The reaction of aryl and heteroarylhydrazines with aryl-trifluoromethyl β-diketones

Article abstract of DOI:10.1002/jhet.5570430428

We report the results obtained when five aromatic or heteroaromatic hydrazines react with six β-diketones bearing trifluoromethyl and aryl substituents. Forty-two compounds have been isolated corresponding to two isomeric trifluoromethyl pyrazoles and the

Full text of DOI:10.1002/jhet.5570430428

Jul-Aug 2006
1003
The Reaction of Aryl and Heteroarylhydrazines with Aryl-
Trifluoromethyl ꢀ-Diketones
Shiv P. Singh*, Vinod Kumar and Ranjana Aggarwal
Department of Chemistry, Kurukshetra University, Kurukshetra- 136 119, India
Fax: +1744-238277, 238628. E-mail: shivpsingh@rediffmail.com
Jose Elguero*
Instituto de Quimica Medica, C.S.I.C., Jaun de la Cierva, 3, E-28006 Madrid, Spain
Fax: +3491/5644853. E-mail: iqmbe17@iqm.csic.es
Received October 20, 2005
3
4
5
6
2
3-CF3-pyrazole
1a, R = H
1e, R = OMe
5-CF3,5-OH-
pyrazoline
1d, R = Br
Acid
1b, R = F
1c, R = Cl
1f, R = NO2
z
x
1a, R = H
1e, R = OMe
1d, R = Br
1b, R = F
1c, R = Cl
1f, R = NO2
Neutral
y
4
5
6
2
3
We report the results obtained when five aromatic or heteroaromatic hydrazines react with six ꢀ-
diketones bearing trifluoromethyl and aryl substituents. Forty-two compounds have been isolated
corresponding to two isomeric trifluoromethyl pyrazoles and the intermediate 5-CF3, 5-OH pyrazolines.
The results have provided useful information for establishing the mechanism of the synthesis of pyrazoles.
J. Heterocyclic Chem., 43, 1003 (2006).
Introduction.
Owing to the presence of the trifluoromethyl group, it is
possible to isolate the corresponding 5-hydroxy-5-
trifluoromethyl-ꢀ2 -pyrazolines [7-10] in some cases.
Therefore, three kinds of compounds are expected from
the reaction between 1 and hydrazines 2-6: 3-trifluoro-
methyl-5-arylpyrazoles 7-11, 3-aryl-5-hydroxy-5-trifluoro-
methyl-ꢀ2-pyrazolines 12-16 and their dehydration
products, 3-aryl-5-trifluoromethylpyrazoles 17-21 (Scheme
II). It is interesting to note that pyrazoles 1-11 are related to
compounds important as COX-2 inhibitors or as starting
materials to prepare them [11,12].
The reaction of N-substituted hydrazines with ꢀ–dicar-
bonyl compounds is one of the most useful methods to
prepare N-substituted pyrazoles. The main problem with this
reaction is that it usually yields the isomeric pyrazoles and
the reasons for obtaining them are generally not well
understood [1-6]. It is the aim of the present paper to report
the study of the reaction between a series of 1-aryl-4,4,4-
trifluorobutane-1,3-diones 1, which are differently substi-
tuted on the phenyl ring with five hydrazines: phenyl-
hydrazine 2, p-nitrophenylhydrazine 3, 6-methylbenzo-
thiazol-2-ylhydrazine 4, 6-fluorobenzothi-azol-2-ylhydrazine
5 and 4-methylquinolin-2-ylhydrazine 6 (Scheme I).
Results and Discussion.
Scheme I
The combination of six ꢀ-diketones, five hydrazines
may generate three kinds of pyrazole derivatives
leading to 90 possible compounds. Using two
experimental conditions, neutral and acidic media, and
a selection of reagents, 42 compounds were actually
isolated (Table 1). Out of these compounds, 7a, 7b, 7c,
7d, 7e, 7f, 8a and 8b have been previously reported
(see Experimental Part). The second reaction of Table
1 corresponds to the dehydration of the 5-hydroxy-5-
NH2
S
NH2
N
NH2
NH2
HN
HN
R
HN
HN
CF3
N
H3C
O
O
NO2
1
2
R'
4, R' = CH3
3
6
a, R = H; b, R = F; c, R = Cl;
d, R = Br; e, R = OCH3; f, R = NO2
5, R' = F

1004
S. P. Singh, V. Kumar and R. Aggarwal
Vol 43
results in two hydrazones and two enehydrazines: xA,
yA, yB and xB. These compounds neither do necessarily
represent the reality (the compounds are probably
hydrated) nor is the following step the formation of
hydroxypyrazolines but most probably dihydroxy-
pyrazolidine is involved as an intermediate [7,9,13,14].
What is more important is that these four possibilities
ended in only two 5-hydroxy-ꢀ2-pyrazolines which are
precursors of two types of pyrazoles. A plausible
explanation why the presence of a CF3 group at the 5-
position stabilizes the two 5-hydroxy-ꢀ2-pyrazolines (in
the present case 12-16) has been proposed previously
[3,7,15].
Scheme II
F3C
F3C
F3C
F3C
N
N
N
N
C6H4-R
C6H4-R
C6H4-R
C6H4-R
N
N
N
N
N
S
N
H3C
7
NO2
R'
11
8
9, R' =CH3
10, R' = F
R-C6H4
R-C6H4
N
R-C6H4
N
R-C6H4
N
OH
CF3
OH
CF3
OH
CF3
OH
CF3
N
N
N
N
N
We will now discuss the role of R and R1 in neutral and
acidic conditions on the orientation of the reaction. It is
evident that R and R1 act only on the molecule that bears
them, i.e., on the ꢁ-diketones and the hydrazines,
respectively. This point is of fundamental importance,
and thus, changes in the final products associated with R
must be assigned to differences in the reactivity of 1
while those associated with R1 must be due to
modifications in the relative reactivity of the NH and the
NH2 of 2.
N
S
N
H3C
12
NO2
R'
16
13
14, R' =CH3
15, R' = F
R-C6H4
R-C6H4
N
R-C6H4
N
R-C6H4
N
N
N
CF3
CF3
CF3
CF3
N
N
N
N
S
N
H3C
In neutral conditions and in what concerns the
hydrazine, to explain the results of Table 1, it must be
assumed that the reactivity of phenylhydrazine (2) is
different than that of the other hydrazines. Even if for the
NO2
17
R'
21
18
19, R' =CH3
20, R' = F
Table 1
Products obtained in the reactions between 1 and 2-6.
Hydrazine
ꢁ-diketone
Conditions
Products
2nd Reaction
2
2
2
3
1a-1e
1f
1a-1f
1a-1f
Neutral
Neutral
Acid
7a-7e
70% 7f / 30% 12f
7a-7f
19-38% (8a-8f) /
62-81% (13a-13f)
8a-8f
14c & 14f
9c & 9f
15c-15d
10c-10d
12f ꢀ 17f
Neutral
13a-13f ꢀ 18a-18f
14c & 14f ꢀ 19c & 19f
15c-15d ꢀ 20c-20d
16c ꢀ 21c
3
4
4
5
5
6
6
1a-1f
1c&1f
1c&1f
1c-1d
1c-1d
1c-1d
1c
Acid
Neutral
Acid
Neutral
Acid
Neutral
Acid
16c-16d
54% 11c / 38% 16c
with ~8% 21c
trifluoromethyl-ꢀ2-pyrazolines into the corresponding 5-
trifluoromethyl pyrazoles. In the case of the reaction
between 3 and all six ꢁ-diketones in neutral conditions,
the relative proportions of 3-trifluoromethylpyrazoles and
5-hydroxypyrazolines are reported in Table 2.
The results of Tables 1 and 2 can be interpreted using
Scheme III. Both, the ꢁ-diketone (electrophilic centers x
and y) and the monosubstituted hydrazine (nucleophilic
centers A and B) have two possibilities for reacting. This
five hydrazines the most basic nitrogen should be the
NH2, the only reasonable hypothesis is that the reactivity
changes from the NH for 2 to the NH2 for 4-6 [p-
nitrophenylhydrazine (3) occupying an intermediate
position]. The opposite assumption is meaningless, thus,
the data of Table 1 correspond to 2 reacting by the yB
way, 3 by the yB + yA ways and 4-6 by yA one. Note that
only the reactivity of the hydrazine changes, A or B,
while apparently the ꢁ-diketone always reacts by the

Jul-Aug 2006
The Reaction of Aryl and Heteroarylhydrazines with Aryl-Trifluoromethyl ꢀ-Diketones
1005
Table 2
Ratios determined by 1H NMR spectroscopy from the crude reaction mixtures obtained by treating
the p-nitrophenylhydrazine (3) with ꢀ–diketones (1a-f).
Compound
% (8)
% (13)
Ln ratio 8/13
F
a, R = H
b, R = F
c, R = Cl
d, R = Br
e, R = OCH3
f, R = NO2
38
27
24
25
30
19
62
73
76
75
70
81
–0.490
–0.995
–1.153
–1.099
–0.847
–1.450
0.000
0.708
0.690
0.727
0.413
1.109
Scheme III
A
R
A
• •
B
• •
B
NH2
•
•
NH2
NH3
•
•
HN
R1
y
CF3
H2N
R1
2H+
HN
R1
x
+
O
O
(3-5)H+
1a-1f
2-6
R
R
R
R
CF3
CF3
CF3
CF3
O
N
N
O
N
O
O
N
HN
R1
R1
NH2
NH
R1
H2N
R1
xB
yA
xA
yB
R
R
F3C
F3C
fast
OH
N
N
R1
slow
N
R
N
R1
OH
R
N
N
CF3
CF3
N
R1
Non-isolable
5-hydroxy-
pyrazoline
N
7-11
R1
12-16
17-21
COAr (y), although probably the COCF3 is more
electrophilic. This apparent inconsistency is probably
related to ꢀ-diketones reacting in the enol form.
most nucleophilic nitrogen atom would be protonated
[19]. Here again, probably the five hydrazines protonate
in both nitrogen atoms (structures I and II) the equilibrium
being shifted towards II but less in 2 than in the other
hydrazines. Thus, the change in reactivity between 2 and
the other hydrazines could correspond to 2 using the A
lone pair and the other the B lone pair.
In the case of the reaction of 3 with different ꢀ-
diketones, the effect of the nitro group at the para position
of the y carbonyl group (compound 1f) lowers its
reactivity and the proportions of 8 and 13 changes
accordingly. The lowering effect of the nitro group on the
rates is related to the dehydration step [16,17]. This
indicates a change in the y/x ratio. Therefore, the data of
Table 2 cannot be explained by a simple change in the
yB/yA ratio and imposes to assume that x ways are
implicated. However, as it is difficult to decide if it is xA
or xB ways, we have assumed that it is the xB.
xA
yB
A
B
R1 NH2 NH2
R1 NH2 NH3
II
I
The yB way decreases and the xB one increases when
the electron-withdrawing ability of R increases. Using as
descriptor the Swain and Lupton F (field effect [18]) the
data of Table 2 are relatively well correlated:
Since in most cases only 3-trifluoromethyl derivatives 7-10
are isolated, the phenylhydrazinium cation could react by the
xA way and the others cations by the yB one. But this
implies a change in the reactivity of the ꢀ-diketones, which is
not reasonable. Hence it is more probable that in all cases the
yB way is followed (structure II). With the quinolylhydrazine
6 a mixture in nearly equal proportions of 11 and of (16+21)
is obtained. Probably, the last compounds result from a 6H+
species protonated in the quinoline ring (yA).
Ln ratio = – (0.49±0.05) – (0.86±0.08) * F, n = 6, r2 = 0.97
In acid medium, hydrazines should be protonated and a
reverse of reactivity is expected if one assumes that the

1006
S. P. Singh, V. Kumar and R. Aggarwal
Vol 43
3
4
5
6
2
EXPERIMENTAL
3-CF3-pyrazole
1a, R = H
1e, R = OMe
1d, R = Br
1b, R = F
1c, R = Cl
1f, R = NO2
5-CF3,5-OH-
pyrazoline
Melting points were determined in open capillaries in an
electrical apparatus and are uncorrected. The ir spectra (in
potassium bromide) of all the compounds were recorded on a
Acid
1
Buck Scientific IR M500 instrument and H nmr and 13C nmr
spectra were run on a Brucker instrument at 300 MHz and 75
MHz, respectively. 19F nmr spectra were run on DRX 300 and
DPX 400 at 282 and 376 MHz, respectively, using CDCl3 as
solvent. The internal standard for 19F spectra was CFCl3, setting
the CFCl3 signal at ꢀ 0.00 ppm. 13C and 19F nmr data for the
compounds are presented in Tables 3, 4, 5 and 6, respectively.
High resolution mass spectra (hrms) were measured in EI mode
on a Kratos MS-50 spectrometer.
z
x
1a, R = H
1e, R = OMe
1d, R = Br
1b, R = F
1c, R = Cl
1f, R = NO2
Neutral
y
4
5
6
2
3
Fluorinated ꢀ-diketones (1a-f) and heteroarylhydazines (4, 5,
6) are well-known compounds often described in the literature:
1a (CAS 326-06-7) is a commercial product (Alfa), the others
1b (CAS 582-65-0), 1c (CAS 18931-60-7), 1d (CAS 18931-61-
8), 1e (CAS 15191-68-1), 1f (CAS 35999-53-2) were
synthesized according to literature procedures [12,20,21].
Phenylhydrazine (2) and p-nitrophenylhydrazine (3) are
commercially available, 4 (CAS 20174-69-0), 5 (CAS 78364-
55-3) and 6 (21703-52-6) were prepared according to literature
procedures [22,23].
Figure 1
Within the experimental space we have plotted
(represented in three dimensions in Fig. 1) the three axis
corresponding to:
i) Vertical or z-axis: on going from neutral to acidic
conditions, the proportion of 3-trifluoromethyl-pyrazoles
always increases (if there are not the 100% of the
mixture).
Reactions Performed in Neutral Medium (EtOH).
Synthesis of 1-Phenyl-5-aryl-3-trifluoromethylpyrazoles (7a-e).
ii) Horizontal or y-axis: the more the electron-
withdrawing effect of the substituent on the hydrazine
(from 2 to 6) the percentage of hydroxypyrazoline
increases.
1-Phenyl-5-(p-chlorophenyl)-3-trifluoromethylpyrazole (7c).
An ethanolic solution (20 ml) of 1-(p-chlorophenyl)-4,4,4-
trifluorobutane-1,3-dione 1c (1.25 g,
5
mmoles) and
phenylhydrazine 2 (0.54 g, 5 mmoles) was refluxed for 3 hours.
The excess of solvent was evaporated and on cooling, a solid
appeared which was recrystallized from ethanol, mp 80° (Lit
[12] yellow syrup), yield 72%; 1H nmr (CDCl3): ꢀ 6.75 (s, 1H, 4-
H), 7.15-7.48 (m, 9H, Ph'-H & p-ClPh''-H); ms: m/z 322 (M+)
324 (M++2) in the ratio showing typical chlorine isotope profile
(3:1).
iii) Tilted or x-axis: the more electron-withdrawing the
substituent on the phenyl ring of the ꢀ-diketone (classified
according to Swain and Lupton field parameter, from 1a
to 1f) the larger the proportion of hydroxypyrazoline.
Conclusions.
Anal. Calcd. for C16H10ClF3N2: C, 59.53; H, 3.10; N, 8.68.
Found: C, 59.32; H, 3.01; N, 8.69.
Other pyrazoles (7a, 7b, 7d, 7e, 7f) were prepared similarly.
We have reported in this paper a large collection of
pyrazole derivatives bearing a trifluoromethyl group. The
combined use of different hydrazines, different ꢀ-
diketones and two experimental conditions (neutral and
acid-catalyzed) has allowed to propose a mechanism that
although explaining the results is not grounded on kinetics
data. For this reason, it should be considered as tentative
accepting that other possibilities remain open.
1,5-Diphenyl-3-trifluoromethylpyrazole (7a).
The compound had mp 79º (Lit [7] 80º, Lit [11] 95º); 1H nmr
(CDCl3): ꢀ 6.75 (s, 1H, 4-H), 7.23-7.34 (m, 10 H, Ph'-H & Ph"-
H).
Anal. Calcd. for C16H11F3N2: C, 66.66; H, 3.82; N, 9.72.
Found: C, 66.43; H, 4.02; N, 9.55.
F3C
F3C
3
F3C
F3C
3
3
3
4
4
4
4
2"
2"
2"
2"
3"
4"
3"
4"
3"
4"
3"
4"
2 N
2 N
1"
6"
1"
6"
1"
6"
1"
6"
2 N
2 N
1
N
1
N
1
N
1
N
5
5
5
5
R
R
R
R
2'
1'
1'
2'
5"
5"
5"
5"
3'
4'
6'
5'
2'
3'
6'
5'
2'
3'
1'
1'
3'
N
S
N
3a'
4'
8a'
7a'
8'
7'
H3C
4a'
5'
4'
4'
7'
NO2
5'
6'
116'
9-10
R'
7
8

Jul-Aug 2006
The Reaction of Aryl and Heteroarylhydrazines with Aryl-Trifluoromethyl ꢀ-Diketones
1007
Table 3
13C NMR data for 3-trifluoromethylpyrazoles (ppm).
Compds. 7 c
7 d
8 b
8 c
8 d
8 e
8 f
9 c
9f
10c
10d
11 c
C-3
143.32
143.34
144.56
144.65
144.67
143.94
144.43
144.90
145.08
144.50
144.80
(q, 2JC-F
39 Hz)
143.90
(q, JC-F
= 39 Hz)
2
2
2
2
2
2
2
2
2
2
(q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, 2JC-F
=
=
= 38.25 = 38.25
Hz)
=
Hz)
39 = 38.25 = 38.25 = 38.25
=
Hz)
39
=
Hz)
39 = 39.75 39 Hz)
Hz)
Hz)
Hz)
Hz)
Hz)
C-4
C-5
105.7
143.48
139.0
125.52
129.28
-
105.67
143.50
138.97
125.51
129.29
-
107.0
144.30
143.79
124.69
125.47
-
107.15
143.63
144.06
124.74
125.49
-
107.13
143.63
144.09
124.75
125.49
-
106.51
145.23
144.08
124.57
125.42
-
108.0
145.20
143.23
124.98
125.67
-
108.20
145.35
-
157.91
-
109.06
143.90
-
157.85
-
106.0
143.48
-
158.54
-
108.5
145.45
-
158.57
-
107.10
145.83
-
149.99
116.58
-
C-1ꢁ
C-2ꢁ
C-3ꢁ
C-3ꢁa
C-4ꢁ
148.29
123.10
148.37
122.98
146.94
146.84
128.71
128.72
146.94
147.0
147.0
146.75
147.33
124.72
124.62
144.66
3
3
(d, JC-F (d, JC-F
=9.75Hz
-
=9.75Hz
-
C-4ꢁa
C-5ꢁ
-
-
-
-
-
-
-
-
-
129.59
127.06
129.28
129.29
125.47
125.49
125.49
125.42
125.67
128.19
128.33
115.29
115.27
2
2
(d, JC-F (d, JC-F
=24.75H
z
=24.75H
z
C-6ꢁ
C-7ꢁ
C-7ꢁa
125.52
125.51
124.69
124.74
124.75
124.57
124.98
136.20
121.16
134.08
136.43
121.21
133.90
160.60
160.70
123.75
128.33
-
(d, 1JC-F
=
(d, 1JC-F
=
245.25Hz 245.25Hz
108.10
(d, 2JC-F
27.75 Hz
134.92
(d, 3JC-F
11.0 Hz
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
107.85
(d, 2JC-F
=
=
27.75 Hz
134.85
(d, 3JC-F
11.0 Hz
-
=
=
C-8ꢁ
C-8ꢁa
C-1ꢁꢁ
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
130.19
148.21
127.50
130.42
-
-
127.63
130.04
128.08
130.20
124.75
130.90
126.99
130.13
127.44
130.32
120.75
130.28
134.62
129.76
127.01
131.02
135.00
130.78
126.88
131.09
127.34
131.30
C-2ꢁꢁ, 6ꢁꢁ
3
(d, JC-F
= 9 Hz)
116.5
(d, JC-F
C-3ꢁꢁ, 5ꢁꢁ
C-4ꢁꢁ
129.04
135.24
-
131.99
122.96
-
129.55
136.16
-
132.50
124.38
114.60
160.61
124.43
148.33
128.50
135.89
21.59
124.30
148.12
21.57
128.99
135.82
131.47
124.56
128.85
134.79
2
= 22.5
Hz)
163.40
1
(d, JC-F
=249.7
5 Hz)
-
CH3
CF3
-
-
18.98
121.2
121.17
120.90
120.83
120.81
121.0
120.65
120.65
120.57
120.31
120.39
(q, 1JC-F
120.75
1
1
1
1
1
1
1
1
1
1
(q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, 1JC-F
=
=
(q, JC-F
=
Hz)
267
=
=267.7
5 Hz)
=267.7
5 Hz)
=267.7
5 Hz)
=267.7
5 Hz)
=267.7
5 Hz)
=267.7
5Hz)
=267.7
5Hz)
270.0Hz) 270.0Hz) =267.75
Hz)
267.75
Hz)
OCH3
55.40
Table 4
13 C NMR data for 5-hydroxy-5-trifluoromethylpyrazolines (ppm).
Compds.
12 f
13 a
13 b
13 c
13 d
13 e
13f
14c
14f
15c
15d
16 c
16 d
C-3
C-4
C-5
145.90
43.65
149.56 148.53
148.42 148.41 149.45 148.05 148.47
148.32
43.89
147.11
44.19
147.41
44.15
147.0
44.05
148.47
43.98
44.64
44.72
44.46
44.46
44.85
43.98
44.14
94.12 (q, 93.54
93.62
93.70
93.70
93.39
94.17
92.90 (q, 93.36 (q, 92.85 (q, 92.86 (q, 93.70 (q, 93.70
2JC-F
31.5 Hz)
=
(q, JC- (q, JC-F (q, JC- (q, JC- (q, JC- (q, JC- 2JC-F
=
2JC-F
33.75
Hz)
=
2JC-F
34.5 Hz)
=
2JC-F
34.5 Hz)
=
2JC-F = 33 (q, JC-F
Hz)
2
2
2
2
2
2
2
=
32.25
Hz)
=
Hz)
33
= 33
=
= 33
=
34.5 Hz)
= 33.75
Hz)
F
F
F
F
F
Hz)
33Hz)
Hz)
33Hz)

1008
S. P. Singh, V. Kumar and R. Aggarwal
Vol 43
Table 4 (continued)
Compds.
12 f
13 a
13 b
13 c
13 d
13 e
13f
14c
14f
15c
15d
16 c
16 d
C-1ꢀ
C-2ꢀ
C-3ꢀ
C-3ꢀa
C-4ꢀ
140.10
124.10
126.32
-
140.61 140.72
115.55 115.55
124.86 124.88
140.77 140.86 140.37 141.34
115.62 115.68 115.30 116.08 162.97
124.84 124.87 125.72 125.04
-
-
-
-
-
-
162.47
-
150.21
121.09
163.21
-
152.0
121.26
(d, JC-F (d, JC-F
163.18
-
152.06
155.13
112.77
-
155.10
112.76
-
-
-
-
-
-
-
-
151.58
124.63
147.94 147.85
147.76 147.71 148.0
147.08 121.03
121.27
144.89
144.79
3
3
=9Hz
-
=9Hz
-
C-4ꢀa
C-5ꢀ
-
-
-
-
-
-
-
-
-
124.74
124.74
124.21
126.32
124.86 124.88
124.84 124.87 125.72 125.04 127.54
127.73
114.3 (d, 114.3 (d, 124.20
2JC-F
2JC-F
=24Hz
159.21
(d, 1JC-F
=24Hz
159.0 (d, 123.82
1JC-F
C-6ꢀ
C-7ꢀ
C-7ꢀa
124.10
115.55 115.55
115.62 115.68 115.30 116.08 136.85
135.85
120.43
131.13
123.82
127.13
-
=
=
241.5Hz
107.8 (d, 107.8 (d, 127.13
2JC-F = 27 2JC-F = 27
241.0Hz
-
-
-
-
-
-
-
-
-
-
-
-
-
-
120.18
131.14
Hz
Hz
132.0 (d, 132.1 (d,
3JC-F
-
=
3JC-F
=
10.5Hz
8.25 Hz
C-8ꢀ
C-8ꢀa
C-1ꢀꢀ
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
129.94
149.07
129.55
129.94
149.12
125.79
137.44
130.99 127.36
(d,4JC-F
129.56 129.99 123.65 137.10 128.92
131.75
128.31
128.74
= 3 Hz)
C-2ꢀꢀ, 6ꢀꢀ
C-3ꢀꢀ, 5ꢀꢀ
C-4ꢀꢀ
129.07
126.72
147.87
-
128.84 128.95
129.50 127.40 127.61 126.57 129.18
127.19
124.17
148.32
21.39
129.23
127.79
137.05
-
127.96
131.94
125.42
129.05
127.38
135.99
19.09
127.58
132.0
3
(d, JC-F
=
Hz)
8.25
125.70 115.95
127.22 132.04 114.27 124.10 127.75
135.91 124.27 161.20 147.32 133.25
2
(d, JC-F
= 21.75
Hz)
130.11 163.78
122.25
19.09
1
(d, JC-F
=250.0
Hz)
CH3
CF3
-
-
-
-
-
-
21.35
-
123.0 (q, 123.66 123.74
1JC-F
282.75H
z)
123.72 123.69 123.82 123.60 123.0 (q, 123.4 (q, 123.12
123.11
(q, 1JC-F
123.9 (q, 123.88
1
1
1
1
1
1
1
=
(q, JC- (q, JC-F (q, JC- (q, JC- (q, JC- (q, JC- 1JC-F
1JC-F
=285.2H
z)
(q, 1JC-F
=
=
1JC-F
(q, JC-F
=286.5
Hz)
=
265.5
Hz)
=285.75
Hz)
=285Hz)
285.5Hz) 285.0Hz) =286.5H
z)
F
F
F
F
F
=285.
=267.
=285.
=285.
75 Hz) 75 Hz) 75 Hz) 75 Hz)
55.43
OCH3
Table 5
13 C NMR data for 5-trifluoromethylpyrazoles (ppm).
Compds. 17 f
18a
18 b
18 c
18 d
18 e
18 f
19 c
19 f
20 c
20 d
21 c
C-3
C-4
C-5
149.30
106.8
134.64
152.93
108.00
152.01
107.00
151.82
107.83
134.15 q, 134.16
151.84
107.83
152.76
107.62
150.55
108.42
134.71
148.87
109.56
133.81
(q, 2JC-F
42 Hz)
148.76
110.10
133.80
147.41
109.82
147.42
109.85
147.65
108.92
133.95
134.08
133.80
134.38 (q, 134.34 (q, 134.06 (q,
2
2
2
2
2
2
(q, JC-F (q, JC-F (q, JC-F 2JC-F
=
Hz)
=
39 = 39Hz) = 39Hz) 39.75Hz) = 39Hz) = 39Hz) 39Hz)
(q, JC-F (q, JC-F (q, 2JC-F
=
=
(q,2JC-F
=
2JC-F = 42 JC-F
=
2JC-F =42
Hz)
42 Hz)
Hz)
42.75 Hz)
C-1ꢀ
C-2ꢀ
C-3ꢀ
C-3ꢀa
C-4ꢀ
138.83
125.67
129.30
-
143.96
124.74
125.60
-
143.87
124.76
125.59
-
143.81
124.77
125.63
-
143.79
124.76
125.61
-
144.04
124.72
125.46
-
143.53
124.86
125.83
-
-
-
-
-
-
157.38
-
151.77
123.06
157.32
-
150.50
123.25
157.82
-
152
124.55
(d,
158.82
-
152.15
150.69
114.61
-
126.40
147.49
147.54
147.58
147.58
147.35
147.89
124.56 (d, 146.03
3
3JC-F JC-F
=9.75Hz
-
=9.75Hz
-
C-4ꢀa
-
-
-
-
-
-
-
-
-
127.42

Jul-Aug 2006
The Reaction of Aryl and Heteroarylhydrazines with Aryl-Trifluoromethyl ꢀ-Diketones
1009
Table 5 (continued)
Compds. 17 f
18a
18 b
18 c
18 d
18 e
18 f
19 c
19 f
20 c
20 d
21 c
C-5ꢁ
C-6ꢁ
C-7ꢁ
C-7ꢁa
129.30
125.60
125.59
125.63
125.61
125.46
125.83
128.14
128.34
115.15 (d, 115.22 (d, 126.64
2
2JC-F =24 JC-F
Hz
160.57 (d, 160.71 (d, 123.73
1JC-F 1JC-F
245.25Hz 245.25Hz
=24.75Hz
125.67
124.74
124.76
124.77
124.76
124.72
124.86
135.80
121.06
133.71
136.22
121.16
133.75
=
=
-
-
-
-
-
-
-
-
-
-
-
-
-
-
107.80 (d, 107.83 (d, 129.64
2
2JC-F = 27 JC-F = 27
Hz
Hz
134.31 (d, 134.28 (d,
-
3JC-F
=
3JC-F
=
11.0 Hz
10.50 Hz
C-8ꢁ
C-8ꢁa
C-1ꢁꢁ
-
-
-
-
-
-
-
-
-
-
-
130.10
149.40
127.42
-
-
-
-
-
-
-
-
-
-
-
137.91
130.99
127.25
(d, JC-F
126.51
129.96
123.64
137.10
129.00
136.50
128.79
129.27
4
=
Hz)
3.75
C-2ꢁꢁ, 6ꢁꢁ 129.79
C-3ꢁꢁ, 5ꢁꢁ 124.25
128.97
125.95
129.25
-
127.80
129.21
127.19
135.19
-
127.45
132.50
123.40
127..30
114.35
160.49
126.59
124.35
148.13
129.18
127.38
135.51
21.59
126.81
124.30
148.27
21.63
129.24
127.39
135.70
-
127.66
132.21
123.94
-
129.04
127.21
134.78
19.04
3
(d, JC-F
=
Hz)
8.25
116.00
2
(d, JC-F
= 21.75
Hz)
C-4ꢁꢁ
147.79
163.40
1
(d, JC-F
=247.5
0 Hz)
-
CH3
CF3
-
119.52
119.72
119.55
119.49
119.50
119.66
119.34
119.22
119.21
119.14 (q, 119.21 (q, 120.00 (q,
1
1
1
1
1
1
1
1
1
1
(q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, JC-F (q, JC-F JC-F
=
1JC-F
=
1JC-F
=
=
=
Hz)
285 =267.7
5 Hz)
=267.75
Hz)
=267.75 =267
=267.75
Hz)
=267.75
Hz)
=
267.75Hz) 267.75Hz) 267.75Hz)
267.75
Hz)
Hz)
Hz)
267.75
Hz)
OCH3
55.38
Table 6
19 F NMR values (ppm) for compounds 7-21.
Compds
CF3,
F
Compds
CF3,
F
Compds
CF3,
F
Compds
CF3,
F
7a
7b
7c
7d
7e
7f
-63.1
-63.0, -112
-
8f
9c
-63.2,
-62.7
-62.7
-
-
-
13e
13f
14c
14f
15c
15d
-80.9
-80.9,
-81.4
-81.2
-82.0, -119
-81.7, -119
-
-
-
-
18c
18d
18e
18f
19c
19f
-57.7
-57.7
-57.6
-57.2
-59.6
-59.7
-
-
-
-
-
-
-62.9
-62.9
-62.9
-63.1
-
-
-
-
9f
10c
10d
11c
-63.4, -115
-62.8, -114
-63.0
-77.94
-76.0
-
-
-
8a
8b
8c
8d
8e
-63.0
-
12f
16c
16d
17f
-81.6
-81.6
-57.8
-57.6
-
-
-
-
20c
20d
21c
-
-60.0,
-59.8,
-59.7
-
-115
-62.9
-
13a
13b
13c
13d
-115
-63.1, -110
-81.0, -111
-
-
-
-63.1
-63.1
-
-
-80.8
-80.8
-
-
18a
18b
-57.7, -112
-
-

1010
S. P. Singh, V. Kumar and R. Aggarwal
Vol 43
1-Phenyl-5-(p-fluorophenyl)-3-trifluoromethylpyrazole (7b).
products in a ratio given in the Table 2. Column chroma-
tographic separation using silica gel (100-200 mesh) and
petroleum ether (60-80º) as eluent afforded 8a, mp 87° (Lit [9]
91º), yield 27%; 1H nmr (CDCl3): ꢀ 6.78 (s, 1H, 4-H), 7.22-7.51
(m, 5H, Ph"-H), 7.50 (d, 2H, 2' & 6'-H, J = 9 Hz), 8.23 (d, 2H, 3'
& 5'-H, J = 9 Hz).
The compound had mp 99º (Lit [24] 101º);1H nmr (CDCl3): ꢀ
6.73 (s, 1H, 4-H), 6.99-7.38 (m, 9H, Ph'-H & p-FPh"-H).
Anal. Calcd. For C16H10F4N2: C, 62.75; H, 3.27; N, 9.15.
Found: C, 62.55; H, 3.12; N, 8.99.
1-Phenyl-5-(p-bromophenyl)-3-trifluoromethylpyrazole (7d).
Anal. Calcd. for C16H10F3N3O2: C, 57.66; H, 3.00; N, 12.61.
Found: C, 57.45; H, 2.94; N, 12.44.
1
The compound had mp 94º (Lit [13] 92-94º), yield 74%; H
Further elution of the column with petroleum ether: ethyl
acetate (99:1) afforded the other product (13a). The compound
had mp 198-99º, yield 45%; ir: ꢁ OH 3410 cm-1; 1H nmr (CDCl3
+ DMSO-d6): ꢀ 3.65 (d, 1H, 4-H, J = 18.6 Hz), 3.80 (d, 1H, 4-H,
J = 18.6 Hz), 7.43-7.48 (m, 3H, 3", 4", 5"-H), 7.71-7.75 (m, 4H,
2", 6", 2' & 6'-H), 8.10 (bs, 1H, OH), 8.15 (d, 2H, 3' & 5'-H, J =
9 Hz); ms: m/z 351 (M+).
nmr (CDCl3): ꢀ 6.76 (s, 1H, 4-H), 7.08 (d, 2H, 2"& 6"-H, J = 8.7
Hz.), 7.28-7.41 (m, 5H, Ph'-H), 7.46 (d, 2H, 3"& 5"-H, J = 8.4
Hz.); ms: m/z 366 (M+) and 368 (M++2) in the ratio showing
typical bromine isotope profile (1:1).
Anal. Calcd. for C16H10BrF3N2: C, 52.46; H, 2.73; N, 7.65.
Found: C, 52.34; H, 2.45; N, 7.65.
Anal. Calcd. for C16H12F3N3O3: C, 54.71; H, 3.42; N, 11.96.
Found: C, 54.65; H, 3.29; N, 11.76.
Using similar procedure, compounds 8b-f and 13b-f were also
prepared and purified. The ratio of the two products is given in
the Table 2.
1-Phenyl-5-(p-methoxyphenyl)-3-trifluoromethylpyrazole (7e).
1
Compound was obtained as a liquid (Lit [24] bp 159º); H
nmr (CDCl3): ꢀ 3.78 (s, 3H, OCH3), 6.69 (s, 1H, 4-H), 6.83 (d,
2H, 3"& 5"-H, J = 9 Hz), 7.14 (d, 2H, 2"& 6"-H, J = 9 Hz),
7.29-7.38 (m, 5H, Ph'-H).
Anal. Calcd. for C17H13F3N2O : C, 64.15; H, 4.10; N, 8.80.
Found: C, 63.97; H, 3.97; N, 8.67.
1-(p-Nitrophenyl)-5-(p-fluorophenyl)-3-trifluoromethyl-pyrazole
(8b).
The compound had mp 98º (Lit [11] 111-113º), yield 21%;
1H nmr (CDCl3): ꢀ 6.78 (s, 1H, 4-H), 7.07-7.13 (m, 2H, 3", 5"-
H), 7.21-7.27 (m, 2H, 2", 6"-H), 7.50 (d, 2H, 2' & 6'-H, J = 9
Hz), 8.24 (d, 2H, 3' & 5'-H, J = 9 Hz); ms: m/z 351 (M+).
Anal. Calcd. for C16H9F4N3O2: C, 54.71; H, 2.56; N, 11.96.
Found: C, 54.65; H, 2.40; N, 11.45.
1-Phenyl-5-(p-nitrophenyl)-3-trifluoromethylpyrazole (7f) and
1-Phenyl-3-(p-nitrophenyl)-5-hydroxy-5-trifluoro-methyl-ꢀ2-
pyrazoline (12f).
A
solution of 1-(p-nitrophenyl)-4,4,4-trifluoro-butane-1,3-
dione 1f (1.3 g, 5 mmoles) and phenylhydrazine 2 (0.54 g, 5
mmoles) in ethanol (20 ml) was refluxed for 3 hours. The
reaction was monitored by tlc. The solvent was evaporated
completely. The tlc and 1H nmr of crude reaction mixture
showed the formation of two products in a 70:30 (7f:12f) ratio.
Column chromatographic separation using silica gel (100-200
mesh) with petroleum ether (60-80º) as eluent afforded 7f, mp
1-(p-Nitrophenyl)-3-(p-fluorophenyl)-5-hydroxy-5-trifluoromethyl-
ꢀ2-pyrazoline (13b).
The compound had mp 176º, yield 45%; ir: ꢁ OH 3410 cm-1;
1H nmr (CDCl3 + DMSO-d6): ꢀ 3.63 (d, 1H, 4-H, J = 18.3 Hz),
3.77 (d, 1H, 4-H, J = 18.6 Hz), 7.09-7.16 (m, 2H, 3", 5"-H),
7.69-7.75 (m, 4H, 2", 6", 2’ & 6'-H), 8.06 (bs, 1H, OH), 8.15 (d,
2H, 3' & 5'-H, J = 9 Hz); ms: m/z 369 (M+).
1
104° (Lit [24] 56º), yield 50%; H nmr (CDCl3): ꢀ 6.89 (s, 1H,
4-H), 7.28-7.45 (m, 7H, Ph', 2"& 6"-H), 8.19 (d, 2H, 3"& 5"-H,
J = 8.7 Hz).
Anal. Calcd. for C16H10F3N3O2: C, 57.66; H, 3.00; N, 12.61.
Found: C, 57.33; H, 2.89; N, 12.46.
Anal. Calcd. for C16H11F4N3O3: C, 52.04; H, 2.98; N, 11.38.
Found: C, 52.15; H, 2.87; N, 11.39.
Further elution of column with petroleum ether afforded the
other product (12f). The compound had mp 144º, yield 22%; ir:
1-(p-Nitrophenyl)-5-(p-chlorophenyl)-3-trifluoromethyl-pyrazole
(8c).
1
ꢁ OH 3430 cm-1; H nmr (CDCl3): ꢀ 3.53 (d, 1H, 4-H, J = 18
The compound had mp 124º, yield 19%; 1H nmr (CDCl3): ꢀ 6.80
(s, 1H, 4-H), 7.18 (d, 2H, 2", 6"-H, J = 8.1 Hz), 7.39 (d, 2H, 3", 5"-
H, J = 8.1 Hz), 7.51 (d, 2H, 2' & 6'-H, J = 8.7 Hz), 8.25 (d, 2H, 3'
& 5'-H, J = 8.7 Hz); ms: m/z 367 (M+) and 369 (M++2) in the ratio
showing typical chlorine isotope profile (3:1).
Hz), 3.74 (d, 1H, 4-H, J = 18 Hz), 7.28-7.45 (m, 5H, Ph'-H),
7.82 (d, 2H, 2"& 6"-H, J = 8.7 Hz), 8.11 (bs, 1H, OH), 8.25 (d,
2H, 3" & 5"-H, J = 8.7 Hz); ms: m/z 351 (M+).
Anal. Calcd. for C16H12F3N3O3: C, 54.71; H, 3.42; N, 11.96.
Found: C, 54.95; H, 3.40; N, 11.90.
Anal. Calcd. for C16H9ClF3N3O2: C, 52.24; H, 2.45; N, 11.43.
Found: C, 52.03; H, 2.33; N, 11.66.
Synthesis of 1-(p-Nitrophenyl)-5-aryl-3-trifluoromethyl-pyra-
zoles (8a-f) and 1-(p-Nitrophenyl)-3-aryl-5-hydroxy-5-trifluoro-
methyl-ꢀ2- pyrazolines (13a-f).
1-(p-Nitrophenyl)-3-(p-chlorophenyl)-5-hydroxy-5-trifluoromethyl-
ꢀ2-pyrazoline (13c).
1-(p-Nitrophenyl)-5-phenyl-3-trifluoromethylpyrazole (8a) and
1-(p-nitrophenyl)-3-phenyl-5-hydroxy-5-trifluoromethyl-ꢀ2-
pyrazoline (13a).
The compound had mp 192-94º, yield 58%; ir: ꢁ OH 3410
cm-1; 1H nmr (CDCl3+DMSO-d6): ꢀ 3.60 (d, 1H, 4-H, J =
18.6Hz), 3.77 (d, 1H, 4-H, J = 18.6 Hz), 7.40 (d, 2H, 2", 6"-H, J
= 8.4 Hz), 7.65 (d, 2H, 3", 5"-H, J = 8.4 Hz), 7.70 (d, 2H, 2' &
6'-H, J = 9.3 Hz), 7.79 (bs, 1H, OH), 8.16 (d, 2H, 3' & 5'-H, J =
9.3 Hz); ms: m/z 385 (M+) and 387 (M++2) in the ratio showing
typical chlorine isotope profile (3:1).
An ethanolic solution of 1-phenyl-4,4,4-trifluorobutane-1,3-
dione 1a (1.075 g, 5 mmoles) and p-nitrophenyl-hydrazine 3
(0.77 g, 5 mmoles) in ethanol (20 ml) was refluxed for 8 hours.
The reaction was monitored by tlc. The solvent was evaporated
completely to give the solid reaction product. The tlc and 1H nmr
of the crude reaction mixture showed the formation of two
Anal. Calcd. for C16H11ClF3N3O3: C, 49.81; H, 2.85; N, 10.89.
Found: C, 49.80; H, 2.71; N, 11.05.

Jul-Aug 2006
The Reaction of Aryl and Heteroarylhydrazines with Aryl-Trifluoromethyl ꢀ-Diketones
1011
1-(p-Nitrophenyl)-5-(p-bromophenyl)-3-trifluoromethyl-pyrazole
(8d).
1-(6'-Methylbenzothiazol-2'-yl)-3-(p-chlorophenyl)-5-hydroxy-5-
trifluoromethyl-ꢁ2–pyrazoline (14c).
1
An ethanolic solution of 1-(p-chlorophenyl)-4,4,4-trifluoro-
butane-1, 3-dione 1c (1.25 g, 5 mmoles) and 6-methyl-
benzothiazol-2-ylhydrazine 4 (0.90 g, 5 mmoles) was refluxed in
ethanol (20 ml) for 8 hours. The reaction was monitored by tlc.
The solvent was evaporated completely to yield a solid reaction
product. The tlc and 1H nmr of the crude reaction mixture
showed the formation of an exclusive single product. The
product was recrystallized from ethanol to yield the pure product
14c, mp 142º, yield 78%; ir: ꢂ OH 3290 cm-1; 1H nmr (CDCl3): ꢀ
2.57 (s, 3H, CH3), 3.62 (d, 1H, 4-H, J = 18.6 Hz), 3.77 (d, 1H, 4-
H, J = 18.6 Hz), 7.17 (d, 1H, 5'-H, J = 8.1 Hz), 7.40 (d, 2H, 3",
5"-H, J = 8.7 Hz), 7.50 (s, 1H, 7'-H), 7.55 (d, 1H, 4'-H, J = 8.4
Hz), 7.64 (d, 2H, 2", 6"-H, J = 8.7 Hz); ms: m/z 411 (M+) and
413 (M++2) in the ratio showing typical chlorine isotope profile
(3:1).
The compound had mp 160º, yield 23%; H nmr (CDCl3): ꢀ
6.80 (s, 1H, 4-H), 7.12 (d, 2H, 2", 6"-H, J = 8.7 Hz), 7.54 (m,
4H, 3", 5", 2' & 6'-H), 8.25 (d, 2H, 3' & 5'-H, J = 9.3 Hz); ms:
m/z 411 (M+) and 413 (M++2) in the ratio showing typical
bromine isotope profile (1:1).
Anal. Calcd. for C16H9BrF3N3O2: C, 46.71; H, 2.18; N, 10.22.
Found: C, 46.29; H, 2.12; N, 10.20.
1-(p-Nitrophenyl)-3-(p-bromophenyl)-5-hydroxy-5-trifluoro-
methyl-ꢁ2-pyrazoline (13d).
The compound had mp 199-200º, yield 56%; ir: ꢂ OH 3414
1
cm-1; H nmr (CDCl3 + DMSO-d6): ꢀ 3.61 (d, 1H, 4-H, J = 19.5
Hz), 3.76 (d, 1H, 4-H, J = 18.9 Hz), 7.55-7.61 (m, 4H, p-BrPh"-
H), 7.70 (d, 2H, 2' & 6'-H, J = 9.3 Hz), 7.88 (bs, 1H, O-H), 8.16
(d, 2H, 3' & 5'-H, J = 9.3 Hz); ms: m/z 429 (M+) and 431 (M++2)
in the ratio showing typical bromine isotope profile (1:1).
Anal. Calcd. for C16H11BrF3N3O3: C, 44.75; H, 2.56; N, 9.79.
Found: C, 44.31; H, 2.65; N, 9.78.
Anal. Calcd. for C18H13ClF3N3OS: C, 52.49; H, 3.16; N,
10.21. Found: C, 52.43; H, 3.09; N, 10.10.
Compounds 14f, 15c and 15d were prepared and purified by
similar procedure.
1-(p-Nitrophenyl)-5-(p-methoxyphenyl)-3-trifluoro-methyl-
pyrazole (8e).
1-(6'-Methylbenzothiazol-2'-yl)-3-(p-nitrophenyl)-5-hydroxy-5-
trifluoromethyl-ꢁ2-pyrazoline (14f).
1
The compound had mp 135º, yield 22%; H nmr (CDCl3): ꢀ
The compound had mp 175-76º, yield 81%; ir: ꢂ OH 3287
cm-1; 1H nmr (CDCl3): ꢀ 2.43 (s, 3H, CH3), 3.69 (d, 1H, 4-H, J =
18.3 Hz), 3.84 (d, 1H, 4-H, J = 18.3 Hz), 7.21 (d, 1H, 5'-H, J =
8.1 Hz), 7.54 (s, 1H, 7'-H), 7.58 (d, 1H, 4'-H, J = 8.4 Hz), 7.88
(d, 2H, 2", 6"-H, J = 8.7 Hz), 8.3 (d, 2H, 3", 5"-H, J = 9 Hz);
ms: m/z 422 (M+).
3.84 (s, 3H, OCH3), 6.73 (s, 1H, 4-H), 6.90 (d, 2H, 3", 5"-H, J =
8.7 Hz), 7.16 (d, 2H, 2", 6"-H, J = 8.7 Hz), 7.52 (d, 2H, 2' & 6'-
H, J = 9Hz), 8.22 (d, 2H, 3' & 5'-H, J = 9 Hz); ms: m/z 363
(M+).
Anal. Calcd. for C17H12F3N3O3: C, 56.20; H, 3.31; N, 11.57.
Found: C, 55.95; H, 3.21; N, 11.60.
Anal. Calcd. for C18H13F3N4O3S: C, 51.18; H, 3.08; N, 13.27.
Found: C, 51.12; H, 2.98; N, 13.01.
1-(p-Nitrophenyl)-3-(p-methoxyphenyl)-5-hydroxy-5-trifluoro-
methyl-ꢁ2-pyrazoline (13e).
1-(6'-Fluorobenzothiazol-2'-yl)-3-(p-chlorophenyl)-5-hydroxy-5-
trifluoromethyl-ꢁ2-pyrazoline (15c).
The compound had mp 176º, yield 57%; ir: ꢂ OH 3417 cm-1;
1H nmr (CDCl3 + DMSO-d6): ꢃ 3.58 (d, 1H, 4-H, J = 19 Hz),
3.77 (d, 1H, 4-H, J = 18.6 Hz), 3.86 (s, 3H, O-CH3), 6.95 (d, 2H,
3", 5"-H, J = 9 Hz), 7.65-7.71 (m, 4H, 2', 6', 2", 6"-H), 7.93 (bs,
1H, O-H), 8.15 (d, 2H, 3' & 5'-H, J = 9 Hz); ms: m/z 381 (M+).
Anal. Calcd. for C17H14F3N3O4: C, 53.54; H, 3.67; N, 11.02.
Found: C, 53.39; H, 3.47; N, 10.87.
The compound had mp 136-37º, yield 75%; ir: ꢂ OH 3305
cm-1; 1H nmr (CDCl3): ꢀ 3.64 (d, 1H, 4-H, J = 18.6 Hz), 3.79 (d,
1H, 4-H, J = 18.6 Hz), 7.06-7.66 (m, 8H, OH, 6-FBz'-H & p-
ClPh"-H); ms: m/z 415 (M+) and 417 (M++2) in the ratio
showing typical chlorine isotope profile (3:1).
Anal. Calcd. for C17H10ClF4N3OS: C, 49.10; H, 2.41; N,
10.11. Found: C, 48.93; H, 2.33; N, 9.89.
1, 5-Bis (p-nitrophenyl)-3-trifluoromethylpyrazole (8f).
1-(6'-Fluorobenzothiazol-2'-yl)-3-(p-bromophenyl)-5-hydroxy-
5-trifluoromethyl-ꢁ2-pyrazolines (15d).
1
The compound had mp 188º, yield 13%; H nmr (CDCl3): ꢀ
6.93 (s, 1H, 4-H), 7.44-7.53 (m, 4H, 2',6',2" & 6"-H), 8.26-8.30
(m, 4H, 3',5', 3" & 5"-H); ms: m/z 378 (M+).
Anal. Calcd. for C16H9F3N4O4: C, 50.80; H, 2.38; N, 14.81.
Found: C, 50.58; H, 2.33; N, 14.68.
The compound had mp 152-54º, yield 76%; ir: ꢂ OH 3298
cm-1; 1H nmr (CDCl3): ꢀ 3.70 (d, 1H, 4-H, J = 18.3 Hz), 3.79 (d,
1H, 4-H, J = 18.3 Hz), 7.06-7.66 (m, 7H, 6-FBz'-H & p-BrPh"-
H); ms: m/z 459 (M+) and 461 (M++2) in the ratio showing
typical isotope bromine profile (1:1).
1,3-Bis(p-nitrophenyl)-5-hydroxy-5-trifluoromethyl-ꢁ2-
pyrazoline (13f).
Anal. Calcd. for C17H10BrF3N3OS: C, 44.44; H, 2.18; N, 9.15.
Found: C, 44.39; H, 1.99; N, 9.18.
The compound had mp 192-94º, yield 65%; ir: ꢂ OH 3421
1
cm-1; H nmr (CDCl3 + DMSO-d6): ꢀ 3.70 (d, 1H, 4-H, J = 18.9
Synthesis of 1-(4'-methylquinolin-2'-yl)-3-aryl-5-hydroxy-5-tri-
fluoromethyl-ꢁ2-pyrazolines (16c, 16d).
Hz), 3.83 (d, 1H, 4-H, J = 18.9 Hz), 7.70-8.29 (m, 8H, p-NO2Ph'
& p-NO2Ph"-H), 8.30 (bs, 1H, OH); ms: m/z 396 (M+).
Anal. Calcd. for C16H11ClF3N3O5: C, 48.49; H, 2.78; N,
14.14. Found: C, 48.42; H, 2.80; N, 13.97.
1-(4'-Methylquinolin-2'-yl)-3-(p-chlorophenyl)-5-hydroxy-5-tri-
fluoromethyl-ꢁ2-pyrazolines (16c).
An ethanolic solution of 1-(p-chlorophenyl)-4,4,4-trifluoro-
butane-1, 3-dione 1c (1.25 g, 5 mmoles) and 4-methylquinolin-
2-ylhydrazine 6 (0.87 g, 5 mmoles) was refluxed in ethanol (20
Synthesis of 1-(6'-Substitutedbenzothiazol-2'-yl)-3-aryl-5-
hydroxy-5-trifluoromethyl-ꢁ2-pyrazolines (14c, 14f, 15c, 15d).

1012
S. P. Singh, V. Kumar and R. Aggarwal
Vol 43
ml) for 8 hours. The reaction was monitored by tlc. The solvent
was evaporated completely to provide a solid reaction mixture.
The tlc and H nmr of the crude reaction mixture showed the
formation of an exclusive single product. The compound was
Hz), 7.40 (d, 2H, 2", 6"-H, J = 8.7 Hz), 7.47 (d, 2H, 3", 5"-H, J
= 8.7 Hz), 7.62 (s, 1H, 7'-H), 7.64 (d, 1H, 4'-H, J = 6.8 Hz); ms:
m/z 393 (M+) and 395 (M++2) in the ratio showing typical
chlorine isotope profile (3:1).
1
recrystallized from ethanol to give pure solid 16c, mp 180º, yield
1
Anal. Calcd. for C18H11ClF3N3S: C, 54.90; H, 2.79; N, 10.67.
Found: C, 54.77; H, 2.68; N, 10.60.
72%; ir: ꢀ OH 3310 cm-1; H nmr (CDCl3): ꢀ 2.69 (s, 3H, CH3),
3.59 (d, 1H, 4-H, J = 18.4 Hz), 3.74 (d, 1H, 4-H, J = 18.3 Hz),
7.37-7.88 (m, 9H, Qu'-H, & p-ClPh"-H), 9.31 (bs, 1H, OH); ms:
m/z 405 (M+) and 407 (M++2) in the ratio of a typical Cl isotope
profile (3:1).
Anal. Calcd. for C20H15ClF3N3O: C, 59.20; H, 3.69; N, 10.35.
Found: C, 59.02; H, 3.57; N, 10.26.
1-(6'-Methylbenzothiazol-2'-yl)-5-(p-nitrophenyl)-3-trifluoro-
methylpyrazole (9f).
The compound had mp 188-190º, yield 76%; 1H nmr (CDCl3):
ꢀ 2.40 (s, 3H, CH3), 6.77 (s, 1H, 4-H), 7.15 (d, 1H, 5'-H, J = 8.4
Hz), 7.47 (d, 1H, 4'-H, J = 8.4 Hz), 7.57 (s, 1H, 7'-H), 7.65 (d,
2H, 2", 6"-H, J = 8.7 Hz), 8.22 (d, 2H, 3", 5"-H, J = 8.7 Hz); ms:
m/z 404 (M+).
Compound 16d was prepared and purified by similar
procedure.
Anal. Calcd. for C18H11F3N4O2S: C, 53.46; H, 2.72; N, 13.86.
Found: C, 53.33; H, 2.56; N, 13.657.
1-(4'-Methylquinolin-2'-yl)-3-(p-bromophenyl)-5-hydroxy-5-tri-
fluoromethyl-ꢁ2-pyrazolines (16d).
1-(6'-Fluorobenzothiazol-2'-yl)-5-(p-chlorophenyl)-3-trifluoro-
methylpyrazole (10c).
The compound had mp 196-97º, yield 74%; ir: ꢀ OH 3306
cm-1; 1H nmr (CDCl3): ꢀ 2.69 (s, 3H, CH3), 3.59 (d, 1H, 4-H, J =
18.6 Hz), 3.74 (d, 1H, 4-H, J = 18.3 Hz), 7.37-7.88 (m, 9H, Qu'-
H, & p-BrPh"-H), 9.40 (bs, 1H, OH); ms: m/z 449 (M+) and 451
(M++2) in the ratio showing typical bromine isotope profile
(1:1).
The compound had mp 152º, yield 71%; 1H nmr (CDCl3): ꢀ
6.75 (s, 1H, 4-H), 7.17-7.19 (m, 1H, 5'-H), 7.44-7.69 (m, 6H, 6-
FBz'-H & p-ClPh"-H); ms: m/z 397 (M+) and 399 (M++2) in the
ratio showing typical chlorine isotope profile (3:1).
Anal. Calcd. for C20H15BrF3N3O: C, 53.45; H, 3.34; N, 9.35.
Found: C, 53.08; H, 3.31; N, 9.23.
Anal. Calcd. for C17H8ClF4N3S: C, 51.33; H, 2.01; N, 10.56.
Found: C, 51.30; H, 1.86; N, 10.56.
Reactions performed under acidic condition (EtOH/ H2SO4).
Synthesis of 1-Phenyl-5-aryl -3-trifluoromethylpyrazoles (7a-f).
1, 5-Diphenyl-3-trifluoromethylpyrazole (7a).
1-(6'-Fluorobenzothiazol-2'-yl)-5-(p-bromophenyl)-3-trifluoro-
methylpyrazole (10d).
The compound had mp 150-52º, yield 73%; 1H nmr (CDCl3):
ꢀ 6.75 (s, 1H, 4-H), 7.16 (m, 1H, 5'-H), 7.41 (d, 2H, 2", 6"-H, J
= 8.7 Hz), 7.52 (m, 1H, 7'-H), 7.61 (d, 2H, 3", 5"-H, J = 8.7 Hz),
7.72 (m, 1H, 4'-H); ms: m/z 441 (M+) and 443 (M++2) in the
ratio showing typical bromine isotope profile (1:1).
An ethanolic solution (20 ml) of 1-phenyl 4,4,4-
trifluorobutane-1, 3-dione 1a (1.075 g, 5 mmoles) and 0.1 ml
conc. sulfuric acid was stirred for 15 minutes. An equimolar
Anal. Calcd. for C17H8BrF3N3S: C, 46.26; H, 1.81; N, 9.52.
Found: C, 45.84; H, 1.70; N, 9.54.
amount of phenylhydrazine
2 (0.54 g, 5 mmoles) was
subsequently added at 50º temperature in small lots with
constant stirring. The reaction mixture was allowed to reflux for
3 hours. Reaction was monitored by tlc. The excess of solvent
Synthesis of 1-(4'-Methylquinolin-2'-yl)-5-(p-chloro-phenyl)-3-
trifluoromethyl pyrazole (11c), 1-(4'-Methylquinolin-2'-yl)-3-(p-
chlorophenyl)-5-hydroxy-5-trifluoro-methyl-ꢁ2-pyrazolines (16c)
and 1-(4'-Methylquinolin-2'-yl)-3-(p-chlorophenyl)-5-trifluoro-
methyl pyrazoles (21c).
1
was evaporated and H nmr of the crude product so obtained
showed the formation of only single product 7a exclusively. The
solid was recrystallized from ethanol to provide the pure
compound 7a, mp 80º, yield 71%, identical to that obtained
above.
Compounds 7b-f were obtained as exclusive products under
the similar conditions.
An ethanolic solution (20 ml) of 1-(p-chlorophenyl)-4,4,4-
trifluorobutane-1, 3-dione 1c (1.25 g, 5 mmoles) and 0.1ml
conc. sulfuric acid was stirred for 15 minutes. An equimolar
amount of 4-methylquinolin-2-ylhydrazine 6 (0.87 g, 5 mmoles)
was subsequently added at 50° temperature in small lots with
constant stirring. The reaction mixture was allowed to reflux for
14 hours. Reaction was monitored by tlc. The excess of solvent
Synthesis of 1-(p-Nitrophenyl)-5-aryl-3-trifluoromethyl-
pyrazole (8a-f).
Compounds 8a-f were obtained exclusively by performing the
similar reactions when refluxed for
recrystallized from ethanol.
1
was evaporated and tlc and H nmr of the crude reaction mixture
5 hours and were
showed the formation of three products 11c, 16c, 21c in a ratio
54:38:8, respectively. These compounds were separated by
column chromatographic technique. Column chromatographic
separation using silica gel (100-200 mesh) and petroleum ether
(60-80º) as eluent afforded 11c, mp 134-135º, yield 44%; 1H nmr
(CDCl3): ꢀ 2.79 (s, 3H, CH3), 6.80 (s, 1H, 4-H), 7.32-7.33 (m,
4H, p-ClPh"-H), 7.60-7.69 (m, 3H, Qu'-H), 7.76 (s, 1H, 3'-H),
8.02 (d, 1H, 8'-H, J = 8.7 Hz); ms: m/z 387 (M+) and 389
(M++2) in the ratio showing typical chlorine isotope profile
(3:1).
Synthesis of 1-(6'-Substitutedbenzothiazol-2'-yl)-5-aryl-3-tri-
fluoromethylpyrazoles (9c, 9f, 10c, 10d).
Compounds 9c, 9f, 10c, 10d were obtained exclusively by
performing the similar reactions when refluxed for 15 hours and
were recrystallized from ethanol.
1-(6'-Methylbenzothiazol-2'-yl)-5-(p-chlorophenyl)-3-trifluoro-
methylpyrazole (9c).
The compound had mp 150º, yield 69%; 1H nmr (CDCl3): ꢀ
2.48 (s, 3H, CH3), 6.74 (s, 1H, 4-H), 7.25 (d, 1H, 5'-H, J = 6.6
Anal. Calcd. for C20H13ClF3N3: C, 61.93; H, 3.35; N, 10.83.
Found: C, 61.77; H, 3.19; N, 10.66.

Jul-Aug 2006
The Reaction of Aryl and Heteroarylhydrazines with Aryl-Trifluoromethyl ꢀ-Diketones
1013
Further elution then afforded 21c, mp 130°, yield 4% and
other product (16c) was afforded by further elution of the
column with petroleum ether: ethyl acetate (99:1), mp 180°,
yield 26%. H nmr data and elemental analysis of compounds
16c and 21c were given in experimental section.
1-(p-Nitrophenyl)-3-(p-methoxyphenyl)-5-trifluoro-methyl-
pyrazole (18e).
The compound had mp 106-07º, yield 70%; 1H nmr (CDCl3):
ꢀ 3.86 (s, 3H, OCH3), 6.98 (d, 2H, 3",5"-H, J = 8.7 Hz), 7.13 (s,
1H, 4-H), 7.77-7.82 (m, 4H, 2', 6', 2" & 6"-H), 8.15 (d, 2H, 3' &
5'-H, J = 9 Hz); ms: m/z 363 (M+).
Anal. Calcd. for C17H12F3N3O3: C, 56.20; H, 3.31; N, 11.57.
Found: C, 56.11; H, 3.00; N, 11.55.
1
Dehydration of 5-Hydroxy-5-trifluoromethyl-ꢁ2-pyrazolines into
5-trifluoromethyl- pyrazoles.
Synthesis of 1-Phenyl-3-(p-nitrophenyl)-5-trifluoro-methyl-
pyrazole (17f).
1,3-Bis(p-nitrophenyl)-5-trifluoromethylpyrazole (18f).
The compound had mp 186º, yield 77%; 1H nmr (CDCl3): ꢀ
7.31 (s, 1H, 4-H), 7.82 (d, 2H, 2', 6'-H, J = 9 Hz), 8.05 (d, 2H, 2"
& 6"-H, J = 9.3 Hz), 8.33 (d, 2H, 3' & 5'-H, J = 9 Hz), 8.39 (d,
2H, 3" & 5"-H, J = 9.3Hz); ms: m/z 378 (M+).
Anal. Calcd. for C16H9F3N4O4: C, 50.79; H, 2.38; N, 15.38.
Found: C, 52.54; H, 2.27; N, 15.08.
An ethanolic solution (20 ml) of 1-phenyl-3-(p-nitrophenyl)-
5-hydroxy-5-trifluoromethyl-ꢁ2-pyrazoline 12f (0.4 g, 1.2
mmoles) and 0.1 ml conc. sulfuric acid was refluxed for 4 hours.
The excess of solvent was evaporated and on cooling a solid
appeared which was recrystallized from ethanol, mp 82 ºC, yield
87 %; 1H NMR (CDCl3): ꢀ 7.21 (s, 1H, 4-H), 7.52-7.55 (m, 5H,
Ph'-H), 8.03 (d, 2H, 2" & 6"-H, J = 9 Hz), 8.30 (d, 2H, 3" & 5"-
H, J = 9 Hz); ms: m/z 333 (M+).
Synthesis of 1-(6'-Substitutedbenzothiazol-2'-yl)-3-aryl-5-
trifluoromethylpyrazoles (19c, 19f, 20c and 20d).
Anal. Calcd. for C16H10F3N3O2: C, 57.66; H, 3.00; N, 12.61.
Found: C, 57.44; H, 2.91; N, 12.24.
Compounds 19c, 19f, 20c and 20d were prepared employing
similar reaction conditions when refluxed for 24 hours.
Synthesis of 1-(p-Nitrophenyl)-3-aryl-5-trifluoromethyl-
pyrazoles (18a-18f).
1-(6'-Methylbenzothiazol-2'-yl)-3-(p-chlorophenyl)-5-trifluoro-
methylpyrazole (19c).
Compounds 18a-18f were prepared by employing similar
procedure when refluxed for 6 hours.
The compound had mp 172º, yield 75%; 1H nmr (CDCl3): ꢀ
2.50 (s, 3H, CH3), 7.18 (s, 1H, 4-H), 7.31 (d, 1H, 5'-H, J = 8.4
Hz), 7.44 (d, 2H, 3", 5"-H, J = 8.7 Hz), 7.64 (s, 1H, 7'-H), 7.81-
7.86 (m, 3H, 4', 2", 6"-H); ms: m/z 393 (M+) and 395 (M++2) in
the ratio showing typical chlorine isotope profile (3:1).
Anal. Calcd. for C18H11ClF3N3S: C, 54.90; H, 2.79; N, 10.67.
Found: C, 54.77; H, 2.50; N, 10.37.
1-(p-Nitrophenyl)-3-phenyl-5-trifluoromethylpyrazole (18a).
The compound had mp 102º, yield 74%; 1H nmr (CDCl3): ꢂ
7.20 (s, 1H, 4-H), 7.39-7.49 (m, 3H, 3", 4" & 5"-H), 7.79-7.88
(m, 4H, 2', 6', 2" & 6"-H), 8.39 (d, 2H, 3' & 5'-H, J = 9 Hz); ms:
m/z 333 (M+).
Anal. Calcd. for C16H10F3N3O2: C, 57.66; H, 3.02; N, 12.61.
Found: C, 57.79; H, 3.13; N, 12.68.
1-(6'-Methylbenzothiazol-2'-yl)-3-(p-nitrophenyl)-5-trifluoromethyl-
pyrazole (19f).
1-(p-Nitrophenyl)-3-(p-fluorophenyl)-5-trifluoromethyl-pyrazole
(18b).
1
The compound had mp 192º, yield 79%; H nmr
(CDCl3): ꢀ 2.45 (s, 3H, CH3), 7.19 (s, 1H, 4-H), 7.26 (d,
1H, 5'-H, J = 8.4 Hz), 7.61 (s, 1H, 7'-H), 7.82 (d, 1H, 4'-
H, J = 8.1 Hz), 8.27 (d, 2H, 3", 5"-H, J = 8.7 Hz), 8.01 (d,
2H, 2", 6"-H, J = 8.7 Hz), 8.27 (d, 2H, 3", 5"-H, J = 8.7
Hz); ms: m/z 404 (M+).
The compound had mp 101º, yield 72%; 1H nmr (CDCl3): ꢀ
7.15 (m, 3H, 4, 3", 5"-H), 7.79-7.86 (m, 4H, 2', 6', 2" & 6"-H),
8.39 (d, 2H, 3ꢃ& 5ꢃ-H, J = 9 Hz); ms: m/z 351 (M+).
Anal. Calcd. for C16H9F4N3O2: C, 54.70; H, 2.56; N, 11.96.
Found: C, 54.573; H, 2.47; N, 11.87.
Anal. Calcd. for C18H11F3N4SO2: C, 53.46; H, 2.72; N, 13.86.
Found: C, 53.27; H, 2.55; N, 13.68.
1-(p-Nitrophenyl)-3-(p-chlorophenyl)-5-trifluoromethyl-pyrazole
(18c).
1-(6'-Fluorobenzothiazol-2'-yl)-3-(p-chlorophenyl)-5-trifluoro-
methylpyrazole (20c).
The compound had mp 121ºC, yield 76%; 1H nmr (CDCl3): ꢀ
7.18 (s, 1H, 4-H), 7.43 (d, 2H, 3", 5"-H, J = 8.4 Hz), 7.78-7.81
(m, 4H, 2', 6', 2" & 6"-H), 8.40 (d, 2H, 3' & 5'-H, J = 9 Hz); ms:
m/z 385 (M+) and 387 (M++2) in the ratio showing typical
chlorine isotope profile (3:1).
The compound had mp 166-68º, yield 74%; 1H nmr (CDCl3):
ꢀ 7.18 (s, 1H, 4-H), 7.21-7.22 (m, 1H, 5ꢃ-H), 7.44 (d, 2H, 3", 5"-
H, J = 8.7 Hz), 7.51 (m, 1H, 7'-H), 7.81 (d, 2H, 2", 6"-H, J = 8.7
Hz), 7.89-7.93 (m, 1H, 4'-H); ms: m/z 397 (M+) and 399 (M++2)
in the ratio showing typical chlorine isotope profile (3:1).
Anal. Calcd. for C17H8ClF4N3S: C, 51.32; H, 2.01; N, 10.58.
Found: C, 51.23; H, 1.94; N, 10.58.
Anal. Calcd. for C16H9ClF3N3O2: C, 52.25; H, 2.45; N, 11.43.
Found: C, 51.99; H, 2.34; N, 11.40.
1-(p-Nitrophenyl)-3-(p-bromophenyl)-5-trifluoromethyl-pyrazole
(18d).
1-(6'-Fluorobenzothiazol-2'-yl)-3-(p-bromophenyl)-5-trifluoro-
methylpyrazole (20d).
The compound had mp 138º, yield 78%; 1H nmr (CDCl3): ꢀ
7.18 (s, 1H, 4-H), 7.59 (d, 2H, 3", 5"-H, J = 8.4 Hz), 7.73 (d, 2H,
2" & 6"-H, J = 8.7 Hz), 7.79 (d, 2H, 2' & 6'-H, J = 9 Hz.), 8.39
(d, 2H, 3' & 5'-H, J = 9 Hz); ms: m/z 411 (M+) and 413 (M++2)
in the ratio showing typical bromine isotope profile (1:1).
Anal. Calcd. for C16H9BrF3N3O2: C, 46.71; H, 2.19; N, 10.22.
Found: C, 46.56; H, 2.00; N, 10.20.
The compound had mp 160º, yield 75%; 1H nmr (CDCl3): ꢀ
7.21 (s, 1H, 4-H), 7.22-7.24 (m, 1H, 5'-H), 7.53-7.56 (m, 1H, 7'-
H) 7.61 (d, 2H, 3", 5"-H, J = 8.7 Hz), 7.76 (d, 2H, 2", 6"-H, J =
8.7 Hz), 7.90-7.95 (m, 1H, 4'-H); ms: m/z 441 (M+) and 441
(M++2) in the ratio showing typical bromine isotope profile (1:1).

1014
S. P. Singh, V. Kumar and R. Aggarwal
Vol 43
[5] K. Kirschke, "1H-Pyrazole" in Methoden der Organische Chemie
(Houben-Weyl), Vol. III/Teil 2, p. 399, Georg Thieme, Stuttgart, 1994.
[6] B. Stanovnik and J. Svete, "Pyrazoles" in Science of
Synthesis (Ed. R. Neier), Vol. 12. chapter 12.1, Georg Thieme, Stuttgart,
2005.
Anal. Calcd. for C17H8BrF4N3S: C, 46.26; H, 1.81; N, 9.52.
Found: C, 45.77; H, 1.71; N, 9.42.
Synthesis of 1-(4'-Methylquinolin-2'-yl)-3-(p-chloro-phenyl)-5-
trifluoromethyl pyrazole (21c).
[7] S. P. Singh, D. Kumar, H. Batra, R. Naithani, I. Rozas and J.
Elguero. Can. J. Chem., 78, 1109 (2000).
[8] M. A. P. Martins, R. F. Blanco, C. M. P. Pereira, P. Beck, S.
Brondani, W. Cunico, N. E. K. Zimmermann, H. G. Bonacorso and N.
Zanatta, J. Fluorine Chem., 118, 69 (2002).
[9] T. Norris, R. Colon-Cruz and D. H. B. Ripin, Org. Biomol.
Chem., 3, 1844 (2005).
[10] D. Sanz, R. M. Claramunt, S. P. Singh, V. Kumar, R.
Aggarwal, J. Elguero and I. Alkorta, Magn. Reson. Chem., 43, 1040
(2005).
An acetic acid solution (15 ml) of compound 16c (0.41 g, 1.2
mmol) and 0.1ml conc. sulfuric acid was refluxed for 20 hours.
The excess of solvent was evaporated and poured the reaction
mixture in cold water. Solid so obtained was recrystallized from
ethanol, mp 130ºC, yield 69%; 1H nmr (CDCl3): ꢀ 2.81 (s, 3H,
CH3), 7.21 (s, 1H, 4-H), 7.45 (d, 2H, 3", 5"-H, J = 8.7 Hz), 7.58-
7.64 (m, 1H, 6'-H), 7.74-7.79 (m, 1H, 7'-H), 7.99 (s, 1H, 3'-H),
8.03 (dd, 1H, 5'-H, Jo = 8.4 Hz, Jm = 0.9 Hz), 8.08 (dd, 1H, 8'-H,
Jo = 8.4 Hz, Jm = 0.9 Hz); ms: m/z 387 (M+) and 389 (M++2) in
the ratio showing typical chlorine isotope profile (3:1).
[11] M. J. Uddin, P. N. Rao, K. Praveen and E. E. Knaus, Bioorg.
Med. Chem., 11, 5273 (2003).
Anal. Calcd. for C20H13ClF3N3: C, 61.93; H, 3.35; N, 10.83.
Found: C, 61.87; H, 3.29; N, 10.63.
[12] T. D. Penning, J. J. Talley, S. R. Bertenshaw, J. S. Carter, P. W.
Collins, S. Docter, M. J. Graneto, L. F. Lee, J. W. Malecha, J. M. Miyashiro,
R. S. Rogers, D. J. Rogier, S. S. Yu, G. D. Anderson, E. G. Burton, J. N.
Cogburn, S. A. Gregory, C. M. Koboldt, W. E. Perkins, K. Siebert, A. M.
Veenhuizen, Y. Y. Zhang and P. C. Isakson, J. Med. Chem. 40, 1347 (1997).
[13] N. S. Zefirov, S. I. Kozhushkov, T. S. Kuznetsova, B. A.
Ershov and S. I. Selivanov, Tetrahedron, 42, 709 (1986).
[14] F. Franco-Fernández, O. Caamaño, M. D. García, I. Alkorta
and J. Elguero, Tetrahedron, 62, in press, 2006.
[15] G. Coispeau and J. Elguero, Bull. Soc. Chim. Fr., 2717
(1970).
[16] W. P. Jencks, Catalysis in Chemistry and Enzymology,
McGraw-Hill, New York, 1969, p. 463.
Acknowledgements.
We are grateful to the UGC, New Delhi, India for financial
assistance. Mass spectra were provided by the UCSF (USA)
Mass Spectrometry Facility (A. L. Burlingame, Director)
supported by the NIH NCRR BRTP RR01614. Thanks are also
due to RSIC, Lucknow, India for providing elemental analysis
and 19F nmr spectra. Support by the Spanish SAF-2003-08003-
C02-02 project was acknowledged.
[17] M. Calzadilla, A. Malpica and T. Cordova, J. Phys. Org.
Chem., 12, 708 (1999).
[18] C. G. Swain and E. C. Lupton, J. Am. Chem. Soc., 90, 4328
(1968).
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