Fluoroalkyl-substituted lithium 1,3-diketonates in reactions with hetarylhydrazines

Article abstract of DOI:10.1134/S1070428014060013

Fluoroalkyl-substituted lithium 1,3-diketonates reacted with 4-hydrazinyl-6-methylpyrimidin-2-amine, 2,6-dimethylpyrimidin-4-ylhydrazine, 7-fluoroquinoxalin-6-ylhydrazine, and benzothiazol-2-ylhydrazine to give the corresponding hetaryl-substituted pyrazo

Full text of DOI:10.1134/S1070428014060013

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 6, pp. 767–777. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © N.S. Boltacheva, L.N. Dianova, P.A. Slepukhin, V.I. Filyakova, V.A. Bakulev, V.N. Charushin, 2014, published in Zhurnal
Organicheskoi Khimii, 2014, Vol. 50, No. 6, pp. 785–795.
Dedicated to Full Member of the Russian Academy of Sciences
O.N. Chupakhin on his 80th anniversary
Fluoroalkyl-Substituted Lithium 1,3-Diketonates
in Reactions with Hetarylhydrazines
N. S. Boltachevaa, L. N. Dianovab, P. A. Slepukhina, V. I. Filyakovaa,
V. A. Bakulevb, and V. N. Charushina
a Postovskii Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences,
ul. S. Kovalevskoi/Akademicheskaya 22/20, Yekaterinburg, 620990 Russia
e-mail: vif@ios.uran.ru
b Institute of Chemical Technology, Ural Federal University, ul. Mira 28, Yekaterinburg, Russia
Received December 27, 2013
Abstract—Fluoroalkyl-substituted lithium 1,3-diketonates reacted with 4-hydrazinyl-6-methylpyrimidin-2-
amine, 2,6-dimethylpyrimidin-4-ylhydrazine, 7-fluoroquinoxalin-6-ylhydrazine, and benzothiazol-2-ylhydra-
zine to give the corresponding hetaryl-substituted pyrazoles. The molecular and crystal structures of 4-methyl-
6-(3-methyl-5-trifluoromethyl-1H-pyrazol-1-yl)pyrimidin-2-amine and 4-(5-difluoromethyl-4,5,6,7-tetrahydro-
2H-indazol-2-yl)-6-methylpyrimidin-2-amine were determined by X-ray analysis.
DOI: 10.1134/S1070428014060013
In recent years, systems composed of two or more
heterocycles of different natures have attracted keen
interest. A huge number of possible ring combinations
make it possible to vary over a wide range properties
and biological activity of the resulting compounds.
1,3-Dicarbonyl compounds and their derivatives,
including fluorine-containing ones, are very important
building blocks in the synthesis of numerous hetero-
cycles. For example, the reaction of trifluoroacetyl-
acetone with hetarylhydrazines (2-hydrazinylthiazoles,
2-hydrazinylbenzothiazoles [1–4], 2-hydrazinylbenz-
oxazole [5], 2-hydrazinylquinolines [6]) gave a series
of bi- and tricyclic compounds containing a pyrazole
ring. However, these reactions are not selective due to
formation of fairly stable intermediate 4,4,4-trifluoro-
butane-1,3-dione hydrazones and mixtures of regio-
isomeric pyrazoles. The reaction selectivity can often
be improved by using the corresponding lithium
enolates instead of fluoroalkyl-substituted unsym-
metrical 1,3-diketones [7–17]; such lithium enolates
are more accessible, stable on storage, and convenient
for use in chemical processes. We previously demon-
strated advantages of lithium 1,3-diketonates I as
three-carbon building blocks in the synthesis of fluoro-
alkyl-substituted heterocycles [7–11, 14, 16, 17], in-
cluding N-unsubstituted and N-phenyl-substituted pyr-
azoles [7, 16, 17].
In the present work we examined reactions of
fluoroalkyl-substituted lithium 1,3-diketonates Ia–Ig
with 4-hydrazinyl-6-methylpyrimidin-2-amine (IIa),
2,6-dimethylpyrimidin-4-ylhydrazine (IIb), 7-fluoro-
quinoxalin-6-ylhydrazine (IIc), and benzothiazol-2-yl-
hydrazine (IId) (Table 1). These, at first glance simple
and predictable, reactions could give rise to regioiso-
meric dihydropyrazole and/or pyrazole derivatives.
However, structural specificities of hetarylhydrazines
IIa–IId may favor alternative reaction paths. For in-
stance, compound IIa possesses an amino group in the
pyrimidine ring, while hydrazine IIc contains a labile
fluorine atom in the quinoxaline fragment. In addition,
opening of carbocycles in initial diketonates Ie, If, and
Ig is possible. The latter transformation was observed
previously in reactions of lithium diketonates contain-
ing cycloalkane fragments [R1R2 = (CH2)n] with ben-
zene-1,2-diamine and 2-aminobenzenethiol [17, 18].
In this work we found that the examined reactions
led to the formation of only pyrazole ring and that the
heterocycle in the initial hetarylhydrazine remains
unchanged (Scheme 1). The composition of products
formed in the reactions of lithium diketonates Ia–Ig
767

BOLTACHEVA et al.
768
Scheme 1.
R1
R1
R1
R1
HO
R2
RF
R2
RF
R2
R2
RF
+
R3NHNH2
RF
N
N
N
N
N
N
OLi
Ia–Ig
O
R3
R3
R3
IIa–IId
IIIa–IIId
IVa–IVg
Va–Vk
3-RF isomer
5-RF isomer
For RF, R1, R2, and R3 in I, III–V, see table.
H2N
N
Me
N
N
N
N
S
II, R3 =
(a),
(b),
(c),
(d).
N
N
F
Me
Me
reacted with hydrazine IIa to produce hydroxydihy-
dropyrazoles IIIb and IIIc, respectively, and no subse-
quent dehydration was observed.
with substituted hydrazines IIa–IId is determined by
the natures of both fluoroalkyl substituent in initial di-
ketonate I and substituents in hydrazines II (Table 1).
The reaction of diketonate Ia with hydrazine IIa con-
taining an amino group in the pyrimidine ring in
ethanol–acetic acid gave a mixture of hydroxydihy-
dropyrazole IIIa and its dehydration product, pyrazole
Va. Compounds IIIa and Va were isolated as pure
substances and characterized. Diketonates Ib and Ic
Reactions of diketonates Ia–Ig with hetarylhydra-
zines under more harsh conditions (in boiling glacial
acetic acid) afforded either mixtures of 3-RF (IVa–IVc,
IVf) and 5-RF isomers (Va, Vb, Ve, Vi) or 5-RF iso-
mers alone (Vc, Vd, Vf–Vh, Vj). An exception was
the reaction of diketonate Ib with benzothiazolyl-
Table 1. Reaction of lithium 1,3-diketonates Ia–Ig with hetarylhydrazines IIa–IId
Product (yield, %)
Compound
RF
R1
H
R2
Ph
R3NHNH2
Methoda
no.
III
IV
V
Ia
HCF2
IIa
a
b
c
IIIa (47)
–
Va (21)
–
IVa, Va, 3:1 (47)
–
–
Va (67)
Ib
Ic
CF3
H
H
H
Ph
IIa
IIa
a
b
a
b
b
b
b
b
b
b
b
b
b
b
b
IIIb (60)
–
–
–
IVb, Vb, 6:1 (42)
HCF2
Me
Me
IIIc (58)b
–
–
–
–
Vc (76)
Vd (69)
Id
Ie
If
CF3
IIa
IIa
IIa
IIa
IIb
IIb
IIc
IIc
IId
IId
IId
–
–
HCF2
HCF2
CF3
(CH2)3
(CH2)4
(CH2)4
–
IVc, Ve, 1:5 (66)
–
–
Vf (81)
Vg (71)
–
Ig
Ia
Ib
Ia
Ib
Ia
Ib
Ig
–
–
HCF2
CF3
H
H
H
H
H
H
Ph
Ph
Ph
Ph
Ph
Ph
–
IVd (56)
–
–
Vh (49)
–
HCF2
CF3
–
IVe (74)
–
IVf, Vi, 1:1 (60)
IVg, Vk, 3:1
–
HCF2
CF3
–
IIId (69)
–
CF3
(CH2)4
–
Vj (49)
a
i: EtOH, AcOH, reflux; ii: AcOH, reflux; iii: (1) CF3COOH, reflux; (2) 2 N NaOH.
Isolated as acetate.
b
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 6 2014

FLUOROALKYL-SUBSTITUTED LITHIUM 1,3-DIKETONATES
769
C5
hydrazine IId, which produced hydroxydihydropyr-
azole IIId. In the reaction of diketonate Ia with hydra-
zine IIa in boiling trifluoroacetic acid (which is known
as one of the most efficient dehydrating agents) we
obtained the corresponding trifluoroacetate, and treat-
ment of the latter with 2 N NaOH gave pyrazole Va.
C4
C10
C3
C2
N4
N3
N1
N5
C9
C8
N2
C1
The structure of compounds III–V was confirmed
C7
C6
1
by elemental analyses and IR and H NMR spectra.
Some compounds were additionally characterized by
19F and 13C NMR spectra, GC/MS data, and X-ray
analysis. The 1H NMR spectra of dihydropyrazoles III
(R1 = H) contained a singlet at δ 5–8 ppm due to OH
proton and an AB pattern in the region δ 3–4 ppm (2J =
18–24 Hz) due to diastereotopic methylene protons on
C3. Singlets at δF 81.40 and 80.37 ppm in the 19F NMR
spectra of IIIb and IIId are typical of CF3 groups
attached to sp3-carbon atom (cf. [19]). The fluorine
atoms in the HCF2 group of IIIa and IIIc are dia-
stereotopic, and they appeared as an AB spin system in
F2
F1
Fig. 1. Structure of the molecule of 4-(5-difluoromethyl-3-
methyl-1H-pyrazol-1-yl)-6-methylpyrimidin-2-amine (Vc)
according to the X-ray diffraction data.
19
the F NMR spectra. Compounds III displayed in the
1H and 19F NMR spectra spin–spin coupling between
the fluorine nuclei and methylene protons on C3 with
4
a coupling constant JHF of ~2.4–2.5 Hz. The above
spectral parameters correspond to 5-hydroxy-5-RF
derivatives rather than to isomeric 3-hydroxy-5-RF-
dihydropyrazoles.
Dehydration of hydroxydihydropyrazoles IIIa and
IIIb could produce exclusively 5-RF isomers Va and
Vb. In fact, compounds Va and Vb were obtained by
heating hydroxy derivatives IIIa and IIIb in boiling
acetic anhydride and subsequent treatment of N,N-di-
acyl derivatives with 2 N aqueous NaOH on heating.
Intermediate N,N-diacetyl derivative VI was isolated
and characterized by spectral data (Scheme 2).
Fig. 2. A fragment of crystal packing of 4-(5-difluoromethyl-
3-methyl-1H-pyrazol-1-yl)-6-methylpyrimidin-2-amine (Vc).
F2
F1
N3
C6
C7
N2
C3
C1
C9
C8
N1
C5
C10
Scheme 2.
N4
F3C
Me
N
NaOH
C13
C2
Ac2O
N
IIIb
Vb
C1
C11
N5
N
N
Ph
C12
Ac2N
VI
Fig. 3. Structure of the molecule of 4-[5-(difluoromethyl)-
4,5,6,7-tetrahydro-2H-indazol-2-yl]-6-methylpyrimidin-2-
amine (Vf) according to the X-ray diffraction data. Non-
hydrogen atoms are shown as thermal vibration ellipsoids
with a probability of 50%.
The structure of the condensation products of
fluoroalkyl-substituted lithium 1,3-diketonates Ia–Ig
with hetarylhydrazines IIa–IId was determined on the
basis of the spectral data for compounds Va–Vc and
Vf, taking into account the data of [4, 19, 20]* where
some diagnostic features for the assignment of substi-
tuted pyrazoles to 3-RF or 5-RF isomers were formulat-
* The chemical shifts of the fluorine nuclei in CF3 groups given
in [19, 20] were recalculated relative to hexafluorobenzene:
δ(C6F6) = δ(CFCl3) + 162.9.
19
ed. In the F NMR spectra of 3-RF pyrazoles the CF3
singlet is observed at δF 99–100 ppm (relative to C6F6)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 6 2014

BOLTACHEVA et al.
fragment ion peaks with the same m/z values: 327
770
b
[M]+ (68.5 and 80.2%), 326 [M – H]+ (83.6 and
15.1%), 250 [M – Ph]+ (79.6 and 14.4%), 224 [M –
PhCN]+ (13.6 and 99.8%), 223 [M – H – PhCN]+ (53.1
and 27.6%). The peaks with m/z 276 [M – HCF2]+ and
275 [M – H – HCF2]+ were present only in the mass
spectrum of 3-RF isomer IVg, while those with
m/z 205, 197, 193 [M – Ht]+, and 174 [M – Ht – F]+
were observed only in the spectrum of 5-RF isomer
Vk. The fragment ion peaks with m/z 134 [Ht]+, 116
[M – Ht – Ph]+, 103 [PhCN]+, 77 [Ph]+, and 51
[HCF2]+ had comparable intensities in the spectra of
both regioisomers.
The structure of compounds Vc and Vf was unam-
biguously determined by X-ray analysis (Figs. 1–4).
Molecule Vc in crystal (Fig. 1) is planar; deviations of
atoms from the mean-square plane do not exceed
0.05 Å, except for the difluoromethyl carbon atom
which deviates from that plane by 0.082 Å. The bond
lengths and bond angles in molecule Vc approach the
corresponding standard values (Table 2). Molecules Vc
in crystal are linked to dimers via intermolecular
hydrogen bond system (Table 3), and the dimers are
packed to form parallel and crosswise layers (Fig. 2).
Within a layer, molecules Vc are linked through
a system of π–π contacts with an interplanar distance
of ~3.25 Å.
0
c
Fig. 4. A fragment of crystal packing of 4-[5-(difluoro-
methyl)-4,5,6,7-tetrahydro-2H-indazol-2-yl]-6-methylpyrim-
idin-2-amine (Vf). A view along the a axis; hydrogen atoms
are not shown.
while the corresponding signal of the 5-CF3 group is
located at δF 102–103 ppm. It was difficult to assign
substituted pyrazoles with RF = HCF2 to 3-RF or 5-RF
isomers by the chemical shifts of the fluorine nuclei in
the HCF2 group, since the difference in the δF 1v9alues of
the 3-RF or 5-RF isomers was too small. The F NMR
spectrum of 5-RF isomer Vi characteristically dis-
played spin–spin coupling of the 6′-F nucleus in the
quinoxaline fragment with the CF3 group; no such
1
coupling is observed in 3-RF isomer IVf. The H and
19F NMR spectra of the product obtained from diketo-
nate Ia and hydrazine IIc were consistent with the
structure of 3-RF isomer IVe: there was no coupling
between 6′-F and HCF2, whereas the =CH singlet
appeared in the 1H NMR spectrum at δ 6.83 ppm.
The crystal structure of compound Vf is formed by
three crystallographically independent molecules A–C.
The bond lengths and bond and torsion angles in mole-
cules A–C differ insignificantly and are close to the
corresponding standard values (Table 4). Figure 3
shows the structure of molecule A. Molecules A–C are
planar; deviation of atoms from the mean-square plane
does not exceed 0.05 (A) and 0.1 Å (B, C). The
fluorine atoms in the difluoromethyl group and the
cyclohexenyl fragment of molecule A are disordered
by two positions with populations of 0.8/0.2 and
0.5/0.5, respectively. Molecules Vf in crystal are
linked to dimers through a system of intermolecular
hydrogen bonds (Table 4). The dimer formed by mole-
cules B is centrosymmetric due to intermolecular hy-
drogen bond between the amino group and nitrogen
atom of the pyrimidine ring: N3B–H3BA···N1B [–x + 2,
–y + 3, –z], while molecules A and B form noncentro-
symmetric dimers where the mean-square planes of the
heterocyclic systems are arranged at a dihedral angle
of 21.5° and the distance N3···N1A 3.04 Å [x + 1, y, z]
appears to be shorter than the distance N3A···N1 3.1 Å
[x – 1, y, z]. As a result, layered structure with the
positions of molecules modulated along the b axis is
GC/MS analysis of the product mixture obtained in
the reaction of lithium diketonate Ia and hydrazine
derivative IId revealed two components with retention
times of 11.86 and 12.58 min. According to the 1H and
19F NMR data, isomer IVg predominated. Therefore,
the peak with τr 11.86 min having a larger area was
assigned to major isomer IVg, and the minor peak with
τr 12.58 min, to isomer Vk. The mass spectra of IVg
and Vk differed only by relative intensities of the main
Table 2. Selected bond lengths and bond angles in the mole-
cule of 4-(5-difluoromethyl-3-methyl-1H-pyrazol-1-yl)-6-
methylpyrimidin-2-amine (Vc)
Bond
d, Å
Angle
ω, deg
C1–N5
C1–N1
C1–N2
C4–C5
N3–C2
N4–N3
F1–C6
F2–C6
1.345(2)
1.341(2)
1.346(2)
1.495(2)
1.408(2)
1.370(2)
1.364(2)
1.363(2)
N1C1N2
N5C1N2
N1C1N5
F2C6F1
F2C6C7
F1C6C7
C8C7C6
N3C7C6
126.41(18)
116.55(19)
117.02(19)
104.90(15)
110.06(15)
107.44(15)
128.19(18)
125.27(17)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 6 2014

FLUOROALKYL-SUBSTITUTED LITHIUM 1,3-DIKETONATES
771
Table 3. Parameters of hydrogen bonds in the crystal structures of compounds Vc and Vf
D–Ha
D–H, Å
H···A
∠DHA, deg
D···A, Å
A
Compound Vc
N5–H5A
N5–H5B
0.88(2)
0.83(2)
2.59(2)
2.23(2)
174.7(2)
174.4(2)
3.468(2)
3.061(2)
F1 [–x + 3/2, y + 1/2, –z – 1/2]
N1 [–x + 2, –y + 3, –z]
Compound Vf
N3B–H3BA
N3A–H3AA
N3–H3B
0.860
0.860
0.860
2.197
2.294
2.187
178.77
157.41
174.44
3.057
3.105
3.044
N1B [–x + 1, –y, –z ]
N1 [x – 1, y, z]
N1A [x + 1, y, z]
a
Atoms in molecule A are numbered without indices, in molecule B, with superscript “A”, and in molecule C, with superscript “B”.
5-hydroxy-5-RF-dihydropyrazoles is consistent with
the known stabilization of adducts with a fluoroalkyl
substituent and a hydroxy group attached to the same
carbon atom. The reaction of fluoroalkyl-substituted
lithium 1,3-diketonates with hydrazine derivatives in
organic acids ensures preparation of 3-RF and/or
5-RF pyrazoles without intermediate isolation of 5-hy-
droxy-5-RF-dihydropyrazoles. Unlike the correspond-
ing 1,3-diketones, no hydrazones were formed from
their lithium enolates. As in reactions of fluoroalkyl-
substituted 1,3-diketones with hydrazines, it is impos-
sible to predict a priori the reaction selectivity on the
basis of the initial reactant structure. Nevertheless, the
use of fluoroalkyl-substituted lithium 1,3-diketonates
instead of the corresponding 1,3-diketones seems to be
more advantageous due to appreciable reactant and
time economy as a result of elimination of several
steps related to the isolation and purification of inter-
mediate products.
obtained (Fig. 4). We believe that such modulation is
related to perturbations introduced by the cyclohexenyl
and difluoromethyl fragments into the common inter-
layer π–π contact system.
Thus, on the basis of fluoroalkyl-substituted lithium
1,3-diketonates and hetarylhydrazines we have synthe-
sized new heterocyclic ensembles composed of pyra-
zole (or dihydropyrazole) and pyrimidine, quinoxaline,
or benzothiazole rings.
Analysis of our results and the data published in
[1–8, 12, 16, 17] showed that fluoroalkyl-substituted
lithium 1,3-diketonates react with hydrazine deriva-
tives to produce compounds containing a pyrazole
ring, namely 5-hydroxy-5-RF-dihydropyrazoles and
regioisomeric 3-RF and/or 5-RF pyrazoles. 3-Hydroxy-
3-RF-dihydropyrazoles were not isolated, presumably
due to their facile dehydration to the corresponding
3-RF pyrazoles. The possibility for the isolation of
Table 4. Selected bond lengths and bond angles in crystallographically independent molecules A–C of compound Vf
Parameter
Molecule A
Molecule B
Molecule C
Bond length, Å
N1–C4
N2–C4
N3–C4
N4–N5
N4–C3
N4–C7
C1–C5
1.346(2)
1.339(2)
1.342(2)
1.348(2)
1.339(2)
1.369(2)
1.407(2)
1.382(2)
1.498(2)
1.342(2)
1.346(2)
1.341(2)
1.336(2)
001.3666(19)
1.414(2)
001.3715(19)
1.410(2)
1.384(2)
1.379(2)
1.502(2)
1.499(2)
Bond angle, deg
N1C4N2
N3C4N1
N3C4N2
126.05(18)
116.48(18)
117.47(18)
126.22(18)
116.78(17)
117.00(18)
125.79(18)
117.07(17)
117.14(18)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 6 2014

BOLTACHEVA et al.
772
Table 5. Principal crystallographic parameters of com-
pounds Vc and Vf and parameters of X-ray diffraction
experiments
monitored by TLC (Silufol UV-254, CHCl3); spots
were developed by treatment with aqueous solutions of
Cu(OAc)2 and KMnO4. The NMR spectra were record-
ed on a Bruker DRX-400 spectrometer [400 (1H), 376
(19F), and 100 MHz (13C)] using tetramethylsilane
Parameter
Formula
Vc
Vf
C10H11F2N5
239.24
C13H15F2N5
279.30
295(2)
13
(1H, C) and C6F6 (19F) as internal standards. The IR
Molecular weight
Temperature, K
Crystal system
Space group
Unit cell parameters:
a, A
spectra were measured on a Perkin Elmer Spectrum
One spectrometer with Fourier transform from samples
dispersed in mineral oil. The elemental compositions
were determined on a Perkin Elmer 2400 analyzer. The
mass spectra were obtained on a Varian Saturn 2100T
GC/MS (GC 3900) system [VF-5ms column, 30 m×
0.25 mm; carrier gas helium, flow rate 1 mL/min; oven
temperature programming from 40 (3 min) to 200°C at
a rate of 20 deg/min].
295(2)
Monoclinic
P21/n
Triclinic
P-1
13.374(4)
005.3977(8)
0015.2818(17)
90
11.8378(7)
12.0160(6)
15.3079(7)
82.942(4)
73.893(4)
70.802(5)
1974.43(18)
6
b, A
c, A
α, deg
The X-ray diffraction data for compounds Vc and
Vf were acquired according to a standard procedure on
an Xcalibur 3 automatic four-circle diffractometer
equipped with a CCD detector (λMoKα radiation,
graphite monochromator, ω-scanning, scan step 1.0°)
from a 0.51×0.12×0.08-mm colorless needle-shaped
single crystal of Vc and a 0.45×0.35×0.29-mm color-
less prismatic crystal of Vf. No correction for absorp-
tion was applied because of its insignificance. The
structure was solved by the direct method using
SHELXS97 [26] and was refined against F2 by the
full-matrix least squares procedure in anisotropic ap-
proximation (isotropic for hydrogen atoms) using
SHELXL97 [26]. Hydrogen atoms were visualized by
the electron density maps, and their positions were
refined according to the riding model with dependent
thermal parameters. The sets of crystallographic data
for compounds Vc and Vf were deposited to the
Cambridge Crystallographic Data Centre (entry
nos. CCDC 1002976, 1002977) and are available at
www.ccdc.cam.ac.uk/data_request/cif. The principal
crystal structure parameters and parameters of X-ray
diffraction experiments are collected in Table 5, and
selected bond lengths and bond angles are given in
Tables 2 and 4.
β, deg
102.826(16)
90
γ, deg
V, Å3
1075.6(4)
4
Z
d, g/cm3
1.477
1.409
μ, mm–1
0.120
0.109
Θ range, deg
2.73 ≤ Θ ≤ 31.78 2.61 ≤ Θ ≤ 28.28
Completeness, %
99.1 (27.00)
97.4 (26.00)
(Θ, deg)
Total number of
reflections
13401
16501
Number of indepen-
dent reflections
03303
09266
Rint
0.0667
01088
0.0232
03828
Number of reflections
with I > 2σ(I)
Number of variables
Goodness of fit (F2)
R1 [I > 2σ(I)]
162
1.0000
586
1.0030
0.0460
0.0466
wR2 [I > 2σ(I)]
0.0778
0.0949
R1 (all reflections)
wR2 (all reflections)
Δemax/min., e/Å3
0.1673
0.1191
0.0845
0.1005
0.288/–0.290
0.358/–0.258
Reaction of lithium 1,3-diketonates Ia–Ig with
hetarylhydrazines IIa–IId (general procedures). a. In
EtOH–AcOH. Equimolar amounts of diketonate I and
hydrazine II were dissolved in a minimum amount of
ethanol, 2 equiv of glacial acetic acid was added, and
the mixture was heated under reflux until the initial
compounds disappeared (TLC). The mixture was then
poured into 20 mL of water, the precipitate was filtered
off, and the filtrate was extracted with two portions of
chloroform. The solvent was removed from the extract,
and the residue was combined with the precipitate and
EXPERIMENTAL
Lithium diketonates Ia–Ig were prepared according
to the procedure described in [7]; their characteristics
were reported in [21]. 4-Hydrazinyl-6-methylpyrimi-
din-2-amine (IIa), 2,6-dimethylpyrimidin-4-ylhydra-
zine (IIb), 7-fluoroquinoxalin-6-ylhydrazine (IIc), and
benzothiazol-2-ylhydrazine (IId) were synthesized as
described in [22–25]. The progress of reactions was
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FLUOROALKYL-SUBSTITUTED LITHIUM 1,3-DIKETONATES
773
subjected to column chromatography using chloroform
as eluent, the separation process being monitored by
TLC. The collected fractions were evaporated, and
compounds V, IV, and III (hereinafter, in order of
elution) were recrystallized from chloroform–
hexane (1:3).
H 4.62; F 11.91; N 22.12. C15H15F2N5O. Calculated,
%: C 56.42; H 4.74; F 11.89; N 21.93.
b. From 1 g (4.9 mmol) of diketonate Ia and 0.6 g
(4.9 mmol) of hydrazine IIa we obtained 0.7 g (48%)
of a mixture of isomers Va and IVa at a ratio of 2:1.
IR spectrum, ν, cm–1: 3450, 3230, 3150 (NH), 1638 s,
1
1567 m (C=N, C=C). The H and 19F NMR spectra
b. In AcOH. Equimolar amounts of diketonate I and
hetarylhydrazine II were dissolved in a minimum
amount of glacial acetic acid, and the mixture was
heated under reflux until the initial compounds dis-
appeared (TLC). The mixture was cooled to room tem-
perature and poured into water, the products were
extracted into chloroform, the extract was filtered
through a layer of silica gel, the solvent was removed,
and the residue was recrystallized from chloroform–
hexane (1:10).
each contained two sets of signals belonging to iso-
mers IVa and Va. The spectral parameters of Va
coincided with those given above. Found, %: C 59.71;
H 4.38; F 12.71; N 23.18. C15H13F2N5. Calculated, %:
C 59.79; H 4.35; F 12.61; N 23.25.
4-(3-Difluoromethyl-5-phenyl-1H-pyrazol-1-yl)-
1
6-methylpyrimidin-2-amine (IVa). H NMR spec-
trum (CDCl3), δ, ppm: 2.45 s (CH3), 5.17 br.s (2H,
NH2); the other signals were overlapped by those of
the phenyl protons. 19F NMR spectrum (CDCl3):
δF 48.04 ppm, d (HCF2, 2JHF = 53.9 Hz).
Reaction of diketonate Ia with 4-hydrazinyl-6-
methylpyrimidin-2-amine (IIa). a. From 1.64 g
(8.1 mmol) of compound Ia and 1 g (8.1 mol) of
hydrazine IIa in 10 mL of ethanol containing 0.98 g
(16.0 mmol) of glacial acetic acid we obtained 0.5 g
(21%) of compound Va and 1.2 g (47%) of IIIa.
c. In CF3COOH. Trifluoroacetic acid, 3 mL, was
added to a solution of 1.71 g (8.4 mmol) of compound
Ia and 1.04 g (8.4 mmol) of hydrazine IIa, and the
mixture was heated under reflux until the initial com-
pounds disappeared (TLC). The solvent was distilled
off, and the solid residue was washed with a 2 N solu-
tion of sodium hydroxide until neutral reaction and
dissolved in chloroform. The solution was filtered
through a layer of silica gel, the solvent was removed,
and the residue was recrystallized from chloroform–
hexane (1:10) to isolate 1.7 g (67%) of Va, mp 184–
185°C.
4-(5-Difluoromethyl-3-phenyl-1H-pyrazol-1-yl)-
6-methylpyrimidin-2-amine (Va). White crystals,
mp 184–185°C. IR spectrum, ν, cm–1: 3470 m, 3297 m,
1
3162 (NH), 1637 s, 1569 (C=N, C=C). H NMR spec-
trum (CDCl3), δ, ppm: 2.33 s (3H, CH3), 4.89 br.s (2H,
NH2), 6.67 s (1H, CH), 6.69 s (1H, CH), 6.78 t (1H,
2
HCF2, JHF = 54.8 Hz), 7.26–7.40 m (5H, Ph).
13C NMR spectrum (CDCl3), δC, ppm: 24.11 s,
1
1-(2-Amino-6-methylpyrimidin-4-yl)-3-phenyl-5-
trifluoromethyl-4,5-dihydro-1H-pyrazol-5-ol (IIIb).
a. From 1.8 g (8 mmol) of diketonate Ib and 1 g
(8 mmol) of hydrazine IIa in 10 mL of ethanol
containing 0.98 g (16 mmol) of glacial acetic acid we
obtained 1.8 g (67%) of compound IIIb. White
powder, mp 245–247°C. IR spectrum, ν, cm–1: 3394,
103.10 s, 106.93 s, 110.95 t (HCF2, JCF = 234.6 Hz),
128.17 s, 128.86 s, 128.95 s, 130.51 s, 130.53 s,
145.99 s, 148.59 t (2JCF = 30.2 Hz), 159.21 s, 162.14 s,
170.44 s. 19F NMR spectrum (CDCl3): δF 49.11 ppm,
2
4
d.d (HCF2, JFH = 54.8, JFH = 0.9 Hz). Found, %:
C 59.73; H 4.47; F 12.60; N 23.23. C15H13F2N5. Cal-
culated, %: C 59.79; H 4.35; F 12.61; N 23.25.
1
3333, 3065 br (NH, OH). H NMR spectrum
1-(2-Amino-6-methylpyrimidin-4-yl)-5-difluoro-
methyl-3-phenyl-4,5-dihydro-1H-pyrazol-5-ol
(IIIa). White powder, mp 165–166°C. IR spectrum, ν,
(DMSO-d6), δ, ppm: 2.39 s (3H, CH3), 3.86 d and
4.12 d (1H each, 4-H, AB system, JAB = 19.5 Hz),
6.90 s (1H, CH), 7.50–7.58 m (3H, Ph), 7.87 br.s (1H,
NH), 7.89–7.92 m (2H, Ph), 8.30 br.s (1H, NH),
1
cm–1: 3418 s, 3285 s (NH), 3133 br (OH). H NMR
13
spectrum (CDCl3), δ, ppm: 2.32 s (3H, CH3), 3.17 d.t
(1H, 4-H, JAB = 24.1, JHF ≈ 2.6 Hz) and 3.52 d.t (1H,
4-H, JAB = 24.1, JHF ≈ 2.4 Hz) (AB system), 4.59 br.s
(2H, NH2), 5.88 br.s (1H, OH), 6.47 t (1H, HCF2,
2JHF = 54.2 Hz), 6.57 s (1H, CH), 7.26–7.38 m (5H,
Ph). 19F NMR spectrum (CDCl3), δF, ppm: 43.5 d.d
(1F, FA, JFF = 321.4, 2JFH = 54.2 Hz), 44.42 d.d (1F, FB,
13.58 br.s (1H, OH). C NMR spectrum (DMSO-d6),
δC, ppm: 18.73 s, 44.02 s, 93.05 q (2JCF = 33.7 Hz),
1
96.17 s, 125.80 q (CF3, JCF = 287.6 Hz), 127.03 s,
128.87 s, 129.55 s, 131.32 s, 154.85 s, 155.56 s,
155.91 s, 160.81 s. 19F NMR spectrum (DMSO-d6):
δF 81.4 ppm, s (CF3). Mass spectrum, m/z (Irel, %): 337
(21.3) [M]+, 336 (7.7), 320 (20.7), 319 (100), 318
(19.2), 268 (47.9), 251 (8.3), 226 (16.8), 212 (22), 108
2
JFF = 321.4, JFH = 54.3 Hz). Found, %: C 56.66;
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 6 2014

BOLTACHEVA et al.
774
1
(12.2), 77 (15.2), 69 (23.5). Found, %: C 53.66;
H 4.22; F 16.92; N 20.81. C15H14F3N5O. Calculated,
%: C 53.41; H 4.18; F 16.89; N 20.76. M 337.
13.72 s, 24.20 s, 99.54 s, 108.88 t (HCF2, JCF =
236.47 Hz), 110.12 s, 139.07 t (2JCF = 31.13 Hz),
151.29 s, 158.97 s, 161.80 s, 170.44 s. Found, %:
C 50.36; H 4.65; F 15.71; N 29.26. C10H11F2N5. Cal-
culated, %: C 50.21; H 4.64; F 15.88; N 29.28.
b. From 1.16 g (5.2 mmol) of diketonate Ib and
0.65 g (5.2 mmol) of hydrazine IIa we obtained 0.7 g
(42%) of a mixture of 4-methyl-6-(5-trifluoromethyl-
3-phenyl-1H-pyrazol-1-yl)pyrimidin-2-amine (Vb) and
4-(3-difluoromethyl-5-phenyl-1H-pyrazol-1-yl)-6-
methylpyrimidin-2-amine (IVb) at a ratio of 6:1. The
1H NMR spectrum contained two sets of signals
belonging to isomers IVb and Vb. Found, %: C 56.46;
H 3.84; F 17.88; N 21.89. C15H12F3N5. Calculated, %:
C 56.42; H 3.79; F 17.85; N 21.93.
4-Methyl-6-(3-methyl-5-trifluoromethyl-1H-pyr-
azol-1-yl)pyrimidin-2-amine (Vd). b. From 0.64 g
(4.0 mmol) of diketonate Id and 0.5 g (4.0 mmol) of
hydrazine IIa (after treatment with 2 N aqueous NaOH
and recrystallization from chloroform–hexane, 1:10)
we obtained 0.7 g (69%) of compound Vd with
mp 171–172°C. IR spectrum, ν, cm–1: 3508, 3302,
1
3107 (N–H), 1644 s, 1564 (C=N, C=C). H NMR
1
spectrum (CDCl3), δ, ppm: 2.35 s (3H, CH3), 2.41 s
(3H, CH3), 5.13 br.s (2H, NH2), 6.67 s (1H, CH),
7.04 s (1H, CH). 13C NMR spectrum (CDCl3), δC,
Compound IVb. H NMR spectrum (CDCl3), δ,
ppm: 2.37 s (CH3), 4.83 br.s (2H, NH2), 6.69 s (1H,
CH), 6.84 m (1H, CH), 7.41–7.49 m (3H, Ph),
7.87–7.89 m (2H, Ph). 19F NMR spectrum (CDCl3):
δF 99.07 ppm, s (CF3).
ppm: 13.57 s, 24.24 s, 100.30 s, 112.64 q (4JCF
=
1
3.36 Hz), 119.84 q (CF3, JCF = 268.40 Hz), 133.31 q
(2JCF = 41.1 Hz), 150.44 s, 158.29 s, 162.13 s,
The spectral parameters of compound Vb are given
below.
19
170.43 s. F NMR spectrum (CDCl3): δF 103.99 ppm,
s (CF3). Found, %: C 46.61; H 3.87; F 22.21; N 27.37.
C10H10F3N5. Calculated, %: C 46.69; H 3.92; F 22.16;
N 27.23.
4-(5-Difluoromethyl-5-hydroxy-3-methyl-4,5-
dihydro-1H-pyrazol-1-yl)-6-methylpyrimidin-2-
aminium acetate (IIIc). a. Compound IIIc was
synthesized from 0.4 g (2.8 mmol) of diketonate Ic,
0.35 g (2.8 mmol) of hydrazine IIa, and 0.35 g
(5.8 mmol) of acetic acid in 10 mL of ethanol. Yield
0.52 g (58%), white powder, mp 128–130°C. IR spec-
4-[3-(Difluoromethyl)-5,6-dihydrocyclopenta[c]-
pyrazol-1(4H)-yl]-6-methylpyrimidin-2-amine (IVc)
and 4-[5-(difluoromethyl)-3,6-dihydrocyclopenta-
[c]pyrazol-1(4H)-yl]-6-methylpyrimidin-2-amine
(Ve). b. From 1.35 g (8.0 mmol) of diketonate Ie and
1 g (8.0 mmol) of hydrazine IIa we obtained a mixture
of compounds IVc and Ve at a ratio of 5:1. Yield 1.4 g
(66%), white powder. IR spectrum, ν, cm–1: 3507 m,
3302 m, 3167 m (NH), 1634 s, 1566 m (C=N, C=C).
1H NMR spectrum (DMSO-d6), δ, ppm: IVc: 2.39 s
(3H, CH3), 2.54–2.65 m (2H, CH2), 2.71–2.75 m (2H,
CH2), 3.15–3.19 m (2H, CH2), 5.05 br.s (2H, NH2),
1
trum, ν, cm–1: 3296 s (NH), 2995 br (OH). H NMR
spectrum (acetone-d6), δ, ppm: 1.96 s (3H, CH3),
2.12 s (3H, CH3), 2.17 s (3H, CH3), 2.90 d.d (1H,
4
2
2JHH = 18.9, JHF = 3.2 Hz) and 3.38 d (1H, JHH
=
18.9 Hz) (4-H), 5.79 br.s (1H, OH), 6.43 s (1H, CH),
2
2
6.53 d.d (1H, HCF2, JHF = 58.06, JHF = 56.40 Hz).
19F NMR spectrum (acetone-d6), δF, ppm: 31.15 d.d
2
2
(1F, JFF = 283.56, JFH = 58.06 Hz) and 37.55 d.d.d
2
2
2
4
6.65 t (1H, HCF2, JHF = 54.9 Hz), 7.08 s (1H, CH);
Ve: 2.37 s (3H, CH3), 2.44–2.50 m (2H, CH2), 2.75–
(1F, JFF = 283.56, JFH = 56.40, JFH = 0.81 Hz)
(HCF2). Found, %: C 45.32; H 5.43; F 11.80; N 22.04.
C10H13F2N5O·CH3CO2H. Calculated, %: C 45.42;
H 5.40; F 11.98; N 22.07.
2.78 m (2H, CH2), 2.79–2.82 m (2H, CH2), 5.05 br.s
2
(NH2), 7.06 s (1H, CH), 7.67 t (1H, HCF2, JHF
=
55.0 Hz). 19F NMR spectrum (DMSO-d6), δF, ppm:
4-(5-Difluoromethyl-3-methyl-1H-pyrazol-1-yl)-
6-methylpyrimidin-2-amine (Vc). b. From 0.4 g
(2.8 mmol) of diketonate Ic and 0.35 g (2.8 mmol) of
hydrazine IIa we obtained 0.5 g (76%) of compound
Vc with mp 205–206°C. IR spectrum, ν, cm–1: 3496,
3305, 3162 (NH), 1650 s, 1564 m (C=N, C=C).
1H NMR spectrum (CDCl3), δ, ppm: 2.29 s (3H, Me),
2.40 s (3H, Me), 5.01 br.s (2H, NH2), 6.59 s (1H, CH),
2
IVc: 48.88 d (HCF2, JHF = 54.9 Hz); Ve: 48.68 d.d.d.
2
5
(HCF2, JFH = 55.0, JFH = 2.6, 2.5 Hz). Found, %:
C 54.35; H 4.99; F 14.33; N 26.35. C12H13F2N5. Cal-
culated, %: C 54.34; H 4.94; F 14.32; N 26.40.
4-[5-(Difluoromethyl)-4,5,6,7-tetrahydro-2H-
indazol-2-yl]-6-methylpyrimidin-2-amine (Vf).
b. From 1.17 g (6.0 mmol) of diketonate If and 0.8 g
(6.0 mmol) of hydrazine IIa we obtained 1.36 g (81%)
of compound Vf. White powder, mp 220–221°C. IR
spectrum, ν, cm–1: 3510, 3308, 3165 (N–H), 1630 s,
2
7.12 s (1H, CH), 7.67 t (1H, HCF2, JHF = 54.8 Hz).
19F NMR spectrum (CDCl3): δF 48.09 ppm, d (HCF2,
2JFH = 54.8 Hz). 13C NMR spectrum (CDCl3), δC, ppm:
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FLUOROALKYL-SUBSTITUTED LITHIUM 1,3-DIKETONATES
775
1
1560 m (C=N, C=C). H NMR spectrum (CDCl3), δ,
s (CF3). Found, %: C 60.28; H 4.07; F 17.61; N 17.83.
C16H13F3N4. Calculated, %: C 60.38; H 4.12; F 17.91;
N 17.60.
ppm: 1.76–1.86 m (4H, CH2), 2.71–2.81 m (4H, CH2),
2.37 s (3H, Me), 5.63 br.s (NH2), 7.08 s (1H, CH),
7.82 t (HCF2, JHF = 54.5 Hz). 13C NMR spectrum
2
7-[3-(Difluoromethyl)-5-phenyl-1H-pyrazol-
1-yl]-6-fluoroquinoxaline (IVe). b. From 0.6 g
(2.9 mmol) of diketonate Ia and 0.5 g (2.9 mmol) of
hydrazine IIc we obtained 0.9 g (92%) of compound
IVe. White powder, mp 134–135°C. IR spectrum, ν,
cm–1: 1510 s, 1490 m (C=N, C=C). 1H NMR spectrum
(CDCl3), δC, ppm: 21.19 s, 22.66 s, 22.70 s, 23.62 s,
1
24.20 s, 99.62 s, 110.38 t (HCF2, JCF = 235.38 Hz),
121.77 t (4JCF = 1.14 Hz), 132.89 t (2JCF = 31.0 Hz),
152.61 t (3JCF = 2.1 Hz), 159.39 s, 161.91 s, 170.31 s.
19F NMR spectrum (CDCl3): δF 48.04 ppm, d.d.d
2
5
(HCF2, JFH = 54.5, JFH = 2.9, 2.8 Hz). Found, %:
C 55.87; H 5.49; F 13.58; N 25.16. C13H15F2N5. Cal-
culated, %: C 55.91; H 5.41; F 13.60; N 25.07.
(CDCl3), δ, ppm: 6.81 t (HCF2, 2JHF = 54.7 Hz), 6.83 s
3
(1H, CH), 7.23–7.35 m (5H, Ph), 7.79 d (1H, JHF
=
=
3
10 Hz), 8.29 d (1H, 4JHF = 7.6 Hz), 8.88 d (1H, JHH
1.7 Hz), 8.90 d (1H, JHH = 1.7 Hz). 19F NMR spec-
trum (CDCl3), δF, ppm: 49.42 d (HCF2, 2JHF = 54.7 Hz),
46.25 d.d (1F, 6-F, 3JFH = 10.00, 4JFH = 7.6 Hz). Found,
%: C 63.55; H 3.24; F 16.76; N 16.44. C18H11F3N4.
Calculated, %: C 63.53; H 3.26; F 16.75; N 16.46.
3
4-Methyl-6-[5-(trifluoromethyl)-4,5,6,7-tetra-
hydro-2H-indazol-2-yl]pyrimidin-2-amine (Vg).
b. From 1.05 g (0.0052 mol) of diketonate Ig and
0.65 g (0.0052 mol) of hydrazine IIa we obtained
1.1 g (71%) of compound Vg. White powder, mp 202–
203°C. IR spectrum, ν, cm–1: 3496, 3288, 3138 (NH),
6-Fluoro-7-[3-phenyl-5-(trifluoromethyl)-1H-
pyrazol-1-yl]quinoxaline (Vi) and 6-fluoro-7-
[5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-
quinoxaline (IVf). b. From 0.93 g (4.2 mmol) of
diketonate Ib and 0.74 g (4.2 mmol) of hydrazine IIc
we obtained a mixture of compounds Vi and IVf at
a ratio of 1:1. Yield 0.9 g (60%), white powder. The
1H and 19F NMR spectra each contained two sets of
1
1637 s, 1572 m (C=N, C=C). H NMR spectrum
(CDCl3), δ, ppm: 1.75–1.86 (4H, CH2), 2.39 s (3H,
Me), 2.73–2.77 m (4H, CH2), 5.13 br.s (2H, NH2),
6.97 m (1H, CH). 19F NMR spectrum (CDCl3):
δF 106.23 ppm, m (CF3). Found, %: C 52.57; H 4.84;
F 19.19; N 23.51. C13H14F3N5. Calculated, %: C 52.52;
H 4.75; F 19.17; N 23.56.
1
6-[3-(Difluoromethyl)-5-phenyl-1H-pyrazol-
1-yl]-2,4-dimethylpyrimidine (IVd). b. From 0.5 g
(2.4 mmol) of diketonate Ia and 0.34 g (2.4 mmol) of
hydrazine IIb we obtained 0.4 g (56%) of compound
IVd. White powder, mp 89–90°C. IR spectrum, ν,
cm–1: 1605 s, 1549 m (C=N, C=C). 1H NMR spectrum
(CDCl3), δ, ppm: 2.38 s (6H, Me), 6.73 s (1H, CH),
signals. H NMR spectrum (CDCl3), δ, ppm: IVf:
6.86 s (1H, CH), 7.24–7.37 m (5H, Ph), 7.78 d (1H,
3JHF = 9.9 Hz), 8.34 d (1H, 4JHF = 7.8 Hz), 8.89 d (1H,
JHH = 2.3 Hz), 8.90 d (1H, JHH = 2.3 Hz); Vi: 7.21 s
(1H, CH), 7.38–7.47 m (3H) and 7.86–7.88 m (2H)
3
4
(Ph), 7.97 d (1H, JHF = 9.8 Hz), 8.36 d (1H, JHF
=
3
7.9 Hz), 8.94 d (1H, JHH = 1.68 Hz), 8.95 d (1H,
2
3JHH = 1.68 Hz). 19F NMR spectrum (CDCl3), δF, ppm:
6.85 t (HCF2, JHF = 54.6 Hz), 6.96 s (1H, CH), 7.26–
7.34 m (5H, Ph). 13C NMR spectrum (CDCl3), δC,
3
IVf: 99.32 s (3F, CF3), 46.13 d.d (1F, 6-F, JFH = 9.9,
1
4JFH = 7.8 Hz); Vi: 102.75 d (3F, CF3, JFF = 4.88 Hz),
44.82 m (1F, 6-F). Found, %: C 60.35; H 2.83;
F 21.29; N 15.62. C18H10F4N4. Calculated, %: C 60.34;
H 2.81; F 21.21; N 15.64.
ppm: 23.73 s, 106.16 s, 111.16 t (HCF2, JCF
=
233.9 Hz), 118.98 s, 127.93 s, 128.42 s, 128.75 s,
130.97 s, 146.50 s, 148.48 t (2JCF = 30.5 Hz), 156.50 s,
19
169.03 s. F NMR spectrum (CDCl3): δF 49.47 ppm,
2
4
d.d (HCF2, JFH = 54.6, JFH = 1.0 Hz). Found, %:
C 63.95; H 4.71; F 12.61; N 18.70. C16H14F2N4. Cal-
culated, %: C 63.99; H 4.69; F 12.65; N 18.65.
2-[5-(Difluoromethyl)-3-phenyl-1H-pyrazol-
1-yl]-1,3-benzothiazole (Vk) and 2-[3-(difluoro-
methyl)-5-phenyl-1H-pyrazol-1-yl]-1,3-benzothia-
zole (IVg). b. From 0.6 g (2.9 mmol) of diketonate Ia
and 0.49 g (2.9 mmol) of hydrazine IId we obtained
a mixture of compounds Vk and IVg at a ratio of 1:3.
2,4-Dimethyl-3-phenyl-6-[5-(trifluoromethyl)-
1H-pyrazol-1-yl]pyrimidine (Vh). b. From 1 g
(4.5 mmol) of diketonate Ib and 0.62 g (4.5 mmol) of
hydrazine IIb we obtained 0.7 g (49%) of compound
Vh with mp 82.5–83.5°C. IR spectrum, ν, cm–1:
1
19
Yield 0.4 g (43%). The H and F NMR spectra each
1
contained two sets of signals. H NMR spectrum
1
2
1610 s, 1520 m (C=N, C=C). H NMR spectrum
(CDCl3), δ, ppm: IVg: 6.80 t (1H, HCF2, JHF
=
(CDCl3), δ, ppm: 2.59 s (6H, Me), 7.05 s (1H, CH),
7.21 s (1H, CH), 7.39–7.46 m (3H, Ph), 7.92–7.95 m
(2H, Ph). 19F NMR spectrum (CDCl3): δF 104.03 ppm,
54.6 Hz), 6.73 s (1H, CH), 7.38–7.54 m and 7.74–
7.80 m (9H, Harom); Vk: 7.17 s (1H, CH), 7.38–7.54 m
19
and 7.74–7.80 m (10H, HCF2, Harom). F NMR spec-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 6 2014

BOLTACHEVA et al.
776
2
trum (CDCl3), δF, ppm: IVg: 48.74 d (HCF2, JHF
=
157.24 s, 158.14 s, 171.60 s, 173.00 s. 19F NMR spec-
trum (DMSO-d6): δF 105.62 ppm, s (CF3). Found, %:
C 56.50; H 3.88; F 14.16; N 17.46. C19H16F3N5O2. Cal-
culated, %: C 56.58; H 3.99; F 14.13; N 17.36.
2
54.6 Hz); Vk: 47.07 d (HCF2, JHF = 53.8 Hz). Mass
spectrum, m/z (Irel, %): IVg): 327 (68.5) [M]+, 326
(83.6), 276 (23.4), 250 (79.6), 77 (72.6), 51 (100); Vk:
327 (80.2) [M]+, 326 (15.1), 250 (14.4), 224 (99.8),
193 (12.7), 134 (21.5), 77 (86.2), 51 (100). Found, %:
C 62.55; H 3.32; F 11.56; N 12.90; S 9.82.
C17H11F2N3S. Calculated, %: C 62.37; H 3.39; F 11.60;
N 12.84; S 9.79.
4-Methyl-6-[3-phenyl-5-(trifluoromethyl)-1H-
pyrazol-1-yl]pyrimidin-2-amine (Vb). A solution of
0.36 g (1.1 mmol) of compound IIIb in 10 mL of
acetic anhydride was heated for 5 h under reflux.
Acetic anhydride was distilled off, the residue was
poured into water, and the precipitate was filtered off.
The product was heated in 2 N aqueous NaOH for
20 min under reflux, and the precipitate was filtered
off and recrystallized from chloroform–hexane (1:10).
Yield 0.33 g (97%), white powder, mp 187–188°C. IR
spectrum, ν, cm–1: 3562, 3238 (NH), 1638 s, 1567 m
1-(1,3-Benzothiazol-2-yl)-3-phenyl-5-(trifluoro-
methyl)-4,5-dihydro-1H-pyrazol-5-ol (IIId). b. From
0.98 g (4.8 mmol) of diketonate Ib and 0.79 g
(4.8 mmol) of hydrazine IId we obtained 1.2 g (69%)
of compound IIId. White powder, mp 116–117°C. IR
spectrum, ν, cm–1: 3442, 3059 br (OH), 1596 s, 1541 m
1
1
(C=N, C=C). H NMR spectrum (CDCl3), δ, ppm:
(C=N, C=C). H NMR spectrum (CDCl3), δ, ppm:
2.45 s (3H, Me), 5.05 br.s (2H, NH2), 7.19 s (1H, CH),
7.21 s (1H, CH), 7.41–7.49 m (3H) and 7.87–7.90 m
3.69 d and 3.81 d (1H each, 4-H, JAB = 18.4 Hz), 7.22–
7.45 m (5H, Harom), 7.67–7.45 m (4H, Harom), 8.00 br.s
13
19
(2H) (Ph). C NMR spectrum (DMSO-d6), δC, ppm:
(1H, OH). F NMR spectrum (CDCl3): δF 80.37 ppm,
23.81 s, 98.72 s, 110.12 q (3JCF = 3.3 Hz), 119.62 q
s (CF3). Found, %: C 56.25; H 3.36; F 15.65; N 11.62;
S 8.56. C17H12F3N3OS. Calculated, %: C 56.19;
H 3.33; F 15.69; N 11.56; S 8.82.
1
(CF3, JCF = 268.4 Hz), 125.88 s, 126.11 s, 128.89 s,
129.27 s, 130.59 s, 132.63 q (2JCF = 40.7 Hz), 151.64 s,
157.69 s, 162.61 s, 170.36 s. 19F NMR spectrum
(CDCl3): δF 104.11 ppm, s (CF3). Found, %: C 56.43;
H 3.82; F 17.89; N 21.90. C15H12F3N5. Calculated, %:
C 56.42; H 3.79; F 17.85; N 21.93.
2-[3-(Trifluoromethyl)-4,5,6,7-tetrahydro-2H-
indazol-2-yl]-1,3-benzothiazole (Vj). b. From 0.88 g
(4.4 mmol) of diketonate Ig and 0.73 g (4.4 mmol) of
hydrazine IId we obtained 0.7 g (49%) of compound
Vj. White powder, mp 132.5–133.5°C. IR spectrum, ν,
cm–1: 1596 s, 1520 m (C=N, C=C). 1H NMR spectrum
(CDCl3), δ, ppm: 1.78–1.89 m (4H, CH2), 2.77–2.81 m
(4H, CH2); 7.36–7.46 m (1H), 7.38–7.47 m (1H),
7.81–7.83 m (1H), and 7.93–7.95 m (1H) (Harom).
19F NMR spectrum (CDCl3): δF: 104.53 ppm, s (CF3).
Found, %: C 55.65; H 3.69; F 17.59; N 13.02, S 9.54.
C15H12F3N3S. Calculated, %: C 55.72; H 3.74; F 17.63;
N 12.99; S 9.92.
Likewise, from 0.5 g (0.0015 mol) of IIIa we
obtained 0.4 g (85%) of compound Va. White powder,
1
19
mp 184–185°C. The IR and H and F NMR spectra
of the product were consistent with those of a sample
prepared by reaction of lithium diketonate Ia with
hydrazine IIa.
This study was performed in the framework of the
Federal Program for Support of Leading Scientific
Schools (project no. NSh-5505.2012.3).
N-Acetyl-N-[4-methyl-6-(3-phenyl-5-trifluoro-
methyl-1H-pyrazol-1-yl)pyrimidin-2-yl]acetamide
(VI). A solution of 0.8 g (2.37 mmol) of dihydropyra-
zole IIIb in 40 mL of acetic anhydride was heated for
5 h under reflux. Excess acetic anhydride was distilled
off, the residue was treated with 10 mL of water, and
the precipitate was filtered off and recrystallized from
ethanol. Yield 0.95 g (98%), mp 163°C. 1H NMR spec-
trum (DMSO-d6), δ, ppm: 2.26 s (6H, MeCO), 2.68 s
(3H, Me), 7.49–7.57 m (3H, Ph), 7.96 s (1H, CH),
8.07–8.09 m (2H, Ph), 8.11 s (1H, CH). 13C NMR
spectrum (DMSO-d6), δC, ppm: 23.81 s, 25.51 s,
25.76 s, 109.39 s, 112.03 q (3JCF = 3.3 Hz), 119.39 q
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