Reaction of 3-(polyfluoroacyl)chromones with hydrazines: New regioselective synthesis of RF-containing pyrazoles

Article abstract of DOI:10.1007/s11172-008-0291-5

Reactions of 3-(polyfluoroacyl)chromones with hydrazine, methyl-and phenylhydrazines proceed by the mechanism of nucleophilic 1,4-addition with subsequent pyrone ring opening and heterocyclization at the polyfluoroacyl group to 4-(2-hydroxyaroyl)-3-polyfl

Full text of DOI:10.1007/s11172-008-0291-5

Russian Chemical Bulletin, International Edition, Vol. 57, No. 10, pp. 2146—2155, October, 2008
2146
Reaction of 3ꢀ(polyfluoroacyl)chromones with hydrazines:
new regioselective synthesis of RFꢀcontaining pyrazoles
V. Ya. Sosnovskikh,a R. A. Irgashev,a V. S. Moshkin,a and M. I. Kodessb
aA. M. Gorky Ural State University,
51 prosp. Lenina, 620083 Ekaterinburg, Russian Federation.
Fax: +7 (343) 261 5978. Eꢀmail: Vyacheslav.Sosnovshikh@usu.ru
bI. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
26 ul. S. Kovalevskoi, 620041 Ekaterinburg, Russian Federation.
Reactions of 3ꢀ(polyfluoroacyl)chromones with hydrazine, methylꢀ and phenylhydrazines
proceed by the mechanism of nucleophilic 1,4ꢀaddition with subsequent pyrone ring opening
and heterocyclization at the polyfluoroacyl group to 4ꢀ(2ꢀhydroxyaroyl)ꢀ3ꢀpolyfluoroꢀ
alkylpyrazoles or at the aroyl group to 4ꢀpolyfluoroalkylꢀ2,4ꢀdihydrochromeno[4,3ꢀc]pyrazolꢀ
4ꢀols. Regiochemistry of the products was established based on the data of 2Dꢀexperiments
HSQC, HMBC, and NOESY and Xꢀray diffraction study.
Key words: 3ꢀ(polyfluoroacyl)chromones, hydrazines, RFꢀcontaining pyrazoles, hydrazones,
nucleophilic 1,4ꢀaddition, heterocyclization, Xꢀray diffraction study.
3ꢀFormylꢀ and 3ꢀacylchromones for a long time atꢀ
monoꢀ and dinucleophiles,15—18 we studied their reacꢀ
tions with hydrazine, methylꢀ and phenylhydrazines
under acidic and basic conditions in order to develop a
new method for the synthesis of RFꢀcontaining pyrazoles
(Scheme 1). In the last years, these compounds attract
great attention, since in the series of RFꢀpyrazoles, espeꢀ
cially the CF3ꢀpyrazoles, many substances with various
kinds of biological activity were found, which are widely
used in medicinal and agrochemical practice.19
tract attention of researches as highly reactive compounds,
which due to the presence of three electrophilic centers
(the C(2) and the C(4) atoms and RCO group at position
3) can serve as the starting compounds in the synthesis of
a whole number of new heterocycles with useful properꢀ
ties.1—3 Reactions of these compounds with such dinucꢀ
leophiles as hydroxylamine and hydrazines predominantly
begin from the attack at the unsubstituted atom C(2)
(1,4ꢀaddition) and are accompanied by the pyrone ring
opening, that leads to the arising of βꢀdicarbonyl interꢀ
mediate capable of intramolecular heterocyclization.4—9
Along with this pathway, the initial attack can also take
place at the 3ꢀRCO group (1,2ꢀaddition), that does not
exclude recyclization by the intramolecular addition—
elimination reaction (AN—E) and explains a variety of
forming products.10—12
Recently,13 we have shown that the principal direction
of the reaction of 3ꢀ(polyfluoroacyl)chromones14 with hyꢀ
droxylamine in basic medium is the attack at the C(2)
atom, which is accompanied by the pyrone ring opening
and cyclization to 4ꢀpolyfluoroalkylꢀ4Hꢀchromeno[3,4ꢀd]ꢀ
isoxazolꢀ4ꢀols, from which 3ꢀcyanoꢀ2ꢀpolyfluoroalkylꢀ
chromones have been obtained. At the same time, the use
of hydroxylamine hydrochloride leads to chromoneꢀ3
oximes (the products of 1,2ꢀaddition) easily recyclizing to
3ꢀpolyfluoroalkylisoxazoles.
Results and Discussion
Reaction of 3ꢀRFCOꢀchromones with hydrazine. Sevꢀ
eral competing pathways for the reaction of 3ꢀRFCOꢀ
chromones 1 with hydrazine in both the initial step of
nucleophilic attack and the subsequent heterocyclization
would have been expected. In addition, it should be taken
into account that these compounds easily add a water
molecule at the carbonyl group and exist in a mixture with
the corresponding covalent hydrates of the type 2 (see
Scheme 1), stability of which considerably depends on a
number of fluorine atoms in the polyfluoroalkyl group.
Thus, according to the 1H and 19F NMR spectral data, the
content of the hydrate form for RF = CF2H is only 1—2%,
for RF = (CF2)2H, it increases to 6—8%, whereas for
RF = CF3, reaches 30—65% (see Refs 14 and 15). Elecꢀ
tronꢀwithdrawing substituents in the benzene ring of
3ꢀCF3COꢀchromones 1 additionally stabilize hydrate 2,
the content of which increases to 70—80% on prolonged
standing. The disposition of 3ꢀCF3COꢀchromones to a
In continuation of our research on chemical properꢀ
ties of 3ꢀ(polyfluoroacyl)chromones 1, which turned out
to be the highly active substrates in the reactions with
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2107—2115, October, 2008.
1066ꢀ5285/08/5710ꢀ2146 © 2008 Springer Science+Business Media, Inc.

Reactions of 3ꢀ(polyfluoroacyl)chromones
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 10, October, 2008
2147
facile hydration, despite the reversibility of the process,
can be a reason of their lower reactivity and selectivity
in comparison with other 3ꢀ(polyfluoroacyl)chromones,
that has been already observed by us in the reactions of
3ꢀCF3COꢀchromones with 1,3ꢀC,Nꢀdinucleophiles.20
We found that the structure of the reaction products
of 3ꢀCF3COꢀchromones 1a—d with hydrazine dihydroꢀ
chloride in the presence of anhydrous sodium acetate (the
molar ratio of 1 : 2 : 4, respectively) in methanol at ~20 °C
(procedure A) considerably depends on the nature of subꢀ
stituent at position 6 of the chromone system. Thus,
chromones 1a,b (R = H, Me) afford 4ꢀsalicylꢀ3ꢀ(trifluoroꢀ
methyl)pyrazoles 3a,b as the only products, whereas 1c
(R = Cl) gives a mixture of pyrazole 3c and chromenoꢀ
[4,3ꢀc]ꢀpyrazole 4a in the ratio of 1 : 4 and only 4b is
formed from 1d (R = NO2). According to the 1H, 19F, and
13C NMR spectra (see below), compounds 3a,b in soluꢀ
tion are predominantly in the form of 1Hꢀ3ꢀCF3ꢀtauꢀ
tomer, whereas 4a,b, in the cyclic form of chromenoꢀ
[4,3ꢀc]pyrazole due to the addition of the phenol hyꢀ
droxyl to the carbonyl group of the trifluoroacetyl subꢀ
stituent of the open form 5. The reaction products yields
varied from 49 to 57% (Scheme 1).
It is important to note that if the formation of pyrazoles
3 can be explained by both the 1,2ꢀAN mechanism (the
Michael cyclization of intermediate A with subsequent
pyrone ring opening) and the 1,4ꢀAN mechanism
(cyclization of intermediate B at the CF3CO group),
then the structure of chromeno[4,3ꢀc]pyrazoles 4 unamꢀ
biguously indicates the initial attack at the C(2) atom
and cyclization at the carbonyl group of the aromatic
ring (only in this case, the CF3CO group remains free
and participates in the formation of cyclic hemiketal
form). On the basis of available literature data on the
reaction of 3ꢀsubstituted chromones with dinucleophiles,6
it can be suggested that in the case of 1,4ꢀaddition direcꢀ
tion of the heterocyclization is defined by both the
configuration of the C=C bond, i.e., the ratio of geoꢀ
metrical isomers B and C, and the reactivity of the aroyl
and polyfluoroacyl groups, of which the latter with
RF = CF3 is possible to turn out less active due to the
partial hydration.
Scheme 1
1, 2: R = H (a), Me (b), Cl (c), NO2 (d)
3: R = H (a), Me (b), Cl (c)
4, 5: R = Cl (a), NO2 (b)

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Sosnovskikh et al.
Scheme 2
electronꢀwithdrawing substituents at position 6 exhibit
higher stability in basic medium and predominantly form
chromeno[4,3ꢀc]pyrazoles 4a,b irrespective of the reacꢀ
tion conditions (see Scheme 1). However, 6,8ꢀdibromoꢀ
3ꢀtrifluoroacetylchromone upon action of hydrazine
undergoes decomposition under both acidic and basic
conditions.
Replacement of the CF3 group for the H(CF2)2 group
in chromone 1b leads to a mixture of pyrazoles 3d and 4c,
the composition and yield of which depends on the reacꢀ
tion conditions. Under acidic conditions (procedure A), a
mixture of the composition 3d : 4c = 65 : 35 was obtained
from chromone 1e (57% yield), whereas under basic conꢀ
ditions (procedure B), 3d : 4c = 28 : 72. In the latter case,
the yield of the mixture was only 16%, from which it can
be concluded that the reaction with hydrazine hydrate, if
it does not lead to the complete decomposition of the
chromone, proceeds predominantly through intermediate
C with participation of the aroyl group in the heteroꢀ
cyclization step (Scheme 2). Possibly, it is caused by higher
stability of the hydrate form under basic conditions, which
masks the RFCO group and thus decreases its reactivity.
Another pathway of the reaction which was found by
us on the example of chromone 1b under conditions of
procedure A for the molar ratio of 1b : N2H4•2HCl :
: AcONa = 1 : 1 : 2, leads to bisꢀadduct 6 (45% yield). The
formation of this compound speaks in favor of the mechaꢀ
nism of nucleophilic 1,4ꢀaddition through intermediate
C with the transꢀarrangement of the hydrazino and
trifluoroacetyl groups. Its ringꢀchain tautomer C´ in the
absence of excess hydrazine reacts as the amine with
the second molecule of 1b at the C(2) atom with subseꢀ
quent recyclization to bisꢀhemiketal C″, the hydroxy group
of which is substituted for the MeO group under the reacꢀ
tion conditions (Scheme 3). Note that in the series of
Under the action of 60% aqueous hydrazine hydrate
at –10 °C (procedure B), chromones 1a,b undergo
detrifluoroacetylation and deformylation to the starting
2ꢀhydroxyacetophenones, whereas chromones 1c,d
under these conditions still give compounds 4a,b with the
only difference that in the case of 1c, regioselectivity of
the reaction increases and the ratio of pyrazoles 3c and 4a
becomes equal to 1 : 13. Thus, chromones 1c,d having
Scheme 3

Reactions of 3ꢀ(polyfluoroacyl)chromones
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 10, October, 2008
2149
Scheme 4
at the CF3CO group (intermediate D) or the 1,4ꢀaddiꢀ
tion of the secondary nitrogen atom (intermediate E)
(Scheme 4). Earlier, 1ꢀmethylꢀ3ꢀ(trifluoromethyl)pyraꢀ
zoles have been obtained by the reaction of methylꢀ
hydrazine with 4ꢀethoxyꢀ1,1,1ꢀtrifluorobutꢀ3ꢀenꢀ2ꢀone21
and 3ꢀacetylꢀ4ꢀethoxyꢀ1,1,1ꢀtrifluorobutꢀ3ꢀenꢀ2ꢀone.22
Interestingly that chromones 1a,b react differently with
MeNHNH2 in methanol at –10 °C (procedure D). Thus,
1a under these conditions affords 2ꢀmethylꢀ4ꢀ(trifluoroꢀ
methyl)ꢀ2,4ꢀdihydrochromeno[4,3ꢀc]pyrazolꢀ4ꢀol 8a
(49% yield), the product of the initial attack at position 2
of the chromone system by more nucleophilic MeNH
group, whereas 1b gives a mixture of pyrazole 7b and
hydrazone 9b, which was successfully separated by recrysꢀ
tallization from methanol (19 and 27% yield, respectively).
An increase of temperature to ~20 °C in the reaction with
1a decreases the regioselectivity and leads to a mixture of
the composition 8a : 9a = 72 : 28. The choice between
structures 8a and 8a´ has been made in favor of the former
one based on the analysis of the 2Dꢀexperiments HSQC,
HMBC, and NOESY (see below).
Since there is no information in the literature on the
possibility of the reaction of 3ꢀacylchromones with hyꢀ
drazines at the C(4) atom, compound 7—9 are most likely
formed under basic conditions through the common inꢀ
termediate E, which in the case of 1a has the transꢀconꢀ
figuration and cyclizes at the carbonyl of the aromatic
ring, whereas in the case of 1b, cisꢀconfiguration facilitates
attack at the CF3CO group. However, for pyrazoles 7a,b
the attack at the CF3CO group by the primary nitrogen
atom under acidic conditions cannot be excluded either
(intermediate D, Scheme 4), as it was observed in the case
Scheme 5
R = H (a), Me (b)
chromeno[4,3ꢀc]pyrazoles 5, we did not observe the subꢀ
stitution of the hemiketal hydroxyl for the alkoxy group.
Bisꢀadduct 6 was obtain as a mixture of two diasteꢀ
reomers in the ratio of 1 : 1, that follows from the 1H
NMR spectral data, in which two mostly overlapping sets
of signals were observed.
Reactions of 3ꢀRFCOꢀchromones with methylꢀ and
phenylhydrazines. The reaction of chromones 1a,b with
MeNHNH2•H2SO4 in methanol in the presence of
AcONa at ~20 °C (procedure C) proceeds with high
regioselectivity and gives rise to 1ꢀmethylꢀ4ꢀsalicylꢀ
3ꢀ(trifluoromethyl)pyrazoles 7a,b (45—48% yield), the
structures of the latter were established by Xꢀray analysis
data (see below) which indicate the 1,2ꢀaddition of the
primary nitrogen atom of the methylhydrazine molecule
R = Me, RF = (CF2)2H (1e, 7c)
R = H, RF = CF2H (1f, 7d)
R = Cl, RF = CF2H (1g, 7e, 9c)

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Sosnovskikh et al.
Scheme 6
of hydroxylamine hydrochloride.13 It should be also noted
that hydrazones 9a,b are formed in the stage of interꢀ
mediates, rather than they are the products of the reaction
of pyrazoles 7a,b with excess of methylhydrazine, since
we failed to obtain 9b from 7b even under increased
temperatures.
On going from compounds 1a,b to 3ꢀRFCOꢀchroꢀ
mones 1e—g, which are not disposed to add water at the
RFCO group under both acidic (procedure C) and basic
conditions (procedure D), the selectivity of the reaction
with methylhydrazine considerably increases resulting
in the formation of 3ꢀRFꢀpyrazoles 7c—e in good yields
(59—74%). Note that the heating of pyrazole 7e with
excess of MeNHNH2 (4 equiv.) without solvent or in
ethanol does not lead to its Nꢀmethylhydrazone, however,
with excess of PhNHNH2 (85 °C, 6 h), Nꢀphenylhydrazone
9c is formed in 82% yield (Scheme 5).
analog of 4ꢀbenzoylꢀ5ꢀ(2ꢀhydroxyphenyl)ꢀ1ꢀphenylpyraꢀ
zole, earlier obtained from 3ꢀbenzoylchromone.4
A comparison of reactivity of 3ꢀ(polyfluoroacyl)ꢀ
chromones 1 with 3ꢀformylchromone 14 on the example
of their reaction with MeNHNH2 under conditions of
procedure D (methanol, –10 °C), allowing to minimize
decomposition of chromones 1 in basic medium, showed
that chromone 14 is stable and inactive under these conꢀ
ditions. However, its reflux with 1 equiv. of MeNHNH2
in ethanol for 4 h leads to 1ꢀmethylꢀ4ꢀsalicylpyrazole 15.
Treatment of chromone 14 or pyrazole 15 with excess
MeNHNH2 (3.5—4 equiv.) under the same conditions
affords Nꢀmethylhydrazone 16. The yields of products 15
and 16 in these reactions were 50—53% (Scheme 8). To
sum up, the reaction of 3ꢀformylchromone with methylꢀ
hydrazine can be directed and predicted, which is not the
In contrast to 3ꢀRFCOꢀchromones 1e—g, the reaction
of 6ꢀtrifluoroacetylnorchellin 10 with methylhydrazine
under conditions of procedure D follows the heterocyclizaꢀ
tion pathway with participation of the carbonyl group at
the aromatic ring and gives furochromenopyrazole 11 in
65% yield (Scheme 6). Under acidic conditions (procedure
C), this reaction does not take place. We assume that the
formation of compound 11, also as 8a from 1a, results
from the partial hydration of furochromone 10 (the conꢀ
tent of covalent hydrate 12 is 56%),16 which decreases
reactivity of the CF3CO group.
Scheme 7
Possibly, this is also the cause that phenylhydrazine
reacts with chromone 1a by its unsubstituted and more
nucleophilic nitrogen atom through the 1,4ꢀaddition with
subsequent recyclization to 1ꢀphenylꢀ4ꢀ(trifluoromethyl)ꢀ
1,4ꢀdihydrochromeno[3,4ꢀd]pyrazolꢀ4ꢀol (13) (procedure
D, 48 h, 30% yield) (Scheme 7), which is a fluorinated

Reactions of 3ꢀ(polyfluoroacyl)chromones
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 10, October, 2008
2151
Scheme 8
in space, and, consequently, that the Me group is at the
atom N(2). This conclusion is also confirmed by the presꢀ
ence of the crossꢀpeaks in the HMBC spectrum between
protons of the NMe group and carbon atom C(3), as well
as between the proton H(3) and carbon atom NMe.
It should be noted that in contrast to the 19F NMR
spectrum of chromenopyrazole 8a, in which only one
signal was present, in the 19F NMR spectra of compounds
11 and 13, two singlets at δ 78.9—79.1 and 88.9—89.0
(DMSOꢀd6) were observed, the former corresponds to
the CF3 group of the cyclic form, whereas the second, to
the open form 11´ or 13´, the content of which in both
cases was about 10%. The ringꢀchain tautomerism in
solution of these compounds in DMSOꢀd6 resulted in the
1
broadening of the most signals in their H NMR spectra.
Similar, but still more complicated picture, was observed
1
for Nꢀunsubstituted chromenopyrazoles 5, the H NMR
spectra of which contained two partially overlapping sets
of broad signals (see Experimental). In this case, the
broadening of the signals is mainly caused by the retardaꢀ
tion of prototropic tautomerization in the pyrazole ring,
whereas the contribution of the open form 5 (Schemes 1
and 2) in comparison with 11´ and 13´ considerably
decreases. Thus, in the 19F NMR spectrum of compound
4a, there are two broad singlets for the CF3 group at
78.4 ppm (the cyclic form, 96%) and 89.0 ppm (the open
form, 4%), the former of which has a shoulder and
belongs to the CF3 groups of the prototropic 1Hꢀ and
2Hꢀtautomers of chromenopyrazole 4a.
XꢀRay diffraction study of hydrazone 9b. In order to
establish position of the Me group in pyrazoles 7 and 9, an
Xꢀray analysis has been carried out for the crystals of
hydrazone 9b, which showed that these compounds
belong to the series of 1ꢀmethylꢀ3ꢀpolyfluoroalkylpyraꢀ
zoles (Fig. 1, Table 1). The framework of the molecule 9b
consists of two virtually plane mutually perpendicular parts
(the dihedral angle is 85.23(5)°): the pyrazole ring (the
mean square deviation is 0.001 Å) and the benzene ring
and the hydrazone group lying in one plane (the mean
square deviation is 0.018 Å). A strong intramolecular
hydrogen bond is formed between the phenol hydroxyl
and the imine nitrogen O(1)—H...N(3) with the following
parameters: O(1)—H 0.94(2) Å, O(1)...N(3) 2.597(2) Å,
H...N(3) 1.73(2) Å, the angle O(1)—H...N(3) 152(2)°. The
bond lengths and bond angles coincide with the average
statistical values within the error limits.25 Note only a
somewhat shorter (1.339(2) Å) N(1)—N(2) bond of the
pyrazole ring in comparison with the average statistical
value of 1.366(19) Å.
case for the analogous reaction with participation of
3ꢀRFCOꢀchromones. Especially, this is characteristic
of partially hydrated 3ꢀCF3COꢀchromones, the heteroꢀ
cyclization of which can take place at both the aroyl and
the trifluoroacetyl group.
NMR spectroscopic data. The structures of all the comꢀ
pounds synthesized are in good agreement with the elꢀ
emental analysis, IR spectroscopic, as well as 1H, 19F, and
1
13C NMR spectroscopic data. In the H NMR spectra of
pyrazoles 3 in DMSOꢀd6, in addition to the signals for the
aromatic protons, the somewhat broadened singlets for
the labile protons OH at δ 10.5—10.7 and NH at δ 14.1
are observed, as well as the singlet for the pyrazole proton
at δ 8.4. Since in the Nꢀunsubstituted pyrazoles 3 and
1ꢀmethylꢀ3ꢀCF3ꢀpyrazoles 7, the regiochemistry of which
has been established by Xꢀray method (see below), the
chemical shifts for the proton H(5) and CF3 group in both
DMSOꢀd6 and CDCl3 are very close, it can be suggested
that pyrazoles 3 exist in the form of 1Hꢀ3ꢀCF3ꢀtautomer
in these solvents. This conclusion is also confirmed by the
19F and 13C NMR spectral data for pyrazole 3a in CDCl3,
in which the singlet for the CF3 group resonates at
δ 100.9, whereas the quartet for the C atom bonded to the
CF3 group, at δ 142.4 (2JC,F = 38.6 Hz). Earlier,19,23,24
the values δCF ≈ 101 and δC(3) ≈ 140—145 have been
3
reported for 3ꢀCF3ꢀpyrazoles, whereas for 5ꢀCF3ꢀpyrazoles,
δ
CF3
≈ 105 and δC(3) ≈ 149.
Isomers 7a and 8a can be easily distinguished by the
19F NMR spectra, in which the singlet for the CF3 group
is observed at δ 100.8 and 78.4, respectively; in the 13C NMR
spectrum of compound 8a, the signal for the C atom
bonded to the CF3 group resonates as the quartet at δ 94.7
(2JC,F = 34.3 Hz). The choice between structures 8a and
8a´ has been made in favor of the former based on the
analysis of the 2Dꢀexperiments HSQC, HMBC, and
NOESY. In particular, in the NOESY spectrum, a crossꢀ
peak between the protons of the NMe group and the
proton H(3) is observed, that suggests that they are close
In conclusion, the main direction of the reaction of
3ꢀ(polyfluoroacyl)chromones with hydrazines is a nucleoꢀ
philic 1,4ꢀaddition with subsequent pyrone ring opening
and heterocyclization at the polyfluoroacyl or aroyl
group, that leads to 3ꢀpolyfluoroalkylꢀ4ꢀsalicylpyrazoles
or 4ꢀpolyfluoroalkylꢀ2,4ꢀdihydrochromeno[4,3ꢀc]pyrazolꢀ
4ꢀols, respectively.

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Sosnovskikh et al.
1 H, H(5´), Jo = 8.1 Hz, 7.2 Hz, Jm = 1.1 Hz); 7.09 (dd, 1 H,
H(3´), Jo = 8.5 Hz, Jm = 1.1 Hz); 7.56 (ddd, 1 H, H(4´), Jo = 8.5 Hz,
7.2 Hz, Jm = 1.7 Hz); 7.63 (dd, 1 H, H(6´), Jo = 8.1 Hz, Jm = 1.7 Hz);
8.01 (q, 1 H, H(5), 5JH,F = 0.9 Hz); 11.5 (br.s, 1 H, NH); 11.76
(s, 1 H, OH). 1H NMR (DMSOꢀd6), δ: 6.95 (t.d, 1 H, H(5´),
Jo = 7.5 Hz, Jm = 1.0 Hz); 7.00 (dd, 1 H, H(3´), Jo = 8.3 Hz,
Jm = 0.7 Hz); 7.48 (ddd, 1 H, H(4´), Jo = 8.3 Hz, 7.3 Hz,
Jm = 1.7 Hz); 7.53 (dd, 1 H, H(6´), Jo = 7.8 Hz, Jm = 1.6 Hz);
8.38 (s, 1 H, H(5)); 10.74 (s, 1 H, OH); 14.12 (br.s, 1 H, NH).
19F NMR (CDCl3), δ: 100.88 (s, CF3). 13C NMR (CDCl3), δ:
C(7)
O(1)
C(9)
N(4)
C(2)
N(3)
C(6)
C(8)
C(10)
C(1)
N(2)
F(1A)
C(13)
1
F(2)
118.80, 118.82, 119.36, 119.97, 120.73 (q, CF3, JC,F = 269.8 Hz),
C(11)
2
131.82, 133.33, 137.15, 142.35 (q, C—CF3, JC,F = 38.6 Hz),
162.97, 191.66.
C(12)
C(14)
C(5)
N(1)
F(3)
F(2A)
F(3A)
4ꢀ(2ꢀHydroxyꢀ5ꢀmethylbenzoyl)ꢀ3ꢀ(trifluoromethyl)pyrazole
(3b) was obtained from chromone 1b according to procedure A,
the yield was 57%, colorless needleꢀlike crystals, m.p. 155–156 °C.
Found (%): C, 53.37; H, 3.28; N, 10.50. C12H9F3N2O2.
Calculated (%): C, 53.34; H, 3.36; N, 10.37. IR, ν/cm–1: 3319,
3195, 2929, 1653, 1632, 1592, 1538, 1524, 1509, 1484. 1H NMR
(DMSOꢀd6), δ: 2.25 (s, 3 H, Me); 6.90 (d, 1 H, H(3´), Jo = 8.3 Hz);
7.30 (dd, 1 H, H(4´), Jo = 8.3 Hz, Jm = 1.7 Hz); 7.32 (d, 1 H,
H(6´), Jm = 1.7 Hz); 8.39 (s, 1 H, H(5)); 10.59 (s, 1 H, OH);
14.10 (br.s, 1 H, NH). 19F NMR (DMSOꢀd6), δ: 102.42 (s, CF3).
8ꢀChloroꢀ4ꢀ(trifluoromethyl)ꢀ2,4ꢀdihydrochromeno[4,3ꢀc]ꢀ
pyrazolꢀ4ꢀol (4a) was obtained from chromone 1c according
to procedure B, the yield was 54%, colorless powder, m.p. 188—
189 °C. According to the 1H NMR spectrum, this sample
contained 7% of 4ꢀ(5ꢀchloroꢀ2ꢀhydroxybenzoyl)ꢀ3ꢀ(trifluoroꢀ
methyl)pyrazole (3c). The second recrystallization from toluene—
butanol (3 : 1) gave pure chromenopyrazole 4a with m.p. 194—
195 °C. Found (%): C, 45.63; H, 2.01; N, 9.45. C11H6ClF3N2O2.
Calculated (%): C, 45.46; H, 2.08; N, 9.64. IR, ν/cm–1: 3400,
3297, 1631, 1596, 1567, 1539, 1466. 1H NMR (DMSOꢀd6), δ:
7.15 (d, 0.7 H, H(6), Jo = 8.7 Hz); 7.19 (br.d, 0.3 H, H(6),
Jo = 8.7 Hz); 7.34 (br.dd, 1 H, H(7), Jo = 8.7 Hz, Jm = 2.0 Hz);
7.70 (br.s, 0.3 H, H(3)); 7.75 (br.d, 0.7 H, H(9), Jm = 2.0 Hz);
7.87 (br.s, 0.3 H, H(9)); 8.10 (br.s, 0.7 H, H(3)); 8.97 (br.s,
0.7 H, OH); 9.06 (br.s, 0.3 H, OH); 13.60 (br.s, 0.7 H, NH);
13.87 (br.s, 0.3 H, NH). 19F NMR (DMSOꢀd6), δ: 78.41 (s, 0.95
CF3), 89.0 (br.s, 0.05 CF3).
F(1)
Fig. 1. Spatial structure of the hydrazone 9b molecule.
Table 1. Selected bond lengths (d) in the structure 9b
Bond
d/Å
Bond
d/Å
N(1)—N(2)
C(3)—N(1)
C(1)—N(2)
C(1)—C(2)
C(2)—C(3)
1.339(2)
1.328(2)
1.341(2)
1.373(2)
1.407(2)
C(2)—C(6)
C(6)—N(3)
N(3)—N(4)
C(6)—C(8)
C(9)—O(1)
1.492(2)
1.295(2)
1.354(2)
1.471(2)
1.360(2)
Experimental
IR spectra were recorded on a PerkinꢀElmer Spectrum BXꢀII
spectrometer in KBr pellets. 1H, 13C, and 19F NMR spectra
were recorded on a Bruker DRXꢀ400 spectrometer (400.1 MHz
(1H), 100.6 MHz (13C), and 376.5 MHz (19F)), Me4Si (1H, 13C)
and C6F6 (
19F) were used as the internal standards. 3ꢀ(Polyꢀ
fluoroacyl)chromones 1a—g, 10 were obtained according to the
procedure described earlier.15
Reaction of chromones 1 and 10 with hydrazine (general
procedure A). A mixture of N2H4•2HCl (125 mg, 1.2 mmol)
and anhydrous AcONa (200 mg, 2.4 mmol) in MeOH (3 mL)
was refluxed for 5 min followed by addition of chromone 1
(0.6 mmol) to the still hot suspension. The mixture obtained was
kept for 2 days at ~20 °C, then it was diluted with water (20 mL),
a precipitate formed was filtered off, dried, and recrystallized
from toluene—hexane (1 : 1).
Procedure B. Hydrazine hydrate (60% aq., 250 mg, 3.0 mmol)
was added to a solution of chromone 1 or 10 (1.2 mmol) in
MeOH (5 mL) cooled to –10 °C. The mixture obtained was kept
at this temperature for 1 day and diluted with water (15 mL)
containing concentrated HCl (0.3 mL). A colorless precipitate
formed was filtered off, dried, and recrystallized from toluene—
butanol (3 : 1).
4ꢀ(5ꢀChloroꢀ2ꢀhydroxybenzoyl)ꢀ3ꢀ(trifluoromethyl)pyrazole
(3c) was not isolated in the individual state, whereas was
registered in a mixture of the composition 3c : 4a = 19 : 81
obtained from chromone 1c according to procedure A. 1H NMR
(DMSOꢀd6), δ: 7.00 (d, 1 H, H(3´), Jo = 8.8 Hz); 7.40 (d, 1 H,
H(6´), Jm = 2.7 Hz); 7.45 (dd, 1 H, H(4´), Jo = 8.8 Hz, Jm = 2.7 Hz);
8.38 (s, 1 H, H(5)); 10.49 (s, 1 H, OH); 14.11 (br.s, 1 H, NH).
8ꢀNitroꢀ4ꢀ(trifluoromethyl)ꢀ2,4ꢀdihydrochromeno[4,3ꢀc]ꢀ
pyrazolꢀ4ꢀol (4b) was obtained from chromone 1d according to
procedures A and B, the yields were 45 and 49%, respectively,
fine yellow crystals, m.p. 167—168 °C. Found (%): C, 43.84; H,
2.02; N, 14.29. C11H6F3N3O4. Calculated (%): C, 43.87; H,
2.01; N, 13.95. IR, ν/cm–1: 3330—3000, 1629, 1601, 1584, 1522,
1480. 1H NMR (DMSOꢀd6), δ: 7.34 (br.s, 1 H, H(6)); 7.7—8.0
(br.s, 0.2 H, H(3)); 8.15—8.25 (m, 1.8 H, H(3), H(7)); 8.54
(br.s, 0.8 H, H(9)); 8.6—9.0 (br.s, 0.2 H, H(9)); 9.40 (br.s, 1 H,
OH); 13.80 (br.s, 0.8 H, NH); 14.0—14.3 (br.s, 0.2 H, NH).
4ꢀ(2ꢀHydroxyꢀ5ꢀmethylbenzoyl)ꢀ3ꢀ(1,1,2,2ꢀtetrafluoroethyl)ꢀ
pyrazole (3d) and 8ꢀmethylꢀ4ꢀ(1,1,2,2ꢀtetrafluoroethyl)ꢀ1(2),4ꢀ
dihydrochromeno[4,3ꢀc]pyrazolꢀ4ꢀol (4c). A mixture of the
composition 3d : 4c = 65 : 35 was obtained from chromone 1e
4ꢀSalicylꢀ3ꢀ(trifluoromethyl)pyrazole (3a) was obtained from
chromone 1a according to procedure A, the yield was 50%,
colorless needleꢀlike crystals, m.p. 146—147 °C. Found (%): C,
51.24; H, 2.49; N, 10.99. C11H7F3N2O2. Calculated (%):
C, 51.57; H, 2.75; N, 10.94. IR, ν/cm–1: 3543, 3138, 2974,
1
1629, 1592, 1545, 1516, 1485. H NMR (CDCl3), δ: 6.94 (ddd,

Reactions of 3ꢀ(polyfluoroacyl)chromones
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 10, October, 2008
2153
according to procedure A, the yield was 57%, colorless powder,
m.p. 119—120 °C (toluene—hexane, 1 : 1). Found (%): C, 52.06;
H, 3.42; N, 9.36. C13H10F4N2O2. Calculated (%): C, 51.66; H,
3.34; N, 9.27. 1H NMR (DMSOꢀd6) of compound 3d (65%), δ:
2.25 (s, 3 H, Me); 6.90 (d, 1 H, H(3´), Jo = 8.4 Hz); 6.96 (tt, 1
H, CF2CF2H, 2JH,F = 52.6 Hz, 3JH,F = 5.7 Hz); 7.29—7.33 (m,
2 H, H(4´), H(6´)); 8.38 (s, 1 H, H(5)); 10.64 (s, 1 H, OH);
13.9—14.2 (br.s, 1 H, NH); of compound 4c (35%): 2.30 (s, 3
H, Me); 6.69 (br.t, 1 H, CF2CF2H, 2JH,F = 52.6 Hz); 7.08 (br.s,
1 H, H(6)); 7.56 (br.s, 2 H, H(7), H(9)); 7.93 (s, 1 H, H(3));
8.64 (s, 1 H, OH); 13.3—13.4 (br.s, 0.7 H, NH); 13.6—13.8
(br.s, 0.3 H, NH). A mixture of the composition 3d : 4c = 28 : 72
was obtained according to procedure B, the yield was 16%,
colorless powder, m.p. 129—130 °C (toluene—hexane, 1 : 1).
N,N’ꢀBis[3ꢀaminomethylideneꢀ2ꢀmethoxyꢀ6ꢀmethylꢀ2ꢀ(triꢀ
fluoromethyl)chromanꢀ4ꢀone] (6). A mixture of chromone 1b
(100 mg, 0.39 mmol) and hydrazine dihydrochloride (35 mg,
0.33 mmol) in methanol (3 mL) was heated to boiling followed
by addition of anhydrous AcONa (55 mg, 0.67 mmol) to the hot
solution. The bright yellow reaction mixture was kept at ~20 °C
for 1 week, the crystals formed were filtered off, washed with
methanol and water and recrystallized from toluene—hexane
(1 : 1). The yield was 45% (50 mg), fine bright yellow crystals,
m.p. 213—214 °C. Found (%): C, 54.19; H, 3.66; N, 4.84.
C26H22F6N2O6. Calculated (%): C, 54.55; H, 3.87; N, 4.89. IR,
ν/cm–1: 1635, 1615, 1563, 1492, 1454. 1H NMR (CDCl3), δ:
2.36 (s, 6 H, 2 Me); 3.43 (s, 3 H, OMe); 3.44 (s, 3 H, OMe);
6.95 (d, 2 H, 2 H(8), Jo = 8.4 Hz); 7.25 (dd, 2 H, 2 H(7), Jo = 8.4
Hz, Jm = 1.8 Hz); 7.62 (br.d, 2 H, 2 H(5), Jm = 1.8 Hz); 7.79
(br.s, 1 H, =CH); 7.80 (br.s, 1 H, =CH); 13.12 (m, 2 H, 2 NH).
Reaction of chromones 1 and 10 with methylhydrazine (general
procedure C). A mixture of MeNHNH2•H2SO4 (360 mg, 2.5 mmol)
and anhydrous AcONa (410 mg, 5.0 mmol) in MeOH (6 mL)
was refluxed for 5 min, after that, chromone 1 (1.2 mmol) was
added to the still hot suspension. The reaction mixture obtained
was kept for 2 days at ~20 °C, then diluted with water (20 mL), a
precipitate formed was filtered off, dried, and recrystallized from
toluene—hexane (1 : 1) or methanol.
Calculated (%): C, 54.93; H, 3.90; N, 9.86. IR, ν/cm–1: 3115,
1634, 1608, 1591, 1541, 1505, 1484. 1H NMR (CDCl3), δ:
2.29 (s, 3 H, Me); 4.06 (s, 3 H, NMe); 6.96 (d, 1 H, H(3´),
Jo = 8.4 Hz); 7.34 (dd, 1 H, H(4´), Jo = 8.4 Hz, Jm = 2.1 Hz);
7.37 (br.s, 1 H, H(6´)); 7.74 (s, 1 H, H(5)); 11.58 (s, 1 H, OH).
1H NMR (DMSOꢀd6), δ: 2.25 (s, 3 H, Me); 3.96 (s, 3 H, NMe);
6.90 (d, 1 H, H(3´), Jo = 8.2 Hz); 7.29 (dd, 1 H, H(4´), Jo = 8.4 Hz,
Jm = 2.2 Hz); 7.30 (br.s, 1 H, H(6´)); 8.35 (s, 1 H, H(5)); 10.48
(s, 1 H, OH). 19F NMR (CDCl3), δ: 100.91 (s, CF3). 19F NMR
(DMSOꢀd6), δ: 102.27 (s, CF3).
4ꢀ(2ꢀHydroxyꢀ5ꢀmethylbenzoyl)ꢀ1ꢀmethylꢀ3ꢀ(1,1,2,2ꢀtetraꢀ
fluoroethyl)pyrazole (7c) was obtained from chromone 1e accordꢀ
ing to procedure D, the yield was 59%, coarse bright yellow
crystals, m.p. 169—170 °C. Found (%): C, 53.24; H, 3.87; N, 8.87.
C14H12F4N2O2. Calculated (%): C, 53.17; H, 3.82; N, 8.86.
IR, ν/cm–1: 3108, 1630, 1602, 1536, 1502, 1485. 1H NMR
(DMSOꢀd6), δ: 2.25 (s, 3 H, Me); 3.96 (s, 3 H, NMe); 6.90 (d,
1 H, H(3´), Jo = 8.4 Hz); 6.93 (tt, 1 H, CF2CF2H, 2JH,F = 52.6 Hz,
3JH,F = 5.7 Hz); 7.28—7.32 (m, 2 H, H(4´), H(6´)); 8.34 (s, 1 H,
H(5)); 10.51 (s, 1 H, OH).
3ꢀDifluoromethylꢀ1ꢀmethylꢀ4ꢀsalicylpyrazole (7d) was obtained
from chromone 1f according to procedure D, the yield was 70%,
colorless crystals, m.p. 114—115 °C. Found (%): C, 56.86; H,
4.07; N, 10.98. C12H10F2N2O2. Calculated (%): C, 57.14;
H, 4.00; N, 11.11. IR, ν/cm–1: 3122, 1627, 1594, 1536, 1486.
1H NMR (CDCl3), δ: 4.03 (s, 3 H, Me); 6.93 (ddd, 1 H,
H(5´), Jo = 8.1 Hz, 7.3 Hz, Jm = 1.1 Hz); 7.04 (dd, 1 H, H(3´),
Jo = 8.4 Hz, Jm = 1.0 Hz); 7.08 (t, 1 H, CF2H, 2JH,F = 54.1 Hz);
7.51 (ddd, 1 H, H(4´), Jo = 8.5 Hz, 7.3 Hz, Jm = 1.6 Hz); 7.70
(dd, 1 H, H(6´), Jo = 8.0 Hz, Jm = 1.6 Hz); 7.82 (s, 1 H, H(5));
11.74 (s, 1 H, OH).
4ꢀ(5ꢀChloroꢀ2ꢀhydroxybenzoyl)ꢀ3ꢀdifluoromethylꢀ1ꢀmethylꢀ
pyrazole (7e) was obtained from chromone 1g according to
procedure D (74% yield) and according to procedure B (66%
yield), bright yellow crystals, m.p. 169—170 °C. Found (%): C,
50.04; H, 3.11; N, 9.76. C12H9ClF2N2O2. Calculated (%):
C, 50.28; H, 3.16; N, 9.77. IR, ν/cm–1: 3106, 1629, 1598, 1539,
1
1502, 1473. H NMR (DMSOꢀd6), δ: 3.92 (s, 3 H, NMe); 7.00
Procedure D. Methylhydrazine (175 mg, 3.8 mmol) was
added to a solution of chromone 1 or 10 (1.3 mmol) in MeOH
(5 mL) cooled to –10 °C and the mixture obtained was kept at
this temperature for 1 day. The crystals formed were filtered off
and washed with cold methanol.
(d, 1 H, H(3´), Jo = 8.7 Hz); 7.23 (t, 1 H, CF2H, 2JH,F = 53.7 Hz);
7.39 (d, 1 H, H(6´), Jm = 2.7 Hz); 7.44 (dd, 1 H, H(4´), Jo = 8.7 Hz,
Jm = 2.7 Hz); 8.26 (s, 1 H, H(5)); 10.48 (s, 1 H, OH). 19F NMR
(DMSOꢀd6), δ: 47.73 (d, CF2H, 2JH,F = 53.7 Hz).
2ꢀMethylꢀ4ꢀ(trifluoromethyl)ꢀ2,4ꢀdihydrochromeno[4,3ꢀc]ꢀ
pyrazolꢀ4ꢀol (8a) was obtained from chromone 1a according to
procedure D, the yield was 49%, colorless needleꢀlike crystals,
m.p. 220—221 °C. Found (%): C, 53.27; H, 3.31; N, 10.39.
C12H9F3N2O2. Calculated (%): C, 53.34; H, 3.36; N, 10.37. IR,
ν/cm–1: 3066, 1620, 1595, 1556, 1472. 1H NMR (DMSOꢀd6), δ:
3.96 (s, 3 H, NMe); 7.07—7.11 (m, 2 H, H(6), H(8)); 7.29 (ddd,
1 H, H(7), Jo = 8.2 Hz, 7.5 Hz, Jm = 1.7 Hz); 7.72 (dd, 1 H,
H(9), Jo = 7.6 Hz, Jm = 1.6 Hz); 8.03 (s, 1 H, H(3)); 8.79 (s,
1 H, OH). 19F NMR (DMSOꢀd6), δ: 78.44 (s, CF3). 13C NMR
(DMSOꢀd6), δ: 39.00 (NMe), 94.73 (q, C(4), 2JC,F = 34.7 Hz);
109.02 (C(3a)), 115.40 (C(9a)), 116.89 (C(6)), 121.66 (C(9)),
122.31 (q, CF3, 1JC,F = 286.2 Hz); 122.38 (C(8)), 129.45 (C(3),
C(7)), 142.18 (C(9b)), 150.83 (C(5a)).
1ꢀMethylꢀ4ꢀsalicylꢀ3ꢀ(trifluoromethyl)pyrazole (7a) was
obtained from chromone 1a according to procedure C, the yield
was 45%, cream needleꢀlike crystals, m.p. 86—87 °C. Found
(%): C, 53.62; H, 3.45; N, 10.59. C12H9F3N2O2. Calculated
(%): C, 53.34; H, 3.36; N, 10.37. IR, ν/cm–1: 3144, 1625, 1599,
1536, 1500, 1486. 1H NMR (CDCl3), δ: 4.05 (s, 3 H, Me); 6.91
(ddd, 1 H, H(5´), Jo = 8.0 Hz, 7.3 Hz, Jm = 1.1 Hz); 7.06 (dd, 1
H, H(3´), Jo = 8.5 Hz, Jm = 1.1 Hz); 7.53 (ddd, 1 H, H(4´),
Jo = 8.5 Hz, 7.3 Hz, Jm = 1.6 Hz); 7.61 (dd, 1 H, H(6´), Jo = 8.0 Hz,
Jm = 1.6 Hz); 7.75 (s, 1 H, H(5)); 11.77 (s, 1 H, OH). 19F NMR
(CDCl3), δ: 100.78 (s, CF3). 13C NMR (CDCl3), δ: 39.87, 118.54,
1
118.90, 119.02, 120.04, 120.41 (q, CF3, JC,F = 269.8 Hz),
2
131.83, 134.30, 136.73, 141.76 (q, C—CF3, JC,F = 38.5 Hz),
162.78, 191.71.
6,10ꢀDimethoxyꢀ2ꢀmethylꢀ4ꢀ(trifluoromethyl)ꢀ2,4ꢀdihydroꢀ
furo[3´,2´:6,7]chromeno[4,3ꢀc]pyrazolꢀ4ꢀol (11) was obtained
from furochromone 10 according to procedure D, the yield was
65%, colorless needleꢀlike crystals, m.p. 200—201 °C. Found (%):
C, 51.78; H, 3.50; N, 7.24. C16H13F3N2O5. Calculated (%): C,
4ꢀ(2ꢀHydroxyꢀ5ꢀmethylbenzoyl)ꢀ1ꢀmethylꢀ3ꢀ(trifluoromethyl)ꢀ
pyrazole (7b) was obtained from chromone 1b according to proꢀ
cedure C, the yield was 48%, bright yellow crystals, m.p. 152—
153 °C. Found (%): C, 54.93; H, 3.82; N, 9.82. C13H11F3N2O2.

2154
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 10, October, 2008
Sosnovskikh et al.
51.90; H, 3.54; N, 7.57. IR, ν/cm–1: 3300—3030, 1626, 1605,
1573, 1556, 1518, 1478. H NMR (DMSOꢀd6), δ: 3.94 (s, 3 H,
H(7), Jo = 7.5 Hz); 7.57 (br.s, 2 H, H(2´), H(6´)); 7.65 (br.s,
3 H, H(3´), H(4´), H(5´)); 7.88 (br.s, 0.9 H, H(3)); 8.42
(br.s, 0.1 H, H(3)); 9.02 (br.s, 0.9 H, OH); 9.90 (br.s, 0.1 H,
OH). 19F NMR (DMSOꢀd6), δ: 79.14 (s, 0.9 CF3); 88.94
(br.s, 0.1 CF3).
1
MeO), 3.98 (s, 3 H, MeO), 3.94—3.98 (br.s, 3 H, MeN), 7.13
(d, 1 H, H(9), J = 2.2 Hz); 7.93 (d, 1 H, H(8), J = 2.2 Hz); 8.05
(br.s, 1 H, H(3)); 8.80 (br.s, 1 H, OH). 19F NMR (DMSOꢀd6),
δ: 78.87 (s, 0.9 CF3), 89.0 (br.s, 0.1 CF3).
2ꢀHydroxyphenyl 1ꢀmethylꢀ3ꢀ(trifluoromethyl)pyrazolꢀ4ꢀyl
ketone Nꢀmethylhydrazone (9a) was not isolated in the individual
state, however it was registered in the mixture of the composition
8a : 9a = 72 : 28 obtained during the reaction between chromone
1a and MeNHNH2 at ~20 °C. 1H NMR (DMSOꢀd6), δ: 2.89 (d,
3 H, NHMe, J = 4.3 Hz); 4.00 (s, 3 H, NMe); 6.38 (q, 1 H, NH,
J = 4.2 Hz); 6.63 (dd, 1 H, H(6´), Jo = 7.9 Hz, Jm = 1.6 Hz);
6.70 (t.d, 1 H, H(5´), Jo = 7.5 Hz, Jm = 1.1 Hz); 6.83 (dd, 1 H,
H(3´), Jo = 8.2 Hz, Jm = 1.1 Hz); 7.06—7.10 (m, 1 H, H(4´));
8.06 (s, 1 H, H(5)); 12.23 (s, 1 H, OH).
2ꢀHydroxyꢀ5ꢀmethylphenyl 1ꢀmethylꢀ3ꢀ(trifluoromethyl)ꢀ
pyrazolꢀ4ꢀyl ketone Nꢀmethylhydrazone (9b) was obtained from
chromone 1b according to procedure D. The irregular crystals
formed, being a mixture of hydrazone 9b and pyrazole 7b
described above, were separated by recrystallization from MeOH.
Pyrazole 7b (70 mg, 19%, m.p. 153—154 °C) and hydrazone 9b
(110 mg, 27%, m.p. 183—184 °C) were isolated. Found (%):
C, 53.84; H, 4.80; N, 17.99. C14H15F3N4O. Calculated (%): C,
53.84; H, 4.84; N, 17.94. IR, ν/cm–1: 3316, 3127, 1600, 1566,
1531, 1493. 1H NMR (DMSOꢀd6), δ: 2.08 (s, 3 H, Me); 2.88 (d,
3 H, NHMe, J = 4.3 Hz); 4.01 (s, 3 H, NMe); 6.32 (q, 1 H, NH,
J = 4.3 Hz); 6.44 (d, 1 H, H(6´), Jm = 2.1 Hz); 6.73 (d, 1 H,
H(3´), Jo = 8.2 Hz); 6.91 (dd, 1 H, H(4´), Jo = 8.2 Hz, Jm = 2.1 Hz);
8.05 (s, 1 H, H(5)); 12.03 (s, 1 H, OH). 19F NMR (DMSOꢀd6),
δ: 102.18 (s, CF3).
1ꢀMethylꢀ4ꢀsalicylpyrazole (15). A solution of 3ꢀformylꢀ
chromone 14 (350 mg, 2.0 mmol) and methylhydrazine (100 mg,
2.2 mmol) in EtOH (10 mL) was refluxed for 4 h, then diluted
with water (20 mL) containing conc. HCl (2 drops) and kept for
16 h. The crystals were filtered off, washed with water, and dried.
The yield was 50% (200 mg), colorless crystals, m.p. 71—72 °C.
Found (%): C, 65.28; H, 4.96; N, 13.85. C11H10N2O2. Calcuꢀ
lated (%): C, 65.34; H, 4.98; N, 13.85. IR, ν/cm–1: 3121, 1621,
1592, 1579, 1539, 1485. 1H NMR (CDCl3), δ: 4.00 (s, 3 H,
MeN); 6.94 (ddd, 1 H, H(5´), Jo = 8.0 Hz, 7.3 Hz, Jm = 1.1 Hz);
7.05 (dd, 1 H, H(3´), Jo = 8.4 Hz, Jm = 1.0 Hz); 7.50 (ddd, 1 H,
H(4´), Jo = 8.5 Hz, 7.3 Hz, Jm = 1.7 Hz); 7.86 (dd, 1 H, H(6´),
Jo = 8.0 Hz, Jm = 1.7 Hz); 7.97 (s, 1 H, H(3) or H(5)); 7.98 (s,
1 H, H(5) or H(3)); 12.04 (s, 1 H, OH).
2ꢀHydroxyphenyl 1ꢀmethylpyrazolꢀ4ꢀyl ketone Nꢀmethylꢀ
hydrazone (16) was obtained from 3ꢀformylchromone 14 and
pyrazole 15 with excess of methylhydrazine (3.5—4 equiv.)
according to procedure described for pyrazole 15. The yield was
53%, fluffy needleꢀlike crystals, m.p. 146—147 °C. Found (%):
C, 62.58; H, 6.21; N, 24.26. C12H14N4O. Calculated (%): C,
62.59; H, 6.13; N, 24.33. IR, ν/cm–1: 3238, 3120, 1618, 1585,
1
1532, 1515, 1481. H NMR (CDCl3), δ: 3.01 (s, 3 H, MeNH);
4.02 (s, 3 H, MeN); 5.3 (br.s, 1 H, NH); 6.73 (ddd, 1 H, H(5´),
Jo = 7.9 Hz, 7.3 Hz, Jm = 1.2 Hz); 6.96 (dd, 1 H, H(3´), Jo = 8.2 Hz,
Jm = 1.2 Hz); 6.99 (dd, 1 H, H(6´), Jo = 7.9 Hz, Jm = 1.7 Hz);
7.17 (ddd, 1 H, H(4´), Jo = 8.2 Hz, 7.3 Hz, Jm = 1.7 Hz); 7.52
(s, 1 H, H(3) or H(5)); 7.57 (s, 1 H, H(5) or H(3)); 12.4 (br.s,
1 H, OH).
5ꢀChloroꢀ2ꢀhydroxyphenyl 3ꢀdifluoromethylꢀ1ꢀmethylpyrazolꢀ
4ꢀyl ketone Nꢀphenylhydrazone (9c). A mixture of pyrazole 7e
(140 mg, 0.5 mmol) and PhNHNH2 (160 mg, 1.5 mmol) was
heated for 6 h at 85 °C without solvent and cooled, a solid
product formed was recrystallized from MeOH. The yield was
82% (150 mg), yellowish crystals, m.p. 224—225 °C. Found
(%): C, 57.12; H, 3.74; N, 14.91. C18H15ClF2N4O. Calculated
(%): C, 57.38; H, 4.01; N, 14.87. IR, ν/cm–1: 3267, 3133, 1600,
XꢀRay diffraction study of compound 9b was performed on a
Bruker P4 diffractometer (MoꢀKαꢀirradiation with graphite
monochromator, 2θ/θꢀscanning in the region 2θ < 52°). A crystal
sample of compound 9b of 0.70Ѕ0.60Ѕ0.30 mm in size has been
chosen for the experiment. Crystals are triclinic: a = 8.489(1),
b = 8.799(1), c = 10.639(1) Å, α = 88.18(1)°, β = 70.393(9)°,
–
1
3
1578, 1532, 1503, 1476. H NMR (DMSOꢀd6), δ: 4.02 (s, 3 H,
γ = 81.60(1)°, V = 740.5(2) Å , space group is P1, Z = 2,
NMe); 6.74 (d, 1 H, H(6´), Jo = 2.6 Hz); 6.87 (t, 1 H, H(4´´),
J = 7.3 Hz); 6.93 (t, 1 H, CF2H, 2JH,F = 53.9 Hz); 6.95 (d, 1 H,
H(3´), Jo = 8.8 Hz); 7.06—7.09 (m, 2 H, H(2´´), H(6´´)); 7.22
(dd, 1 H, H(4´), Jo = 8.7 Hz, Jm = 2.6 Hz); 7.26—7.031 (m, 2 H,
H(3´´), H(5´´)); 8.12 (s, 1 H, H(5)); 9.41 (s, 1 H, NH); 12.32 (s,
1 H, OH).
1ꢀPhenylꢀ4ꢀ(trifluoromethyl)ꢀ1,4ꢀdihydrochromeno[3,4ꢀd]ꢀ
pyrazolꢀ4ꢀol (13). Phenylhydrazine (220 mg, 2.0 mmol) was
added to a solution of chromone 1a (250 mg, 1.0 mmol) in
MeOH (5 mL) cooled to –10 °C. The mixture obtained was kept
at this temperature for 2 days, then heated to boiling and diluted
with hot water (5 mL) containing conc. HCl (0.3 mL) to remove
residual excess of PhNHNH2. After cooling, a precipitate formed
was filtered off, washed with water and recrystallized from
toluene—hexane (1 : 1). The yield was 30% (100 mg), cream
needleꢀlike crystals, m.p. 185—186 °C. Found (%): C, 61.20; H,
3.41; N, 8.34. C17H11F3N2O2. C, 61.45; H, 3.34; N, 8.43. IR,
ν/cm–1: 3077, 1613, 1591, 1523, 1498. 1H NMR (DMSOꢀd6), δ:
6.78 (br.d, 1 H, H(6), Jo = 7.5 Hz); 6.90 (br.t, 1 H, H(8),
Jo = 7.5 Hz); 7.19 (br.d, 1 H, H(9), Jo = 7.5 Hz); 7.32 (br.t, 1 H,
C14H15F3N4O, dcalc = 1.401 g cm–3, μ = 0.118 mm–1. Intensities
of 2910 independent reflections were measured. A correction on
absorption of the crystal cutting was made (transmission was
0.92—0.97). The structure was decoded by direct method using
the SHELXSꢀ97 program.26 Refining of the structural parameters
was carried out by the least squares method in the fullꢀmatrix
anisotropicꢀisotropic approximation using the SHELXLꢀ97
program.26 Positions of the H atoms of the hydroxy and amino
groups were localized from the differential synthesis and refined
isotropically. Parameters of other H atoms were calculated
geometrically in every cycle of refining based on the coordinates
of the corresponding carbon atoms. The CF3 group is disordered
over two position with the ratio of weights of 0.563 : 0.437(4).
The final refining of the structure was made on all the F 2 to
wR2 = 0.1386, S = 1.027, 235 parameters were refined (R = 0.0477
for 2487 F > 4σ). The Cambridge Structural Database Number
is 643201.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 06ꢀ03ꢀ32388).

Reactions of 3ꢀ(polyfluoroacyl)chromones
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 10, October, 2008
2155
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Received December 13, 2007 ;
in revised form May 7, 2008