Microwave assisted one pot synthesis of a series of trifluoromethyl substituted spiro [indole-triazoles]

Article abstract of DOI:10.1016/S0022-1139(01)00429-8

A series of trifluoromethyl substituted spiro [3H-indole-3,3′-[3H-1,2,4]triazoles]-2(1H)-ones have been synthesized in 85-90% yield by one pot environmentally benign microwave induced techniques involving the condensation of 3-arylimino-2H-indol-2-ones (III) with thiosemicarbazide (IV) using montmorillonite as solid support. This 3-arylimino-2H-indol-2-ones (III) was synthesized in situ by the reaction of fluorinated indole-2,3-diones (I) and fluorinated anilines (II). The advantages obtained by the use of microwave irradiation were demonstrated.

Full text of DOI:10.1016/S0022-1139(01)00429-8

Journal of Fluorine Chemistry 111 ,2001) 61±67
Microwave assisted one pot synthesis of a series of tri¯uoromethyl
substituted spiro [indole±triazoles]
Anshu Dandia*, Ruby Singh, Harshita Sachdeva, Kapil Arya
Department of Chemistry, University of Rajasthan, Jaipur 302004, India
Received 14 March 2000; accepted 10 June 2001
Abstract
A series of tri¯uoromethyl substituted spiro [3H-indole-3,30-[3H-1,2,4]triazoles]-2,1H)-ones have been synthesized in 85±90% yield by
one pot environmentally benign microwave induced techniques involving the condensation of 3-arylimino-2H-indol-2-ones ,III) with
thiosemicarbazide ,IV) using montmorillonite as solid support. This 3-arylimino-2H-indol-2-ones ,III) was synthesized in situ by the
reaction of ¯uorinated indole-2,3-diones ,I) and ¯uorinated anilines ,II). The advantages obtained by the use of microwave irradiation were
demonstrated. # 2001 Elsevier Science B.V. All rights reserved.
Keywords: Microwave irradiations; Indole-2,3-diones; 3-Arylimino-2H-indol-2-ones spiro [indole±triazoles]
1. Introduction
dependent cell fusion. Fluorinated triazole derivatives have
also shown remarkable antibacterial, antifungal and herbi-
cidal activities [11±14].
The indole nucleus has been found to be associated with
diverse biological activities [1]. Further, if the indole-3-
carbon is in the form of a spiro atom, the compounds exhibit
enhanced biological activities [2,3]. Along with spiro indo-
lines, the great importance of triazole derivatives in the ®eld
of biochemistry [4±6] and pesticidal chemistry has also
attracted the attention of chemist and biochemists for a long
time.
Fluorine incorporation in heterocycles is known to affect
the course of the reaction besides in¯uencing the biological
activity [7]. It has been observed that introduction of a
¯uorine atom or CF3 group to heterocycles may act as a
pharmacophore, enhancing pharmacological properties of
the compounds as compared to their non-¯uorinated analo-
gues [8]. Incorporation of a tri¯uoromethyl substituent also
increases the phytotoxicity along with selectivity and arenes
bearing a tri¯uoromethyl substituent comprise the largest
sub-group of commercially promising pesticides and herbi-
cides. Fluorinated 3-phenyl imino indol-2,3H)-ones have
been reported to possess remarkable antimicrobial activities
against Mycobacterium paratuberculosis, E. coli, Salmo-
nella typhi and Aspergillus niger [9]. Tri¯uoromethyl sub-
stitutions in the aromatic ring are favorable for antimicrobial
activity [10]. The derivatives also represent a novel class of
anti HIV agents which appear to act by inhibiting virus
In spiro indoles also, ¯uorine incorporation alters bioac-
tivity and the chemistry of ¯uorinated spiro indole deriva-
tives has been of considerable interest due to the variation in
the physico-chemical properties of these derivatives as
compared to their non-¯uorinated analogues [2,15,16].
In spite of the immense biological activities displayed by
¯uorinated 3-arylimino-2H-indol-2-ones and ¯uorinated
triazol derivatives, no attention has been paid so far to
the synthesis of ¯uorinated spiro [3H-indole-3,30-[3H-
1,2,4]triazoles]-2,1H)-ones. Recently, we have reported a
one pot synthesis of novel spiro [indole-1,2,4-triazoles] for
the ®rst time [17].
Further utilization of `microwave-oven induced reaction
enhancement' ,MORE) chemistry for highly accelerated
synthesis of divergent types of heterocycles is of current
interest due to the rapid heating associated with microwave
technology [18].
However, greater interest has been focused recently on
``dry media'' synthesis using inorganic solid supports under
microwave irradiation. The coupling of a microwave heating
mode with the use of a mineral solid support has allowed the
synthesis of several organic compounds with higher selec-
tivity, yield and purity compared to traditional methods [19].
Formation of ¯uoro compounds by usual methods is tedious
and expensive, now that the potential of microwave chem-
istry can be utilized in the synthesis of these compounds.
* Corresponding author. Tel.: ‡91-141-520301; fax: ‡91-141-523637.
0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 , 0 1 ) 0 0 4 2 9 - 8

62
A. Dandia et al. / Journal of Fluorine Chemistry 111 /2001) 61±67
Table 1
Physical and analytical data VI,a±e)a
Compound
number
X
Y
Reaction
Melting point
Yield
Molecular
formula
Elemental analysis ,calculated/found) ,%)
time ,min)
,8C)
,%)
C
N
VI,a)
VI,b)
VI,c)
VI,d)
VI,e)
H
2CF3
3CF3
3CF3
3CF3
3CF3
6 ‡ 2
6 ‡ 2
2 ‡ 2
7 ‡ 2
5 ‡ 2
250
280
85.6
84.8
80.7
80.0
82.0
C18H14F3N5O2
C18H13ClF3N5O2
C18H13F4N5O2
C18H13F3N6O4
C19H16F3N5O2
55.52/55.45
51.00/51.22
53.07/53.19
49.76/49.85
56.57/56.68
17.99/17.86
16.52/16.70
17.19/17.85
19.35/19.45
17.36/17.48
5Cl
5F
200
7NO2
5CH3
265±266 ,d)
180
a VI,a±e) were synthesized at 360 W using ethanol as energy transfer medium, e.g. VI,a), 6 ‡ 2 indicates, first irradiation for 6 min gives compound III
,detected by TLC) and then further irradiation after adding thiosemicarbazide for 2 min yield VI,a).
Table 2
Comparative results of the synthesis of V/VI using ethanol/ethanol with acetic acid ,method a) and montmorillonite/montmorillonite with acetic acid ,method
b) under microwave irradiationa
Compound X
Y
Classical method
Microwave method
a
Melting
Molecular
Elemental analysis
number
point ,8C) formula
,calculated/found) ,%)
Time ,h)
Yield ,%)
b
C
N
,first/second ,first/second
step)
step)
Time
Yieldb Time
Yieldb
,min)
,%)
,min)
,%)
V,a)
V,b)
VI,f)
VI,g)
5Cl
2CF3
4/2
±
76/32
±
6 ‡ 2 65.2
6 ‡ 1 60.2
6 ‡ 2 75.6
6 ‡ 2 78.0
5 ‡ 2
4 ‡ 2
5 ‡ 1
93.6
95.2
94.7
275 ,d)
285
C16H11ClF3N5O
C16H11F3N6O3
50.32/50.70 18.34/18.20
48.97/48.85 21.42/21.50
7NO2 2CF3
5Cl
2CF3
2/5
±
77/60
±
290
C18H13ClF3N5O2 51.00/51.30 16.52/16.24
C18H13F3N6O4 49.76/49.84 19.35/19.40
7NO2 2CF3
4 min ‡ 4 s 92.8
260 ,d)
a Irradiations were carried out at 360 and 480 W in methods a and b, respectively; montmorillonite 20 wt.%.
b Final isolated yield from single step.
Hence, in continuation to our earlier interest on the
synthesis of ¯uorine containing bio-dynamic heterocycles
[20±26] using non-conventional method of organic synth-
esis, we report here the one pot synthesis of ¯uorinated spiro
[3H-indole-3,30-[3H-1,2,4-triazoles]-2,1H)-ones, using ,a)
ethanol as energy transfer medium and ,b) montmorillonite
as inorganic solid support under microwave irradiation.
Further, the amount of montmorillonite also plays a very
important role as reactions occur rapidly along with
enhanced yields when an optimum quantity ,20 wt.%) of
montmorillonite is used. However, excess of solid support
,50 wt.%) reduces the yield with an increase in reaction
time. The results are summarized in Tables 1 and 2. The
possible existence of a speci®c microwave effect ,non-
thermal) has been studied by carrying out the reactions
using a preheated oil bath under similar condition ,same
2. Results and discussion
Table 3
The condensation of ¯uorinated indole-2,3-diones ,I)
with ¯uorinated anilines ,II) yielded ¯uorine containing
3-arylimino-2H-indol-2-ones ,III) which in situ were cyclo-
condensed with thiosemicarbazide ,IV) in the presence/
absence of acetic acid to give VI/V, respectively.
Reaction occurs rapidly in both cases, i.e. with/without
acetic acid with the evolution of H2Sgas [27], the presence
of which is detected by its characteristic odor and rendering
a ®lter paper wet with lead acetate, black during the progress
of the reaction.
We have extensively studied the title reaction varying
different parameters, viz. medium, solid support, power
level, etc. Montmorillonite ef®ciently catalyzed the reaction
giving maximum yield ,94±98%) with shortest period and
easiest work up.
Comparative results obtained in the synthesis of V,a) and VI,f) using
conventional synthesis ,a) and microwave method ,b) using ethanol as the
energy transfer mediuma
Compound
number
Method
Reaction
time
Temperature
Yield
,b) ,8C)
,%)
V,a)
b
a
a
a
6 ‡ 2
6 ‡ 2
78
78
78
78
65.2
Nil
15 ‡ 2
15 ‡ 8
Traces
39
VI,f)
b
a
a
a
6 ‡ 2
78
78
78
78
75.6
Nil
6 ‡ 2
15 ‡ 2
15 ‡ 6
Traces
42.8
a Final temperature ,b) is measured by immersing a glass thermometer
in the reaction mixture at the end of exposure to microwave irradiation.

A. Dandia et al. / Journal of Fluorine Chemistry 111 /2001) 61±67
63
Scheme 1.
time, temperature and vessel) as carried out during micro-
wave experiments. Under these conditions it has been
observed that poor yields are obtained using the preheated
oil bath which indicates that the effect of microwave irradia-
tion is not purely thermal ,Table 3).
The present new method of the formation of V and VI
under microwave irradiation offers several advantages
over traditional methods faster reaction rates, fewer
byproducts ,TLC), smaller amounts of solvent and simple,
less expensive equipment while the classical method of
formation of spiro [indole-4H-[1,2,3]triazoles] involves a
long tedious process ,more than 21 days) in two steps [28]
with the requirement of puri®cation and crystallization,
while the present method involves the synthesis of spiro
derivatives in only 10±15 min without any need of further
puri®cation.

Table 4
Spectroscopic data
Compound
number
IR ,cmÀ1
)
1H NMR ,d, ppm)
19F NMR ,d, ppm)
À63.249 ,s, CF3)
V,a)
V,b)
VI,a)
3400±3265 ,NH2 and NH), 1743 ,C=O), 1625 ,C=N), 1465, 1051, 920
6.91 ,dd, 1H, J1 ˆ 8:4, J2 ˆ 7:6, 500-H), 6.99 ,dd, 1H, J1 ˆ 8:9, J2 ˆ 2:4, 6H),
7.07±7.58 ,m, 2H, 600-H, 7H), 7.66 ,d, 1H, J ˆ 2:4, 4H), 7.77 ,dd, 1H, J1 ˆ 8:4,
J2 ˆ 7:5, 400-H), 7.91 ,d, 1H, J ˆ 7:5, 300-H), 8.38 ,br, 1H, NH of triazole) 8.85
,br, 2H, NH2), 11.09 ,br, 1H, indole NH)
6.86±7.15 ,m, 3H, 500-H, 5H, 600-H), 7.24 ,dd, 1H, J1 ˆ 8.3, J2 ˆ 1.2, 60-H), 7.47
,dd, 1H, J1 ˆ 8.9, J2 ˆ 1.2, 4H), 7.71 ,dd, 1H, J1 ˆ 8.4, J2 ˆ 7.6, 400-H), 7.93
,d, 1H, 7.6, 300-H), 8.39 ,br, 1H, NH of triazo1e), 8.85 ,br, 2H, NH2), 11.09
,br, 1H, indole NH)
2.11 ,s, 3H, NHCOCH3), 6.85 ,dd, 1H, J1 ˆ 8.5, J2 ˆ 7.6, 500-H), 6.90 ,dd, 1H,
J1 ˆ 8.5, J2 ˆ 7.4, 400-H), 7.21 ,td, 1H, J1 ˆ 8.3, J2 ˆ 6.8, J3 ˆ 1.3, 5H), 7.24
,td, 1H, J1 ˆ 8.4, J2 ˆ 6.8, J3 ˆ 1.3, 6H), 7.65 ,dd, 1H, J1 ˆ 8.3, J2 ˆ 1.4, 4H), 7.71
,d, 1H, J1 ˆ 7.6, 600-H), 7.82 ,d, 1H, J1 ˆ 7.4 ,300-H), 8.30 ,s, 1H, NH triazole), 8.79
,s, 1H, NHCOCH3), 11.09 ,br, 1H, NH indole)
3400±3300 ,NH2 and NH), 1740 ,C=O), 1620 ,C=N), 1460, 1050, 920
À64.046 ,s, CF3)
À63.021 ,s, CF3)
3300±3068 ,NH), 1730 ,C=O), 1697 ,C=O), 1614 ,C=N), 1465, 1396,
1336, 1269, 1240, 1120, 945, 842, 746
VI,b)
VI,c)
VI,d)
VI,e)
3290±3060 ,NH), 1720 ,C=O), 1695 ,C=O), 1613 ,C=N), 1460, 1390,
1335, 1260, 1240, 1120, 947, 843, 745
2.13 ,s, 3H, NHCOCH3), 6.89 ,dd, 1H, J1 ˆ 8.6, J2 ˆ 7.3, 500-H), 6.96 ,d, 1H,
J ˆ 7.3, 600-H), 7.15 ,dd, 1H, J1 ˆ 9.1, J2 ˆ2.3, 6H), 7.31 ,d, 1H, J ˆ 9.1, 7H),
7.68 ,d, 1H, J ˆ 2.3, 4H), 7.75 ,d, 1H, J ˆ 8.6, 400-H), 7.87 ,s, 1H, 200-H), 8.29
,br, 1H, NH triazole), 8.80 ,br, 1H, NHCOCH3), 11.08 ,br, 1H, NH, indole)
2.09 ,s, 3H, NHCOCH3), 6.88 ,dd, 1H, J1 ˆ 8.7, J2 ˆ 7.6, 500-H), 6.97 ,d, 1H,
J ˆ 7.6, 600-H), 7.18 ,dd, 1H, J1 ˆ 9.2, J2 ˆ 2.5, 6H), 7.35 ,d, 1H, 9.2, 7H), 7.68
,d, 1H, J ˆ 2.5, 4H), 7.76 ,d, 1H, J ˆ 8.7, 400-H), 7.86 ,s, 1H, 200-H), 8.31 ,br, 1H,
NH triazole), 8.80 ,br, 1H, NHCOCH3), 11.09 ,br, 1H, NH indole)
2.12 ,s, 3H, NHCOCH3), 6.96±7.10 ,m, 3H, 500-H, 5H, 600-H), 7.21 ,dd, 1H, J1 ˆ 8.1,
J2 ˆ 1.1, 6H), 7.40 ,dd, 1H, J1 ˆ 8.9, J2 ˆ 1.1, 4H), 7.78 ,d, IH, J ˆ 8.6, 400-H), 7.89
,s, 1H, 200-H), 8.30 ,br, 1H, NH triazole), 8.78 ,br, 1H, NHCOCH3), 11.09 ,br, 1H,
NH indole)
À63.859 ,s, CF3)
À63.041 ,s, CF3)
À65.142 ,s, CF3)
3305±3060 ,NH), 1725 ,C=O), 1697 ,C=O), 1610 ,C=N), 1455, 1390,
1330, 1260, 1245, 1120, 947, 846, 745
3300±3065 ,NH), 1728 ,C=O), 1698 ,C=O), 1612 ,C=N), 1465, 1385,
1330, 1260, 1240, 1120, 947, 840
3285±3060 ,NH), 1730 ,C=O), 1690 ,C=O), 1610 ,C=N), 1460, 1390,
2.09 ,s, 3H, NHCOCH3), 2.27 ,s, 3H, CH3), 6.89 ,dd, 1H, J1 ˆ 8.8, J2 ˆ 7.6,
500-H), 6.92 ,dd, 1H, J1 ˆ 8.5, J2 ˆ 1.7, 6H), 7.05 ,d, 1H, J ˆ 7.6, 600-H), 7.13
,d, 1H, J1 ˆ 1.7, 4H), 7.55 ,d, 1H, J ˆ 8.5, 7H), 7.76 ,d, 1H, J1 ˆ 8.8, 400-H),
7.84 ,s, 1H, 200-H), 8.32 ,br, 1H, NH triazole), 8.81 ,br, 1H, NHCOCH3), 11.10
,br, 1H, NH indole)
À62.698 ,s, CF3),
À119.82 ,s, 5-F)
1250, 1230, 1120, 45, 840, 740
VI,f)
VI,g)
3310±3100 ,NH), 1725 ,C=O), 1695 ,C=O), 1610 ,C=N), 1465, 1340,
2.11 ,s, 3H, NHCOCH3), 6.90 ,dd, 1H, J1 ˆ 8.4, J2 ˆ 7.6), 6.99 ,dd, 1H, J1 ˆ 8.9,
J2 ˆ 2.4, 6H), 7.07±7.58 ,m, 2H, 600-H, 7H) 7.66 ,d, 1H, J ˆ 2.4, 4H), 7.77
,dd, 1H, J1 ˆ 8.4, J2 ˆ 7.5, 400-H), 7.91 ,d, 1H, J ˆ 7.5, 300-H), 8.31 ,br, 1H,
NH triazole), 8.79 ,br, 1H, NHCOCH3), 11.11 ,br, 1H, NH indole)
2.13 ,s, 3H, NHCOCH3), 6.86±7.15 ,m, 3H, 500-H, 5H, 600-H), 7.24 ,dd, 1H, J1 ˆ 8.3,
J2 ˆ 1.2, 6H), 7.47 ,dd, 1H, J1 ˆ 8.9, J2 ˆ 1.2), 7.71 ,dd, 1H, J1 ˆ 8.4, J2 ˆ 7.6,
400-H), 7.93 ,d, 1H, J1 ˆ 7.6, 300-H), 8.33 ,br, 1H, NH triazole), 8.80 ,br, 1H,
NHCOCH3), 11.12 ,br, 1H, NH indole)
À63.928 ,s, CF3)
À64.729 ,s, CF3)
1250, 1120, 945, 840, 740
3305±3068 ,NH), 1730 ,C=O), 1695 ,C=O), 1614 ,C=N), 1460, 1390,
1330, 1265, 1240, 1120, 945, 842, 746

A. Dandia et al. / Journal of Fluorine Chemistry 111 /2001) 61±67
65
Table 5
13C NMR spectroscopic data
Compound number
13C NMR ,d, ppm)
V,a)
164.02 ,C=O), 152.08 ,N±C=N), 125.55 ,CF3), 111.62 ,spiro carbon), 148.28, 147.51, 146.31, 142.10, 132.34, 130.39, 123.01,
120.35, 119.39, 118.06, 117.22, 116.51 ,12 aromatic ring carbons)
V,b)
165.12 ,C=O), 152.76 ,N±C=N), 126.05 ,CF3), 112.16 ,spiro carbon), 150.01, 149.21, 147.98, 144.23, 140.05, 131.12, 130.62,
124.77, 121.03, 118.92, 117.56, 115.99 ,12 aromatic ring carbons)
VI,a)
VI,b)
VI,c)
VI,d)
VI,e)
VI,f)
VI,g)
162.05 ,C=O), 179.18 ,C=O), 152.28 ,N±C=N), 126.11 ,CF3), 110.78 ,spiro carbon), 148.29, 147.55, 146.38, 142.11, 132.36,
130.38, 123.12, 120.38, 119.28, 118.10, 117.21, 116.52 ,12 aromatic ring carbons), 38.62 ,CH3)
162.79 ,C=O), 179.64 ,C=O), 153.01 ,N±C=N), 125.03 ,CF3), 111.09 ,spiro carbon), 148.66, 147.11, 146.56, 143.02, 131.98,
130.65, 123.52, 121.36, 119.51, 118.96, 117.34, 116.92 ,12 aromatic ring carbons), 38.65 ,CH3)
163.11 ,C=O), 179.98 ,C=O), 153.02 ,N±C=N), 125.76 ,CF3), 111.48 ,spiro carbon), 148.35, 147.66, 145.87, 146.21, 133.35,
131.27, 125.14, 122.26, 120.02, 118.92, 117.25, 116.88 ,12 aromatic ring carbons), 39.01 ,CH3)
163.85 ,C=O), 180.12 ,C=O), 153.21 ,N±C=N), 126.36 ,CF3), 111.52 ,spiro carbon), 148.95, 147.68, 146.82, 143.15, 133.02,
130.78, 123.44, 121.05, 119.88, 119.01, 117.56, 116.72 ,12 aromatic ring carbons), 39.05 ,CH3)
161.98 ,C=O), 178.01 ,C=O), 152.11 ,N±C=N), 126.31 ,CF3), 110.56 ,spiro carbon), 148.24, 147.51, 147.02, 142.22, 132.06,
132.99, 122.87, 121.06, 119.98, 118.21, 117.15, 116.39 ,12 aromatic ring carbons), 38.34 ,CH3)
162.68 ,C=O), 179.78 ,C=O), 153.11 ,N±C=N), 125.44 ,CF3), 111.15 ,spiro carbon), 148.01, 147.23, 146.77, 143.56, 132.01,
130.48, 123.69, 121.91, 119.15, 118.71, 117.21, 116.98 ,12 aromatic ring carbons), 38.45 ,CH3)
163.89 ,C=O), 179.95 ,C=O), 153.29 ,N±C=N), 126.96 ,CF3), 111.41 ,spiro carbon), 148.82, 147.99, 146.59, 143.38, 132.98,
131.01, 123.86, 120.97, 119.65, 118.03, 117.51, 116.81 ,12 aromatic ring carbons), 38.86 ,CH3)
Formation of spiro compounds ,V or VI) may be ratio-
nalized by the mechanism proposed in Scheme 1. The
structures of synthesized compounds have been con®rmed
on the basis of analytical and spectral studies as given in
Tables 1±5. On the basis of spectral data, compounds
obtained in the presence and absence of acetic acid have
been identi®ed as 50-,N-acetyl amino)-40-aryl-20,40-dihydro-
spiro[3H-indole-3,30-[3H-1,2,4]triazoles]-2,1H)-ones ,VI)
and 50-amino-40-aryl-20,40-dihydro-spiro[3H-indole-3,30-
[3H-1,2,4]-triazoles]-2,1H)-ones ,V).
Classical method: V,a) has been synthesized by classical
methods in two steps.
1. Synthesis of intermediate anil ,III,a)): a mixture of 5-
chloroindole-2,3-dione ,I) ,0.005 mol) and 2-trifluor-
omethyl aniline ,II) ,0.005 mol) was refluxed in dry
toluene ,15 ml) for 4 h. Crystals separated out on
cooling were dried and recrystallized from ethanol [29].
IIIꢀa† : X ˆ 5Cl;
Y ˆ 2CF3;
mp ˆ 167ꢁC;
yield ˆ 76% ꢀmp ˆ 167ꢁC; yield ˆ 66:5%†
2. Synthesis of spiro product: a mixture of III,a)
,0.005 mol) and thiosemicarbazide ,IV) ,0.005 mol) in
ethanol ,20 ml) was refluxed for 2 h. Reaction occurs
with the evolution of H2S. The solid obtained on cooling
was crystallized from ethanol.
3. Experimental
Melting points were determined in open glass capillaries
and were uncorrected. IR spectra were recorded on a Perkin-
Elmer ,model 577) in KBr pellets. 1H NMR and 13C NMR
were recorded on model Bruker MW-200, using CDCl3 as
solvent at 200.13 and 50.3 MHz, respectively. 19F NMR was
recorded on a Jeol ,model FX-90Q) using CDCl3 at
84.25 MHz. TMSwas used as internal reference for 1H
NMR and 13C NMR and hexa¯uorobenzene as external
reference for 19F NMR. All compounds were found homo-
geneous on TLC in various solvent systems.
The induced microwave convection system used has
microwaves generated at a frequency of 2450 MHz. The
oven has a range of microwave output energy of 1200 W.
Montmorillonite K10 and ¯uorinated anilines were
Aldrich products and were used as received.
Vꢀa† : mp ˆ 275ꢁC ꢀd†;
yield ˆ 32%
Microwave irradiation method: V,a) has been synthesized
in one step without isolation of the intermediate anil by two
different methods under microwave irradiation.
,a) An equimolar mixture of I and II ,0.001 mol) in the
minimum quantity of ethanol required to form a slurry was
irradiated inside a microwave oven at 360 W. After every
2 min an interval of 1 min is allowed, to avoid excessive
evaporation of solvent, until the completion of the reaction
,6 min). As the reactants disappeared ,TLC), thiosemicarba-
zide ,IV) ,0.001 mol) was added to the reaction mixture
which was again irradiated for 2 min. On cooling crystals
separated out which were dried and found to be pure by
TLC.
3.1. 50-Amino-40-/2-trifluoromethyl phenyl)-20,40-dihydro-
5-chloro-spiro[3H-indole-3,30-[3H-1,2,4]triazoles]-2/1H)-
ones /V/a))
Vꢀa† : mp ˆ 275ꢁC ꢀd†;
,b) The compounds I and II ,0.001 mol) were taken in a
borosil beaker ,50 ml) and dissolved in minimum amount
yield ˆ 65:2%
The compound V,a) has been synthesized by ,1) classical
method; and ,2) microwave irradiation method.

66
A. Dandia et al. / Journal of Fluorine Chemistry 111 /2001) 61±67
of methanol and to this solution, montmorillonite K10
,20 wt.%) was added. The mixture was swirled for a while
and the solvent was removed under vacuum to obtain free
¯owing powder and irradiated inside a microwave oven for
5 min at 480 W. As the reactants disappeared ,TLC), IV
,0.001 mol) adsorbed on montmorillinite K10 was added to
the reaction mixture and again irradiated for 2 min. The
product was extracted from methanol and the excess solvent
was evaporated on a roto-evaporator to give a solid which
was found to be pure by TLC.
,b) The compounds I and II ,0.001 mol) were adsorbed on
montmorillonite K10 and irradiated for 5 min at 480 W. As
the reactants disappeared, IV ,0.001 mol) and two to three
drops of acetic acid were adsorbed on clay, added to the
reaction mixture and irradiated for 1 min. The product was
extracted from methanol and the excess solvent was evapo-
rated on a roto-evaporator to give a solid which was found to
be pure by TLC.
VIꢀf† : mp ˆ 290ꢁC;
yield ˆ 94:7%
The remaining compounds listed in Tables 1 and 2 were
synthesized by methods ,a) and ,b) under microwave irra-
diation. Compounds V,a) and VI,f) were synthesized by the
classical method for comparative yield.
Vꢀa† : mp ˆ 275ꢁC ꢀd†;
yield ˆ 93:6%
The identity of the compounds synthesized by various
methods was con®rmed by mixed melting points and spec-
tral studies. The presence of primary NH2 group in com-
pounds V is also con®rmed by the `diazotization test' [30].
The compound V,b) was synthesized by methods ,a) and
,b) under microwave irradiation only because the thermal
method gives poor yield.
The identity of the compounds synthesized by various
methods was established by their mixed mp, IR and 1H NMR
spectral studies.
Acknowledgements
3.2. 50-/N-acetylamino)-40-/2-trifluoromethyl phenyl)-20,40-
dihydro-5-chloro-spiro[3H-indole-3,30-[3H-
1,2,4]triazoles]-2/1H)-ones /VI/f))
Financial assistance from UGC, New Delhi is acknowl-
edged. We are also thankful to Regional Sophisticated
Instrumentation Center, CDRI, Lucknow for elemental ana-
lyses and spectral studies.
Classical method: VI,f) was synthesized by the classical
method in two steps.
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