Reactions of 3-acetyl-and 3-acetimidoyl-5,6,7,8-tetrafluoro-4- hydroxycoumarins with substituted hydrazines

Article abstract of DOI:10.1007/s11172-009-0166-4

3-Acetyl-and 3-acetimidoyl-5,6,7,8-tetrafluoro-4-hydroxycoumarins react with methyl-and phenylhydrazines giving either condensation products at the acyl substituent, i.e., 5,6,7,8-tetrafluoro-3-(1-hydrazino)ethylidenebenzopyran-2,4- diones, or recyclizati

Full text of DOI:10.1007/s11172-009-0166-4

Russian Chemical Bulletin, International Edition, Vol. 58, No. 6, pp. 1270—1275, June, 2009
1270
Reactions of 3ꢀacetylꢀ and 3ꢀacetimidoylꢀ5,6,7,8ꢀtetrafluoroꢀ
4ꢀhydroxycoumarins with substituted hydrazines*
K. V. Shcherbakov, Ya. V. Burgart, and V. I. Saloutin
I. Ya. Postovskii Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
22/20 ul. S. Kovalevskoi, 620041 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 5954. Eꢀmail: specialk@mail.ru
3ꢀAcetylꢀ and 3ꢀacetimidoylꢀ5,6,7,8ꢀtetrafluoroꢀ4ꢀhydroxycoumarins react with methylꢀ
and phenylhydrazines giving either condensation products at the acyl substituent, i.e., 5,6,7,8ꢀ
tetrafluoroꢀ3ꢀ(1ꢀhydrazino)ethylidenebenzopyranꢀ2,4ꢀdiones, or recyclization products,
i.e., 6,7,8ꢀtrifluoroꢀ5ꢀhydroxybenzopyrano[2,3ꢀc]pyrazolꢀ4ꢀones, depending on nucleophilicity
of the diamine and the nature of the solvent used. In the reaction with phenylhydrazine, the
formation of 1ꢀphenylꢀ3Hꢀpyrazolꢀ3ꢀone derivative is also possible, and in the reaction with
methylhydrazine, the formation of 7ꢀmethylhydrazinobenzopyrano[2,3ꢀc]pyrazolone, too.
Key words: 3ꢀacylꢀ4ꢀhydroxycoumarins, hydrazines, αꢀpyrone ring opening, recyclization,
selectivity.
Coumarins are known for their biological activity and
high reactivity, due to which they are widely used in
organic synthesis.1,2 We have developed methods for the
synthesis of fluorineꢀcontaining derivatives of 4ꢀhydroxyꢀ
coumarin3 and studied their transformations in the reacꢀ
tions with primary,4 secondary5 monoamines, and oꢀpheꢀ
nylenediamine.6 It has been found that the reactions
of 3ꢀacetyl(acetimidoyl)ꢀ5,6,7,8ꢀtetrafluoroꢀ4ꢀhydroxyꢀ
coumarins with primary monoamines, depending on
nucleophilicity of the amine and the solvent used,4 can
take two competing directions: a condensation at the acyl
group and substitution of F atoms at position 7 (in seldom
cases, at position 5), whereas in the reactions with
secondary amines, a substitution of F atom is the major
process. It was also found that αꢀpyrone ring is more
stable to nucleophilic attack as compared to nonfluoriꢀ
nated analogs, since the ring opening was observed only
upon the action of oꢀphenylenediamine.6
pyrano[2,3ꢀc]pyrazolꢀ4ꢀones. In addition, the cyclization
of 3ꢀhydrazinoethylideneꢀ4ꢀhydroxycoumarins can take
place at position 4 leading to 1ꢀarylꢀ3ꢀmethylbenzoꢀ
pyrano[4,3ꢀc]pyrazolꢀ4ꢀones. And finally, they can
give isomeric 2ꢀarylꢀ3ꢀmethylbenzopyrano[4,3ꢀc]pyrazolꢀ
4ꢀones as a result of condensation with arylhydrazine
hydrochloride.7—13 In the series of benzopyranopyrazolꢀ
ones, there are found compounds possessing significant
activity with respect to central nervous system.
The rich opportunities of 3ꢀacylꢀ4ꢀhydroxycoumarins
in the reactions with arylhydrazines prompted us to study
reactions of 3ꢀacetimidoylꢀ and 3ꢀacetylꢀ5,6,7,8ꢀtetraꢀ
fluoroꢀ4ꢀhydroxycoumarins (1, 2) with substituted
hydrazines under various conditions in order to broaden
the use of fluorinated coumarins in organic synthesis as
synthetic blocks.
For this research, we have chosen hydrazines with
various nucleophilicity. It is known that nucleophilicity
in the series of related compounds is correlated with the
base strength,14 therefore, the hydrazines used by us
can be arranged in the following order according to their
basicity: phenylhydrazine (pKa = 5.27), methylhydrazine
(pKa = 7.87).15
According to the literature data, nonfluorinated
3ꢀacylꢀ4ꢀhydroxycoumarins
with
arylhydrazines
form condensation products at the acyl substituent, viz.,
3ꢀhydrazinoethylideneꢀ4ꢀhydroxycoumarins, which
depending on the reaction conditions can undergo
various cyclizations. For instance, they can cyclize at
the C(2) center with the αꢀpyrone ring opening and forꢀ
mation of 1ꢀarylꢀ4ꢀ(2ꢀhydroxybenzoyl)ꢀ5ꢀmethylꢀ
1,2ꢀdihydroꢀ3Hꢀpyrazolꢀ3ꢀones, the intramolecular
condensation of which leads to 1ꢀarylꢀ3ꢀmethylbenzoꢀ
Results and Discussion
We have found that coumarins 1 and 2, irrespective
of the solvent used, react with phenylhydrazine at room
temperature giving rise to the condensation product
at the acetimidoyl (acetyl) substituent, 5,6,7,8ꢀtetraꢀ
* Dedicated to Academician O. N. Chupakhin in honor of his
75th anniversary.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1234—1239, June, 2009.
1066ꢀ5285/09/5806ꢀ1270 © 2009 Springer Science+Business Media, Inc.

Hydrazination of fluorinated 3ꢀacylꢀ4ꢀhydroxycoumarines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 6, June, 2009
1271
Scheme 1
dione 3 on the C(2) atom of the carbonyl group, which
leads to the αꢀpyrone ring opening and the intermediate
formation of 4ꢀ(2,3,4,5ꢀtetrafluoroꢀ6ꢀhydroxybenzoyl)ꢀ
5ꢀmethylꢀ2ꢀphenylꢀ1,2ꢀdihydroꢀ3Hꢀpyrazolꢀ3ꢀone (5).
The ready cyclization of the latter into benzopyranoꢀ
pyrazolone 4 is explained by the presence of F atoms in
the benzoyl substituent. As a result, the pyrone ring is
formed through the intramolecular substitution of the F
atom for the OH group of the pyrazole residue, whereas
nonfluorinated analogs can give only intramolecular conꢀ
densation with participation of hydroxy groups of the aryl
and pyrazole fragments, which requires dehydrating
agents.
We succeeded in obtaining pyrazolone 5, which has
been earlier indicated as an intermediate during formaꢀ
tion of benzopyranopyrazolone 4, by the use of a mixture
of 30% aq. HCl and ethanol as a reaction media for couꢀ
marin 1 and phenylhydrazine (see Scheme 1). Attempted
transformation of obtained pyrazolone 5 to product 4 upon
heating in toluene led to resinification of the reaction
mixture and formation of a mixture of products difficult
to separate. However, the cyclization was accomplished
upon reflux in acetic acid.
Results of the study of coumarins 1 and 2 reaction
with oꢀphenylenediamine6 testified that carrying out the
reaction in the highꢀboiling solvents promotes formaꢀ
tion of new heterocyclic systems. In fact, the reflux of
coumarins 1 and 2 with phenylhydrazine in toluene led
directly to the formation of benzopyranopyrazolone 4
(see Scheme 1).
When the reaction of coumarins 1 and 2 with methylꢀ
hydrazine, which is more nucleophilic than phenylhydrꢀ
azine, was studied, we found that directions of transformaꢀ
tions even at room temperature depends on the nature of
solvent used. For instance, in diethyl ether or acetonitrile
methylhydrazine reacts with coumarins 1 and 2 at the acyl
substituent to form 5,6,7,8ꢀtetrafluoroꢀ3ꢀ[1ꢀ(2ꢀmethylꢀ
hydrazino)ethylidene]benzopyranꢀ2,4ꢀdione (6) (Scheme 2).
However, when these reactions were performed in
ethanol even at room temperature, 6,7,8ꢀtrifluoroꢀ5ꢀ
hydroxyꢀ1,3ꢀdimethylbenzopyrano[2,3ꢀc]pyrazolꢀ4(1H)ꢀ
one (7) was isolated as the product (see Scheme 2). The
same heterocycle was obtained upon keeping coumarin 6
in ethanol.
It is possible that the formation of benzopyranoꢀ
pyrazolone 7 in ethanol proceeds through the step of the
formation of adduct of coumarin 6 with the solvent molꢀ
ecule (Scheme 3). The РM3 calculations of relative
charges for competing electrophilic centers C(2) and C(4)
in benzopyrandione 6 and its adduct with ethanol showed
an increase in the charge absolute value on the C(2) atom
in the adduct. As a consequence, the rate of nucleophilic
substitution at this reaction center increases. Nucleophiꢀ
licity of the NHMe group in benzopyrandione 6 is higher
than that of the NHPh group in compound 3. Apparently,
Reagents and conditions: i, Et2O (EtOH, MeCN, DMSO,
AcOH), 25 °C, 24 h; ii, PhMe, 110 °C, 72 h; iii, EtOH—HCl
(30 wt.%), 25 °C, 72 h; iv, PhMe, 110 °C, pꢀTsOH; v, AcOH,
80 °C, 72 h; vi, AcOH, 80 °C, 28 h.
fluoroꢀ3ꢀ[1ꢀ(2ꢀphenylhydrazino)ethylidene]benzopyranꢀ
2,4ꢀdione (3), like nonfluorinated analogs (Scheme 1).
Further, we attempted to transform the product 3
obtained. Thus, under cyclization conditions of nonfluorꢀ
inated analogs (heating in toluene in the presence of cataꢀ
lytic amount of pꢀtoluenesulfonic acid) into benzopyranoꢀ
[4,3ꢀc]pyrazolones,7,9 only coumarin 1 was isolated, which
is apparently formed after reductive cleavage of the N—N
bond of the hydrazine fragment (see Scheme 1). The presꢀ
ence of the peak with m/z 274 (Irel = 23.23%) correspondꢀ
ing to the fragment [M – NH2Ph] in the mass spectrum
of compound 3 indicates lability of this bond.
The heating of compound 3 in acetic acid furnished
6,7,8ꢀtrifluoroꢀ5ꢀhydroxyꢀ3ꢀmethylꢀ1ꢀphenylbenzopyranoꢀ
[2,3ꢀc]pyrazolꢀ4(1H)ꢀone (4) (see Scheme 1). Note that
transformations of nonfluorinated analogs under given
conditions led to 1ꢀarylꢀ5ꢀhydroxyꢀ4ꢀ(2ꢀhydroxybenzoyl)ꢀ
pyrazoles,9,10,12 which only upon heating with POCl3
underwent the intramolecular condensation giving triꢀ
cyclic methylbenzopyrano[2,3ꢀc]pyrazolones.
It is obvious that compound 4 results from the attack
of the NH group at the phenyl substituent in benzopyranꢀ

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Shcherbakov et al.
Scheme 2
O(2)
H(3)
C(4)
O(3)
C(12)
C(1)
F(1)
C(5)
C(3)
C(2)
C(6)
C(7)
N(2)
C(9)
N(1)
C(10)
C(8)
F(2)
O(1)
C(11)
F(3)
Fig. 1. Crystal structure of 6,7,8ꢀtrifluoroꢀ5ꢀhydroxyꢀ
1,3ꢀdimethylbenzopyrano[2,3ꢀc]pyrazolꢀ4(1H)ꢀone (7). Therꢀ
mal ellipsoids of 50% probability are shown.
The reactions of coumarins 1 and 2 with methylꢀ
hydrazine in DMSO at room temperature give rise to
6,8ꢀdifluoroꢀ5ꢀhydroxyꢀ1,3ꢀdimethylꢀ7ꢀ(2ꢀmethylhydrꢀ
azino)benzopyrano[2,3ꢀc]pyrazolꢀ4(1H)ꢀone (8) (see
Scheme 2).
Results of our preceding studies4 showed that in the
reactions of 3ꢀacylꢀ5,6,7,8ꢀtetrafluoroꢀ4ꢀhydroxycoumaꢀ
rins 1 and 2 with primary monoamines in strongly polar
DMSO, the condensation at the acyl fragment is accomꢀ
panied by substitution of the F atom at position 7 of the
fluoroaromatic ring. Therefore, it can be suggested that
the reaction of coumarins 1 and 2 with methylhydrazine
proceeds with the intermediate formation of 5,6,8ꢀtriꢀ
fluoroꢀ7ꢀmethylhydrazinoꢀ3ꢀ(2ꢀmethylhydrazinoethylꢀ
idene)benzopyranꢀ2,4ꢀdione. The formation of 7ꢀsubstiꢀ
tuted benzopyranopyrazolone 8 in DMSO can be explained
by the fact that the electronꢀwithdrawing character of
polyfluoroaryl ring (and, therefore, ability to nucleophilic
substitution of the F atom) considerably increases
when aprotic dipolar solvents are used: Et2O (ε = 4.27,
μ = 1.15 D), EtOH (ε = 24.5, μ = 1.68 D), MeCN
(ε = 35.9, μ = 3.44 D), DMSO (ε = 48.5, μ = 3.96 D).16
To sum up, we found that the final result of the transꢀ
formations in the reaction of coumarins 1 and 2 with
substituted hydrazines is considerably influenced by
Reagents and conditions: i, Et2O (MeCN), 25 °C, 24 h; ii, PhMe,
110 °C, 72 h (EtOH, 25 °C, 72 h); iii, DMSO, 25 °C, 72 h;
iv, EtOH, 25 °C.
this has a decisive influence on the possible formation of
benzopyranopyrazolone 7 in ethanol.
The reaction of coumarins 1 and 2 with methylꢀ
hydrazine in boiling toluene leads to the formation of
benzopyranopyrazolone 7, like in analogous transformaꢀ
tions with phenylhydrazine (see Scheme 2).
According to the Xꢀray diffraction data, compound 7
has the structure of 6,7,8ꢀtrifluoroꢀ5ꢀhydroxyꢀ1,3ꢀdimethylꢀ
benzopyrano[2,3ꢀc]pyrazolꢀ4(1H)ꢀone (Fig. 1). The benzoꢀ
pyranopyrazole ring of the molecule is virtually planar.
The molecule of heterocycle is characterized by the
presence of one intramolecular hydrogen bond
(IMHB) between the O(2) and H(3) atoms: the distance
...
...
O(2) H(3) is 1.82(4) Å; the angles O(3)—H(3) O(2)
...
and C(3)—O(2) H(3) are 149.53° and 99.60°, respectively.
Scheme 3

Hydrazination of fluorinated 3ꢀacylꢀ4ꢀhydroxycoumarines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 6, June, 2009
1273
nucleophilicity of the reacting hydrazine and the nature
of the solvent used.
accompanied by elimination of hydrogen fluoride, which
leads to the formation of benzopyranopyrazoles containꢀ
ing a hydroxy substituent.
Considering the reactivity of hydrazines under study
in the course of the reactions with coumarins 1 and 2, it
should be noted that more nucleophilic methylhydrazine
exhibits higher tendency to cyclization. This is also
indicated by the relative analysis of the mass spectra of
3ꢀ(1ꢀhydrazinoethylidene)substituted coumarins 3 and 6.
Thus, in the mass spectrum of methylꢀcontaining
coumarin 6, there is observed the peak with m/z 284
(Irel = 25.57%) related to the fragment [M – HF], whereas
in the mass spectrum of phenylꢀsubstituted analog 3, the
intensity of such peak is lower: m/z 346 [M – HF]
(Irel = 1.57%), m/z 345 [M – H – HF] (Irel = 7.33%).
Taking into account experimental data, we can sugꢀ
gest a general scheme for the formation of benzopyranoꢀ
pyrazolones 4, 7, and 8 in the reactions of coumarins 1
and 2 with substituted hydrazines (Scheme 4).
In addition, it should be noted that the regioselectivity
of transformations of fluorinated coumarins 1 and 2 is
higher as compared to the case of nonfluorinated analogs,
of which various directions of cyclization are characterisꢀ
tic.9,10 A predominance of attack of the NH group in
fluorinated 3ꢀ(1ꢀhydrazinoethylidene)ꢀsubstituted benzoꢀ
pyrandiones 3 and 6 at the C(2) atom, possibly, is also
determined by the readiness and irreversibility of recycliꢀ
zation due to the ipsoꢀsubstitution of F atom.
In conclusion, it should be noted that reactions of
fluorinated 3ꢀacetyl(acetimidoyl)ꢀ4ꢀhydroxycoumarins
with hydrazines studied in this work can be used as method
for annulation of benzopyrone ring with pyrazole ring.
Experimental
Melting points were measured on a Stuart SMP3 instrument
in open capillary tubes and uncorrected. IR spectra were recorded
on a Perkin—Elmer Spectrum One spectrometer in the range
4000—400 cm–1 in Nujol. NMR spectra were recorded on a
Bruker DRXꢀ400 spectrometer (1H: 400 MHz, relatively to
SiMe4; 19F: 376.4 MHz, relatively to C6F6). Elemental analysis
was performed using a Perkin—Elmer PE 2400 series II CHNSꢀ
O EA 1108 analyzer. Mass spectra were recorded on a Shimadzu
LCMSꢀ2010 instrument (chemical ionization at atmospheric
pressure (APCI), mobile phase, MeCN). Thinꢀlayer chromatoꢀ
graphy was performed on Alugram SIL G/UV254 plates (silica
gel, 60 μm, layer was 0.20 mm thick, a UV additive, UV254
indicator, support, aluminum foil), eluent, chloroform—ethanol
(10 : 1), visualization of compounds was performed under
the UV light. Monocrystals of 6,7,8ꢀtrifluoroꢀ5ꢀhydroxyꢀ
1,3ꢀdimethylbenzopyrano[2,3ꢀc]pyrazolꢀ4(1H)ꢀone (7) were
obtained by crystallization from toluene. Xꢀray diffraction
experiment was performed on a Xcalibur 3 diffractometer with a
CCD detector (graphite monochromator, λ(MoꢀKα) = 0.71073 Å,
T = 295(2) К, ϕ,ωꢀscanning). Allowance for the absorption was
made analytically by the multifaceted crystal model using the
CrysAlis RED 1.171.28c4 programs. The structure was solved
by the direct method from the differential Fourier syntheses.
Positions and temperature parameters of nonhydrogen atoms
were refined by the least squares method in anisotropic fullꢀ
matrix approximation.
Scheme 4
The starting coumarins 1 and 2 were obtained according to
the procedure described earlier.17
Reaction of coumarins 1 and 2 with hydrazines (general
procedure). A. Methylꢀ or phenylhydrazine (0.5 mmol) was added
to a solution of coumarin 1 or 2 (0.5 mmol) in the corresponding
solvent (30 mL). The reaction mixture was vigorously stirred.
Conversion of starting reagents was monitored by TLC. After
the reaction was complete, the solvent was evaporated, a solid
residue was crystallized from the appropriate solvent.
B. Methylꢀ or phenylhydrazine (0.5 mmol) was added to a
solution of coumarin 1 or 2 (0.5 mmol) in the corresponding
solvent (60 mL). The reaction mixture was heated to the boiling
point of the solvent. Conversion of starting reagents was
R = Me, Ph; R´ = F, NHNHMe
A specific feature of coumarins 1 and 2 containing
F atoms in the aromatic ring in the reactions with hydrꢀ
azines consists in the change of the pathway of their
recyclization as compared to similar transformations of
nonfluorinated analogs in the step of transformations
of pyrazole intermediates. In the case of fluorinated comꢀ
pounds, the formation of new heterocycle occurs due to
the intramolecular nucleophilic substitution of F atom

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Shcherbakov et al.
monitored by TLC. After the reaction was complete, the solvent
was evaporated, a solid residue was crystallized from the
appropriate solvent.
C, 47.38; H, 2.65; F, 24.98; N, 9.21. IR, ν/cm–1: 3306 (NH);
1718 (O—C=O); 1648 (C=O); 1591, 1525 (NH, C=C); 1032
(CF). 1H NMR ((CD3)2CO), δ: 2.77, 2.87 (both s, 3 H each,
2 Me); 5.64, 14.79 (both br.s, 1 H each, NH). 19F NMR
((CD3)2CO), δ: –2.94, 2.33, 11.27, 18.31 (all m, 1 F each).
MS, m/z (Irel (%)): 304 [M] (14.56); 303 [M – H] (100); 284
[M – HF] (25.57).
6,7,8ꢀTrifluoroꢀ5ꢀhydroxyꢀ1,3ꢀdimethylbenzopyrano[2,3ꢀc]ꢀ
pyrazolꢀ4(1H)ꢀone (7). Compound 7 was obtained (71 mg, 50%)
by method B from coumarin 1 and methylhydrazine after reflux
in toluene for 72 h. Similarly, compound 7 was obtained from
coumarin 2 (72 mg, 51%) and by keeping benzopyrandione 6 in
ethanol (65 mg, 46%), a yellow powder, m.p. 137—139 °C (from
ethanol). Found (%): C, 50.47; H, 2.30; F, 19.75; N, 9.71.
C12H7F3N2O3. Calculated (%): C, 50.72; H, 2.48; F, 20.05;
N, 9.86. IR, ν/cm–1: 1641 (C=O); 1581, 1517 (C=C); 1001
(CF). 1H NMR ((CD3)2SO), δ: 2.47 (s, 3 H, Me); 3.85 (s, 3 H,
Me); 12.99 (s, 1 H, OH). 19F NMR ((CD3)2SO), δ: –5.58
(dd, 1 F, 4J = 5.3 Hz, 3J = 22.2 Hz); –2.46 (dd, 1 F, 4J = 5.3 Hz,
3J = 22.2 Hz); 13.38 (tm, 1 F, 3J = 22.2 Hz).
3ꢀAcetimidoylꢀ5,6,7,8ꢀtetrafluoroꢀ4ꢀhydroxycoumarin (1).
Compound 1 (110 mg, 80%) was obtained by method B from
benzopyrandione 3 after reflux in toluene for 72 h, a white
powder, m.p. 165 °C (data in Ref. 17: m.p. 171—173 °C).
5,6,7,8ꢀTetrafluoroꢀ3ꢀ[1ꢀ(2ꢀphenylhydrazino)ethylidene]ꢀ
benzopyranꢀ2,4ꢀdione (3). Compound 3 was obtained by method
A from acetimidoylcoumarin 1 and phenylhydrazine after stirring
at 20 °C for 24 h, the yield was 170 mg (93%) in Et2O, 114 mg
(62%) in MeCN, 64 mg (35%) in DMSO. Similarly, compound
3 was obtained from acetylcoumarin 2, the yield was 172 mg
(94%) in Et2O, 110 mg (60%) in EtOH, a yellow powder,
m.p. 221—224 °C (from diethyl ether). Found (%): C, 55.64;
H, 2.54; F, 20.87; N, 7.62. C17H10F4N2O3. Calculated (%):
C, 55.75; H, 2.75; F, 20.75; N, 7.65. IR, ν/cm–1: 3312 (NH);
1690 (O—C=O); 1650 (C=O); 1602, 1523 (NH, C=C); 1015
(CF). 1H NMR ((CD3)2CO), δ: 2.85 (s, 3 H, Me); 3.77 (s, 2 H,
2 NH); 7.18 (dm, 5 H, Ph). 19F NMR ((CD3)2CO), δ: –2.54,
2.55, 12.04, 18.96 (all m, 1 F each). MS, m/z (Irel (%)): 366 [M]
(14.06); 365 [M – H] (70.80); 274 [M – C6H5NH2] (23.23); 233
[C9HF4O3] (11.41); 216 [C9F4O2] (51.38).
Crystallographic data and parameters of Xꢀray structural
experiment for compound 7: C12H7F3N2O3, M = 284.20,
monoclinic crystal system, space group Р2(1)/n, a = 7.5687(9) Å,
b = 11.0239(14) Å, c = 13.0614(16) Å, α = 90.00°, β =
6,7,8ꢀTrifluoroꢀ5ꢀhydroxyꢀ3ꢀmethylꢀ1ꢀphenylbenzopyranoꢀ
[2,3ꢀc]pyrazolꢀ4(1H)ꢀone (4). Compound 4 was obtained
(130 mg, 75%) by method B from coumarin 1 and phenylꢀ
hydrazine after reflux in toluene for 72 h. Similarly, compound
4 was obtained (119 mg, 69%) from coumarin 2 and phenylꢀ
hydrazine. Compound 4 was also obtained (73 mg, 42%) by
heating benzopyrandione 3 in acetic acid in a water bath at
100 °C for 72 h and by heating pyrazolone 5 in acetic acid in a
water bath at 100 °C for 28 h (23 mg, 38%), a brown powder,
m.p. 215 °C (from ethanol). Found (%): C, 58.50; H, 2.63;
F, 16.55; N, 8.03. C17H9F3N2O3. Calculated (%): C, 58.97;
H, 2.62; F, 16.46; N, 8.09. IR, ν/cm–1: 1671, 1640 (C=O);
= 91.565(10)°, γ = 90.00°; V = 1089.4(2) Å3; Z = 4; dcalc
=
= 1.733 g cm–3, μ = 0.0159 mm–1, the total number of reflecꢀ
tions were 3469, the number of independent reflections were
1644, the Rꢀfactor was 0.0412, the number of refining parameters
were 197.
6,8ꢀDifluoroꢀ5ꢀhydroxyꢀ1,3ꢀdimethylꢀ7ꢀ(2ꢀmethylhydrazino)ꢀ
benzopyrano[2,3ꢀc]pyrazolꢀ4(1H)ꢀone (8). Compound 8 was
obtained (59 mg, 38%) by method A from coumarin 1 and
methylhydrazine upon stirring in DMSO at ~20 °C for 72 h, a
pale yellow powder, m.p. 185—190 °C (from ethanol). Found (%):
C, 50.04; H, 3.78; F, 12.01; N, 17.97. C13H12F2N4O3. Calcuꢀ
1
1623, 1596, 1541 (C=C); 1020 (CF). H NMR ((CD3)2SO), δ:
lated (%): C, 50.33; H, 3.90; F, 12.25; N, 18.06. IR, ν/cm–1
:
2.58 (s, 3 H, Me); 7.49—7.87 (m, 5 H, Ph); 12.80 (s, 1 H,
OH). 19F NMR ((CD3)2CO), δ: –5.36 (dd, 1 F, 4J = 4.9 Hz,
3J = 21.9 Hz); –1.93 (dd, 1 F, 4J = 4.9 Hz, 3J = 21.9 Hz); 13.79
(tm, 1 F, 3J = 21.9 Hz).
3354 (NH); 1660 (C=O); 1626, 1584 (NH, C=C); 1000 (CF).
1H NMR ((CD3)2SO), δ: 2.41, 3.79 (both s, 3 H each, 2 Me);
3.18 (m, 3 H, Me); 4.89 (br.s, 2 H, 2 NH); 12.54 (br.s, 1 H, OH).
19F NMR ((CD3)2SO), δ: 7.27, 10.32 (both br.s, 1 F each).
4ꢀ(2,3,4,5ꢀTetrafluoroꢀ6ꢀhydroxybenzoyl)ꢀ5ꢀmethylꢀ
2ꢀphenylꢀ1,2ꢀdihydroꢀ3Hꢀpyrazolꢀ3ꢀone (5). Compound 5 was
obtained (84 mg, 46%) by method A from coumarin 1 and
phenylhydrazine after stirring in ethanolic HCl (30 wt.%) at
~20 °C for 72 h, a brown powder, m.p. 198—205 °C (from
ethanol). Found (%): C, 58.33; H, 2.82; F, 20.92; N, 7.49.
C17H10F4N2O3. Calculated (%): C, 55.75; H, 2.75; F, 20.75;
N, 7.65. IR, ν/cm–1: 3062 (OH); 1691, 1655 (C=O); 1596, 1520
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 09ꢀ03ꢀ002742)
and Council on Grants of the President of the Russian
Federation (Program for the State Support of Leading
Scientific Schools, Grant NSh 3758.2008.3).
1
References
(C=C); 992 (CF). H NMR ((CD3)2SO), δ: 2.31 (s, 3 H, Me);
6.43 (s, 1 H, NH); 7.22—7.39 (m, 5 H, Ph); 10.95 (s, 1 H,
OH). 19F NMR ((CD3)2CO), δ: –8.14, 1.94, 6.49, 21.80 (all m,
1 F each).
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Received March 21, 2008;
in revised form November 14, 2008