3-(Polyhaloacyl)chromones and their hetero analogues: Synthesis and reactions with amines

Article abstract of DOI:10.1055/s-2006-942508

2-Hydroxy-2-(polyhaloalkyl)chroman-4-ones react with diethoxymethyl acetate at 140-150°C for 15 minutes to give 3-(polyhaloacyl)chromones in good yields. The reactions of these compounds with amines proceeds at C-2 with pyrone ring-opening and formation o

Full text of DOI:10.1055/s-2006-942508

PAPER
2707
3-(Polyhaloacyl)chromones and their Hetero Analogues: Synthesis and
Reactions with Amines
3
-(Polyhaloacyl)ch
y
romones: Sy
a
nthesis and
c
Reactions
h
w
ith
A
mineseslav Ya. Sosnovskikh,* Roman A. Irgashev, Mikhail A. Barabanov
Department of Chemistry, Ural State University, 620083 Ekaterinburg, Russian Federation
Fax +7(343)2615978; E-mail: Vyacheslav.Sosnovskikh@usu.ru
Received 20 April 2006
synthetic utility and the present great interest in 3-formyl-
chromone chemistry.1,7
Abstract: 2-Hydroxy-2-(polyhaloalkyl)chroman-4-ones react with
diethoxymethyl acetate at 140–150 °C for 15 minutes to give 3-
(polyhaloacyl)chromones in good yields. The reactions of these
compounds with amines proceeds at C-2 with pyrone ring-opening
and formation of 2-(alkyl/arylaminomethylene)-2-hydroxy-2-
(polyfluoroalkyl)chroman-4-ones.
The synthesis of specifically trifluoromethylated mole-
cules is an ongoing area of research due to the unique
physical and biological properties imparted by the CF3
group.8 Therefore, the development of simple methods for
the preparation of fluorinated building blocks and their
further utilisation for the synthesis of desired RF-contain-
ing heterocyclic compounds are essential. As a continua-
tion of our studies on the synthetic potential of 2-
(polyfluoroalkyl)chromones, which turned out to be high-
ly reactive substrates in the reactions with N-,9 S-,10 and
C-nucleophiles,11 and owing to the increasing importance
of fluorine-containing heterocycles in biology, pharma-
cology, and industrial applications,12 we decided to devel-
Key words: chroman-4-ones, diethoxymethyl acetate, formylation,
3-(polyhaloacyl)chromones, amines
The synthetic utility of 2-unsubstituted 3-formyl- and 3-
acylchromones derives primarily from the reactivity of
their three electron-deficient centres at C-2, C-4 and the 3-
formyl or 3-acyl groups. The majority of the reactions
with these compounds are nucleophilic additions with
concomitant opening of the pyrone ring leading to various
types of heterocyclic products. In addition, some of them
can react as heterodienes and as dienophiles.1
op
a
convenient and general synthesis of 3-
(polyhaloacyl)chromones as useful precursors of a wide
variety of heterocycles with a RHlg group.13
Chromones unsubstituted at C-2 and with 3-formyl or 3-
acetyl groups were first prepared in low yields from 3-(2-
hydroxyphenyl)-3-oxopropanal and 1-(2-hydroxyphen-
yl)butane-1,3-dione with ethyl orthoformate and acetic
anhydride.2 The synthesis of 3-acetylchromone has also
been achieved by acetylation of 3-(2-hydroxyphenyl)-3-
oxopropanal with acetic anhydride/sodium acetate2,3 and
formylation of 1-(2-hydroxyphenyl)butane-1,3-dione
with acetic formic anhydride/sodium formate4a and di-
methylformamide dimethyl acetal.4b In 1973, a convenient
synthesis of 3-formylchromone from 2-hydroxyacetophe-
none and the Vilsmeier reagent was reported.5
Our new approach to 3-(polyhaloacyl)chromones follows
the same design as many older methods in that an appro-
priately substituted 1,3-diketone is reacted with a one car-
bon unit of the correct oxidation level. In view of the
observation that the readily available diethoxymethyl ac-
etate reacts with 4-(acylacetyl)-1-phenyl-2-pyrazolin-5-
ones to yield 5-acyl-4-oxo-1H-pyrano[2,3-c]pyrazoles,14
we decided to use diethoxymethyl acetate as an active
formylating agent for the synthesis of chromones having
a polyhaloacyl group at the 3-position. It should be noted
that previously this cyclisation reagent was successfully
employed for the preparation of various nitrogen-contain-
ing heterocycles, for example purines from the appropri-
ate pyrimidines.15
3-Polyfluoroacyl substituted chromones, despite their po-
tential interest as building blocks in organic synthesis for
the construction of more complex polyfluoroalkyl-con-
taining heterocycles have not received much attention,
probably owing to the lack of general methods for the
preparation of these compounds. To the best of our knowl-
edge, there has been only one report on the preparation of
3-(trifluoroacetyl)- and 3-(trichloroacetyl)chromones by
the reaction of 3-(dimethylamino)-1-(2-hydroxyphen-
yl)prop-2-en-1-one with trifluoro- and trichloroacetic an-
hydrides.6 The procedure for the synthesis of 3-
(trihaloacetyl)chromone and its spectroscopic data were
not presented, a surprising fact in view of their potential
We report here a practical preparation of 3-(polyfluoro-
acyl)chromones characterised by the use of an excess (6
equiv) of diethoxymethyl acetate as both the formylating
agent and solvent, starting from the condensation products
of 2-hydroxyacetophenones with RFCO2Et. The latter
compounds exist in a solution of CDCl3 as a mixture of
ring-chain tautomers 1a–l with the cyclic hemiketal form
predominating.16 The reaction is simply carried out by
heating the components for 15 minutes at 140–150 °C,
followed by dilution of the resulting mixture with hexane
and filtration of the crystalline 3-(polyfluoro-
acyl)chromones 2a–l (Table 1). Classical ethyl orthofor-
mate–acetic anhydride mixture failed to give useful
results. Compounds 2 were obtained in good yields with-
out the formation of any side products arising from
SYNTHESIS 2006, No. 16, pp 2707–2718
x
x.
x
x
.
2
0
0
6
Advanced online publication: 19.07.2006
DOI: 10.1055/s-2006-942508; Art ID: Z08106SS
© Georg Thieme Verlag Stuttgart · New York

2708
V. Ya. Sosnovskikh et al.
PAPER
Table 1 Synthesis of 3-(Polyhaloacyl)chromones 2 by Reaction of Chromanones 1 with Diethoxymethyl Acetate
Chromone
RHlg
R1
H
R2
H
R3
H
R4
H
H
H
H
H
H
H
Br
H
H
H
H
H
H
Yield (%)
77
Mp (°C)
165–166
119–120
133–134
2a
2b
2c
2d
2e
2f
CF2H
CF2H
CF2H
CF3
H
Me
Cl
H
H
62
H
H
73
H
H
74
124–125 (125 °C)6
114–115
CF3
H
Me
H
H
64
CF3
Me
H
Me
H
67
129–130
2g
2h
2i
CF3
NO2
Br
H
81
130–131
CF3
H
H
53
116–117
(CF2)2H
(CF2)2H
(CF2)2H
(CF2)2H
CCl3
H
H
77
104–105
2j
H
Me
H
H
69
104–105
2k
2l
Me
H
Me
OMe
H
73
109–110
H
63
105–106
2m
2n
H
H
30
117–118 (120 °C)6
114–115
CCl3
H
H
OMe
78
Michael-type additions onto the C=C bond of the pyrone The reaction appears to be general and a variety of substi-
moiety or dehydration of the starting chromanones 1 to 2- tuted 3-(polyfluoroacyl)chromones 2a–l were obtained by
(polyfluoroalkyl)chromones. However, in marked con- varying the 2-hydroxy-2-(polyfluoroalkyl)chroman-4-
trast to the 3-formyl- and 3-acetylchromones,2–5 the ones 1a–l. It is important that trichloromethyl derivatives
chromones obtained in this work were prone to facile and 1m and 1n17 also reacted with diethoxymethyl acetate un-
reversible covalent hydrate formation as observed from der the same reaction conditions to give 3-(trichloro-
1
19
their H and F NMR spectra, which contained two sets acetyl)chromones 2m and 2n (Table 1). It should be noted
of signals. The diagnostic signal for H-2 in chromones 2, that chromones 2 were essentially pure and the yields cit-
which appeared at 8.5–8.7 ppm, was shifted upfield in hy- ed in the Table 1 were determined before recrystallisation.
drates 3 (8.3–8.4 ppm). A plausible pathway leading to the The structures of the chromones 2 was confirmed by ele-
formation of these compounds is outlined in Scheme 1.
mental analysis, 1H, 19F NMR, and IR spectroscopy.
We consider the present method a useful and convenient
alternative to the existing one.6 Although in some cases
the reaction affords chromones 2 in moderate yields, this
approach has advantages with regard to ease of operation
and the ready availability of starting materials. The meth-
od is experimentally simple and may be of value in RF-
containing building blocks chemistry since chromones 2
may be regarded as latent 1,3-dicarbonyl compounds,
having at the 2-position a masked salicyloyl fragment.
H
R1
O
O
R1
O
O
R2
R3
R2
R3
RHlg
OH
RHlg
OH
1a–n
R4
R4
AcO–
+
+CH(OEt)2
AcO-CH(OEt)2
– AcOH
R1
R1
O
O
O
O
O
R2
R3
On the basis of the elemental analyses and the IR spectra
in KBr (the absorption band of the OH group at around
3300–3370 cm–1 is absent and two bands of the C=O
groups at 1710–1720 and 1650 cm–1 are present), it is pos-
sible to assume that compounds 2a–c (RF = CF2H) and 2i–
l (RF = CF2CF2H) in the solid state are pure substances
and exist in equilibrium in solution between the non-hy-
drate 2 and hydrate 3 due to water present in CDCl3 or
DMSO-d6. The ratio of 2 and 3 depends on the number of
fluorine atoms present in the RF group [1–2% of 3 for
RF = CF2H and 6–8% for RF = (CF2)2H]. At the same
time, trifluoro- and trichloromethylated products are mix-
R2
RHlg
RHlg
CH(OEt)2
– EtOH
R3
OEt
– EtOH
O
OH
R4
R1
R4
R1
H
O
O
O
O
OH
R2
R3
R2
R3
H2O
RHlg
RHlg
O
R4
R4
3a–n
2a–n
Scheme 1
Synthesis 2006, No. 16, 2707–2718 © Thieme Stuttgart · New York

PAPER
3-(Polyhaloacyl)chromones: Synthesis and Reactions with Amines
2709
H
tures of 2d–h, 2m and 2n and 3d–h, 2m and 2n as evi-
denced by their IR spectra (the band corresponding to the
OH group at 3300–3370 cm–1 and two bands correspond-
ing to the C=O groups at 1720–1740 and 1640–1680 cm–1
are present) and the combustion analysis (0.2–0.8 mole-
cule of H2O). The 1H and 19F NMR spectra of these com-
pounds in a solution of CDCl3 contained two sets of
signals, one of which belonged to chromones 2 (40–80%)
and another set was attributed to their hydrates 3 (the
amount of 3 present increased with storage). The facile
formation of hydrates 3 probably arises from the high hy-
drophilicity of chromones 2 due to the electrophilic char-
acter of the carbonyl carbon atom connected to a
polyhaloalkyl substituent and the formation of an in-
tramolecular hydrogen bond between the OH and C=O
groups. The facile formation of covalent hydrates from
the CF3-containing b-dicarbonyl compounds is a well-
known phenomenon.18
Me
O
O
O
Me
N
O
O
RF
OH
RF
Me
N
H
Me
5a–c
AcOCH(OEt)2
H
Me
N
O
O
Me
N
O
O
O
OH
RF
+ H2O
RF
Me
O
Me
7a–c
6a–c
RF = CF2H (a), CF3 (b), (CF2)2H (c)
Scheme 3
ysis. The 1H NMR spectrum of this compound showed, in
particular, two singlets at 8.56 and 8.35 ppm assigned to
the olefinic protons of 6b and 7b, respectively. In the 19F
NMR spectrum the CF3 group manifests itself as a singlet
at 87.1 and 74.9 ppm for 6b and 7b, respectively. The IR
spectrum showed strong absorption bands in the range
3400–3210 cm–1 (O–H) and 1730–1650 cm–1 (C=O) re-
gions.
As expected, the reaction of chromones 2d and 2l with
alkyl orthoformates in the corresponding alcohol contain-
ing HCl or p-TsOH resulted in the formation of hemiket-
als 4a–c in 55–66% yields (Scheme 2), but all our
attempts to prepare ketals using methanol or ethylene gly-
col were fruitless. For instance, attempts to obtain the ket-
als under the same conditions that had previously been
used for the acetalisation of 3-formylchromone19 failed.
The failure of the latter reaction possibly results from the
destabilisation of the intermediate carbocation by the CF3
group. In the cases of 4b and 4c, the attachment of the
ethoxy group to a chiral centre is clearly supported by the
1H NMR spectra, in which the ethyl group displays an
ABX3 instead of the usual A2X3 spin pattern. Note that the
starting chromanone 1k resulted when chromone 2k was
boiled with ethanol in the presence of Et3N.19c
A Claisen condensation of 4-acetyl-5-hydroxy-3-methyl-
1-phenylpyrazole with ethyl di(tri)fluoroacetates in the
presence of lithium hydride in THF afforded diketones 8a
and 8b in 93% and 87% yields, respectively. These com-
pounds, in solution with CDCl3, exist almost exclusively
in their keto-enol forms stabilised by two intramolecular
1
hydrogen bonds (Scheme 4). The H NMR spectra of 8a
and 8b exhibit a singlet corresponding to the olefinic pro-
ton at 6.16 and 6.24 ppm and two strongly broadened sin-
glets of the enol (14.4 and 14.5 ppm) and pyrazole (11.7
ppm) hydroxyls. This is in accordance with the data for
non-fluorinated analogues of compounds 8a and 8b de-
scribed by Gelin et al.14 According to the relative integral
intensity of the CH2 group (singlet at 4.14–4.16 ppm), the
contents of the diketo form did not exceed 3–4% that is
appreciably lower than in the case of 4-acylacetyl-5-hy-
droxy-1-phenylpyrazoles (6–20%).14
H
O
O
O
O
OR2
RF
HC(R2O)3
R2OH, H+
RF
R1
O
R1
O
2d,l
4a–c
RF = CF3, R1 = H, R2 = Me (4a);
RF = CF3, R1 = H, R2 = Et (4b);
RF = (CF2)2H, R1 = MeO, R2 = Et (4c)
When compound 8a was treated with diethoxymethyl
acetate at 140–150 °C for 15 minutes, 5-(difluoroacetyl)-
3-methyl-1-phenylpyrano[2,3-c]pyrazol-4(1H)-one (9)
was obtained in 64% yield, whereas the analogous reac-
tion with 8b gave covalent hydrate 10 as the only isolated
product (yield 60%). The structure of 10 was confirmed
Scheme 2
Extending our studies to the synthesis of hetero analogues
of 3-polyfluoroacylchromones 2, we found that b-dike-
tones 5a–c, prepared from 3-acetyl-4,6-dimethyl-2-pyri-
done and RFCO2Et in the presence of LiH in dioxane and
existing in both CDCl3 and DMSO-d6 as a mixture of ring-
chain tautomers,20 also undergo this type of reaction with
diethoxymethyl acetate under the same experimental con-
ditions (Scheme 3).
1
by elemental analysis, IR and H NMR spectra. The IR
spectrum in KBr displayed the characteristic absorption
band for the pyrone ring carbonyl at 1654 cm–1 and a
broad band for the hydroxyl groups at 3220 cm–1. The 1H
NMR spectrum of the same sample in DMSO-d6 (10 is in-
soluble in CDCl3) showed two singlets at 8.25 ppm (2 H)
and 8.48 ppm (1 H) due to the two OH groups and the H-
6 proton, respectively, and the remaining signals corre-
spond to the other protons contained in the substituents.
Again, the trifluoromethylated azachromone was ob-
tained as a mixture of non-hydrate 6b and hydrate 7b (1:1)
as can be seen in both the spectral data and elemental anal-
Synthesis 2006, No. 16, 2707–2718 © Thieme Stuttgart · New York

2710
V. Ya. Sosnovskikh et al.
PAPER
H
RF
O
RF
R2
O
O
O
O
N
O
R2NH2
RF
Me
N
Me
H
R1
R1
OH
RF
O
O
H
O
H
N
O
O
N
N
2a,d,g,l
11a–j
Ph
Ph
RF = CF2H (8a), CF3 (8b)
HN
O
O
N
AcOCH(OEt)2
H
O
O
O
O
H2N
O
+
CF3COO
Me
Me
O
OH
CF3
OH
CF2H
N
N
N
N
Scheme 5
O
O
Ph
Ph
9
10
Scheme 4
line reacted with 2d under the same reaction conditions to
give a 1:1 mixture of the previously known aminoenone,
trans-1-(2-hydroxyphenyl)-3-morpholinoprop-2-en-1-
one23 and morpholinium trifluoroacetate in 74% yield. In
this case, detrifluoroacetylation took place as an unwanted
reaction.
The presence of the electron-withdrawing CORF group in
compounds 2 enhances the electrophilicity of the C-2
atom of the pyrone ring, from the attack of which, as a
rule, the interaction of chromones with nucleophilic
agents begins.21,22 Due to this fact, 3-polyfluoroacyl-
chromones and their hetero analogues are promising sub-
strates for the syntheses of new compounds containing the
RF group. Indeed, we have found that the reaction of
chromones 2a, 2d, 2g and 2l with primary amines in
methanol at room temperature for two days afforded
3-(alkyl/arylaminomethylene)-2-hydroxy-2-(polyfluoro-
alkyl)chroman-4-ones 11a–j in 42–78% yields. Both ali-
phatic and aromatic amines with electron-donating or
electron-withdrawing groups can be employed. The reac-
tion includes the nucleophilic 1,4-addition of the amine
with concomitant opening of the pyrone ring and subse-
quent intramolecular cyclisation of the intermediate at the
CORF group. The driving force for the process is the sta-
bilisation of the enamines 11 by a hydrogen bond between
the pyranone carbonyl oxygen and the hydrogen of the
NH group (Scheme 5). Unlike primary amines, morpho-
It should be noted that the reaction between equimolar
quantities of 3-formylchromone and a primary aromatic
amine leads to a mixture of the 3-(aryliminometh-
yl)chromone and 2-arylamino-3-(arylaminomethyl-
ene)chroman-4-one, making the isolation of pure
compounds difficult.24 This different behaviour is not un-
expected, considering that the RF group complicates the
dehydration stage. Recently, 3-(arylaminomethylene)-2-
hydroxychroman-4-ones were prepared by the acid-catal-
ysed reaction of 3-formylchromones with aromatic amino
carboxylic acids in benzene or toluene.25
The structures of compounds 11a–j are consistent with the
1
IR, H and 19F NMR spectra. The IR spectra of 11a–j
showed absorption bands in two ranges 3290–3130 and
1650–1600 cm–1 due to the OH and NH groups and the
1
aminoenone fragment. A characteristic feature of the H
NMR spectra in DMSO-d6 is the appearance of one sin-
Table 2 Reaction of 3-(Polyfluoroacyl)chromones 2 with Primary Amines
Compd
11a
11b
11c
11d
11e
11f
RF
R1
R2
Yield (%)
Mp (°C)
149–150
178–179
133–134
122–123
143–144
184–185
194–195
213–214
221–222
182–183
CF2H
CF2H
CF3
H
Bn
61
75
50
42
76
62
77
68
61
78
H
p-MeOC6H4
c-C6H11
Bn
H
CF3
H
CF3
H
Ph
CF3
H
p-MeC6H4
p-MeOC6H4
p-NO2C6H4
Ph
11g
11h
11i
CF3
H
CF3
H
CF3
6-NO2
7-OMe
11j
(CF2)2H
p-MeOC6H4
Synthesis 2006, No. 16, 2707–2718 © Thieme Stuttgart · New York

PAPER
3-(Polyhaloacyl)chromones: Synthesis and Reactions with Amines
2711
6a,b
glet at 8.3–9.6 ppm for the OH proton (4.0–4.2 ppm in
CDCl3), and two AX doublets (JAX = 12.6–13.3 Hz) at
7.8–8.1 and 12.5–12.6 ppm for the =CH and NH protons,
respectively. The addition of CD3CO2D to a solution of
11e in DMSO-d6 results in the disappearance of the sig-
nals due to OH and NH protons, whereas the doublet at
8.00 ppm (=CH) turns into a singlet.
R1R2NH
R1
H
Me
O
O
Me
N
O
O
N
RF
NR1R2
OH
RF
Me
N
H
O
Me
12a–h
13e–h
Since the key step of the transformation 2→11 is the in-
teraction of primary amines with the C-2 atom, we were
interested in introducing 8-aza-5,7-dimethyl-3-(polyfluo-
roacyl)chromones 6a and 6b into this reaction. In this
case, opening of the pyrone ring results in the appearance
of the amide-type oxygen atom with decreased nucleophi-
licity instead of the phenol OH group. This allowed us to
expect the isolation of open-chained products. In fact,
chromone 6a in THF or MeOH reacted with isopropyl-
amine and secondary cyclic amines (pyrrolidine, piperi-
dine and morpholine) to give acyclic compounds 12a–d as
the only geometric isomer (configuration of the double
bond was not determined); no detectable amount of the
cyclic isomer was found in the 1H NMR spectra of these
compounds in DMSO-d6. However, the reactions of 6a
with aromatic amines (aniline and p-anisidine) led to the
adducts as a mixture of ring-chain isomers (4–8% of cy-
clic form 13e and 13f in DMSO-d6). It is interesting that
an increase from two to three fluorine atoms in a polyflu-
oroacyl group resulted in an increase in the cyclic isomer,
for 13g and 13h up to 56–64%; this fact indicated that the
CF3 group is more capable of stabilising hemiketal 13
(Scheme 6). In the crystalline state, compounds 12a–h ex-
ist in a cyclic hemiketal form 13 as evidenced by their IR
spectra recorded in KBr (the absorption band of the RFCO
group at around 1700 cm–1 is absent and bands in the two
ranges 3280–2640 and 1660–1580 cm–1 due to the OH and
NH groups and the aminoenone fragment are present).
The products 12 appeared as colourless or yellow com-
pounds decomposing near their melting points.
Scheme 6
action of 10 with less basic p-nitroaniline ceased at the py-
rone ring-opening step, resulting in trifluoroacetylated
acyclic compound 15 (DMSO-d6) in 72% yield
(Scheme 7). On the basis of the elemental analysis data
and a broadened singlet at 3.6 ppm in the 1H NMR spec-
trum, one can conclude that this compound exists as a hy-
drate.
O
Me
PhNH2
NHPh
9,10
N
N
OH
Ph
14
O
O
Me
N
p-O2NC6H4NH2
CF3
NHC6H4NO2-p
10
N
OH
Ph
15
Scheme 7
Thus, the reaction of 3-(polyfluoroacyl)chromones and
their hetero analogues with amines starts from attack at C-
2 of the pyrone ring and affords, depending on the nature
of the reactant and substrate, compounds of two types:
RFCO-containing aminoenones, which exist only in a cy-
clic form in a solid state, and aminoenones without the
RFCO group.
It was also found that upon reaction with aniline, pyrano-
pyrazoles 9 and 10 lost the di(tri)fluoroacetyl group and
gave aminoenone 14 as a mixture of E- and Z-isomers in
a ratio of 9:1 (Jtrans = 12.5 Hz, Jcis = 7.9 Hz), while the re-
In conclusion, we have developed an easy and convenient
one-step synthesis of 3-(polyhaloacyl)chromones and
Table 3 Reaction of 8-Aza-5,7-dimethyl-3-(polyfluoroacyl)chromones 6a and 6b with Amines
12
a
b
c
RF
R1
R2
H
Ratio of 12/13
100:0
Yield (%)
Mp (°C)
186–187
221–222
216–217
217–218
232–234
234–235
233–235
182–183
CF2H
CF2H
CF2H
CF2H
CF2H
CF2H
CF3
i-Pr
72
54
74
51
88
86
76
52
(CH2)4
(CH2)5
(CH2)2O(CH2)2
p-MeOC6H4
Ph
100:0
100:0
d
e
100:0
H
H
H
H
96:4
f
92:8
g
h
p-MeOC6H4
Ph
44:56
CF3
36:64
Synthesis 2006, No. 16, 2707–2718 © Thieme Stuttgart · New York

2712
V. Ya. Sosnovskikh et al.
PAPER
their hetero analogues, starting from readily obtainable 2- synthesis of other useful organic materials with polyfluo-
hydroxy-2-(polyhaloalkyl)chroman-4-ones and commer- roalkyl and trichloromethyl groups.
cially available diethoxymethyl acetate. These com-
pounds are of much interest as reactive precursors in the
Table 4 Analytical and Spectral Data for 3-(Polyhaloacyl)chromones 2a–na
Chromone/
Hydrate
Molecular
formula
IR (KBr, cm–1)
1H NMR (CDCl3)
d, J (Hz)
2ab,c
C11H6F2O3
3076, 1711, 1654, 6.97 (t, 2JH,F = 53.3, 1 H, CF2H), 7.54 (t, oJ = 7.6, 1 H, H-6), 7.57 (d, oJ = 8.4,
1614, 1560
1 H, H-8), 7.79 (ddd, oJ = 8.6, 7.2, mJ = 1.6, 1 H, H-7), 8.30 (dd, oJ = 8.0,
mJ = 1.6, 1 H, H-5), 8.68 (s, 1 H, H-2)
3a (1%)
5.47 (s, 2 H, 2 × OH), 5.78 (t, 2JH,F = 56.1, 1 H, CF2H), 8.35 (s, 1 H, H-2)
2b
C12H8F2O3
3063, 1718, 1654, 2.50 (s, 3 H, Me), 6.97 (t, 2JH,F = 53.3, 1 H, CF2H), 7.46 (d, oJ = 8.5, 1 H, H-
1620, 1600, 1561 8), 7.58 (dd, oJ = 8.5, mJ = 2.1, 1 H, H-7), 8.07 (br d, mJ = ca. 1.5, 1 H, H-5),
8.65 (s, 1 H, H-2)
3b (2%)
2.47 (s, 3 H, Me), 5.51 (s, 2 H, 2 × OH), 5.77 (t, 2JH,F = 56.1, 1 H, CF2H), 8.32
(s, 1 H, H-2)
2c
C11H5ClF2O3
3085, 1717, 1654, 6.93 (t, 2JH,F = 53.2, 1 H, CF2H), 7.54 (d, oJ = 8.9, 1 H, H-8), 7.73 (dd,
1610, 1560
oJ = 8.9, mJ = 2.6, 1 H, H-7), 8.25 (d, mJ = 2.6, 1 H, H-5), 8.66 (s, 1 H, H-2)
5.31 (s, 2 H, 2 × OH), 5.80 (t, 2JH,F = 56.0, 1 H, CF2H), 8.34 (s, 1 H, H-2)
3c (1%)
2dd
C11H5F3O3⋅
0.5H2O
3343, 1640, 1599, 7.50–7.58 (m, 2 H, H-6, H-8), 7.79 (ddd, oJ = 8.6, 7.0, mJ = 1.7, 1 H, H-7),
1573
8.30 (dd, oJ = 8.0, mJ = 1.7, 1 H, H-5), 8.62 (s, 1 H, H-2)
3d (50%)
6.06 (s, 2 H, 2 × OH), 7.50–7.58 (m, 2 H, H-6, H-8), 7.78 (ddd, oJ = 8.6, 7.0,
mJ = 1.7, 1 H, H-7), 8.26 (dd, oJ = 8.0, mJ = 1.7, 1 H, H-5), 8.40 (s, 1 H, H-2)
2e
C12H7F3O3
3309, 3059, 1718, 2.49 (s, 3 H, Me), 7.44 (d, oJ = 8.6, 1 H, H-8), 7.57 (ddq, oJ = 8.6, mJ = 2.0,
1664, 1635, 1601, 4JH,CH3 = 0.6, 1 H, H-7), 8.07 (dq, mJ = 2.0, 4JH,CH3 = 0.6, 1 H, H-5), 8.59 (s,
1558
1 H, H-2)
3e (30%)
2.49 (s, 3 H, Me), 6.16 (s, 2 H, 2 × OH), 7.45 (d, oJ = 8.6, 1 H, H-8), 7.59
(ddq, oJ = 8.6, mJ = 2.0, 4J = 0.6, 1 H, H-7), 8.02 (dq, mJ = 2.0, 4J = 0.6, 1 H,
H-5), 8.37 (s, 1 H, H-2)
2f
C13H9F3O3⋅
0.8H2O
3337, 1638, 1584, 2.45 (s, 3 H, Me), 2.83 (s, 3 H, Me), 7.06 (s, 1 H, H-6), 7.15 (s, 1 H, H-8),
1559, 1517
8.44 (s, 1 H, H-2)
3f (65%)
2.45 (s, 3 H, Me), 2.80 (s, 3 H, Me), 6.24 (s, 2 H, 2 × OH), 7.03 (s, 1 H, H-
6), 7.15 (s, 1 H, H-8), 8.24 (s, 1 H, H-2)
2g
C11H4F3NO5⋅
0.25H2O
3352, 3104, 3058, 7.76 (dd, oJ = 9.2, pJ = 0.3, 1 H, H-8), 8.61 (dd, oJ = 9.2, mJ = 2.8, 1 H, H-7),
1717, 1680, 1630, 8.66 (s, 1 H, H-2), 9.15 (dd, mJ = 2.8, pJ = 0.3, 1 H, H-5)
1553, 1536
3g (45%)
5.82 (s, 2 H, 2 × OH), 7.75 (dd, oJ = 9.2, pJ = 0.3, 1 H, H-8), 8.45 (s, 1 H, H-
2), 8.61 (dd, oJ = 9.2, mJ = 2.8, 1 H, H-7), 9.12 (dd, mJ = 2.8, pJ = 0.3, 1 H, H-
5)
2h
C11H3Br2F3O3⋅
0.5H2O
3369, 1638, 1589, 8.11 (d, mJ = 2.3, 1 H, H-7), 8.36 (d, mJ = 2.3, 1 H, H-5), 8.67 (s, 1 H, H-2)
1555
3h (57%)
2ie,f
5.79 (s, 2 H, 2 × OH), 8.13 (d, mJ = 2.3, 1 H, H-7), 8.32 (d, mJ = 2.3, 1 H, H-
5), 8.47 (s, 1 H, H-2)
C12H6F4O3
3077, 1718, 1650, 6.80 (tt, 2JH,F = 53.3, 3JH,F = 5.8, 1 H, CF2CF2H,), 7.54 (ddd, oJ = 8.0, 7.2,
1614, 1561
mJ = 1.0, 1 H, H-6), 7.57 (ddd, oJ = 8.5, mJ = 1.0, pJ = 0.4, 1 H, H-8), 7.79
(ddd, oJ = 8.6, 7.2, mJ = 1.7, 1 H, H-7), 8.27 (ddd, oJ = 8.0, mJ = 1.7, pJ = 0.4,
1 H, H-5), 8.55 (s, 1 H, H-2)
3i (6%)
6.28 (tt, 2JH,F = 53.2, 3JH,F = 6.2, 1 H, CF2CF2H), 6.31 (s, 2 H, 2 × OH), 7.51
(ddd, oJ = 8.0, 7.2, mJ = 1.0, 1 H, H-6), 7.57 (dd, oJ = 8.5, mJ = 1.0, 1 H, H-8),
7.79 (ddd, oJ = 8.6, 7.2, mJ = 1.7, 1 H, H-7), 8.23 (dd, oJ = 8.0, mJ = 1.7, 1 H,
H-5), 8.37 (s, 1 H, H-2)
Synthesis 2006, No. 16, 2707–2718 © Thieme Stuttgart · New York

PAPER
3-(Polyhaloacyl)chromones: Synthesis and Reactions with Amines
2713
Table 4 Analytical and Spectral Data for 3-(Polyhaloacyl)chromones 2a–na (continued)
Chromone/
Hydrate
Molecular
formula
IR (KBr, cm–1)
1H NMR (CDCl3)
d, J (Hz)
2j
C13H8F4O3
C14H10F4O3
C13H8F4O4
3064, 1715, 1648, 2.50 (s, 3 H, Me), 6.81 (tt, 2JH,F = 53.3, 3JH,F = 5.8, 1 H, CF2CF2H), 7.46 (d,
1619, 1601, 1560 oJ = 8.5, 1 H, H-8), 7.59 (ddq, oJ = 8.5, mJ = 2.3, 4JH,CH3 = 0.6, 1 H, H-7), 8.05
(br s, 1 H, H-5), 8.53 (s, 1 H, H-2)
3j (6%)
2k
6.27 (s, 2 H, 2 × OH), 6.28 (tt, 2JH,F = 53.2, 3JH,F = 6.2, 1 H, CF2CF2H), 8.02
(br s, 1 H, H-5), 8.35 (s, 1 H, H-2)
3094, 1720, 1650, 2.45 (s, 3 H, Me), 2.80 (s, 3 H, Me), 6.78 (tt, 2JH,F = 53.3, 3JH,F = 5.8, 1 H,
1621, 1599, 1554 CF2CF2H), 7.06 (s, 1 H, Ar), 7.15 (s, 1 H, Ar), 8.36 (s, 1 H, H-2)
3k (8%)
2.45 (s, 3 H, Me), 2.78 (s, 3 H, Me), 6.27 (tt, 2JH,F = 53.2, 3JH,F = 6.3, 1 H,
CF2CF2H), 6.41 (s, 2 H, 2 × OH), 7.03 (s, 1 H, Ar), 7.15 (s, 1 H, Ar), 8.22 (s,
1 H, H-2)
2l
3077, 1711, 1657, 3.94 (s, 3 H, OMe), 6.83 (tt, 2JH,F = 53.3, 3JH,F = 5.8, 1 H, CF2CF2H,), 6.93 (d,
1621, 1557, 1502 oJ = 2.3, 1 H, H-8), 7.07 (dd, oJ = 8.9, mJ = 2.3, 1 H, H-6), 8.16 (d, oJ = 8.9, 1
H, H-5), 8.47 (s, 1 H, H-2)
3l (8%)
2m
3.93 (s, 3 H, OMe), 6.36 (s, 2 H, 2 × OH), 6.28 (tt, 2JH,F = 53.2, 3JH,F = 6.1, 1
H, CF2CF2H), 6.90 (d, oJ = 2.3, 1 H, H-8), 7.03 (dd, oJ = 8.9, mJ = 2.3, 1 H,
H-6), 8.11 (d, oJ = 8.9, 1 H, H-5), 8.28 (s, 1 H, H-2)
C11H5Cl3O3
3202, 3081, 1742, 7.51 (ddd, oJ = 8.0, 7.2, mJ = 1.0, 1 H, H-6), 7.54 (d, oJ = 8.6, 1 H, H-8), 7.77
1643, 1618, 1569 (ddd, oJ = 8.6, 7.2, mJ = 1.7, 1 H, H-7), 8.28 (dd, oJ = 8.0, mJ = 1.7, 1 H, H-5),
8.57 (s, 1 H, H-2)
3m (20%)
6.66 (s, 2 H, 2 × OH), 7.52 (m, 1 H, H-6), 7.57 (d, oJ = 8.5, 1 H, H-8), 7.79
(ddd, oJ = 8.7, 7.2, mJ = 1.7, 1 H, H-7), 8.27 (dd, oJ = 8.0, mJ = 1.7, 1 H, H-5),
8.60 (s, 1 H, H-2)
2n
C12H7Cl3O4
3355, 1743, 1635, 3.93 (s, 3 H, OMe), 6.90 (d, oJ = 2.4, 1 H, H-8), 7.05 (dd, oJ = 8.9, mJ = 2.4,
1581, 1566, 1507 1 H, H-6), 8.17 (d, oJ = 8.9, 1 H, H-5), 8.48 (s, 1 H, H-2)
3n (29%)
3.94 (s, 3 H, OMe), 6.78 (s, 2 H, 2 × OH), 6.92 (d, oJ = 2.4, 1 H, H-8), 7.07
(dd, oJ = 8.9, mJ = 2.4, 1 H, H-6), 8.15 (d, oJ = 8.9, 1 H, H-5), 8.51 (s, 1 H, H-
2)
a Elemental analyses were within allowed error, C 0.35; H 0.39.
b 13C NMR (CDCl3): d = 109.03 (t, 1JC,F = 247.6 Hz), 118.45, 120.25, 124.74, 126.50, 126.97, 135.10, 155.84, 162.85, 174.42, 186.51 (t,
2JC,F = 25.6 Hz).
c 2a 19F NMR (CDCl3): d = 30.81 (d, 2JF,H = 53.3 Hz, HCF2); 3a 19F NMR (CDCl3, 2%): d = 28.72 (d, 2JF,H = 56.1 Hz, HCF2).
d 2d 19F NMR (CDCl3): d = 86.93 (s, CF3); 3d 19F NMR (CDCl3, 50%): d = 74.85 (s, CF3).
e 13C NMR (CDCl3): d = 109.07 (tt, 1JC,F = 252.0 Hz, 2JC,F = 30.5 Hz), 110.54 (tt, 1JC,F = 262.1 Hz, 2JC,F = 27.4 Hz), 118.40, 120.85, 124.61,
126.39, 127.03, 135.17, 155.69, 162.30 (t, 4JC,F = 2.2 Hz), 173.69, 185.58 (t, 2JC,F = 29.3 Hz).
f 2i 19F NMR (CDCl3): d = 24.06 (dt, 2JH,F = 53.3 Hz, 3JF,F = 7.3 Hz HCF2CF2), 38.73 (td, 3JF,F = 7.3 Hz, 3JF,H = 5.8 Hz, HCF2CF2); 3i 19F
NMR (CDCl3, 10%): d =25.39 (dt, 2JF,H = 53.1 Hz, 3JF,F = 7.7 Hz, HCF2CF2, 2JF,H = 53.1 Hz, 3JF,F = 7.7 Hz), 30.78 (q, 3JF,F = 3JF,H = ca. 7.0
Hz, HCF2CF2).
Table 5 Analytical and Spectral Data for Compounds 11a–j and 12a–ha
Compd
Molecular
formula
IR (KBr, cm–1)
1H NMR (DMSO-d6) d, J (Hz)
11ab
C18H15F2NO3
C18H15F2NO4
3240, 1643, 1609, 4.12 (br s, 1 H, OH), 4.41 (d, J = 6.1, 2 H, CH2), 5.70 (t, 2JH,F = 56.2, 1 H,
1594, 1540
CF2H), 6.94 (dd, oJ = 8.2, mJ = 0.9, 1 H, H-8), 7.05 (ddd, oJ = 7.8, 7.2,
mJ = 0.9, 1 H, H-6), 7.23–7.43 (m, 7 H, Ph, H-7, =CH), 7.86 (dd, oJ = 7.8,
mJ = 1.7, 1 H, H-5), 11.16 (br s, 1 H, NH)
11b
3287, 1637, 1604, 3.77 (s, 3 H, OMe), 6.07 (t, 2JH,F = 55.4, 1 H, CF2H), 6.99 (dd, oJ = 8.3,
1587, 1544, 1516 mJ = 1.0, 1 H, H-8), 7.00 (d, 2 H, H-2¢, H-6¢), 7.08 (ddd, oJ = 9.0, 1 H, H-6,
oJ = 7.8, 7.3, mJ = 1.0), 7.34 (d, oJ = 9.0, 2 H, H-3¢, H-5¢), 7.48 (ddd, oJ = 8.3,
7.3, mJ = 1.7, 1 H, H-7), 7.79 (dd, oJ = 7.8, mJ = 1.7, 1 H, H-5), 7.82 (d,
J = 12.8, 1 H, =CH), 8.33 (s, 1 H, OH), 12.57 (d, J = 12.8, 1 H, NH)
Synthesis 2006, No. 16, 2707–2718 © Thieme Stuttgart · New York

2714
V. Ya. Sosnovskikh et al.
PAPER
Table 5 Analytical and Spectral Data for Compounds 11a–j and 12a–ha (continued)
Compd
Molecular
formula
IR (KBr, cm–1)
1H NMR (DMSO-d6) d, J (Hz)
11cb
C17H18F3NO3⋅
0.25H2O
3200, 1646, 1610, 1.30–1.97 [m, 10 H, (CH2)5], 3.12–3.22 (m, 1 H, CHN), 4.03 (br s, 1 H, OH),
1596, 1547
6.95 (dd, oJ = 8.2, mJ = 1.0, 1 H, H-8), 7.07 (ddd, oJ = 7.8, 7.3, mJ = 1.0, 1 H,
H-6), 7.39 (ddd, oJ = 8.2, 7.3, mJ = 1.7, 1 H, H-7), 7.47 (d, J = 13.4, 1
H, =CH), 7.88 (dd, oJ = 7.8, mJ = 1.7, 1 H, H-5), 11.10 (br s, 1 H, NH)
11db
11ec,d
11f
C18H14F3NO3⋅
3251, 1644, 1610, 4.19 (br s, 1 H, OH), 4.43 (d, J = 6.1, 1 H, CH2), 6.97 (dd, oJ = 8.3, mJ = 1.0,
1594, 1544
0.5H2O
1 H, H-8), 7.08 (ddd, oJ = 7.8, 7.3, mJ = 1.0, 1 H, H-6), 7.22–7.26 (m, 2 H, H-
2¢, H-6¢), 7.29–7.39 (m, 3 H, H-3¢, H-4¢, H-5¢), 7.41 (ddd, oJ = 8.3, 7.3,
mJ = 1.7, 1 H, H-7), 7.45 (d, J = 14.0, 1 H, =CH), 7.88 (dd, oJ = 7.8, mJ = 1.7,
1 H, H-5), 11.21 (br s, 1 H, NH)
C17H12F3NO3
C18H14F3NO3
C18H14F3NO4
3228, 1639, 1599, 7.07 (dd, oJ = 8.3, mJ = 1.0, 1 H, H-8), 7.15 (ddd, oJ = 7.7, 7.3, mJ = 1.0, 1 H,
1588, 1548
H-6), 7.18–7.23 (m, 1 H, H-4¢), 7.40–7.46 (m, 4 H, H-2¢, H-3¢, H-5¢, H-6¢),
7.55 (ddd, oJ = 8.3, 7.3, mJ = 1.7, 1 H, H-7), 7.83 (dd, oJ = 7.7, mJ = 1.7, 1 H,
H-5), 8.00 (d, J = 12.9, 1 H, =CH), 9.12 (s, 1 H, OH), 12.53 (d, J = 12.9, 1 H,
NH)
3254, 1642, 1604, 2.30 (s, 3 H, Me), 7.06 (d, oJ = 8.2, mJ = 1.0, 1 H, H-8), 7.14 (ddd, oJ = 7.8,
1587, 1545, 1519 7.3, mJ = 1.0, 1 H, H-6), 7.24 (d, oJ = 8.4, 2 H, H-2¢, H-6¢), 7.31 (d, oJ = 8.4, 2
H, H-3¢, H-5¢), 7.53 (ddd, oJ = 8.3, 7.3, mJ = 1.7, 1 H, H-7), 7.82 (dd, oJ = 7.8,
mJ = 1.7, 1 H, H-5), 7.96 (d, J = 12.9, 1 H, =CH), 9.08 (s, 1 H, OH), 12.55 (d,
J = 12.9, 1 H, NH)
11g
3278, 1639, 1602, 3.77 (s, 3 H, OMe), 7.00 (d, oJ = 9.0, 2 H, H-2¢, H-6¢), 7.05 (dd, oJ = 8.3,
1587, 1544, 1516 mJ = 1.0, 1 H, H-8), 7.13 (ddd, oJ = 7.8, 7.3, mJ = 1.0, 1 H, H-6), 7.37 (d,
oJ = 9.0, 2 H, H-3¢, H-5¢), 7.53 (ddd, oJ = 8.3, 7.3, mJ = 1.7, 1 H, H-7), 7.81
(dd, oJ = 7.8, mJ = 1.7, 1 H, H-5), 7.89 (d, J = 13.0, 1 H, =CH), 9.05 (s, 1 H,
OH), 12.60 (d, J = 13.0, 1 H, NH)
11h
C17H11F3N2O5⋅
0.5H2O
3130, 1639, 1585, 7.10 (dd, oJ = 8.3, mJ = 1.0, 1 H, H-8), 7.18 (ddd, oJ = 7.8, 7.3, mJ = 1.0, 1 H,
1564, 1524
H-6), 7.59 (ddd, oJ = 8.3, 7.3, mJ = 1.7, 1 H, H-7), 7.69 (d, oJ = 9.2, 2 H, H-2¢,
H-6¢), 7.85 (dd, oJ = 7.8, mJ = 1.7, 1 H, H-5), 8.09 (d, J = 12.6, 1 H, =CH),
8.27 (d, oJ = 9.2, 2 H, H-3¢, H-5¢), 9.28 (s, 1 H, OH), 12.47 (d, J = 12.6, 1 H,
NH)
11i
11j
C17H11F3N2O5
3316, 1642, 1618, 7.25 (t, oJ = 6.8, 1 H, H-4¢), 7.35 (d, oJ = 9.0, 1 H, H-8), 7.44–7.50 (m, 4 H,
1600, 1588, 1560, H-2¢, H-3¢, H-5¢, H-6¢), 8.10 (d, J = 13.3, 1 H, =CH), 8.38 (dd, oJ = 9.0,
1521
mJ = 2.9, 1 H, H-7), 8.58 (d, mJ = 2.9, 1 H, H-5), 9.61 (s, 1 H, OH), 12.59 (d,
J = 13.3, 1 H, NH)
C20H17F4NO5
3208, 1644, 1607, 3.76 (s, 3 H, OMe), 3.82 (s, 3 H, OMe), 6.52 (d, mJ = 2.4, 1 H, H-8), 6.69 (tdd,
1584, 1535, 1518 2JH,F = 52.2, 3JH,F = 5.9, 7.4, 1 H, CF2CF2H), 6.69 (dd, oJ = 8.7, mJ = 2.4, 1 H,
H-6), 6.99 (d, oJ = 9.0, 2 H, H-2¢, H-6¢), 7.31 (d, oJ = 9.0, 2 H, H-3¢, H-5¢),
7.71 (d, oJ = 8.7, 1 H, H-5), 7.75 (dd, J = 12.8, 1.3, 1 H, =CH), 8.94 (d,
J = 4.1, 1 H, OH), 12.47 (d, J = 12.8, 1 H, NH)
12a
12b
C15H18F2N2O3
3220–2650, 1656, 1.21 (d, J = 6.3, 6 H, 2 × Me), 1.98 (s, 3 H, Me), 2.16 (s, 3 H, Me), 3.79 (d
1636, 1592, 1541 sept, JCH,NH = 7.3, J = 6.3, 1 H, CH), 5.96 (s, 1 H, Py), 6.84 (t, 2JH,F = 54.8, 1
H, CF2H), 7.75 (br d, J = ca. 12.0, 1 H, =CH,), 10.77 (br s, 1 H, NH), 11.68
(br s, 1 H, PyNH)
C16H18F2N2O3
3280–2650, 1660, 1.85 (quint, J = 6.8, 2 H, CH2), 1.95 (quint, J = 6.8, 2 H, CH2), 2.00 (s, 3 H,
1635, 1600, 1575 Me), 2.15 (s, 3 H, Me), 2.88 (t, J = 6.8, 2 H, CH2), 3.70 (t, J = 6.8, 2 H, CH2),
5.93 (s, 1 H, Py), 6.61 (t, 2JH,F = 54.7, 1 H, CF2H), 7.66 (s, 1 H, =CH), 11.58
(br s, 1 H, PyNH)
12c
12d
C17H20F2N2O3
C16H18F2N2O4
3280–2650, 1659, 1.60–1.65 (br s, 6 H, 3 × CH2), 2.02 (s, 3 H, Me), 2.15 (s, 3 H, Me), 3.10–3.24
1636, 1602, 1579 (br s, 2 H, CH2), 3.55–3.65 (m, 2 H, CH2), 5.93 (s, 1 H, Py), 6.64 (t,
2JH,F = 54.8, 1 H, CF2H), 7.59 (s, 1 H, =CH), 11.59 (br s, 1 H, PyNH)
3280–2650, 1659, 2.03 (s, 3 H, Me), 2.15 (s, 3 H, Me), 3.30 (s, 4 H, 2 × CH2), 3.67–3.71 (m, 4
1633, 1608, 1575 H, 2 × CH2), 5.94 (s, 1 H, Py), 6.63 (t, 2JH,F = 54.6, 1 H, CF2H), 7.65 (s, 1
H, =CH), 11.62 (br s, 1 H, PyNH)
Synthesis 2006, No. 16, 2707–2718 © Thieme Stuttgart · New York

PAPER
3-(Polyhaloacyl)chromones: Synthesis and Reactions with Amines
2715
Table 5 Analytical and Spectral Data for Compounds 11a–j and 12a–ha (continued)
Compd
Molecular
formula
IR (KBr, cm–1)
1H NMR (DMSO-d6) d, J (Hz)
12e
C19H18F2N2O4⋅
0.5H2O
3120–2660, 1630, Major isomer (80%): 2.05 (s, 3 H, Me), 2.17 (s, 3 H, Me), 3.76 (s, 3 H, OMe),
1581, 1550, 1513 6.01 (s, 1 H, Py), 6.92 (t, 2JH,F = 54.1, 1 H, CF2H), 6.98–7.00 (m, 2 H, Ar),
7.28–7.30 (m, 2 H, Ar), 7.93 (br s, 1 H, =CH), 11.80 (br s, 1 H, PyNH), 12.26
(br s, 1 H, NH)
Minor isomer (16%): 2.03 (s, 3 H, Me), 2.16 (s, 3 H, Me), 3.76 (s, 3 H, OMe),
5.93 (s, 1 H, Py), 7.0 (m, 2 H, Ar), 7.5 (br s, 2 H, Ar), 8.35 (br s, 1 H, =CH),
11.5 (br s, 1 H, PyNH), 12.6 (br s, 1 H, NH)
12f
C18H16F2N2O3⋅
0.5H2O
3130–2670, 1640, Major isomer (75%): 2.07 (s, 3 H, Me), 2.18 (s, 3 H, Me), 6.03 (s, 1 H, Py),
1618, 1582, 1545, 6.93 (t, 2JH,F = 54.1, 1 H, CF2H), 7.25–7.50 (m, 5 H, Ph), 8.04 (d, J = 13.9, 1
1498
H, =CH), 11.83 (br s, 1 H, PyNH), 12.24 (d, J = 14.0, 1 H, NH)
Minor isomer (17%): 2.01 (s, 3 H, Me), 2.15 (s, 3 H, Me), 5.91 (s, 1 H, Py),
6.84 (t, 2JH,F = 53.4, 1 H, CF2H), 7.4–7.6 (m, 5 H, Ph), 8.43 (d, J = 12.0, 1
H, =CH), 11.55 (br s, 1 H, PyNH), 12.59 (d, J = 12.3, 1 H, NH)
13f (8%)
12ge
2.37 (s, 3 H, Me), 2.67 (s, 3 H, Me), 6.10 (t, 2JH,F = 55.4, 1 H, CF2H), 6.87 (s,
1 H, Py), 7.4 (m, 5 H, Ph), 7.86 (d, J = 12.8, 1 H, =CH), 12.33 (d, J = 12.7, 1
H, NH)
C19H17F3N2O4⋅
0.5H2O
3130–2670, 1624, 2.08 (s, 3 H, Me), 2.16 (s, 3 H, Me), 3.78 (s, 3 H, OMe), 5.96 (br s, 1 H, Py),
1585, 1558, 1514 7.01 (m, 2 H, Ar), 7.44 (br s, 2 H, Ar), 7.9–8.1 (br m,1 H, =CH), 11.6–12.6
(br m, 2 H, 2 × NH)
13g (56%)
12he
2.38 (s, 3 H, Me), 2.68 (s, 3 H, Me), 3.77 (s, 3 H, OMe), 6.91 (s, 1 H, Py), 6.99
(d, J = 9.0, 2 H, Ar), 7.36 (d, J = 9.0, 2 H, Ar), 7.84 (d, J = 13.0, 1 H, =CH),
9.07 (s, 1 H, OH), 12.43 (d, J = 13.0, 1 H, NH)
C18H15F3N2O3⋅
0.5H2O
3100–2640, 1646, 2.10 (s, 3 H, Me), 2.16 (s, 3 H, Me), 5.97–6.03 (br s, 1 H, Py), 7.2–7.5 (m, 5
1599, 1576, 1550, H, Ph), 8.0–8.2 (br m, 1 H, =CH), 11.6–12.5 (br m, 2 H, 2 × NH)
1504
13h (64%)
2.39 (s, 3 H, Me), 2.69 (s, 3 H, Me), 6.93 (s, 1 H, Py), 7.40–7.45 (m, 5 H, Ph),
7.94 (d, J = 12.9, 1 H, =CH), 9.14 (s, 1 H, OH), 12.37 (d, J = 12.9, 1 H, NH)
a Elemental analyses were within allowed error, C 0.36; H 0.37; N 0.29.
b 1H NMR spectrum recorded in CDCl3.
c 13C NMR (DMSO-d6): d = 97.98 (q, 2JC,F = 32.6 Hz), 98.98, 116.53, 117.45, 119.98, 122.21, 122.87 (q, 1JC,F = 290.3 Hz), 124.98, 125.67,
129.87, 135.03, 139.18, 147.21, 155.80, 179.81.
d 19F NMR (DMSO-d6): d = 77.75 (s, CF3).
e A mixture of Z- and E-isomers.
1H (400 MHz), 13C (100 MHz) and 19F (376 MHz) NMR spectra
were recorded on a Bruker DRX-400 spectrometer in CDCl3 or
DMSO-d6 with TMS and C6F6 as internal standards, respectively.
The digital resolution for the 1H NMR spectra was 0.12–0.14 Hz per
point. IR spectra were recorded on an Perkin-Elmer Spectrum BX-
II instrument as KBr discs. Elemental analyses were performed at
the Microanalysis Services of the Institute of Organic Synthesis,
Ural Branch, Russian Academy of Sciences. Melting points are un-
corrected. All solvents used were dried and distilled per standard
procedures. The starting compounds 1 and 5 were prepared by reac-
tion of the appropriate o-hydroxyacetyl derivatives with RFCO2Et
according to described procedures.20,26 4-Acetyl-5-hydroxy-3-
methyl-1-phenylpyrazole was synthesised by a procedure described
elsewhere.27
3-(1-Methoxy-2,2,2-trifluoro-1-hydroxyethyl)-4H-chromen-4-
one (4a)
A solution of chromone 2d (250 mg, 1.0 mmol) in MeOH (2 mL)
and CH(OMe)3 (1 mL) was saturated with HCl for 10 min at ca.
20 °C. After partial evaporation of the solvent the mixture was left
at –10 °C for 2 h. The precipitate of 4a that formed was filtered and
washed with cold MeOH. Without recrystallisation, 4a was isolated
as colourless crystals in analytically pure form; yield: 150 mg
(55%); mp 102–103 °C.
IR (KBr): 3345, 3218, 3103, 1639, 1620, 1602, 1574 cm–1.
1H NMR (CDCl3): d = 3.44 (s, 3 H, OMe), 7.53 (ddd, oJ = 8.1, 7.2
o
Hz, mJ = 1.0 Hz, 1 H, H-6), 7.57 (ddd, J = 8.6 Hz, mJ = 1.0 Hz,
pJ = 0.5 Hz, 1 H, H-8), 7.81 (ddd, oJ = 8.6, 7.2 Hz, mJ = 1.7 Hz, 1 H,
H-7), 8.25 (s, 1 H, H-2), 8.27 (ddd, oJ = 8.1 Hz, mJ = 1.7 Hz, pJ = 0.5
Hz, 1 H, H-5), 8.94 (s, 1 H, OH).
3-(Polyhaloacyl)chromones (2) and their Hetero Analogues (6,
9, 10); General Procedure
Anal. Calcd for C12H9F3O4: C, 52.57; H, 3.31. Found: C, 52.44; H,
2.96.
A solution of chromanone 1 or 5 or diketone 8 (1.0 mmol) in di-
ethoxymethyl acetate (1.0 g, 6.0 mmol) was heated at 140–150 °C
for 15–20 min. After cooling, the resulting mixture was diluted with
hexane (3 mL). The solid product obtained on standing was collect-
ed by filtration, washed with hexane, and dried to give chromones
2, 6, 9 or 10 as colourless crystals (see Table 4).
3-(1-Ethoxy-2,2,2-trifluoro-1-hydroxyethyl)-4H-chromen-4-
one (4b)
This compound was synthesised according to the described
procedure19b in 56% yield as colourless crystals; mp 105–106 °C.
Synthesis 2006, No. 16, 2707–2718 © Thieme Stuttgart · New York

2716
V. Ya. Sosnovskikh et al.
PAPER
IR (KBr): 3345, 3104, 1640, 1599, 1574 cm–1.
Anal. Calcd for C13H9F4NO3: C, 51.50; H, 2.99; N, 4.62. Found: C,
51.35; H, 3.04; N, 4.60.
1H NMR (CDCl3): d = 1.28 (t, J = 7.1 Hz, 3 H, Me), 3.57 (dq,
J = 9.6, 7.1 Hz, 1 H, CHH), 3.92 (dq, J = 9.6, 7.1 Hz, 1 H, CHH),
7.52 (ddd, oJ = 8.1, 7.2 Hz, mJ = 1.0 Hz, 1 H, H-6), 7.56 (br d, 1 H,
H-8, oJ = 8.6 Hz), 7.80 (ddd, oJ = 8.6, 7.2 Hz, mJ = 1.7 Hz, 1 H, H-
7), 8.26 (dd, oJ = 8.1 Hz, mJ = 1.7 Hz, 1 H, H-5), 8.27 (s, 1 H, H-2),
8.86 (s, 1 H, OH).
7c
1H NMR (CDCl3, 13%): d = 2.63 (s, 3 H, Me), 2.84 (d, J = 0.7 Hz,
3 H, Me), 6.23 (s, 2 H, 2 × OH), 6.26 (tt, 2JH,F = 53.2 Hz, 3JH,F = 6.3
Hz, 1 H, CF2CF2H), 7.13 (s, 1 H, H-6), 8.33 (s, 1 H, H-2).
Anal. Calcd for C13H11F3O4⋅0.25H2O: C, 53.34; H, 3.96. Found: C,
53.24; H, 3.63.
1-(5-Hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-4,4,4-triflu-
orobutane-1,3-dione (8b); Typical Procedure
Finely powdered LiH (0.28 g, 35.0 mmol) was added to a solution
of ethyl trifluoroacetate (2.0 g, 14.1 mmol) and 4-acetyl-5-hydroxy-
3-methyl-1-phenylpyrazole (2.0 g, 9.3 mmol) in anhyd THF (10
mL). The resulting reaction mixture was refluxed for 3 h. Then the
solvent was removed by distillation in a water bath under reduced
pressure, and a mixture of AcOH (5 mL) and concd HCl (4 mL) was
added to the residue. The mixture was refluxed for 5 min and poured
onto crushed ice (40 g). The precipitate that formed was filtered off,
washed with H2O, dried, and recrystallised from toluene to give
diketone 8b as yellowish crystals in a yield of 2.7 g (93%); mp 116–
117 °C.
3-(1-Ethoxy-2,2,3,3-tetrafluoro-1-hydroxypropyl)-7-methoxy-
4H-chromen-4-one (4c)
This compound was synthesised analogously to 4a in 66% yield as
colourless crystals; mp 97–98 °C.
IR (KBr): 3200, 3093, 1633, 1593, 1567, 1503 cm–1.
1H NMR (CDCl3): d = 1.24 (t, J = 7.1 Hz, 3 H, Me), 3.46 (dq,
J = 9.6, 7.1 Hz, 1 H, CHH), 3.87 (dq, J = 9.6, 7.1 Hz, 1 H, CHH),
3.94 (s, 3 H, OMe), 6.24 (tdd, 2JH,F = 53.3 Hz, 3JH,F = 5.6, 7.4 Hz, 1
H, CF2CF2H), 6.91 (d, mJ = 2.4 Hz, 1 H, H-8), 7.06 (dd, oJ = 9.0 Hz,
mJ = 2.4 Hz, 1 H, H-6), 8.13 (s, 1 H, H-2), 8.14 (d, oJ = 9.0 Hz, 1 H,
H-5), 9.18 (s, 1 H, OH).
IR (KBr): 1655, 1590, 1568, 1501 cm–1.
1H NMR (CDCl3): d = 2.50 (s, 3 H, Me), 6.24 (s, 1 H, =CH), 7.34
(tt, oJ = 7.5 Hz, mJ = 1.3 Hz, 1 H, H-4¢), 7.45–7.50 (m, 2 H, H-3¢, H-
5¢), 7.77–7.81 (m, 2 H, H-2¢, H-6¢), 11.7 (br s, 1 H, pyrazole-OH),
14.5 (br s, 1 H, enol-OH).
Anal. Calcd for C15H14F4O5: C, 51.44; H, 4.03. Found: C, 51.38; H,
3.95.
3-(2,2-Difluoroacetyl)-5,7-dimethyl-4H-pyrano[2,3-b]pyridin-
4-one (6a)
Yield: 77%; mp 151–152 °C.
IR (KBr): 3079, 1720, 1641, 1609, 1537 cm–1.
1H NMR (CDCl3): d = 2.63 (s, 3 H, Me), 2.87 (d, J = 0.7 Hz, 3 H,
Me), 6.86 (t, 2JH,F = 53.3 Hz, 1 H, CF2H), 7.15 (s, 1 H, H-6), 8.62 (s,
1 H, H-2).
Anal. Calcd for C14H11F3N2O3: C, 53.85; H, 3.55; N, 8.97. Found:
C, 53.66; H, 3.39; N, 8.74.
1-(5-Hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-4,4-difluo-
robutane-1,3-dione (8a)
This compound was synthesised similarly to 8b in 87% yield as co-
lourless needle-like crystals; mp 89–90 °C (toluene).
Anal. Calcd for C12H9F2NO3: C, 56.92; H, 3.58; N, 5.53. Found: C,
56.62; H, 3.51; N, 5.57.
IR (KBr): 1643, 1563, 1495 cm–1.
1H NMR (CDCl3): d = 2.50 (s, 3 H, Me), 6.10 (t, 2JH,F = 54.2 Hz, 1
H, CF2H), 6.16 (s, 1 H, =CH), 7.33 (tt, oJ = 7.5 Hz, mJ = 1.3 Hz, 1
H, H-4¢), 7.45–7.49 (m, 2 H, H-3¢, H-5¢), 7.78–7.82 (m, 2 H, H-2¢,
H-6¢), 11.7 (br s, 1 H, pyrazole-OH), 14.4 (br s, 1 H, enol-OH).
7a
1H NMR (CDCl3, 2%): d = 2.63 (s, 3 H, Me), 2.85 (d, J = 0.7 Hz, 3
H, Me), 6.10 (s, 2 H, 2 × OH), 7.13 (s, 1 H, H-6), 8.35 (s, 1 H, H-2).
Anal. Calcd for C14H12F2N2O3: C, 57.15; H, 4.11; N, 9.52. Found:
C, 57.37; H, 4.23; N, 9.64.
5,7-Dimethyl-3-(trifluoroacetyl)-4H-pyrano[2,3-b]pyridin-4-
one (6b) and 5,7-Dimethyl-3-(2,2,2-trifluoro-1,1-dihydroxyeth-
yl)-4H-pyrano[2,3-b]pyridin-4-one (7b)
Yield: 68%; mp 171–172 °C.
IR (KBr): 3400–3210, 3072, 1732, 1647, 1619, 1604, 1545 cm–1.
5-Difluoroacetyl-3-methyl-1-phenylpyrano[2,3-c]pyrazol-
4(1H)-one (9)
Yield: 64%; mp 185–186 °C.
1H NMR (CDCl3): d = 2.63 (s, 3 H, Me), 2.87 (d, J = 0.7 Hz, 3 H,
1H NMR (CDCl3): d = 2.66 (s, 3 H, Me), 6.91 (t, 2JH,F = 53.3 Hz, 1
H, CF2H), 7.43 (tt, oJ = 7.5 Hz, mJ = 1.3 Hz, 1 H, H-4¢), 7.52–7.57
(m, 2 H, H-3¢, H-5¢), 7.73–7.77 (m, 2 H, H-2¢, H-6¢), 8.35 (s, 1
H, =CH).
Me), 7.15 (s, 1 H, H-6), 8.56 (s, 1 H, H-2).
19F NMR (CDCl3): d = 87.12 (s, CF3).
Anal. Calcd for C12H8F3NO3⋅0.25H2O: C, 52.28; H, 3.11; N, 5.08.
Found: C, 52.26; H, 3.13; N, 4.48.
19F NMR (CDCl3): d = 31.03 (d, CF2H, 2JH,F = 53.3 Hz).
Anal. Calcd for C15H10F2N2O3: C, 59.22; H, 3.31; N, 9.21. Found:
C, 59.20; H, 3.28; N, 9.23.
7b
1H NMR (CDCl3, 50%): d = 2.63 (s, 3 H, Me), 2.85 (d, J = 0.7 Hz,
3 H, Me), 6.10 (s, 2 H, 2 × OH), 7.13 (s, 1 H, H-6), 8.35 (s, 1 H, H-
2).
19F NMR (CDCl3, 55%): d = 74.93 (s, CF3).
Hydrate
1H NMR (CDCl3, 7%): d = 2.63 (s, 3 H, Me), 5.57 (s, 2 H, 2 × OH),
5.77 (t, 2JH,F = 56.1 Hz, 1 H, CF2H), 8.09 (s, 1 H, =CH).
19F NMR (CDCl3, 9%): d = 28.98 (d, 2JH,F = 56.1 Hz, CF2H).
5,7-Dimethyl-3-(2,2,3,3-tetrafluoropropanoyl)-4H-pyrano[2,3-
b]pyridin-4-one (6c)
Yield: 63%; mp 119–120 °C.
IR (KBr): 3540–3200, 3082, 1713, 1660, 1635, 1611, 1540 cm–1.
3-Methyl-1-phenyl-5-(2,2,2-trifluoro-1,1-dihydroxyethyl)pyra-
no[2,3-c]pyrazol-4(1H)-one (10)
Yield: 60%; mp 150–151 °C.
IR (KBr): 3220, 1654, 1597, 1538, 1508 cm–1.
1H NMR (CDCl3): d = 2.63 (s, 3 H, Me), 2.86 (d, J = 0.7 Hz, 3 H,
Me), 6.69 (tt, 2JH,F = 53.2 Hz, 3JH,F = 5.8 Hz, 1 H, CF2CF2H), 7.15
(s, 1 H, H-6), 8.48 (s, 1 H, H-2).
Synthesis 2006, No. 16, 2707–2718 © Thieme Stuttgart · New York

PAPER
3-(Polyhaloacyl)chromones: Synthesis and Reactions with Amines
2717
1H NMR (CDCl3): d = 2.54 (s, 3 H, Me), 7.46 (t, oJ = 7.4 Hz, 1 H,
H-4¢), 7.57–7.62 (m, 2 H, H-3¢, H-5¢), 7.80–7.84 (m, 2 H, H-2¢, H-
6¢), 8.25 (br s, 2 H, 2 × OH), 8.48 (s, 1 H, =CH).
7.61–7.73 (m, 4 H, C6H4), 7.95 (d, J = 12.3 Hz, 1 H, =CH), 8.22–
8.26 (m, 2 H, H-2¢, H-6¢), 10.25 (br s, 1 H, OH), 12.14 (br d, J = 12.0
Hz, 1 H, NH).
Anal. Calcd for C15H11F3N2O4: C, 52.95; H, 3.26; N, 8.23. Found:
C, 52.61; H, 3.21; N, 7.90.
Anal. Calcd for C21H15F3N4O5⋅H2O: C, 52.73; H, 3.58; N, 11.71.
Found: C, 52.76; H, 3.60; N, 11.48.
2-(Alkyl/arylaminomethylene)-2-hydroxy-2-(polyfluoro-
alkyl)chroman-4-ones (11a–j); General Procedure
Acknowledgment
A solution of 3-(polyfluoroacyl)chromone 2 (0.4 mmol) and the pri-
mary aliphatic or aromatic amine (0.6–0.8 mmol) in MeOH (2–3
mL) was allowed to stand at r.t. for 2 d. The crystalline product that
precipitated was filtered off, washed with cold MeOH (1 mL), and
dried to give 11 as colourless or yellow crystals (Table 5). Com-
pounds 12a–h were prepared analogously to 11, with the exception
that the reaction was completed in 1–3 h and was carried out in THF
(12a, 12c) or dioxane (12e–h).
This work was financially supported by the Russian Foundation for
Basic Research (grant 06-03-32388).
References
(1) (a) Ghosh, C. K. J. Heterocycl. Chem. 1983, 20, 1437.
(b) Sabitha, G. Aldrichimica Acta 1996, 29, 15.
(2) Eiden, F.; Haverland, H. Arch. Pharm. (Weinheim, Ger.)
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trans-1-(2-Hydroxyphenyl)-3-morpholinoprop-2-en-1-one and
Morpholinium Trifluoroacetate
Yield: 74%; 1:1 mixture; mp 89–90 °C.
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1H NMR (CDCl3): d = 3.17–3.20 (m, 4 H, 2 × CH2), 3.44–3.47 (m,
4 H, 2 × CH2), 3.77–3.80 (m, 4 H, 2 × CH2), 3.93–3.96 (m, 4 H, 2 ×
CH2), 5.94 (d, J = 12.4 Hz, 1 H, =CH), 6.82 (ddd, oJ = 8.1, 7.2 Hz,
mJ = 1.2 Hz, 1 H, H-5), 6.95 (dd, oJ = 8.4 Hz, mJ = 1.2 Hz, 1 H, H-
o
3), 7.37 (ddd, J = 8.4, 7.2 Hz, mJ = 1.6 Hz, 1 H, H-4), 7.66 (dd,
oJ = 8.1 Hz, mJ = 1.6 Hz, 1 H, H-6), 7.83 (d, J = 12.4 Hz, 1
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J. S. J. Chem. Soc., Perkin Trans. 1 2000, 2827.
(c) Bandyopadhyay, C.; Sur, K. R.; Patra, R.; Sen, A.
Tetrahedron 2000, 56, 3583. (d) Sandulache, A.; Silva, A.
M. S.; Cavaleiro, J. A. S. Tetrahedron 2002, 58, 105.
(e) Singh, G.; Singh, G.; Ishar, M. P. S. Synlett 2003, 256.
(f) Singh, G.; Singh, L.; Ishar, M. P. S. Tetrahedron 2002,
58, 7883. (g) Kaye, P. T.; Nchinda, A. T.; Sabbagh, L. V.;
Bacsa, J. J. Chem. Res., Synop. 2003, 111. (h) Ryabukhin,
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Synlett 2004, 2287. (i) Kumar, K.; Kapoor, R.; Ishar, M. P.
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Rengifo, A.; Insuasty, B.; Abonía, R.; Nogueras, M.;
Sánchez, A. Tetrahedron Lett. 2002, 43, 9061. (l) Lacova,
M.; Loos, D.; Furdik, M.; Matulova, M.; El-Shaaer, H. M.
Molecules 1998, 3, 149.
+
H, =CHN), 9.93 (br s, 2 H, NH2 ).
Anal. Calcd for C13H15NO3⋅C6H10F3NO3: C, 52.53; H, 5.80; N, 6.45.
Found: C, 52.09; H, 5.84; N, 6.30.
(E)-3-Anilino-1-(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-
yl)prop-2-en-1-one (14)
A solution of pyranopyrazole 9 (70 mg, 0.23 mmol) and aniline (43
mg, 0.46 mmol) in MeOH (1 mL) was kept for 24 h at ca. 20 °C. The
precipitated crystals were filtered off, washed with MeOH and
dried. Compound 14 was obtained as yellow crystals in a yield of 40
mg (55%); mp 156–157 °C. The same compound was obtained
from pyranopyrazole 10 after refluxing for 10 min with aniline in
i-PrOH; yield: 43%.
IR (KBr): 3290, 3208, 3115, 3054, 1671, 1643, 1600, 1591, 1531,
1499 cm–1.
Anal. Calcd for C19H17N3O2⋅0.25H2O: C, 70.46; H, 5.45; N, 12.97.
Found: C, 70.11; H, 5.23; N, 12.99.
E-Isomer (90%)
(8) (a) Welch, J. T. Tetrahedron 1987, 43, 3123.
(b) McClinton, M. A.; McClinton, D. A. Tetrahedron 1992,
48, 6555. (c) Lin, P.; Jiang, J. Tetrahedron 2000, 56, 3635.
(d) Burton, D. J.; Yang, Z.-Y. Tetrahedron 1992, 48, 189.
(9) (a) Sosnovskikh, V. Ya.; Usachev, B. I. Russ. Chem. Bull.
2001, 50, 1426. (b) Sosnovskikh, V. Ya.; Vorontsov, I. I.;
Kutsenko, V. A. Russ. Chem. Bull. 2001, 50, 1430.
(c) Sosnovskikh, V. Ya.; Kutsenko, V. A.; Yachevskii, D. S.
Mendeleev Commun. 1999, 204. (d) Sosnovskikh, V. Ya.;
Usachev, B. I.; Sizov, A. Yu.; Barabanov, M. A. Synthesis
2004, 942.
(10) (a) Sosnovskikh, V. Ya.; Usachev, B. I.; Sevenard, D. V.;
Röschenthaler, G.-V. Tetrahedron 2003, 59, 2625.
(b) Sosnovskikh, V. Ya.; Usachev, B. I.; Vorontsov, I. I.
Tetrahedron 2003, 59, 2549. (c) Sosnovskikh, V. Ya.;
Barabanov, M. A.; Usachev, B. I. Org. Lett. 2003, 5, 2501.
(d) Sosnovskikh, V. Ya.; Barabanov, M. A.; Usachev, B. I.
J. Org. Chem. 2004, 69, 8297. (e) Sosnovskikh, V. Ya.;
Usachev, B. I.; Vorontsov, I. I. J. Org. Chem. 2002, 67,
6738.
1H NMR (CDCl3): d = 2.44 (s, 3 H, Me), 5.87 (d, J = 12.5 Hz, 1
H, =CH), 7.07–7.22 (m, 5 H, NH, Ar), 7.35–7.44 (m, 4 H, Ar),
7.92–7.96 (m, 2 H, Ar), 8.30 (t, J = 13.0 Hz, 1 H, =CHN).
Z-Isomer (10%)
1H NMR (CDCl3): d = 2.49 (s, 3 H, Me), 5.53 (d, J = 7.9 Hz, 1
H, =CH), 7.07–7.44 (m, 8 H, Ar), 7.85–7.88 (m, 2 H, Ar), 11.24 (d,
J = 13.0 Hz, 1 H, NH).
1-(5-Hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-2-(4-nitro-
anilinomethylene)-4,4,4-trifluorobutane-1,3-dione (15)
A solution of pyranopyrazole 10 (100 mg, 0.29 mmol) and p-nitro-
aniline (60 mg, 0.44 mmol) in i-PrOH (3 mL) was refluxed for 10
min. Then the solvent was evaporated, and the residue was recrys-
tallised from MeOH. Compound 15 was obtained as yellow crystals
in a yield of 100 mg (72%); mp 157–158 °C.
IR (KBr): 3200–3080, 1644, 1599, 1555, 1534, 1504, 1490 cm–1.
1H NMR (DMSO-d6): d = 2.44 (s, 3 H, Me), 3.58 (br s, 2 H, H2O),
o
7.41 (t, J = 7.4 Hz, 1 H, H-4¢), 7.55–7.60 (m, 2 H, H-3¢, H-5¢),
Synthesis 2006, No. 16, 2707–2718 © Thieme Stuttgart · New York

2718
V. Ya. Sosnovskikh et al.
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Synthesis 2006, No. 16, 2707–2718 © Thieme Stuttgart · New York