Transformations of 3-(1-aminoethylidene)-5,6,7,8-tetrafluorobenzopyran-2,4-dione with hydrazines

Article abstract of DOI:10.3987/COM-08-11495

3-(1-Aminoethylidene)-5,6,7,8-tetrafluorobenzopyran-2,4-dione reacts with the substituted hydrazines depending on hydrazine nucleophilicity and the reaction conditions. 3-R-hydrazinoethylidene-5,6,7,8-tetrafluorobenzopyrandiones are formed as a result of

Full text of DOI:10.3987/COM-08-11495

HETEROCYCLES, Vol. 78, No. 2, 2009
347
HETEROCYCLES, Vol. 78, No. 2, 2009, pp. 347 - 356. © The Japan Institute of Heterocyclic Chemistry
Received, 17th July, 2008, Accepted, 25th September, 2008, Published online, 29th September, 2008.
DOI: 10.3987/COM-08-11495
TRANSFORMATIONS OF 3-(1-AMINOETHYLIDENE)-5,6,7,8-
TETRAFLUOROBENZOPYRAN-2,4-DIONE WITH HYDRAZINES
Konstantin V. Shcherbakov, Yanina V. Burgart, and Victor I. Saloutin*
I. Ya. Postovski Institute of Organic Synthesis of Urals Division of Russian
Academy of Sciences, 22/20, S. Kovalevskoi / Akademicheskaya Str.,
Ekaterinburg, GSP-147, Russia, 620041, fax (+7343) 374 5954; e-mail:
saloutin@ios.uran.ru, specialk@mail.ru
Abstract – 3-(1-Aminoethylidene)-5,6,7,8-tetrafluorobenzopyran-2,4-dione reacts
with the substituted hydrazines depending on hydrazine nucleophilicity and the
reaction
conditions.
3-R-hydrazinoethylidene-5,6,7,8-tetrafluorobenzo-
pyrandiones are formed as a result of the transamination at aminoethylidene
fragment by hydrazine NH2-group. In the case of methylhydrazine and hydrazine
the transamination can be accompanied by the substitution of fluorine atom at the
atom C-7. Benzopyrano[2,3-c]pyrazolone derivatives are produced due to the
intramolecular addition of the RNH-group at the C-2 atom followed by the
intramolecular substitution of fluorine atom by hydroxyl group.
INTRODUCTION
Coumarins are well-known for their biological activity and high-reaction ability and widely used in
organic synthesis.1,2 We have developed the effective methods for the synthesis of the fluorinated
4-hydroxycoumarin derivatives.3 Reactions of these compounds with primary and secondary monoamines
and with o-phenylenediamine have been studied in our previous investigations.4-6 It was found that
condensation at the acyl group and the substitution of the fluorine atom at the C(7) position (or
substitution of the fluorine atom at the C(5) position in some cases) are the competitive reactions in the
transformations of the 3-acyl-5,6,7,8-tetrafluoro-4-hydroxycoumarins with primary amines. This is
depended on the solvent used and the amine nucleophilicity.4 Whereas, substitution of the fluorine atom
is the initial process in the reactions of coumarins with secondary amines. α-Pyrone ring was found to be
stable to attack of the nucleophiles in comparison with the non-fluorinated analogues.
Herein, we report the transformations of 3-(1-aminoethylidene)-5,6,7,8-tetrafluorobenzopyran-2,4-dione

348
HETEROCYCLES, Vol. 78, No. 2, 2009
(1) with hydrazines under the different reaction conditions to show the utility of the fluorinated coumarins
as block-synthons in organic synthesis.
It is widely known that the non-fluorinated 3-acetyl-4-hydroxycoumarins react with arylhydrazines to
give 3-arylhydrazinoethylidene-4-hydroxycoumarins which can undergo further cyclizations depending
on the reaction conditions (Scheme 1). There are two ways for cyclization: firstly, at the C(2) position
with formation of 1-aryl-5-hydroxy-4-(2-hydroxybenzoyl)-3-methyl-1H-pyrazole which can be
transformed into 1-aryl-3-methylbenzopyrano[2,3-c]pyrazol-4-ones, and secondly, at the C(4) position
with formation of 1-aryl-3-methylbenzopyrano[4,3-c]pyrazol-4-ones. The last-ones can lead to the
isomeric 2-aryl-3-methylbenzopyrano[4,3-c]pyrazol-4-ones in the reaction with arylhydrazine
hydrochloride.7-13
H
N
Ar
N
N
OH
O
N
O
Ar
O
Me
Me
C(4)
C(2)
Me
N
N
TsOH/PhMe, 110 oC
AcOH, 118 oC
O
O
OH OH
Ar
.
ArNHNH2 HCl
EtOH,
ArNHNH2
ArNHNH2
POCl3
(AcOH), 25 oC
Ar
O
O
AcOH, 118 oC
N
N
OH NH
Me
AcOH
Me
Me
N
N
O
O
O
O
Ar
Scheme 1
We selected hydrazines having the different nucleophilicity for our investigation. Nucleophilicity are
known to correlate with basicity in the series of the related nucleophiles. Therefore, we can set our
hydrazines in order to their basicity: phenylhydrazine (pKa = 5.27), hydrazine hydrate (pKa = 6.50), and
methylhydrazine (pKa = 7.87).14
RESULTS AND DISCUSSION
2.1. Reactions of 3-(1-aminoethylidene)-5,6,7,8-tetrafluorobenzopyran-2,4-dione (1) with
phenylhydrazine.
It was found that coumarin (1) reacts with phenylhydrazine at room temperature to result in the formation
of 5,6,7,8-tetrafluoro-3-[1-(2-phenylhydrazino)ethylidene]benzopyran-2,4-dione (2), similarly to the non-
fluorinated analogues (Scheme 2). The way of reaction does not depend on type of solvent used.
Our attempts to convert benzopyrandione (2) into benzopyrano[4,3-c]pyrazolone under reaction
conditions of the non-fluorinated analogues (in refluxing toluene with a catalytic quantity of p-toluene
sulfonic acid) have led to coumarin (1), which are formed as a result of the hydrazine fragment N-N bond

HETEROCYCLES, Vol. 78, No. 2, 2009
349
cleavage (Scheme 2). Hydrazone derivatives can be undergone to such cleavage in the reactions with the
bases.15 The mass spectrum of compound (2) has the peak m/z 274 (23.23 %) corresponding to the
fragment [M-NH2Ph]. This fact confirms the N-N bond instability under the influence of high-temperature.
Nevertheless 6,7,8-trifluoro-5-hydroxy-3-methyl-1-phenylbenzopyrano[2,3-c]pyrazol-4(1H)-one (3) was
obtained from benzopyrandione (2) upon heating in acetic acid (Scheme 2). It is significant that the
transformations of the non-fluorinated analogues under the similar reaction conditions have resulted in
1-aryl-5-hydroxy-4-(2-hydroxybenzoyl)-3-methylpyrazols,9,10,12 which were undergone intramolecular
condensation by heating with POCl3 only to give benzopyrano[2,3-c]pyrazolones (Scheme 1).
Obviously compound (3) is generated by the attack of the phenyl substituent NH-group of
benzopyrandione (2) at the C(2) atom to form 4-(2,3,4,5-tetrafluoro-6-hydroxybenzoyl)-1,2-dihydro-5-
methyl-2-phenyl-3H-pyrazol-3-one intermediate (4). Easy cyclization of pyrazolone (4) into
benzopyranopyrazolone (3) could be explained by the presence of the fluorine atoms at the benzoyl
substituent. Pyrone ring formation is occurred via intramolecular substitution of the fluorine atom to
hydroxyl group of the pyrazole fragment. The non-fluorinated analogues can be converted into the
benzopyranopyrazolones due to H2O elimination by heating with dehydrating agents only.
PhMe, 110 oC,
p-TsOH
O
Ph
HN N
H
Me
F4
80%
NH2
Et2O,
(MeCN, Me2SO),
25 oC, 24 h
O
O
2, 35 - 93 %
AcOH,
100 oC,
72 h
O
O
H
OH
F3
O
O
Me
N
N
Me
75%
F4
Ph
NH2
O
PhMe,
110 oC,
72 h
1
38%
N
3
Ph
AcOH,
100 oC,
28 h
OH
O
Me
NH
F4
resinification
N
HCl (30% w.)/EtOH,
25 oC, 72 h
PhMe,
110 oC
O
Ph
4, 46 %
Scheme 2
Coumarin (1) reacted with phenylhydrazine in water-ethanol solution of hydrochloric acid at the room
temperature to result in pyrazolone (4) (Scheme 2). Attempt to convert pyrazolone (4) to compound (3) in
refluxing toluene led to resinification of the reaction mixture. However, this conversion was realized in
acetic acid (Scheme 2). According to our researches in the field of transformations of 3-acyl-4-

350
HETEROCYCLES, Vol. 78, No. 2, 2009
hydroxycoumarins with o-phenylenediamine,6 we proved the formation of the new heterocyclic systems
by heating in high-boiling solvents. Thus, coumarin (1) with phenylhydrazine formed
benzopyranopyrazolone (3) in refluxing toluene.
2.2. Reactions of 3-(1-aminoethylidene)-5,6,7,8-tetrafluorobenzopyran-2,4-dione (1) with
methylhydrazine.
The reaction of coumarin (1) with methylhydrazine was found to depend on the solvent even at room
temperature. Methylhydrazine reacted with coumarin (1) in diethyl ether or acetonitrile to give
5,6,7,8-tetrafluoro-3-[1-(2-methylhydrazino)ethylidene]benzopyran-2,4-dione (5) (Scheme 3).
O
Me
HN N
H
Me
F4
Et2O, (MeCN),
25 oC, 24 h
EtOH,
25 oC
O
O
5, 79 - 88 %
O
O
NH2
Me
H
OH
O
Me
N
N
Me
NH2
F4
PhMe, 110 oC, 72 h,
(EtOH, 25 oC, 72 h)
F3
O
N
O
1
Me
6, 50 - 65 %
OH
O
Me
F
Me
HN
Me2SO,
25 oC, 72 h
N
N
N
O
H
Me
F
7, 38 %
Scheme 3
However 6,7,8-trifluoro-5-hydroxy-1,3-dimethylbenzopyrano[2,3-c]pyrazol-4(1H)-one (6) was obtained
from the same reaction in ethanol at the room temperature. Benzopyrandione (5) was converted into
compound (6) by the stirring in ethanol.
The reaction of coumarin (1) with methylhydrazine in boiling toluene resulted in benzopyranopyrazolone
(6) similarly to transformations with phenylhydrazine.
Coumarin (1) with methylhydrazine in DMSO at the room temperature gave 6,8-difluoro-5-hydroxy-1,3-
dimethyl-7-(2-methylhydrazino)benzopyrano[2,3-c]pyrazol-4(1H)-one (7) (Scheme 3). According to our
research on the transformations of 3-acetyl- and 3-acetimidoyl-5,6,7,8-tetrafluoro-4-hydroxycoumarins
with monoamines, we have shown that the condensation at the acyl fragment of coumarins was
accompanied by the substitution of the fluorine atom at the C(7) position in high-polar DMSO.
It is significant that the peak at δ 3.18 ppm corresponding to signal of Me-NHNH-group methyl protons
in 1H NMR spectrum of compound (7) is coupled in triplet with the coupling constant 6JH-F = 2.5 Hz due

HETEROCYCLES, Vol. 78, No. 2, 2009
351
to the interaction with fluorine atoms. An alternative structure attached Me(NH2)N-group at C-7 atom
must be assumed for compound (7), however the IR spectrum excepts such structure because it does not
contain doublet absorption bands corresponding to asymmetrical and symmetrical vibrations of NH2-
group.
The comparative analysis of the mass spectra of the 3-(1-methyl(phenyl)hydrazinoethylidene)-substituted
benzopyrandiones (2,5) was evidence of this fact also More nucleophilic methylhydrazine showed high
ability to the cyclization.. The mass spectrum of the methyl-substituted benzopyrandione (5) has peak m/z
284 (25.57%), corresponding to [M-HF] fragment, while the similar peak in mass spectrum of the phenyl-
substituted benzopyrandione (2) has lesser intensity - m/z 346 (1.57%) [M-HF], m/z 345 (7.33%) [M-H-
HF].
We can propose the general scheme of the benzopyranopyrazolones (3,6,7) formation in the reactions of
coumarin (1) and the substituted hydrazines based on the experimental data (Scheme 4).
H
N
O
O
HN
O
Me
NH
R
Me
F3
F3
N
R'
O
R'
O
OH
R
OH
O
Me
OH
O
O
OH
F3
O
Me
Me
N
F
NH
F3
N
- HF
N
N
N
R'
R'
O
R'
HO
R
R
R
F
R = Me, Ph; R' = F, NHNHMe
Scheme 4
Change of the recyclization way on the stage of pyrazole intermediates conversion is the distinguishing
feature of reactions of the fluorinated coumarin (1) with the substituted hydrazines in contrast to the non-
fluorinated analogues. In the case of coumarin (1), the formation of the new heterocycle is a result of the
intramolecular nucleophilic substitution of the fluorine atom accompanied by HF elimination. It must be
noted that transformations of the fluorinated coumarin (1) are more selective in contrast to the non-
fluorinated analogues. The preferable attack of the NH-group at the C(2) atom in the fluorinated 3-(1-
methyl(phenyl)hydrazinoethylidene)-substituted benzopyrandiones (2,5) is determined by easiness and
irreversibility of the recyclization due to the substitution of the fluorine atom.
2.3. Reactions of 3-(1-aminoethylidene)-5,6,7,8-tetrafluorobenzopyran-2,4-dione (1) with hydrazine
hydrate.
The reactions of coumarin (1) with hydrazine hydrate were found to pass unequally under the similar
reaction conditions to the transformations with methyl- and phenylhydrazines. Thus, the reaction of

352
HETEROCYCLES, Vol. 78, No. 2, 2009
coumarin (1) with excess of hydrazine hydrate in diethyl ether at the room temperature gave 5,6,8-
trifluoro-7-hydrazino-3-(1-hydrazinoethylidene)benzopyran-2,4-dione (8) (Scheme 5).
Then we made an attempt to obtain benzopyranopyrazolone system by heating in high-boiling solvents
similarly to the reactions with methyl- and phenylhydrazines. 5,6,7,8-Tetrafluoro-3-(1-
hydrazinoethylidene)benzopyran-2,4-dione (9) was formed from coumarin (1) and hydrazine hydrate in
refluxing benzene (Scheme 5). Refluxing of coumarin (1) and hydrazine hydrate in toluene resulted in the
inseparable mixture of products. The conversion of coumarin (1) was not achieved by heating in acetic
acid.
It was shown that benzopyrandione (9) easily reacted with some electrophilic agents. Thus, compound (9)
converted rapidly into 5,6,7,8-tetrafluoro-3-{1-[2-(1-methylethylidene)hydrazino]ethylidene}benzopyran-
2,4-dione (10) by standing in acetone at room temperature. Product (10) was obtained by refluxing of
coumarin (1) with hydrazine hydrate in acetone as well (Scheme 5). These transformations are acid- or
base catalytic reactions usually. Compound (9) probably serves as a base catalyst in this case.
NH2
O
HN
Me
Et2O, 25 oC,
24 h
F3
O
H2N
N
H
O
O
8, 68 %
NH2
O
O
NH2
Me N2H4 aq
HN
Me
F4
F4
PhH, 80 oC,
72 h
O
O
O
Me
1
Me
9, 48 %
N
O
HN
Me
F4
Me2CO, 25 oC
Me2CO, 56 oC,
24 h
O
O
10, 45 - 76 %
Scheme 5
CONCLUSION
So, we have found that the transformations of coumarin (1) with hydrazines depended on hydrazine
nucleophilicity and the solvent nature. The initial act in these reactions is the transamination of coumarin
(1) at aminoethylidene fragment by hydrazine NH2-group. In the case of more nucleophilic
methylhydrazine and hydrazine the transamination can be accompanied by the substitution of fluorine
atom at the atom C-7. Further the intramolecular attack of the RNH-group at the C-2 atom can lead to
opening α-pyrone ring and the intermediate formation of pyrazole derivative such as (4). The latter is

HETEROCYCLES, Vol. 78, No. 2, 2009
353
turned readily into benzopyrano[2,3-c]pyrazolone in a result of the intramolecular substitution of fluorine
atom by hydroxyl group. The derivative of more nucleophilic methylhydrazine reveals the most tendency
to recyclization. Thus, we can mark more regioselectivity of the reactions of coumarin (1) with
hydrazines as compared with the similar conversions of non-fluorinated analogs. We can offer also to use
the reactions of 3-(1-aminoethylidene)-5,6,7,8-tetrafluorobenzopyran-2,4-dione (1) with substituted
hydrazines as a method for annelations of pyrazole ring to the benzopyranone ring.
EXPERIMENTAL
The melting points were measured on «Stuart SMP3» in open capillaries and are uncorrected. The
infrared spectra were recorded on Perkin Elmer Spectrum One FT-IR spectrometer at 4000 – 400 cm-1 in
the nujol mulls. The 1H and 19F NMR spectra were measured on Bruker DRX-400 spectrometer (1H, 400,
relative to Me4Si, 19F, 376 MHz relative to С6F6). The mass spectra were recorded on «Shimadzu LCMS-
2010» (APC-ionization, mobile phase – acetonitrile). The microanalyses were carried out on Perkin-
Elmer PE 2400 series II elemental analyzer.
The starting coumarin (1) was obtained by a known method.16
4.1. The general procedure of the reactions of the coumarin (1) with hydrazines.
Method A. Hydrazine (0.5 mmol) was added to a solution of the coumarin (1) (0.5 mmol) in suitable
solvent (30 mL). The reaction mixture was stirred at rt. The reaction control was monitored by TLC
method. The solvent was removed and the residue was recrystallized from the corresponding solvent.
Method B. Hydrazine (0.5 mmol) was added to a solution of the coumarin (1) (0.5 mmol) in suitable
solvent (60 mL). The reaction mixture was refluxed. The reaction control was monitored by TLC method.
The solvent was removed and the residue was recrystallized from the corresponding solvent.
4.2.1. 3-(1-Aminoethylidene)-5,6,7,8-tetrafluorobenzopyran-2,4-dione (1).
Compound (1) was obtained from benzopyrandione (2) in refluxing toluene in the presence of p-TsOH as
catalyst for 72 h according to method B. Yield after recrystallization from hexane, 80 % (110 mg); mp
165 oC.16
4.2.2. 5,6,7,8-Tetrafluoro-3-[1-(2-phenylhydrazino)ethylidene]benzopyran-2,4-dione (2).
Compound (2) was obtained from coumarin (1) and phenylhydrazine according to method A. Yield after
recrystallization from Et2O, 93 % (170 mg) in Et2O, 62 % (114 mg) in MeCN, 35 % (64 mg) in DMSO;
mp 221-224 oC. 1Н NMR [(CD3)2CO] δ: 2.85 (3Н, s, СН3); 3.77 (2Н, s, 2 NH); 7.18 (5Н, d.m, С6Н5). 19F
NMR [(CD3)2CO] δ: -2.54, 2.55, 12.04, 18.96 (all m, in 1F). MS, m/z (rel. int): 366 [M] (14.06); 365 [M-
H] (70.80); 274 [M-C6H5NH2] (23.23); 233 [C9HF4O3] (11.41); 216 [C9F4O2] (51.38). IR, ν: 3312 (NH);
1690 (ОС=О); 1650 (C=O); 1602, 1523 (NH, C=C); 1015 (CF) cm-1. Anal. Calcd for С17Н10F4N2O3: C,
55.75; H, 2.75; F, 20.75; N, 7.65. Found: C, 55.64; H, 2.54; F, 20.87; N, 7.62.

354
HETEROCYCLES, Vol. 78, No. 2, 2009
4.2.3. 6,7,8-Trifluoro-5-hydroxy-3-methyl-1-phenylbenzopyrano[2,3-c]pyrazol-4(1H)-one (3).
Compound (3) was obtained from coumarin (1) and phenylhydrazine in refluxing toluene for 72 h
according to method B. Yield after recrystallization from ethanol, 75 % (130 mg). Compound (3) was
o
obtained from benzopyrandione (2) by heating in acetic acid at 100 C for 72 h according to method B.
Yield after recrystallization from EtOH, 42 % (73 mg). Compound (3) was obtained from pyrazolone (4)
o
by heating in acetic acid at 100 C for 28 h according to method B. Yield after recrystallization from
EtOH, 38 % (23 mg); mp 215 oC. 1Н NMR [DMSO-d6] δ: 2.58 (3Н, s, СН3); 7.49 – 7.87 (5Н, m, С6Н5);
12.80 (1H, s, OH). 19F NMR [DMSO-d6] δ: -5.36 (1F, d.d, 4J = 4.9, 3J = 21.9 Hz); -1.93 (1F, d.d, 4J = 4.9,
3
3J = 21.9 Hz); 13.79 (1F, t.m, J = 21.9 Hz). IR, ν: 3100 (OH); 1671 (С=О); 1623, 1596, 1541 (C=C);
1020 (CF) cm-1. Anal. Calcd for С17Н9F3N2O3: C, 58.97; H, 2.62; F, 16.46; N, 8.09. Found: C, 58.50; H,
2.63; F, 16.55; N, 8.03.
4.2.4. 4-(2,3,4,5-Tetrafluoro-6-hydroxybenzoyl)-1,2-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one (4).
Compound (4) was obtained from coumarin (1) and phenylhydrazine by stirring in EtOH solution of
hydrochloric acid (30 % w.) according to method A. Yield after recrystallization from EtOH, 46 % (84
mg); mp 205 oC. 1Н NMR [DMSO-d6] δ: 2.31 (3Н, s, СН3); 6.43 (1Н, s, NH); 7.22 – 7.39 (5Н, m, С6Н5);
10.95 (1H, s, OH). 19F NMR [DMSO-d6] δ: -8.14, 1.94, 6.49, 21.80 (all m, in 1F). IR, ν: 3062 (NH); 3020
(ОН); 1691, 1655 (С=О); 1596, 1520 (C=C); 992 (CF) cm-1. Anal. Calcd for С17Н10F4N2O3: C, 55.75; H,
2.75; F, 20.75; N, 7.65. Found: C, 55.33; H, 2.82; F, 20.92; N, 7.49.
4.2.5. 5,6,7,8-Tetrafluoro-3-[1-(2-methylhydrazino)ethylidene]benzopyran-2,4-dione (5).
Compound (5) was obtained from coumarin (1) and methylhydrazine according to method A. Yield after
recrystallization from Et2O, 88 % (134 mg) in Et2O, 79 % (120 mg) in MeCN; mp 164-166 oC. 1Н NMR
[(CD3)2CO] δ: 2.77, 2.87 (6Н, both s, 2 СН3); 5.64, 14.79 (2Н, both s, 2 NH). 19F NMR [(CD3)2CO] δ: -
2.94, 2.33, 11.27, 18.31 (all m, in 1F). IR, ν: 3306 (NH); 1718 (OC=O); 1648 (C=O); 1591, 1525 (NH,
C=C); 1032 (CF) cm-1. MS, m/z (rel. int): 304 [M] (14.56); 303 [M-H] (100); 284 [M-HF] (25.57). Anal.
Calcd for С12Н8F4N2O3.: C, 47.38; H, 2.65; F, 24.98; N, 9.21. Found: C, 47.12; H, 2.45; F, 24.67; N, 9.11.
4.2.6. 6,7,8-Trifluoro-5-hydroxy-1,3-dimethylbenzopyrano[2,3-c]pyrazol-4(1H)-one (6).
Compound (6) was obtained from coumarin (1) and methylhydrazine in refluxing toluene for 72 h
according to method B. Yield after recrystallization from hexane, 50 % (71 mg). Compound (6) was
obtained from benzopyrandione (5) by stirring in EtOH for 24 h according to method A. Yield after
o
1
recrystallization from hexane, 65 % (46 mg). mp 137-139 C. Н NMR [DMSO-d6] δ: 2.47 (3Н, s, C-
СН3), 3.85 (3Н, s, N-СН3); 12.99 (1Н, s, ОН). 19F NMR [DMSO-d6] δ: -5.58 (1F, d.d, 4J = 5.3, 3J = 22.2
Hz); -2,46 (1F, d.d, 4J = 5.3, 3J = 22.2 Hz); 13,38 (1F, t.m, 3J = 22.2 Hz). IR, ν: 3060 (OH); 1641 (C=O);
1581, 1517 (C=C); 1001 (CF) cm-1. Anal. Calcd for С12Н7F3N2O3: C, 50.72; H, 2.48; F, 20.05; N, 9.86.
Found: C, 50.47; H, 2.30; F, 19.75; N, 9.71.

HETEROCYCLES, Vol. 78, No. 2, 2009
355
4.2.7. 6,8-Difluoro-5-hydroxy-1,3-dimethyl-7-(2-methylhydrazino)benzopyrano[2,3-c]pyrazol-4(1H)-one
(7).
Compound (7) was obtained from coumarin (1) and methylhydrazine by stirring in DMSO for 72 h
o
1
according to method A. Yield after recrystallization from EtOH, 38 % (59 mg); mp 190 C. Н NMR
[DMSO-d6] δ: 2.41 (3Н, s, C-СН3), 3.79 (3Н, s, N-СН3); 3.18 (3Н, t, N-СН3, 6JH-F = 2.5 Hz); 4.89 (2Н, s,
2 NH); 12.54 (1Н, s, ОН). 19F NMR [DMSO-d6] δ: 7.27 (1F, dq, 4JF-F = 1.2 Hz, 6JF-H = 2.5 Hz), 10.32 (1F,
4
6
dq, JF-F = 1.2 Hz, JF-H = 2.5 Hz). IR, ν: 3354 (NH); 3050 (OH); 1660 (C=O); 1626, 1584 (NH, C=C);
1000 (CF) cm-1. Anal. Calcd for С13Н12F2N4O3: C, 50.33; H, 3.90; F, 12.25; N, 18.06. Found: C, 50.04; H,
3.78; F, 12.01; N, 17.97.
4.2.8. 5,6,8-Trifluoro-7-hydrazino-3-(1-hydrazinoethylidene)benzopyran-2,4-dione (8).
Compound (8) was obtained from coumarin (1) and hydrazine hydrate by stirring in Et2O for 24 h
according to method A. Yield after recrystallization from Et2O, 68 % (103 mg); mp 226-227 oC. 1Н NMR
[DMSO-d6] δ: 2.57 (3Н, s, СН3); 4.60 (2Н, s, NH2); 6.05 (2H, s, NH2); 7.50 (1H, s, NH); 12.20 (1Н, s,
19
3
4
3
NH). F NMR [DMSO-d6] δ: 1.00 (1F, d.m, J = 19.9 Hz); 4.01(1F, m), 13.57 (1F, d.d, J = 10.6, J =
19.9 Hz). IR, ν: 3346 (NH); 1719 (OC=O); 1651 (C=O); 1574, 1505 (NH, C=C); 997 (CF) cm-1. Anal.
Calcd for С11Н9F3N4O3: C, 43.72; H, 3.00; F, 18.86; N, 18.54. Found: C, 43.80; H, 2.92; F, 19.01; N,
18.24.
4.2.9. 5,6,7,8-Tetrafluoro-3-(1-hydrazinoethylidene)benzopyran-2,4-dione (9).
Compound (9) was obtained from coumarin (1) and hydrazine hydrate in refluxing benzene during 72 h
according to method B. Yield after recrystallization from EtOH-water solution, 48 % (70 mg); mp 169 oC.
1Н NMR [DMSO-d6] δ: 2.58 (3Н, s, СН3); 6.24 (2Н, s, NH2); 14.73 (1Н, s, NH). 19F NMR DMSO-d6] δ:
-3.12, 1.73, 10.56, 16.46 (all m, in 1F). IR, ν: 3328 (NH); 1709 (OC=O); 1649 (C=O); 1576, 1525 (NH,
C=C); 996 (CF) cm-1. Anal. Calcd for С11Н6F4N2O3: C, 45.53; H, 2.08; F, 26.19; N, 9.65. Found: C,
45.72; H, 2.22; F, 25.94; N, 9.82.
4.2.10. 5,6,7,8-Tetrafluoro-3-{1-[2-(1-methylethylidene)hydrazino]ethylidene}benzopyran-2,4-dione (10).
Compound (10) was obtained from benzopyrandione (9) by stirring in acetone for 2 h according to
method A. Yield after recrystallization from EtOH, 76 % (125 mg). Compound (10) was obtained from
coumarin (1) and hydrazine hydrate by refluxing in acetone for 24 h according to method B. Yield after
recrystallization from EtOH, 45 % (74 mg); mp 192-195 oC. 1Н NMR [DMSO-d6] δ: 2.16, 2.18, 2.82 (9Н,
19
all s, 3 СН3); 15.72 (1Н, s, NH). F NMR [DMSO-d6]: -2.36, 2.26, 12.60, 17.74 (all m, in 1F). IR, ν:
3371, 3349 (NH); 1725 (OC=O); 1650 (C=O); 1589, 1579, 1525 (NH, C=C); 1001 (CF) cm-1. MS, m/z
(rel. int): 329 [М-Н] (100); 310 [M-HF], (14.67). Anal. Calcd for С14Н10F4N2O3: C, 50.92; H, 3.05; F,
23.01; N, 8.48. Found: C, 50.96; H, 2.73; F, 23.25; N, 8.68.

356
HETEROCYCLES, Vol. 78, No. 2, 2009
ACKNOWLEDGEMENTS
This work was supported by the State Programme for supporting leading scientific schools of Russian
Federation (grant 3758.2008.3).
REFERENCES
1. I. Kostova, Curr. Med. Chem.-Anti-Cancer Agents, 2005, 5, 29.
2. M. D. Mashkovski, ‘Drugs’, Novaya Volna, Moscow, 2002.
3. V. I. Saloutin, Z. E. Skryabina, I. T. Bazil', and S. P. Kisil', J. Fluor. Chem., 1999, 94, 83.
4. K. V. Shcherbakov, Ya. V. Burgart, V. I. Saloutin, and O. N. Chupakhin, Heterocycles, 2006, 69, 319.
5. I. T. Bazyl’, S. P. Kisil’, A. E. Sharapko, Ya. V. Burgart, V. I. Saloutin, and O. N. Chupakhin, Russ. J.
Org. Chem., 1998, 34, 363.
6. Ya. V. Burgart, K. V. Shcherbakov, V. I. Saloutin, and O. N. Chupakhin, Russ. Chem. Bull., 2004, 53,
1237.
7. N. S. Vul’fson and R. B. Zhurin, Zhur. Obshch. Khim., 1961, 31, 3381 (Russ. Transl.).
8. А. Mustafa, O. H. Hishmat, A. A. Nawar, and Kh. M. A. Khalil, Justus Liebigs Ann. Chem., 1965, 684,
194.
9. B. Chantegrel, A.-I. Nadi, and S. Gelin, Synthesis, 1983, 3, 214.
10. B. Chantegrel, A.-I. Nadi, and S. Gelin, Tetrahedron Lett., 1983, 24, 381.
11. V. Colotta, L. Cecchi, G. Filacchioni, F. Melani, G. Palazzino, C. Martini, G. Giannaccini, and A.
Lucacchini, J. Med. Chem., 1988, 31, 1.
12. W. Stadlbauer and G. Hojas, J. Heterocycl. Chem., 2004, 41, 681.
13. A. Manvar, P. Bochiya, V. Virsodia, R. Khunt, and A. Shah, J. Mol. Cat. A: Chemical, 2007, 275, 148.
14. J. March, ‘Advanced Organic Chemistry. Reactions, Mechanisms and Structure’, A Wiley-
Interscience, John Wiley & Sons Inc., New York, 1985.
15. Yu. P. Kitaev, B. N. Buzykin, ‘Hydrazones’, Nauka, Moscow, 1970, 277.
16. Ya. V. Burgart, V. I. Saloutin, and O. N. Chupakhin, ‘Fluorinated Tricarbonyl Compounds’, UD RAS,
Ekaterinburg, 2002 (Russ. Transl.).