Features of reactions of polyfluorinated ethyl 4-oxo-2-pnenyl-4H-chromene- 3-carboxylates with N-nucleophiles

Article abstract of DOI:10.1134/S1070428013050151

Ethyl 5,6,7,8-tetrafluoro-4-oxo-2-phenyl-4H-chromene-3-carboxylate in reactions with primary amines is characterized by a chromone-coumarin rearrangement affording 3-[amino(phenyl)methylene]-6,7,8-trifluoro-2H-chromene- 2,4(3H)-diones, and ethyl 4-oxo-2-phenyl-5,6,7,8-tetrafluoro-4H-chromene-3- carboxylate characteristically adds the amine at the C² site of the flavone furnishing 3-amino-3-phenyl-2-(2,3,4,5-tetrafluoro-6-hydroxybenzoyl) acrylates which depending on the substituent at the amino group are capable of intramolecular cyclization into 3-[(alkylamino)(phenyl)methylene]-5,6,7,8- tetrafluoro-2H-chromene-2,4(3H)-dione or in the case of benzylamine substituent, into ethyl 1-benzyl-5-hydroxy-4-oxo-2-phenyl-6,7,8-trifluoro-1,4- dihydroquinoline-3-carboxylate. The main process in the reaction of tri- and tetrafluoroflavones with secondary amine (1-methylpiperazine) is the nucleophilic substitution at the C⁷ of flavone. In the reaction with 1,2-phenylenediamine 3-[(2-aminophenyl)amino]-3-phenyl-2-(2,3,4,5-tetrafluoro-6- hydroxybenzoyl)acrylate was obtained from tetrafluoroflavone and 1H-benzimidazol-2-yl(3,4,5-trifluoro-2-hydroxyphenyl)methanone, from trifluoroflavone.

Full text of DOI:10.1134/S1070428013050151

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 5, pp. 719−729. © Pleiades Publishing, Ltd., 2013.
Original English Text © K.V. Shcherbakov, Ya.V. Burgart, V. I. Saloutin, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 5, pp. 736−746.
Dedicated to Full Member of the Russian Academy of Sciences
I.P. Beletskaya on occasion of her jubilee
Features of Reactions of Polyfluorinated
Ethyl 4-Oxo-2-pnenyl-4Н-chromene-3-carboxylates
with N-Nucleophiles
K. V. Shcherbakov, Ya. V. Burgart, and V. I. Saloutin
Postovsky Institute o Organic Chemistry, Ural Division, Russian Academy of Sciences,
Yekaterinburg, 620990 Russia
e-mail: specialk@mail.ru, saloutin@ios.uran.ru
Received October 15, 2012
Abstract—Ethyl 5,6,7,8-tetrafluoro-4-oxo-2-phenyl-4H-chromene-3-carboxylate in reactions with primary
amines is characterized by a chromone-coumarin rearrangement affording 3-[amino(phenyl)methylene]-
6,7,8-trifluoro-2Н-chromene-2,4(3Н)-diones, and ethyl 4-oxo-2-phenyl-5,6,7,8-tetrafluoro-4Н-chromene-3-
carboxylate characteristically adds the amine at the С2 site of the flavone furnishing 3-amino-3-phenyl-2-(2,3,4,5-
tetrafluoro-6-hydroxybenzoyl)acrylates which depending on the substituent at the amino group are capable of
intramolecular cyclization into 3-[(alkylamino)(phenyl)methylene]-5,6,7,8-tetrafluoro-2Н-chromene-2,4(3Н)-
dione or in the case of benzylamine substituent, into ethyl 1-benzyl-5-hydroxy-4-oxo-2-phenyl-6,7,8-trifluoro-
1,4-dihydroquinoline-3-carboxylate. The main process in the reaction of tri- and tetrafluoroflavones with
secondary amine (1-methylpiperazine) is the nucleophilic substitution at the С7 of flavone. In the reaction with
1,2-phenylenediamine 3-[(2-aminophenyl)amino]-3-phenyl-2-(2,3,4,5-tetrafluoro-6-hydroxybenzoyl)acrylate
was obtained from tetrafluoroflavone and 1Н-benzimidazol-2-yl(3,4,5-trifluoro-2-hydroxyphenyl)methanone,
from trifluoroflavone.
DOI: 10.1134/S1070428013050151
Flavones belong to an important class of heterocycles
of the chromen-4-ones series that besides the versatile
biological activity are attractive as objects for chemical
modification [1, 2]. Both to flavones and 2-unsubstituted
chromones and their methyl analogs are characteristic
the reactions of pyrone ring opening under the action of
amines leading to 1,3-aminoenones. The presence of an
alkoxycarbonyl substituent in the position 3 of chromen-
4-one provides a possibility of subsequent cyclization of
1,3-aminoenones into 3-substituted 4-hydroxycoumarins
[3, 4]. The most versatile reactivity in reactions with
nucleophiles was exhibited by ethyl 2-methyl-4-oxo-
5,6,7,8-tetrafluoro-4Н-chromene-3-carboxylate. It
reacted with primary amines with the opening of the
heterocycle giving ethyl 3-amino-2-(2-hydroxy-3,4,5,6-
tetrafluorobenzoyl)but-2-enoates and (or) their cyclic
derivatives, N-substituted 4-hydroxy-5,6,7,8-tetrafluoro-
3-ethanimidoylcoumarins [4, 5]. Its reactions with
secondary amines occur with the retention of the pyrone
ring and the formation of 7-substituted chromones [4],
at the use of S-nucleophiles three fluorine atoms at
С5, С7, and С8 are substituted [6]. At the action of the
α-dinucleophiles the pyrone ring undergoes the opening
leading to the formation of substituted azoles which may
suffer cyclization into azolocoumarins [4].
The goal of this work was the study of the features
of the conversions of polyfluorinated ethyl 4-oxo-2-
phenyl-4Н-chromene-3-carboxylates under the action of
N-mononucleophiles.
Ethyl 6,7,8-tri- and 6,7,8-tetrafluoroflavone-3-
carboxylates IIIа, IIIb were obtained by one-pot
synthesis via the acylation of benzoylacetic ester (Iа)
with tetra- and pentafluorobenzoyl chlorides IIа, IIb in
the presence of magnesium ethylate (Scheme 1) along
procedure [7, 8]. The formation of flavones IIIа, IIIb
719

SHCHERBAKOV et al.
720
Scheme 1.
R2
Cl
O
R2
R2
F3
O
O
F3
F3
CO2Et
R1
O
R1
IIа, Ib
CO2Et
Iа, Ib
(EtO)2Mg, PhMe
HO
O
CO2Et
R1
IIIа, IIIb, VII
R1 = Ph (Ia); R2 = H (IIa, IIIa), F (IIb, IIIb); R1 = Me (Ib), R2 = H (VII).
is due to the ease and irreversibility of the cyclization
of the formed in situ and nonisolable 3-hydroxy-3-
phenyl-2-(polyfluorobenzoyl)acrylates resulting from
the intramolecular nucleophilic substitution reaction of
the ortho-fluorine atom in the polyfluorophenyl ring for
a hydroxy group [7–10].
with ammonium hydroxide, benzyl-, hexyl, and cyclohex-
ylamines with the formation exclusively of the products
of the opening of the pyrone ring, 3-amino-2-(2-hydroxy-
3,4,5,6-tetrafluorobenzoyl)-3-phenylacrylates Vа, Vc–Ve
(Scheme 3). However from the reaction products of
flavone IIIb with hexyl- and cyclohexylamines alongside
esters Vd, Ve after stirring for 24 h in ethanol we isolated
coumarins VId, VIe as minor components (10–15%). A
selective synthesis of these coumarins was performed
by heating. The one-pot preparation of coumarin VIа
from tetrafluoroflavone IIIb is only possible at carrying
out the reaction with ammonium chloride in anhydrous
ethanol in the presence of sodium hydrogen carbonate
at heating. We failed to obtain [(benzylamino)(phenyl)
methylidene]-substituted coumarin VIc from flavone IIIb
and benzylamine.
The ethyl 2-methyl-4-oxo-5,6,7,8-tetrafluoro-4Н-
chromene-3-carboxylate in reactions with primary amines
(methylamine, benzylamine) and ammonium hydroxide
in mild conditions characteristically suffered an open-
ing of the pyrone ring to give a mixture of 3-amino-2-
(2-hydroxy-3,4,5,6-tetrafluorobenzoyl)but-2-enoates
and the products of their intramolecular condensation,
3-(1-aminoethylidene)-5,6,7,8-tetrafluoro-2Н-chromene-
2,4(3Н)-diones [4, 5].
We found that the reactions of trifluoro-substituted
flavone IIIа with the same amines at room temperature
did not stop at the stage of the pyrone ring opening and
the corresponding enamioesters formation, but results in
the cyclization products of the latter, 3-[amino(phenyl)
methylene]-6,7,8-trifluoro-2Н-chromene-2,4(3Н)-diones
IVа–IVc due to the chromone-coumarin rearrangement
(Scheme 2).
At vigorous stirring at room temperature of a mix-
ture of flavone IIIb even with equimolar amount of
methylamine sulfate in ethanol in the course of 24 h we
obtained ethyl 2-[2-hydroxy-4-(methylamino)-3,5,6-
trifluorobenzoyl]-3-(methylamino)-3-phenylacrylate
(Vb), formed as a result of two parallel reactions: the
nucleophilic addition of the amine to the atom С2 and
the nucleophilic substitution of a fluorine atom at the
atom С7 of flavone (Scheme 3). The reaction in ethanol
at heating carried out for 72 h led to the formation of a
Unlike trifluoro-containing analog IIIa the
tetrafluoroflavone IIIb under similar conditions reacted
Scheme 2.
NHR2
R1
H
O
O
H
O
OH
CO2Et
R1
CO2Et
R2NH2 (NH4OH)
F3
R1
F3
F3
EtOH (MeCN),
24 h, 25oC
O
O
NHR2
H
O
IVа_IVc, VIIIа, VIIIb
IIIа, VII
R1 = Ph (IIIa, IVа–IVc); R2 = H (IVa), Me (IVb), PhCH2 (IVc); R1 = Me (VII, VIIIа, VIIIb), R2 = H (VIIIa), Me (VIIIb).
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FEATURES OF REACTIONS OF POLYFLUORINATED ETHYL 4-OXO-2-PNENYL-4Н-...
721
Scheme 3.
EtOH
(MeCN),
25oC, 24 h
OH
F3
O
CO2Et
Ph
CO2Et
iii, v
F4
Ph
R = CH2Ph
N
OH
O
NHR
Vа, Vc_Ve
NH2R
(NH4Cl)
Ph
IX
iii, iv
O
NHR
Ph
i, ii
F4
O
CO2Et
Ph
O
O
VIа, VId, VIe
F4
MeHN
EtOH,
O
CO2Et
25oC, 24 h
F3
Intractable mixture
IIIb
Ph
NHMe
NHMe
Ph
145_150oC
OH
O
Vb
O
O
NHMe
Ph
(MeNH2)2 . H2SO4,
NaHCO3
1 mol
2 mol
+
F4
F3
EtOH,
MeHN
O
VIb
O
O
X
O
50oC, 72 h
R = H (Va, VIa), PhCH2 (Vc), C6H13 (Vd, VId), cyclo-C6H11 (Ve, VIe); i: NH4Cl–anhydr. EtOH, NaHCO3, 50°C, 24 h;
ii: NH2R–EtOH, 50°C, 24 h; iii: (AcO)2Ni, EtOH, 25°C, 24 h; iv: 120–125°C, 1 h; v: 175–180°C, 1 h.
mixture of coumarins VIb, X in approximately equal
amounts. The use under these conditions of excess of the
methylamine salt made it possible to obtain as a single
reaction product 7-(methylamino)-3-[(methylamino)
(phenyl)methylidene]-5,6,8-trifluoro-2Н-chromene-
2,4(3Н)-dione (X).
three tautomeric forms (Scheme 4).
However in the 1Н and 19F NMR spectra of compounds
Vа–Ve in (CD3)2SO a set of signals of a single tautomeric
form is observed. The presence in the downfield part of
1Н NMR spectra of two or three proton signals from
the protons of hydroxy and amino groups alongside the
absence of the methine proton signal allows the exclu-
sion of the keto-imine form. It is not possible to choose
between the remaining tautomeric forms due to the scanty
information contained in the spectral data. However the
literature data suggest the preferred existence of the
enamino-ketone form in similar systems [4, 5].
The attempts to bring into the reaction with flavones
IIIa, IIIb the aromatic amines (aniline and p-anisidine)
were unsuccessful, even after long boiling in ethanol or
acetonitrile only the initial heterocycles were isolated.
The capability of aliphatic amines in contrast to aromatic
amines to react with flavones IIIa, IIIb is due to the
higher nucleophilicity of the former which correlates
with the basicity.
The preferred formation of 3-amino-2-(2-hydroxy-
3,4,5,6-tetrafluorobenzoyl)-3-phenylacrylates Vа–Ve
in the reactions of tetrafluoroflavone IIIb with pri-
mary amine as compared with the transformations of
trifluoroflavone IIIa leading under similar conditions to
3-Amino-2-(2-hydroxy-3,4,5,6-tetrafluorobenzoyl)-
3-phenylacrylates Vа–Ve may be liable to keto-enol and
imino-enamine tautomerism, therefore they may exist in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013

SHCHERBAKOV et al.
722
Scheme 4.
R1 = F, R2 = H (Va), CH2Ph (Vc), Hex (Vd), cyclo-Hex (Ve); R1 = R2 = NHMe (Vb).
the products of further cyclization, coumarins IVа–IVc,
is apparently caused by the higher acidity of the hydroxy
group in the intermediate enaminoesters Vа–Ve due to
the combined effect of the four fluorine atoms. Owing
to the increased acidity of the hydroxy group in the
tetrafluorophenyl substituent the esters Vа–Ve may exist
in the form of internal salts whose cyclization requires
more severe conditions.
tion [4, 5].
The heterocyclic compounds IVа–IVc, VIа, VIb,
VId, VIe, VIIIа, VIIIb, X are prototropic systems hav-
ing three functional groups in their composition (at atoms
С2, С4, and С9) capable of participation in keto-enol and
imino-enamine transformations, therefore four tautomeric
forms are expectable (Scheme 5).
According to XRD data compound VIа exists in
the crystal as a crystal solvate of 3-[amino-(phenyl)
methylidene]-5,6,7,8-tetrafluoro-2Н-chromene-2,4(3Н)-
dione with an ethanol molecule (Fig. 1). The carbonyl
atom O3 and the atom Н1А of the amino group are
linked by an intramolecular hydrogen bond [O3⋯Н1A
1.83(2), O3⋯N1 2.596(3) Å; N1Н1АO3 139(2), Н1АO3С4
101.2(7)°]. The chromene fragment of molecule VIa is
practically flat. The greatest deflection from the plane go-
ing through the carbon atoms of the fluoroaromatic ring
is the position of the lactone atom С2 (0.115 Å).
Evidently the fluorine substitution observed in the
reaction with the highly nucleophilic methylamine is also
due to the higher electrophilicity of the tetrafluorinated
benzene ring of flavone IIIb.
We studied for comparison the reactions of 2-methyl-
4-oxo-6,7,8-trifluoro-4Н-chromene-3-carboxylate (VII)
(Scheme 1) with ammonium hydroxide and methylamine.
It turned out that in these reaction the only separable
products were 3-(1-aminoethylidene)-6,7,8-trifluoro-2Н-
chromene-2,4(3Н)-diones VIIIа, VIIIb (Scheme 2). This
fact proves the effect of the fluorine atoms in the benzene
ring on the recyclization process: tetrafluoro-substituted
analog of chromone VII afforded under these conditions
a mixture of the products of ring opening and recycliza-
The unit cell of coumarin VIа crystal is formed of two
molecules placed antiparallel one over another. In the
molecular packing layers form by the АВАВ type owing to
shortened intermolecular contacts between atoms С8а⋯O2
Scheme 5.
H
R2
R1
O
4
N
5
6
9
3
Fn
2
H
R3
7
O
O
8
O
O
NR2
R1
IVа_IVc, VIIIа, VIIIb, X (n = 3),
VIа, VIb, VId, VIe (n = 4)
O
O
NR2
R1
Fn
Fn
O
R1
R3
R3
O
O
R2
N
H
Fn
R3
O
O
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013

FEATURES OF REACTIONS OF POLYFLUORINATED ETHYL 4-OXO-2-PNENYL-4Н-...
723
Fig. 2. Unit cell of the crystal of coumarin VIа according to
XRD data.
Fig. 1. Structure of 3-[amino(phenyl)methylidene]-5,6,7,8-
tetrafluoro-2Н-chromene-2,4(3Н)-dione (VIа) crystal solvate
according to XRD data.
of two contiguous molecules [3.174(3) Å] (Fig. 2).
Within the layer the molecules of coumarin VIа are
stabilized by ethanol molecules due to the formation of the
intermolecular hydrogen bonds. The distances O2⋯O4''
...
and N1 O4» are 2.745(2) and 2.801(3) Å (Fig. 3). The
hydrogen atoms involved in the formation of the hydro-
gen bonds are present materially on the line connecting
the atoms of the corresponding intermolecular contacts,
angles N1аHO4» and O2НO4» equal respectively 168(2)
and 174.9(1) deg.
The comparative analysis of IR spectra of compounds
IVа–IVc, VIа, VIb, VId, VIe, VIIIа, VIIIb, X did not
reveal essential difference in their structure. The char-
acteristic absorption bands for these heterocycles are
those of the lactone carbonyl group (1736–1705 cm–1), of
γ-carbonyl group involved in the intramolecular hydrogen
bond (1648–1604 cm–1), and of the stretching vibrations
of the amino group (3418–3029 cm–1).
Fig. 3. Stabilization of coumarin VIа molecules in a layer.
atoms. The chemical shifts of the atoms С2, С4, and
С9 decisive for the structure of coumarin IVа coincide
completely with the shifts of these atoms in the previ-
ously obtained and extensively characterized methyl
analogs, 3-(1-aminoethylidene)- and 3-[1-(methylamino)
ethylidene]-5,6,7,8-tetrafluoro-2Н-chromene-2,4(3Н)-
diones [12, 13].
The combined spectral data make it possible to con-
clude on the common property of the 4-hydroxypoly-
fluorocoumarins containing in the position С3 alkyl-
amino(phenyl)methylidene substituent consisting in the
capability to exist in the diketoenamine tautomeric form
2Н-chromene-2,4(3Н)-diones independent of the number
1
The Н, 19F NMR spectra of compounds IVа–IVc,
VIа, VIb, VId, VIe, VIIIа, VIIIb, X in (CD3)2SO are
characterized by a single set of signals indicating the pres-
ence of one tautomer. The lack of the signals of methine
proton attached to the atom С3 allows the exclusion from
the consideration of the diketoimine form. The downfield
shifts of the protons of hydroxy and amino groups of the
alternative tautomers confirm their involvement into the
intramolecular hydrogen bond.
The 13С NMR spectrum of compound IVа in
(CD3)2SO proved to be more informative. It indicated
the presence of lactone С2 (δ 159.87 ppm), ketone С4
(δ 176.75 ppm), and enamine С9 (δ 175.89 ppm) carbon
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013

SHCHERBAKOV et al.
724
Scheme 6.
R
O
F
F
CO2Et
Ph
O
F
IIIа, IIIb
R
F
O
NH
F
CO2Et
Ph
MeN
DMSO, 25oC
N
O
MeN
XIа, XIb
Fig. 4. Structure of ethyl 1-benzyl-5-hydroxy-4-oxo-2-phenyl-
6,7,8-trifluoro-1,4-dihydroquinoline-3-carboxylate (IX) accord-
R = H (a), F (b).
ing to XRD data.
hydroxy group involved in the condensation with the
ethoxycarbonyl substituent in the course of coumarin
formation is blocked due to the covalent bonding to the
metal, and the cyclization occurs by the alternative route
through the fluorine substitution.
of the fluorine atoms in the aromatic ring.
We attempted to bring 3-amino-2-(2-hydroxy-3,4,5,6-
tetrafluorobenzoyl)-3-phenylacrylates Vа–Vc into the
cyclization. In the enaminoesters obtained from 2-methyl-
4-oxo-5,6,7,8-tetrafluoro-4Н-chromene-3-carboxylate
and primary amines are characteristic of the thermal cy-
clization into 3-(1-aminoethylidene)-5,6,7,8-tetrafluoro-
2Н-chromene-2,4(3Н)-diones occurred at their melting
point [4]. The cyclization of esters Vа–Vc was carried
out at temperatures close to their melting points: 120–125
(Va), 145–150 (Vb), 175–180°С (Vc).
We tried to extend the discovered effect of the metal
complex catalysis to the cyclization of enaminesters
Vа, Vb, Vd, Ve. However in the presence of nickel(II)
acetate tetrahydrate we obtained only the corresponding
coumarins VIа, VIb, VId, VIe formed by intramolecular
condensation.
The structure of quinolone IX was proved by XRD
analysis (Fig. 4), according to which the compound
in the crystal existed as ethyl 1-benzyl-5-hydroxy-4-
oxo-2-phenyl-6,7,8-trifluoro-1,4-dihydroquinoline-3-
carboxylate. In the molecule of compound IX an intra-
molecular hydrogen bond is present between atoms O1
of the carbonyl group and Н2 of the hydroxy group of
quinoline [O1⋯Н2 1.59(2), O1⋯O2 2.500(1) Å; O2Н2O1
155(1), Н2O1С4 99.7(6)°]. The quinoline fragment of the
molecule IX is virtually planar, the strongest deflection
from the plane going through the carbon atoms of the
fluoroaromatic ring is observed for the atoms С2 and С3
(0.190 and 0.243 Å). Practically normal to this plane are
located the benzene rings at the atoms N1 and С2 of the
quinolone moiety.
Enaminoester Vа under the conditions of the thermal
cyclization afforded coumarin VIа (Scheme 3) due to the
intramolecular condensation involving hydroxy groups of
the benzoyl fragment and ethoxycarbonyl substituent with
ethanol elimination. Enaminoester Vb at 145–150°С fur-
nished an intractable mixture of substances. Enaminoester
Vc instead of giving the expected 3-[(benzylamino)
(phenyl)methylidene]-5,6,7,8-tetrafluoro-2Н-chromene-
2,4(3Н)-dione suddenly suffered the cyclization at
175–180°С into quinolone IX (Scheme 3) resulting from
the nucleophilic substitution of the ortho-fluorine atom
for an amino group with hydrogen fluoride liberation.
However the thermal cyclization of ester Vc into qui-
nolone IX is not selective and is accompanied with the
formation of intractable side products. The cyclization
can be performed better at milder conditions: in ethanol,
at room temperature, in the presence of nickel(II) acetate
tetrahydrate. Apparently ester Vc forms with the nickel
cation an intermediate complex compound where the
The conversion of enaminoester Vc (and only this
one) into quinolone IX is found for the first time. The
possibility of cyclization through intramolecular nucleo-
philic substitution exists only for tetrafluoro-substituted
esters possessing an ortho-fluorine. This cyclization
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FEATURES OF REACTIONS OF POLYFLUORINATED ETHYL 4-OXO-2-PNENYL-4Н-...
725
Scheme 7.
Thus we discovered the characteristic features of
the reactions of polyfluorinated flavones IIIа, IIIb
with amines. The reaction with primary amines of both
trifluoroflavone IIIа and trifluorochromone VII is char-
acterized by the chromone–coumarin rearrangement to
form in mild conditions coumarins IVа–IVc. Tetrafluo-
roflavone IIIb in similar conditions only adds amine to
the atom С2 resulting in the opening of the pyrone ring
and in the formation of enaminoesters Vа–Ve. The re-
duced ability of tetrafluoroflavone IIIb to reciclization in
coumarins VI is apparently due to the higher acidity of the
hydroxy group of the tetrafluorophenyl substituent in the
intermediate enaminoesters V. It was found for the first
time that enaminoesters V depending on the substituent
at the amino group are capable of intramolecular cycliza-
tion forming not only coumarins VI, but in the case of a
benzyl substituent, quinolone IX. However in the reaction
with the secondary amine (1-methylpiperazine) tri- and
tetrafluoroflavones IIIа, IIIb demonstrated the same
reactivity as previously studied tetrafluorochromones [4,
5]. This is evidently due to the steric factors impeding
the attack of the secondary amino group on the atom С2.
Methylamine, combining the high basicity with a small
size of the molecule is able to react simultaneously in
both directions.
occurs only in ester Vc containing two closely situated
bulky phenyl substituents. These groups probably due
to the steric hindrances take a position which favors an
increased nucleophilicity of the amino group involved
into the cyclization.
With the secondary amine (1-methylpiperazine)
flavones IIIа, IIIb react analogously to ethyl 2-methyl-
4-oxo-5,6,7,8-tetrafluorochromene-3-carboxylate form-
ing in DMSO at room temperature the polyfluorinated
7-(4-methylpiperazin-1-yl)-4-oxo-2-phenyl-4Н-
chromene-3-carboxylates XIа, XIb through a nucleo-
philic aromatic substitution of the fluorine atom in the
position С7 of the flavone (Scheme 6).
However in the reaction with 1,2-phenylenediamine
flavones IIIа, IIIb exhibit different reactivities. The
tetrafluoroflavone IIIb yielded ethyl 3-[(2-aminophenyl)
amino]-2-(2-hydroxy-3,4,5,6-tetrafluorobenzoyl)-3-
phenylacrylate (XII) (Scheme 7) resulting from the
opening of the pyrone ring at the addition of the amine
to the atom С2 of the flavone. Just in this way flavone IIIb
reacted with primary monoamines (Scheme 3). The at-
tempts to force ester XII into cyclization under heating or
acid catalysis provided intractable mixture of substances.
ThereactionofflavoneIIIаwith1,2-phenylenediamine
under the same conditions led to the formation of a
mixture of compounds from which we succeeded to
isolate only 1Н-benzimidazol-2-yl(2-hydroxy-3,4,5-tri-
fluorophenyl)methanone (XIII) (Scheme 7). Obviously
compound XIII results from the decomposition of the
intermediately formed enaminoester. The structure of
compound XIII is confirmed by the mass spectrum where
the maximum registered peak corresponded to the dide-
protonated molecular ion [M – 2H]+, m/z 290.
EXPERIMENTAL
Melting points have been measured on an instrument
Stuart SMP3 in open capillaries and are reported without
correction. IR spectra were recorded on a spectrometer
Perkin Elmer Spectrum One using Diffuse ReflectionAc-
cessory (DRA) in the range 4000–400 cm–1. NMR spectra
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013

SHCHERBAKOV et al.
726
were registered on a spectrometer Bruker DRX-400 (1Н:
400 MHz with respect to SiMe4; 19F: 376.4 MHz relative
to С6F6) (CD3)2SO. Mass spectrum of compound XIII
was taken on an instrumentAgilent GC 7890AMS 5975C
(EI). Single crystals of compounds VIа, IX were obtained
by crystallization from ethanol. XRD experiment was
performed on a diffractometer Xcalibur 3 equipped with a
CCD-detector [graphite monochromator, λ(MoKα) 0.71073
Е, 293(2) (VIа), 150(2) K (IX), ω-scanning] (see the table).
The extinction was accounted for analytically along the
model of multifacet crystal using the program CrysAlis
RED v.1.171.29.9. The structure was solved by the di-
rect method from the difference Fourier syntheses. The
positions and the thermal parameters of the nonhydrogen
atoms were refined by least-squares method in the full-
matrix anisotropic approximation. Elemental analysis was
carried out on an analyzer Perkin Elmer PE 2400 series
II CHNS-O EA 1108. For TLC were used ALUGRAM®
SIL G/ UV254 plates.
Ethyl 4-oxo-2-phenyl-5,6,7,8-tetrafluoro-4Н-
chromene-3-carboxylate (IIIb). Yield 12.819 g (70%),
colorless powder, mp 111°С. IR spectrum, ν, cm–1:
1735 (CO2Et), 1650 (C=O), 1594, 1573, 1522, 1498,
1
1447 (C=C), 1122, 1112 (CF). Н NMR spectrum,
3
δ, ppm: 1.11 t (3Н, СН3СН2, J 7.1 Hz), 4.21 q (2Н,
СН3СН2, 3J 7.1 Hz), 7.60–7.73 m (5Н, С6Н5). 19F NMR
spectrum, δ, ppm: 1.41 m, 4.39 m, 14.69 m, 18.43 m
(1F each). Found, %: C 58.88; H 2.76; F 20.69.
С18Н10F4O4. Calculated, %: C 59.03; H 2.75; F 20.75.
Ethyl 2-methyl-4-oxo-6,7,8-trifluoro-4Н-chromene-
3-carboxylate (VII). Yield 9.731 g (68%), colorless
powder, mp 100°С. IR spectrum, ν, cm–1: 1723 (CO2Et),
1634 (C=O), 1592, 1522, 1481 (C=C), 1121, 1087
(CF). 1Н NMR spectrum, δ, ppm: 1.30 t (3Н, СН3СН2,
3J 7.1 Hz), 2.51 s (3Н, СН3), 4.33 q (2Н, СН3СН2,
3J 7.1 Hz), 7.83 m (1Н, Н5). 19F NMR spectrum, δ, ppm:
11.11 m, 12.45 m, 26.23 m (1F each). Found, %: C 54.19;
H 2.79; F 20.37. С13Н9F3O4. Calculated, %: C 54.56;
H 3.17; F 19.91.
Flavones (IIIа, IIIb, VII). To 1.2 g (50 mmol) of
magnesium turnings several iodine crystals were added.
The flask was heated till vigorous iodine sublimation,
then 3 ml of anhydrous ethanol was added dropwise and
several drops of tetrachloromethane. At the beginning of
the intensive self-heating of the reaction mixture 20 ml
of anhydrous toluene and 3 ml of anhydrous ethanol was
added. Then 50 mmol of ester Ia, Ib in 20 ml of anhydrous
toluene was added dropwise. The reaction mixture was
maintained till complete dissolution of the magnesium
turnings and cooled to room temperature. At stirring the
equimolar amount of polyfluorobenzoyl chloride IIa, IIb
in 20 ml of anhydrous toluene was added dropwise. The
reaction mixture was stirred for 6 h. On the completion
of the reaction the reaction mixture was poured into ice-
cold H2SO4 solution (50 ml, 10 wt%), toluene layer was
separated and dried with Na2SO4. Toluene was distilled
off in a vacuum, the residue was crystallized from ethanol.
Reaction of flavones IIIа, IIIb and chromone VII
with amines. To a solution of 1 mmol of compound IIIа,
IIIb, VII in 15 ml of an appropriate solvent was added
1 mmol of amine (or 1 mmol of methylamine sulfate
at the preparation of ester Vb, coumarins mixture VIb,
VII, 2 mmol for the synthesis of coumarin X). Ethanol
or acetonitrile were used in the syntheses of compounds
Vа–Ve, XII, VIа, VIb, VId, VIe, X, XIII, DMSO, for
preparation of chromones XIа, XIb. The reaction mixture
was vigorously stirred for 24 h at 25°С (at the synthesis
of compounds Vа–Ve, XII, IVа–IVc, VIIIа, VIIIb, XIа,
Xb, XIII) or at 50°С (at the synthesis of coumarins VIа,
VIb, VId, VIe, X). The reaction progress was monitored
by TLC. The solvent was distilled off, the solid residue
was crystallized from an appropriate solvent.
The mixtures of esters Vd, Ve or coumarins VId, VIe,
and also the mixture of coumarins VIb, X were separated
by column chromatography, eluent chloroform.
Ethyl 4-oxo-2-phenyl-6,7,8-trifluoro-4Н-chromene-
3-carboxylate (IIIа). Yield 11.493 g (66%), colorless
powder, mp 114°С. IR spectrum, ν, cm–1: 1732 (CO2Et),
1653, 1638 (C=O), 1589, 1568, 1521, 1484, 1447 (C=C),
1109, 1083 (CF). 1Н NMR spectrum, δ, ppm: 1.10 t (3Н,
СН3СН2, J 7.1 Hz), 4.20 q (2Н, СН3СН2, J 7.1 Hz),
7.59–7.75 m (5Н, С6Н5), 7.90 m (1Н, Н5). 19F NMR
spectrum, δ, ppm: 11.44 m, 12.84 m, 26.60 m (1F each).
Found, %: C 61.83; H 2.92; F 16.86. С18Н11F3O4.
Calculated, %: C 62.08; H 3.18; F 16.36.
3-[Amino(phenyl)methylidene]-6,7,8-trifluoro-2Н-
chromene-2,4(3Н)-dione (IVа). Yield 0.185 g (58%),
colorless powder, mp 214–217°С (from ethanol). IR
spectrum, ν, cm–1: 3292 (NH2), 1712 (O–C=O), 1630
(C=O), 1599, 1520, 1482, 1450, 1435 (C=C, NH2), 1017,
1000, 989 (CF). 1Н NMR spectrum, δ, ppm: 7.42–7.57 m
(5Н, С6Н5), 7.92 d.d.d (1Н, Н5, JHF 10.0, 8.1, 2.2 Hz),
11.06 s (2H, NH2). 19F NMR spectrum, δ, ppm: 9.09 m,
10.46 m, 21.92 m (1F each). 13С NMR spectrum, δ, ppm:
176.75 s (С9), 175.89 s (С4), 159.87 s (С2), 146.21 d.m
3
3
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FEATURES OF REACTIONS OF POLYFLUORINATED ETHYL 4-OXO-2-PNENYL-4Н-...
727
(С7, J 258 Hz), 142.47 d.m (С6, J 236 Hz), 139.70 m (С8а),
3
δ, ppm: 0.51 t (3Н, СН3СН2, J 7.1 Hz), 2.31 s, 2.76 s
138.54 d.m (С8, J 254 Hz), 136.09 s (Си), 130.35 s (Сp),
127.81 s (Cm), 127.33 s (Сo), 116.97 s (С5), 107.24 s
(С4а), 94.91 s (С9). Found, %: C 60.27; H 2.48; F 17.66;
N 4.08. С16Н8F3NO3. Calculated, %: C 60.20; H 2.53;
F 17.85; N 4.39.
3
(po 3Н, 2NHCH3), 3.41 q (2Н, СН3СН2, J 7.0 Hz),
7.27–7.48 m (5Н, С6Н5), 8.60 br.s, 12.05 br.s (1H each,
2NH). 19F NMR spectrum, δ, ppm: –3.21 m, –0.34 m,
14.16 m (1F each). Found, %: C 58.66; H 4.40; F 13.81;
N 6.62. С20Н19F3N2O4. Calculated, %: C 58.82; H 4.69;
F 13.96; N 6.86.
3-[(Methylamino)(phenyl)methylidene]-6,7,8-
trifluoro-2Н-chromene-2,4(3Н)-dione (IVb). Yield
0.317 g (95%), colorless powder, mp 240°С (from
ethanol). IR spectrum, ν, cm–1: 3418 (NH), 1723 (O–
C=O), 1646 (C=O), 1595, 1569, 1522, 1489, 1461,
Ethyl 3-(benzylamino)-2-(2-hydroxy-3,4,5,6-
tetrafluorobenzoyl)-3-phenylacrylate (Vc). Yield
0.322 g (68%), colorless powder, mp 175°С (from
ethanolа). IR spectrum, ν, cm–1: 3232 (NH), 1711
(CO2Et), 1670 (C=O), 1590, 1521, 1491, 1442, 1423
(C=C, NH), 1000, 981 (CF). 1Н NMR spectrum, δ, ppm:
1
1415 (C=C, NH), 1063, 1039, 1007 (CF). Н NMR
spectrum, δ, ppm: 2.89 s (3Н, СН3), 7.32–7.53 m (5Н,
С6Н5), 7.71d.d.d (1Н, Н5, JHF 10.4, 8.3, 2.3 Hz), 13.06 s
(1Н, NH). 19F NMR spectrum, δ, ppm: 9.13 m, 10.54 m,
21.98 m (1F each). Found, %: C 61.54; H 2.98; F 17.40;
N 3.93. С17Н10F3NO3. Calculated, %: C 61.27; H 3.02;
F 17.10; N 4.20.
3
0.51 t (3Н, СН3СН2, J 7.0 Hz), 3.44 q (2Н, СН3СН2,
3J 7.0 Hz), 4.37 d (2Н, СН2С6Н5, J 6.1 Hz), 7.19–7.49 m
(10Н, 2С6Н5), 10.69 br.s (1Н, NH), 12.40 br.s (1Н, OН).
19F NMR spectrum, δ, ppm: –9.10 m, 1.10 m, 3.19 m,
16.23 m (1F each). Found, %: C 63.39; H 3.74; F 16.22;
N 3.08. С25Н19F4NO4. Calculated, %: C 63.43; H 4.05;
F 16.05; N 2.96.
3-[(Benzylamino)(phenyl)methylidene]-6,7,8-
trifluoro-2Н-chromene-2,4(3Н)-dione (IVc). Yield
0.397 g (97%), colorless powder, mp 176°С (from
ethanol). IR spectrum, ν, cm–1: 3068, 3029 (NH), 1723
(O–C=O), 1646 (C=O), 1595, 1569, 1504, 1489, 1461
(C=C, NH), 1063, 1039, 1007 (CF). 1Н NMR spectrum,
δ, ppm: 4.46 s (2Н, СН2), 7.21–7.53 m (10Н, 2С6Н5),
7.73 d.d.d (1Н, Н5, JHF 10.3, 8.3, 2.1 Hz), 13.58 с (1Н,
NH). 19F NMR spectrum, δ, ppm: 9.15 m, 10.94 m,
22.13 m (1F each). Found, %: C 67.31; H 3.12; F 14.09;
N 3.19. С23Н14F3NO3. Calculated, %: C 67.48; H 3.45;
F 13.92; N 3.42.
Ethyl 3-(hexylamino)-2-(2-hydroxy-3,4,5,6-
tetrafluorobenzoyl)-3-phenylacrylate (Vd). Yield
0.257 g (55%), yellow powder, mp 173°С (from ethanol).
IR spectrum, ν, cm–1: 3275 (NH), 1708 (CO2Et), 1645
(C=O), 1553, 1483, 1445 (C=C, NH), 1030, 992 (CF).
1Н NMR spectrum, δ, ppm: 1.06 t (3Н, СН3СН2,
3J 7.0 Hz), 1.15–1.95 m (11Н, NHC6H13), 3.44 m (2Н,
NHC6H13), 4.17 q (2Н, СН3СН2, 3J 7.0 Hz), 7.29–7.46 m
(5Н, С6Н5), 12.38 br.s (1Н, OН). 19F NMR spectrum, δ,
ppm: 4.16 m, 5.02 m, 14.60 m, 15.09 m (1F each). Found,
%: С 61.24; Н 5.43; F 16.13; N 3.07. C24H25F4NO4.
Calculated, %: С 61.67; Н 5.39; F 16.26; N 3.00.
Ethyl 3-amino-2-(2-hydroxy-3,4,5,6-tetrafluoro-
benzoyl)-3-phenylacrylate (Vа). Yield 0.284 g (74%),
yellow powder, mp 117°С (from ethanolа). IR spectrum,
ν, cm–1: 3381 (NH2), 1735 (CO2Et), 1648 (C=O), 1594,
1523, 1492, 1447 (C=C, NH2), 1036, 1030 (CF). 1Н NMR
spectrum, δ, ppm: 0.54 t (3Н, СН3СН2, 3J 7.1 Hz), 3.53 q
Ethyl 2-(2-hydroxy-3,4,5,6-tetrafluorobenzoyl)-
3-phenyl-3-(cyclohexylamino)acrylate (Ve).
Yield 0.223 g (48%), yellow powder, mp 178°С (from
ethanol). IR spectrum, ν, cm–1: 3303 (NH), 1700
(CO2Et), 1651 (C=O), 1552, 1475, 1440 (C=C, NH),
1014, 981 (CF). 1Н NMR spectrum, δ, ppm: 1.06 t (3Н,
3
(2Н, СН3СН2, J 7.1 Hz), 7.37–7.53 m (5Н, С6Н5),
9.13 br.s, 10.65 br.s, 10.84 br.s (1H each, NH2, OH).
19F NMR spectrum, δ, ppm: –9.17 m, 0.98 m, 2.85 m,
16.06 m (1F each). Found, %: C 56.24; H 3.52; F 19.99;
N 3.46. С18Н13F4NO4. Calculated, %: C 56.40; H 3.42;
F 19.83; N 3.65.
3
СН3СН2, J 7.0 Hz), 1.20–1.96 m (10Н, NHC6H11),
3.46 m (1Н, NHC6H11), 4.17 q (2Н, СН3СН2, 3J 7.0 Hz),
7.36–7.52 m (5Н, С6Н5), 12.42 br.s (1Н, OН). 19F, δ,
ppm: 4.10 m, 4.99 m, 14.09 m, 15.09 m (1F each). Found,
%: С 61.71; Н 5.13; F 16.18; N 3.07. C24H23F4NO4.
Calculated, %: С 61.93; Н 4.98; F 16.33; N 3.01.
Ethyl 2-[2-hydroxy-4-(methylamino)-3,5,6-
trifluorobenzoyl]-3-(methylamino)-3-phenylacrylate
(Vb). Yield 0.233 g (57%), colorless powder, mp 151°С
(from ethanol). IR spectrum, ν, cm–1: 3352, 3248 (NH),
1704 (CO2Et), 1632 (C=O), 1585, 1557, 1499, 1470,
3-[Amino(phenyl)methylene]-5,6,7,8-tetrafluoro-
2Н-chromene-2,4(3Н)-dione (VIа). Yield 0.263 g
(78%), colorless powder, mp 240°С (from ethanol). IR
spectrum, ν, cm–1: 3301, 3133 (NH2), 1711 (O–C=O),
1
1443 (C=C, NH), 1032, 984 (CF). Н NMR spectrum,
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SHCHERBAKOV et al.
728
1648 (C=O), 1610, 1524, 1490, 1451, 1435 (C=C, NH2),
1032, 986 (CF). 1Н NMR spectrum, δ, ppm: 7.43–7.56 m
(5Н, С6Н5), 10.38 br.s, 11.64 br.s (1H each, NH2).
19F NMR spectrum, δ, ppm: –2.74 m, 2.17 m, 11.82 m,
1672 m (1F each). Found, %: C 56.65; H 2.00; F 22.56;
N 3.94. С16Н7F4NO3. Calculated, %: C 56.99; H 2.09;
F 22.53; N 4.15.
(1Н, Н5, JHF 10.4, 8.3, 2.3 Hz), 10.23 br.s, 11.80 br.s (1H
each, NH2). 19F NMR spectrum, δ, ppm: 9.03 m, 10.33 m,
21.91 m (1F each). Found, %: C 51.20; H 2.21; F 22.41;
N 5.21. С11Н6F3NO3. Calculated, %: C 51.37; H 2.35;
F 22.16; N 5.45.
3-[1-(Methylamino)ethylidene]-6,7,8-trifluoro-2Н-
chromene-2,4(3Н)-dione (VIIIb). Yield 0.258 g (95%),
colorless powder, mp 236°С (from ethanol). IR spectrum,
ν, cm–1: 3074 (NH), 1736 (O–C=O), 1622 (C=O), 1520,
1493 (C=C, NH), 1068, 1048 (CF). 1Н NMR spectrum,
δ, ppm: 2.64 с, 3.24 с (po 3Н, 2СН3), 7.69 d.d.d (1Н, Н5,
JHF 10.4, 8.3, 2.3 Hz), 13.09 br.s (1H, NH). 19F NMR
spectrum, δ, ppm: 8.90 m, 10.21 m, 21.93 m (1F each).
Found, %: C 52.99; H 2.87; F 20.82; N 5.13. С12Н8F3NO3.
Calculated, %: C 53.15; H 2.97; F 21.02; N 5.16.
3-[(Methylamino)(phenyl)methylene]-5,6,7,8-
tetrafluoro-2Н-chromene-2,4(3Н)-dione (VIв). Yield
0.155 g (44%), yellow powder, mp 201°С (from ethanol).
IR spectrum, ν, cm–1: 3011 (NH), 1715 (O–C=O),
1648 (C=O), 1499, 1452, 1414 (C=C, NH), 1027, 1001
(CF). 1Н NMR spectrum, δ, ppm: 2.80 d (3Н, NHCH3,
3J 4.8 Hz), 7.28–7.35 m (5Н, С6Н5), 12.99 br.s (1Н,
NHCH3). 19F NMR spectrum, δ, ppm: –2.77 m, 2.15 m,
11.84 m, 16.78 m (1F each). Found, %: C 58.63; H 2.39;
F 22.02; N 3.95. С17Н9F4NO3. Calculated, %: C 58.13;
H 2.58; F 21.64; N 3.99.
Ethyl 1-benzyl-5-hydroxy-4-oxo-2-phenyl-6,7,8-
trifluoro-1,4-dihydroquinoline-3-carboxylate (IX). а.
To a solution of 0.47 g (1 mmol) of ester Vb in 10 ml
of ethanol was added 0.30 g (1.2 mmol) of nickel(II)
tetrahydrate. The reaction mixture was vigorously stirred
for 24 h at 25°С. Then ethanol was distilled off in a
vacuum, the solid residue was crystallized from a mixture
acetone–hexane, 1:5. Yield 0.339 g (75%).
3-[(Hexylamino)(phenyl)methylidene]-5,6,7,8-
tetrafluoro-2Н-chromene-2,4(3Н)-dione (VId). Yield
0.270 g (64%), colorless powder, mp 206°С (from
ethanol). IR spectrum, ν, cm–1: 3060 (NH), 1744 (O–C=O),
1650 (C=O), 1574, 1489, 1455, 1408 (C=C, NH), 1030,
1
1011 (CF). Н NMR spectrum, δ, ppm: 1.09–1.73 m
b. 0.47 g (1 mmol) of ester Vb was heated with-
out solvent at 180°С for 2 h. Yield 0.226 g (50%),
yellow powder, mp >300°С. IR spectrum, ν, cm–
1: 1729 (CO2Et), 1566 (C=O), 1453, 1421 (C=C,
(12Н, NHC6H13), 3.20 m (1Н, NHC6H13), 7.36–7.52 m
(5Н, С6Н5), 12.60 br.s (1Н, NHC6H13). 19F NMR spec-
trum, δ, ppm: –2.61 m, 2.21 m, 12.23 m, 17.20 m (1F
each). Found, %: C 62.63; H 4.64; F 17.76; N 3.53.
С22Н19F4NO3. Calculated, %: C 62.71; H 4.54; F 18.03;
N 3.32.
1
C–N), 1071, 1027 (CF). Н NMR spectrum, δ, ppm:
3
0.80 t (3Н, СН2СН3, J 7.1 Hz), 3.86 q (2Н, СН2СН3,
3J 7.1 Hz), 5.34 s (2Н, СН2С6Н5), 6.98–7.54 m (10Н,
2С6Н5), 14.90 s (1Н, OH). 19F NMR spectrum, δ, ppm:
–1.53 m, 8.31 m, 14.02 m (1F each). Found, %: C 66.49;
H 3.54; F 12.71; N 3.01. С25Н18F3NO4. Calculated, %:
C 66.22; H 4.00; F 12.57; N 3.09.
5,6,7,8-Tetrafluoro-3-[(cyclohexylamino)-(phenyl)
methylene]-2Н-chromene-2,4(3Н)-dione (VIe).
Yield 0.298 g (71%), yellow powder, mp 210°С (from
ethanol). IR spectrum, ν, cm–1: 3063 (NH), 1742
(O–C=O), 1646 (C=O), 1583, 1489, 1455, 1408 (C=C,
7-(Methylamino)-3-[(methylamino)(phenyl)
methylidene]-5,6,8-trifluoro-2Н-chromene-2,4(3Н)-
dione (X). Yield 0.341 g (94%), yellow powder, mp
1
NH), 1011, 989 (CF). Н NMR spectrum, δ, ppm:
1.09–1.78 m (10Н, NHC6H11), 3.20 m (1Н, NHC6H11),
7.36–7.53 m (5Н, С6Н5), 13.50 br.s (1Н, NHC6H11).
19F NMR spectrum, δ, ppm: –2.60 m, 2.22 m, 12.26 m,
17.24 m (1F each). Found, %: C 63.23; H 4.28; F 17.81;
N 3.77. С22Н17F4NO3. Calculated, %: C 63.01; H 4.09;
F 18.12; N 3.34.
1
221°С (from ethanol). Н NMR spectrum, δ, ppm:
2.80 s (3Н, С7NHCH3), 3.33 s (3Н, C9NHCH3), 6.62
br.s (С7NHCH3), 7.28–7.51 m (5Н, С6Н5), 12.19 br.s
(1Н, C9NHCH3). 19F NMR spectrum, δ, ppm: –1.37 m,
1.59 m, 14.09 m (1F each). Found, %: C 63.18; H 4.59;
F 15.61; N 8.05. С19Н15F3N2O2. Calculated, %: C 63.33;
H 4.20; F 15.82; N 7.77.
3-(1-Aminoethylidene)-6,7,8-trifluoro-2Н-
chromene-2,4(3Н)-dione (VIIIа). Yield 0.190 g (74%),
colorless powder, mp 291°С (from ethanol). IR spectrum,
ν, cm–1: 3238, 3071 (NH2), 1705 (O–C=O), 1631 (C=O),
1604, 1523, 1488, 1462 (C=C, NH2), 1061, 1008 (CF).
1Н NMR spectrum, δ, ppm: 2.58 s (3Н, СН3), 7.66 d.d.d
Ethyl 7-(4-methylpiperazin-1-yl)-4-oxo-2-phenyl-
6,8-difluoro-4Н-chromene-3-carboxylate (XIа).
Yield 0.266 g (62%), colorless powder, mp 236°С
(from ethanol). IR spectrum, ν, cm–1: 2974, 2942, 2845,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013

FEATURES OF REACTIONS OF POLYFLUORINATED ETHYL 4-OXO-2-PNENYL-4Н-...
729
2799 (N–СН3, СН), 1727 (CO2Et), 1644 (C=O), 1630,
1566, 1504, 1465 (C=C), 1395, 1372 (С–N), 1029, 1005
(CF). 1Н NMR spectrum, δ, ppm: 1.09 t (3Н, СН2СН3,
3J 7.1 Hz), 2.23 s (3H, CH3), 2.45–2.53 m [4Н, (СН2)2],
3.32–3.34 m [4Н, (СН2)2], 4.18 q (2Н, СН2СН3,
3J 7.1 Hz), 7.58–7.72 m (5Н, С6Н5), 7.53 d.d (1Н, Н5,
JHF 11.9, 1.8 Hz). 19F NMR spectrum, δ, ppm: 20.63 m,
41.52 m (1F each). Found, %: C 64.46; H 4.98; F 9.15;
N 6.36. С23Н22F2N2O4. Calculated, %: C 64.48; H 5.18;
F 8.87; N 6.54.
spectrum, δ, ppm: 5.89 m, 9.07 m, 14.51 m (1F each).
Mass spectrum (EI, 70 eV), m/z (Irel, %): 290 [M – 2H]+
(100), 262 [M – 2H – CO]+ (73). Found, %: C 57.98;
H 2.72; F 19.78; N 9.25. С14Н7F3N2O2. Calculated, %:
C 57.74; H 2.41; F 19.50; N 9.59.
ACKNOWLEDGMENTS
The study was carried out under the financial support
of the program of the President of the Russian Federation
supporting the leading scientific schools (grant NSh-
5505.2012.3), of the Ministry of Education and Science
of the Russian Federation (contract no. 8430), and of the
program of the Ural Division of the RussianAcademy of
Sciences (no. 12-P-3-1030).
Ethyl 7-(4-methylpiperazin-1-yl)-4-oxo-2-phenyl-
5,6,8-trifluoro-4Н-chromene-3-carboxylate (XIb).
Yield 0.344 g (77%), colorless powder, mp 163°С (from
ethanol). IR spectrum, ν, cm–1: 2979, 2947, 2848, 2799
(C–H, N–CH3), 1727 (CO2Et), 1645 (C=O), 1615, 1567,
1507, 1478, 1448 (C=C), 1372, 1341 (C–N), 1020, 1004
(CF). 1Н NMR spectrum, δ, ppm: 1.10 t (3Н, СН2СН3,
3J 7.1 Hz), 2.25 s (3H, CH3), 2.48–2.51 m [4Н, (СН2)2],
3.34–3.40 m [4Н, (СН2)2], 4.19 q (2Н, СН2СН3,
3J 7.1 Hz), 7.58–7.70 m (5Н, С6Н5). 19F NMR spectrum,
δ, ppm: 12.51 m, 14.11 m, 16.09 m (1F each). Found,
%: C 61.61; H 4.62; F 12.71; N 6.34. С23Н21F3N2O4.
Calculated, %: C 61.88; H 4.74; F 12.77; N 6.28.
Ethyl 3-[(2-aminophenyl)amino]-2-(2-hydroxy-
3,4,5,6-tetrafluorobenzoyl)-3-phenylacrylate (XII).
Yield 0.289 g (61%), colorless powder, mp 133°С (from
a mixture ethanol–water). IR spectrum, ν, cm–1: 3406,
3190 (NH, NH2), 1745 (CO2Et), 1670, 1655 (C=O),
1639, 1541, 1523, 1494, 1459 (C=C, NH), 1036, 1001
(CF). 1Н NMR spectrum, δ, ppm: 1.23 t (3Н, СН2СН3,
3J 7.1 Hz), 4.12 q (2Н, СН2СН3, 3J 7.1 Hz), 6.43–7.51 m
(9Н, С6Н5, С6Н4); 9.72 s, 10.57 s, 11.34 s (1H each, NH,
NH2). 19F NMR spectrum, δ, ppm: –8.24 m, 2.07 m,
6.21 m, 19.23 m (1F each). Found, %: C 61.05; H 3.74;
F 16.33; N 5.58. С24Н18F4N2O4. Calculated, %: C 60.76;
H 3.82; F 16.02; N 5.90.
REFERENCES
1. Heterocyclic Compounds, Elderfield, R.C., Ed., NewYork:
Wiley, 1957.
2. Comprehensive Organic Chemistry, Barton, D. and Ol-
lis, W.D., Eds., Oxford: Pergamon, 1979, vol. 4.
3. Budzisz, E., Malecka, M., Lorenz, I.-P., Mayer, P.,
Kwiecien, R.A., Paneth, P., Krajewska, U., and Rozal-
ski, M., Inorg. Chem., 2006, vol. 45, p. 9688.
4. Saloutin, V.I., Skryabina, Z.E., Bazyl’, I.T., and Kisil’, S.P.,
J. Fluor. Chem., 1999, vol. 94, p. 83.
5. Shcherbakov, K.V., Burgart, Ya.V., and Saloutin, V.I.,
Fromv. Akad. Nauk, Ser. Khim., 2005, vol. 9, p. 2093.
6. Bazyl’, I.T., Kisil’, S.P., Burgart, Ya.V., and Saloutin, V.I.,
J. Fluor. Chem., 2000, vol. 103, p. 3.
7. Vorozhtsov, N.N., Barkhash, V.A., Prudchenko, A.T., and
Khomenko, T.I., Zh. Obchsh. Khim., 1965, vol. 35, p. 1501.
8. Vorozhtsov, N.N., Brakhash, V.A., Prudchenko, A.T., and
Khomenko, T.I., Dokl. Akad/ Nauk SSSR, 1965, vol. 164,
p. 1046.
9. Coppola, G.M. and Dodsworth, R.W., Synthesis, 1981,
vol. 7, p. 523.
10. Kisil’, S.P., Burgart, Ya.V., and Saloutin, V.I., Zh. Org.
Khim., 2001, vol. 37, p. 1524.
11. Albert, A. and Serjeant, E., Ionization Constants of Acids
and Bases, London: Methuen, 1962.
12. Shcherbakov, K.V., Burgart, Ya.V., and Saloutin, V.I., Zh.
Org. Khim., 2006, vol. 42, p. 1848.
1Н-Benzimidazol-2-yl(2-hydroxy-3,4,5-trifluoro-
phenyl)methanone (XIII). Yield 0.222 g (76%),
colorless powder, t.subl. 333°С (from ethanol). IR
spectrum, ν, cm–1: 3076, 2921, 2593 (NH, OH), 1620
(С=O), 1593, 1566, 1507, 1464 (C=C, CN, NH), 1022
1
(CF). Н NMR spectrum, δ, ppm: 6.58–7.20 m (4Н,
13. Shcherbakov, K.V., Burgart, Ya.V., Saloutin, V.I., and
Chupakhin, O.N., Heterocycles, 2006, vol. 69, p. 319.
С6Н4), 8.01 m (1Н, =С–Н), 10.11 br.s (1Н, NH). 19F NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013