Synthesis of 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones from 4-aryl-3-carbethoxy-6-(trifluoromethyl)-2-pyrones and their reaction with sodium azide leading to new carbostyril derivatives

Article abstract of DOI:10.1016/j.tet.2013.11.033

Treatment of ethyl 4-aryl-6-(trifluoromethyl)-2-oxo-2H-pyran-3- carboxylates, prepared from 4,4,4-trifluorobutane-1,3-diones, PCl₅ and sodium diethyl malonate, with sulfuric acid afforded the intramolecular Friedel-Crafts acylation products, 3-

Full text of DOI:10.1016/j.tet.2013.11.033

Accepted Manuscript
Synthesis of 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones from 4-aryl-3-
carbethoxy-6-(trifluoromethyl)-2-pyrones and their reaction with sodium azide leading
to new carbostyril derivatives
Sergey A. Usachev, Boris I. Usachev, Vyacheslav Ya. Sosnovskikh
PII:
S0040-4020(13)01721-3
10.1016/j.tet.2013.11.033
TET 25010
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 26 September 2013
Revised Date: 31 October 2013
Accepted Date: 12 November 2013
Please cite this article as: Usachev SA, Usachev BI, Sosnovskikh VY, Synthesis of 3-
(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones from 4-aryl-3-carbethoxy-6-(trifluoromethyl)-2-pyrones
and their reaction with sodium azide leading to new carbostyril derivatives, Tetrahedron (2013), doi:
10.1016/j.tet.2013.11.033.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
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ACCEPTED MANUSCRIPT
Graphical Abstract
Synthesis of 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones from 4-aryl-3-carbethoxy-6-(trifluoromethyl)-2-
pyrones and their reaction with sodium azide leading to new carbostyril derivatives
Sergey A. Usachev, Boris I. Usachev, Vyacheslav Ya. Sosnovskikh*
R
R
R
R
OEt
NH
NH
H2SO4
NaN3
NaN3
H
N
H2SO4
DMSO
O
O
O
O
N
CO2H
CF3
N
F3C
O
O
F3C
O
O
F3C
O
O
________________________________________________________________________________________________________________________
Corresponding author. Fax: +7 343 261 59 78;
E-mail addresses: vyacheslav.sosnovskikh@usu.ru (V. Ya. Sosnovskikh)
Department of Chemistry, Ural Federal University, pr. Lenina 51, 620000 Ekaterinburg, Russian Federation

ACCEPTED MANUSCRIPT
2
Synthesis of 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones from 4-aryl-3-
carbethoxy-6-(trifluoromethyl)-2-pyrones and their reaction with sodium azide
leading to new carbostyril derivatives
Sergey A. Usachev, Boris I. Usachev, Vyacheslav Ya. Sosnovskikh*
vyacheslav.sosnovskikh@usu.ru
Department of Chemistry, Ural Federal University, pr. Lenina 51, 620000 Ekaterinburg, Russian
Federation
A B S T R A C T
Treatment of ethyl 4-aryl-6-(trifluoromethyl)-2-oxo-2H-pyran-3-carboxylates, prepared from 4,4,4-
trifluorobutane-1,3-diones, PCl5, and sodium diethyl malonate, with sulfuric acid afforded the
intramolecular Friedel-Crafts acylation products, 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones,
from which 2-(trifluoromethyl)-6H-pyrano[3,4-c]quinoline-4,5-diones were obtained via the
Schmidt reaction in moderate yields. The latter reacted with sodium azide to give 2-oxo-4-(5-
trifluoromethyl-1,2,3-triazol-4-yl)-1,2-dihydroquinoline-3-carboxylic acids in good yields.
Keywords: 2-Pyrones; Friedel-Crafts acylation; Indeno[2,1-c]pyran-1,9-diones; Schmidt reaction;
Pyrano[3,4-c]quinoline-4,5-diones; Triazoles; Trifluoromethylated heterocycles.
1. Introduction
Much attention has been given to trifluoromethylated heterocyclic compounds because they
often show unique biological and physiological activities.1 In particular, trifluoromethyl-substituted
chromones2 and other six-membered oxygen-containing heterocycles3 have drawn considerable
attention. The search for a simple and efficient access to such compounds with a CF3 group at a
specific position is one of the important goals in this area. However, there are a limited number of
regioselective syntheses of CF3-containing 2H-pyran derivatives, including 3,4-fused 6-
trifluoromethyl-2-pyrones, that proceed in good yields.4
Most reports concerning 2H-pyran-2-ones (2-pyrones, α-pyrones) involve non-fluorinated
derivatives, which perform important biological functions in nature and have great synthetic

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3
potential for the construction of a variety of arenes and heteroarenes.5 It is evident that their C-2, C-
4 and C-6 positions are electrophilic in nature and prone to nucleophilic attack. Activation of 2-
pyrones by the introduction of the electron-withdrawing CF3 group at the 6-position makes this
heterocyclic system more electrophilic and enables a diverse range of productive chemistry, with or
without ring opening.6,7
Only a few methods for the preparation of 6-(trifluoromethyl)-2-pyrones have been reported to
date. Most of them typically suffer from a narrow scope of substrates, long reaction time, tedious
synthetic routes, drastic reaction conditions, low yields, as well as a very limited variety of
substituents. The parent 6-(trifluoromethyl)-2-pyrone (1) has been synthesized by the reaction of 2-
pyrone-6-carboxylic acid with SF4–HF at 100 °C in 65% yield.8 The ethyl 6-(trifluoromethyl)-2-
pyrone-3-carboxylate (2) was prepared by condensation of trifluoroacetone with diethyl
ethoxymethylenemalonate,
followed
by
cyclization
of
intermediate
diethyl
(trifluoroacetonyl)methylenemalonate; this pyrone was used for the preparation of cage derivatives
to explore their usefulness as antiviral agents.9 A three-step formation of ethyl 6-(trifluoromethyl)-
2-pyrone-4-carboxylate (3) in 28% overall yield was achieved by Cu-catalysed addition of 1,1,1-
trichloro-2,2,2-trifluoroethane to methyl itaconate, followed by double HCl elimination with
triethylamine and subsequent thermal elimination reaction of MeCl.10 Dealkoxylation of
trifluoroacetoacetic ester by P2O5 leads to trifluoroacetylketene, which quickly dimerizes to
hexafluorodehydroacetic acid (4).11 Moreover, Gerus et al. reported that heating of
trifluoromethylated β-alkoxyvinyl ketones and N-acylglycines in acetic anhydride gave the
corresponding 3-acylamino-6-(trifluoromethyl)-2-pyrones (5), the chemical properties of which
were investigated in detail.12 Apart from these approaches towards the synthesis of 6-CF3-2-
pyrones, a simple procedure for the preparation of pyrones 6 and 7 bearing an aryl substituent at the
4-position and a carbethoxy group or hydrogen at the position 3 from commercial 1-aryl-4,4,4-
trifluorobutane-1,3-diones 8, PCl5, and sodium diethyl malonate, has been developed by us

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4
recently.6 This promising reaction deserves further investigations in order to expand the scope of its
possible applications.
CO2Et
CO2Et
F3C
O
O
F3C
O
O
F3C
O
O
1
2
3
OH
Ar
COCF3
O
NHCOR
O
X
F3C
O
F3C
O
F3C
O
O
4
5
6 (X = CO2Et)
7 (X = H)
Figure 1. Known 6-trifluoromethyl-2-pyrone derivatives.
Herein we wish to demonstrate utility of readily available ethyl 4-aryl-6-(trifluoromethyl)-2-oxo-
2H-pyran-3-carboxylates as valuable building blocks for the construction of 3-
6
(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones 9 via an intramolecular Friedel-Crafts acylation. On
the basis of these compounds, 2-(trifluoromethyl)-6H-pyrano[3,4-c]quinoline-4,5-diones 10 and 2-
oxo-4-(5-trifluoromethyl-1,2,3-triazol-4-yl)-1,2-dihydroquinoline-3-carboxylic acids 12 were
prepared by reactions with sodium azide. Moreover, in addition to our preliminary communication,6
full experimental details concerning the synthesis of pyrones 6 and 7 are also reported.
2. Results and discussion
We found that the reaction of 1-aryl-4,4,4-trifluorobutane-1,3-diones 8 with PCl5 (the first stage)
and sodium diethyl malonate (the second stage) can be employed to generate ethyl 4-aryl-6-
(trifluoromethyl)-2-oxo-2H-pyran-3-carboxylates 6. After several trials, it became clear that the first
stage is a slow reaction while the second stage is fast. In our initial studies, we optimized the
reaction conditions by using 1-phenyl-4,4,4-trifluorobutane-1,3-dione (8a) and monitored the
reaction progress using 19F NMR. To subsequently design a preparative procedure and determine
the scope of the reaction, products of the first stage were not isolated but were observed by 19F

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5
NMR spectroscopy. When 1-phenyl-4,4,4-trifluorobutane-1,3-dione was treated with 1.1 equiv of
PCl5 for 30 hours at room temperatures, 19F NMR analysis of the reaction mixture showed
formation of a mixture of products containing a major intermediate. Thus, four signals
corresponding to the CF3-bearing intermediates were observed in C6D6:
δ –79.8 (3%), δ –70.5 (8%),
δ
–70.0 (80%, major intermediate),
δ –63.5 (3%). The reaction mixture also contained 6% of the
starting diketone 8a (
δ
–77.4). The 19F NMR spectral data for the mixtures prepared from the other
diketones 8 and PCl5 were similar to those observed for the mixture of 8a and PCl5.
Probably, the major intermediates A with the signal at about δ –70 ppm are responsible for the
formation of the intermediate α,β-unsaturated chloro ketones B' and B'', from which ketones B'
then react with sodium diethyl malonate to produce 2-pyrones 6 through intermediates C and D.
The reaction time of the first stage depends strongly on the nature of the aryl substituent. An
electron-withdrawing substituent (F, Cl, NO2) at the para position of the aromatic ring retards the
reaction (24–48 h), whereas an electron-donating aromatic moiety (p-tolyl, 2-naphthyl, 2-thienyl)
greatly accelerates it (0.5–7 h). The temperature level of the reactions should be as low as possible
(25–35 °C). Prolonged heating at higher temperatures resulted in a more complex mixture of
intermediates and decrease in the yields of 6. Nevertheless, in order to reduce the reaction time as
much as possible, in the case of diketone 8e the reaction was carried out at 45–50 °C to give pyrone
6e in 18% yield.
The reaction mixture was then treated with sodium diethyl malonate at –50 to 0 °C within 1 h
(the second stage). After some optimization, we were pleased to find that with the use of 4.5 equiv
of sodium diethyl malonate relative to starting diketones 8, the maximum yield of the desired
products 6 was reached. No pyrone 6a was obtained, when the same reaction was conducted using
1.1 or 9.5 equiv of sodium diethyl malonate. A plausible pathway leading to the formation of
compounds 6a–g via intermediates A, B, C, and D is outlined in Scheme 1.

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6
F3C
Ar
O
O
8a-g
F3C
F3C
Ar
25-50 oC
0.5-48 h
PCl5
Cl
O
O B''
+
Cl
F3C
Ar
Ar
-POCl3
O
O
B'
Cl
P
Cl
Cl
Cl
A
EtO
OEt
ONa
-50 oC
0 oC
1 h
O
F3C
Ar
F3C
Ar
[1,5] H
OH
O
EtO2C CO2Et
EtO2C CO2Et
D
C
-EtOH
Ar
Ar
CO2Et
AcOH
H2SO4
F3C
O
O
F3C
O
O
6a-g
7a-g
Ar
Ph
4-ClC6H4
4-FC6H4
4-MeC6H4
4-NO2C6H4
2-C10H7
Yield (%)
Yield (%)
6
a
b
c
d
e
f
7
a
b
c
d
e
f
24
29
39
39
18
45
22
83
90
87
74
69
70
64
2-C4H3S
g
g
Scheme 1. Synthesis of 6-CF3-2-pyrones 6a–g and 7a–g.
It was also found that ethyl 4-aryl-6-(trifluoromethyl)-2-oxo-2H-pyran-3-carboxylates 6 are
convenient precursors of 4-aryl-6-(trifluoromethyl)-2H-pyran-2-ones 7 because of their ability to
undergo easy decarbethoxylation. Thus, when pyrones 6a–g were refluxed in aqueous acetic acid
with addition of H2SO4, compounds 7a–g were isolated in high yields (Scheme 1). The structure of
the synthesized 6-CF3-2H-pyran-2-ones 6 and 7 was confirmed by NMR, EI-MS, HRMS, IR
spectra, and elemental analysis. The H-5 proton of 6 appeared as a singlet at
δ 6.75–6.92 ppm,
4
while H-3 and H-5 of 7 appeared as doublets with J = 0.8–1.1 Hz at
δ
6.60–6.79 and 6.92–7.12
–72.4 ppm. In the 13C
ppm, respectively; their CF3 group manifests itself as a singlet at about
δ

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7
NMR spectrum of compound 6a, the characteristic quartets of the CF3 group at
δ =
117.7 (1JC,F
273.2 Hz), C-6 at
δ δ
148.0 (2JC,F = 39.7 Hz), and C-5 at 107.1 (3JC,F = 3.6 Hz) were observed. In
the EI-MS spectra, fragmentation of pyrones 6 was presented by intense ion peaks [M]+, [M–28]+,
[M–45]+, [M–28–69]+, and by ion peak [CF3]+ (~30%).
Taking into account the arrangement of the aryl moiety and carbethoxy group in pyrones 6 to
each other, we envisaged that the reaction of 6 with sulfuric acid would produce the corresponding
fused indone derivatives 9 as a result of intramolecular Friedel-Crafts acylation. Indeed, we found
that treatment of 6a with H2SO4 at 110–125 °C for 10 min afforded 3-(trifluoromethyl)indeno[2,1-
c]pyran-1,9-dione (9a) (yield 41%), the first representative of a novel polynuclear fused
heterocyclic system. The more reactive pyrone 6d gave indone 9d in 61% yield under the same
conditions, whereas the less reactive pyrones 6b,c bearing Cl and F atoms in the benzene ring
required a longer period of time and only partial hydrolysis followed by decarboxylation had
occurred. Since the protocol for 6b,c requires anhydrous conditions and to avoid the formation of
pyrones 7, the reaction was carried out in the presence of P2O5 to remove traces of water and
compounds 9b and 9c were obtained in 47% and 65% yield, respectively.
We next investigated the reaction of indones 9 with sodium azide in concentrated H2SO4 with the
intention of forming the 3,4-fused 2-quinolone (carbostyril) derivatives 10 via the Schmidt reaction.
The carbostyril system constitutes the skeleton of a number of physiologically active natural
products and drugs and its derivatives have attracted strong interest due to their useful biological
and pharmacological properties.13 In contrast to the various classical approaches towards the
synthesis of carbostyrils, such as Vilsmeier–Haack, Knorr, and Friedlander reactions,14 azido-
Schmidt reaction has not drawn much attention, probably due to the use of strong protic acids
(H2SO4, CCl3CO2H), which result in a large number of side-products. Most pertinent to the present
research are the reactions involving the additions of azide to 2,3-disubstituted indone
derivatives.15,16

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8
To optimize the Schmidt reaction conditions, we investigated the transformation of indone 9b as
a model substrate. The reaction of 9b with sodium azide was examined in concentrated sulfuric acid
at heating for several hours (the progress of the reaction was monitored by TLC, eluent –
chloroform). The desired product, 8-chloro-2-(trifluoromethyl)-4H-pyrano[3,4-c]quinoline-4,5(6H)-
dione (10b), was obtained at 90 °C for 3 hours in 56% yield. This compound has fused cyclic
structure, which is difficult synthesize using other methods.17 A similar reaction, when performed in
the presence of MeSO3H at 70 °C for 6 hours, provided 10b only in 21% yield. In contrast, the use
of such catalysts as PPA,18 CF3SO3H/CH2Cl2,19 AlCl3 or FeCl3 in 1,2-dichloroethane20 for the
preparation of quinolone 10b was not satisfactory.
With optimized reaction conditions established, the substrate scope was briefly studied. Indone
9c with a fluorine atom on the benzene ring reacted smoothly under the same conditions to give
quinolone 10c in 47% yield. However, substrates 9a,d (R = H, Me) were too active to the reaction,
leading to a complicated mixture of products. The use of a mixture of H2SO4, P2O5, and CCl3CO2H
allowed us to prepare carbostyril 10a albeit in only 23% yield and we could not improve the yield
significantly. It was also found that pyrones 6a–c could be employed directly under similar
conditions to give carbostyrils 10a–c in 39–56%. It is important that a higher yield and easier
purification of products was possible if the transformation was performed by using a one-pot
approach. Thus, compounds 9 and 10 could be synthesized from the same starting material 6 simply
by the choice of the reaction conditions.
The structure of the quinolone product merits some comment. In accord with the previously
reported mechanism,15,16,20 the Schmidt reaction involves acid activation of the indone keto group
followed by the addition of hydrazoic acid (intermediate E). After the elimination of water the
iminodiazonium ion F is formed, which by loss of nitrogen and migration of the anti-substituent to
the electron deficient nitrogen (intermediate G) can give either carbostyril 10 or isocarbostyril 10'
derivatives. It is known that 2,3-diphenylindone can be converted into 3,4-diphenylcarbostyril and
3,4-diphenylisocarbostyril derivatives by the Schmidt reaction (the former in greater amount).15 In

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9
some cases, a conjugate addition of hydrazoic acid to C-3 of indones was observed to give 4-
quinolones.16 Thus, the formation of intermediate H leading to 4-quinolone 10'' could not be ruled
out (Scheme 2).
NaN3, H2SO4
R
R
8
R
7
6
9
7
8
5
10
6
H2SO4
OEt
NH
NaN3
H2SO4
O
9
4
5
1
O
O
3
1
2
4
F3C
O
O
F3C
O
O
F3C
O
O
6a-d
9a-d
10a-c
R
R
R
N
O
OH
-H2O
-N2
N
N2
N N2
H
F3C
O
O
F3C
O
O
F3C
O
F
E
G
X
R
R
R
O
H
HN
O
N2
N
X
OH
NH
O
O
F3C
O
F3C
O
O
F3C
O
H
10''
10'
R
Yield
(%)
41
47
65
Yield
Yield
(%)b
39
49
43
9
10
(%)a
23
56
47
–
H
Cl
F
a
b
c
a
b
c
Me
61
–
d
a From 9.
b From 6.
Scheme 2. Synthesis of compounds 9a–d and 10a–c.
The choice between the isomeric quinolones 10, 10', and 10'' (the latter can be explained in
terms of the rearrangement of an intermediate originated from a conjugate addition of the reagent)
was made in favor of the former on the basis of degradation of compound 10a at refluxing in

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10
ethanol solution in the presence of base. We found that 10a is opened to the intermediate salt 11',
which could not be isolated and underwent spontaneous detrifluoroacetylation to give via
acidification of 11'' known 4-methylcarbostyril-3-carboxylic acid 11 in 92% yield (Scheme 3).21
1
Comparison of the melting point and H NMR spectrum of acid 11 prepared by us with the data
reported for this compound in the literature21 indicates that they are identical and, hence, the
carbostyril structure 10 is proved. Thus, the reactions of compounds 6 and 9 with sodium azide lead
to the successful synthesis of fused carbostyrils 10 containing a CF3 group in the pyran ring, a
previously unknown group of 2-quinolone derivatives.
CF3
O
Me
CO2H
O
O
1) NaOH
2) HCl
N
H
O
N
H
10a
11 (92%)
NaOH
HCl
CF3
O
Me
CO2Na
O
CO2Na
NaOH
-CF3CO2Na
N
H
N
H
O
11'
11''
Scheme 3. Synthesis of known acid 11.
Recently, we reported that pyrones 6 and 7 react with sodium azide to produce highly
functionalized triazolyl derivatives of cinnamic acid.7 Bearing this in mind, we envisaged that
pyranocarbostyrils 10 could be converted into previously unknown 4-triazolylcarbostyrils 12 by
their reaction with sodium azide. In fact, we found that when pyranocarbostyrils 10a,b were heated
in DMSO with NaN3 (2 equiv) at 120 °C for 3 h, the desired products 12a,b were obtained in good
yields and presumably arise via intermediate vinyl azide I or ring-opening of the initially formed
fused intermediate J (Scheme 4). In case of pyranocarbostyril 10c this reaction failed presumably

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11
due to facile nucleophilic aromatic substitution of a fluorine in the quinolone moiety and further
degradation of formed arylazide.
The structures of compounds 9–12 were confirmed by elemental analysis, 1H, 19F, 13C NMR, and
IR spectroscopy. In the 19F NMR spectra, the trifluoromethyl group appeared as a singlet at
for 9 (CDCl3), –70.6 for 10 (DMSO-d6), and –59.5 ppm for 12 (DMSO-d6). The 13C NMR spectrum
δ –71.4
of 9a showed that the C-4 atom at
δ 99.8 ppm was coupled with the fluorine atoms of the
trifluoromethyl group with 3JC,F = 3.5 Hz and the C-3 atom at
δ
156.1 ppm with 2JC,F = 39.6 Hz.
N N
HN
CF3
O
CF3
CO2H
1) NaN3, DMSO
O
2) HCl
R
N
H
O
R
N
O
H
10a,b
12a (80%)
12b (66%)
N
N
NaN
N2
N
CF3
CF3
O
CO2Na
or
O
R
N
O
R
N
O
H
H
I
J
Scheme 4. Synthesis of 4-triazolylcarbostyrils 12a,b.
3. Conclusion
In conclusion, we have shown that the synthesized 6-CF3-2H-pyran-2-ones can be used as
perspective building blocks for the preparation of novel trifluoromethylated heterocycles, which are
not readily available by other methods. In particular, a series of indone and carbostyril derivatives
were obtained in moderate to good yields. These products constitute an important structural subunit
of a variety of biologically active compounds and could be serve as useful substrates in the
construction of more complex heterocyclic systems.
4. Experimental

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12
4.1. General
NMR spectra were recorded on Bruker DRX-400 and Bruker Avance II spectrometers (1H – 400 MHz,
19F – 376 MHz, and 13C – 100 MHz) in DMSO-d6 and CDCl3 with TMS, CFCl3, and C6F6 as internal
standards. IR spectra were recorded on a Perkin–Elmer Spectrum BX-II and Nicolet 6700 instruments (KBr
pellets, FTIR mode). Elemental analyses were performed at the Microanalysis Services of the Institute of
Organic Synthesis, Ural Branch, Russian Academy of Sciences. All solvents used were dried and distilled
per standard procedures. The starting 1-aryl-4,4,4-trifluorobutane-1,3-diones 8 were prepared according to
described procedure.22
4.2. General procedure for the synthesis of compounds (6a–g)
A mixture of the corresponding 1-aryl-4,4,4-trifluorobutane-1,3-dione 8 (0.16 mol), PCl5 (37.1 g, 0.18
mol), and CCl4 (10 mL) was stirred at 25–35 °C for several hours. After complete conversion as indicated by
19F NMR, volatile components were removed under reduced pressure. The residue was diluted with dry
CH2Cl2 (100 mL), cooled to –50 °C and quenched with a cooled to –50 °C suspension of sodium diethyl
malonate (0.72 mol) in absolute ethanol (450 mL). After achieving 0 °C, the reaction was left under stirring
for 1 h at this temperature. The dark red reaction mixture was quenched with 10% H2SO4 (1.5 L) and the
organic layer was washed once with water, distilled under reduced pressure and crystallized from ethanol
(cooling to –30 °C) to afford pure 6.
4.2.1. Ethyl 2-oxo-4-phenyl-6-(trifluoromethyl)-2H-pyran-3-carboxylate (6a). Yield 24% (30 h), colourless
crystals, mp 90 °C. IR (ATR): 1758, 1714, 1667, 1581, 1559, 1494, 1471 cm–1; 1Н NMR (400 MHz, CDCl3)
δ
1.11 (t, J = 7.1 Hz, 3H, Me), 4.21 (q, J = 7.1 Hz, 2H, CH2O), 6.80 (s, 1H, H-5), 7.42–7.55 (m, 5H, Ph); 1Н
NMR (200 MHz, C6D6) 0.75 (t, J = 7.0 Hz, 3H, Me), 3.90 (q, J = 7.0 Hz, 2H, CH2O), 5.89 (s, 1H, H-5),
7.00 (s, 5H, Ph); 19F NMR (188 MHz, C6D6) –72.3 (s, CF3); 13C NMR (100 MHz, CDCl3)
13.6, 62.4,
δ
δ
δ
3
1
107.1 (q, JC,F = 3.6 Hz, C-5), 117.7 (q, JC,F = 273.2 Hz, CF3), 121.9, 127.3, 129.2, 131.0, 134.4, 148.0 (q,
2JC,F = 39.7 Hz, C-6), 152.1, 156.5, 163.4; MS (EI, 70 eV) m/z (%) 312 (100, [M]+), 284 (72), 267 (75), 215
(69); HRMS (ESI): calcd for C15H11F3O4 [M]+ 312.06094, found 312.05989. Anal. Calcd for C15H11F3O4: C,
57.70; H, 3.55. Found: C, 57.77; H, 3.53.
4.2.2. Ethyl 4-(4-chlorophenyl)-2-oxo-6-(trifluoromethyl)-2H-pyran-3-carboxylate (6b). Yield 29% (24 h),
colourless crystals, mp 78 °C. IR (ATR): 1760, 1709, 1663, 1595 cm–1; 1Н NMR (200 MHz, CDCl3)
δ
1.17
1
(t, J = 7.1 Hz, 3H, Me), 4.24 (q, J = 7.1 Hz, 2H, CH2O), 6.77 (s, 1H, H-5), 7.36–7.52 (m, 4H, arom.); H
NMR (400 MHz, DMSO-d6) δ 1.06 (t, J = 7.1 Hz, 3H, Me), 4.17 (q, J = 7.1 Hz, 2H, CH2O), 7.42 (s, 1H, H-
5), 7.55 (d, J = 8.6 Hz, 2H, arom.), 7.64 (d, J = 8.6 Hz, 2H, arom.); 19F NMR (188 MHz, CDCl3)
CF3); 19F NMR (376 MHz, DMSO-d6) –70.3 (s, CF3); 13C NMR (126 MHz, CDCl3)
13.9, 62.8, 106.8 (q,
3JC,F = 3.5 Hz, C-5), 117.8 (q, 1JC,F = 273.4 Hz, CF3), 122.3, 128.9, 129.7, 132.9, 137.7, 148.5 (q, 2JC,F = 39.9
δ –72.4 (s,
δ
δ

ACCEPTED MANUSCRIPT
13
Hz, C-6), 150.9, 156.4, 163.4; MS (EI, 70 eV) m/z (%) 346 (79, [M]+), 318 (87), 301 (67), 249 (100), 183
(39); HRMS (ESI): calcd for C15H10ClF3O4 [M]+ 346.02197, found 346.02203.
4.2.3. Ethyl 4-(4-fluorophenyl)-2-oxo-6-(trifluoromethyl)-2H-pyran-3-carboxylate (6c). Yield 39% (36 h),
1
colourless crystals, mp 121–123 °C. IR (ATR): 1755, 1708, 1663, 1601, 1560, 1510 cm–1; Н NMR (200
MHz, CDCl3)
δ 1.15 (t, J = 7.1 Hz, 3H, Me), 4.23 (q, J = 7.1 Hz, 2H, CH2O), 6.78 (s, 1H, H-5), 7.14–7.24
(m, 2H, arom.), 7.41–7.51 (m, 2H, arom.); 19F NMR (188 MHz, CDCl3)
δ
–109.0 (m, F), –72.5 (s, CF3); 13
C
2
NMR (126 MHz, CDCl3)
δ
13.8, 62.6, 106.9 (q, 3JC,F = 3.6 Hz, C-5), 116.6 (d, JC,F = 22.1 Hz, C-3', C-5'),
1
3
4
117.7 (q, JC,F = 273.4 Hz, CF3), 122.1, 129.7 (d, JC,F = 8.8 Hz, C-2', C-6'), 130.5 (d, JC,F = 3.4 Hz, C-1'),
148.2 (q, 2JC,F = 39.9 Hz, C-6), 150.9, 156.4, 163.4, 164.3 (d, 1JC,F = 253.4 Hz, C-4'); MS (EI, 70 eV) m/z (%)
330 (41, [M]+), 302 (50), 285 (46), 261 (25), 233 (100), 167 (46); HRMS (ESI): calcd for C15H10F4O4 [M]+
330.05152, found 330.05168.
4.2.4. Ethyl 4-(4-tolyl)-2-oxo-6-(trifluoromethyl)-2H-pyran-3-carboxylate (6d). Yield 39% (7 h), colourless
crystals, mp 60 °C. IR (ATR): 1769, 1740, 1716, 1663, 1610 cm–1; 1Н NMR (400 MHz, CDCl3)
δ 1.16 (t, J =
7.1 Hz, 3H, Me), 2.42 (s, 3H, Me), 4.23 (q, J = 7.1 Hz, 2H, CH2O), 6.80 (s, 1H, H-5), 7.27–7.36 (m, 4H,
arom.); MS (EI, 70 eV) m/z (%) 326 (100, [M]+), 298 (93), 281 (69), 257 (29), 229 (62). Anal. Calcd for
C16H13F3O4: C, 58.90; H, 4.02. Found: C, 58.77; H, 3.90.
4.2.5. Ethyl 4-(4-nitrophenyl)-2-oxo-6-(trifluoromethyl)-2H-pyran-3-carboxylate (6e). Yield 18% (45–50 °C,
48 h), light yellow crystals, mp 134–136 °C. IR (ATR): 1758, 1714, 1667, 1581, 1559, 1494, 1471 cm–1; 1Н
NMR (400 MHz, CDCl3)
δ 1.16 (t, J = 7.1 Hz, 3H, Me), 4.23 (q, J = 7.1 Hz, 2H, CH2O), 6.75 (s, 1H, H-5),
7.63 (dd, J = 9.0, 2.2 Hz, 2H, arom.), 8.35 (dd, J = 9.0, 2.2 Hz, 2H, arom.); MS (EI, 70 eV) m/z (%) 357 (48,
[M]+), 329 (47), 312 (53), 288 (27), 260 (100); HRMS (ESI): calcd for C15H10F3NO6 [M]+ 357.04602, found
357.04674.
4.2.6. Ethyl 4-(2-naphthyl)-2-oxo-6-(trifluoromethyl)-2H-pyran-3-carboxylate (6f). Yield 45% (6 h), yellow
powder, mp 108–110 °C. IR (ATR): 1762, 1714, 1663, 1627, 1548 cm–1; 1Н NMR (400 MHz, CDCl3)
δ 1.07
(t, J = 7.1 Hz, 3H, Me), 4.21 (q, J = 7.1 Hz, 2H, CH2O), 6.92 (s, 1H, H-5), 7.49 (dd, J = 8.5, 1.8 Hz, 1H,
arom.), 7.56–7.64 (m, 2H, arom.), 7.90 (dd, J = 8.3, 1.0 Hz, 2Н, arom.), 7.94–7.97 (m, 2Н, arom.); 19F NMR
(471 MHz, CDCl3) δ –72.3 (s, CF3); 13C NMR (126 MHz, CDCl3) δ 13.7, 62.5, 107.2 (q, 3JC,F = 3.6 Hz, C-5),
1
117.8 (q, JC,F = 273.3 Hz, CF3), 122.0, 123.7, 127.5, 127.90, 127.91, 128.2, 128.7, 129.3, 131.6, 132.8,
2
134.0, 148.1 (q, JC,F = 39.8 Hz, C-6), 152.1, 156.6, 163.6; MS (EI, 70 eV) m/z (%) 362 (100, [M]+), 334
(35), 317 (29), 247 (39); HRMS (ESI): calcd for C19H13F3O4 [M]+ 362.07659, found 362.07727.
4.2.7. Ethyl 4-(2-thienyl)-2-oxo-6-(trifluoromethyl)-2H-pyran-3-carboxylate (6g). Yield 22% (0.5 h), light
1
yellow crystals, mp 112–113 °C. IR (ATR): 1747, 1712, 1671, 1557, 1476 cm–1; Н NMR (400 MHz,
CDCl3)
δ 1.33 (t, J = 7.2 Hz, 3H, Me), 4.40 (q, J = 7.2 Hz, 2H, CH2O), 6.92 (s, 1H, H-5), 7.20 (dd, J = 5.0,
3.9 Hz, 1H, H-4'), 7.53 (dd, J = 3.9, 1.1 Hz, 1H, H-3'), 7.68 (dd, J = 5.0, 1.1 Hz, 1H, H-5'); 13C NMR (126

ACCEPTED MANUSCRIPT
14
3
1
MHz, CDCl3)
δ 13.8, 62.9, 106.0 (q, JC,F = 3.7 Hz, C-5), 117.7 (q, JC,F = 273.3 Hz, CF3), 118.7, 129.0,
131.3, 132.3, 135.2, 142.6, 147.6 (q, 2JC,F = 39.7 Hz, C-6), 156.9, 164.0; MS (EI, 70 eV) m/z (%) 318 (100,
[M]+), 290 (69), 273 (55), 262 (30), 221 (55). Anal. Calcd for C13H9F3O4S: C, 49.06; H, 2.85. Found: C,
48.98; H, 2.79.
4.3. General procedure for the synthesis of compounds (7a–g)
A solution of the corresponding pyrone 6 (32 mmol) in AcOH–H2O–H2SO4 (4:2:1, 100 mL) was refluxed
for 4 h. When the reaction was complete, the reaction mixture was allowed to cool to room temperature and
then diluted with water (100 mL). The solid that formed was filtered and recrystallized from hexane.
4.3.1. 4-Phenyl-6-(trifluoromethyl)-2H-pyran-2-one (7a). Yield 83%, colourless crystals, mp 60 °C. IR
(ATR): 1744, 1698, 1666, 1560 cm–1; 1Н NMR (400 MHz, CDCl3)
δ 6.67 (d, J = 0.9 Hz, 1H, H-3), 6.97 (d, J
= 0.9 Hz, 1H, H-5), 7.50–7.62 (m, 5H, Ph); 19F NMR (188 MHz, C6D6)
δ
–72.4 (s, CF3); 13C NMR (100
3
MHz, CDCl3)
δ
104.8 (q, JC,F = 3.8 Hz, C-5), 113.8, 118.0 (q, 1JC,F = 272.9 Hz, CF3), 126.6, 129.5, 131.5,
134.1, 148.5 (q, 2JC,F = 39.2 Hz, C-6), 153.3, 159.3; MS (EI, 70 eV) m/z (%) 240 (100, [M]+), 212 (92), 171
(58), 115 (80); HRMS (ESI): calcd for C12H7F3O2 [M]+ 240.03981, found 240.03995. Anal. Calcd for
C12H7F3O2: C, 60.01; H, 2.94. Found: C, 59.85; H, 3.00.
4.3.2. 4-(4-Chlorophenyl)-6-(trifluoromethyl)-2H-pyran-2-one (7b). Yield 90%, colourless crystals, mp 101–
102 °C. IR (ATR): 1741, 1670, 1590 cm–1; 1Н NMR (400 MHz, CDCl3)
(d, J = 0.9 Hz, 1H, H-5), 7.49–7.57 (m, 4H, arom.); 19F NMR (471 MHz, CDCl3)
δ
6.64 (d, J = 0.9 Hz, 1H, H-3), 6.92
–72.4 (s, CF3); 13C NMR
δ 104.4 (q, JC,F = 3.7 Hz, C-5), 113.9, 118.0 (q, JC,F = 273.0 Hz, CF3), 128.0, 129.9,
δ
3
1
(126 MHz, CDCl3)
132.6, 138.1, 148.8 (q, 2JC,F = 39.3 Hz, C-6), 152.1, 159.1; MS (EI, 70 eV) m/z (%) 274 (52, [M]+), 246 (79),
205 (59), 149 (100); HRMS (ESI): calcd for C12H6ClF3O2 [M]+ 274.00084, found 274.00052.
4.3.3. 4-(4-Fluorophenyl)-6-(trifluoromethyl)-2H-pyran-2-one (7c). Yield 87%, colourless crystals, mp 60
°C. IR (ATR): 1740, 1669, 1597, 1566, 1515 cm–1; 1Н NMR (200 MHz, CDCl3)
δ 6.63 (s, 1H, H-3), 6.94 (s,
1H, H-5), 7.18–7.30 (m, 2H, arom.), 7.57–7.67 (m, 2Н, arom.); 19F NMR (188 MHz, CDCl3)
δ
–108.7 (m,
3
2
1F), –72.4 (s, CF3); 13C NMR (126 MHz, CDCl3)
δ
104.5 (q, JC,F = 3.7 Hz, C-5), 113.6, 116.9 (d, JC,F
=
=
22.1 Hz, C-3', C-5'), 118.1 (q, JC,F = 273.0 Hz, CF3), 128.9 (d, 3JC,F = 8.8 Hz, C-2', C-6'), 130.4 (d, JC,F
1
4
3.3 Hz, C-1'), 148.8 (q, 2JC,F = 39.3 Hz, C-6), 152.2, 159.1, 164.8 (d, 1JC,F = 253.8 Hz, C-4'); MS (EI, 70 eV)
m/z (%) 258 (17, [M]+), 230 (33), 189 (29), 133 (100); HRMS (ESI): calcd for C12H6F4O2 [M]+ 258.03039,
found 258.03052.
4.3.4. 4-(4-Tolyl)-6-(trifluoromethyl)-2H-pyran-2-one (7d). Yield 74%, colourless crystals, mp 114–115 °C.
IR (ATR): 1737, 1666, 1609, 1578, 1557 cm–1; 1Н NMR (400 MHz, CDCl3)
0.8 Hz, 1H, H-3), 6.97 (d, J = 0.8 Hz, 1H, H-5), 7.33 (d, J = 8.2 Hz, 2H, arom.), 7.51 (d, J = 8.2 Hz, 2Н,
δ 2.44 (s, 3H, Me), 6.64 (d, J =

ACCEPTED MANUSCRIPT
15
arom.); MS (EI, 70 eV) m/z (%) 254 (100, [M]+), 226 (87), 185 (46), 129 (50); HRMS (ESI): calcd for
C13H9F3O2 [M]+ 254.05546, found 254.05500.
4.3.5. 4-(4-Nitrophenyl)-6-(trifluoromethyl)-2H-pyran-2-one (7e). Yield 69%, colourless crystals, mp 178–
180 °C. IR (ATR): 1741, 1667, 1520 cm–1; 1Н NMR (400 MHz, CDCl3)
(d, J = 1.0 Hz, 1H, H-5), 7.78 (dd, J = 9.0, 2.3, 2H, arom.), 8.39 (dd, J = 9.0, 2.3 Hz, 2Н, arom.); 13C NMR
δ 6.73 (d, J = 1.0 Hz, 1H, H-3), 6.95
3
1
(126 MHz, CDCl3)
δ
103.7 (q, JC,F = 3.7 Hz, C-5), 110.2, 118.0 (q, JC,F = 273.1 Hz, CF3), 129.1, 129.2,
2
131.2, 137.4, 146.0, 148.5 (q, JC,F = 39.2 Hz, C-6), 159.2; MS (EI, 70 eV) m/z (%) 285 (100, [M]+), 257
(86), 216 (80), 160 (36); HRMS (ESI): calcd for C12H6F3NO4 [M]+ 285.02489, found 285.02490.
4.3.6. 4-(2-Naphthyl)-6-(trifluoromethyl)-2H-pyran-2-one (7f). Yield 74%, colourless crystals, mp 114–115
1
°C. IR (ATR): 1736, 1669, 1629, 1553 cm–1; Н NMR (400 MHz, CDCl3)
δ 6.79 (d, J = 1.1 Hz, 1H, H-3),
7.12 (q, J = 1.1 Hz, 1H, H-5), 7.58–7.68 (m, 3H, arom.), 7.88–8.00 (m, 3Н, arom.), 8.10 (d, J = 1.7 Hz, 1Н,
3
arom.); 19F NMR (471 MHz, CDCl3)
δ
–72.3 (s, CF3); 13C NMR (126 MHz, CDCl3)
δ
104.8 (q, JC,F = 3.7
1
Hz, C-5), 113.8, 118.1 (q, JC,F = 273.0 Hz, CF3), 123.0, 127.3, 127.4, 127.9, 128.3, 128.9, 129.6, 131.2,
2
133.0, 134.5, 148.5 (q, JC,F = 39.1 Hz, C-6), 153.1, 159.4; MS (EI, 70 eV) m/z (%) 290 (100, [M]+), 262
(71), 221 (39), 165 (55); HRMS (ESI): calcd for C16H9F3O2 [M]+ 290.05546, found 290.05519.
4.3.7. 4-(2-Thienyl)-6-(trifluoromethyl)-2H-pyran-2-one (7g). Yield 64%, colourless crystals, mp 141–143
1
°C. IR (ATR): 1733, 1668, 1560, 1508 cm–1; Н NMR (400 MHz, CDCl3)
δ 6.60 (d, J = 1.1 Hz, 1H, H-3),
6.93 (d, J = 1.1 Hz, 1Н, H-5), 7.21 (dd, J = 5.0, 3.8 Hz, 1H, H-4'), 7.57 (dd, J = 3.8, 1.1 Hz, 1H, H-3'), 7.61
(dd, J = 5.0, 1.1 Hz, 1H, H-5'); 13C NMR (126 MHz, CDCl3) 104.2 (q, 3JC,F = 3.7 Hz, C-5), 116.1, 117.9 (q,
δ
1JC,F = 273.4 Hz, CF3), 124.2, 127.9, 140.2, 149.3 (q, 2JC,F = 39.7 Hz, C-6), 149.5, 151.1, 158.4; MS (EI, 70
eV) m/z (%) 246 (100, [M]+), 218 (69), 177 (36); HRMS (ESI): calcd for C10H5F3O2S [M]+ 245.99624, found
245.99670.
4.4. Compounds 9a–d
4.4.1. 3-(Trifluoromethyl)indeno[2,1-c]pyran-1,9-dione (9a). A solution of 6a (200 mg, 0.64 mmol) in 96%
H2SO4 (2.0 mL) was heated at 110–125 °C for 10 min. The reaction mixture was cooled to 0 °C and diluted
with H2O (100 mL). The solid that formed was filtered and recrystallized from toluene to give 0.07 g (41%)
1
of 9a, yellow crystals, mp 244–245 °C. IR (KBr) 1776, 1698, 1633, 1599, 1550 cm–1; Н NMR (400 MHz,
CDCl3):
δ
7.14 (s, 1H, Н-4), 7.56–7.60 (m, 1H), 7.62–7.66 (m, 2H), 7.74–7.78 (m, 1H); 19F NMR (376 MHz,
3
CDCl3)
δ
–72.5 (s, CF3); 13C NMR (100 MHz, CDCl3)
δ
99.8 (q, JC,F = 3.5 Hz, C-4), 114.6, 123.1, 125.0,
132.5, 134.4, 134.7, 137.4, 152.7, 156.1 (q, 2JC,F = 39.6 Hz, C-3), 164.8, 188.2 (the quartet of the CF3 carbon
atom was not observed due to its intensity being too low). Anal. Calcd for C13H5F3O3: C, 58.66; H, 1.89.
Found: C, 58.31; H, 1.76.

ACCEPTED MANUSCRIPT
16
4.4.2. 7-Chloro-3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-dione (9b). A mixture of 6b (200 mg, 0.58
mmol), 96% H2SO4 (1.0 mL), and P2O5 (1.0 g, 7.0 mmol) was heated at 120–125 °С for 1–1.5 h. The
reaction mixture was cooled to 0 °C and diluted with H2O (70 mL). The solid that formed was filtered and
recrystallized from p-xylene to give 80 mg (47%) of 9b as orange crystals, mp 255–257 °C. IR (ATR): 1778,
1764, 1716, 1630, 1608, 1582, 1573, 1548 cm–1; 1Н NMR (400 MHz, CDCl3):
= 7.8 Hz, 1H, Н-5), 7.62 (dd, J = 7.8, 1.7 Hz, 1H, Н-6), 7.74 (d, J = 1.7 Hz, 1H, H-8); 19F NMR (376 MHz,
CDCl3): –71.4 (s, CF3). Anal. Calcd for C13H4ClF3O3: C, 51.94; H, 1.34. Found: C, 52.13; H, 1.36.
δ 7.13 (s, 1H, Н-4), 7.53 (d, J
δ
4.4.3. 7-Fluoro-3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-dione (9c). This product was prepared according
to the procedure described for compound 9b. Yield 110 mg (65%), orange crystals, mp 232–234 °C. IR
1
(ATR): 1771, 1700, 1632, 1596, 1548 cm–1; Н NMR (400 MHz, CDCl3):
δ 7.13 (s, 1H, Н-4), 7.31 (td, J =
8.3, 2.3 Hz, 1H, Н-6), 7.47 (dd, J = 6.7, 2.3 Hz, 1H, Н-8), 7.59 (dd, J = 8.0, 4.2 Hz, 1H, H-5). Anal. Calcd
for C13H4F4O3: C, 54.95; H, 1.42. Found: C, 54.94; H, 1.33.
4.4.4. 7-Methyl-3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-dione (9d). This product was prepared according
to the procedure described for compound 9a. Yield 79 mg (61%), orange crystals from petroleum
1
ether/toluene (2:1), mp 210–220 °C (subl.). IR (KBr): 1778, 1698, 1632, 1599, 1550 cm–1; Н NMR (400
MHz, CDCl3):
δ 2.47 (s, 3H, Me), 7.10 (s, 1H, Н-4), 7.41 (d, J = 7.6 Hz, 1H, Н-6), 7.45 (d, J = 7.6 Hz, 1H,
Н-5), 7.57 (s, 1H, H-8); 19F NMR (376 MHz, DMSO-d6):
δ –71.4 (s, CF3). Anal. Calcd for C14H7F3O3: C,
60.01; H, 2.52. Found: C, 59.84; H, 2.53.
4.5. Compounds 10a–c
4.5.1. 2-(Trifluoromethyl)-6H-pyrano[3,4-c]quinoline-4,5-dione (10a). From 9a. A mixture of 96% H2SO4
(0.13 g), P2O5 (0.07 g), and CCl3CO2H (1.0 g) was heated until complete melting and 9a (50 mg, 0.19 mmol)
was added. After that, carefully milled NaN3 (25 mg, 0.38 mmol) in five equal portions was added during 1
h. The reaction mixture was heated at 65 °C for 1.5 h and then diluted with ice H2O (15 mL). The solid that
formed was filtered and recrystallized from ethyl acetate to give 12 mg (23%) of 10a as light yellow crystals,
mp 250 °C (subl.). From 6a. A mixture of 96% H2SO4 (0.27 g), P2O5 (0.13 g), and 6a (0.20 g, 0.64 mmol)
was heated with stirring at 110 °С over 10 min. After that, CCl3CO2H (2.0 g) was added, the reaction
mixture was heated to 60 °С, and NaN3 (84 mg, 1.29 mmol) in several small portions over 0.5 h was added.
The reaction mixture was heated at 65 °C for 1.5 h and then diluted with ice H2O (15 mL), the solid that
formed was filtered, washed with water, and recrystallized from ethyl acetate (the mother liquor was
evaporated and crystallized again) to give 70 mg (39%) of 10a as light yellow crystals, mp 250 °C (subl.). IR
(ATR): 1770, 1651, 1616, 1596, 1538, 1504, 1475 cm–1; 1Н NMR (400 MHz, DMSO-d6):
Hz, 1H, Н-9), 7.38 (d, J = 8.2 Hz, 1H, Н-7), 7.75 (t, 1H, J = 7.6 Hz, Н-8), 8.08 (s, 1H, Н-1), 8.46 (d, J = 8.3
Hz, 1H, Н-10), 12.25 (s, 1H, NH); 19F NMR (376 MHz, DMSO-d6): –70.6 (s, CF3); 13C NMR (126 MHz,
δ 7.33 (t, J = 7.6
δ

ACCEPTED MANUSCRIPT
17
1
DMSO-d6)
δ
101.6, 110.8, 114.1, 115.8, 118.0 (q, JC,F = 273.3 Hz, CF3), 122.6, 126.6, 134.8, 141.1, 147.5
2
(q, JC,F = 38.4 Hz, C-2), 149.1, 154.3, 157.2. Anal. Calcd for C13H6F3NO3: C, 55.53; H, 2.15; N, 4.98.
Found: C, 55.32; H, 2.29; N, 4.90.
4.5.2. 8-Chloro-2-(trifluoromethyl)-6H-pyrano[3,4-c]quinoline-4,5-dione (10b). From 9b. A solution of 9b
(100 mg, 0.33 mmol) in 96% H2SO4 (2.75 g) was heated to 90 °C and NaN3 (28 mg, 0.43 mmol) was added
in several small portions during 0.5 h. Then the reaction mixture was heated at the same temperature for 2.5
h and diluted with ice H2O (10 mL). The solid that formed was filtered, washed with water, and
recrystallized from ethyl acetate to give 59 mg (56%) of 10b as light yellow crystals, mp 280 °C (subl.).
From 6b. A mixture of 96% H2SO4 (9.0 g), P2O5 (5.0 g), and 6b (0.50 g, 1.44 mmol) was heated with
stirring at 110 °С over 1 h. The resulting mixture was cooled to room temperature and NaN3 (187 mg, 2.87
mmol) was added with vigorous stirring. Then the reaction mixture was heated at 90 °C for 2 h and diluted
with ice H2O (20 mL). The solid that formed was filtered, washed with water, and recrystallized from ethyl
acetate (the mother liquor was evaporated and crystallized again) to give 210 mg (49%) of 10b as light
1
yellow crystals, mp 280 °C (subl.). IR (ATR): 1754, 1651, 1614, 1587, 1471 cm–1; Н NMR (400 MHz,
DMSO-d6):
δ
7.37 (d, J = 8.6 Hz, 1H, Н-9), 7.39 (s, 1H, Н-7), 8.08 (s, 1H, Н-1), 8.51 (d, J = 8.6 Hz, 1H, Н-
–70.6 (s, CF3); 13C NMR (100 MHz, DMSO-d6)
10), 12.30 (s, 1H, NH); 19F NMR (376 MHz, DMSO-d6):
δ
δ
102.2, 111.4, 113.6, 115.5, 118.5 (q, 1JC,F = 273.8 Hz, CF3), 123.3, 129.3, 140.0, 142.3, 148.3 (q, 2JC,F = 38.6
Hz, C-2), 149.2, 154.7, 157.6. Anal. Calcd for C13H5ClF3NO3: C, 49.47; H, 1.60; N, 4.44. Found: C, 49.35;
H, 1.56; N, 4.48.
4.5.3. 8-Fluoro-2-(trifluoromethyl)-6H-pyrano[3,4-c]quinoline-4,5-dione (10c). This product was prepared
from 9c (yield 47%) and from 6c (yield 43%) according to the procedures described for compound 10b,
white crystals, mp 295–297 °C. IR (ATR): 1774, 1678, 1664, 1624, 1603, 1515, 1465, 1428 cm–1; 1Н NMR
4
3
(400 MHz, DMSO-d6):
4JH,H = 2.4 Hz, 1H, H-9), 8.06 (s, 1H, Н-1), 8.57 (dd, 3JH,H = 9.0 Hz, 4JH,F = 5.8 Hz, 1H, H-10), 12.31 (s, 1H,
NH); 19F NMR (376 MHz, DMSO-d6): –102.8 (td, J = 9.0, 6.0 Hz, F), –70.6 (s, CF3); 13C NMR (126 MHz,
DMSO-d6)
101.4 (d, 2JC,F = 25.5 Hz), 101.6 (q, 3JC,F = 3.4 Hz, C-1), 109.9, 111.1, 111.3, 117.9 (q, 1JC,F
δ
7.10 (dd, 3JH,F = 9.8 Hz, JH,H = 2.4 Hz, 1H, H-7), 7.22 (td, 3JH,F = JH,H = 8.7 Hz,
δ
δ
=
273.5 Hz, CF3), 130.0 (d, 3JC,F = 11.1 Hz), 143.0 (d, 3JC,F = 13.2 Hz), 147.6 (q, 2JC,F = 38.4 Hz, C-2), 148.7,
1
154.1, 157.2, 165.5 (d, JC,F = 253.6 Hz, C-4'). Anal. Calcd for C13H5F4NO3: C, 52.19; H, 1.68; N, 4.68.
Found: C, 51.95; H, 1.48; N, 4.69.
4.5.4. 4-Methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid (4-methylcarbostyril-3-carboxylic acid) (11).
A solution of 10a (18 mg, 0.06 mmol) and NaOH (40 mg, 1.0 mmol) in 70% ethanol (1 mL) was heated to
reflux with stirring for 1.5 h. Then the reaction mixture was diluted with HCl (1:2, 5 mL) and the formed
precipitate was filtered and recrystallized from 70% ethanol to give 12 mg (92%) of 11 as colourless crystals,
mp 273–274 °C (lit.21 274–276 °C). 1Н NMR (400 MHz, DMSO-d6):
δ 2.56 (s, 3H, Me), 7.29 (ddd, J = 8.2,

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18
7.3, 1.0 Hz, 1H, H-6), 7.37 (dd, J = 8.2, 1.0 Hz, 1H, H-8), 7.60 (ddd, J = 8.2, 7.3, 1.0 Hz, 1H, H-7), 7.88 (dd,
J = 8.2, 1.0 Hz, 1H, H-5), 12.20 (br s, 1H, NH), 13.77 (br s, 1H, OH).
4.6. Compounds 12a,b
4.6.1. 2-Oxo-4-(5-trifluoromethyl-1,2,3-triazol-4-yl)-1,2-dihydroquinoline-3-carboxylic acid (12a).
A
mixture of 10a (50 mg, 0.18 mmol) and NaN3 (23 mg, 0.35 mmol) in DMSO (1 mL) was heated at 120 °C
for 3 h. Then the reaction mixture was diluted with HCl (1:2, 8 mL), the formed precipitate was filtered,
washed with water, and recrystallized from 50% ethanol to give 46 mg (80%) of 12a as white crystals, mp
280 °C (decomp.). IR (ATR): 1721, 1623, 1598, 1551, 1523, 1472, 1453 cm–1; 1Н NMR (400 MHz, DMSO-
d6):
7.5 Hz, 1H, H-7), 12.85 (s, 1H, CO2H), 13.93 (br s, 1H, NH), 16.47 (br s, 1H, NH triaz.); 19F NMR (376
MHz, DMSO-d6):
–59.5 (s, CF3); 13C NMR (126 MHz, DMSO-d6) 116.1, 118.3, 120.8 (q, 1JC,F = 268.4
δ 6.96 (d, J = 7.7 Hz, 1H, H-8), 7.24 (t, J = 7.4 Hz, 1H, H-6), 7.51 (d, J = 8.0 Hz, 1H, H-5), 7.69 (t, J =
δ
δ
Hz, CF3), 123.4, 126.3, 126.4, 132.8, 135.2 (q, 2JC,F = 36.6 Hz, C-5'), 138.2, 159.7, 164.5 (two carbon atoms
were not observed due to their intensity being too low). Anal. Calcd for C13H7F3N4O3: C, 48.16; H, 2.18; N,
17.28. Found: C, 48.30; H, 1.90; N, 17.04.
4.6.2. 7-Chloro-2-oxo-4-(5-trifluoromethyl-1,2,3-triazol-4-yl)-1,2-dihydroquinoline-3-carboxylic acid (12b).
This product was prepared according to the procedure described for compound 12а. Yield 66%, light yellow
1
crystals, mp 286–288 °C (decomp.). IR (ATR): 1705, 1614, 1595, 1494, 1474 cm–1; Н NMR (400 MHz,
DMSO-d6):
2H, NH, OH), 15.0–17.5 (br s, 1H, NH triaz.); 19F NMR (376 MHz, DMSO-d6):
(126 MHz, DMSO-d6)
115.2, 117.0, 120.7 (q, 1JC,F = 268.5 Hz, CF3), 123.4, 128.1, 128.3, 135.3 (q, 2JC,F
δ
7.01 (d, J = 8.6 Hz, 1H, H-6), 7.26 (d, J = 8.6 Hz, 1H, H-5), 7.49 (s, 1H, H-8), 11.0–15.0 (br s,
δ
–59.4 (s, CF3); 13C NMR
δ
=
38.0 Hz, C-5'), 137.0, 139.1, 158.9, 164.5 (two carbon atoms were not observed due to their intensity being
too low). Anal. Calcd for C13H6ClF3N4O3: C, 43.53; H, 1.69; N, 15.62. Found: C, 43.16; H, 1.52; N, 15.57.
References and notes
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