2-methylsulfanyl-6-polyfluoroalkyl-pyrimidin-4-ones: Synthesis and nucleophilic substitution reactions

Article abstract of DOI:10.1007/s10593-014-1539-7

We have optimized the reaction conditions for the synthesis of 2-methylsulfanyl-6-polyfluoro-alkylpyrimidin-4-ones. In particular the yield of trifluoromethyl-substituted heterocycle was increased to 96%, and new polyfluoroalkyl-substituted analogs were prepared. The interaction of these heterocycles with morpholine or hydrazine was shown to result in nucleophilic substitution of the methylsulfanyl group, leading to 2-morpholino- and 2-hydrazino-6-polyfluoroalkylpyrimidin-4-ones. The reaction of 2-(2-phenylhydrazino)-6-trifluoromethylpyrimidin-4-one with paraform produced 5-oxo-2-phenyl-7-tri-fluoromethyl-5H-1,2,4-triazolo[4,3-a]pyrimidin-1-id-2-ium. The lactam structure of the synthesized heterocycles was established by X-ray structural analysis, as well as by IR and NMR spectroscopy.

Full text of DOI:10.1007/s10593-014-1539-7

Chemistry of Heterocyclic Compounds, Vol. 50, No. 6, September, 2014 (Russian Original Vol. 50, No. 6, June, 2014)
2-METHYLSULFANYL-6-POLYFLUOROALKYL-
PYRIMIDIN-4-ONES: SYNTHESIS AND
NUCLEOPHILIC SUBSTITUTION REACTIONS
1
1
1
*
O. G. Khudina , Ya. V. Burgart , and V. I. Saloutin
We have optimized the reaction conditions for the synthesis of 2-methylsulfanyl-6-polyfluoro-
alkylpyrimidin-4-ones. In particular the yield of trifluoromethyl-substituted heterocycle was increased to
96%, and new polyfluoroalkyl-substituted analogs were prepared. The interaction of these heterocycles
with morpholine or hydrazine was shown to result in nucleophilic substitution of the methylsulfanyl
group, leading to 2-morpholino- and 2-hydrazino-6-polyfluoroalkylpyrimidin-4-ones. The reaction of
2-(2-phenylhydrazino)-6-trifluoromethylpyrimidin-4-one with paraform produced 5-oxo-2-phenyl-7-tri-
fluoromethyl-5H-1,2,4-triazolo[4,3-а]pyrimidin-1-id-2-ium. The lactam structure of the synthesized
heterocycles was established by X-ray structural analysis, as well as by IR and NMR spectroscopy.
Keywords: hydrazines, 2-methylsulfanyl-6-polyfluoroalkylpyrimidin-4-one, morpholine, nucleophilic
substitution, X-ray structural analysis.
The biological activity of pyrimidine-2-thione, in particular 2-alkylsulfanylpyrimidin-4-ones [1-5],
creates a considerable amount of interest towards the development of optimal synthetic methods, as well as
approaches to chemical modification of this type of compounds.
Methods of 2-alkylsulfanylpyrimidin-4-one transformations have been described for all five reactive
sites of these molecules: the N-1 and N-3 nitrogen atoms, the carbonyl oxygen atom, the С-5 carbon atom, and
the alkylsulfanyl group. The alkylation of 2-methylsulfanylpyrimidin-4-ones, depending on the reaction
conditions and the alkylating agent, occurs at the N-1 [6-8], N-3 [9-11] atoms, or the carbonyl oxygen atom [9,
11, 12]. The epoxidation [13] and acylation reactions [14] proceed at the N-1 atom of the lactam fragment. A
characteristic reaction of 2-methylsulfanylpyrimidin-4-ones is the nucleophilic substitution of methylsulfanyl
group for an amino group [15, 16]. 2-Methylsulfanylpyrimidin-4-ones can interact with bifunctional reagents at
several reactive sites: alkylation with Br(CH2)nOH produces a mixture of O- and N-alkyl derivatives [17], while
using 1,2-dibromoethane gives a mixture of bis-N,N-, N,O-, and O,O-isomers [18]. Fusion of
2-methylsulfanylpyrimidin-4-one with carbonic acid hydrazide is not limited to the nucleophilic substitution of
SMe group, but is accompanied by cyclization at the N-1 atom, producing [1,2,4]triazolo[4,3-a]pyrimidin-
7(8H)-ones [19].
_______
*To whom correspondence should be addressed, e-mail: burgart@ios.uran.ru.
1I. Ya. Postovskii Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences, 22 S. Kovalevskoi
St. / 20 Akademicheskaya St., Yekaterinburg 620990, Russia.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 928-935, June, 2014. Original
article submitted March 24, 2014.
856
0009-3122/14/5006-0856©2014 Springer Science+Business Media New York

At the same time, the chemical transformations of 2-methylsulfanylpyrimidin-4-one polyfluoroalkyl
derivatives have been studied only in few cases [20-23], apparently due to the lack of effective methods for the
synthesis of these compounds.
2-Methylsulfanyl-6-trifluoromethylpyrimidin-4-one (2а) was previously obtained in 67% yield by
condensation of 4,4,4-trifluoro-3-oxobutanoate 1а with S-methylisothiourea sulfate under alkaline conditions
[24, 25]. Performing the synthesis in aqueous K2CO3 solution (instead of 10% NaOH) allowed us to increase the
yield of the target heterocycle 2а from 67% to nearly quantitative (96%). The 3-oxoesters 1b,с were similarly
converted to the new 2-methylsulfanyl-6-polyfluoroalkylpyrimidinones 2b,с in 81-92% yields. In the case of the
heptafluoropropyl analog 2d the yield was 40% and could be increased to 65% only by performing the reaction
in aqueous acetonitrile solution.
RF
OMe
RF
OMe
K2CO3
H2O, (MeCN)
...
RF
O
O
O
1a–d
OH
O
+
N
NH
SMe
room temp., 8 h
65–96%
SMe
a RF = CF3, b RF = CHF2, c RF = CF2CHF2, d RF = C3F7
HN
NH2
·0.5H2SO4
2a–d
The synthesized pyrimidines 2а-d may exist in four tautomeric forms A-D due to the possible
participation in keto-enol and/or amine-imine tautomerism (Fig. 1).
RF
O
RF
O
RF
O
RF
OH
HN
N
N
N
N
NH
SMe
N
N
SMe
SMe
SMe
B
C
A
D
Fig. 1. Tautomeric forms of pyrimidines 2.
According to X-ray structural analysis data (Fig. 2), compound 2а exists in crystalline state in the amide
form (isomer А) as dimers linked by a double intermolecular interaction between the С(4)=О(1) carbonyl group
of one molecule and the N(3)'–Н amino group of another molecule, and vice versa (О(1)···НN(3)' 1.738 Å).
Fig. 2. The molecular structure of compound 2a with atoms represented by thermal vibration ellipsoids of 50%
probability.
857

The IR spectra of compounds 2a-d proved to be identical in СHCl3 solution and in crystalline state. The
characteristic absorption bands correspond to the stretching and deformation vibrations of the amino group
(3103-3226 and 1583-1627 cm-1) and the carbonyl group (1663-1684 cm-1).
According to 1Н and 19F NMR spectra, compounds 2a-d exist in DMSO-d6 and СDCl3 solutions as one
1
isomer with characteristic Н NMR signals for the methyl group protons at 2.50 ppm, methine proton at
6.31-6.64 ppm, and a downfield signal of amine or hydroxyl proton at 13.02-13.44 ppm.
Based on these data, we can conclude that compounds 2a-d exist in solution exclusively as a single
species, the "amide" isomer А.
The biological activity data for the non-fluorinated 2-hydrazinopyrimidinones [26, 27] led us to study
the possibilities for the synthesis of their polyfluoroalkyl analogs by nucleophilic substitution of methylsulfanyl
group in compounds 2а,c for a hydrazine group.
The reaction of 2-methylsulfanyl-6-trifluoromethylpyrimidin-4-one (2а) with 40% aqueous hydrazine
hydrate in refluxing acetonitrile gave the 2-hydrazinopyrimidine 3а in 21% yield. Performing the synthesis by
refluxing in 2-propanol allowed to increase the yield of compound 3а to 42%.
RF
O
F3C
O
(from 3b)
40–44%
(R = Ph)
(CH2O)n, MeCN
, 3 h
N
N
N
NH
N–
N+
Ph
HN
3a–c
78%
RNHNH2
–MeSH
NHR
2a,c
4
RF
O
N
N
NH
3 a R = H, RF = CF3;
b R = Ph, RF = CF3;
c R = Ph, RF = CF2CHF2
Ph
NH2
M
The reaction of pyrimidine 2а with phenylhydrazine could be achieved in 2-propanol at 135°С, while
the 6-tetrafluoroethyl-substituted analog 2с reacted in n-butanol at 160°С under microwave irradiation.
Compounds 3b,c were obtained in 40-44% yields.
1
The Н and 19F NMR spectral data acquired for DMSO-d6 or CDCl3 solutions showed that the
compounds 3а-с exist in solution as one of the several possible tautomeric forms (Fig. 3).
RF
O
RF
O
RF
O
RF
O
HN
NH
N
N
N
NH
HN
HN
N
N
HN
HN
NHR
NHR
NHR
NHR
E
F
G
H
RF
OH
RF
OH
RF
OH
RF
OH
N
NH
N
N
N
N
HN
N
N
HN
N
N
NHR
NHR
NHR
NHR
I
J
K
L
Fig. 3. Tautomeric forms of pyrimidines 3.
858

Fig. 4. The molecular structure of compound 4 with atoms represented by thermal vibration ellipsoids of 50%
probability.
1
The Н NMR spectra featuring a methine proton singlet at 5.44-6.02 ppm and broadened downfield
singlet signals of amino or hydroxy groups allowed to exclude the possibility of tautomers G and I with
methylеne groups.
The IR spectra of compounds 3а-с recorded for solid samples and СНСl3 solutions had characteristic
absorption bands at 3360-3090 and 1651-1608 cm-1 (amide II) and at 1667-1672 cm-1 (amide I), which allowed
to exclude the possible contribution from the hydroxy forms I-L. The high intensity of absorption bands due to
amino group deformation vibrations (amide II) pointed to the amide forms E or F. The absence of additional IR
absorption band for the isolated С=N bond in the region of 1665-1630 cm-1 for the form F pointed to the
preferred aminoamide isomer E structure for compounds 3а-с.
Phenylhydrazine may be involved in nucleophilic substitution of primary, as well as secondary amino
groups [28], forming the isomeric 2-(1-phenylhydrazino)pyrimidinones М or 2-(2-phenylhydrazino)-pyrimi-
dinones 3b,c.
We performed a reaction of the 2-hydrazinopyrimidine 3b with paraform in refluxing acetonitrile in
order to establish the structure of products formed by the reactions of compounds 2а,с with phenylhydrazine.
The isolated product 4 had the mesoionic structure of 1,2,4-triazolo[4,3-а]pyrimidin-5-one according to X-ray
structural analysis (Fig. 4), which could be formed only by heterocyclization of 2-phenylhydrazino-substituted
heterocycle 3b with paraform at the amide N-3 and hydrazine β-nitrogen atom. This points to the participation
of phenylhydrazine primary amino group in the nucleophilic substitution reaction of methylsulfanyl group in the
pyrimidinones 2.
Based on the example of 2-methylsulfanyl-6-polyfluoroalkylpyrimidin-4-one 2 reactions with morpholine,
we demonstrated the possibility of nucleophilic substitution of methylsulfanyl group to a heterocyclic amine
fragment. The most suitable conditions for obtaining the substitution products 5а,b was the refluxing of compounds
2b,c in excess of morpholine. The IR and NMR spectral data provided evidence for the existence of heterocycles
5а,b in the amide form А.
RF
O
H
N
N
NH
, 7 h
2b,c
+
–MeSH
66–68%
N
O
O
5 a RF = CHF2,
b RF = CF2CHF2
Thus, we propose a convenient preparative method for the synthesis of 2-methylsulfanyl-6-poly-
fluoroalkylpyrimidin-4-ones, providing an improved access to these compounds as starting materials for further
transformations, such as nucleophilic substitution reactions with amines.
859

EXPERIMENTAL
IR spectra were recorded on a Perkin Elmer Spectrum One FTIR spectrometer with an ATR accessory
(compound 4) or diffuse reflectance accessory (the rest of the compounds). 1Н and 19F NMR spectra were acquired
on a Bruker DRX-400 spectrometer (400 and 376 MHz, respectively) in CDCl3 (compound 3с), acetone-d6
(compound 4), and DMSO-d6 (the rest of the compounds). The internal standards: TMS (for 1Н nuclei) and С6F6 (for
19F nuclei). Mass spectra were recorded on an Agilent GC 7890A MSD 5975C inert XL EI/CI instrument with an
HP5-MS quartz capillary column (dimethylpolysiloxane with 5% of phenyl groups, 30 m × 0.25 mm, coating
thickness 0.25 µm) and quadrupole mass spectral detector, EI ionization (70 eV). The carrier gas was helium, the
solvent was EtOH. Elemental analysis was performed on a Perkin Elmer PE 2400 series II elemental analyzer.
Melting points were determined in open capillaries on a Stuart SMP30 melting point apparatus. Merck silica gel 60
(0.063-0.020 mm) was used for column chromatography. The reactions of pyrimidines 2а,с with phenylhydrazine
were performed in an Explorer 12 (Hybrid) microwave synthesis system from CEM.
2-Methylsulfanyl-6-trifluoromethylpyrimidin-4(3Н)-one (2a). The 3-oxoester 1a (170 mg, 1.00 mmol)
was added to a solution of S-methylthiourea (153 mg, 0.55 mmol) and K2CO3 (138 mg, 1.00 mmol) in H2O (300
ml). The solution was stirred for 8 h. The reaction mixture was neutralized with 15% АсОН to рН 8. The
precipitate was filtered off, washed with water, and recrystallized from AcOH. Yield 96%, white powder, mp
178-179°С (mp 179-180°С [24], mp 181-182°С (EtOH) [25]).
Compounds 2b-d were obtained analogously to compound 2а (in the case of compound 2d, the reaction
was performed in a 2:1 mixture of H2O and MeCN).
6-Difluoromethyl-2-methylsulfanylpyrimidin-4(3Н)-one (2b). Yield 92%, white powder, mp 198-
1
199°С. IR spectrum, ν, cm-1: 3103 (NHstretch), 1684 (C=O), 1627 (NHdeform), 1104-1059 (C–F). H NMR
spectrum, δ, ppm (J, Hz): 2.49 (3H, s, CH3); 6.31 (1H, s, H-5); 6.67 (1H, t, J = 54.3, CHF2); 13.02 (1H, br. s,
19
NH). F NMR spectrum, δ, ppm (J, Hz): 41.1 (2F, d, J = 54.3, CHF2). Found, %: С 37.65; Н 3.05; N 14.41.
С6Н6F2N2ОS. Calculated, %: С 37.50; Н 3.15; N 14.58.
6-(1,1,2,2-Tetrafluoroethyl)-2-methylsulfanylpyrimidin-4(3Н)-one (2c). Yield 81%, white powder, mp
1
152-153°С. IR spectrum, ν, cm-1: 3011 (NHstretch), 1663 (C=O), 1591 (NHdeform), 1125-1102 (C–F). H NMR
spectrum, δ, ppm (J, Hz): 2.52 (3H, s, CH3); 6.51 (1H, s, H-5); 6.87 (1H, tt, 2JH–F = 51.8, 3JH–F = 5.8, (CF2)2H);
19
2
3
13.31 (1H, br. s, NH). F NMR spectrum, δ, ppm (J, Hz): 23.5 (2F, dt, JF–Н = 51.8, JF–F = 8.4, CF2H); 40.4
(2F, br. s, CF2CF2H). Found, %: С 34.58; Н 2.46; N 11.69. С7Н6F4N2ОS. Calculated, %: С 34.71; Н 2.50;
N 11.57.
6-Heptafluoropropyl-2-methylsulfanylpyrimidin-4(3Н)-one (2d). Yield 65%, white powder,
mp 106-108°С. IR spectrum, ν, cm-1: 3030 (NHstretch), 1669 (C=O), 1583 (NHdeform), 1231-1124 (C–F). 1H NMR
19
spectrum, δ, ppm: 2.49 (3H, s, CH3); 6.64 (1H, s, H-5); 13.44 (1H, br. s, NH). F NMR spectrum, δ, ppm (J,
Hz): 36.4-36.8 (2F, m, CF2); 45.5-45.9 (2F, m, CF2); 82.7 (3F, t, J = 8.8, CF3). Found, %: С 31.11; Н 1.58;
N 9.16. С8Н5F7N2ОS. Calculated, %: С 30.98; Н 1.62; N 9.03.
2-Hydrazino-6-trifluoromethylpyrimidin-4(3Н)-one (3а). А. A solution of compound 2a (164 mg,
0.78 mmol) in 2-PrOH (8 ml) was treated with 40% N2H4·H2O (173 mg, 3.46 mmol). The solution was refluxed for
14 h in a flask equipped with a trap filled with solid NaOH. The solvent was removed by distillation, and the residue
was purified by column chromatography (eluent CHCl3).
B. A solution of compound 2a (164 mg, 0.78 mmol) in MeCN (8 ml) was treated with 40% N2H4·H2O
( 173 mg, 3.46 mmol). The solution was refluxed for 14 h in a flask equipped with a trap filled with solid NaOH.
The precipitate formed was filtered off, washed with MeCN, and dried.
Yield 42% (method A), 21% (method B), white powder, mp 165-167°С. IR spectrum, ν, cm-1: 3360,
1
3090 (NHstretch), 1672 (C=O), 1651 (NHdeform), 1598, 1485 (C=C, C=N), 1182-1128 (C–F). H NMR spectrum,
19
δ, ppm: 5.44 (1H, s, H-5); 7.56 (4H, br. s, 2NH, NH2). F NMR spectrum, δ, ppm: 92.5 (3F, s, CF3). Mass
spectrum, m/z (Irel, %): 194 [M]+ (100), 175 [M-F]+ (11), 163 [M-N2H3]+ (25), 138 (26), 125 [M-CF3]+ (48), 75 (23),
860

69 [CF3]+ (61), 68 (60), 67 (25), 57 (25), 43 [CONH]+ (29), 42 [CON]+ (33), 32 [NH2-NH2]+ (44), 31 [N2H3]+ (68),
29 (32), 28 [CO]+ (64). Found, %: С 31.21; Н 2.64; N 29.06. С5Н5F3N4О. Calculated, %: С 30.94; Н 2.60;
N 28.86.
2-(2-Phenylhydrazino)-6-trifluoromethylpyrimidin-4(3Н)-one (3b). Phenylhydrazine (108 mg, 1 mmol)
was added to a solution of pyrimidin-4-one 2a (210 mg, 1 mmol) in 2-PrOH (8 ml). The reaction mixture was heated
for 2 h in a microwave synthesis reactor (40 W, 135°С). The solvent was removed by distillation at reduced pressure,
using a trap filled with solid NaOH. The residue was purified by column chromatography (eluent CHCl3), then
additionally recrystallized from CH2Cl2. Yield 42%, white powder, mp 219-220°С. IR spectrum, ν, cm-1: 3183,
1
3311, 3345 (NHstretch), 1677 (C=O), 1621 (NHdeform), 1587, 1500, 1484 (C=C, C=N), 1190-1141 (C–F). H NMR
spectrum, δ, ppm: 6.02 (1H, s, H-5); 6.72-6.80 (3H, m, H-3,4,5 Ph); 7.20 (2H, br. s, H-2,6 Ph); 7.95 (1H, s,
NH); 9.85 (1H, br. s, NH); 11.58 (1H, s, NH). 19F NMR spectrum, δ, ppm: 92.2 (3F, s, CF3). Found, %: С 49.14;
Н 3.35; N 20.86. С11Н9F3N4О. Calculated, %: С 48.90; Н 3.36; N 20.73.
2-(2-Phenylhydrazino)-6-(1,1,2,2-tetrafluoroethyl)pyrimidin-4(3Н)-one (3c). Phenylhydrazine
(108 mg, 1 mmol) was added to a solution of pyrimidin-4-one 2с (242 mg, 1 mmol) in n-BuOH (8 ml). The
reaction mixture was heated for 2 h in a microwave synthesis reactor (50W, 160°С). The solvent was removed by
distillation at reduced pressure, using a trap filled with solid NaOH. The residue was purified by column
chromatography (eluent CHCl3), followed by additional recrystallization from a 1:1 mixture of ССl4 and CH2Cl2.
Yield 40%, white powder, mp 211-212°С. IR spectrum, ν, cm-1: 3311, 3182 (NH), 1667 (C=O), 1608 (NHdeform),
1
1584, 1490 (C=C, C=N), 1116-1087(C–F). H NMR spectrum, δ, ppm (J, Hz): 5.82 (1H, s, H-5); 6.14 (1H,
2
tt, JH–F = 53.3, 3JH–F = 5.2, (CF2)2H); 6.29 (1H, s, NH); 6.86-6.88 (3H, m, NH, H-3,5 Ph); 7.06 (1H, t, J = 7.6, H-4
Ph); 7.33 (2H, t, J = 7.6, H-2,6 Ph); 9.66 (1H, br. s, NH). 19F NMR spectrum, δ, ppm (J, Hz): 23.4 (2F, dt, 2JF–Н
3
= 53.3, JF–F = 7.2, CF2H); 38.4–38.7 (2F, m, CF2CF2H). Found, %: С 47.82; Н 3.33; N 18.66. С12Н10F4N4О.
Calculated, %: С 47.69; Н 3.34; N 18.54.
5-Oxo-2-phenyl-7-trifluoromethyl-5H-1,2,4-triazolo[4,3-а]pyrimidin-1-id-2-ium (4). Paraform
(36 mg, 1.2 mmol) was added with stirring to a solution of compound 3b (270 mg, 1.0 mmol) in MeCN (8 ml).
The reaction mixture was refluxed for 3 h. The unreacted excess paraform was removed by filtration, the filtrate
was evaporated, the residue was purified by column chromatography (eluent 30:1 CHCl3–EtOH). Yield 78%,
light-pink powder, subl. 261-263°С. IR spectrum, ν, cm-1: 1681 (C=O), 1625, 1563, 1531, 1511 (C=C, C=N),
1188–1107 (C–F). 1H NMR spectrum, δ, ppm: 6.08 (1H, s, Н-6); 7.70–7.77 (3H, m, H-3,4,5 Ph); 8.20-8.22 (2H,
m, H-2,6 Ph); 10.67 (1Н, s, Н-3). 19F NMR spectrum, δ, ppm: 94.0 (3F, s, CF3). Mass spectrum, m/z (Irel, %): 280
[M]+ (24), 211 [M-CF3]+ (10), 104 (26), 93 [C6H7N]+ (19), 77 [C6H5]+ (100), 69 [CF3]+ (22), 65 (18), 64 (17), 51
[CHF2]+ (56), 50 [CF2]+ (15), 39 (18). Found, %: С 51.24; Н 2.51; N 20.16. С12Н7F3N4О. Calculated, %:
С 51.44; Н 2.52; N 19.99.
Reaction of 2-Methylsulfanyl-6-polyfluoroalkylpyrimidin-4(3Н)-ones 2b,c with Morpholine
(General Method). A mixture of pyrimidin-4-one 2b,c (1 mmol) and morpholine (4 ml) was refluxed for 7 h in
a flask equipped with a trap filled with solid NaOH. The excess of morpholine was removed on a rotary
evaporator, the residue was recrystallized from 70% EtOH.
6-Difluoromethyl-2-(morpholin-4-yl)pyrimidin-4(3Н)-one (5а). Yield 66%, white powder,
mp 203-205°С. IR spectrum, ν, cm-1: 3087 (NHstretch), 1674 (C=O), 1594, 1576, 1509 (C=C, C=N), 1079-1060
1
(C–F). H NMR spectrum, δ, ppm (J, Hz): 3.63 (8Н, s, 4СН2 morpholine); 5.91 (1H, br. s, H-5); 6.54 (1H, t,
J = 54.7, CHF2); 11.57 (1H, br. s, NH). 19F NMR spectrum, δ, ppm: 41.1 (2F, br. s, CHF2). Found, %: С 46.59;
Н 4.82; N 18.16. С9Н11F2N3О2. Calculated, %: С 46.76; Н 4.80; N 18.17.
6-(1,1,2,2-Tetrafluoroethyl)-2-(morpholin-4-yl)pyrimidin-4(3Н)-one (5b). Yield 68%, white
powder, mp 213-214°С. IR spectrum, ν, cm-1: 3111 (NHstretch), 1664 (C=O), 1571, 1498 (C=C, C=N),
1
1144-1108 (C–F). H NMR spectrum, δ, ppm (J, Hz): 3.65 (8Н, s, 4СН2 morpholine); 6.03 (1H, br. s, H-5);
6.83 (1H, tt, J = 52.0, J = 5.9, CF2CF2H); 11.73 (1H, br. s, NH). 19F NMR spectrum, δ, ppm (J, Hz): 23.1 (2F, d,
2JF–Н = 52.0, CF2H); 40.1 (2F, br. s, CF2CF2H). Found, %: С 42.95; Н 3.96; N 15.01. С10Н11F4N3О2. Calculated, %:
С 42.71; Н 3.94; N 14.94.
861

TABLE 1. The Main Crystallographic Parameters and Structure
Refinement Characteristics for Compounds 2a, 4.
Parameter
Compound 2а
Compound 4
C12H7F3N4O
Empirical formula
C6H5F3N2OS
M, g/mol
Temperature, K
Wavelength, Å
Syngony
210.18
295(2)
0.71073
Triclinic
P1
280.22
295(2)
0.71073
Triclinic
P1
Space group
Unit cell parameters:
a, Å
b, Å
c, Å
α, deg.
5.7796(8)
7.6046(14)
9.7626(15)
84.857(14)
79.584(13)
89.705(13)
420.28(12)
2
4.9603(7)
10.2665(7)
12.2966(13)
69.997(10)
85.402(10)
82.111(11)
582.49(11)
2
β, deg.
γ, deg.
Unit cell volume, V, Å3
Number of molecules in unit cell, Z
Density, dcalc, g/cm3
Absorption coefficient, μ, mm–1
F(000)
1.661
0.395
212
1.598
0.140
284
θmax
28.27
26.37
Crystal dimensions, mm3
The total number of reflections
Number of independent reflections
Number of reflections with I > 2σ(I)
Number of parameters to be refined
Probability factors (I > 2σ(I))
Probability factors (all reflections)
0.25 × 0.15 × 0.05
3352
1974
997
154
0.25 × 0.20 × 0.15
4825
2311
1255
216
R1 0.0447, wR2 0.0895
R1 0.1042, wR2 0.0978
R1 0.0308, wR2 0.0608
R1 0.0734, wR2 0.065
X-ray Structural Investigation of Compounds 2а, 4. Monocrystals of compound 2а were obtained by
crystallization from CHCl3, while monocrystals of triazolo[4,3-а]pyrimidin-1-id-2-ium 4 were grown from
EtOH. The X-ray diffraction experiments were performed on an Xcalibur 3 diffractometer with a CCD detector
(MoKα radiation, graphite monochromator, ω-scanning). The structures were solved by direct methods and
subsequent Fourier synthesis with SHELXS-97 software, and refined by the least squares method in anisotropic
full matrix approximation for all non-hydrogen atoms with SHELXL-97 software [29]. The coordinates of
hydrogen atoms were determined by placing these atoms in the calculated positions and refined with the "rider"
method. The principal crystallographic parameters and structural refinement characteristics for compounds 2а, 4
are presented in Table 1. The full crystallographic data sets for compounds 2а, 4 have been deposited at the
Cambridge Crystallographic Data Center (deposits CCDC 968207 and CCDC 968208, respectively).
The work was performed with financial support from the Russian Foundation for Basic Research (grant
13-03-00617) and the Grants Council of the President of the Russian Federation (grant NSh-3656.2014.3).
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