Alkyl 3-fluoroalkyl-3-oxopropionates in reactions with azolyldiazonium salts

Article abstract of DOI:10.1007/s11172-008-0096-6

Alkyl 3-fluoroalkyl-3-oxopropionates react with antipyrinyldiazonium chloride to form 2-antipyrinylhydrazono-3-fluoroalkyl-3-oxopropionates. The use in these reactions of hetaryldiazonium salts, containing NH group in the α position, leads to alkyl 7-fluo

Full text of DOI:10.1007/s11172-008-0096-6

Russian Chemical Bulletin, International Edition, Vol. 57, No. 3, pp. 612—616, March, 2008
612
Alkyl 3ꢀfluoroalkylꢀ3ꢀoxopropionates in reactions
with azolyldiazonium salts
E. V. Shchegol'kov,a E. V. Sadchikova,b Ya. V. Burgart,a and V. I. Saloutina
aI. Ya. Postovskii Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
22 ul. S. Kovalevskoi, 620041 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 5954. Eꢀmail: saloutin@ios.uran.ru
bUral State Technical University,
19 ul. Mira, 620002 Ekaterinburg, Russian Federation
Alkyl 3ꢀfluoroalkylꢀ3ꢀoxopropionates react with antipyrinyldiazonium chloride to form
2ꢀantipyrinylhydrazonoꢀ3ꢀfluoroalkylꢀ3ꢀoxopropionates. The use in these reactions of hetaryldiazꢀ
onium salts, containing NH group in the α position, leads to alkyl 7ꢀfluoroalkylꢀ7ꢀhydroxyꢀ4,7ꢀ
dihydroazolo[5,1ꢀc]triazineꢀ6ꢀcarboxylates. 3ꢀAminoꢀ1Hꢀ1,2,4ꢀtriazole, 3ꢀaminoꢀ4ꢀethoxycarꢀ
bonylꢀ1Hꢀpyrazole, and 5ꢀaminoꢀ4ꢀethoxycarbonylꢀ1Hꢀimidazole were used as the heterocyclic
component.
Key words: 3ꢀfluoroalkylꢀ3ꢀoxopropionates, azocoupling, azolyldiazonium salts, dihydroazoloꢀ
triazines, cyclization, isomerism.
Acetylꢀ and benzoylacetic esters (3ꢀoxo esters) are
of both the openꢀchain and the heterocyclic products
depending on the identity of the hetaryldiazonium comꢀ
ponent. Thus, esters 1a,b react with antipyrinyldiazoniꢀ
um chloride 2a to form 2ꢀantipyrinylhydrazonoꢀ3ꢀfluoꢀ
roalkylꢀ3ꢀoxopropionates 3a,b similarly to the transforꢀ
mations of acetylꢀ and benzoylacetic esters.3 However,
when hetaryldiazonium salts 2b—d, containing an NH
group in the α position, are used in these reactions, alkyl
7ꢀfluoroalkylꢀ7ꢀhydroxyꢀ4,7ꢀdihydroazolo[5,1ꢀc]triꢀ
azineꢀ6ꢀcarboxylates 4a—e, 5a,b, and 6a,b are formed.
Obviously, that in this case the openꢀchain 3ꢀfluoroalkylꢀ
2ꢀhetarylhydrazonoꢀ3ꢀoxopropionates A are the intermeꢀ
diate products, undergoing the intramolecular cyclizaꢀ
tion through the addition of the NH group to the fluoroꢀ
acyl fragment (Scheme 1).
In contrast to this, according to the literature data
acetylꢀ and benzoylacetic esters in the reaction of azoꢀ
coupling with triazolylꢀ11,12 and pyrazolyldiazonium
salts9,10 gave the corresponding azolotriazines, while
the reaction with imidazolyldiazonium salts initially
leads to 2ꢀimidazolylhydrazones, which cyclize to imiꢀ
dazotriazines only under reflux in acidic medium.6 Atꢀ
tempted dehydration of heterocycles 4a, 5a, and 6a upon
heating in acetic acid or acetic anhydride did not lead to
their noticeable changes.
subjected to the azocoupling reaction with hetaryldiazoꢀ
nium salts at the activated methylene group giving rise to
2ꢀhetarylhydrazonoꢀ3ꢀoxo esters,1—8 some of which are
able to undergo various intramolecular cyclizations2—6
primarily with participation of the acyl substituent
and the NH group of the hetaryl fragment to form heteꢀ
roannulated triazines, including biologically active
ones.1,7 In the literature, there are described examples
when the azocoupling reaction of 3ꢀoxo esters with
hetaryldiazonium salts directly leads to the fused triazꢀ
ines, resulting from the spontaneous cyclization of
2ꢀhetarylhydrazonoꢀ3ꢀoxo esters. Bicyclic pyrazolo[3,2ꢀc]ꢀ
triazines9,10 and triazolo[5,1ꢀc][1,2,4]triazines11,12, triꢀ
cyclic triazino[4,3ꢀb]indazoles13,14 and pyrimidoꢀ
[5´,4´:4,5]pyrazolo[3,2ꢀc][1,2,4]triazines15 were obꢀ
tained by this way. Among the latter, azolotriazines are of
particular interest since they are isosteric to purine bases.
Information on azocoupling of alkyl 3ꢀfluoroalkylꢀ3ꢀ
oxopropionates with hetaryldiazonium salts is absent in
the literature.
In the present work, reactions of azocoupling of 3ꢀfluoꢀ
roalkylꢀ3ꢀoxopropionates 1a—e with hetaryldiazonium
chlorides 2a—d have been studied. 4ꢀAminoꢀ2,3ꢀdimeꢀ
thylꢀ5ꢀoxoꢀ1ꢀphenylꢀ3ꢀpyrazoline (2a), 3ꢀaminoꢀ1Hꢀ
1,2,4ꢀtriazole (2b), 3ꢀaminoꢀ4ꢀethoxycarbonylꢀ1Hꢀpyraꢀ
zole (2c), and 5ꢀaminoꢀ4ꢀethoxycarbonylꢀ1Hꢀimidazole
(2d) have been used as the heterocyclic component.
It was found that the azocoupling of 3ꢀoxo esters 1
with hetaryldiazonium salts can be used for the synthesis
The formation of stable 4,7ꢀdihydroazolotriazines,
containing gemꢀaminohydroxy fragment, in the reaction
of fluoroalkylated 3ꢀoxo esters 1 is their distinguishing
feature, caused by the presence of the electronꢀwithdrawꢀ
ing polyfluoroalkyl substituent. From the one hand, this
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 599—603, March, 2008.
1066ꢀ5285/08/5703ꢀ612 © 2008 Springer Science+Business Media, Inc.

Azocoupling 3ꢀfluoroalkylꢀ3ꢀoxopropionates
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 3, March, 2008
613
Scheme 1
1: Alk = Et, RF = CF3 (a), H(CF2)2 (b); Alk = Me, RF = HCF2 (c), C3F7 (d), C4F9 (e)
2: Het is antipyrinꢀ4ꢀyl (a), 1,2,4ꢀtriazolꢀ3ꢀyl (b); 4ꢀEtO2Cꢀpyrazolꢀ3ꢀyl (c), 4ꢀEtO2Cꢀimidazolꢀ3ꢀyl (d)
3: RF = CF3, Alk = Et (a); RF = C4F9, Alk = Me (b)
4: X = Z = N, Y = CH, Alk = Et, RF = CF3 (a), H(CF2)2 (b); Alk = Me, RF = HCF2 (c), C3F7 (d), C4F9 (e)
5: X = N, Y = CH, Z = CCO2Et, RF = CF3, Alk = Et (a); RF = C3F7, Alk = Me (b)
6: X = CH, Y = N, Z = CCO2Et, RF = CF3, Alk = Et (a), RF = C3F7, Alk = Me (b)
group facilitates addition of a nucleophile (in this case,
the NH group of the azole ring) at the neighboring carboꢀ
nyl atom, but from the other hand, it prevents the ready
elimination of a water molecule.
The openꢀchain 2ꢀhetarylhydrazonoꢀ3ꢀoxo esters 3
and dihydroazolotriazines 4—6 are the structural isoꢀ
mers, having an identical elemental analysis and molecuꢀ
lar ion peaks. There arises a problem of developing of
the strict criteria for the assignment of the openꢀchain or
heterocyclic structures to the products obtained.
the stretching vibrations of the three nonequivalent carꢀ
bonyl groups (see Experimental). In contrast to this,
the IR spectra of triazolotriazines 4a—e, having only one
alkoxycarbonyl substituent, contain one highꢀfrequency
band each, caused by the vibration of this carbonyl group,
whereas the spectra of dialkoxycarbonylꢀsubstituted pyraꢀ
zolotriazines 5a,b, have two bands, corresponding to
the stretching vibrations of the two carbonyl groups.
In the IR spectra of imidazotriazines 6a,b, containing
XꢀRay analysis, performed for a crystal of product 4d,
unambiguously point out its heterocyclic structure.
Moreover, it was found that the annulation of the triazole
ring occurs with the formation of a single isomer, triꢀ
azolo[5,1ꢀc]triazine. According to the Xꢀray data, in
the molecule of compound 4d there is an intramolecular
hydrogen bond between the oxygen carbonyl atom
(O(10)) of the methoxycarbonyl group and the hydrogen
atom (H(1)) of the hydroxy substituent. Thus, the inꢀ
tramolecular distance O(10)...H(1) is 2.37(4) Å, the anꢀ
gle O(7)—H(1)...O(10) is 118.77, C(10)—O(10)...H(1)
is 108.93° (Fig. 1).
A comparative analysis of the IR spectra of comꢀ
pounds 3—6, recorded in Nujol, showed a distinction in
the character of the spectra for the openꢀchain hetarylhyꢀ
drazones 3 and for the cyclic azolotriazines 4—6. Thus,
in the IR spectra of 2ꢀantipyrinylhydrazonoꢀ3ꢀfluoroꢀ
alkylꢀ3ꢀoxopropionates 3a,b, there are three highꢀfreꢀ
quency absorption bands in each spectrum, caused by
F(5)
F(6)
F(2)
F(1)
C(14)
H(1)
O(7)
F(7)
F(4)
C(12)
O(10)
C(13)
F(3)
C(7)
C(10)
O(11)
C(11)
N(8)
N(1)
C(2)
C(6)
N(5)
C(9)
N(4)
N(3)
Fig. 1. General view of a molecule of compound 4d.

614
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 3, March, 2008
Shchegol'kov et al.
also two dialkoxycarbonyl substituents, one broad highꢀ
frequency absorption band of the two carbonyl groups are
present in each spectrum. In addition, the IR spectra of
azolotriazines 4—6 contain two or more intensive abꢀ
sorption bands, caused by the stretching vibrations of
the OH and NH groups, whereas in the IR spectra of
2ꢀhydrazonoꢀ3ꢀoxo esters 3, a very weak broad absorpꢀ
tion band of the NH group of the hetarylhydrazone fragꢀ
the content of isomer A significantly increases in CDCl3
(see Experimental). Apparently, heptafluoropropylꢀsubꢀ
stituted imidazotriazine 6b is able to undergo a ringꢀ
chain isomerism since it exists as a heterocycle in the solid
state and as a mixture of cyclic and hydrazone forms in
solution (DMSOꢀd6 and CDCl3). The assignment of the
isomers was carried out proceeding from the analysis
of the chemical shift values of the fluorine atoms of
the αꢀCF2 group in its 19F NMR spectra.
ment is present in the region of 3100 cm–1
.
In this way, the Xꢀray data and the distinctions found by
us in the IR spectra allow us to conclude that compounds
4—6 exist in the solid state in a cyclic isomeric form.
The structures of products 3—6 in solutions were
investigated by 13C, 1H, and 19F NMR spectroscopy. The
NMR spectra of compounds 3a,b, 4a—e, 5a,b, and 6a,
recorded in CDCl3 and DMSOꢀd6, contain only one set of
signals, pointed out their existence in solution in the form of
one from possible isomers. As expected, in the 13C NMR
spectrum of ester 3a, a signal of the carbon atom adjacent
to the trifluoromethyl group is found at δ ≈ 172, which
corresponds to the carbon atom of the trifluoroacetyl
fragment, whereas, in the 13C NMR spectrum of triazoꢀ
lotriazine 4a, a quartet signal of the carbon atom adjacent
to the trifluoromethyl group is observed at δ ≈ 82, which
is characteristic of a quaternary carbon atom.
The synthesized dihydroazolotriazines 4—6 have
alkoxycarbonyl substituents in their structure, therefore,
they can be converted to the corresponding carboxylic
acid. Thus, acid 7 was obtained by the alkali hydrolysis of
compound 4c.
The research carried out by us showed that the azoꢀ
coupling reaction of fluoroalkylated 3ꢀoxo esters with
aryldiazonium salts, containing NH groups in the αꢀpoꢀ
sition to the diaza group, can be used as the oneꢀstep
method for the synthesis of dihydroazolotriazines.
Experimental
IR spectra were recorded on a Perkin Elmer Spectrum One
and Thermo Nicolet 6700 Fourier spectrometers in the region
1
4000—400 cm–1 in Nujol. H, 19F, and 13C NMR spectra were
recorded on a Bruker DRXꢀ400 spectrometer (1H: 400 MHz; 13C:
100.6 MHz, relatively to SiMe4, 19F: 376 MHz, relatively to C6F6).
Elemental analysis was performed on a Carlo Erba CHN/SꢀO EA
1108 elemental analyzer. Column chromatography was carried out
on Merck 60 silica gel (0.063—0.200 mm). Melting points were
determined in unsealed capillary tubes on a Stuart SMP3 apparatus.
Monocrystals of azolotriazine 4d were obtained by crystallizaꢀ
tion from acetone. XꢀRay diffraction experiment was performed on
a Xcalibur 3 diffractometer with a CCDꢀdetector (graphite moꢀ
nochromator, λ(MoꢀKα) = 0.71073 Å, the temperature was
295(2) °C, φꢀ and ωꢀscanning technique). An absorption correction
was carried out analytically using a multifacet crystal model with
the use of the CrysAlis RED 1.171.29.9 program. The crystal strucꢀ
ture was solved by the direct method and subsequent Fourierꢀ
syntheses using the SHELXSꢀ97 program.17 The structure was
refined by the leasts squares method in anisotropic fullꢀmatrix
approximation for all the nonhydrogen atoms with the use of
the SHELXLꢀ97 program.17
1
The H NMR spectroscopy data cannot be used for
the assignment of a cyclic or openꢀchain structure to
the azocoupling products 3—6 because of the similarities
in the spectroscopic characteristics of azolotriazines and
hetarylhydrazones. However, we have shown that 19F
NMR spectroscopy is a source of reliable criteria for the
solution of this problem since the chemical shift values of
the fluorine atom signals in the CF3 and αꢀCF2 groups
depend on the character of the neighboring to them carbon
atoms. Thus, for azolotriazines 4a—e, 5a,b, and 6a, signals
of the fluorine atoms in the CF3 and αꢀCF2 group, bonded
to the sp3ꢀhybridized carbon atom, are observed in the
more strong region (δCF ≈ 83—85, δαꢀCF ≈ 45) as compaꢀ
3
red to the corresponding signals of their2openꢀchain anaꢀ
logs, 2ꢀantipyrinylhydrazonoꢀ3ꢀfluoroalkylꢀ3ꢀoxopropiꢀ
onates 3a,b (δCF ≈ 90, δαꢀCF ≈ 49), and earlier obꢀ
3
2
The main crystallographic data for compound 4d and some
experimental characteristics are given in Table 1.*
tained 2ꢀarylhydrazonoꢀ3ꢀfluoroalkylꢀ3ꢀoxopropionates
(δCF ≈ 91—93, δαꢀCF ≈ 50—52),16 in which the CF3 and
3
2
Synthesis of compounds 3a,b, 4a—e, 5a,b, and 6a,b (general
procedure). To obtain hetaryldiazonium salt 2, hetarylamine (10
mmol) was placed into a twoꢀneck flask with a stirrer and dropping
funnel followed by addition of a solution of diluted hydrochloric
acid (prepared from concentrated HCl (3 mL) and water (10 mL)),
then, a solution of sodium nitrite (0.70 g) in water (3 mL) was added
dropwise and slowly under vigorous stirring and cooling down
to 0 °C. A solution of sodium acetate (4.55 g) in acetone (31 mL)
αꢀCF2 groups are at the sp2ꢀhybridized carbon atom.
In addition, signals of the fluorine atoms in the αꢀCF2
groups of the polyfluoroalkyl substituents in azolotriazꢀ
ines 4b—e reveal themselves as an AВꢀsystem due to the poꢀ
sition of this group next to the asymmetric carbon atom.
Thus, the NMR spectroscopic investigations of azoꢀ
lotriazines 4a—e, 5a,b, and 6a showed that they exist in
CDCl3 and DMSOꢀd6 solutions in a cyclic form.
* Full crystallographic parameters of compound 4d were deposited
with the Cambridge Structural Database (CCDC 652043) and
are available at www.ccdc.cam.ac.uk/conts/retrieving.html
(CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; eꢀmail:
deposit@ccdc.cam.ac.uk).
However, imidazotriazine 6b is an exception since in
its 1H and 19F NMR spectra, recorded in DMSOꢀd6 and
CDCl3, two sets of signals are present, which correspond
to a cyclic and openꢀchain hydrazone form A, and

Azocoupling 3ꢀfluoroalkylꢀ3ꢀoxopropionates
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 3, March, 2008
615
Table. XꢀRay crystallographic data and parameters for compound 4d
3070 (NHstr, OH); 1710 (CO2Et); 1610, 1560, 1540, 1480, 1465
(C=N, C=C, NHbend); 1275—1110 (C—F). 1H NMR (DMSOꢀd6),
δ: 1.27 (t, 3 H, OCH2Me, 3JH,H = 7.1 Hz); 4.26 (q, 2 H, OCH2Me,
3JH,H = 7.1 Hz); 8.06 (s, 1 H, =CH); 9.30 (s, 1 H, OH); 13.34
(s, 1 H, NH). 13C NMR (DMSOꢀd6), δ: 10.49 (OCH2Me); 61.33
Parameter
4d
Molecular formula
Molecular weight
Crystal system
Space group
С9H6F7N5O3
369.15
Monoclinic
P21/c
2
(OCH2Me); 82.00 (q, C(7), JC,F = 35.0 Hz); 121.71 (q, CF3,
1JC,F = 290.4 Hz); 126.29 (C(6)); 146.08 (CH); 151.35 (C(9));
160.91 (COOEt). 19F NMR (DMSOꢀd6), δ: 85.24 (s, 3 F, CF3).
Found (%): C, 34.62; H, 2.99; F, 20.30; N, 25.00. C8H8F3N5O3.
Calculated (%): C, 34.42; H, 2.89; F, 20.42; N, 25.09.
a/Å
b/Å
c/Å
α/deg
11.398(1)
16.380(1)
7.231(1)
90
Ethyl 7ꢀtetrafluoroethylꢀ7ꢀhydroxyꢀ4,7ꢀdihydro[1,2,4]triꢀ
azolo[5,1ꢀc][1,2,4]triazineꢀ6ꢀcarboxylate (4b). The yield was 72%,
m.p. 170—172 °C. IR, ν/cm–1: 3265, 3205, 3050 (NHstr, OH);
1715 (CO2Et); 1610, 1565, 1530, 1475, 1460 (C=N, C=C, NHbend);
1235—1120 (C—F). 1H NMR (DMSOꢀd6), δ: 1.27 (t, 3 H,
OCH2Me, 3JH,H = 7.1 Hz); 4.26 (q, 2 H, OCH2Me, 3JH,H = 7.1 Hz);
6.73 (dddd, 1 H, H(CF2)2, 2JH,F = 51.7 Hz, 3JH,F = 8.9 Hz); 8.05
(s, 1 H, =CH); 9.10 (br.d, 1 H, OH, 4JH,F = 2.4 Hz); 13.24 (s, 1 H,
NH). 19F NMR (DMSOꢀd6), δ: 27.77 (m, 2 F, CF2, ABꢀsystem,
β/deg
94.12(1)
90
1346.5(5)
4
1.801
0.197
γ/deg
V/Å3
Z
dcalc/g cm–3
µ/mm–1
Total number of reflections
Number of independent reflections
R1ꢀfactor
2711
2006
0.048
∆
= 2.98, 2JAB = 297.1 Hz, 2JF,H = 51.7 Hz, 2JF,F = 10.7 Hz,
AB
4JF,H = 2.4 Hz); 34.84 (m, 1 F, HCF2, 2JAB = 266.2 Hz, 2JF,F
=
Number of refined parameters
275
9.9 Hz); 41.00 (m, 1 F, HCF2, 2JAB = 266.2 Hz, 2JF,F = 10.2 Hz).
Found (%): C, 34.60; H, 2.71; F, 24.35; N, 22.43. C9H9F4N5O3.
Calculated (%): C, 34.72; H, 2.92; F, 24.42; N, 22.50.
and 3ꢀoxo ester 1 (10 mmol) were mixed in another flask. A solution
of hetaryldiazonium salt 2 was added dropwise and slowly to thus
obtained mixture at 10 °C. A precipitate was filtered off, recrystalꢀ
lized from ethanol, and dried in vacuo.
Methyl 7ꢀdifluoromethylꢀ7ꢀhydroxyꢀ4,7ꢀdihydro[1,2,4]triꢀ
azolo[5,1ꢀc][1,2,4]triazineꢀ6ꢀcarboxylate (4c). The yield was 54%,
m.p. 212—214 °C. The product was purified by column chromatogꢀ
raphy (chloroform was the eluent). IR, ν/cm–1: 3275, 3210, 3110,
3075 (NHstr, OH); 1705 (CO2Me); 1615, 1570, 1540, 1450 (C=N,
C=C, NHbend); 1215—1145 (C—F). 1H NMR (DMSOꢀd6), δ: 3.81
(s, 3 H, OMe); 6.77 (t, 1 H, HCF2, 2JH,F = 54.5 Hz); 7.99 (s, 1 H,
Ethyl 2ꢀ(2,3ꢀdimethylꢀ5ꢀoxoꢀ1ꢀphenylꢀ3ꢀpyrazolinꢀ4ꢀyl)ꢀhyꢀ
drazonoꢀ4,4,4ꢀtrifluorobutyrate (3a). The yield was 57%, m.p.
158—160 °C. The product was purified by column chromatography
(chloroform was the eluent). IR, ν/cm–1: 3100 (NHstr); 1695, 1670,
1650 (C=O); 1595, 1530, 1495 (NHbend, C=N, C=C); 1295—1150
(C—F). 1H NMR (CDCl3), δ: 1.39 (t, 3 H, OCH2Me, 3JH,H = 7.1
Hz); 2.52 (s, 3 H, Me); 3.15 (s, 3 H, NMe); 4.39 (q, 2 H, OCH2Me,
3JH,H = 7.1 Hz); 7.35—7.51 (m, 5 H, Ph); 13.37 (s, 1 H, NH).
19F NMR (CDCl3), δ: 90.81 (s, 3 F, CF3). 1H NMR (DMSOꢀd6),
δ: 1.30 (t, 3 H, OCH2Me, 3JH,H = 7.1 Hz); 2.48 (s, 3 H, Me); 3.20
(s, 3 H, NMe); 4.31 (q, 2 H, OCH2Me, 3JH,H = 7.1 Hz); 7.38—7.58
(m, 5 H, Ph); 13.18 (s, 1 H, NH). 13C NMR (DMSOꢀd6), δ: 10.49
(OCH2Me); 13.86 (Me); 35.13 (NMe); 61.22 (OCH2Me); 111.42
(C(4´)); 117.03 (q, C(4), 1JC,F = 292.7 Hz); 121.23 (C(2)); 124.94
(oꢀC); 127.60 (pꢀC); 129.34 (mꢀC); 133.74 (ipsoꢀC); 144.04 (C(3´));
158.00 (C(5´)); 162.87 (C(1)); 172.39 (q, C(3), 2JC,F = 31.3 Hz).
Found (%): C, 51.38; H, 4.35; F, 14.20; N, 14.10. C17H17F3N4O4.
Calculated (%): C, 51.26; H, 4.30; F, 14.31; N, 14.06.
4
=CH); 8.60 (d, 1 H, OH, JH,F = 3.0 Hz); 13.17 (s, 1 H, NH).
19F NMR (DMSOꢀd6), δ: 33.85 (m, 2 F, HCF2, ABꢀsystem, ∆ΑΒ
=
2
2
2
3.47, JAB = 282.1 Hz, JF(A),H = 55.0 Hz, JF(B),H = 54.8 Hz,
4JF(A),H = 3.0 Hz). Found (%): C, 34.15; H, 2.80; F, 15.48; N, 28.18.
C7H7F2N5O3. Calculated (%): C, 34.02; H, 2.85; F, 15.37; N, 28.33.
Methyl 7ꢀheptafluoropropylꢀ7ꢀhydroxyꢀ4,7ꢀdihydro[1,2,4]triꢀ
azolo[5,1ꢀc][1,2,4]triazineꢀ6ꢀcarboxylate (4d). The yield was 74%,
m.p. 198—200 °C. IR, ν/cm–1: 3290, 3210, 3120, 3080 (NHstr
,
OH); 1725 (CO2Me); 1615, 1560, 1540, 1475 (C=N, C=C,
NHbend); 1215—1100 (C—F). 1H NMR (DMSOꢀd6), δ: 3.79
(s, 3 H, OMe); 8.07 (s, 1 H, =CH); 9.43 (br.s, 1 H, OH); 13.40
(s, 1 H, NH). 19F NMR (DMSOꢀd6), δ: 36.99 (m, 2 F, βꢀCF2);
45.31 (m, 2 F, αꢀCF2, ABꢀsystem, ∆AB = 1.08, 2JAB = 283.4 Hz);
82.37 (t, 3 F, CF3, J = 11.2 Hz). Found (%): C, 29.84; H, 1.66;
F, 36.42; N, 19.28. C9H6F7N5O3. Calculated (%): C, 29.60;
H, 1.66; F, 36.42; N, 19.18.
Methyl 2ꢀ(2,3ꢀdimethylꢀ5ꢀoxoꢀ1ꢀphenylꢀ3ꢀpyrazolinꢀ4ꢀyl)ꢀ
hydrazonoꢀ4,4,5,5,6,6,7,7,7ꢀnonafluorohexanoate (3b). The yield
was 68%, m.p. 129—131 °C. The product was purified by column
chromatography (chloroform was the eluent). IR, ν/cm–1: 3090
Methyl 7ꢀnonafluorobutylꢀ7ꢀhydroxyꢀ4,7ꢀdihydro[1,2,4]triꢀ
azolo[5,1ꢀc][1,2,4]triazineꢀ6ꢀcarboxylate (4e). The yield was 77%,
m.p. 179—181 °C. IR, ν/cm–1: 3275, 3215, 3115, 3080 (NHstr
,
(NHstr); 1690, 1675, 1655 (C=O); 1595, 1530, 1490 (NHbend
,
OH); 1710 (CO2Me); 1615, 1565, 1540, 1440 (C=N, C=C, NHbend);
1275—1115 (C—F). 1H NMR (DMSOꢀd6), δ: 3.79 (s, 3 H,
OMe); 8.07 (s, 1 H, =CH); 9.45 (br.s, 1 H, OH); 13.41 (s, 1 H,
NH). 19F NMR (DMSOꢀd6), δ: 37.05 (m, 2 F, βꢀCF2, ABꢀsystem,
C=N, C=C); 1280—1130 (C—F). 1H NMR (CDCl3), δ: 2.49 (s, 3 H,
Me); 3.16 (s, 3 H, NMe); 3.91 (s, 3 H, OMe), 7.34—7.52 (m, 5 H,
Ph); 13.40 (s, 1 H, NH). 19F NMR (CDCl3), δ: 36.88 (m, 2 F, βꢀCF2);
40.49 (m, 2 F, γꢀCF2); 49.56 (m, 2 F, αꢀCF2); 80.75 (m, 3 F, CF3).
Found (%): C, 42.76; H, 2.66; F, 31.69; N, 10.50. C19H15F9N4O4.
Calculated (%): C, 42.71; H, 2.83; F, 32.00; N, 10.49.
∆
AB = 0.86, 2JAB = 284.8 Hz); 40.23 (m, 2 F, γꢀCF2); 45.69 (m, 2 F,
αꢀCF2, ABꢀsystem, ∆AB = 0.96, 2JAB = 284.1 Hz); 82.26 (m, 3 F,
CF3). Found (%): C, 29.09; H, 1.28; F, 41.22; N, 16.88.
C10H6F9N5O3. Calculated (%): C, 28.93; H, 1.46; F, 41.18; N, 16.87.
Diethyl 7ꢀtrifluoromethylꢀ7ꢀhydroxyꢀ4,7ꢀdihydropyrazoꢀ
lo[5,1ꢀc][1,2,4]triazineꢀ3,6ꢀdicarboxylate (5a). The yield was 65%,
m.p. 203—205 °C. IR, ν/cm–1: 3340, 3150, 3070 (NHstr, OH);
Ethyl 7ꢀtrifluoromethylꢀ7ꢀhydroxyꢀ4,7ꢀdihydro[1,2,4]triꢀ
azolo[5,1ꢀc][1,2,4]triazineꢀ6ꢀcarboxylate (4a). The yield was 52%,
m.p. 164—166 °C. The product was purified by column chromatogꢀ
raphy (chloroform was the eluent). IR, ν/cm–1: 3270, 3205, 3120,

616
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 3, March, 2008
Shchegol'kov et al.
1735, 1705 (2 CO2Et); 1615, 1565, 1465 (C=N, C=C, NHbend);
(1 mmol) was dissolved in 2N NaOH (10 mL) and kept for 16 h at
~20 °C. Then, conc. HCl was added to рH ~1, a precipitate formed
was filtered off, washed with water, and dried in vacuo. The yield
was 87%, m.p. 199—201 °C. IR, ν/cm–1: 3325, 3310 (NHstr, OH);
1720 br. (CO2H); 1605, 1555, 1500 (C=N, C=C, NHbend);
1210—1080 (C—F). 1H NMR (DMSOꢀd6), δ: 3.41 (s, 1 H, COOH);
6.73 (dddd, 1 H, H(CF2)2, 2JH,F = 52.2 Hz, 3JH,F = 8.6 Hz); 8.02
(s, 1 H, =CH); 9.10 (br.s, 1 H, OH); 13.10 (s, 1 H, NH). 19F NMR
1230—1125 (C—F). 1H NMR (DMSOꢀd6), δ: 1.27, 1.29 (both t,
3
6 H, OCH2Me, JH,H = 7.0 Hz); 4.26 (m, 4 H, OCH2Me,
3JH,H = 7.0 Hz); 8.03 (s, 1 H, =CH); 9.22 (br.s, 1 H, OH); 12.68
(br.s, 1 H, NH). 19F NMR (DMSOꢀd6), δ: 85.40 (s, 3 F, CF3).
Found (%): C, 41.60; H, 3.52; F, 16.07; N, 15.79. C12H13F3N4O5.
Calculated (%): C, 41.15; H, 3.74; F, 16.27; N, 16.00.
Methyl 3ꢀethoxycarbonylꢀ7ꢀheptafluoropropylꢀ7ꢀhydroxyꢀ4,7ꢀ
dihydropyrazolo[5,1ꢀc][1,2,4]triazineꢀ6ꢀcarboxylate (5b). The
yield was 78%, m.p. 193—195 °C. IR, ν/cm–1: 3340, 3150, 3075
(NHstr, OH); 1740, 1715 (CO2Et, CO2Me); 1620, 1570, 1465
(C=N, C=C, NHbend); 1230—1125 (C—F). 1H NMR (DMSOꢀd6),
δ: 1.30 (t, 3 H, OCH2Me, 3JH,H = 7.1 Hz); 3.80 (s, 3 H, OMe);
4.28 (q, 2 H, OCH2Me, 3JH,H = 7.1 Hz); 8.07 (s, 1 H, =CH); 9.35
(s, 1 H, OH); 12.75 (s, 1 H, NH). 19F NMR (DMSOꢀd6), δ: 36.95
(m, 2 F, βꢀCF2); 45.65 (m, 2 F, αꢀCF2); 82.41 (m, 3 F, CF3).
Found (%): C, 35.61; H, 2.73; F, 30.28; N, 12.79. C13H11F7N4O5.
Calculated (%): C, 35.79; H, 2.54; F, 30.48; N, 12.84.
(DMSOꢀd6), δ: 27.87 (m, 2 F, CF2, ABꢀsystem, ∆ = 2.93,
AB
2JAB = 296.4 Hz, 2JF,H = 52.2 Hz, 2JF,F = 10.7 Hz, 4JF,H = 3.2 Hz);
2
35.29 (m, 1 F, HCF2, JAB = 265.7 Hz); 40.81 (m, 1 F, HCF2,
2JAB = 265.7 Hz). Found (%): C, 29.78; H, 1.80; F, 26.54; N, 24.62.
C7H5F4N5O3. Calculated (%): C, 29.69; H, 1.78; F, 26.84; N, 24.73.
This work was financially supported by the Ural
Branch of the Russian Academy of Sciences (Program for
Support of Young Scientists and Postgraduate Students of
UB RAS), the Russian Foundation for Basic Research
(Project No. 05ꢀ03ꢀ32384), the American Civilian Reꢀ
search and Development Foundation (CRDF), and
the Ministry of Education and Science of the Russian
Federation (Joint Grant Y3ꢀCꢀ05ꢀ15).
Diethyl 7ꢀtrifluoromethylꢀ7ꢀhydroxyꢀ4,7ꢀdihydroimidazoꢀ
[5,1ꢀc][1,2,4]triazineꢀ3,6ꢀdicarboxylate (6a). The yield was 62%,
m.p. 95—96 °C. The product was purified by column chromatograꢀ
phy (chloroform—ethanol (10 : 1) was the eluent). IR, ν/cm–1
:
3340, 3225, 3135 (NHstr, OH); 1680 br (CO2Et); 1610, 1565, 1480
(C=N, C=C, NHbend); 1225—1095 (C—F). 1H NMR (DMSOꢀd6),
δ: 1.27, 1.29 (both t, 6 H, 2 OCH2Me, 3JH,H = 7.1 Hz); 4.25, 4.28
(both q, 4 H, OCH2Me, 3JH,H = 7.1 Hz); 7.88 (br.s, 1 H, OH); 9.57
(br.s, 1 H, =CH); 12.60 (br.s, 1 H, NH). 19F NMR (DMSOꢀd6), δ:
82.95 (s, 3 F, CF3). 1H NMR (CDCl3), δ: 1.43, 1.44 (both t, 6 H,
2 OCH2Me, 3JH,H = 7.1 Hz); 4.44 (m, 4 H, OCH2Me); 7.47 (br.s,
1 H, OH); 7.64 (s, 1 H, =CH); 10.17 (s, 1 H, NH). 19F NMR
(CDCl3), δ: 78.80 (d, 3 F, CF3, J = 0.9 Hz). Found (%): C, 41.25;
H, 3.68; F, 16.16; N, 15.89. C12H13F3N4O5. Calculated (%):
C, 41.15; H, 3.74; F, 16.27; N, 16.00.
References
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Methyl 3ꢀethoxycarbonylꢀ7ꢀheptafluoropropylꢀ7ꢀhydroxyꢀ4,7ꢀ
dihydroimidazo[5,1ꢀc][1,2,4]triazineꢀ6ꢀcarboxylate (6b). The yield
was, 69%, m.p. 70—72 °C. The product was purified by column
chromatography (chloroform was the eluent). IR, ν/cm–1: 3270,
3100 (NHstr, OH); 1710 (br. CO2Me, CO2Et); 1610, 1590, 1555,
1530, 1460 (C=N, C=C, NHbend); 1225—1120 (C—F). 1H NMR
(DMSOꢀd6), δ: ring (90%): 1.30 (t, 3 H, OCH2Me, 3JH,H = 7.1 Hz);
3.79 (s, 3 H, OMe); 4.29 (q, 2 H, OCH2Me, 3JH,H = 7.1 Hz); 7.86
(s, 1 H, =CH); 9.72 (s, 1 H, OH); 12.65 (s, 1 H, NH); hydrazone
3
(10%): 1.38 (t, 3 H, OCH2Me, JH,H = 7.1 Hz); 3.86 (s, 3 H,
3
OMe); 4.37 (q, 2 H, OCH2Me, JH,H = 7.1 Hz); 7.90 (s, 1 H,
=CH); 13.47 (br.s, 1 H, OH); 13.88 (s, 1 H, NH). 19F NMR
(DMSOꢀd6), δ: ring (90%): 36.88 (m, 2 F, βꢀCF2); 44.07 (m, 2 F,
αꢀCF2); 82.40 (m, 3 F, CF3); hydrazone (10%): 40.79 (m, 2 F,
1
βꢀCF2); 50.93 (m, 2 F, αꢀCF2); 83.32 (m, 3 F, CF3). H NMR
(CDCl3), δ: ring (75%): 1.43 (t, 3 H, OCH2Me, 3JH,H = 7.1 Hz);
4.00 (s, 3 H, OMe); 4.41 (q, 2 H, OCH2Me, 3JH,H = 7.1 Hz); 7.64
(br.s, 1 H, OH); 7.67 (s, 1 H, =CH); 10.18 (br.s, 1 H, NH);
hydrazone (25%): 1.46 (t, 3 H, OCH2Me, 3JH,H = 7.1 Hz); 3.96
(s, 3 H, OMe); 4.47 (q, 2 H, OCH2Me, 3JH,H = 7.1 Hz); 7.63 (br.s,
1 H, OH); 7.65 (s, 1 H, =CH); 14.08 (br.s, 1 H, NH). 19F NMR
(CDCl3), δ: ring (75%): 36.05 (m, 2 F, βꢀCF2); 41.10 (m, 2 F,
αꢀCF2); 81.12 (m, 3 F, CF3); hydrazone (25%): 37.64 (m, 2 F,
βꢀCF2); 49.13 (m, 2 F, αꢀCF2); 81.49 (m, 3 F, CF3). Found (%):
C, 35.95; H, 2.42; F, 30.57; N, 12.89. C13H11F7N4O5. Calculatꢀ
ed (%): C, 35.79; H, 2.54; F, 30.48; N, 12.84.
7ꢀTetrafluoroethylꢀ7ꢀhydroxyꢀ4,7ꢀdihydro[1,2,4]triazoloꢀ
[5,1ꢀc][1,2,4]triazineꢀ6ꢀcarboxylic acid (7). Azolotriazine 4c
Received July 27, 2007;
in revised form December 21, 2007