Microwave-induced one-pot synthesis of some new spiro[3H-indole-3,5′(4′H)-[1,2,4]triazoline]-2-ones

Article abstract of DOI:10.1081/SCC-100103539

A rapid and efficient method for the synthesis of title compounds by 1,3-dipolar cycloaddition reaction or nitrilimines with isatin imines using microwave-induced and conventional methods is reported.

Full text of DOI:10.1081/SCC-100103539

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MICROWAVE-INDUCED ONE-
POT SYNTHESIS OF SOME NEW
SPIRO[3H-INDOLE-3,5′(4′H)-
[
1,2,4]- TRIAZOLINE]-2-ONES
a
b
Javad Azizian , Saeed Soozangarzadeh
&
a
Khosrow Jadidi
a
Department of Chemistry, Faculty of Science,
Shahid Beheshty University, P. O. Box 19395-4716,
Tehran, Iran
b
Department of Chemistry, Science and Research
Campus, Islamic Azad University, P. O. Box
19395-1775, Tehran, Iran
Published online: 09 Nov 2006.
To cite this article: Javad Azizian , Saeed Soozangarzadeh & Khosrow Jadidi
2001) MICROWAVE-INDUCED ONE-POT SYNTHESIS OF SOME NEW SPIRO[3H-
(
INDOLE-3,5′(4′H)-[1,2,4]- TRIAZOLINE]-2-ONES, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry,
31:7, 1069-1073, DOI: 10.1081/SCC-100103539
To link to this article: http://dx.doi.org/10.1081/SCC-100103539
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SYNTHETIC COMMUNICATIONS, 31(7), 1069–1073 (2001)
MICROWAVE-INDUCED ONE-POT
SYNTHESIS OF SOME NEW
SPIRO[3H-INDOLE-3,5 (4 H)-[1,2,4]-
0
0
TRIAZOLINE]-2-ONES
1
,
2
*
Javad Azizian,
Saeed Soozangarzadeh, and
Khosrow Jadidi
1
1
Department of Chemistry, Faculty of Science, Shahid
Beheshty University, P. O. Box 19395-4716, Tehran, Iran
2
Department of Chemistry, Science and Research Campus,
Islamic Azad University, P. O. Box 19395-1775,
Tehran, Iran
ABSTRACT
A rapid and efficient method for the synthesis of title
compounds by 1,3-dipolar cycloaddition reaction or nitril-
imines with isatin imines using microwave-induced and
conventional methods is reported.
Recent research has demonstrated that synthesis of a variety of
heterocyclic compounds can be conducted safely in commercial micro-
wave ovens with remarkable rate enhancements and dramatic reductions
1
,2
of reaction times.
In continuation of our earlier work on the synthesis of spiroindoles,
3
,4
a series of novel spiroindoles with new skeleton 3 has been synthesized.
Spiro compounds 3 are prepared because these molecules would have
*
Corresponding author.
1
069
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

1
070
AZIZIAN, SOOZANGARZADEH, AND JADIDI
Scheme.
enhanced biological activities, since they incorporate both indole with C-3
5
as spiro atom and triazole moieties.
,6
0
0
The spiro[3H-indole-3,5 (4 H)-[1,2,4]triazoline]-2-ones (3) were obtained
thermally and under microwave irradiation by reaction of corresponding
imines of isatin 1 with nitrilimines 2, generated in situ from the corres-
7
,8
ponding hydrazonyl chlorides. Yields are 85–95% and the reaction is
complete in 5 min, compared to 20–30% with 6–10 h under thermal
conditions.
However, when the reaction is carried out at ambient temperature, the
products are obtained in excellent yields but in very long time (30 h).
The structures of compounds 3a–g were assigned on the basis
1
13
of their elemental analysis, H NMR, C NMR and mass spectral data

NITRILIMINES WITH ISATIN IMINES
1071
(
absorption at 1710–1740 cm region, a peak at 1670–1690 cm , which is
see Experimental), as well as the IR spectra, which exhibited carbonyl
À1
À1
À1
due to ꢀ
, and a band at 3140–3240 cm for the N-H group.
C ¼ N
1
3
Inthe C NMRspectra, thecarbonylabsorptionatabout173–175 ppm,
imine carbon (C ¼ N) at 147–149ppm, and a signal at 88–89ppm
attributable to the spiro carbon atom, are in agreement with proposed
0
structure 3, but not with structure 3 .
EXPERIMENTAL
Melting points were measured on the Electrothermal 9100 apparatus
and are uncorrected. Elemental analyses for C, H, and N were performed
using a Heracus CHN-O-Rapid analyzer. IR spectra were measured on a
1
13
Bomem FT-IR-MB100 spectrometer. H and C NMR spectra were mea-
sured with a Bruker DRX-300 Avance spectrometer. Mass spectra were
recorded on a Hewlett-Packard 5973 mass spectrometer operating at an
ionization potential of 70 eV. Microwave irradiations were carried out in
a National oven, Model 5250 at 2450 MHz.
Benzoyl chloride, p-flourobenzoyl chloride, and phenylhydrazine
were obtained from Merck and were used without further purification.
Imines of isatin 1 were prepared in quantitative yields according to standard
9
procedures.
General Procedure
Microwave
A mixture of isatin imine (5 mmol), triethylamine (5 mmol), and
hydrazonyl chloride (5 mmol) in N,N-dimethylacetamide (DMA) (1 mL)
was placed in an Erlenmeyer flask covered with a watch glass and irradiated
in the microwave oven at 200 W for 5 min. After completion of the reaction
(
monitored by TLC), ethanol (10 mL) and ice water (5 mL) were added to
the reaction mixture and kept at room temperature. The crystalline product
was filtered, washed with light petroleum, and the analytical samples were
obtained by recrystallization twice from ethanol/water.
Conventional
To a magnetically stirred solution of hydrazonyl chloride (5 mmol)
and isatin imine (5 mmol) in CH CN (15 mL), a mixture of triethylamine
3

1
072
AZIZIAN, SOOZANGARZADEH, AND JADIDI
(
5 mmol) in CH CN (5 mL) at room temperature was added dropwise over
3
1
5 min. The reaction mixture was then stirred for 30 h. Then the reaction
mixture was filtrated to remove triethylamine hydrochloride, washed with
water, dried, and the solvent was removed under reduced pressure for
obtained crude product. While the above reaction mixture was refluxed
for 6–10 h, mixture of product and by-product were obtained in low yields
(
20–30%).
a: yellow crystal, yield 95% (conventional 90%), m.p. 201 C;
ꢀmax/cmÀ1 3219(N-H), 1735 (C ¼ O), 1595 (C ¼ N); ꢁ (CDCl ) 6.77–7.49
ꢀ
3
H
3
(
19H, m, Ar), 9(1, brs, NH),
ꢁc (CDCl ) 88.47 (spiro carbon),
3
1
(
11.93–143.79 (aromatic carbons), 148.60 (C ¼ N), 174.20 (C ¼ O); MS
þ þ þ
m/z, %) 416 (M , 8), 388 (M -CO, 80), 194 (M -C H N O, 13)
14 10 2
(
N, 13.02%).
Found: C, 78.0; H, 5.2; N, 13.1. C H N O requires C, 78.14; H, 5.11;
27 20 4
ꢀ
3
b: yellow crystal, yield 92% (conventional 85%), m.p. 210 C;
ꢀmax/cmÀ1 3258 (N-H), 1735 (C ¼ O), 1597 (C ¼ N); ꢁ (CDCl ) 2.22 (3H,
H
3
S, CH ), 6.66–7.62 (19H, m, Ar), 9(1, brs, NH),
3
ꢁC (CDCl ) 22.12
3
(
(
1
CH ), 88.45 (spiro carbon), 111.80–143.75 (aromatic carbons), 148.50
3
þ
þ
C ¼ N), 173.50 (C ¼ O); MS (m/z, %) 430 (M , 18), 403 (M -CO, 95),
þ
94 (M -C H N O, 18) (Found: C, 78.2; H, 5.2; N, 12.9. C H N O
1
4
9
2
28 22
4
requires C, 78.12; H, 5.15; N, 13.01%).
c: yellow crystal yield 88% (conventional 85%), m.p. 199 C;
ꢀmax/cmÀ1 3212 (N-H), 1738 (C ¼ O), 1597 (C ¼ N); ꢁ (CDCl ) 6.66–7.62
ꢀ
3
H
3
(
19H, m, Ar), 9(1, brs, NH),
ꢁ
(CDCl ) 88.42 (spiro carbon),
C 3
1
(
11.64–143.70 (aromatic carbons), 148.19(C ¼ N), 173.48 (C ¼ O); MS
þ þ þ
m/z, %) 49 5 (M, 13), 468 (M -CO, 35), 195 (M -C H N OBr, 18)
14 9 2
(
N, 2.82%).
Found: C, 65.4; H, 4.1; N, 2.8. C H N OBr requires C, 65.33; H, 5.06;
27 20 4
ꢀ
3
d: yellow crystal, yield 95% (conventional 90%), m.p. 199 C,
ꢀmax/cmÀ1 3214 (N-H), 1737 (C ¼ O), 1596 (C ¼ N); ꢁ (CDCl ) 6.76–7.52
H
3
(
18 H, m, Ar), 8.35 (1, brs, NH), ꢁC (CDCl ) 88.59(spiro carbon),
3
1
11.70–165.23 (aromatic carbons), 147.81 (C ¼ N), 174.20 (C ¼ O); MS
þ þ þ
14 10 2
(
m/z, %) 434 (M , 8), 407 (M -CO, 95), 194 (M -C H N OF, 12)
(
N, 12.89%).
Found: C, 74.7; H, 4.4; N, 12.9. C H N OF requires C, 74.64; H, 4.41;
27 19 4
ꢀ
3
e: yellow crystal, yield 90% (conventional 85%), m.p. 215 C;
ꢀmax/cmÀ1 3254 (N-H), 1737 (C ¼ O), 1601 (C ¼ N); ꢁ (CDCl ) 2.22 (3H, s,
H
3
CH ), 6.65–7.63 (17 H, m, Ar), 8.35 (1, brs, NH), ꢁ (CDCl ) 21.39(CH ),
3
C
3
3
8
1
8.59(spiro carbon), 111.22–165.16 (aromatic carbons), 147. 69 (C ¼ N),
þ þ
73.30 (C ¼ O); MS (m/z, %) 434 (M , 8), 407 (M -CO, 95), 194
þ
(M -C H N OF, 12) (Found: C, 75.0; H, 4.6; N, 12.5. C H N OF
4
requires C, 74.99; H, 4.72; N, 12.49%).
1
4
10
2
28 21

NITRILIMINES WITH ISATIN IMINES
1073
ꢀ
3
f: yellow crystal, yield 95% (conventional 87%), m.p. 195 C;
ꢀmax/cmÀ1 3268 (N-H), 1740 (C ¼ O), 1612 (C ¼ N); ꢁ (CDCl ), 6.64–7.73
H
3
(
17 H, m, Ar), 8.14 (1, brs, NH), ꢁC (CDCl ) 88.53 (spiro carbon),
3
1
11.20–165.10 (aromatic carbons), 147.45 (C ¼ N), 173.40 (C ¼ O); MS
þ þ þ
14 10 2
(m/z, %) 434 (M , 8), 407 (M -CO, 95), 194 (M -C H N OF, 12)
(
Found: C, 63.2; H, 3.4; N, 10.8. C H N OFBr requires C, 63.17, H,
27 18 4
3
.53; N, 10.91%).
g: yellow crystal, yield 95% (conventional 90%), m.p. 167 C;
ꢀmax/cmÀ1 3298 (N-H), 1731 (C ¼ O), 1596 (C ¼ N); ꢁ (CDCl ) 1.13 (3H, t,
ꢀ
3
H
3
CH ), 2.51 (2 H, q, CH ), 6.68–7.64 (19H, m, Ar), 7.58 (1, brs, NH), ꢁ
C
3
2
(
(
4
CDCl ) 88.53 (spiro carbon), 111.36–143.89(aromatic carbons), 148.83
3
þ
þ
C ¼ N), 173.84 (C ¼ O); MS (m/z, %) 444 (M , 1), 429(M -CH ,38),
3
þ þ þ
16 (M -CO, 92), 401 (M -CO-CH , 30), 387 (M -CO-C H , 5), 194
3 2 5
þ
(
C, 78.36; H, 5.44; N, 12.60%).
M -C H N O, 42) (Found: C, 78.4; H, 5.5; N, 12.5. C H N O requires
4
1
6
14
2
29 24
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1
2
3
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. Galema, A. Chem. Soc. Rev. 1997, 26, 223.
. Azizian, J.; Jadidi, K.; Mehrdad, M.; Sarrafi, Y. Synth. Commun.
in press.
4
. Azizian, J.; Varasteh Morady, A.; Jadidi, K.; Mehrdad, M.; Sarrafi, Y.
Synth. Commun. in press.
5
6
7
8
9
. Joshi, K.C.; Jain, R.; Chand, P. Heterocycles 1985, 23, 957.
. Silvester, M.J. Adv. Heterocycl. Chem. 1994, 59, 1.
. Cohen, S.G.; Nicholson, J. J. Org. Chem. 1965, 30, 1162.
. Wolkoff, P. Can. J. Chem. 1975, 53, 1333.
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Received in Japan March 14, 2000