7,
115.4, 128.8, 129.0, 129.3, 129.6, 130.4, 130.6,134.2, 138.7, 153.1,
158.5, 159.5, 160.7. Anal. Calcd for C20H14ClN3O2Se: C, 54.25;
H, 3.19; N, 9.49. Found: C, 54.27; H, 3.20; N, 9.49.
Ethyl 3-(4-chlorophenyl)-2-cyano-5-phenyl-2-penten-4-ynoate
1
(7b): mp ) 116 °C; IR (cm-1) 2192, 1727, 1535, 1241; H NMR
(300 MHz, CDCl3) δ 1.41 (t, J ) 7.2 Hz, 3H), 4.40 (q, J ) 7.2
Hz, 2H), 7.35-7.50 (m, 5H), 7.60 (d, J ) 8.4 Hz, 2H), 7.75 (d, J
) 8.7 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 14.3, 62.9,88.8,
109.1, 114.5, 116.5, 121.8, 129.0, 129.5, 130.6, 131.3, 133.0, 134.8,
138.1, 148.4, 161.5. Anal. Calcd for C20H14ClNO2: C, 71.54; H,
4.20; N, 4.17. Found: C, 71.55; H, 4.24; N, 4.19.
J. Org. Chem, Vol. 73, No. 6, 2008 2327

Saravanan et al.
Ethyl 5-benzoyl-3-cyano-2,4-bis(4-chlorophenyl)-1-phenyl-2,3-
dihydro-1H-pyrrole-3-carboxylate (9b) was obtained by following
the typical procedure with 7b and 8a (yield ) 34%; mp )
139 °C): IR (cm-1) 2244, 1741, 1673, 1592, 1230; 1H NMR (300
MHz, CDCl3) δ 0.95 (t, J ) 7.2 Hz, 3H), 3.86 (m, 2H), 5.48 (s,
1H) 6.86 (d, J ) 7.2 Hz, 2H), 7.00-7.86 (m, 14H), 8.15 (d, J )
7.5 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 13.5, 61.1, 63.4, 77.0,
112.9, 117.7, 124.4, 126.2, 128.5, 128.7, 128.8, 128.9, 129.2,
129.7,* 131.7, 133.4, 134.5,* 135.4, 135.5, 141.5, 148.8, 164.7,
190.7. Anal. Calcd for C33H24Cl2N2O3: C, 69.85; H, 4.26; N, 4.94.
Found: C, 69.84; H, 4.28; N, 4.96.
Hz, 2H), 7.93 (d, J ) 8.7 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ
13.9, 55.1, 62.8, 63.9, 75.5, 113.9, 115.5, 115.6, 122.8, 122.9, 125.3,
129.1, 129.2, 129.3, 129.4, 129.6, 130.8, 131.2, 134.1, 135.4, 140.6,
141.8, 145.5, 159.4, 166.9, 188.9.
Ethyl 5-benzoyl-3-cyano-2-(4-methoxyphenyl)-1,4-diphenyl-
2,3-dihydro-1H-pyrrole-3-carboxylate (9e) was obtained by fol-
lowing the typical procedure with 7a and 8b (yield ) 35%; mp )
1
99 °C): IR (cm-1) 2223, 1745, 1671, 1606, 1025; H NMR (300
MHz, CDCl3) δ 0.95 (t, J ) 7.2 Hz, 3H), 3.80 (s, 3H), 3.84 (m,
2H), 5.71 (s, 1H), 6.85-.55 (m, 17H), 8.17 (d, J ) 8.4 Hz, 2H);
13C NMR (75 MHz, CDCl3) δ 13.4, 55.2, 61.5, 63.0, 77.8, 113.9,
118.2, 124.2, 125.2, 125.6, 127.2, 127.4, 128.2, 128.4, 128.6, 129.0,
129.6, 129.7, 131.4, 134.1, 135.8, 142.0, 148.1, 160.2, 165.1, 191.0.
Anal. Calcd for C34H28N2O4: C, 77.25; H, 5.34; N, 5.30. Found:
C, 77.28; H, 5.37; N, 5.33.
Ethyl 5-benzoyl-3-cyano-2,4-bis(4-chlorophenyl)-1-phenyl-2,3-
dihydro-1H-pyrrole-3-carboxylate (10b) was obtained by fol-
lowing the typical procedure with 7b and 8a (yield ) 27%; viscous
1
liquid): IR (cm-1) 2238, 1743, 1670, 1598, 1213; H NMR (300
MHz, CDCl3) δ 1.24 (t, J ) 7.2 Hz, 3H), 4.34 (m, 2H), 5.73 (s,
1H) 6.84 (d, J ) 7.5 Hz, 2H), 6.98 (d, J ) 7.5 Hz, 2H), 7.09 (t, J
) 7.8 Hz, 2H), 7.14 (d, J ) 7.4 Hz, 2H), 7.22 (d, J ) 8.7 Hz, 2H),
7.35-7.55 (m, 6H), 7.99 (d, J ) 7.5 Hz, 2H); 13C NMR (75 MHz,
CDCl3) δ 13.9, 62.4, 64.0, 76.5, 112.8, 115.6, 123.2, 125.6, 128.6,
128.8, 129.2,* 129.3, 129.4,* 129.5, 132.7, 133.7, 134.5, 135.4,
135.5, 141.3, 147.4, 166.7, 189.9.
Ethyl 5-benzoyl-3-cyano-2-(4-methoxyphenyl)-1,4-diphenyl-
2,3-dihydro-1H-pyrrole-3-carboxylate (10e) was obtained by
following the typical procedure with 7a and 8b (yield ) 29%;
viscous liquid): IR (cm-1) 2244, 1741, 1670, 1610, 1031; 1H NMR
(300 MHz, CDCl3) δ 1.22 (t, J ) 7.2 Hz, 3H), 3.80 (s, 3H), 4.30
(m, 2H), 5.67 (s, 1H), 6.85-7.55 (m, 17H), 8.00 (d, J ) 8.7 Hz,
2H); 13C NMR (75 MHz, CDCl3) δ 13.8, 55.1, 62.9, 63.7, 75.9,
114.2, 115.9, 122.0, 124.9, 127.2, 127.7, 127.9, 128.2, 128.4, 128.6,
129.0, 129.3, 129.5, 131.1, 134.1, 135.7, 141.8, 146.8, 160.2, 167.2,
190.3.
Ethyl 5-(4-chlorobenzoyl)-3-cyano-2,4-bis(4-chlorophenyl)-1-
phenyl-2,3-dihydro-1H-pyrrole-3-carboxylate (9c) was obtained
by following the typical procedure with 7c and 8a (yield ) 40%;
mp ) 147 °C): IR (cm-1) 2244, 1743, 1671, 1587, 1093; 1H NMR
(300 MHz, CDCl3) δ 0.95 (t, J ) 7.2 Hz, 3H), 3.87 (m, 2H), 5.69
(s, 1H), 6.87 (d, J ) 7.2 Hz, 2H), 7.02-7.20 (m, 7H), 7.36 (d, J
) 8.4 Hz, 2H), 7.42 (d, J ) 8.7 Hz, 2H), 7.50 (d, J ) 8.7 Hz, 2H),
8.11 (d, J ) 8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 13.4,
61.1, 63.6, 77.6, 113.3, 117.5, 124.7, 126.5, 128.5, 128.9, 129.0,
129.3, 129.4, 129.6, 129.7, 131.0, 131.5, 133.7, 133.9, 135.5, 141.1,
141.4, 148.5, 164.7, 189.5. Anal. Calcd for C33H23Cl3N2O3: C,
65.85; H, 3.85; N, 4.65. Found: C, 65.86; H, 3.87; N, 4.66.
Ethyl 5-(4-chlorobenzoyl)-3-cyano-2,4-bis(4-chlorophenyl)-1-
phenyl-2,3-dihydro-1H-pyrrole-3-carboxylate (10c) was obtained
by following the typical procedure with 7c and 8a (yield ) 29%;
viscous liquid): IR (cm-1) 2227, 1745, 1670, 1589, 1093; 1H NMR
(300 MHz, CDCl3) δ 1.23 (t, J ) 6.9 Hz, 3H), 4.32 (m, 2H), 5.68
(s, 1H), 6.82 (d, J ) 7.2 Hz, 2H), 7.00 (t, J ) 7.2 Hz, 1H), 7.09
(t, J ) 7.8 Hz, 2H), 7.14 (d, J ) 8.4 Hz, 2H), 7.20 (d, J ) 8.4 Hz,
2H), 7.36 (d, J ) 6.9 Hz, 2H), 7.40 (d, J ) 8.7 Hz, 2H), 7.50 (d,
J ) 8.4 Hz, 2H), 7.92 (d, J ) 8.7 Hz, 2H); 13C NMR (75 MHz,
CDCl3) δ 13.9, 22.3, 64.1, 75.6, 113.2, 115.5, 123.3, 125.8, 128.7,
129.2, 129.3,* 129.4, 130.7,* 130.8, 132.5, 133.8, 134.0, 135.6,
141.1, 142.2, 147.0, 166.6, 188.7.
Ethyl 5-benzoyl-3-cyano-4-(4-chlorophenyl)-2-(4-methoxyphe-
nyl)-1-phenyl-2,3-dihydro-1H-pyrrole-3-carboxylate (9f) was
obtained by following the typical procedure with 7b and 8b (yield
1
) 33%; mp ) 157 °C): IR (cm-1) 2244, 1739, 1668, 1255; H
NMR (300 MHz, CDCl3) δ 0.96 (t, J ) 7.2 Hz, 3H), 3.79 (s, 3H),
3.86 (m, 2H), 5.70 (s, 1H), 6.85-7.60 (m, 16H), 8.16 (d, J ) 8.4
Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 13.5, 55.2, 61.3, 63.2, 77.9,
112.8, 113.9, 118.0, 124.5, 124.9, 125.9, 128.5, 128.7, 128.8, 129.1,
129.6, 129.7, 130.0, 133.2, 134.4, 135.6, 141.7, 148.9, 160.3, 165.0,
190.9. Anal. Calcd for C34H27ClN2O4: C, 72.53; H, 4.83; N, 4.98.
Found: C, 72.53; H, 4.84; N, 4.99.
Ethyl 5-benzoyl-3-cyano-4-(4-chlorophenyl)-2-(4-methoxyphe-
nyl)-1-phenyl-2,3-dihydro-1H-pyrrole-3-carboxylate (10f) was
obtained by following the typical procedure with 7b and 8b (yield
1
) 27%; mp ) 107 °C): IR (cm-1) 2337, 1741, 1668, 1247; H
NMR (300 MHz, CDCl3) δ 1.24 (t, J ) 7.2 Hz, 3H), 3.80 (s, 3H),
4.33 (m, 2H), 5.68 (s, 1H), 6.82-7.60 (m, 16H), 8.00 (d, J ) 8.4
Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 13.9, 55.2, 62.7, 63.8, 75.9,
112.7, 114.3, 115.9, 123.2, 125.3, 126.0, 128.5, 128.8, 129.0, 129.1
129.3, 129.4, 129.7, 133.4, 134.4, 135.6, 141.5, 147.5, 160.3, 166.9,
190.2. Anal. Calcd for C34H27ClN2O4: C, 72.53; H, 4.83; N, 4.98.
Found: C, 72.55; H, 4.83; N, 4.99.
Ethyl 5-(4-chlorobenzoyl)-3-cyano-2-(4-chlorophenyl)-4-(4-
methoxyphenyl)-1-phenyl-2,3-dihydro-1H-pyrrole-3-carboxy-
late (9d) was obtained by following the typical procedure with 7d
and 8a (yield ) 36%; mp ) 116 °C): IR (cm-1) 2246, 1741, 1671,
Ethyl 5-(4-chlorobenzoyl)-3-cyano-4-(4-chlorophenyl)-2-(4-
methoxyphenyl)-1-phenyl-2,3-dihydro-1H-pyrrole-3-carboxy-
late (9g) was obtained by following the typical procedure with 7c
and 8b (yield ) 46%; mp ) 153 °C): IR (cm-1) 2360, 1668, 1610,
1
1590, 1249; H NMR (300 MHz, CDCl3) δ 0.95 (t, J ) 7.2 Hz,
3H), 3.79 (s, 3H), 3.85 (disturbed multiplet, 2H), 5.60 (s, 1H), 6.73
(d, J ) 8.7 Hz, 2H), 6.89 (d, J ) 7.2 Hz, 2H), 6.99 (t, J ) 7.2 Hz,
1H), 7.08 (t, J ) 7.2 Hz, 2H), 7.19 (d, J ) 9.0 Hz, 2H), 7.38 (d,
J ) 9.0 Hz, 2H), 7.48 (d, J ) 8.4 Hz, 2H), 8.12 (d, J ) 7.2 Hz,
2H); 13C NMR (75 MHz, CDCl3) δ 13.5, 55.1, 61.8, 63.1, 78.2,
114.1, 115.4, 117.8, 123.1, 124.6, 126.2, 128.8, 128.9, 129.1, 129.3,
129.7, 131.0, 131.7, 134.2, 135.3, 140.7, 142.2, 147.1, 159.2, 164.9,
190.0. Anal. Calcd for C34H26Cl2N2O4: C, 68.35; H, 4.39; N, 4.69.
Found: C, 68.36; H, 4.41; N, 4.68.
1
1376; H NMR (300 MHz, CDCl3) δ 0.96 (t, J ) 7.2 Hz, 3H),
3.80 (s, 3H), 3.89 (m, 2H), 5.66 (s, 1H), 6.85-7.50 (m, 15H), 8.12
(d, J ) 8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 13.5, 55.2,
61.3, 63.3, 78.1, 113.2, 113.9, 117.8, 124.6, 124.7, 126.6, 128.4,
128.8, 129.1, 129.2, 129.6, 129.7, 131.0, 133.4, 133.9, 140.9, 141.7,
148.6, 160.3, 164.9, 189.7. Anal. Calcd for C34H26Cl2N2O4: C,
68.35; H, 4.39; N, 4.69. Found: C, 68.36; H, 4.41; N, 4.70.
Ethyl 5-(4-chlorobenzoyl)-3-cyano-4-(4-chlorophenyl)-2-(4-
methoxyphenyl)-1-phenyl-2,3-dihydro-1H-pyrrole-3-carboxy-
late (10g) was obtained by following the typical procedure with
7c and 8b (yield ) 36%; viscous liquid): IR (cm-1) 2246, 1741,
Ethyl 5-(4-chlorobenzoyl)-3-cyano-2-(4-chlorophenyl)-4-(4-
methoxyphenyl)-1-phenyl-2,3-dihydro-1H-pyrrole-3-carboxy-
late (10d) was obtained by following the typical procedure with
7d and 8a (yield ) 28%; viscous liquid): IR (cm-1) 2246, 1741,
1671, 1590, 1249; 1H NMR (300 MHz, CDCl3) δ 1.27 (t, J ) 7.2
Hz, 3H), 3.72 (s, 3H), 4.32 (disturbed multiplet, 2H), 5.62 (s, 1H),
6.71 (d, J ) 8.7 Hz, 2H), 6.82 (d, J ) 7.2 Hz, 2H), 6.98 (d, J )
7.5 Hz, 2H), 7.09 (d, J ) 7.5 Hz, 2H), 7.18 (d, J ) 9.0 Hz, 2H),
7.34 (d, J ) 8.7 Hz, 2H), 7.41 (d, J ) 8.7 Hz, 2H) 7.54 (d, J ) 8.7
1
1670, 1211; H NMR (300 MHz, CDCl3) δ 1.24 (t, J ) 7.2 Hz,
3H), 3.80 (s, 3H), 4.32 (m, 2H), 5.65 (s, 1H), 6.80-7.55 (m, 15H),
7.95 (d, J ) 8.7 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 13.9,
55.1, 62.7, 63.9, 76.1, 113.1, 114.3, 115.7, 123.3, 125.5, 125.9,
128.6, 129.1, 129.2,* 129.3, 129.5, 130.7, 133.7, 133.9, 140.9,
141.5, 147.1, 160.4, 166.9, 188.9.
2328 J. Org. Chem., Vol. 73, No. 6, 2008

Synthesis of Highly Substituted 2,3-Dihydro-1H-pyrrole DeriVatiVes
Ethyl 5-(4-chlorobenzoyl)-3-cyano-2,4-bis-(4-methoxyphenyl)-
1-phenyl-2,3-dihydro-1H-pyrrole-3-carboxylate (9h) was ob-
tained by following the typical procedure with 7d and 8b (yield )
28%; mp ) 158 °C): IR (cm-1) 2238, 1737, 1666, 1589, 1255; 1H
NMR (300 MHz, CDCl3) δ 0.95(t, J ) 7.2 Hz, 3H), 3.72 (s, 3H),
3.80 (s, 3H), 3.85 (m, 2H), 5.60 (s, 1H), 6.70-7.50 (m, 15H), 8.12
(d, J ) 8.7 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 13.5, 55.1,
55.3, 61.8, 63.1, 78.2, 113.9, 114.0, 115.3, 118.1, 123.4, 124.5,
125.1, 125.9, 128.9, 129.0, 129.1, 129.6, 131.6, 134.3, 140.5, 142.5,
147.2, 159.1, 160.2, 165.1, 189.9. Anal. Calcd for C35H29ClN2O5:
C, 70.88; H, 4.93; N, 4.72. Found: C, 70.90; H, 4.95; N, 4.75.
Ethyl 5-(4-chlorobenzoyl)-3-cyano-2,4-bis-(4-methoxyphenyl)-
1-phenyl-2,3-dihydro-1H-pyrrole-3-carboxylate (10h) was ob-
tained by following the typical procedure with 7d and 8b (yield )
24%; viscous liquid): IR (cm-1) 2244, 1741, 1668, 1178; 1H NMR
(300 MHz, CDCl3) δ 1.26 (t, J ) 7.2 Hz, 3H), 3.71 (s, 3H), 3.80
(s, 3H), 4.33 (m, 2H), 5.58 (s, 1H), 6.70-7.55 (m, 15H), 7.95 (d,
J ) 8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 13.9, 55.0, 55.1,
63.1, 63.7, 76.0, 113.8, 114.0, 115.5, 115.9, 122.9, 123.1, 124.9,
126.5, 128.9, 129.0, 129.5, 129.6, 130.8, 134.2, 140.5, 142.2, 145.5,
159.3, 160.3, 167.1, 189.1.
phenylnitrone (8a). A solution of ethyl 2-cyano-3-phenyl-3-(4-
phenyl-1,2,3-selenadiazol-5-yl)-2-propenoate 6a (0.06 g, 0.00015
mol) and R-(4-chlorophenyl)-N-phenylnitrone 8a (0.046 g, 0.0002
mol) in toluene (20 mL) was refluxed for 2-3 h. After completion
of the reaction, the solvent was evaporated under reduced pressure,
and the products were separated by column chromatography using
silica gel (60-120 mesh) with 97:3 petroleum ether: ethyl acetate
as eluent. Yield of 9a: 42%. Yield of 10a: 35%.
Acknowledgment. We thank DST, New Delhi, for assistance
under the IRHPA program for the NMR facility. We thank the
School of Physics, Madurai Kamaraj University, and Department
of Chemistry, Indian Institute of Technology, Chennai, for the
single-crystal X-ray analyses. Financial support from CSIR, New
Delhi, to S.S. is gratefully acknowledged.
Supporting Information Available: General experimental
1
procedures, H and 13C NMR spectra for synthesized compounds,
and crystallographic information files (CIF) for compounds 6b and
9g. This material is available free of charge via the Internet at
http://pubs.acs.org.
Reaction of Ethyl 2-Cyano-3-phenyl-3-(4-phenyl-1,2,3-sel-
enadiazol-5-yl)-2-propenoate (6a) with R-(4-Chlorophenyl)-N-
JO702610J
J. Org. Chem, Vol. 73, No. 6, 2008 2329