A unique approach to catalyst-free, one-pot synthesis of spirooxindole-pyrazolines

Article abstract of DOI:10.1055/s-0031-1290322

A pseudo-five-component synthesis of spirooxindole-pyrazolines via a one-pot and catalyst-free reaction under mild conditions is reported. The 1,1-bishydrazino-2-nitroethylene intermediate generated in situ from the addition of aqueous hydrazine to 1,1-bi

Full text of DOI:10.1055/s-0031-1290322

428
LETTER
A Unique Approach to Catalyst-Free, One-Pot Synthesis of
Spirooxindole-Pyrazolines
S
ynthesis of Spiro
b
oxindole-Pyr
d
azolines olali Alizadeh,* Nasrin Zohreh
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran
Fax +98(21)88006544; E-mail: abdol_alizad@yahoo.com; E-mail: aalizadeh@modares.ac.ir
Received 21 October 2011
there are only three5–7 procedures for the synthesis of
spirooxindole-pyrazolines, and all of them require at least
two steps starting from the condensation of isatine and a
reactive methylene nucleophile (Scheme 1).
Abstract: A pseudo-five-component synthesis of spirooxindole-
pyrazolines via a one-pot and catalyst-free reaction under mild con-
ditions is reported. The 1,1-bishydrazino-2-nitroethylene interme-
diate generated in situ from the addition of aqueous hydrazine to
1,1-bis(methylthio)-2-nitroethylene is trapped by two equivalents
of isatin derivatives to obtain the title compounds.
N
Key words: spirooxindole, isatin, spiropyrazole, pyrazoline, 1,1-
bis(methylthio)-2-nitroethylene, one-pot reaction
H
HO
Me
N
H
O
N
MeN
H
The biological activity and structural complexity found in
nature has stimulated generations of synthetic chemists to
design strategies for assembling challenging structures
found in natural products.1
NH
O
N
H
coerulescine
strychnofoline
antitumor agent
Spirooxindole heterocycles, in which the indole ring is
linked to the other heterocyclic system through the spiro
carbon atom at C-3, show an increased spectrum of bio-
logical activities.2 In addition they are commonly found in
pharmaceuticals and a number of natural spirooxindole al-
kaloids.3 For example, coerulescine, the simplest spiroox-
indole found in nature, displays a local anesthetic effect.
Figure 1 shows some of the naturally occurring and bio-
logically active spirooxindoles.4
F
Cl
HN
NH
Cl
O
N
H
NITD609
treatment of malaria
Although spirooxindole-pyrazolines are an interesting
class of spirooxindoles, they have been less studied than
spirooxindole-pyrrolidines. To the best of our knowledge
Figure 1 Examples of naturally occurring and biologically active
spirooxindoles
Ar
N
HN
R
NH2NH2⋅H2O
MW, alumina
O
N
H
Ar
Ar
H
N
O
O
HN
R
O
R
R
OH
O
Ar
H2O2, Na2CO3, MeOH
MW, 2–3 min, 240 W
NH2NH2⋅H2O
O
O
MW
N
N
H
N
H
H
O
CH2N2
CHCl3–Et2O
NH2NH2⋅H2O
EtOH, reflux
Ar
N
or
N
N
Ar
HN
R
or
O
O
R
N
H
N
H
Scheme 1 Reported synthesis of spirooxindole-pyrazolines under various conditions requiring at least two steps
SYNLETT 2012, 23, 428–432
x
x.
x
x.
2
0
1
2
Advanced online publication: 25.01.2012
DOI: 10.1055/s-0031-1290322; Art ID: D58611ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Spirooxindole-Pyrazolines
429
The importance of spirooxindoles has led to a demand for The molecular structure of all spiro compounds 2a–h was
a synthetic methodology; particularly to access those that elucidated from their mass spectrometric analyses, IR,
are fused to a pyrazole ring. Recently, we became interest- and high-field 1H NMR and 13C NMR spectra as described
ed in the application of ketene aminal intermediates re- for 2a.10 The mass spectrum of 2a displayed the molecular
sulting from the reaction of 1,1-bis(methylthio)-2- ion peak at m/z = 319 with low intensity. In the IR spec-
nitroethylene and nitrogen nucleophiles such as diamines trum, stretching frequencies of five NH groups appear as
or ammonia for the synthesis of interesting heterocycles in two broad bands in the region of 3100–3500 cm–1. Ab-
one-pot processes8 (Scheme 2). Following this lead and in sorption bands at 1715, 1616, 1558, and 1340 cm–1 are re-
the context of our ongoing investigations on the construc- lated to NC=O, C=N, C=C, and NO2 groups, respectively,
tion of two-nitrogen heterocycles,9 we decided to evaluate and indicate the most important functional groups of the
the reaction of hydrazine hydrate and 1,1-bis(methylthio)- product.
2-nitroethylene in the presence of isatin for the synthesis
of spirooxindole-pyrazolines. Initial investigation of the
The 1H NMR spectrum of 2a exhibited four singlets at d =
6.13, 10.79, 11.21, and 13.37 ppm and were assigned as
NMR spectrum of the product showed that two equiva-
NH protons, as all were exchangeable with D2O. The first
lents of isatin have been consumed in the reaction. Thus
signal is due to the two NH protons of the pyrazoline ring.
we then optimized the amount of reagents as well as reac-
The second and third signals are attributed to the two NH
groups of isatins and are not present when N-alkyl isatins
tion conditions such as solvent, temperature, and time.
are used. The latter is related to the NHN=C which reso-
NO2
H
H2N
O2N
H
nates downfield due to intramolecular hydrogen bonding
with the NO2 group, in addition of conjugation with
C=CNO2. Observation of 18 distinct signals in the 1H-de-
coupled 13C NMR spectrum of 2a is in agreement with the
proposed structure. In the aliphatic region there is one
characteristic signal at d = 74.33 ppm corresponding to the
C-3 spiro carbon. Signals of two amidic carbonyls appear
at d = 162.46 and 164.24 ppm. It is proposed that intramo-
lecular hydrogen bonding results in the formation of the
Z-isomer around the C=N bond in the products 2.
N
N
NH2
N
X
CN
O
O
O
N
N
H
R
H2N
H2N
NO2
H
NH
NH
NO2
H
Although no detailed mechanistic studies have been car-
ried out at this point, our postulated reaction pathway is
shown in Scheme 4. Based on the established chemistry of
isatin in the presence of compounds containing two nu-
cleophilic centers,11 1,1-bishydrazino-2-nitroethylene (3)
apparently results from the addition of two equivalents of
hydrazine to 1,1-bis(methylthio)-2-nitroethylene fol-
lowed by the loss of two equivalents of methanethiol. Nu-
cleophilic addition via the NH2 of ketene aminal 3 to the
reactive ketonic carbonyl of isatin followed by loss of two
equivalents of H2O affords intermediate 4 which is a bis-
hydrazone. Finally, intermediate 4 undergoes an intramo-
lecular cyclization to form spirooxindole-pyrazoline 2.
Scheme 2 Synthesis of spirooxindoles using ketene aminal interme-
diates
As shown in Scheme 3, the reaction of two equivalents of
hydrazine hydrate, one equivalent of 1,1-bis(methylthio)-
2-nitroethylene, and two equivalents of isatin 1 proceeds
smoothly in EtOH at room temperature in eight hours to
produce spirooxindole-pyrazolines 2 in 60–70% yields.
2 H2N NH2⋅H2O
+
Me
Me
S
S
NO2
R2
NH2
H
O
H
R1
N
Me
Me
S
S
NO2
+
HN
HN
NO2
HN
1 (2 equiv)
– 2 MeSH
N
EtOH, r.t
12 h
N
H2N NH2
N
+
– 2 H2O
O
R2
2
NO2
N
NH2
O
R1
O
2
3
R2
N
R1
R1
N
1
O
N
Scheme 3 General one-pot reaction for the synthesis of spirooxin-
dole-pyrazolines
H
..
H
N
N
2
N
N
R2
R2
NO2
Different types of isatin such as 5-bromo, 5-nitro, and N-
alkyl isatins were used under the same conditions to in-
vestigate the reaction scope and limitations. As depicted
in Table 1, the reaction is general with regard to the isatin
component (Table 1).
O
R1
4
Scheme 4 Proposed mechanism for the one-pot synthesis of
spirooxindole-pyrazoline 2
© Thieme Stuttgart · New York
Synlett 2012, 23, 428–432

430
A. Alizadeh, N. Zohreh
LETTER
Table 1 Synthetic Spirooxindole-pyrazolines from the One-Pot Re-
action of Hydrazine Hydrate, 1,1-Bis(methylthio)-2-nitroethylene,
and Various Isatins
Table 1 Synthetic Spirooxindole-pyrazolines from the One-Pot Re-
action of Hydrazine Hydrate, 1,1-Bis(methylthio)-2-nitroethylene,
and Various Isatins (continued)
Entry R1
R2
Product
Yield
(%)
Entry R1
R2
Product
Yield
(%)
O
H
O
H
Br
PMB
N
H
N
N
H
N
HN
NH
HN
N
N
N
1
2
H
H
76
70
NO2
8
PMB Br
63
NO2
N
O
N
O
H
PMB
2a
2b
Br
O
H
2h
Me
N
H
N
HN
N
N
Me
H
H
Overall, we have succeeded in developing a novel syn-
thetic method for spirooxindole-pyrazolines of potential
synthetic and pharmacological interest from the reaction
of hydrazine hydrate, 1,1-(bismethylthio)-2-nitroethyl-
ene, and isatin derivatives. Our work presents a very sim-
ple one-pot reaction performed under neutral conditions
and in the absence of catalyst. From a structural view-
point, the products are polynitrogen compounds that will
be suitable for further elaboration. The products are
strongly colored with high heat resistance. High yields
and simple reaction and purification procedures are ad-
vantages of this approach.
NO2
N
O
Me
H
N
O
HN
NH
Bn
N
N
3
4
Bn
65
65
N
NO2
O
Bn
2c
H
N
O
HN
NH
N
PMB
N
PMB
H
References and Notes
N
NO2
O
PMB
(1) (a) Nicolaou, K. C.; Vourloumis, D.; Winssinger, N.; Baran,
P. S. Angew. Chem. Int. Ed. 2000, 39, 44. (b) Nicolaou, K.
C.; Snyder, S. A. Proc. Natl. Acad. Sci. U.S.A. 2004, 101,
11929. (c) Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G.
Angew. Chem. Int. Ed. 2006, 45, 7134. (d) Li, J. W. H.;
Vederas, J. C. Science 2009, 325, 161. (e) Gaich, T.; Baran,
P. S. J. Org. Chem. 2010, 75, 4657.
2d
O
H
O2N
N
H
HN
NH
N
N
5
6
7
H
NO2
64
68
60
NO2
N
O
(2) Edmondson, S.; Danishefsky, S. J.; Sepp-Lorenzino, L.;
H
Rosen, N. J. Am. Chem. Soc. 1999, 121, 2147.
O2N
(3) (a) Trost, B. M.; Jiang, C. Synthesis 2006, 369.
(b) Williams, R. M.; Cox, R. J. Acc. Chem. Res. 2003, 36,
127. (c) Galliford, C. V.; Scheidt, K. A. Angew. Chem. Int.
Ed. 2007, 46, 8748. (d) Marti, C.; Carreira, E. M. Eur. J.
Org. Chem. 2003, 2209. (e) Lin, H.; Danishefsky, S. J.
Angew. Chem. Int. Ed. 2003, 42, 36.
(4) (a) Kornet, M. J.; Thio, A. P. J Med Chem. 1976, 19, 892.
(b) Rottmann, M.; McNamara, C.; Yeung, B. K. S.; Lee, M.
C. S.; Zou, B.; Russell, B.; Seitz, P.; Plouffe, D. M.; Dharia,
N. V.; Tan, J.; Cohen, S. B.; Spencer, K. R.; González-Páez,
G. E.; Lakshminarayana, S. B.; Goh, A.; Suwanarusk, R.;
Jegla, T.; Schmitt, E. K.; Beck, H.-P.; Brun, R.; Nosten, F.;
Renia, L.; Dartois, V.; Keller, T. H.; Fidock, D. A.;
Winzeler, E. A.; Diagana, T. T. Science 2010, 329, 1175.
(5) Dandia, A.; Singh, R.; Saha, M.; Shivpuri, A. Pharmazie
2002, 57, 602.
2e
O
H
Br
N
H
N
HN
NH
Br
N
H
Br
Br
NO2
N
O
H
2f
O
H
Br
Bn
N
H
HN
N
N
N
Bn
NO2
N
O
Bn
(6) Mishra, A. D. J. Nepal Chem. Soc. 2009, 24, 49.
(7) Velikorodov, A. V.; Poddubnyi, O. Yu.; Kuanchalieva, A.
K.; Krivosheev, O. O. Russ. J. Org. Chem. 2010, 46, 1826.
(8) (a) Alizadeh, A.; Firuzyar, T.; Mikaeili, A. Synthesis 2010,
3913. (b) Alizadeh, A.; Mikaeili, A.; Firuzyar, T. Helv.
Chim. Acta 2011, 94, 1343.
Br
2g
(9) (a) Zohreh, N.; Alizadeh, A.; Bijanzadeh, H. R.; Zhu, L. G.
J. Comb. Chem. 2010, 12, 497. (b) Zohreh, N.; Alizadeh, A.
Tetrahedron 2009, 65, 2684. (c) Alizadeh, A.; Zohreh, N.;
Synlett 2012, 23, 428–432
© Thieme Stuttgart · New York

LETTER
Zhu, L. G. Tetrahedron 2009, 65, 268. (d) Alizadeh, A.;
Zohreh, N. Helv. Chim. Acta 2010, 93, 1221. (e) Alizadeh,
A.; Zohreh, N.; Zhu, L. G.; Oskueyan, G. Synlett 2011, 2491.
(10) Synthesis of Compound 2
Synthesis of Spirooxindole-Pyrazolines
431
3JHH = 15.2 Hz, 2 CH2), 6.18 (2 H, s, 2 NH), 6.96–7.04 (4 H,
m, 4 CH of Ar), 7.14 (2 H, d, 3JHH = 5.8 Hz, 4 CH of Ar),
7.26 (2 H, d, 3JHH = 6.5 Hz, 4 CH of Ar), 7.35–7.42 (4 H, m,
4 CH of Ar), 8.25 (1 H, d, 3JHH = 6.4 Hz, CH of Ar), 13.41
(1 H, s, NH). 13C NMR (125.7 MHz, DMSO-d6): d = 20.6 (2
Me), 42.3 (CH2), 42.5 (CH2), 74.3 (Cspiro), 109.9 (CH), 110.6
(CH), 116.1 (C), 118.9 (C), 119.6 (C), 120.2 (CH), 122.7
(CH), 123.1 (CH),127.3 (2 CH), 127.3 (2 CH), 129.2 (4 CH),
131.4 (C), 131.5 (C), 132.2 (CH), 132.5 (CH), 133.7 (CH),
136.7 (C), 136.8 (C), 145.1 (C), 149.6 (C), 151.5 (C), 160.8
(C=O), 163.1 (C=O). MS: m/z (%) = 551 (5), 523 (7), 368
(26), 353 (8), 313 (11), 285 (6), 255 (14), 236 (45), 221 (11),
194 (13), 152 (17), 123 (21), 105 (72), 83 (65), 77 (81), 57
(100).
Compound 2e: yield 0.31 g (64%); mustard powder; up
300 °C. IR (KBr): 3000–3500 (2 br bands, 5 NH), 1732 (2
NC=O), 1618 (C=N, C=C), 1545 and 1339 (NO2) cm–1. 1H
NMR (500 MHz, DMSO-d6): d = 6.28 (2 H, s, 2 NH), 6.98–
7.11 (2 H, m, 2 CH of Ar), 8.17–8.30 (3 H, m, 3 CH of Ar),
8.85 (1 H, br, CH of Ar), 11.53 (1 H, s, NH), 11.87 (1 H, s,
NH), 13.42 (1 H, s, NH). 13C NMR (125.7 MHz, DMSO-d6):
d = 74.2 (Cspiro), 110.9 (C), 111.5 (CH), 115.6 (CH), 116.3
(C), 120.2 (C), 123.9 (CH), 127.6 (CH), 129.8 (CH), 134.7
(CH), 142.2 (C), 142.7 (C), 147.6 (C), 147.0 (C), 150.5 (C),
153.4 (C), 162.9 (C=O), 164.4 (C=O). MS: m/z (%) = 206
(47), 191 (19), 177 (10), 163 (31), 149 (23), 133 (82), 105
(39), 90 (91), 77 (75), 63 (100), 57 (86).
Compound 2f: yield 0.37 g (68%); dark brown powder; mp
up 280 °C. IR (KBr): 3000–3500 (2 br bands, 5 NH), 1718
(2 NC=O), 1600 (C=N, C=C), 1549 and 1367 (NO2) cm–1.
1H NMR (500 MHz, DMSO-d6): d = 6.22 (2 H, s, 2 NH),
6.85–6.90 (2 H, m, 2 CH of Ar), 7.39–7.52 (3 H, m, 3 CH of
Ar), 8.30 (1 H, br, CH of Ar), 10.95 (1 H, s, NH), 11.35 (1
H, s, NH), 13.36 (1 H, s, NH). 13C NMR (125.7 MHz,
DMSO-d6): d = 74.1 (Cspiro), 112.6 (C), 113.2 (CH), 113.6
(C), 114.1 (CH), 118.1 (C), 121.6 (C), 122.7 (CH), 131.0
(CH), 133.8 (CH), 134.68 (C), 136.07 (CH), 141.54 (C),
144.18 (C), 149.5 (C), 152.2 (C), 162.1 (C=O), 163.8 (C=O).
MS: m/z (%) = 551 (6) [M+ + 4], 549 (12), 547 (6), 523 (9),
368 (47), 353 (7), 313 (22), 285 (13), 264 (19), 240 (20), 238
(20), 237 (42), 152 (24), 98 (75), 83 (83), 71 (85), 57 (100).
Compound 2g: yield 0.44 g (60%); orange powder; mp
220 °C. IR (KBr): 3437 (br, 3 NH), 1721 (2 NC=O), 1600
(C=N, C=C), 1562 and 1342 (NO2) cm–1. 1H NMR (500
MHz, DMSO-d6): d = 4.97 (4 H, d, 3JHH = 14.6 Hz, 2 CH2),
6.27 (2 H, s, 2 NH), 6.93–6.96 (2 H, m, 2 CH of Ar), 7.27–
7.34 (10 H, m, 10 CH of Ar), 7.53 (3 H, br, 3 CH of Ar), 8.35
(1 H, br, CH of Ar), 13.41 (1 H, s, NH). 13C NMR (125.7
MHz, DMSO-d6): d = 42.7 (CH2), 42.8 (CH2), 74.1 (Cspiro),
111.9 (C), 112.6 (C), 114.5 (CH), 115.0 (CH), 117.6 (C),
121.1 (C), 122.7 (C), 127.2 (CH), 127.3 (CH), 127.5 (CH),
127.6 (CH), 128.6 (C), 128.7 (2 CH), 130.9 (CH), 133.7 (C),
133.9 (C), 135.3 (CH), 135.7 (CH), 135.9 (CH), 141.8 (C),
144.2 (C), 148.6 (C), 160.5 (C=O), 162.6 (C=O). MS: m/z
(%) = 331 (7), 329 (7), 317 (7), 315 (7), 258 (5), 256 (5), 224
(13), 170 (12), 168 (12), 91 (100), 65 (33).
To a magnetically stirred 10 mL flask containing 1,1-
bis(thiomethyl)-2-nitroethylene (0.17 g, 1 mmol) in EtOH (4
mL) was added NH2NH2·H2O (80% aq, 0.12g, 2 mmol).
After 5 h, isatin (0.30 g, 2 mmol) was added to the reaction
mixture, and stirring was allowed to continue for 3 h. After
the completion of the reaction, the precipitated product was
filtered and washed with cold EtOH. Product 2a was
obtained as an orange powder.
Analytical Data for Compounds 2
Compound 2a: yield 0.30 g (76%); mp >300 °C (dec.). IR
(KBr): 3100–3500 (2 br bands, 5 NH), 1715 (2 NC=O), 1616
(C=N, C=C), 1558 and 1340 (NO2) cm–1. 1H NMR (500
MHz, DMSO-d6): d = 6.13 (2 H, s, 2 NH), 6.87–7.07 (4 H,
m, 4 CH of Ar), 7.36 (3 H, br, 3 CH of Ar), 8.17 (1 H, br, CH
of Ar), 10.79 (1 H, s, NH), 11.21 (1 H, s, NH), 13.37 (1 H, s,
NH). 1H NMR (500 MHz, DMSO-d6–D2O): d = 6.84 (1 H,
d, 3JHH = 7.6 Hz, CH of Ar), 6.88 (1 H, d, 3JHH = 7.6 Hz, CH
of Ar), 6.96 (1 H, t, 3JHH = 8.1 Hz, CH of Ar), 7.02 (1 H, t,
3JHH = 7.5 Hz, CH of Ar), 7.29–7.34 (3 H, m, 3 CH of Ar),
8.11 (1 H, d, 3JHH = 7.4 Hz, CH of Ar). 13C NMR (125.7
MHz, DMSO-d6): d = 74.3 (Cspiro), 110.6 (CH), 111.2 (CH),
116.6 (C), 119.4 (C), 120.3 (CH), 122.0 (CH), 122.4 (CH),
129.1 (CH), 131.6 (CH), 133.8 (CH), 135.4 (C), 142.4 (C),
145.0 (C), 150.3 (C), 151.0 (C), 162.5 (C=O), 164.2 (C=O).
MS: m/z (%) = 391 (4) [M+], 368 (10), 313 (7), 239 (13), 147
(30), 132 (25), 118 (55), 104 (49), 91 (37), 77 (78), 67 (30),
57 (100), 56 (85).
Compound 2b: yield 0.29 g (70%); orange powder; mp
280 °C (dec). IR (KBr): 3440 (br, 3 NH), 1715 (2 NC=O),
1613 (C=N, C=C), 1561 and 1360 (NO2) cm–1. 1H NMR
(500 MHz, DMSO-d6): d = 3.21 (3 H, s, Me), 3.33 (3 H, s,
Me), 6.15 (2 H, s, 2 NH), 7.06–7.15 (4 H, m, 4 CH of Ar),
7.38–7.49 (3 H, m, 3 CH of Ar), 8.20 (1 H, d, 3JHH = 7.4 Hz,
CH of Ar), 13.36 (1 H, s, NH). 13C NMR (125.7 MHz,
DMSO-d6): d = 25.7 (Me), 26.0 (Me), 74.3 (Cspiro), 109.3
(CH), 110.0 (CH), 116.0 (C), 118.7 (C), 120.0 (CH), 122.6
(CH), 123.0 (CH), 128.8 (CH), 131.6 (CH), 133.8 (CH),
134.8 (C), 143.6 (C), 146.1 (C), 149.7 (C), 151.1 (C), 160.8
(C=O), 162.7 (C=O). MS: m/z (%) = 419 (9) [M+], 373 (10),
232 (12), 214 (13), 200(7), 187 (30), 186 (30), 185 (31), 173
(21), 160 (59), 146 (45),131 (100), 117 (95), 104 (63), 90
(86), 77 (55), 63 (17), 51 (22).
Compound 2c: yield 0.37 g (65%); orange powder; mp 238–
240 °C. IR (KBr): 3447 and 3201 (br, 3 NH), 1722 (2
NC=O), 1610 (C=N, C=C), 1559 and 1353 (NO2) cm–1. 1H
NMR (500 MHz, DMSO-d6): d = 4.97 (4 H, d, 3JHH = 15.7
Hz, 2 CH2), 6.20 (2 H, s, 2 NH), 6.97–7.11 (6 H, m, 5 CH of
Ar), 7.27–7.374 (12 H, m, 10 CH of Ar), 8.29 (1 H, d,
3JHH = 6.9 Hz, CH of Ar), 13.42 (1 H, s, NH). 13C NMR
(125.7 MHz, DMSO-d6): d = 42.6 (CH2), 42.8 (CH2), 74.3
(Cspiro), 109.9 (CH), 110.5 (CH), 116.1 (C), 118.9 (C), 119.5
(C), 120.2 (CH), 122.8 (CH), 123.1 (CH),127.2 (2 CH),
127.3 (2 CH), 127.5 (CH), 127.5 (CH), 128.7 (4 CH), 129.0
(CH), 131.5 (CH), 133.7 (CH), 134.7 (C), 135.6 (C), 136.0
(C), 145.08 (C), 149.54 (C),151. 51 (C), 160.81 (C=O),
163.0 (C=O). MS: m/z (%) = 368 (20), 353 (5), 339 (3), 313
(14), 299 (12), 285 (8), 255 (16), 236 (48), 222 (10), 208
(12), 194 (22), 152 (24), 125 (19), 111 (36), 97 (67), 83 (76),
69 (90), 57 (100).
Compound 2h: yield 0.48 g (63%); dark brown powder; mp
163 °C. IR (KBr): 3308 and 3203 (br, 3 NH), 1719 (2
NC=O), 1604 (C=N, C=C), 1557 and 1348 (NO2) cm–1. 1H
NMR (500 MHz, DMSO-d6): d = 2.21 (6 H, s, 2 Me), 4.88
(4 H, br, 2 CH2), 6.23–7.47 (14 H, m, 14 CH of Ar), 8.31 (1
H, s, NH), 10.17 (1 H, s, NH). 13C NMR (125.7 MHz,
DMSO-d6): because of insolubility, only some of the
resonances are distinguishable including: d = 20.6 (2 Me),
74.1 (Cspiro), 127.2 (2 CH of Ar), 127.3 (2 CH of Ar), 129.2
(4 CH of Ar). MS: m/z (%) = 410 (5), 368 (7), 341 (8), 279
Compound 2d: yield 0.38 g (65%); orange powder; mp
249 °C. IR (KBr): 3440 (br, 3 NH), 1722 (2 NC=O), 1607
(C=N and C=C), 1561 and 1352 (NO2) cm–1. 1H NMR (500
MHz, DMSO-d6): d = 2.25 (6 H, s, 2 Me), 4.93 (4 H, d,
© Thieme Stuttgart · New York
Synlett 2012, 23, 428–432

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A. Alizadeh, N. Zohreh
LETTER
(7), 236 (11), 213 (6), 173 (18), 149 (42), 127 (38), 105 (25),
97 (70), 83 (74), 69 (100), 57 (97).
(11) (a) Jadidi, K.; Ghahremanzadeh, R.; Bazgir, A. J. Comb.
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S.; Ghahremanzadeh, R.; Mirzaei, P.; Bazgir, A.
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Synlett 2012, 23, 428–432
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