Synthesis of new 2-(alkenylsulfanyl)pyrimidine derivatives

Article abstract of DOI:10.1134/S1070428014030221

Isothiuronium salts prepared by treatment of allyl bromide, 2,3- and 1,3-dichloropropenes, and 1,3-dichlorobut-2-ene with thiourea reacted with pentane-2,4-dione and 4,4,4-trifluoro-1-(thiophen-2-yl)-butane-1,3-dione to afford new pyrimidine derivatives, 2-(alkenylsulfanyl)-4,6-dimethyl- and 2-(alkenylsulfanyl)-4-(thiophen-2-yl)-6-(trifluoromethyl)pyrimidines.

Full text of DOI:10.1134/S1070428014030221

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 3, pp. 429–433. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © E.P. Levanova, V.A. Grabel’nykh, V.S. Vakhrina, N.V. Russavskaya, A.I. Albanov, N.A. Korchevin, I.B. Rozentsveig, 2014,
published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50, No. 3, pp. 440–444.
Synthesis of New 2-(Alkenylsulfanyl)pyrimidine Derivatives
E. P. Levanova, V. A. Grabel’nykh, V. S. Vakhrina, N. V. Russavskaya, A. I. Albanov,
N. A. Korchevin, and I. B. Rozentsveig
Favorskii Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: i_roz@irioch.irk.ru
Received September 20, 2013
Abstract—Isothiuronium salts prepared by treatment of allyl bromide, 2,3- and 1,3-dichloropropenes, and
1,3-dichlorobut-2-ene with thiourea reacted with pentane-2,4-dione and 4,4,4-trifluoro-1-(thiophen-2-yl)-
butane-1,3-dione to afford new pyrimidine derivatives, 2-(alkenylsulfanyl)-4,6-dimethyl- and 2-(alkenylsul-
fanyl)-4-(thiophen-2-yl)-6-(trifluoromethyl)pyrimidines.
DOI: 10.1134/S1070428014030221
2-(Organylsulfanyl)pyrimidine derivatives are very
significant among diverse practically important com-
pounds of the pyrimidine series. A combination of
pharmacophoric pyrimidine and sulfanyl moieties in
a single molecule gives rise to versatile biological
activity. 2-(Organylsulfanyl)-substituted pyrimidines
were found to act as enzyme inhibitors and antagonists
of some receptors affecting nucleic acids synthesis
[1, 2] and cell growth, proliferation, and metabolism
[3], which leads to the appearance of antiviral (includ-
ing anti-HIV) [4, 5], anticancer [3, 6–8], antidiabetic
[9], and antiphlogistic activity [8].
Sulfanylpyrimidine derivatives are used as model
structures in theoretical studies [10] and are also im-
portant and often indispensable reagents in the
chemistry of pyrimidines. The synthesis of biologically
active pyrimidinamines based on the transformations
of sulfanylpyrimidine is well known [11–18]. Selective
cross-couplings involving a sulfanylpyrimidine frag-
ment were reported [19], and reactions were described
[20, 21] where pyrimidine moiety behaves as a leaving
group providing an approach to selective preparation
of difficultly accessible polysubstituted alkenes.
Sulfanyl-substituted pyrimidines were synthesized
in two steps (Scheme 1). Preliminarily, allyl bromide
(Ia), 2,3-dichloropropene (Ib), 1,3-dichloropropene
(Ic), and 1,3-dichlorobut-2-ene (Id) were reacted with
thiourea to obtain isothiuronium salts IIa–IId in 82–
1
97% yield. The H and 13C NMR spectra of IIa–IId
contained proton and carbon signals from the alkenyl
groups, a signal from the NH2 protons at δ 8.4–
9.4 ppm, and C=S carbon signal at δC 169–170 ppm.
The target sulfanyl-substituted pyrimidines IVa–
IVd and Va–Vd were obtained by reaction of iso-
thiuronium salts IIa–IId with 1,3-diketones IIIa and
IIIb. The maximum yields of IVa–IVd and Va–Vd
(57–88%) were achieved by heating the reactants in
boiling acetic acid in the presence of sodium acetate.
Isothiuronium salts IIc and IId and 2-sulfanyl-sub-
stituted pyrimidines IVc, IVd, Vc, and Vd derived
from 1,3-dichloropropene (Ic) and 1,3-dichlorobut-2-
ene (Id) were obtained as mixtures of E and Z isomers.
The E/Z isomer ratios for compounds IIc, IVc, Vc and
IId, IVd, Vd were estimated at 1:1 and 1:9, respec-
tively, on the basis of their 1H NMR spectra, and these
ratios coincided with the isomeric compositions of
initial dichloroalkenes Ic and Id.
Compounds IVa–IVd were isolated as viscous
liquids, and 4-(2-thienyl)-6-trifluoromethyl derivatives
Va–Vd are low melting crystalline substances. Their
structure was unambiguously proved by spectral
methods and elemental analysis. Signals in the NMR
spectra of IVa–IVd and Va–Vd were assigned, and the
Taking into account high importance of organyl-
sulfanyl-substituted pyrimidines, the synthesis of their
new derivatives is a topical goal.
In this paper we describe the synthesis of previ-
ously unknown 2-(alkenylsulfanyl)pyrimidine deriva-
tives necessary for the preparation of functionalized
fused pyrimidines which are promising from the view-
point of their biological activity.
429

LEVANOVA et al.
Scheme 1.
430
R1
R1
S
EtOH, 78–80°C, 17–18 h
R2
X
R2
S
IIa–IId
S
NH2
+
X–
H2N
NH2
R3
Ia–Id
R3
NH2
R1
R2
N
R4
O
O
AcOH, AcONa, 116–118°C, 14 h
IIa–IId
+
R3
N
R4
R5
R5
IIIa, IIIb
IVa–IVd, Va–Vd
I, II, X = Br, R1 = R2 = R3 = H (a); X = R1 = Cl, R2 = R3 = H (b); X = R2 = Cl, R1 = R3 = H (c); X = R2 = Cl, R1 = H, R3 = Me (d);
III, R4 = R5 = Me (a); R4 = CF3, R5 = thiophen-2-yl (b); IV, R4 = R5 = Me: R1 = R2 = R3 = H (a); R1 = Cl, R2 = R3 = H (b); R1 = R3 =
H, R2 = Cl (c); R1 = H, R2 = Cl, R3 = Me (d); V, R4 = CF3, R5 = thiophen-2-yl: R1 = R2 = R3 = H (a); R1 = Cl, R2 = R3 = H (b); R1 =
R3 = H, R2 = Cl (c); R1 = H, R2 = Cl, R3 = Me (d).
structure of Z and E isomers was determined, using
5% of XE-60 on Chromaton N-AW-HMDS; oven tem-
perature programming from 30 to 230°C at a rate of
12 deg/min; carrier gas helium. The mass spectra were
obtained on a Shimadzu GCMS-QP5050A instrument
(SPB-5 column, 60000 × 0.25 mm, film thickness
0.25 µm; injector temperature 250°C; carrier gas
helium, flow rate 0.7 mL/min; oven temperature pro-
gramming from 60 to 260°C at a rate of 15 deg/min;
detector temperature 250°C; quadrupole mass ana-
lyzer; electron impact, 70 eV; ion source temperature
200°C; a.m.u. range 34–650).
two-dimensional NMR techniques.
1
In the H and 13C NMR spectra of IVa–IVd and
Va–Vd we observed signals belonging to protons and
carbon atoms in both alkenyl fragments and substit-
uents in the pyrimidine ring. The 5-H proton in the
pyrimidine ring gave rise to a singlet at δ 6.70 ppm for
dimethyl-substituted derivatives IVa–IVd or δ 7.45–
7.60 ppm for trifluoromethyl derivatives Va–Vd,
indicating 2,4,6-substitution pattern. Signals from the
C–S carbon atom in the 13C NMR spectra of isothiuro-
nium salts IIa–IId appeared in the same region as
those belonging to C2 in the spectra of pyrimidines IV
and V (δC 169–173 ppm). The transformation of the
carbonyl carbon atoms of initial diketones IIIa and
IIIb into C4 and C6 in the pyrimidine ring of IV and V
was accompanied by considerable upfield of the corre-
sponding signals.
S-Allylisothiuronium bromide (IIa). A mixture of
12.10 g (0.10 mol) of allyl bromide (Ia), 7.61 g
(0.10 mol) of thiourea, and 60 mL of ethanol was
heated for 20 h under reflux. The mixture was cooled
and diluted with 60 mL of diethyl ether, and the pre-
cipitate was filtered off, washed with diethyl ether, and
dried under reduced pressure. Yield 19.17 g (97%),
mp 74–76°C. IR spectrum (KBr), ν, cm–1: 3307, 3254
Thus, we have synthesized new pyrimidine deriva-
tives which attract interest as substrates for further
transformations due to the presence of alkenylsulfanyl
substituents in their molecules.
1
(NH); 1639 (C=C); 681 (C–S). H NMR spectrum
3
4
(D2O), δ, ppm: 3.83 d.d (2H, CH2S, J = 6.5, J =
3
2
4
1.1 Hz), 5.32 m (1H, =CH2, Jcis = 10.2, J = 1.1, J =
1.1 Hz), 5.43 m (1H, =CH2, 3Jtrans = 17.1, 2J = 1.1, 4J =
3
3
1.1 Hz), 5.94 m (1H, =CH, J = 6.5, Jcis = 10.2,
EXPERIMENTAL
3Jtrans = 17.1 Hz), 8.44 br.s (NH2). C NMR spectrum
13
(D2O), δC, ppm: 33.1 (SCH2), 119.9 (CH2=), 131.6
(CH=), 169.3 (SCN). Found, %: C 24.57; H 4.61;
Br 40.62; N 14.19; S 16.75. C4H9BrN2S. Calculated,
%: C 24.38; H 4.60; Br 40.54; N 14.21; S 16.27.
S-(2-Chloroprop-2-en-1-yl)isothiuronium chlo-
ride (IIb). A mixture of 22.19 g (0.20 mol) of 2,3-di-
chloroprop-1-ene (Ib) and 15.22 g (0.20 mol) of thio-
urea in 120 mL of ethanol was heated for 17 h under
The IR spectra were recorded on a Bruker IFS spec-
trometer. The 1H and 13C NMR spectra were measured
on a Bruker DPX-400 spectrometer at 400.13 and
100.61 MHz, respectively, using hexamethyldisilox-
ane as internal reference. The purity of initial com-
pounds was checked, and the products were analyzed,
by GLC on an LKhM 80-MD-2 chromatograph
equipped with a 2000 ×3-mm column packed with
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 3 2014

SYNTHESIS OF NEW 2-(ALKENYLSULFANYL)PYRIMIDINE DERIVATIVES
431
reflux, and the mixture was treated as described above.
Yield 33.60 g (90%), mp 135–137°C. IR spectrum
(KBr), ν, cm–1: 3274, 3187 (N–H); 1656 (C=C); 721
S 16.41. C5H10Cl2N2S. Calculated, %: C 29.86; H 5.01;
Cl 35.26; H 13.93; S 15.94.
4,6-Dimethyl-2-(prop-2-en-1-ylsulfanyl)pyrimi-
dine (IVa). A mixture of 2.50 g (0.013 mol) of salt IIa,
2.08 g (0.025 mol) of sodium acetate, and 2.54 g
(0.025 mol) of acetylacetone (IIIa) in 20 mL of glacial
acetic acid was heated for 14 h under reflux. The
mixture was cooled to room temperature and filtered,
the precipitate was washed on a filter with glacial
acetic acid, and acetic acid was distilled off from the
filtrate under reduced pressure (40 mm). The dark
brown residue was dissolved in water, the product was
extracted into methylene chloride (3×20 mL), the
extract was dried over MgSO4, and the solvent was
distilled off under reduced pressure. Yield 1.89 g
(83%), light yellow liquid, bp 114–115°C (2 mm). IR
spectrum (film), ν, cm–1: 3082–3057, 3008–2923
1
(C–Cl); 629 (C–S). H NMR spectrum (DMSO-d6), δ,
ppm: 4.45 s (2H, SCH2), 5.46 d and 5.81 d (1H each,
2
=CH2, J = 1.3 Hz), 9.41 br.s and 9.54 br.s (2H each,
NH2). 13C NMR spectrum (DMSO-d6), δC, ppm: 37.9
(CH2S), 118.1 (=CH2), 135.6 (=CCl), 168.6 (SCN).
Found, %: C 25.61; H 4.27; Cl 37.86; N 15.07;
S 17.24. C4H8Cl2N2S. Calculated, %: C 25.68; H 4.31;
Cl 37.90; N 14.97; S 17.14.
S-(3-Chloroprop-2-en-1-yl)isothiuronium chlo-
ride (IIc, a mixture of Z and E isomers). A mixture of
5.55 g (0.05 mol) of 1,3-dichloroprop-1-ene (Ic) and
3.85 g (0.05 mol) of thiourea in 30 mL of ethanol was
heated for 12 h under reflux. The mixture was cooled
and diluted with 50 mL of diethyl ether, and compound
IIc (E/Z isomer mixture) separated as a yellow oily
substance. It was isolated by decanting and dried under
reduced pressure. Yield 8.51 g (91%). IR spectrum
(film), ν, cm–1: 3289, 3192 (N–H); 1649 (C=C); 707
1
(C–H); 1582 (C=C). H NMR spectrum (CDCl3), δ,
3
ppm: 2.37 s (6H, CH3), 3.80 d (2H, SCH2, J =
6.7 Hz), 5.07 d.d (1H, =CH2, 3Jcis = 10.4, 2J = 1.3 Hz),
5.28 d.d (1H, =CH2, 3Jtrans = 17.0, 2J = 1.3 Hz), 5.96 m
1
3
3
3
(C–Cl); 675 (C–S). H NMR spectrum (DMSO-d6), δ,
(1H, =CH, Jcis = 10.4, Jtrans = 17.0, J = 6.7 Hz),
6.66 s (1H, 5-H). 13C NMR spectrum (CDCl3), δC,
ppm: 23.7 (CH3), 33.6 (=CH2), 115.5 (=CH), 133.9
(C5), 166.8 (C4, C6), 170.6 (C2). Mass spectrum:
m/z 180 [M]+. Found, %: C 59.88; H 6.72; N 15.60;
S 17.68. C9H12N2S. Calculated, %: C 59.96; H 6.71;
N 15.54; S 17.79.
3
ppm: Z isomer: 4.07 d (2H, CH2S, J = 7.7 Hz),
3
6.12 d.t (1H, =CH, J = 7.0, 7.7 Hz), 6.61 d (1H,
3
=CHCl, J = 7.0 Hz), 9.40 br.s (4H, NH2); E isomer:
3
4.05 d (2H, CH2S, J = 7.7 Hz), 6.03 d.t (1H, =CH,
3
3J = 13.2, 7.7 Hz), 6.73 d (1H, =CHCl, J = 13.2 Hz),
9.40 br.s (4H, NH2). 13C NMR spectrum (DMSO-d6),
δC, ppm: Z isomer: 30.6 (CH2S), 122.8 (=CHCl), 128.1
(=CH), 169.3 (SCH); E isomer: 27.6 (CH2S), 124.1
(=CHCl), 125.4 (=CH), 169.8 (SCN). Found, %:
C 25.66; H 4.17; Cl 32.31; N 15.01; S 17.18.
C4H8Cl2N2S. Calculated, %: C 25.68; H 4.31;
Cl 37.90; N 14.97; S 17.14.
2-(2-Chloroprop-2-en-1-ylsulfanyl)-4,6-dimeth-
ylpyrimidine (IVb) was synthesized in a similar way
from 2.50 g (0.013 mol) of compound IIb and 2.67 g
(0.027 mol) of acetylacetone (IIIa). Yield 2.53 g
(88%), light yellow liquid, bp 117–120°C (2 mm). IR
spectrum (film), ν, cm–1: 3055, 2959–2852 (C–H);
1
1583, 1536 (C=C); 765 (C–Cl). H NMR spectrum
S-(3-Chlorobut-2-en-1-yl)isothiuronium chloride
(IId, a mixture of Z and E isomers). A mixture of
6.25 g (0.05 mol) of 1,3-dichlorobut-2-ene (Id) and
3.85 g (0.50 mol) of thiourea in 30 mL of ethanol was
heated for 9.5 h under reflux. The mixture was then
treated as described above for the synthesis of IIa.
Yield 8.28 g (82%), mp 121–122°C. IR spectrum
(KBr), ν, cm–1: 3206 (N–H), 1656 (C=C), 716 (C–Cl),
(CDCl3), δ, ppm: 2.37 s (6H, CH3), 4.08 s (2H, CH2S),
5.24 s and 5.54 s (2H, =CH2), 6.69 s (1H, 5-H).
13C NMR spectrum (CDCl3), δC, ppm: 23.7 (CH3),
38.1 (CH2S), 114.4 (=CH2), 115.9 (C5), 138.2 (=CCl),
167.1 (C4, C6), 169.5 (C2). Mass spectrum: m/z 215
[M]+. Found, %: C 50.38; H 5.11; Cl 16.72; N 13.21;
S 14.53. C9H11ClN2S. Calculated, %: C 50.34; H 5.16;
Cl 16.51; N 13.05; S 14.93.
1
700 (C–S). H NMR spectrum (DMSO-d6), δ, ppm:
2.14 s (3H, CH3, Z), 2.16 d (3H, CH3, E), 3.97 d (2H,
2-(3-Chloroprop-2-en-1-ylsulfanyl)-4,6-dimeth-
ylpyrimidine (IVc, a mixture of Z and E isomers) was
synthesized as described above for IVa from 2.53 g
(0.014 mol) of salt IIc and 2.70 g (0.027 mol) of
acetylacetone (IIIa). Yield 2.32 g (81%). Light yellow
liquid, bp 122–123°C (2 mm). IR spectrum (film), ν,
cm–1: 3063, 2960–2924 (C–H); 1583, 1536 (C=C); 765
3
3
CH2S, Z, J = 7.5 Hz), 4.03 d (2H, CH2S, E, J =
3
7.5 Hz), 5.87 t (1H, =CH, Z, J = 7.5 Hz), 5.72 t (1H,
3
13
=CH, E, J = 7.5 Hz), 9.39 br.s (4H, NH2). C NMR
spectrum (DMSO-d6), δC, ppm: Z isomer: 25.8 (CH3),
29.0 (CH2S), 119.2 (=CH), 135.9 (=CCl), 169.7
(SCN). Found, %: C 30.07; H 5.10; Cl 35.00; N 14.06;
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LEVANOVA et al.
432
1
2
(C–Cl). H NMR spectrum (CDCl3), δ, ppm: 2.38 s
(C5′), 141.0 (C2′), 156.2 q (C6, JCF = 36.0 Hz), 161.1
3
(6H, CH3), 3.77 d (2H, CH2S, Z, J = 7.6 Hz), 3.94 d
(C4), 173.3 (C2). Mass spectrum: m/z 302 [M]+. Found,
%: C 47.78; H 3.11; N 9.10; S 21.65. C12H9F3N2S2.
Calculated, %: C 47.67; H 3.00; N 9.27; S 21.21.
(2H, CH2S, E, 3J = 6.9 Hz), 6.05 d.t (1H, =CH, E, 3J =
3
6.9, 13.2 Hz), 6.07 d.t (1H, =CH, Z, J = 7.6, 7.2 Hz),
6.10 d (1H, ClCH=, E, 3J = 13.2), 6.24 d (1H, ClCH=,
Z, 3J = 7.2 Hz), 6.68 s and 6.69 s (1H each, 5-H, E, Z).
13C NMR spectrum (CDCl3), δC, ppm: 23.7 (CH3),
27.1 (CH2S, E), 30.6 (CH2S, Z), 115.6 (=CH, E), 115.8
(=CH, Z), 120.1 (ClCH=, E), 120.4 (ClCH=, Z), 127.9
(C5, E), 129.2 (C5, Z), 166.9 (C4, C6), 169.7 (C2, Z),
170.2 (C2, E). Mass spectrum: m/z 214 [M]+. Found,
%: C 50.33; H 5.28; Cl 15.97; N 13.00; S 14.88.
C9H11ClN2S. Calculated, %: C 50.34; H 5.16;
Cl 16.51; N 13.05; S 14.93.
2-(2-Chloroprop-2-en-1-ylsulfanyl)-4-(thiophen-
2-yl)-6-(trifluoromethyl)pyrimidine (Vb) was
synthesized as described above for IVa from 2.00 g
(0.011 mol) of IIb and 2.38 g (0.011 mol) of IIIb.
Yield 2.62 g (57%), mp 91–93°C. IR spectrum (KBr),
ν, cm–1: 3094, 2994–2918 (C–H); 1665, 1592, 1531
1
(C=C); 1143, 1127 (C–F); 728 (C–Cl). H NMR spec-
trum (CDCl3), δ, ppm: 4.12 s (2H, CH2S), 5.30 d and
2
5.63 d (1H each, =CH2, J = 1.0 Hz), 7.17 d.d (1H,
3
4′-H, J = 5.0, 3.8 Hz), 7.47 s (1H, 5-H), 7.60 d (1H,
3
3
2-(3-Chlorobut-2-en-1-ylsulfanyl)-4,6-dimethyl-
pyrimidine (IVd, a mixture of Z and E isomers) was
synthesized in a similar way from 2.50 g (0.012 mol)
of salt IId and 2.49 g (0.025 mol) of acetylacetone
(IIIa). Yield 2.48 g (87%), light yellow liquid, bp 128–
129°C (2 mm). IR spectrum (film), ν, cm–1: 2921
(C–H); 1582, 1536 (C=C); 765 (C–Cl). 1H NMR spec-
trum (CDCl3), δ, ppm: 2.09 s (3H, CH3CCl=, E), 2.18 s
(3H, CH3CCl=, Z), 2.38 s (6H, CH3), 3.77 d (2H,
5′-H, J = 5.0 Hz), 7.82 d (1H, 3′-H, J = 3.8 Hz).
13C NMR spectrum (CDCl3), δC, ppm: 38.6 (CH2S),
106.4 q (C5, JCF = 2.1 Hz), 115.2 (=CH2), 120.4 q
3
(CF3, JCF = 275.5 Hz), 128.8 (C4′), 129.4 (C3′), 132.1
1
(C5′), 137.3 (=CCl), 140.8 (C2′), 155.9 q (C6, JCF
=
2
36.0 Hz), 161.3 (C4), 172.3 (C2). Mass spectrum:
m/z 336 [M]+. Found, %: C 42.93; H 2.27; N 8.31;
S 19.13. C12H8ClF3N2S2. Calculated, %: C 42.80;
H 2.39; N 8.32; S 19.04.
3
3
SCH2, E, J = 8.1 Hz), 3.89 d (2H, SCH2, Z, J =
3
2-(3-Chloroprop-2-en-1-ylsulfanyl)-4-(thiophen-
2-yl)-6-(trifluoromethyl)pyrimidine (Vc) was syn-
thesized in a similar way from 2.00 g (0.011 mol) of
isothiuronium salt IIc and 2.38 g (0.011 mol) of com-
pound IIIb. Yield 2.10 g (58%), mp 79°C. IR spectrum
(KBr), ν, cm–1: 3086–2938 (C–H); 1627, 1581, 1538
7.2 Hz), 5.74 t (1H, =CH, Z, J = 7.2 Hz), 5.85 t (1H,
3
=CH, E, J = 8.1 Hz), 6.67 s (1H, 5-H, Z), 6.68 s (1H,
5-H, E). 13C NMR spectrum (CDCl3), δC, ppm: 23.8
(CH3), 26.1 (CH3SCl=), 29.0 (CH2S, E), 29.1 (CH2S,
Z), 115.6 (C5, Z), 115.8 (C5, E), 121.9 (=CH, Z), 123.5
(=CH, E), 132.8 (CCl=), 167.0 (C4, C6), 170.8 (C2).
Mass spectrum: m/z 228 [M]+. Found, %: C 52.60;
H 5.88; Cl 15.36; N 12.22; S 13.92. C10H13ClN2S.
Calculated, %: C 52.51; H 5.73; Cl 15.50; N 12.25;
S 14.02.
1
(C=C); 1182, 1147, 1116 (C–F); 725 (C–Cl). H NMR
3
spectrum (CDCl3), δ, ppm: 3.83 d (2H, CH2S, Z, J =
3
7.7 Hz), 4.00 d (2H, CH2S, E, J = 6.5 Hz), 6.07 d.t
(1H, =CH, E, 3J = 6.5, 13.2 Hz), 6.15 d.t (1H, =CH, Z,
3J = 7.1, 7.7 Hz), 6.18 d (1H, ClCH=, Z, J = 7.1 Hz),
3
2-(Prop-2-en-1-ylsulfanyl)-4-(thiophen-2-yl)-6-
(trifluoromethyl)pyrimidine (Va) was synthesized
as described above for compound IVa from 2.50 g
(0.013 mol) of salt IIa and 2.82 g (0.013 mol) of
compound IIIb. Yield 2.93 g (77%), mp 38–40°C. IR
spectrum (KBr), ν, cm–1: 3085, 2953–2851 (C–H);
1663, 1583, 1531 (C=C); 1432, 1404, 1388 (C–F).
1H NMR spectrum (CDCl3), δ, ppm: 3.84 d.t (2H,
3
6.37 d (1H, ClCH=, E, J = 13.2 Hz), 7.17 d.d (1H,
3
3
4′-H, Z, J = 2.1, 3.8 Hz), 7.18 d.d (1H, 4′-H, E, J =
2.1, 3.8 Hz), 7.47 s (1H, 5-H, Z), 7.48 s (1H, 5-H, E),
3
7.59 d (1H, 5′-H, Z, J = 3.8 Hz), 7.60 d (1H, 5′-H, E,
3J = 3.8 Hz), 7.82 d (1H, 3′-H, Z, J = 2.1 Hz), 7.83 d
3
(1H, 3′-H, E, J = 2.1 Hz). 13C NMR spectrum
3
(CDCl3), δC, ppm: 27.5 (SCH2, E), 31.1 (SCH2, Z),
106.1 q (C5, Z, JCF = 2.2 Hz), 106.3 q (C5, E, JCF
=
3
3
3
4
CH2S, J = 7.0, J = 1.1 Hz), 5.13 d.d.t (1H, =CH2,
3Jcis = 10, 2J = 1.1, 4J = 1.1 Hz), 5.36 d.d.t (1H, =CH2,
1
2.2 Hz), 120.4 q (CF3, JCF = 257.4 Hz), 121.3
(ClCH=, Z), 121.6 (ClCH=, E), 127.1 (=CH, Z), 128.3
(=CH, E), 128.8 (C4′, Z), 128.8 (C4′, E), 129.3 (C3′, Z),
129.3 (C3′, E), 132.1 (C5′, Z), 132.1 (C5′, E), 140.8 (C2′,
3Jtrans = 17, J = J = 1.1 Hz), 5.98 d.d.t (1H, =CH,
2
4
3Jtrans = 17.0, Jcis = 10.0, J = 7.0 Hz), 7.13 d.d (1H,
3
3
4′-H, 3J = 5.0, 3.8 Hz), 7.55 d (1H, 5′-H, J = 5.0 Hz),
3
E), 140.9 (C2′, Z), 156.1 q (C6, E, JCF = 36.2 Hz),
2
3
7.78 d (1H, 3′-H, J = 3.8 Hz), 7.42 s (1H, 5-H).
156.2 q (C6, Z, JCF = 36.2 Hz), 161.2 (C4, Z), 161.3
2
13C NMR spectrum (CDCl3), δC, ppm: 34.0 (CH2S),
(C4, E), 173.3 (C2, Z), 172.6 (C2, E). Mass spectrum:
m/z 336 [M]+. Found, %: C 42.95; H 2.28; N 8.11;
105.9 (C5), 118.2 (=CH2), 120.4 q (CF3, JCF
=
1
275.7 Hz), 128.7 (C4′), 129.1 (C3′), 131.9 (=CH), 133.0
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 3 2014

SYNTHESIS OF NEW 2-(ALKENYLSULFANYL)PYRIMIDINE DERIVATIVES
433
Xu, Y., Yakowec, P., Yang, K., Zalameda, L.P.,
Zhang, N., Hughes, P., and Norman, M.H., J. Med.
Chem., 2011, vol. 54, p. 1789.
S 18.94. C11H8ClF3N2S2. Calculated, %: C 42.80;
H 2.39; N 8.32; S 19.04.
2-(3-Chlorobut-2-en-1-ylsulfanyl)-4-(thiophen-2-
yl)-6-(trifluoromethyl)pyrimidine (Vd) was synthe-
sized in a similar way from 1.50 g (0.007 mol) of IId
and 1.66 g (0.007 mol) of IIIb. Yield 2.14 g (82%),
mp 84–85°C. IR spectrum (KBr), ν, cm–1: 3110–3046,
2983–2850 (C–H); 1660, 1590, 1529 (C=C); 1180,
4. Mai, A., Artico, M., Sbardella, G., Massa, S., Novel-
lino, E., Greco, G., Loi, A.G., Tramontano, E.,
Marongiu, M.E., and La Colla, P., J. Med. Chem., 1999,
vol. 42, p. 619.
5. Mai, A., Sbardella, G., Artico, M., Ragno, R., Massa, S.,
Novellino, E., Greco, G., Lavecchia, A., Musiu, C., La
Colla, M., Murgioni, C., La Colla, P., and Loddo, R.,
J. Med. Chem., 2001, vol. 44, p. 2544.
1
1146, 1125 (C–F); 719 (C–Cl). H NMR spectrum
(CDCl3), δ, ppm: Z isomer: 2.12 s (3H, CH3), 3.95 d
3
3
(2H, CH2S, J = 7.1 Hz), 5.83 t (2H, =CH, J =
6. Laufer, S.A. and Wagner, G.K., J. Med. Chem., 2002,
3
vol. 45, p. 2733.
7.1 Hz), 7.17 d.d (1H, 4′-H, J = 4.8, 3.3 Hz), 7.45 s
3
(1H, 5-H), 7.58 d (1H, 5′-H, J = 4.8 Hz), 7.82 d (1H,
7. Parent, A.A., Gunther, J.R., and Katzenellenbogen, J.A.,
3
J. Med. Chem., 2008, vol. 51, p. 6512.
3′-H, J = 3.3 Hz); E isomer: 2.18 s (3H, CH3), 3.80 d
3
3
(2H, CH2S, J = 7.1 Hz), 5.90 t (2H, =CH, J =
8. Hieke, M., Greiner, C., Dittrich, M., Reisen, F.,
Schneider, G., Schubert-Zsilavecz, M., and Werz, O.,
J. Med. Chem., 2011, vol. 54, p. 4490.
9. Seto, S., Okada, K., Kiyota, K., Isogai, S., Iwago, M.,
Shinozaki, T., Kitamura, Y., Kohno, Y., and Mura-
kami, K., J. Med. Chem., 2010, vol. 53, p. 5012.
3
7.1 Hz), 7.17 d.d (1H, 4′-H, J = 4.8, 3.3 Hz), 7.45 s
3
(1H, 5-H), 7.58 d (1H, 5′-H, J = 4.8 Hz), 7.82 d (1H,
3′-H, J = 3.3 Hz). 13C NMR spectrum (CDCl3), δC,
3
ppm: Z isomer: 26.2 (CH3), 29.6 (CH2S), 106.1 q (C5,
3JCF = 2.7 Hz), 120.5 q (CF3, JCF = 275.7 Hz), 121.1
1
(=CH), 128.8 (C4′), 129.3 (C3′), 132.0 (C5′), 134.1
10. Freeman, F., Po, H.N., Ho, T.S., and Wang, X., J. Phys.
(ClC=), 141.1 (C2′), 156.23 q (C6, JCF = 36.0 Hz),
2
Chem. A, 2008, vol. 112, p. 1643.
161.23 (C4), 173.71 (C2). Mass spectrum: m/z 350
[M]+. Found, %: C 44.67; H 2.79; N 7.98; S 18.46.
C13H10ClF3N2S2. Calculated, %: C 44.51; H 2.87;
N 7.99; S 18.28.
11. Matloobi, M. and Kappe, C.O., J. Comb. Chem., 2007,
vol. 9, p. 275.
12. Arvanitis, E.A., Chadha, N., Pottorf, R.S., and
Player, M.R., J. Comb. Chem., 2004, vol. 6, p. 414.
13. Vanden Eynde, J.J., Labuche, N., van Haverbeke, Y.,
The principal results were obtained using the
facilities of the Baikal Joint Analytical Center, Siberian
Branch, Russian Academy of Sciences.
and Tietze, L., Arkivoc, 2003, part (xv), p. 22.
14. Watanabe, M., Koike, H., Ishiba, T., Okada, T., Seo, S.,
and Hirai, K., Bioorg. Med. Chem., 1997, vol. 5, p. 437.
15. Kim, D.C., Lee, Y.R., Yang, B.-S., Shin, K.J., Kim, D.J.,
Chung, B.Y., and Yoo, K.H., Eur. J. Med. Chem., 2003,
vol. 38, p. 525.
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