Regioselective synthesis of polyfluoroalkyl-substituted 7-(1H-1,2,3-triazol-1-yl)-6,7-dihydro-1H-indazol-4(5H)-ones

Article abstract of DOI:10.1134/S1070428012030128

3-Polyfluoroalkyl-6,6-dimethyl-7-(1H-1,2,3-triazol-1-yl)-6, 7-dihydro-1H-indazol-4(5H)-ones were synthesized with high regioselectivity by 1,3-dipolar cycloaddition of terminal alkynes (phenylacetylene, hex- 1-yne, hept-1-yne, and but-3-yn-1-ol) to 7-azid

Full text of DOI:10.1134/S1070428012030128

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 3, pp. 411–418. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © T.S. Khlebnikova, Yu.A. Piven’, A.V. Baranovskii, F.A. Lakhvich, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48,
No. 3, pp. 414–421.
Regioselective Synthesis of Polyfluoroalkyl-Substituted
7-(1H-1,2,3-Triazol-1-yl)-6,7-dihydro-1H-indazol-4(5H)-ones
T. S. Khlebnikova, Yu. A. Piven’, A. V. Baranovskii, and F. A. Lakhvich
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus,
ul. Akademika Kuprevicha 5/2, Minsk, 220141 Belarus
e-mail: khlebnicova@iboch.bas-net.by
Received October 11, 2011
Abstract—3-Polyfluoroalkyl-6,6-dimethyl-7-(1H-1,2,3-triazol-1-yl)-6,7-dihydro-1H-indazol-4(5H)-ones were
synthesized with high regioselectivity by 1,3-dipolar cycloaddition of terminal alkynes (phenylacetylene, hex-
1-yne, hept-1-yne, and but-3-yn-1-ol) to 7-azido-6,6-dimethyl-3-polyfluoroalkyl-6,7-dihydro-1H-indazol-
4(5H)-ones which were prepared by bromination of 6,6-dimethyl-3-polyfluoroalkyl-6,7-dihydro-1H-indazol-
4(5H)-ones with N-bromosuccinimide in anhydrous carbon tetrachloride, followed by treatment of the corre-
sponding 7-bromo derivatives with sodium azide.
DOI: 10.1134/S1070428012030128
Numerous heterocyclic compounds possessing
a pyrazole ring (both isolated and fused to other mono-
or polycyclic systems) have been used as base struc-
tures for the design of many pharmaceutical and agro-
chemical agents, components of modern dyes and
luminophores, polymers, etc. [1]. Diverse physiolog-
ical activity of indazole derivatives, in particular anti-
tumor, antitubercular, anti-inflammatory, antimicrobial,
herbicidal, etc., should specially be noted [2]. Fluorine
compounds, including fluorinated heterocyclic struc-
tures, are widely used in organic synthesis, especially
in the synthesis of drugs and pesticides [3]. Introduc-
tion of fluorine atoms and fluoroalkyl groups into
molecules of organic compounds considerably affects
their physical and chemical properties, reactivity, and
biological activity [4]. Selective introduction of
fluorine atoms or fluoroalkyl groups is a widely used
method for modification of biological activity of
various compounds, including steroids, nucleosides,
antibiotics, prostaglandins, etc. [5].
We recently developed an efficient one-step proce-
dure for the synthesis of polyfluoroalkyl derivatives of
regioisomeric 6,7-dihydro-1H-indazol-4(5H)-ones [6],
which made these compounds accessible and favored
further studies on their reactivity. Polyfluoroalkyl-
substituted 6,7-dihydro-1H-indazol-4(5H)-ones are
polyfunctional compounds which may be used as start-
ing materials for the preparation of various hetero-
cyclic systems containing polyfluoroalkyl groups.
Compounds possessing a 1,2,3-triazole fragment
are components of pharmaceuticals and agrochemicals,
and they exhibit a broad spectrum of biological activ-
ity, such as antibacterial, herbicidal, fungicidal, antial-
lergic, anti-HIV, etc. [7]. In recent time much effort
was made to obtain triazole-containing analogs of nu-
cleosides, peptides, and other natural compounds [8].
At present, so-called click chemistry reactions are
widely used in organic synthesis and medicinal chem-
istry. These reactions must be stereospecific, efficient,
and environmentally safe, and they should occur under
simple experimental conditions with no necessity of
protecting functional groups [9]. Among these, a par-
ticular place is occupied by the azide–alkyne cycload-
dition. Huisgen 1,3-dipolar cycloaddition between
azides and alkynes leads to the formation of 1,2,3-tri-
azoles as mixtures of 1,4- and 1,5-substituted regio-
isomers [10]. The use as catalyst in this reaction of
copper(I) salts (such as iodide, bromide, chloride, and
acetate) and complexes {[Cu(CH3CN)4]PF6 and
[Cu(CH3CN)4]OTf}, as well as of the CuSO4–NaAsc
couple where sodium ascorbate acts as reducing agent,
ensures considerable acceleration of the process under
mild conditions (generally at room temperature in
aqueous medium, i.e., under conditions of click chem-
istry) and regioselective addition of azides to terminal
alkynes with formation of exclusively 1,4-substituted
1,2,3-triazoles [11].
411

KHLEBNIKOVA et al.
412
Scheme 1.
X
X
X
N3
Y
Br
Me
Me
Me
Me
Me
NaN3
NBS
N
N
N
Me
N
N
N
RF
RF
O
RF
O
O
Ia–Ie
IIa–IIe, IIIa, IIIb
IVa–IVe
X
R
4''
5'
4'
N
3'
5''
N6'
N
2'
R
CH, Cu
1'
Me
Me
CuSO4 ·5H2O
N
N
RF
O
Va–Vi
I, IV, X = H, RF = CF3 (a), C2F5 (b), C3F7 (c); X = F, RF = CF3 (d), C3F7 (e); II, X = Y = H, RF = CF3 (a), C2F5 (b), C3F7 (c); X = F,
Y = H, RF = CF3 (d), C3F7 (e); III, Y = Br, RF = CF3, X = H (a), F (b); V, X = H, R = Ph, RF = CF3 (a), C2F5 (b), C3F7 (c); X = H,
RF = CF3, R = Bu (d), C5H11 (e); X = H, R = HOCH2CH2, RF = CF3 (f), C3F7 (g); X = F, R = Ph, RF = CF3 (h), C3F7 (i).
The goal of the present work was to develop a pro-
cedure for regioselective synthesis of 7-(1H-1,2,3-tri-
azol-1-yl)-substituted 6,7-dihydro-1H-indazol-4(5H)-
ones having polyfluoroalkyl groups.
Azides IVa−IVe were obtained in 70−90% yield by
treatment of 7-bromoindazolones IIa−IIe with 4 equiv
of sodium azide in boiling aqueous acetone (reaction
time 48 h). Azides IVa−IVe reacted with terminal
alkynes (phenylacetylene, hex-1-yne, hept-1-yne, and
but-3-yn-1-ol) in a 2:1 mixture of tert-butyl alcohol
and water in the presence of catalytic amounts of
CuSO4·5H2O and copper powder to afford 68−90% of
7-[4-aryl(alkyl)-1H-1,2,3-triazol-1-yl]indazolones
Va−Vi with high selectivity.
1,2,3-Triazole fragment was regioselectively intro-
duced into the 7-position of 3-polyfluoroalkyl-6,7-di-
hydro-1H-indazol-4(5H)-ones Ia−Ie via 1,3-dipolar
cycloaddition of alkynes to azides according to
Huisgen as the key stage. The reaction was carried out
in the presence of copper powder and CuSO4·5H2O
where the latter acted as oxidant [12]. Organic azides
are generally synthesized by nucleophilic substitution
of halogen by azide ion [13]. Therefore, we examined
bromination of indazolones Ia−Ie with N-bromo-
succinimide (NBS). By heating compounds Ia−Ie with
NBS (30% excess) in boiling anhydrous carbon tetra-
chloride for 8 h we obtained the corresponding mono-
bromination products, 1-aryl-7-bromo-3-polyfluoroal-
kyl-6,7-dihydro-1H-indazol-4(5H)-ones IIa−IIe, in
high yield (Scheme 1). Nonfluorinated analogs reacted
with NBS to give the corresponding monobromo
derivatives in 4 h, and no further bromination occurred
in the presence of excess NBS over a longer time [14].
By contrast, heating of indazolones Ia and Id with
5 equiv of NBS in anhydrous carbon tetrachloride over
a period of 50 h gave 7,7-dibromo derivatives IIIa and
IIIb in 52 and 55% yield, respectively.
The structure of the newly synthesized compounds
was confirmed by their elemental compositions and
1
IR, H, 13C, and 19F NMR, and mass spectra. In the
1H NMR spectra of compounds II, IV, and V, the 7-H
signal was displaced downfield relative to the corre-
sponding signal of initial compounds I due to effect of
the substituent on C7 (bromine atom, azido group, or
triazole ring), δ ~4.77−4.90, 4.24−4.29, and 5.52−
5.54 ppm, respectively. The presence of a substituent
on C7 in the indazole ring makes the methyl groups on
C6 magnetically nonequivalent, and they appeared in
the 1H NMR spectra as two singlets at δ 0.93−1.23 and
1.27−1.35 ppm; the same factor was responsible for
magnetic nonequivalence of methylene protons on C5,
which resonated as two doublets at δ ~2.31−2.51 and
2
2.78−3.00 ppm (AB system, J = 16.8−17.1 Hz). The
1H NMR spectra of dibromides IIIa and IIIb lacked
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 3 2012

REGIOSELECTIVE SYNTHESIS OF POLYFLUOROALKYL-SUBSTITUTED
413
7-H signal, and the molecular ion peak cluster in their
mass spectra was characterized by an intensity ratio
corresponding to the presence of two bromine atoms in
their molecules.
Vd, and Ve were analogous to those observed for
compound IId. Therefore, we concluded that the tri-
azole ring in their molecules occupies pseudoaxial
position. Unlike 4-phenyl-1,2,3-triazole Vb, alkyl-sub-
stituted triazole derivatives Vd and Ve were charac-
terized by broadened signals from protons and C4″ and
1
The H NMR spectra of triazoles Va−Vi contained
signals from methyl, methylene, and 7-H protons
together with a signal at δ 7.46−7.56 ppm due to 5-H
in the triazole ring. In the 13C NMR spectra of II–V
signals from the carbonyl carbon atom (C4), C7a (C–N),
and C3 (C=N) were observed at δC 187.9−188.2,
145.5−150.9, and 139.4−140.4 ppm, respectively. In
the 19F NMR spectra of II–V, fluorine nuclei in the
trifluoromethyl group resonated at δF −63.3 ppm, and
compounds having perfluoroethyl and perfluoropropyl
substituents were characterized by fluorine signals at
δF −83.2 (CF3), −113.3 (CF2) and −80.4 (CF3), −109.5
to −109.7 (CF2), and −125.8 to −126.0 ppm (CF2),
respectively.
1
C5″ carbon atoms in the H and 13C NMR spectra.
Presumably, this is the reason for the lack of cross
peak between 5″-H and 7-H in the COSY spectra of
Vd and Ve (the corresponding cross peak is present in
the spectrum of Vb). Analogous pattern is observed in
the HMBC spectra for C4″. Phenyl-substituted triazole
Vb displayed in the HMBC spectrum fairly intense
cross peaks of C4″ with o-H and 5″-H, whereas very
weak cross peaks with 1′′′-H and 2′′′-H were observed
for alkyl derivatives Vd and Ve. Carbon atoms in the
indazole ring of Vb revealed the same correlations in
the HMBC spectrum as those found for compound IId.
To conclude, we have synthesized 3-perfluoroalkyl-
7-[4-alkyl(aryl)-1H-1,2,3-triazol-1-yl]-6,7-dihydro-
1H-indazol-4(5H)-ones in good yield and high regio-
selectivity by Huisgen 1,3-dipolar cycloaddition of
terminal alkynes to 7-azido-3-perfluoroalkyl-6,7-dihy-
dro-1H-indazol-4(5H)-ones in the presence of Cu–
CuSO4·5H2O. The presence of reactive substituents in
the product molecules provides the possibility for their
further functionalization with a view to obtain bio-
logically active substances.
The structure of 7-bromo derivative IId and con-
formation of its molecule in solution were determined
by two-dimensional NMR spectroscopy. Pseudoaxial
orientation of the bromine atom followed from long-
range coupling between pseudoequatorial protons on
C5 and C7 in the HH COSY spectrum. Long-range cou-
pling was also observed between pseudoaxial proton
on C5 and protons in one methyl group (δ 1.19 ppm),
which indicated orthogonal orientation of the C7–Br
bond with respect to the ring plane. The bridgehead
carbon atoms were identified by analysis of the HMBC
spectrum. The C3a atom displayed cross peaks with the
pseudoequatorial proton on C5 and 7-H. Unlike C3a, the
C7a nucleus showed coupling only with 7-H. No cross
peaks for C3 were observed in the HMBC spectrum,
but its signal was readily identified by coupling with
fluorine.
EXPERIMENTAL
The 1H, 13C, and 19F NMR spectra were recorded on
a Bruker BioSpin Avance 500 spectrometer at 500.13,
125.77, and 470.59 MHz, respectively (5 mm z-gradi-
ent QNP probe) from solutions in CDCl3 at 293 K
using the solvent signals as reference (CHCl3,
δ 7.26 ppm; CDCl3, δC 77.16 ppm). The 19F chemical
shifts were measured relative to trifluoromethylben-
zene (δF −63 ppm) as external reference. Homo- and
heteronuclear correlation experiments (HSQC, COSY,
TOCSY, HMBC) were performed using standard
Bruker BioSpin procedures.
Two-dimensional NMR experiments were also per-
formed for compounds Vb, Vd, and Ve in order to
refine their structure. Correlations between the 5-H,
7-H, and methyl protons in the COSY spectra of Vb,
F
F
The IR spectra were measured in KBr on a Bomem
Michelson 100 instrument. The mass spectra (atmos-
pheric pressure chemical ionization) were obtained
using an Accela HPLC instrument equipped with
an LCQ-Fleet mass-selective detector (3D ion trap).
The melting points were determined on a Boetius
melting point apparatus. The elemental analyses were
obtained on a Eurovector EA3000 CHNS–O analyzer.
The progress of reactions and the purity of products
1
N
7a
N2
N
N
H
Br
Br
3
CF3
CF3
H
H
3a
7
6
H 4
Me
H
Me
H
O
O
5
H
H
COSY
HMBC
IId
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 3 2012

KHLEBNIKOVA et al.
414
were monitored by TLC on Silufol UV-254 plates
using ethyl acetate–hexane as eluent. Initial poly-
fluoroalkyl-substituted indazolones Ia−Ie were synthe-
sized according to the procedure described in [6]. The
properties of compounds Ia, Id, and Ie were consistent
with published data [6]. Compounds I and V were
recrystallized from diethyl ether–hexane, and com-
pounds II−IV, from ethanol; all products were isolated
as colorless crystals.
7-Bromo-6,6-dimethyl-1-phenyl-3-trifluoro-
methyl-6,7-dihydro-1H-indazol-4(5H)-one (IIa).
Yield 80%, mp 115–118°C. IR spectrum, ν, cm–1:
1
1700, 1550, 1505. H NMR spectrum, δ, ppm: 1.13 s
(3H, CH3), 1.27 s (3H, CH3), 2.31 d and 2.83 d (1H
each, 5-H, 2J = 17.1 Hz), 4.77 s (1H, 7-H), 7.52 m (3H,
H
arom), 7.57 m (2H, Harom). 13C NMR spectrum, δC,
ppm: 25.2 and 29.4 (6-CH3), 40.0 (C6), 48.4 (C5), 49.1
(C7), 114.6 (C3a), 120.5 q (CF3, JCF = 270 Hz), 125.4
1
(Carom), 130.0 (Carom), 130.3 (Carom), 137.3 (Carom),
6,6-Dimethyl-3-perfluoroethyl-1-phenyl-6,7-dihy-
2
140.4 q (C3, JCF = 40 Hz), 150.7 (C7a), 188.8 (C4).
dro-1H-indazol-4(5H)-one (Ib). Yield 69%, mp 88−
19F NMR spectrum: δF –63.3 ppm (CF3). Found, %:
C 49.52; H 3.55; N 7.13. C16H14BrF3N2O. Calculated,
%: C 49.63; H 3.64; N 7.23.
1
91°C. IR spectrum, ν, cm–1: 1695, 1505. H NMR
spectrum, δ, ppm: 1.12 s (6H, CH3), 2.49 s (2H, 7-H),
2.83 s (2H, 5-H), 7.51 m (5H, Harom). 13C NMR spec-
trum, δC, ppm: 28.2 (6-CH3), 35.5 (C6), 37.1 (C7), 52.7
7-Bromo-6,6-dimethyl-3-perfluoroethyl-1-phen-
yl-6,7-dihydro-1H-indazol-4(5H)-one (IIb). Yield
71%, mp 102–105°C. IR spectrum, ν, cm–1: 1700,
(C5), 110.5 t.q (CF2, 1JCF = 253, JCF = 39 Hz), 117.4
2
1
2
(C3a), 118.9 q.t (CF3, JCF = 286, JCF = 36 Hz), 124.3
1
(Carom), 129.3 (Carom), 129.6 (Carom), 137.8 (Carom),
1515, 1500. H NMR spectrum, δ, ppm: 1.19 s (3H,
2
139.5 t (C3, JCF = 31 Hz), 150.5 (C7a), 189.5 (C4).
CH3), 1.34 s (3H, CH3), 2.39 d and 2.92 d (1H each,
2
19F NMR spectrum, δF, ppm: –83.2 (CF3), –111.44
(CF2). Found, %: C 56.71; H 4.02; N 7.71.
C17H15F5N2O. Calculated, %: C 56.99; H 4.22; N 7.82.
5-H, J = 17.0 Hz), 4.84 s (1H, 7-H), 7.60 m (3H,
H
arom), 7.65 m (2H, Harom). 13C NMR spectrum, δC,
ppm: 25.1 and 29.2 (CH3), 39.7 (C6), 48.5 (C5), 49.1
(C7), 110.5 t.q (CF2, JCF = 253, JCF = 39 Hz), 115.9
1
2
6,6-Dimethyl-3-perfluoropropyl-1-phenyl-6,7-di-
hydro-1H-indazol-4(5H)-one (Ic). Yield 72%,
mp 100–101°C. IR spectrum, ν, cm–1: 1710, 1510.
1H NMR spectrum, δ, ppm: 1.12 s (6H, CH3), 2.48 s
(2H, 7-H), 2.83 s (2H, 5-H), 7.51 m (5H, Harom).
(C3a), 118.9 q.t (CF3, JCF = 286, JCF = 36 Hz), 125.2
1
2
(Carom), 129.9 (Carom), 130.2 (Carom), 137.2 (Carom),
2
139.4 t (C3, JCF = 31 Hz), 150.6 (C7a), 188.1 (C4).
19F NMR spectrum, δF, ppm: –83.2 (CF3), –113.3(CF2).
Found, %: C 46.61; H 3.15; N 6.31. C17H14BrF5N2O.
Calculated, %: C 46.70; H 3.23; N 6.41.
13C NMR spectrum, δC, ppm: 28.1 (6-CH3), 35.4 (C6),
1
37.1 (C7), 52.7 (C5), 108.9 t.m (CF3CF2, JCF
=
1
2
266 Hz), 112.6 t.t (3-CF2, JCF = 255, JCF = 32 Hz),
7-Bromo-6,6-dimethyl-3-perfluoropropyl-1-
phenyl-6,7-dihydro-1H-indazol-4(5H)-one (IIc).
Yield 85%, mp 83–86°C. IR spectrum, ν, cm–1: 1700,
117.6 (C3a), 118.0 q.t (CF3, JCF = 288, JCF = 34 Hz),
1
2
124.4 (Carom), 129.3 (Carom), 129.7 (Carom), 137.8 (Carom),
2
1
139.4 t (C3, JCF = 30 Hz), 150.6 (C7a), 189.4 (C4).
1515, 1500. H NMR spectrum, δ, ppm: 1.23 s (3H,
19F NMR spectrum, δF, ppm: –80.40 (CF3), –109.57
(CF2), –125.85 (CF2). Found, %: C 52.84; H 3.55;
N 6.78. C18H15F7N2O. Calculated, %: C 52.95; H 3.70;
N 6.86.
CH3), 1.39 s (3H, CH3), 2.43 d and 2.97 d (1H each,
2
5-H, J = 17.1 Hz), 4.90 s (1H, 7-H), 7.64 m (3H,
H
arom), 7.69 m (2H, Harom). 13C NMR spectrum, δC,
ppm: 25.1 and 29.3 (CH3), 39.8 (C6), 48.7 (C5), 49.3
(C7), 108.9 t.m (CF3CF2, JCF = 266 Hz), 112.6 t.t
1
Bromination of polyfluoroalkyl-substituted ind-
azolones Ia–Ie (general procedure). N-Bromosuccin-
imide, 0.23 g (1.3 mmol), was added to a solution of
1 mmol of indazolone Ia–Ie in 30 ml of anhydrous
carbon tetrachloride. The mixture was heated for 8 h
under reflux with vigorous stirring and cooled to room
temperature, the precipitate was filtered off, the sol-
vent was distilled off under reduced pressure, the resi-
due was ground with a small amount of hexane, and
the precipitate was filtered off and recrystallized to
obtain 7-bromo derivative IIa−IIe. The reaction of
compounds Ia and Id with 5 equiv of NBS on heating
for 50 h gave (after analogous treatment and recrystal-
lization) 7,7-dibromo derivatives IIIa and IIIb.
(3-CF2, 1JCF = 255, 2JCF = 32 Hz), 117.6 (C3a), 118.0 q.t
1
2
(CF3, JCF = 288, JCF = 34 Hz), 124.4 (Carom), 130.0
(Carom), 130.4 (Carom), 137.4 (Carom), 139.4 t (C3, 2JCF
=
30 Hz), 150.8 (C7a), 188.1 (C4). 19F NMR spectrum, δF,
ppm: –80.4 (CF3), –109.6 (CF2), –126.0 (CF2). Found,
%: C 45.49; H 2.97; N 5.84. C18H14BrF7N2O. Calculat-
ed, %: C 45.37; H 2.90; N 5.75.
7-Bromo-1-(4-fluorophenyl)-6,6-dimethyl-3-tri-
fluoromethyl-6,7-dihydro-1H-indazol-4(5H)-one
(IId). Yield 73%, mp 119–121°C. IR spectrum, ν,
1
cm–1: 1700, 1500. H NMR spectrum, δ, ppm: 1.19 s
(3H, CH3), 1.35 s (3H, CH3), 2.38 d and 2.90 d (1H
each, 5-H, 2J = 17.1 Hz), 4.78 s (1H, 7-H), 7.28 m (2H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 3 2012

REGIOSELECTIVE SYNTHESIS OF POLYFLUOROALKYL-SUBSTITUTED
415
Harom), 7.64 m (2H, Harom). 13C NMR spectrum, δC,
270 Hz), 129.7 d (C2′, C6′, JCF = 9 Hz), 134.9 d (C1′,
ppm: 25.2 and 29.4 (CH3), 40.0 (C6), 48.3 (C5), 48.9
2
JCF = 3 Hz), 139.1 q (C3, JCF = 40 Hz), 150.2 (C7a),
(C7), 114.7 (C3a), 117.1 d (C3′, C5′, JCF = 23 Hz),
1
163.6 d (C4′, JCF = 252 Hz), 187.7 (C4). 19F NMR
1
120.2 q (CF3, JCF = 270 Hz), 127.6 d (C2′, C6′, JCF
=
=
spectrum, δF, ppm: –63.5 (CF3), –109.3 (4′-F). Mass
spectrum: m/z 484 [M]+. Found, %: C 40.84; H 2.57;
N 5.86. C16H12Br2F4N2O. Calculated, %: C 39.70;
H 2.50; N 5.79. M 484.09.
9 Hz), 133.3 d (C1′, JCF = 3 Hz), 140.6 q (C3, JCF
2
40 Hz), 150.8 (C7a), 163.4 d (C4′, 1JCF = 252 Hz), 188.6
(C4). 19F NMR spectrum, δF, ppm: –63.3 (CF3),
–109.5 (4′-F). Found, %: C 47.31; H 3.15; N 6.83.
C16H13BrF4N2O. Calculated, %: C 47.43; H 3.23;
N 6.91.
1-Aryl-7-azido-6,6-dimethyl-3-polyfluoroalkyl-
6,7-dihydro-1H-indazol-4(5H)-ones IVa–IVe (gen-
eral procedure). A solution of 0.26 g (4 mmol) of
sodium azide in 20 ml of water was added to a solution
of 1 mmol of bromo derivative IIa−IIe in 60 ml of
acetone. The mixture was heated for 48 h under reflux
with stirring, acetone was distilled off under reduced
pressure, the residue was treated with 60 ml of chloro-
form, the organic phase was separated and dried over
MgSO4, the solvent was distilled off under reduced
pressure, and the residue was recrystallized.
7-Bromo-1-(4-fluorophenyl)-6,6-dimethyl-3-per-
fluoropropyl-6,7-dihydro-1H-indazol-4(5H)-one
(IIe). Yield 81%, mp 103–105°C. IR spectrum, ν,
1
cm–1: 1700, 1520, 1490. H NMR spectrum, δ, ppm:
1.18 s (3H, CH3), 1.34 s (3H, CH3), 2.38 d and 2.91 d
(1H each, 5-H, 2J = 17.1 Hz), 4.78 s (1H, 7-H), 7.29 m
(2H, Harom), 7.64 m (2H, Harom). 13C NMR spectrum,
δC, ppm: 25.1 and 29.3 (CH3), 39.7 (C6), 48.6 (C5),
49.0 (C7), 108.9 t.m (CF3CF2, 1JCF = 266 Hz), 112.6 t.t
1
2
7-Azido-6,6-dimethyl-1-phenyl-3-trifluorometh-
yl-6,7-dihydro-1H-indazol-4(5H)-one (IVa). Yield
81%, mp 95–97°C. IR spectrum, ν, cm–1: 2100, 1690,
(3-CF2, JCF = 255, JCF = 32 Hz), 116.2 (C3a), 117.1 d
(C3′, C5′, JCF = 23 Hz), 118.0 q.t (CF3, JCF = 288,
1
2JCF = 34 Hz), 127.6 d (C2′, C6′, JCF = 9 Hz), 133.3 d
1
(C1′, JCF = 3 Hz), 139.4 t (C3, JCF = 30 Hz), 150.9
2
1500. H NMR spectrum, δ, ppm: 1.10 s (3H, CH3),
(C7a), 163.4 d (C4′, JCF = 252 Hz), 187.9 (C4).
1
1.27 s (3H, CH3), 2.36 d and 2.78 d (1H each, 5-H,
2J = 16.8 Hz), 4.29 s (1H, 7-H), 7.54 m (2H, Harom),
7.57 m (3H, Harom). 13C NMR spectrum, δC, ppm: 25.9
and 26.1 (CH3), 40.6 (C6), 48.0 (C5), 61.7 (C7), 115.8
19F NMR spectrum, δF, ppm: –80.4 (CF3), –109.5
(4′-F), –109.7 (CF2), –125.9 (CF2). Found, %: C 42.67;
H 2.51; N 5.48. C18H13BrF8N2O. Calculated, %:
C 42.79; H 2.59; N 5.55.
1
(C3a), 120.0 q (CF3, JCF = 270 Hz), 125.5 (Carom),
130.0 (Carom), 130.3 (Carom), 137.2 (Carom), 140.3 q (C3,
2JCF = 40 Hz), 147.9 (C7a), 188.7 (C4). 19F NMR spec-
trum: δF –63.3 ppm (CF3). Found, %: C 55.21; H 4.12;
N 20.15. C16H14F3N5O. Calculated, %: C 55.02;
H 4.04; N 20.05.
7,7-Dibromo-6,6-dimethyl-1-phenyl-3-trifluoro-
methyl-6,7-dihydro-1H-indazol-4(5H)-one (IIIa).
Yield 52%, mp.174–177°C. IR spectrum, ν, cm–1:
1
1700, 1515, 1500. H NMR spectrum, δ, ppm: 1.34 s
(3H, CH3), 1.55 s (3H, CH3), 2.54 d and 3.15 d (1H
2
7-Azido-6,6-dimethyl-3-perfluoroethyl-1-phenyl-
6,7-dihydro-1H-indazol-4(5H)-one (IVb). Yield
70%, mp 110–113°C. IR spectrum, ν, cm–1: 2100,
each, 5-H, J = 16.6 Hz), 7.57 m (3H, Harom), 7.75 m
(2H, Harom). 13C NMR spectrum, δC, ppm: 24.9 and
27.1 (CH3), 49.4 (C6), 50.9 (C5), 62.7 (C7), 113.0 (C3a),
1
1
1690, 1500. H NMR spectrum, δ, ppm: 1.09 s (3H,
119.9 q (CF3, JCF = 270 Hz), 127.6 (Carom), 129.0
(Carom), 130.5 (Carom), 139.0 (Carom), 139.0 q (C3, 2JCF
=
CH3), 1.26 s (3H, CH3), 2.36 d and 2.78 d (1H each,
2
41 Hz), 150.0 (C7a), 188.8 (C4). 19F NMR spectrum:
δF –63.4 ppm (CF3). Mass spectrum: m/z 466 [M]+.
Found, %: C 41.35; H 2.89; N 6.11. C16H13Br2F3N2O.
Calculated, %: C 41.23; H 2.81; N 6.01. M 466.10.
5-H, J = 16.7 Hz), 4.29 s (1H, 7-H), 7.54 m (2H,
Harom), 7.61 m (3H, Harom). 13C NMR spectrum, δC,
ppm: 25.8 and 26.0 (CH3), 40.4 (C6), 48.2 (C5), 61.8
1
2
(C7), 110.5 t.q (CF2, JCF = 253, JCF = 39 Hz), 117.1
1
2
(C3a), 118.9 q.t (CF3, JCF = 286, JCF = 36 Hz), 125.5
7,7-Dibromo-1-(4-fluorophenyl)-6,6-dimethyl-3-
trifluoromethyl-6,7-dihydro-1H-indazol-4(5H)-one
(IIIb). Yield 55%, mp.190–192°C. IR spectrum, ν,
(Carom), 130.0 (Carom), 130.4 (Carom), 137.2 (Carom),
2
139.5 t (C3, JCF = 31 Hz), 147.9 (C7a), 188.1 (C4).
19F NMR spectrum, δF, ppm: –83.2 (CF3), –111.4 (CF2).
Found, %: C 51.21; H 3.60; N 17.63. C17H14F5N5O.
Calculated, %: C 51.13; H 3.53; N 17.54.
1
cm–1: 1700, 1510. H NMR spectrum, δ, ppm: 1.34 s
(3H, CH3), 1.55 s (3H, CH3), 2.54 d and 3.14 d (1H
2
each, 5-H, J = 16.6 Hz), 7.26 m (2H, Harom), 7.74 m
(2H, Harom). 13C NMR spectrum, δC, ppm: 20.5 and
7-Azido-6,6-dimethyl-3-perfluoropropyl-1-phen-
yl-6,7-dihydro-1H-indazol-4(5H)-one (IVc). Yield
81%, mp 85–88°C. IR spectrum, ν, cm–1: 2100, 1700,
27.1 (CH3), 49.4 (C6), 50.9 (C5), 62.7 (C7), 113.1 (C3a),
1
116.2 d (C3′, C5′, JCF = 23 Hz), 119.8 q (CF3, JCF
=
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KHLEBNIKOVA et al.
416
1
1495. H NMR spectrum, δ, ppm: 1.08 s (3H, CH3),
1.26 s (3H, CH3), 2.35 d and 2.78 d (1H each, 5-H,
2J = 16.8 Hz), 4.29 s (1H, 7-H), 7.56 m (2H, Harom),
7.61 m (3H, Harom). 13C NMR spectrum, δC, ppm: 25.8
and 25.9 (CH3), 40.4 (C6), 48.2 (C5), 61.7 (C7),
of the corresponding alkyne (phenylacetylene, hex-
1-yne, hept-1-yne, or but-3-yn-1-ol), 0.038 g
(0.15 mmol) of CuSO4·5H2O, and 150 mg of copper
powder were added, and the mixture was stirred for 5 h
at 50°C in the reactions with hex-1-yne and hept-1-
yne, for 8 h at 50°C in the reaction with phenylacety-
lene, and for 18 h at 80°C in the reaction with but-
3-yn-1-ol. The mixture was cooled, 70 ml of ethyl
acetate was added, the precipitate was filtered off,
the filtrate was dried over MgSO4, the solvent was
distilled off under reduced pressure, and the residue
was recrystallized.
1
108.9 t.m (CF3CF2, JCF = 266 Hz), 112.6 t.t (3-CF2,
1JCF = 255, JCF = 32 Hz), 117.4 (C3a), 118.0 q.t (CF3,
2
1JCF = 288, JCF = 34 Hz), 125.5 (Carom), 130.0 (Carom),
2
130.4 (Carom), 137.2 (Carom), 139.4 t (C3, 2JCF = 30 Hz),
147.9 (C7a), 188.0 (C4). 19F NMR spectrum, δF, ppm:
–80.4 (CF3), –109.6 (CF2), –126.0 (CF2). Found, %:
C 48.00; H 3.06; N 15.48. C18H14F7N5O. Calculated,
%: C 48.12; H 3.14; N 15.59.
6,6-Dimethyl-1-phenyl-7-(4-phenyl-1H-1,2,3-tri-
azol-1-yl)-3-trifluoromethyl-6,7-dihydro-1H-indaz-
ol-4(5H)-one (Va). Yield 74%, mp 86–89°C. IR spec-
trum, ν, cm–1: 1700, 1630, 1600, 1515, 1500. 1H NMR
spectrum, δ, ppm: 0.93 s (3H, CH3), 1.28 s (3H, CH3),
2.51 d and 2.99 d (1H each, 5-H, 2J = 17.1 Hz), 5.54 s
(1H, 7-H), 7.00 m (2H, Harom), 7.37−7.47 m (6H,
7-Azido-1-(4-fluorophenyl)-6,6-dimethyl-3-tri-
fluoromethyl-6,7-dihydro-1H-indazol-4(5H)-one
(IVd). Yield 90%, mp 93–96°C. IR spectrum, ν, cm–1:
1
2100, 1690, 1510. H NMR spectrum, δ, ppm: 1.10 s
(3H, CH3), 1.27 s (3H, CH3), 2.37 d and 2.77 d (1H
each, 5-H, 2J = 16.9 Hz), 4.25 s (1H, 7-H), 7.31 m (2H,
H
arom), 7.55 m (2H, Harom). 13C NMR spectrum, δC,
Harom), 7.48 s (1H, 5″-H), 7.76 m (2H, Harom).
ppm: 25.8 and 26.2 (CH3), 40.7 (C6), 48.0 (C5), 61.6
13C NMR spectrum, δC, ppm: 25.7 and 27.2 (CH3),
(C7), 115.8 (C3a), 117.1 d (C3′, C5′, JCF = 23 Hz),
39.9 (C6), 48.4 (C5), 60.8 (C7), 117.2 (C3a), 119.0 (C5″),
120.0 q (CF3, JCF = 270 Hz), 127.6 d (C2′, C6′, JCF
=
=
119.5 q (CF3, JCF = 270 Hz), 125.0 (Carom), 125.8
1
1
9 Hz), 133.2 d (C1′, JCF = 3 Hz), 139.6 q (C3, JCF
(Carom), 128.8 (Carom), 129.0 (Carom), 129.5 (Carom),
129.8 (Carom), 130.5 (Carom), 136.6 (C1′), 139.6 q (C3,
2JCF = 41 Hz), 145.5 (C7a), 148.2 (C4″), 188.3 (C4).
19F NMR spectrum: δF –63.2 ppm (CF3). Found, %:
C 63.73; H 4.39; N 15.40. C24H20F3N5O. Calculated,
%: C 63.85; H 4.47; N 15.51.
2
41 Hz), 148.0 (C7a), 163.3 d (C4′, 1JCF = 252 Hz), 188.6
(C4). 19F NMR spectrum, δF, ppm: –63.4 (CF3),
–109.2 s (4′-F). Found, %: C 55.19; H 3.48; N 18.93.
C16H13F4N5O. Calculated, %: C 55.32; H 3.57; N 19.07.
7-Azido-1-(4-fluorophenyl)-6,6-dimethyl-3-per-
fluoropropyl-6,7-dihydro-1H-indazol-4(5H)-one
(IVe). Yield 82%, mp 97–100°C. IR spectrum, ν, cm–1:
6,6-Dimethyl-3-perfluoroethyl-1-phenyl-7-
(4-phenyl-1H-1,2,3-triazol-1-yl)-6,7-dihydro-1H-
indazol-4(5H)-one (Vb). Yield 90%, mp 243–246°C.
IR spectrum, ν, cm–1: 1700, 1630, 1600, 1495.
1H NMR spectrum, δ, ppm: 0.92 s (3H, CH3), 1.28 s
1
2100, 1695, 1515, 1490. H NMR spectrum, δ, ppm:
1.08 s (3H, CH3), 1.27 s (3H, CH3), 2.36 d and 2.77 d
(1H each, 5-H, 2J = 16.8 Hz), 4.24 s (1H, 7-H), 7.31 m
(2H, Harom), 7.55 m (2H, Harom). 13C NMR spectrum,
δC, ppm: 25.7 and 26.0 (CH3), 40.4 (C6), 48.3 (C5),
61.7 (C7), 108.9 t.m (CF3CF2, 1JCF = 266 Hz), 112.6 t.t
2
(3H, CH3), 2.50 d and 3.01 d (1H each, 5-H, J =
17.0 Hz), 5.54 s (1H, 7-H), 7.00 m (2H, Harom),
7.37−7.46 m (6H, Harom), 7.47 s (1H, 5″-H), 7.76 m
(2H, Harom). 13C NMR spectrum, δC, ppm: 25.7 and
27.3 (CH3), 39.9 (C6), 48.6 (C5), 61.0 (C7), 110.5 t.q
(3-CF2, JCF = 255, JCF = 32 Hz), 117.1 d (C3′, C5′,
1
2
JCF = 23 Hz), 117.5 (C3a), 118.0 q.t (CF3, JCF = 288,
1
2JCF = 34 Hz), 127.6 d (C2′, C6′, JCF = 9 Hz), 133.2 d
(CF2, JCF = 253, JCF = 39 Hz), 118.7 (C3a), 118.9 q.t
1
2
(C1′, JCF = 3 Hz), 139.4 t (C3, JCF = 30 Hz), 148.0
(CF3, JCF = 286, JCF = 36 Hz), 119.3 (C5″), 125.1
(C2′), 125.9 (C2′′′), 128.9 (C4′′′), 129.1 (C3′′′), 129.7
(C1′′′), 129.9 (C3′), 130.6 (C4′), 136.8 (C1′), 139.9 t (C3,
2JCF = 32 Hz), 145.5 (C7a), 148.3 (C4″), 187.9 (C4).
19F NMR spectrum, δF, ppm: –83.2 (CF3), –111.4 (CF2).
Found, %: C 59.76; H 3.94; N 13.90. C25H20F5N5O.
Calculated, %: C 59.88; H 4.02; N 13.97.
2
1
2
(C7a), 163.3 d (C4′, JCF = 252 Hz), 187.8 (C4).
1
19F NMR spectrum, δF, ppm: –80.4 (CF3), –109.5
(4′-F), –109.7 (CF2), –125.9 (CF2). Found, %: C 46.37;
H 2.89; N 15.10. C18H14F7N5O. Calculated, %:
C 46.26; H 2.80; N 14.99.
1-Aryl-6,6-dimethyl-3-polyfluoroalkyl-7-
[4-phenyl(alkyl)-1H-1,2,3-triazol-1-yl]-6,7-dihydro-
1H-indazol-4(5H)-ones Va–Vi (general procedure).
Azide IVa−IVe, 1 mmol, was dissolved in a mixture of
6 ml of tert-butyl alcohol and 3 ml of water, 1.1 mmol
6,6-Dimethyl-3-perfluoropropyl-1-phenyl-7-
(4-phenyl-1H-1,2,3-triazol-1-yl)-6,7-dihydro-1H-
indazol-4(5H)-one (Vc). Yield 68%, mp 227−230°C.
1
IR spectrum, ν, cm–1: 1700, 1510, 1495. H NMR
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REGIOSELECTIVE SYNTHESIS OF POLYFLUOROALKYL-SUBSTITUTED
417
spectrum, δ, ppm: 0.93 s (3H, CH3), 1.27 s (3H, CH3),
2.50 d and 3.00 d (1H each, 5-H, 2J = 17.0 Hz), 5.54 s
(1H, 7-H), 7.00 m (2H, Harom), 7.36−7.49 m (6H,
7-[4-(2-Hydroxyethyl)-1H-1,2,3-triazol-1-yl]-6,6-
dimethyl-1-phenyl-3-trifluoromethyl-6,7-dihydro-
1H-indazol-4(5H)-on (Vf). Yield 75%, mp.178–82°C.
IR spectrum, ν, cm–1: 3300, 1690, 1500. H NMR
spectrum, δ, ppm: 0.86 s (3H, CH3), 1.24 s (3H, CH3),
2.47 d and 2.92 d (1H each, 5-H, 2J = 17.0 Hz), 2.88 t
H
arom), 7.46 s (1H, 5″-H), 7.76 m (2H, Harom). 13C NMR
spectrum, δC, ppm: 25.6 and 27.0 (CH3), 39.6 (C6),
1
48.6 (C5), 60.8 (C7), 108.9 t.m (CF3CF2, JCF
=
1
2
3
3
266 Hz), 112.6 t.t (3-CF2, JCF = 255, JCF = 32 Hz),
(2H, CH2, J = 5.9 Hz), 3.87 t (2H, CH2, J = 5.9 Hz),
5.48 s (1H, 7-H), 6.96 m (2H, Harom), 7.16 s (1H,
5″-H), 7.41 m (2H, Harom), 7.47 m (1H, Harom).
13C NMR spectrum, δC, ppm: 25.7 and 27.3 (CH3),
28.6 (C1′′′), 40.0 (C6), 48.4 (C5), 60.8 (C7), 61.5 (C2′′′),
118.0 q.t (CF3, JCF = 288, JCF = 34 Hz), 118.8 (C3a),
119.0 (C5″), 125.0 (Carom), 125.7 (Carom), 128.8 (Carom),
129.0 (Carom), 129.5 (Carom), 129.8 (Carom), 130.5
1
2
(Carom), 136.6 (C1′), 139.4 t (C3, JCF = 30 Hz), 145.6
2
(C7a), 148.2 (C4″), 187.6 (C4). 19F NMR spectrum, δF,
ppm: –80.4 (CF3), –109.5 (CF2), –125.9 (CF2). Found,
%: C 56.51; H 3.59; N 12.61. C26H20F7N5O. Calculat-
ed, %: C 56.63; H 3.66; N 12.70.
1
117.3 (C3a), 120.1 q (CF3, JCF = 270 Hz), 121.8 (C5″),
125.0 (C2′), 129.9 (C3′), 130.5 (C4′), 136.7 (C1′),
2
140.5 q (C3, JCF = 41 Hz), 145.7 (C7a), 146.2 (C4″),
188.6 (C4). 19F NMR spectrum: δF –63.2 ppm (CF3).
Found, %: C 57.18; H 4.72; N 16.60. C20H20F3N5O2.
Calculated, %: C 57.28; H 4.81; N 16.70.
7-(4-Butyl-1H-1,2,3-triazol-1-yl)-6,6-dimethyl-
1-phenyl-3-trifluoromethyl-6,7-dihydro-1H-indazol-
4(5H)-one (Vd). Yield 84%, mp 44–47°C. IR spec-
trum, ν, cm–1: 1700, 1500. 1H NMR spectrum, δ, ppm:
0.85 s (3H, CH3), 0.93 t (3H, CH3, 3J = 7.4 Hz), 1.24 s
(3H, CH3), 1.33 m (2H, CH2), 1.59 m (2H, CH2),
2.46 d and 2.93 d (1H each, 5-H, 2J = 17.0 Hz), 2.67 m
(2H, CH2), 5.46 s (1H, 7-H), 6.96 m (2Harom), 7.03 s
(1H, 5″-H), 7.41 m (2H, Harom), 7.48 m (1H, Harom).
13C NMR spectrum, δC, ppm: 13.9 (C4′′′), 22.3 (C3′′′),
25.3 (C1′′′), 25.8 and 27.3 (6-CH3), 31.4 (C2′′′), 39.9
(C6), 48.6 (C5), 60.7 (C7), 117.3 (C3a), 120.2 q (CF3,
1JCF = 270 Hz), 120.6 (C5″), 125.1 (C2′), 129.9 (C3′),
7-[4-(2-Hydroxyethyl)-1H-1,2,3-triazol-1-yl]-6,6-
dimethyl-3-perfluoropropyl-1-phenyl-6,7-dihydro-
1H-indazol-4(5H)-one (Vg). Yield 75%, mp 171–
174°C. IR spectrum, ν, cm–1: 3300, 1700, 1500.
1H NMR spectrum, δ, ppm: 0.87 s (3H, CH3), 1.24 s
2
(3H, CH3), 2.47 d and 2.93 d (1H each, 5-H, J =
3
16.9 Hz), 2.89 t (2H, CH2, J = 5.9 Hz), 3.89 t (2H,
3
CH2, J = 5.9 Hz), 5.50 s (1H, 7-H), 6.97 m (2H,
H
arom), 7.14 s (1H, 5″-H), 7.42 m (2H, Harom), 7.49 m
(1H, Harom). 13C NMR spectrum, δC, ppm: 25.5 and
27.0 (CH3), 28.5 (C1′′′), 39.6 (C6), 48.7 (C5), 60.8 (C7),
61.3 (C2′′′), 108.9 t.m (CF3CF2, 1JCF = 266 Hz), 112.6 t.t
2
130.5 (C4′), 136.8 (C1′), 140.7 q (C3, JCF = 41 Hz),
145.8 (C7a), 149.2 (C4″), 188.5 (C4). 19F NMR spec-
trum: δF –63.2 ppm (CF3). Found, %: C 61.36; H 5.69;
N 16.31. C22H24F3N5O. Calculated, %: C 61.24;
H 5.61; N 16.23.
1
2
(3-CF2, JCF = 255, JCF = 32 Hz), 118.0 q.t (CF3,
1JCF = 288, JCF = 34 Hz), 118.8 (C3a), 121.6 (C5″),
2
124.9 (C2′), 129.7 (C3′), 130.4 (C4′ ), 136.7 (C1′), 139.4 t
.
(C3, 2JCF = 30 Hz), 145.7 (C7a), 146.0 (C4″), 187.6 (C4).
Found, %: C 50.78; H 3.82; N 13.40. C22H20F7N5O2.
Calculated, %: C 50.87; H 3.88; N 13.48.
6,6-Dimethyl-7-(4-pentyl-1H-1,2,3-triazol-1-yl)-
1-phenyl-3-trifluoromethyl-6,7-dihydro-1H-indazol-
4(5H)-one (Ve). Yield 72%, mp.42–45°C. IR spectrum,
ν, cm–1: 1700, 1500. 1H NMR spectrum, δ, ppm: 0.85 s
1-(4-Fluorophenyl)-6,6-dimethyl-7-(4-phenyl-
1H-1,2,3-triazol-1-yl)-3-trifluoromethyl-6,7-dihy-
dro-1H-indazol-4(5H)-one (Vh). Yield 84%, mp 122–
125°C. IR spectrum, ν, cm–1: 1700, 1515, 1500.
1H NMR spectrum, δ, ppm: 0.94 s (3H, CH3), 1.29 s
3
(3H, CH3), 0.90 t (3H, CH3, J = 7.1 Hz), 1.23 s (3H,
CH3), 1.28 m (2H, CH2), 1.32 m (2H, CH2), 1.60 m
2
(2H, CH2), 2.46 d and 2.93 d (1H each, 5-H, J =
17.0 Hz), 2.66 m (2H, CH2), 5.46 s (1H, 7-H), 6.94 m
(2H, Harom), 7.03 s (1H, 5″-H), 7.41 m (2H, Harom),
7.48 m (1H, Harom). 13C NMR spectrum, δC, ppm: 14.1
(C5′′′), 22.5 (C4′′′), 25.6 (C1′′′), 25.8 and 27.3 (6-CH3),
29.1 (C2′′′), 31.4 (C3′′′), 40.0 (C6), 48.5 (C5), 60.6 (C7),
2
(3H, CH3), 2.50 d and 2.97 d (1H each, 5-H, J =
17.1 Hz), 5.52 s (1H, 7-H), 6.98 m (2H, Harom), 7.09 m
(2H, Harom), 7.38 m (1H, Harom), 7.45 m (2H, Harom),
13
7.56 s (1H, 5″-H), 7.78 m (2H, Harom). C NMR spec-
trum, δC, ppm: 25.7 and 27.1 (CH3), 39.9 (C6), 48.3
1
117.3 (C3a), 120.2 q (CF3, JCF = 270 Hz), 120.6 (C5″),
(C5), 60.7 (C7), 116.9 d (C3′, C5′, JCF = 23 Hz), 117.2
125.0 (C2′), 129.9 (C3′), 130.5 (C4′), 136.8 (C1′), 140.6
1
(C3a), 118.9 (C5″), 119.5 q (CF3, JCF = 270 Hz), 125.8
2
q (C3, JCF = 41 Hz), 145.8 (C7a), 149.4 (C4″), 188.6
(Carom), 127.1 d (C2′, C6′, JCF = 9 Hz), 128.9 (Carom),
129.0 (Carom), 129.3 (Carom), 132.5 d (C1′, JCF = 3 Hz),
(C4). 19F NMR spectrum: δF –63.2 ppm (CF3). Found,
%: C 62.15; H 5.98; N 15.81. C23H26F3N5O. Calculat-
ed, %: C 62.01; H 5.88; N 15.72.
2
139.6 t (C3, JCF = 41 Hz), 145.7 (C7a), 148.4 (C4″),
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1
163.3 d (C4′, JCF = 252 Hz), 188.2 (C4). 19F NMR
spectrum, δF, ppm: −63.2 (CF3), −108.7 (4′-F). Found,
%: C 61.55; H 4.19; N 15.01. C24H19F4N5O. Calculat-
ed, %: C 61.41; H 4.08; N 14.92.
3. O’Hagan, D., J. Fluorine Chem., 2010, vol. 131,
p. 1071; Hagmann, W.K., J. Med. Chem., 2008, vol. 51,
p. 4359; Jeschke, P., ChemBioChem, 2004, vol. 5,
p. 571; Furin, G.G., Ftorsoderzhashchie geterotsikliche-
skie soedineniya. Sintez i primenenie (Fluorine-Contain-
ing Heterocyclic Compounds. Synthesis and Applica-
tions), Novosibirsk: Nauka, 2001.
4. Kirsch, P., Modern Fluoroorganic Chemistry, Wein-
heim: Wiley, 2004; Isakova, V.G., Khlebnikova, T.S.,
and Lakhvich, F.A., Usp. Khim., 2010, vol. 79, p. 929.
1-(4-Fluorophenyl)-6,6-dimethyl-3-perfluoro-
propyl-7-(4-phenyl-1H-1,2,3-triazol-1-yl)-6,7-dihy-
dro-1H-indazol-4(5H)-one (Vi). Yield 79%, mp 242–
245°C. IR spectrum, ν, cm–1: 1700, 1515, 1490.
1H NMR spectrum, δ, ppm: 0.93 s (3H, CH3), 1.27 s
(3H, CH3), 2.50 d and 2.97 d (1H each, 5-H, J =
17.0 Hz), 5.52 s (1H, 7-H), 6.98 m (2H, Harom), 7.10 m
(2H, Harom), 7.38 m (1H, Harom), 7.43 m (2H, Harom),
2
5. Begue, J.-P. and Bonnet-Delpon, D., J. Fluorine Chem.,
2006, vol. 127, p. 992.
6. Khlebnikova, T.S., Isakova, V.G., and Lakhvich, F.A.,
Dokl. Nats. Akad. Navuk Belarusi, 2007, vol. 51, no. 6,
p. 55; Khlebnikova, T.S., Isakova, V.G., Baranov-
skii, A.V., and Lakhvich, F.A., Russ. J. Gen. Chem.,
2008, vol. 78, p. 1954.
7. Comprehensive Heterocyclic Chemistry, Katritzky, A.R.
and Rees, C.W., Eds., Oxford: Pergamon, 1984, vol. 5,
p. 669; Katritzky, A.R., Zhang, Yu., and Singh, S.K.,
Heterocycles, 2003, vol. 60, p. 1225; Li, J., Zheng, M.,
Tang, W., He, P-L., Zhu, W., Li, T., Zuo, J.-P., Liu, H.,
and Jiang, H., Bioorg. Med. Chem. Lett., 2006, vol. 16,
p. 5009.
13
7.51 s (1H, 5″-H), 7.77 m (2H, Harom). C NMR spec-
trum, δC, ppm: 25.6 and 27.0 (CH3), 39.6 (C6), 48.5
(C5), 60.8 (C7), 108.9 t.m (CF3CF2, JCF = 266 Hz),
1
1
2
112.6 t.t (3-CF2, JCF = 255, JCF = 32 Hz), 116.9 d
(C3′, C5′, JCF = 23 Hz), 118.0 q.t (CF3, JCF = 288,
1
2JCF = 34 Hz), 118.8 (C3a), 118.9 (C5″), 125.6 (Carom),
127.2 d (C2′, C6′, JCF = 9 Hz), 128.9 (Carom), 129.0
(Carom), 129.3 (Carom), 132.6 d (C1′, JCF = 3 Hz), 139.6 t
(C3, JCF = 30 Hz), 145.8 (C7a), 148.4 (C4″), 163.3 d
2
(C4′, JCF = 252 Hz), 187.4 (C4). 19F NMR spectrum,
1
δF, ppm: –80.4 (CF3), –108.6 (4′-F), –109.5 (CF2),
–125.8 (CF2). Found, %: C 54.72; H 3.25; N 12.20.
C26H19F8N5O. Calculated, %: C 54.84; H 3.36; N 12.30.
8. Xiong, Z., Qiu, X.-L., Huang, Ya., and Qing, F.-L.,
J. Fluorine Chem., 2011, vol. 127, p. 166; Ustinov, A.V.,
Stepanova, I.A., Dubnyakova, V.V., Zatsepin, T.S., No-
zhevnikova, E.V., and Korshun, V.A., Bioorg. Khim.,
2010, vol. 36, p. 437; Xia, Y., Liu, Y., Wang, J.,
Rocchi, P., Qu, F., Iovanna, J., and Peng, L., J. Med.
Chem., 2009, vol. 52, p. 6083; Meldal, M. and
Tornǿe, W., Chem. Rev., 2008, vol. 108, p. 2969.
9. Gil, M.A., Arevalo, M.J., and Lopez, O., Synthesis,
2007, p. 1589; Tron, G.C., Pirali, T., Billington, R.A.,
Canonico, P.L., Sorba, G., and Genazzani, A.A., Med.
Res. Rev., 2008, vol. 28, p. 278; Kolb, H.C. and Sharp-
less, K.B., Drug Discovery Today, 2003, vol. 8, p. 1128.
This study was performed under financial support
by the State Committee of Science and Technology of
Belarus Republic and by the Belarusian Republican
Foundation for Fundamental Research (project
no. Kh10LAT-005).
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 3 2012