Alkylation of 1-phenyl-3,5-disubstituted pyrazoles with polyfluorinated aliphatic aldehydes: Properties of 1-phenyl-4-(1-hydroxypolyfluoroalkyl)pyrazole derivatives

Article abstract of DOI:10.1016/S0022-1139(99)00212-2

Polyfluorinated aliphatic aldehydes react with 1-phenyl-3-methylpyrazole-5-one, 1-phenyl-3-methyl-5-amino (N,N-dimethylaminomethylenamino)pyrazole and 1-phenyl-3-aminopyrazole-5-one at room temperature in the absence of catalyst with formation of 4-(1-hydroxypolyfluoroalkyl)pyrazoles. Dehydration of 4-(1-hydroxypolyfluoroalkyl)pyrazoles with morpholinosulfur trifluoride generates 4-polyfluoroalkylidenepyrazoles, which are active dienophiles and react with 2,3-dimethylbutadiene and cyclopentadiene forming spirocyclic pyrazole derivatives.

Full text of DOI:10.1016/S0022-1139(99)00212-2

Journal of Fluorine Chemistry 101 (2000) 111±116
Alkylation of 1-phenyl-3,5-disubstituted pyrazoles with
poly¯uorinated aliphatic aldehydes
Properties of 1-phenyl-4-(1-hydroxypoly¯uoroalkyl)pyrazole
derivatives
Yu.G. Shermolovich*, S.V. Yemets
Institute of Organic Chemistry of the National Academy of Sciences of Ukraine, 253660,
Murmanskaya st. 5, Kyiv 94, Ukraine
Received 25 June 1999; accepted 31 August 1999
Abstract
Poly¯uorinated aliphatic aldehydes react with 1-phenyl-3-methylpyrazole-5-one, 1-phenyl-3-methyl-5-amino (N,N-dimethylamino-
methylenamino)pyrazole and 1-phenyl-3-aminopyrazole-5-one at room temperature in the absence of catalyst with formation of 4-(1-
hydroxypoly¯uoroalkyl)pyrazoles. Dehydration of 4-(1-hydroxypoly¯uoroalkyl)pyrazoles with morpholinosulfur tri¯uoride generates 4-
poly¯uoroalkylidenepyrazoles, which are active dienophiles and react with 2,3-dimethylbutadiene and cyclopentadiene forming spirocyclic
pyrazole derivatives. # 2000 Elsevier Science S.A. All rights reserved.
Keywords: Pyrazole; Alkylation; Poly¯uorinated aliphatic aldehyde
1. Introduction
Poly- and per¯uoroalkyl derivatives of aromatic and
heteroaromatic compounds are intensively studied [1±5].
One of the possible approaches to the synthesis of these
compounds consists in interaction of per¯uoroketones [6] or
aldehydes [2] with aromatic or heteroaromatic derivatives.
Poly¯uorinated tertiary or secondary alcohols containing
aryl or heteroaryl substituent in the a-position, are formed in
these reactions. Compounds of this type are used for synth-
esis of substances with analgesic and antinociceptive activ-
2. Results and discussion
ity [7,8].
2.1. Interaction of 1-phenyl-3,5-disubstituted pyrazoles
The reactions of per¯uoroaldehydes with heteroaromatic
with polyfluorinated aldehydes
compounds have been studied on the example of 3-pyridyl-
lithium [2]. The thermal condensation of 1-phenyl-3-
We have found that the aldehydes (2a, b) react with such
methylpyrazole-5-one with the hydrate of tri¯uoroacetic
electron rich heteroaromatic compounds as 1-phenyl-3,5-
aldehyde is known among other heteroaromatic compounds.
disubstituted pyrazoles (3a±d) at room temperature and in
1,1-bis-(1-phenyl-3-methyl-5-hydroxypyrazole-4-yl)-2,2,2-
the absence of catalysts or condensing agents forming
tri¯uoroethane (1) (see Section 2.2) is formed in this exam-
heterocyclic products alkylated on the 4-position. The 1-
ple [9].
phenyl-3,5-disubstituted-4-(1-hydroxypoly¯uoroalkyl)pyr-
azoles (4a±e) were accordingly obtained. Up to 17% of
compound (1) has been formed also when the pyrazole (3a)
interacts with tri¯uoroacetic aldehyde.
*Corresponding author. Fax: ‡380-44-573-2693
0022-1139/00/$ ± see front matter # 2000 Elsevier Science S.A. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 9 9 ) 0 0 2 1 2 - 2

112
Yu.G. Shermolovich, S.V. Yemets / Journal of Fluorine Chemistry 101 (2000) 111±116
The compounds (4a, b) have been obtained also by
It would be possible to expect the formation of half-
aminales (7) and (8) as the products of addition of ami-
nogroup to a molecule of aldehyde in the case of the
pyrazoles (3b, d). However, the alkylated pyrazoles (4c,
e) are not changed in boiling methanol in the presence of
hydrochloric acid. Such behavior is not characteristic of
half-aminales of per¯uoroaldehydes which are easily hydro-
lyzed under these conditions [11].
reaction of 1-phenyl-3-methylpyrazole-5-one with the
ethylhemiacetal of tri¯uoroacetic aldehyde or 1,1,2,2,
3,3,4,4-octa¯uoropentanal hydrate. These processes occur
at room temperature over 1±5 days, whereas reactions of the
1-phenyl-3-methylpyrazole-5-one with aldehydes (2a, b)
are complete in 2±5 h.
The nature of the substituent in a 5-position of the
heterocycle (3) in¯uences the path of the reaction. 1-Phe-
nyl-3-methylpyrazole, 1-phenyl-3,5-dimethylpyrazole and
1-phenyl-3-methyl-5-ethoxypyrazole cannot be alkylated
with aldehyde (2b) even on long heating in the presence
of BF3ÁOEt2 catalyst. Only polymerization of aldehyde (2b)
is observed in that case.
IR and NMR spectroscopic data have proved the structure
of the compounds (4a±e).
The compounds (4a±e) are high melting, colorless, crys-
talline and soluble in polar organic solvents. They are the
®rst representatives of pyrazoles containing 1-hydroxypoly-
¯uoroalkyl substituents. It is necessary to note that much
attention has been paid to investigation of other hetero-
cycles, obtained by more dif®cult methods, containing
similar substituents, over recent years. The 1-hydroxypoly-
¯uoroalkyl derivatives of pyridine [2,3], quinoline, pyrimi-
dine [4], thiophene and furan [5] have been studied. We have
investigated some chemical properties of the compounds
(4a, b) with the purpose to obtain new ¯uorine containing
derivatives of pyrazoles.
2
3
RFˆ CF3 (a), (CF2)4H (b);
R ˆ CH3, X ˆ OH (a), NH2 (b), N=CHN (CH3)2 (c);
R ˆ NH2, X ˆ OH (d);
4
RF ˆ CF3, R ˆ CH3, X ˆ OH (a); RF ˆ (CF2)4 H,
R ˆ CH3, X ˆ OH (b), X ˆ NH2 (c), X ˆ N=CHN
(CH3)2 (d); RF ˆ (CF2)4, R ˆ NH2, X ˆ OH (e).
2.2. Thermal transformations of 1-phenyl-3-methyl-4-(1-
hydroxypolyfluoroalkyl)-5-hydroxypyrazoles
The absorption of OH groups in 3200±3400 cm 1 region
and absence of signals of carbonyl groups of possible
isomers (5a, b, e) and (50a, b, e) is observed in the IR
spectra of compounds (4a, b, e). Only one set of signals of
1H and 19F nuclei is present in the 1H and 19F NMR
spectra of DMSO-d6, CD3CN, CH3OH solutions of
compounds (4a, b, e). That testi®es the absence (within
sensitivity of the method) of possible isomers (5a, b, e).
There are no signals of connected proton nuclei of the
heterocycle in the 13C NMR spectrum of the solution of
compound (4a) in DMSO-d6 recorded with application of
APT technique [10]. That proves the structure of compound
(4a) and also testi®es the absence of another possible
product of alkylation on the second nitrogen atom of the
pyrazole cycle (6).
1
4
9
RF ˆ CF3;
RF ˆ CF3 (a), RF ˆ (CF2)4H (b);
RF ˆ CF3 (a), RF ˆ (CF2)4H (b);
5
RF ˆ CF3, R ˆ CH3 (a); RF ˆ (CF2)4H, R ˆ CH3 (b),
R ˆ NH2 (e);
10 RF ˆ (CF2)4H.
Pyrazoles (4a, b) have been transformed into 1,1-bis-
(1-phenyl-3-methyl-5-hydroxypyrazole-4-yl)-2, 2, 2-tri-
50 R ˆ CF3, R ˆ CH3 (a); R ˆ (CF2)4H, R ˆ CH3 (b),
R ˆ NH2 (e).

Yu.G. Shermolovich, S.V. Yemets / Journal of Fluorine Chemistry 101 (2000) 111±116
113
¯uoroethane (1) and 1,1-bis-(1-phenyl-3-methyl-5-hydro-
xypyrazole-4-yl)-2,2,3,3,4,4,5,5-octa¯uoropentane (10) on
heating to 1308C for a long time. It is possible to propose
two mechanisms for course of this process. The 1-phenyl-3-
methyl-5-hydroxypyrazole is formed by eliminating a mole-
cule of aldehyde (2a) or (2b) from a molecule of pyrazole
(4a) or (4b). This then interacts with another molecule of
pyrazole (4a) or (4b) or with a molecule of 4-poly¯uor-
oalkylidenepyrazole (9a) or (9b), that can be formed by
elimination of a molecule of water from a molecule of
pyrazole (4a) or (4b). Compound (10) has been obtained
by interaction of 4-poly¯uoroalkylidenepyrazole (9b) with
1-phenyl-3-methyl-5-hydroxypyrazole.
increases its activity in reactions with dienes. The products
of Diels±Alder reactions with 2,3-dimethylbutadiene and
cyclopentadiene are spirocyclic compounds (12a, b) and
(13) formed when reaction is carried out at room tempera-
ture and in the absence of catalysts. The product of reaction
of unstable compound (9a) with 2,3-dimethylbutadiene had
been obtained when this diene was added directly to the
reaction mixture of compound (4a) and morpholinosulfur
tri¯uoride. It should be noted that intramolecular Diels±
Alder reactions of the un¯uorinated a-oxoalkylidenes of a
pyrazole have been published recently. But they proceed
under rather harsh conditions and a-oxoalkylidenes behave
as dienes [12].
The presence of four chiral atoms of carbon in a molecule
1
of compound (13) causes complication in the H and 19F
2.3. Dehydration of 1-phenyl-3-methyl-4-(1-
hydroxypolyfluoroalkyl)-5-hydroxypyrazoles
NMR spectra. Comparison of integrated intensities of
the signals gives the conclusion that there occurs more
than 80% formation of one of six possible pairs of
diastereomers. The formation of only one pair of diaster-
eomers has been observed in the case of compounds
(12a, b).
The corresponding 4-¯uoroalkylpyrazoles (11) are not
formed by reactions of compounds (4a, b) with morpholi-
nosulfur tri¯uoride. Only 4-poly¯uoroakylydenepyrazoles
(9a, b) are obtained as the products of dehydration. It was
not possible to isolate 4-tri¯uoroethylidenepyrazole-5-one
(9a) from the reaction mixture because of its decomposition.
It was identi®ed as the cycloadduct with diene (12a).
Compound (9b) is a red crystalline product, which is soluble
in non-polar organic solvents in contrast to the precursor
(4b). The process of dehydration is stereospeci®c as the
presence of a single set of signals in spectrum 19F NMR of
reaction mixture indicates that only one of two possible
geometrical isomers of compound (9b) has been formed.
9
RF ˆ CF3 (a), RF ˆ (CF2)4H (b);
12 RF ˆ CF3 (a), RF ˆ (CF2)4H (b);
13 RF ˆ (CF2)4H.
4
9
RF ˆ CF3 (a), RF ˆ (CF2)4H;
RF ˆ CF3 (a), RF ˆ (CF2)4H.
Compound (9b) easily adds a molecule of methanol
forming the corresponding 4-(1-methoxypoly¯uoroalkyl)-
pyrazole (14). The signal of the proton for the 4-position
1
of pyrazole nucleus is absent from the H NMR spectrum
2.4. Reactions of 1-phenyl-3-methyl-4-
polyfluoroalkylidenepyrazole-5-ones
of compound (14) recorded in CDCl3. The characteristic
carbonyl group IR absorption is absent in a KBr disc
indicating the presence of this compound in the 5-hydroxy
form (14), instead of in the form of pyrazole-5-ones (15a) or
(150a).
The presence of the poly¯uoroalkyl substituent at the
exocyclic carbon at the double bond of compounds (9a, b)

114
Yu.G. Shermolovich, S.V. Yemets / Journal of Fluorine Chemistry 101 (2000) 111±116
408C. The mixture was stirred at 208C for 1 h and
then heated up to 208C and stirred for 15 h. The
precipitate containing compound (4a) and 17% of
compound (1), judging from its solution in DMSO 19F
NMR spectrum, was filtered. It was washed with boiling
chloroform (20 ml) to remove compound (1).
2. The ethylhemiacetal of trifluoroacetic aldehyde
(4 mmol) at 208C was added to a suspension of
equimolar amounts of pyrazole (3a) in chloroform
(10 ml). The mixture was maintained at 208C for 5 days
and compound (4a) was filtered off.
3. A solution of aldehyde (2b) (3.1 mmol) in chloroform
(5 ml) at 208C was added to a stirred suspension of
pyrazole (3a) or (3b±d) (3.0 mmol) in chloroform
(5 ml). The mixture was stirred at 208C for 24 h and
then the compounds (4b, c, e) were filtered off. In the
case of compound (4d), chloroform was removed in
vacuo (20 torr), the oily residue was treated with n-
hexane (5 ml) and pyrazole (4d) was filtered off.
4. The hydrate of aldehyde (2b) (6.76 mmol) at 208C was
added to a stirred suspension of equimolar amounts of
pyrazole (3a) in chloroform (10 ml). The mixture was
stirred for 24 h and compound (4b) was filtered off.
3. Experimental
IR spectra were measured on a UR-10 spectrometer; 1H,
19F, 13C NMR spectra were recorded on Varian-VXR (1H:
300 MHz, 19F: 282 MHz, 13C: 75 MHz) using TMS as
internal standard for H and 13C NMR spectra, and C6F6
1
( 162.9 ppm) as internal standard for 19F NMR spectra.
Puri®cation of products was by column chromatography on
silica gel, the eluent used was CHCl3/MeO ˆ 9/1. Analysis
and spectroscopic data are given in Tables 1 and 2.
3.2. Thermolysis of 1-phenyl-3-methyl-4-(1-hydroxy-2,2,2-
trifluoroethyl)-5-hydroxypyrazole (4a) and 1-phenyl-3-
methyl-4-(1-hydroxy-2,2,3,3,4,4,5,5-octafluoropentyl)-5-
hydroxypyrazole (4b)
3.1. Synthesis of 4-(1-hydroxy-2,2,2-
trifluoroethyl)pyrazole (4a) and 4-(1-hydroxy-
2,2,3,3,4,4,5,5-octafluoropentyl)pyrazoles (4b±e)
1. Pyrazole (4a) or (4b) (5 mmol) was heated at 1308C for
5 h. Compound (1) was recrystallized from methanol;
compound (10) was washed with n-hexane (5 ml).
2. The mixture of 1-phenyl-3-methyl-5-hydroxypyrazole
(4 mmol) and of equimolar amounts of 1-phenyl-3-
methyl-4-(2,2,3,3,4,4,5,5-octafluoropentylidene)pyra-
zole-5-one (9b) was heated at 1308C for 5 h then
compound (10) was washed with n-hexane (5 ml).
1. Trifluoroacetic aldehyde (8.67 mmol) was obtained by
heating at 908C of ethylhemiacetal of trifluoroacetic
aldehyde (17.23 mmol) with a mixture of P2O5 (1 g)
and 98% H2SO4 (4 ml) and condensed at 708C. Then
it was passed for 10 min into a stirred suspension of
pyrazole (3a) (6.63 mmol) in chloroform (10 ml) at
Table 1
Yields, melting points and analytical data for compounds 1, 4a±e, 9b, 10, 12a, b, 13, 14
N
Melting point (8C)
Yield (%)
Found (%)
C
Formula
Calculated (%)
H
N
C
H
N
1
279±281
118±120
82±85
147±148
88±91
168±169
38±41
122±123
Oil
34
(i) 34b, (ii) 14b
±
±
±
±
±
±
±
4a
4b
4c
52.77
44.54
44.64
47.23
41.46
46.50
53.51
64.27
53.72
53.06
45.92
4.18
3.04
3.28
4.05
2.67
2.78
3.61
5.49
4.32
3.77
3.60
10.42
6.90
C12H11F3N2O2
C15H12F8N2O2
C15H13F8N3O
52.94
44.57
44.68
47.17
41.49
46.65
53.58
64.28
53.85
53.10
45.94
4.07
2.99
3.25
3.96
2.74
2.61
3.60
5.69
4.30
3.57
3.37
10.29
6.93
(iii) 91b, (iv) 75b
78
10.40
12.17
10.30
7.18
10.42
12.22
10.37
7.25
4d
4ea
9b
10
12a
12b
13
14
90
C
18H18F8N4O
C14H11F8N3O2
15H10F8N2O
70
62
(i) 24b, (ii) 75b
C
10.02
8.35
C25H20F8N4O2
C18H19F3N2O
10.00
8.33
26
72
53
56
26±27
Oil
6.05
6.29
C
C
C
21H20F8N2O
20H16F8N2O
16H14N2O2F8
5.98
6.19
57±59
6.70
6.70
‡
a ES mass spectroscopy M ˆ 405.
b See Section 3.

Yu.G. Shermolovich, S.V. Yemets / Journal of Fluorine Chemistry 101 (2000) 111±116
115
Table 2
IR and NMR spectral characteristics of compounds 1, 4a±e, 9b, 10, 12a, b, 13, 14
1
N
1H NMR, ꢀ (ppm), J (Hz)
19F NMR, ꢀ (ppm), J (Hz)
IR, ꢁ (cm 1), in range 3400±950 cm
3
1
(DMSO-d6): 2.27 (6H, s, CH3); 4.34 (1H, q,
3
(DMSO): 67.47 (d, JHF ˆ 10.2)
(Kbr): 3100, 2950, 1615, 1590, 1510,
1470, 1420, 1380, 1330, 1290, 1260,
1170, 1140, 1110, 1065, 1130
CHCF3, JHF ˆ 10.5); 7.26 (2H, t, Ar); 7.44
(4H, t, Ar); 7.67 (4H, d, Ar); 14.73 (2H, w.s, OH)
4a
(DMSO-d6): 2.24 (3H, s, CH3); 5.06 (1H, m, CH);
6.53 (1H, s, OH); 7.24 (1H, t, Ar); 7.45 (2H, t, Ar);
7.69 (2H, d, Ar); 11.32 (1H, w.s, OH)
(DMSO): 77.00 (s); (CH3OH): 77.50
3
(KBr): 3300, 3100, 2940, 2820, 1615,
1580, 1510, 1460, 1430, 1390, 1365,
1305, 1275, 1230, 1180, 1130, 990, 960
(d, JHF ˆ 5.6)
2
(DMSO-d6)a: 17.78; 50.86 (q, JCF ˆ 32.5);
1
107.35; 112.50; 112.93 (q, JCF ˆ 282.6);
116.12; 124.79; 135.33
2
4b
4c
(DMSO-d6): 2.26 (3H, s, CH3); 5.24 (1H, d, CH);
2
(CH3OH): 137.39 (2F, d, JHF ˆ 50.5);
(KBr): 3200±2600, 1615, 1580, 1510,
1470, 1420, 1385, 1370, 1320, 1290,
1180, 1140, 1090, 1050
2
6.48 (1H, s, OH); 7.01 (1H, t.t, CF2H, JHF ˆ 50.5,
130.45, 128.92 (2F, JAB ˆ 287.6);
3JHF ˆ 5.1); 7.24 (1H, t, Ar); 7.46 (2H, t, Ar);
7.69 (2H, d, Ar)
123.77, 116.31 (2F, JAB ˆ 279.4);
2
2
123.62, 122.41 (2F, JAB ˆ 318.0)
2
(DMSO-d6): 2.21 (3H, s, CH3); 5.20 (1H, m, CH);
5.27 (2H, s, NH2); 6.53 (1H, d, OH); 7.02
(CH3OH): 137.34 (2F, d, JHF ˆ 50.2);
(KBr): 3500, 3410, 3150, 2950, 2890,
2750, 1620, 1580, 1540, 1510, 1460,
1410, 1370, 1350, 1340, 1310, 1290,
1240, 1180, 1130, 1100, 1055, 1010, 980
2
130.48, 128.61 (2F, JAB ˆ 285.9);
2
3
2
(1H, t.t, CF2H, JHF ˆ 50.6, JHF ˆ 5.4); 7.32
122.27, 123.50 (2F, JAB ˆ 300.0);
2
(1H, t, Ar); 7.48 (2H, t, Ar); 7.54 (2H, d, Ar)
124.39, 115.67 (2F, JAB ˆ 281.1)
(Toluene): 137.51 (d), 136.91 (d)
4d
4e
(C6D6): 1.84 (3H, s, CH3); 2.36 (6H, s, 2CH3);
5.12 (1H, d, CH); 5.71 (1H, t.t, CF2H,
(KBr): 3200, 3000, 2980, 2940, 2750,
1650, 1605, 1565, 1510, 1490, 1440,
1390, 1310, 1260, 1220, 1180, 1120,
1090, 1080, 1065, 1040, 1020, 1000
2
2
(2F, JHF ˆ 44.5, JAB ˆ 296.3);
3
2
2JHF ˆ 51.9, JHF ˆ 5.4); 6.20 (1H, s, OH); 6.84
132.37, 128.53 (2F, JAB ˆ 288.7);
2
(1H, s, CH); 6.95 (1H, t, Ar); 7.16 (2H, t, Ar); 7.80
(2H, d, Ar)
125.07, 113.48 (2F, JAB ˆ 277.7);
2
124.89, 124.43 (2F, JAB ˆ 285.6)
(CD3CN): 3.54 (2H, s, NH2); 5.17 (1H, s, OH);
5.96 (1H, m, CH); 6.22 (1H, d, OH); 6.43
(CH3CN): 137.45 (2F, d,
2JHF ˆ 51.4); 129.57, 128.99
(KBr): 3390, 3275, 3110, 2990, 2910,
2760, 1670, 1620, 1575, 1500, 1470,
1455, 1420, 1380, 1360, 1350, 1300,
1240, 1225, 1190, 1140, 1105, 1080,
1040, 970, 960
2
3
2
(1H, t.t, CF2H, JHF ˆ 51.6, JHF ˆ 5.4); 7.13
(2F, JAB ˆ 289.3); 126.53, 121.82
2
(1H, t, Ar); 7.38 (2H, t, Ar); 7.88 (2H, d, Ar)
(2F, JAB ˆ 276.3); 123.07, 122.58
2
(2F, JAB ˆ 292.9)
5
9b
10
(C6D6): 1.90 (3H, t, CH3, JHH ˆ 2.7); 5.10
(n-hexane): 137.49 (2F, d,
2JHF ˆ 51.4); 129.57 (2F, s); 124.67
(2F, s); 105.93 (2F, s)
(KBr): 3100, 2950, 2880, 1730, 1675,
1610, 1510, 1470, 1450, 1420, 1355,
1325, 1180, 1130, 1090, 1060, 1040,
1010, 1000, 960
2
3
(1H, t, CF2H, JHF ˆ 51.0, JHF ˆ 5.7); 6.58
3
(1H, t, CHCF2, JHF ˆ 15.9); 6.97 (1H, t, Ar);
7.21 (2H, t, Ar); 8.11 (2H, d, Ar)
2
(DMSO-d6): 2.27 (6H, s, 2CH3); 4.31 (1H, t,
3
(CH3OH): 137.23 (2F, d, JHF ˆ 49.7);
(KBr): 3100, 2940, 1610, 1590, 1510,
1470, 1420, 1380, 1290, 1180, 1130,
1050, 1030
CHCF2, JHF ˆ 19.5); 6.96 (1H, t.t,
129.02 (2F, s); 121.41 (2F, s);
107.59 (2F, s)
2
CF2H, JHF ˆ 50.4); 7.27 (2H, t, Ar);
7.47 (4H, t, Ar); 7.71 (4H, d, Ar);
14.56 (2H, w.s, 2OH)
(C6D6): 1.20 2.45 (13H, Alk); 2.81 (1H, m, CH);
6.94 (1H, t, Ar); 7.21 (2H, t, Ar); 8.38 (2H, d, Ar)
3
12a
12b
(CHCl3): 70.35 (d, JHF ˆ 7.9)
(Film): 3080, 3010, 2930, 2870, 1720,
1610, 1510, 1460,1440, 1410, 1375,
1355, 1325, 1305, 1265, 1240, 1235,
1175, 1150, 1120, 1090, 1040, 1015
(C6D6): 1.19 2.45 (13H, Alk); 3.14 (1H, m, CH);
3
(CHCl3): 139.23 (d), 137.43 (d)
2
(Film): 3080, 3010, 2940, 2880, 1720,
1605, 1510, 1460, 1440, 1410, 1375,
1360, 1325, 1300, 1280, 1180, 1140,
1080, 1050, 1020, 1005, 950
2
2
5.14 (1H, t.t, CF2H, JHF ˆ 51.3, JHF ˆ 5.1);
(2F, JHF ˆ 54.2, JAB ˆ 307.6);
2
6.94 (1H, t, Ar); 7.21 (2H, t, Ar); 8.39 (2H, d, Ar)
131.94, 130.34 (2F, JAB ˆ 289.8),
2
124.19, 123.08 (2F, JAB ˆ 293.8);
3
118.65, 110.49 (2F, JHA ˆ 11.7,
3JHB ˆ 25.4, JAB ˆ 276.3)
2
2
13
14
(C6D6): 1.02±2.93 (7H, Alk); 3.59 (1H, d.d, CH);
3
(C6D6): 136.77 (2F, d, JHF ˆ 51.4);
(KBr): 2980, 1720, 1605, 1510, 1420,
1370, 1310, 1290, 1180, 1135, 1050
2
2
5.08 (1H, t.t, CF2H, JHF ˆ 51.6, JHF ˆ 5.1);
5.75 (1H, m, CH); 6.00 (1H, m, CH);
129.74, 129.16 (2F, JAB ˆ 291.0);
2
123.22, 122.74 (2F, JAB ˆ 300.3);
2
6.94 (1H, t, Ar); 7.21 (2H, t, Ar); 8.34 (2H, d, Ar)
(CDCl3): 2.18 (3H, s, CH3); 3.21 (3H, s, OCH3);
4.73 (1H, d.d, CHCF2); 6.05 (1H, t.t,
109.56, 104.72 (2F, JAB ˆ 274.3)
2
(CDCl3): 138.69 (2F, d, JHF ˆ 54.7);
(KBr): 3100, 3050, 1630, 1580, 1510,
1470, 1420, 1370, 1315, 1285, 1235,
1180, 1140, 1070, 1045, 985, 955
2
132.77, 131.23 (2F, JAB ˆ 287.8);
2
3
2
CF2H, JHF ˆ 51.9, JHF ˆ 5.4); 7.15 (1H, t, Ar);
126.23, 125.02 (2F, JAB ˆ 295.2);
2
7.24 (2H, t, Ar); 7.48 (2H, d, Ar)
125.30, 117.77 (2F, JAB ˆ 285.6)
a 13C NMR, ꢀ (ppm), J (Hz).

116
Yu.G. Shermolovich, S.V. Yemets / Journal of Fluorine Chemistry 101 (2000) 111±116
3.3. Synthesis of 1-phenyl-3-methyl-4-(2,2,3,3,4,4,5,5-
octafluoropentylidene)pyrazole-5-one (9b)
amount of residue after 4 h, washed with 3 Â 50 ml of water
and dried over Na2SO4. The solvent was removed in vacuo
(20 torr) and the oily residue was purified by column
chromatography (see Section 3).
Morpholinosulfur tri¯uoride [13] (7.2 mmol) was added
to a stirred suspension of pyrazole (4b) (6 mmol) in dichlor-
omethane (30 ml) at 08C. The obtained red solution was
stirred at 08C for 30 min and then heated up to 208C. The
solution was ®ltered from an insigni®cant amount of residue
after 6 h, washed with 3 Â 50 ml of water and dried over
Na2SO4. The solvent was removed in vacuo (20 torr) and the
oily residue was treated with n-hexane (20 ml). The red
solution was ®ltered from insoluble residue and n-hexane
was removed in vacuo (20 torr). Compound (9b) crystallizes
on storage at 208C over 24 h.
3.5. Synthesis of 1-phenyl-3-methyl-4-(1-methoxy-
2,2,3,3,4,4,5,5-octafluoropentyl)-5-hydroxypyrazole (14)
1-Phenyl-3-methyl-4-(2,2,3,3,4,4,5,5-octa¯uoropentyli-
dene)pyrazole-5-one (1.34 mmol) was dissolved in metha-
nol (15 ml). The solvent was removed in vacuo (20 torr) for
6 h and the oily residue was puri®ed by column chromato-
graphy (see Section 3).
References
3.4. Synthesis of spiro[(1-phenyl-3-methylpyrazole-5-one)-
4,50-(10,20-dimethyl-40-trifluoromethyl-cyclohexene)] (12a),
spiro[(1-phenyl-3-methyl-pyrazole-5-one)-4,50-(10,20-
dimethyl-40-(1,1,2,2,3,3,4,4-octafluorobutyl)cyclohexene)]
(12b), spiro-[(1-phenyl-3-methylpyrazole-5-one)-4,50-(60-
(1,1,2,2,3,3,4,4-octafluorobutyl)bicyclo[2.2.1]hept-2-ene)]
(13)
[1] L.M. Yagupolskii, Aromatic and Heterocyclic Compounds with
Fluorocontaining Substituents, Naukova Dumka, Kiev, 1988, 320pp.
[2] F. Sauter, P. Stanetty, W. Ramer, W. Sittenthaler, Monatshefte 122
(1991) 879.
[3] C. Francese, M. Tordeux, C. Wakselman, J. Chem. Soc., Perkin
Trans. 1 (1990) 1951.
[4] A. Sugimori, T. Yamada, H. Ishida, M. Nose, K. Terashima, N.
Oohata, Bull. Chem. Soc. Jpn. 59 (1986) 3905.
1. Diene (Aldrich) (1.26 mmol) was added to the solution
of equimolar amounts of 1-phenyl-3-methyl-4-
(2,2,3,3,4,4,5,5-octafluoropentylidene)pyrazole-5-one
(9b) in chloroform (8 ml). The solvent was removed in
vacuo (20 torr) over 24 h. The oily residue was purified
by column chromatography (see Section 3).
2. Morpholinosulfur trifluoride (7.38 mmol) was added to
a stirred suspension of pyrazole (4a) (5.68 mmol) in
chloroform (20 ml) at 08C. The obtained red solution
was stirred at 08C for 30 min and then heated to 208C.
The mixture was stirred at 208C for 20 min and then
2,3-dimethylbutadiene (Aldrich) (8.52 mmol) was
added. The solution was filtered from an insignificant
[5] R.J. Linderman, D.M. Graves, J. Org. Chem. 54 (1989) 661.
[6] W.A. Sheppard, J. Am. Chem. Soc. 87 (1965) 2410.
[7] E.A. Halliman, T.G. Hagen, R.K. Husa, S. Tsymbalov, S.N. Rao,
J.-P. Van Hoeck, M.F. Raffery, A. Stapelfeld, M.A. Savage, M.
Reichman, J. Med. Chem. 36 (1993) 3293.
[8] E.A. Halliman, T.G. Hagen, S. Tsymbalov, R.K. Husa, A.C. Lee, A.
Stapelfeld, M.A. Savage, J. Med. Chem. 39 (1996) 609.
[9] H. Gourlaouen, P. Pastour, Compt. Rend. 256 (1963) 3319.
[10] A.E. Derome, Modern NMR Techniques for Chemical Research,
Pergamon Press, Oxford, 1988.
[11] A.R. Katritzky, W.Q. Fan, J. Fluor. Chem. 51 (1991) 33.
[12] E. Ceulemans, M. Voets, S. Emmers, W. Dehaen, Synlett (1997)
1155.
[13] L.N. Markovskij, V.E. Pashinnik, A.V. Kirsanov, Synthesis 51 (1973)
3203.