Synthesis of fluoroalkyl-containing 1,2,3-triketone 2-hetarylhydrazones and their reactions with hydrazines

Article abstract of DOI:10.1007/s11172-005-0158-y

Fluoroalkyl-containing 1,2,3-triketone 2-(2,3-dimethyl-5-oxo-1-phenyl-1,2- dihydropyrazol-4-yl)-, 2-(4-ethoxycarbonylpyrazol-3-yl)-, and 2-(1,2,4-triazol-3-yl)hydrazones were synthesized by the azo coupling reactions of fluorinated 1,3-diketones with the

Full text of DOI:10.1007/s11172-005-0158-y

2584
Russian Chemical Bulletin, International Edition, Vol. 53, No. 11, pp. 2584—2590, November, 2004
Synthesis of fluoroalkylꢀcontaining 1,2,3ꢀtriketone 2ꢀhetarylhydrazones
and their reactions with hydrazines
ꢀ
E. V. Shchegol´kov, Ya. V. Burgart, O. G. Khudina, V. I. Saloutin, and O. N. Chupakhin
I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
20 ul. S. Kovalevskoi, 620219 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 5954. Eꢀmail: saloutin@ios.uran.ru
Fluoroalkylꢀcontaining 1,2,3ꢀtriketone 2ꢀ(2,3ꢀdimethylꢀ5ꢀoxoꢀ1ꢀphenylꢀ1,2ꢀdihydroꢀ
pyrazolꢀ4ꢀyl)ꢀ, 2ꢀ(4ꢀethoxycarbonylpyrazolꢀ3ꢀyl)ꢀ, and 2ꢀ(1,2,4ꢀtriazolꢀ3ꢀyl)hydrazones were
synthesized by the azo coupling reactions of fluorinated 1,3ꢀdiketones with the corresponding
hetaryldiazonium chlorides. The hetarylhydrazones thus synthesized were subjected to
cyclocondensation with hydrazines at the 1,3ꢀdicarbonyl fragment to give 3ꢀfluoroalkylꢀ4ꢀ
hetarylazopyrazoles.
Key words: fluoroalkylꢀcontaining 1,3ꢀdiketones, hetaryldiazonium salts, 1,2,3ꢀtriketone
2ꢀhetarylhydrazones, hydrazines, pyrazoles.
Scheme 1
Nonfluorinated 1,3ꢀdiketones are involved in azo couꢀ
pling reactions with diazolylꢀ1—3 and triazolyldiazonium4,5
salts in an aqueousꢀalcoholic medium in the presence of
sodium acetate to form 1,2,3ꢀtriketone 2ꢀhetarylhydrꢀ
azones. The construction of new heterocyclic 1,2,3ꢀtriꢀ
ketone hydrazones and investigation of their properties
are of interest because of the complexꢀforming ability of
these compounds,1 their tendency to undergo intramoꢀ
lecular cyclization,2,4,5 and the possibility of condensaꢀ
tion with nucleophilic reagents at the 1,3ꢀdicarbonyl fragꢀ
ment. For fluorineꢀcontaining representatives of this class
of compounds, only the synthesis of trifluoromethylꢀ and
pentafluoroethylꢀsubstituted 1,2,3ꢀtriketone 2ꢀ(4ꢀphenylꢀ
1Hꢀpyrazolꢀ5ꢀyl)hydrazones was described.6
1: R = Bu, RF = H(CF2)2 (a);
R = Me, RF = HCF2 (b), CF3 (c);
R = Ph, RF = C3F7 (d), CF3 (e), H(CF2)2 (f)
The present study was aimed at synthesizing fluoroꢀ
alkylꢀcontaining 1,2,3ꢀtriketone 2ꢀ(2,3ꢀdimethylꢀ5ꢀ
oxoꢀ1ꢀphenylꢀ1,2ꢀdihydropyrazolꢀ4ꢀyl)ꢀ, 2ꢀ(4ꢀethoxyꢀ
carbonylpyrazolꢀ3ꢀyl)ꢀ, and 2ꢀ(1,2,4ꢀtriazolꢀ3ꢀyl)hydrꢀ
azones and investigating their heterocyclization with hydrꢀ
azines.
It was found that fluoroalkylꢀcontaining 1,3ꢀdiketones
1a—f are coupled with (2,3ꢀdimethylꢀ5ꢀoxoꢀ1ꢀphenylꢀ
1,2ꢀdihydropyrazolꢀ4ꢀyl)ꢀ, (4ꢀethoxycarbonylpyrazolꢀ
3ꢀyl)ꢀ, and (1,2,4ꢀtriazolylꢀ3ꢀyl)diazonium chlorides in
the presence of sodium acetate to give 1,2,3ꢀtriketone
2ꢀhetarylhydrazones 2a—i in 38—70% yields (Scheme 1).
Moderate yields of hetarylhydrazones 2a—i are attribꢀ
utable to various side reactions with Japp—Klingemann
hydrolysis predominating. In the azo coupling reaction of
1,3ꢀdiketone 1g containing the bulky tertꢀbutyl substituꢀ
ent, the Japp—Klingemann cleavage becomes the major
process, because compound 3 was isolated as the main
reaction product. According to the 1H NMR spectroꢀ
scopic data, the latter exists in a CDCl3 solution as a
mixture of hydrazoneꢀketone (A) and azoꢀenol (B) tauꢀ
tomers (Scheme 2).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2478—2483, November, 2004.
1066ꢀ5285/04/5311ꢀ2584 © 2004 Springer Science+Business Media, Inc.

1,2,3ꢀTriketone 2ꢀhetarylhydrazones
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 11, November, 2004 2585
Scheme 2
Since both azoꢀhydrazone and ketoꢀenol tautomerꢀ
isms are possible for compounds 2a—i, they can exist as
three tautomers (C, D, and E).
and a downfield shift of the signal for the proton of the
hydrazone group in the 1H NMR spectra (see the Experiꢀ
mental section). The presence of one set of signals in the
1H and 19F NMR spectra of hetarylhydrazones 2a,c,e—i
indicates that these compounds exist as one isomer. The
exceptions are hetarylhydrazones 2b,d, whose NMR specꢀ
tra have two sets of identical signals.
In our opinion, the structures of isomers cannot unꢀ
ambiguously be judged from the available data. However,
we succeeded in establishing the structure of an isomer
for one compound. In the 13C NMR spectrum of comꢀ
pound 2c, the signal of the methyl group at the C=C bond
of the antipyrine fragment appears as a quartet (δC of
C(9) 11.27) with a coupling constant of 1.5 Hz due to
spinꢀspin coupling between the carbon nucleus of this
methyl group and the fluorine nuclei of the trifluoromethyl
substituent. This is possible only in the case of the isoꢀ
mer D (see the Experimental section).
Taking into account that the IR spectra of these comꢀ
pounds show characteristic absorption bands of carbonyl
groups at 1650—1700 cm–1 and the fact that a signal for
the methine proton is absent in the 1H NMR spectra (see
the Experimental section), the hydrazoneꢀdiketo form D
seems to be preferable for these products.
In addition, 1,2,3ꢀtriketone 2ꢀhetarylhydrazones 2 are
characterized by isomerism associated with the different
positions of the hetarylhydrazone substituent with respect
to the C=N bond (structures D and D´).
Most likely, other 1,2,3ꢀtriketone 2ꢀhetarylhydrazones
2a,e—i also exist in CDCl3 and DMSOꢀd6 solutions as
the isomer D, whereas 1,2,3ꢀtriketone 2ꢀ(2,3ꢀdimethylꢀ
5ꢀoxoꢀ1ꢀphenylꢀ1,2ꢀdihydropyrazolꢀ4ꢀyl)hydrazones
These isomers are stabilized through an intramolecuꢀ
lar hydrogen bond, resulting in a lowꢀfrequency shift of
absorption bands of the carbonyl groups in the IR spectra

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Russ.Chem.Bull., Int.Ed., Vol. 53, No. 11, November, 2004
Shchegol´kov et al.
2b,d exist as mixtures of the isomers D and D´, with the
former essentially predominating.
We demonstrated that the aboveꢀdescribed 1,2,3ꢀtriꢀ
ketone 2ꢀhetarylhydrazones can be used for the construcꢀ
tion of new heterocyclic systems. These compounds react
with hydrazine hydrate, methylhydrazine, (2ꢀhydroxyꢀ
ethyl)hydrazine, and phenylhydrazine at the 1,3ꢀdicarboꢀ
nyl fragment to give pyrazole derivatives 4a—c, 5a,b, 6a,b,
and 7a—c in 58—77% yields (Scheme 3). In some cases
(see the Experimental section), BF3•Et2O was added as a
catalyst.
For compounds 4a—c, azoꢀhydrazone tautomerism
can occur, as opposed to Nꢀsubstituted pyrazoles 5—7
existing in the azo form. However, the same character of
absorption bands in the UV spectra of pyrazoles 4c and 7b
provides evidence in favor of the 4ꢀtriazolylazo form of
pyrazole 4c (see the Experimental section). A comparaꢀ
tive analysis of the IR and NMR spectroscopic characterꢀ
istics of pyrazoles 4a—c led us to the conclusion that
these compounds exist in the azo form.
Scheme 3
Cyclocondensation of 1,2,3ꢀtriketone 2ꢀhetarylhydrꢀ
azones with substituted hydrazines can afford 3ꢀRF and
5ꢀRF regioisomers or their mixtures.
Earlier,7 we have synthesized pyrazoles from the corꢀ
responding fluoroalkylꢀcontaining 1,2,3ꢀtriketone 2ꢀarylꢀ
hydrazones by the reaction with phenylhydrazine. Howꢀ
ever, the position of the Nꢀphenyl substituent in these
heterocycles was not determined. To establish the regioꢀ
isomeric structures of the pyrazoles, we synthesized
Nꢀmethylꢀsubstituted pyrazoles by condensation of triꢀ
fluoromethylꢀcontaining 1,2,3ꢀtriketone 2ꢀarylhydrazones
with methylhydrazine (see Scheme 3).
1
It is known that the H NMR spectrum of 1ꢀmethylꢀ
5ꢀtrifluoromethylpyrazole derived from 5ꢀtrifluoroacetylꢀ
adamantanꢀ4ꢀone has signals for the protons of the meꢀ
thyl group as a quartet with a coupling constant of 1.2 Hz
due to spinꢀspin coupling with the vicinal trifluoromethyl
group,8 whereas the spinꢀspin coupling constant in the
spectra of 1ꢀmethylꢀ3ꢀtrifluoromethylpyrazoles prepared
from 2ꢀtrifluoroacetylcyclohexanone and 5ꢀtrifluoroꢀ
acetyladamantanꢀ4ꢀone is either equal to 0.6 Hz or is not
observed at all.8,9
1
In the H and 19F NMR spectra of trifluoromethylꢀ
and Nꢀmethylꢀsubstituted pyrazoles 5a,b,d, the signals of
the methyl and trifluoromethyl groups appear as singlets.
Only the 19F NMR spectrum of pyrazole 5c shows a quarꢀ
tet of the trifluoromethyl group with a spinꢀspin coupling
constant of 0.5 Hz (see the Experimental section). In
addition, the 2D NOESY spectrum of pyrazole 5c has a
crossꢀpeak between the protons of the Nꢀmethyl group

1,2,3ꢀTriketone 2ꢀhetarylhydrazones
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 11, November, 2004 2587
and the Cꢀmethyl protons, which can occur in the 3ꢀRF
isomer.
selective cyclocondensation with hydrazines to give
3ꢀRFꢀpyrazoles.
The results of NMR spectroscopy indicate that
pyrazoles 5a—c have 3ꢀRFꢀregioisomeric structures.
Heterocycles 6a,b containing the Nꢀ(2ꢀhydroxyethyl) subꢀ
stituent exist as 3ꢀRF regioisomers, because the 1H NMR
spectra of these compounds do not show an additional
coupling between the methylene protons and the fluorine
nuclei.
Experimental
The IR spectra were measured on a Perkin Elmer Spectrum
One Fourierꢀtransform IR spectrometer in a 4000—400ꢀcm–1
region. The NMR spectra were recorded on a Bruker DRXꢀ400
spectrometer (400 MHz for 1H and 100.6 MHz for 13C, relative
to SiMe4; 75 MHz for 19F, relative to C6F6). The UV spectra
were measured on a Shimadzu UVꢀ2401 PC spectrophotometer.
Elemental analysis was carried out on a Carlo Erba CHNSꢀO
EA 1108 elemental analyzer.
In the study,10 the authors reasoned that the regioꢀ
isomeric structures of pyrazoles can be judged from the
chemical shifts of the protons of the Cꢀmethyl groups in
1
the H NMR spectra recorded in CDCl3, because these
Synthesis of 1,2,3ꢀtriketone 2ꢀhetarylhydrazones (general
procedure). Hetaryldiazonium salts were prepared as follows.
Hetarylamine (10 mmol) was placed in a twoꢀneck flask equipped
with a stirrer and a dropping funnel. Then a dilute hydrochloric
acid solution, which was prepared from concentrated HCl (3 mL)
and water (10 mL), was added, and a solution of sodium nitrite
(0.70 g) in water (3 mL) was slowly added dropwise with vigorꢀ
ous stirring and cooling to 0 °C. In another flask, a solution of
sodium acetate (4.55 g) in water (8 mL) was mixed with a soluꢀ
tion of 1,3ꢀdiketone 1a—g (10 mmol) in ethanol (31 mL).
A solution of the hetaryldiazonium salt was slowly added
dropwise to the resulting mixture at 10 °C. At the end of the
addition of the salt, precipitation of crystals of hydrazone started.
The precipitate was filtered off, recrystallized from ethanol, and
dried in vacuo.
signals in the spectra of 3ꢀmethylꢀ and 5ꢀmethylpyrazoles
are observed at δ 2.3 and 2.7, respectively. The 1H NMR
spectra of all Cꢀmethylꢀcontaining pyrazoles synthesized
in the present study, which were recorded both in CDCl3
and DMSOꢀd6, show signals of the methyl group at
δ 2.58—2.63, which indicates that these compounds have
5ꢀMeꢀregioisomeric structures.
In addition, the regioisomeric structures of these comꢀ
pounds are also evidenced by the position of the signal of
the trifluoromethyl group in the 19F NMR spectra. The
signal of the trifluoromethyl substituent in the 19F NMR
spectra of 4ꢀfluorineꢀsubstituted11 and 4ꢀunsubstituted
pyrazoles12 is observed at δ ~101 (C6F6 as the internal
standard) and ~105 for the 3ꢀCF3 and 5ꢀCF3 isomers,
respectively. Pyrazoles 4c, 5a—d, 6a, and 7b containing
the trifluoromethyl substituent are characterized by the
chemical shift at δ 99.76—100.27 in CDCl3 and at
δ 100.32—102.33 in DMSOꢀd6, which corresponds to the
3ꢀCF3 isomer.
Earlier,13 it has been found that the signals of the
αꢀCF2ꢀgroup in the 3ꢀfluoroalkyl substituent of pyrazoles
have a diamagnetic shift relative to 54 ppm (C6F6 as the
internal standard). Since the chemical shifts of the αꢀCF2
group of the polyfluoroalkyl substituents in the spectra of
pyrazoles 4a,b, 6b, and 7a,c are 48.02—53.10 ppm (in
DMSOꢀd6), we studied the structures of the 3ꢀfluoroalkyl
derivatives of pyrazoles containing the HCF2 and H(CF2)2
substituents.
It is known that the reactions of fluorineꢀcontaining
enolized 1,3ꢀdiketones with hydrazines can afford two
regioisomers, whereas 1,3ꢀdiketones, which exist predomiꢀ
nantly in the diketo form (for example, 1,1,1,3ꢀtetraꢀ
fluoromethylpentaneꢀ2,4ꢀdione), form the 3ꢀCF3 regioꢀ
isomer11 due to the attack of the primary amino group of
hydrazine on the more electrophilic carbonyl group, i.e.,
on the trifluoroacetyl group. 1,2,3ꢀTriketone 2ꢀ(het)arylꢀ
hydrazones 2a—i synthesized in the present study exist
exclusively in the hydrazoneꢀdiketo form D and, apparꢀ
ently, that is why they react with hydrazines to form exꢀ
clusively the 3ꢀRF regioisomers.
1,1,2,2ꢀTetrafluorononaneꢀ3,4,5ꢀtrione 4ꢀ(2,3ꢀdimethylꢀ5ꢀ
oxoꢀ1ꢀphenylꢀ1,2ꢀdihydropyrazolꢀ4ꢀyl)hydrazone (2a). The yield
was 50%, m.p. 124—126 °C. IR (CHCl3), ν/cm–1: 3310, 1590
(NH); 1680, 1670 (C=O); 1615, 1520, 1500 (C=N, C=C);
1070—1140 (C—F). 1H NMR (CDCl3), δ: 0.93 (t, 3 H,
3
(CH2)3Me, JH,H = 7.5 Hz); 1.38, 1.61, and 2.97 (all m, 2 H
each, (CH2)3Me); 2.49 (s, 3 H, Me); 3.19 (s, 3 H, NMe); 6.77
(tt, 1 H, H(CF2)2, 2JH,F = 53.0 Hz, 3JH,F = 5.8 Hz); 7.36—7.52
(m, 5 H, Ph); 15.44 (s, 1 H, NH). 19F NMR (CDCl3), δ: 24.16
(dt, 2 F, HCF2, 2JF,H = 53.0 Hz, 3JF,F = 8.0 Hz); 41.42 (m, 2 F,
CF2). Found (%): C, 54.13; H, 5.16; F, 17.17; N, 12.77.
C
20H22F4N4O3. Calculated (%): C, 54.30; H, 5.01; F, 17.18;
N, 12.66.
1,1ꢀDifluoropentaneꢀ2,3,4ꢀtrione 3ꢀ(2,3ꢀdimethylꢀ5ꢀoxoꢀ
1ꢀphenylꢀ1,2ꢀdihydropyrazolꢀ4ꢀyl)hydrazone (2b). The yield
was 45%, m.p. 158—160 °C. IR (CHCl3), ν/cm–1: 3445, 1595
(NH); 1700, 1665, 1660 sh (C=O); 1615, 1525, 1490 (C=N,
C=C); 1050—1180 (C—F). 1H NMR (CDCl3, δ) of a mixture of
isomers D—D´ (85 : 15); isomer D, 2.52 and 2.62 (both s,
3 H each, Me); 3.19 (s, 3 H, NMe); 6.57 (t, 1 H, HCF2, 2JH,F
=
53.0 Hz); 7.27—7.52 (m, 5 H, Ph); 15.05 (s, 1 H, NH); isoꢀ
mer D´, 2.43 and 2.59 (both s, 3 H each, Me); 3.20 (s, 3 H,
2
NMe); 6.83 (t, 1 H, HCF2, JH,F = 53.0 Hz); 7.27—7.52 (m,
5 H, Ph); 14.38 (s, 1 H, NH). 19F NMR (CDCl3), δ: isomer D,
2
34.45 (d, HCF2, JF,H = 53.0 Hz); isomer D´, 33.21 (d, HCF2,
2JF,H = 53.0 Hz). Found (%): C, 53.47; H, 4.46; F, 11.14;
N, 16.23. C15H16F2N4O3. Calculated (%): C, 53.25; H, 4.74;
F, 11.23; N, 16.56.
1,1,1ꢀTrifluoropentaneꢀ2,3,4ꢀtrione 3ꢀ(2,3ꢀdimethylꢀ5ꢀoxoꢀ
1ꢀphenylꢀ1,2ꢀdihydropyrazolꢀ4ꢀyl)hydrazone (2c). The yield
was 43%, m.p. 173—175 °C. IR (CHCl3), ν/cm–1: 3450, 1595
(NH); 1695, 1685, 1670 (C=O); 1610, 1525, 1490 (C=N, C=C);
Therefore, we established that fluoroalkylꢀcontaining
1,2,3ꢀtriketone 2ꢀ(het)arylhydrazones undergo regioꢀ

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Russ.Chem.Bull., Int.Ed., Vol. 53, No. 11, November, 2004
Shchegol´kov et al.
3
3
1120—1230 (C—F). 1H NMR (CDCl3), δ: 2.56 and 2.59 (both s,
3 H each, Me); 3.21 (s, 3 H, NMe); 7.35—7.52 (m, 5 H, Ph);
15.34 (s, 1 H, NH). 13C NMR (CDCl3), δ: 11.27 (q, C(9),
JC,F = 1.5 Hz); 30.99 (C(1)); 35.60 (C(10)); 113.29—129.53
(C(11), C(12), C(13), C(14), C(15), C(16)); 117.52 (q, C(5),
JC,F = 292.4 Hz); 133.79 (C(3)); 144.22 (C(8)); 158.50 (C(7));
176.45 (q, C(4), JC,F = 32.2 Hz); 196.94 (C(2)); 196.95
2JH,F = 53.0 Hz, JH,F = 10.0 Hz, JH,F = 3.1 Hz); 7.48—7.91
(m, 5 H, Ph); 7.91 (s, 1 H, CH=), 8.97 (d, 1 H, NH, J =
3.1 Hz); 13.09 (s, 1 H, NH). 19F NMR (DMSOꢀd6/CCl4), δ:
2
27.66 (m, 2 F, CF2, AB system, ∆ν = 268.9, JF,F = 296.6 Hz);
38.08 (m, 2 F, HCF2, AB system, ∆ν = 557.7, 2JF,F = 266.1 Hz,
2JF,H = 53.0 Hz). Found (%): C, 45.41; H, 2.51; F, 22.25;
N, 20.33. C13H9F4N5O2. Calculated (%): C, 45.49; H, 2.64;
F, 22.14; N, 20.40.
2
(C(6)). 19F NMR (CDCl3), δ: 91.06 (d, CF3, JF,H = 0.7 Hz).
Found (%): C, 52.19; H, 3.93; F, 15.51; N, 15.37.
4,4,5,5,6,6,6ꢀHeptafluoroꢀ1ꢀphenylhexaneꢀ1,2,3ꢀtrione
2ꢀ(1Hꢀ1,2,4ꢀtriazolꢀ3ꢀyl)hydrazone (2i). The yield was 61%,
m.p. 181—183 °C. IR (Nujol mulls), ν/cm–1: 3250, 3210, 1590
(NH); 1655 sh, 1650 (C=O), 1610, 1550, 1500 (C=N, C=C);
1100—1200 (C—F). 1H NMR (DMSOꢀd6/CCl4), δ: 7.30—7.80
(m, 5 H, Ph); 7.93 (s, 1 H, CH=); 9.20 and 13.23 (both s,
1 H each, 2 NH). Found (%): C, 40.80; H, 1.83; F, 32.18;
N, 16.76. C14H8F7N5O2. Calculated (%): C, 40.89; H, 1.96;
F, 32.34; N, 17.03.
3,3ꢀDimethylbutaneꢀ1,2ꢀdione 1ꢀ(2,3ꢀdimethylꢀ5ꢀoxoꢀ1ꢀ
phenylꢀ3ꢀpyrazolinꢀ4ꢀyl)hydrazone (3). The yield was, 35%, m.p.
164—165 °C. IR (CHCl3), ν/cm–1: 3440, 1590 (NH); 1680
(C=O); 1610, 1550, 1500 (C=N, C=C). 1H NMR (CDCl3, δ) of
a mixture of tautomers A—B (85 : 15), tautomer A, 1.22 (s, 9 H,
CMe3); 2.43 and 2.99 (both s, 3 H each, NMe); 7.19 (s, 1 H,
CH=); 7.26—7.47 (m, 5 H, Ph); 13.96 (s, 1 H, NH); tauꢀ
tomer B, 1.30 (s, 9 H, CMe3); 2.44 (s, 3 H, Me); 3.01 (s, 3 H,
NMe); 7.19 (s, 1 H, CH=); 7.26—7.47 (m, 5 H, Ph); 7.87 (s,
1 H, OH). Found (%): C, 64.74; H, 7.27; N, 18.30. C17H22N4O2.
Calculated (%): C, 64.95; H, 7.05; N, 17.82.
C
16H15F3N4O3. Calculated (%): C, 52.18; H, 4.11; F, 15.47;
N, 15.21.
4,4,4,5,5,6,6ꢀHeptafluoroꢀ1ꢀphenylhexaneꢀ1,2,3ꢀtrione
2ꢀ(2,3ꢀdimethylꢀ5ꢀoxoꢀ1ꢀphenylꢀ1,2ꢀdihydropyrazolꢀ4ꢀ
yl)hydrazone (2d). The yield was 38%, m.p. 119—120 °C.
IR (CHCl3), ν/cm–1: 3445, 1600 (NH); 1690, 1680 (C=O);
1630, 1610, 1530, 1500 (C=N, C=C); 1125—1240 (C—F).
1H NMR (CDCl3, δ) of a mixture of isomers D—D´ (90 : 10),
isomer D, 2.56 (s, 3 H, Me); 3.19 (s, 3 H, NMe); 7.35—7.57 (m,
10 H, 2Ph); 13.87 (s, 1 H, NH); isomer D´, 2.59 (s, 3 H, Me);
3.09 (s, 3 H, NMe); 7.35—7.57 (m, 10 H, 2 Ph); 13.94 (s, 1 H,
NH). 19F NMR (CDCl3), δ: isomer D, 37.37 and 48.88 (both m,
2 F each, CF2); 81.76 (m, 3 F, CF3); isomer D´, 35.15 and 48.32
(both m, 2 F each, (CF2)2); 81.32 (m, 3 F, CF3). Found (%):
C, 51.91; H, 3.34; F, 24.84; N, 10.50. C23H17F7N4O3. Calcuꢀ
lated (%): C, 52.08; H, 3.23; F, 25.07; N, 10.56.
1,1,1ꢀTrifluoropentaneꢀ2,3,4ꢀtrione 3ꢀ(1Hꢀ4ꢀethoxycarꢀ
bonylpyrazolꢀ3ꢀyl)hydrazone (2e). The yield was 66%, m.p.
152—154 °C. IR (CHCl3), ν/cm–1: 3270, 3210 (NH); 1700,
1680 (C=O); 1610, 1560 (C=N, C=C); 1100—1235 (C—F).
1H NMR (DMSOꢀd6), δ: 1.30 (t, 3 H, CO2CH2CH3, J = 7.1 Hz);
2.44 (s, 3 H, MeCO); 4.29 (q, 3 H, CO2CH2CH3, J = 7.1 Hz);
8.03 (s, 1 H, CH=); 8.94 and 12.74 (both s, 1 H each, 2 NH).
19F NMR (DMSOꢀd6), δ: 85.71 (t, CF3, J = 0.8 Hz). Found (%):
C, 41.29; H, 3.53; F, 17.53; N, 17.33. C11H11F3N4O4. Calcuꢀ
lated (%): C, 41.26; H, 3.46; F, 17.80; N, 17.50.
4,4,4ꢀTrifluoroꢀ1ꢀphenylbutaneꢀ1,2,3ꢀtrione 2ꢀ(1Hꢀ4ꢀ
ethoxycarbonylpyrazolꢀ3ꢀyl)hydrazone (2f). The yield was 62%,
m.p. 183—185 °C. IR (CHCl3), ν/cm–1: 3250, 3205, 1600 (NH);
1690 (C=O); 1635, 1610 (C=N, C=C); 1145—1245 (C—F).
1H NMR (DMSOꢀd6), δ: 1.99 (t, 3 H, CO2CH2CH3, J = 7.1 Hz);
4.28 (m, 2 H, CO2CH2CH3, J = 7.1 Hz); 7.53—7.80 (m, 5 H,
Ph); 8.07 (s, 1 H, CH=); 9.32 and 12.65 (both s, 1 H each,
2 NH). 19F NMR (DMSOꢀd6), δ: 85.84 (s, CF3). Found (%):
C, 50.00; H, 3.38; F, 14.89; N, 14.57. C16H13F3N4O4. Calcuꢀ
lated (%): C, 49.62; H, 3.38; F, 14.91; N, 14.66.
4,4,4ꢀTrifluoroꢀ1ꢀphenylbutaneꢀ1,2,3ꢀtrione 2ꢀ(1Hꢀ1,2,4ꢀ
triazolꢀ3ꢀyl)hydrazone (2g). The yield was 58%, m.p.
225—227 °C. IR (Nujol mulls), ν/cm–1: 3270, 3205, 1590 (NH);
1655 sh, 1650 (C=O); 1600, 1550, 1530 (C=N, C=C);
1100—1200 (C—F). 1H NMR (DMSOꢀd6/CCl4), δ: 7.46—7.82
(m, 5 H, Ph); 7.86 (s, 1 H, CH=); 9.04 and 13.09 (both s,
1 H each, 2 NH). 19F NMR (DMSOꢀd6/CCl4), δ: 84.26 (s,
CF3). Found (%): C, 46.48; H, 2.64; F, 18.04; N, 22.49.
C12H8F3N5O2. Calculated (%): C, 46.31; H, 2.59; F, 18.31;
N, 22.50.
Reaction of 1,2,3ꢀtriketone 2ꢀhydrazones with hydrazines
(general procedure). 1,2,3ꢀTriketone hydrazone (3 mmol) was
dissolved in ethanol (in isobutanol for 5d) (30 mL). Then hydrꢀ
azine (3 mmol) was added, and boron trifluoride etherate
(0.5 mL) (for compounds 4b,c, 5a,c,d, and 6a) was added
dropwise. The reaction mixture was refluxed for 4 h. The preꢀ
cipitate that formed was filtered off and dried in vacuo.
4ꢀ(3ꢀDifluoromethylꢀ5ꢀmethylꢀ1Hꢀpyrazolꢀ4ꢀylazo)ꢀ2,3ꢀ
dimethylꢀ1ꢀphenylꢀ1,2ꢀdihydropyrazolꢀ5ꢀone (4a). The yield
was 62%, m.p. 219—221 °C (from ethanol). IR (Nujol mulls),
ν/cm–1: 3200, 1580 (NH); 1660 (C=O); 1600, 1545, 1490 (C=N,
C=C, N=N); 1020—1100 (C—F). 1H NMR (DMSOꢀd6), δ:
2.45 and 2.58 (both s, 3 H each, 2 Me); 3.33 (s, 3 H, NMe); 7.10
(t, 1 H, HCF2, 2JH,F = 53.0 Hz); 7.24—7.57 (m, 5 H, Ph); 13.24
(s, 1 H, NH). 19F NMR (DMSOꢀd6), δ: 48.31 (d, HCF2, 2JF,H
=
53.0 Hz). Found (%): C, 55.20; H, 4.56; F, 10.77; N, 24.28.
C16H16F2N6O. Calculated (%): C, 55.49; H, 4.66; F, 10.97;
N, 24.27.
4ꢀ(5ꢀButylꢀ3ꢀtetrafluoroethylꢀ1Hꢀpyrazolꢀ4ꢀylazo)ꢀ2,3ꢀdiꢀ
methylꢀ1ꢀphenylꢀ1,2ꢀdihydropyrazolꢀ5ꢀone (4b). The yield
was 69%, m.p. 215—216 °C (reprecipitated from chloroform
with hexane). IR (Nujol mulls), ν/cm–1: 3100, 1550 (NH);
1635 (C=O); 1600, 1490 (C=N, C=C, N=N); 1100—1220
3
(C—F). 1H NMR (DMSOꢀd6), δ: 0.93 (t, 3 H, Me, JH,H
=
=
3
7.5 Hz); 1.40, 1.69, and 2.97 (all m, 2 H each, 3 CH2, JH,H
7.5 Hz); 2.61 (s, 3 H, Me); 3.33 (s, 3 H, NMe); 6.93 (tt,
1 H, H(CF2)2, 2JH,F = 53.0 Hz, 3JH,F = 5.7 Hz); 7.35—7.52 (m,
5 H, Ph); 10.11 (s, 1 H, NH). 19F NMR (DMSOꢀd6), δ: 23.58
(dt, 2 F, HCF2, 2JF,H = 53.0 Hz, 3JF,F = 9.5 Hz); 48.54 (m, 2 F,
CF2). Found (%): C, 54.51; H, 4.97; F, 17.15; N, 19.29.
4,4,5,5ꢀTetrafluoroꢀ1ꢀphenylpentaneꢀ1,2,3ꢀtrione
2ꢀ(1Hꢀ1,2,4ꢀtriazolꢀ3ꢀyl)hydrazone (2h). The yield was 70%,
m.p. 205—206 °C. IR (Nujol mulls), ν/cm–1: 3290, 3190, 1580
(NH); 1650 (C=O); 1600, 1540 (C=N, C=C); 1110—1210
(C—F). 1H NMR (DMSOꢀd6/CCl4), δ: 6.75 (tdd, 1 H, H(CF2)2,
C
20H22F4N6O. Calculated (%): C, 54.79; H, 5.06; F, 17.33;
N, 19.17.

1,2,3ꢀTriketone 2ꢀhetarylhydrazones
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 11, November, 2004 2589
3ꢀ(5ꢀPhenylꢀ3ꢀtrifluoromethylꢀ1Hꢀpyrazolꢀ4ꢀylazo)ꢀ1Hꢀ
1,2,4ꢀtriazole (4c). The yield was 68%, m.p. 167—168 °C. The
product was purified by column chromatography (chloroform as
the eluent). IR (Nujol mulls), ν/cm–1: 3110, 1580 (NH); 1480
(C=C, C=N); 1080—1220 (C—F). UV (MeOH), λmax/nm (ε):
3ꢀ[1ꢀ(2ꢀHydroxyethyl)ꢀ5ꢀphenylꢀ3ꢀtetrafluoroethylpyrazolꢀ
4ꢀylazo]ꢀ1Hꢀ1,2,4ꢀtriazole (6b). The yield was 58%, m.p.
168—170 °C. The product was purified by column chromatoꢀ
graphy (chloroform—ethanol, 1 : 50, as the eluent). IR (Nujol
mulls), ν/cm–1: 3100, 1550 (NH); 1500, 1480 (C=N, C=C,
1
1
206 (10560), 248 (10980), 335 (11980), 436 sh (720). H NMR
N=N); 1080—1190 (C—F). H NMR (DMSOꢀd6), δ: 3.82 (q,
(DMSOꢀd6/CCl4), δ: 7.47—8.06 (m, 5 H, Ph); 8.52 (s, 1 H,
CH=); 14.40 (s, 2 H, 2 NH). 19F NMR (DMSOꢀd6/CCl4), δ:
100.32 (s, CF3). Found (%): C, 46.95; H, 3.10; F, 18.36;
N, 29.75. C12H8F3N7. Calculated (%): C, 46.91; H, 2.62;
F, 18.52; N, 31.91.
2 H, CH2; 3JH,H = 5.4 Hz); 4.21 (t, 2 H, CH2; 3JH,H = 5.4 Hz);
3
5.07 (t, 1 H, OH; JH,H = 5.4 Hz); 6.95 (tt, 1 H, H(CF2)2;
2JH,F = 53.0 Hz; 3JH,F = 5.0 Hz); 7.45—7.69 (m, 5 H, Ph); 8.62
(s, 1 H, CH=); 14.53 (s, 1 H, NH). 19F NMR (DMSOꢀd6), δ:
2
3
25.73 (dt, 2 F, HCF2, JF,H = 53.0 Hz, JF,F = 10.0 Hz); 48.02
4ꢀ(1,5ꢀDimethylꢀ3ꢀtrifluoromethylpyrazolꢀ4ꢀylazo)ꢀ2,3ꢀ
dimethylꢀ1ꢀphenylꢀ1,2ꢀdihydropyrazolꢀ5ꢀone (5a). The yield
was 67%, m.p. 222—223 °C. The product was purified by colꢀ
umn chromatography (chloroform as the eluent). IR (Nujol
mulls), ν/cm–1: 1660 (C=O); 1590, 1490 (C=C, C=N, N=N);
1130—1190 (C—F). 1H NMR (CDCl3), δ: 2.57 and 2.62
(both s, 3 H each, 2 Me); 3.32 and 3.84 (both s, 3 H each,
2 NMe); 7.34—7.50 (m, 5 H, Ph). 19F NMR (CDCl3), δ: 99.76
(s, CF3). Found (%): C, 53.88; H, 4.65; F, 14.52; N, 22.32.
(m, 2 F, CF2). Found (%): C, 46.76; H, 3.19; F, 19.85; N, 25.22.
C
15H13F4N7O. Calculated (%): C, 47.00; H, 3.42; F, 19.83;
N, 25.58.
4ꢀ(3ꢀDifluoromethylꢀ5ꢀmethylꢀ1ꢀphenylpyrazolꢀ4ꢀylazo)ꢀ
2,3ꢀdimethylꢀ1ꢀphenylꢀ1,2ꢀdihydropyrazolꢀ5ꢀone (7a). The yield
was 63%, m.p. 225—227 °C (from a 10 : 1 chloroform—hexane
mixture). IR (Nujol mulls), ν/cm–1: 1670 (C=O); 1600, 1540,
1500 (C=N, C=C, N=N); 1100—1170 (C—F). 1H NMR
(DMSOꢀd6), δ: 2.45 and 2.63 (both s, 3 H each, 2 Me); 3.39 (s,
2
C
17H17F3N6O. Calculated (%): C, 53.97; H, 4.53; F, 15.06;
N, 22.21.
3ꢀ(1ꢀMethylꢀ5ꢀphenylꢀ3ꢀtrifluoromethylpyrazolꢀ4ꢀylazo)ꢀ
3 H, NMe); 7.28 (t, 1 H, HCF2, JH,F = 53.0 Hz); 7.38—7.58
(m, 10 H, 2 Ph). 19F NMR (DMSOꢀd6), δ: 51.52 (d, HCF2,
2JF,H = 53.0 Hz). Found (%): C, 61.37; H, 4.90; F, 9.46;
N, 20.31. C21H20F2N6O. Calculated (%): C, 61.46; H, 4.91;
F, 9.26; N, 20.48.
1Hꢀ1,2,4ꢀtriazole (5b). The yield was 75%, m.p. 235—236 °C
(washed with chloroform). IR (Nujol mulls), ν/cm–1: 3110,
1540 (NH); 1490, 1470 (C=N, C=C, N=N); 1080—1220
(C—F). 1H NMR (DMSOꢀd6), δ: 3.93 (s, 3 H, NMe); 7.58—7.68
(m, 5 H, Ph); 8.58 (s, 1 H, CH=); 14.57 (br.s, 1 H, NH).
19F NMR (DMSOꢀd6), δ: 101.53 (s, CF3). Found (%): C, 48.49;
H, 3.42; F, 17.51; N, 30.58. C13H10F3N7. Calculated (%):
C, 48.60; H, 3.14; F, 17.74; N, 30.52.
1,5ꢀDimethylꢀ4ꢀphenylꢀ3ꢀtrifluoromethylazopyrazole (5c).
The yield was 65%, m.p. 93—95 °C (from ethanol). IR (Nujol
mulls), ν/cm–1: 1550, 1500, 1480 (C=N, C=C, N=N);
1120—1200 (C—F). 1H NMR (CDCl3), δ: 2.63 (s, 3 H, Me);
3.89 (s, 3 H, NMe); 7.41—7.85 (m, 5 H, Ph). 19F NMR (CDCl3),
δ: 100.27 (q, CF3, J = 0.5 Hz). Found (%): C, 53.50; H, 4.17;
F, 21.00; N, 20.72. C12H11F3N4. Calculated (%): C, 53.73;
H, 4.13; F, 21.25; N, 20.89.
1ꢀMethylꢀ4ꢀ(4ꢀmethylphenyl)ꢀ5ꢀphenylꢀ3ꢀtrifluoroꢀ
methylazopyrazole (5d). The yield was 68%, m.p. 89—91 °C
(from ethanol). IR (Nujol mulls), ν/cm–1: 1600, 1490, 1475
(C=N, C=C, N=N); 1090—1160 (C—F). 1H NMR (CDCl3),
δ: 2.42 (s, 3 H, Me); 3.96 (s, 3 H, NMe); 7.24—7.65 (m, 4 H,
C6H4); 7.53—7.59 (m, 5 H, Ph). 19F NMR (CDCl3), δ: 99.81
(s, CF3). Found (%): C, 62.50; H, 4.36; F, 16.50; N, 16.15.
3ꢀ(1,5ꢀDiphenylꢀ3ꢀtrifluoromethylpyrazolꢀ4ꢀylazo)ꢀ1Hꢀ
1,2,4ꢀtriazole (7b). The yield was 71%, m.p. >250 °C (washed
with chloroform). IR (Nujol mulls), ν/cm–1: 3100, 1540 (NH);
1585, 1490 (C=N, C=C, N=N); 1120—1180 (C—F).
UV (MeOH), λmax/nm (ε): 205 (22600), 255 (10460), 310 (8640),
436 sh (800). 1H NMR (DMSOꢀd6—CCl4), δ: 7.36—7.46 (m,
10 H, 2 Ph); 8.49 (s, 1 H, CH=); 14.46 (s, 1 H, NH). 19F NMR
(DMSOꢀd6—CCl4), δ: 100.57 (s, CF3). Found (%): C, 56.44;
H, 3.12; F, 14.68; N, 25.77. C18H12F3N7. Calculated (%):
C, 56.40; H, 3.16; F, 14.87; N, 25.58.
3ꢀ(1,5ꢀDiphenylꢀ3ꢀtetrafluoroethylpyrazolꢀ4ꢀylazo)ꢀ1Hꢀ
1,2,4ꢀtriazole (7c). The yield was 74%, m.p. 215—217 °C (washed
with chloroform). IR (Nujol mulls), ν/cm–1: 3120, 1540 (NH);
1590, 1500 (C=N, C=C, N=N); 1100—1220 (C—F). 1H NMR
(DMSOꢀd6), δ: 7.05 (tt, 1 H, H(CF2)2, 2JH,F = 53.0 Hz, 3JH,F
=
5.5 Hz); 7.43—7.90 (m, 10 H, 2 Ph); 8.72 (s, 1 H, CH=); 14.72
(s, 1 H, NH). 19F NMR (DMSOꢀd6), δ: 26.52 (dt, 2 F, HCF2,
3
3
2JF,H = 53.0 Hz, JF,F = 10.0 Hz); 53.10 (m, 2 F, CF2, JF,H
=
5.5 Hz, 3JF,F = 10.0 Hz). Found (%): C, 54.79; H, 3.31; F, 18.80;
N, 24.40. C19H13F4N7. Calculated (%): C, 54.94; H, 3.15;
F, 18.30; N, 23.61.
C
18H15F3N4. Calculated (%): C, 62.79; H, 4.39; F, 16.27;
N, 16.55.
4ꢀ[1ꢀ(2ꢀHydroxyethyl)ꢀ5ꢀmethylꢀ3ꢀtrifluoromethylpyrazolꢀ4ꢀ
This study was financially supported by the Russian
Foundation for Basic Research (Project Nos 03ꢀ03ꢀ33118
and 03ꢀ03ꢀ06471).
ylazo]ꢀ2,3ꢀdimethylꢀ1ꢀphenylꢀ1,2ꢀdihydropyrazolꢀ5ꢀone (6a).
The yield was 77%, m.p. 218—219 °C (washed with chloroꢀ
form). IR (Nujol mulls), ν/cm–1: 3330, 3290 (OH); 1640 (C=O);
1540, 1510, 1490 (C=N, C=C, N=N); 1120—1210 (C—F).
1H NMR (DMSOꢀd6), δ: 2.52 and 2.58 (both s, 3 H each,
2 Me); 3.34 (s, 3 H, NMe); 3.75 (q, 2 H, CH2, 3JH,H = 5.5 Hz);
References
3
3
4.20 (t, 2 H, CH2, JH,H = 5.5 Hz); 5.00 (t, 1 H, OH, JH,H
=
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N, 20.54. C18H19F3N6O2. Calculated (%): C, 52.94; H, 4.69;
F, 13.96; N, 20.58.
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Received December 29, 2003;
in revised form June 2, 2004