Synthesis of 2,4,6-trisubstituted 5-(2-alkylsulfanylethyl)-pyrimidines and some their transformations

Article abstract of DOI:10.1134/S1070428013120087

New 2,4,6-trisubstituted 5-(2-alkylsulfanylethyl)pyrimidines were synthesized by condensation of ethyl 2-(2-alkylsulfanylethyl)-3-oxobutanoates with various amidines and thiourea. Fusion of substituted 2,6-dimethylpyrimidin- 4(3H)-ones with aromatic aldeh

Full text of DOI:10.1134/S1070428013120087

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 12, pp. 1753–1758. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © A.A. Arutyunyan, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 12, pp. 1773–1777.
Synthesis of 2,4,6-Trisubstituted 5-(2-Alkylsulfanylethyl)-
pyrimidines and Some Their Transformations
A. A. Arutyunyan
Mndzhoyan Institute of Fine Organic Chemistry, Research Technological Center of Organic and Pharmaceutical Chemistry,
National Academy of Sciences of Armenia, pr. Azatutyan 26, Yerevan, 0014 Armenia
e-mail: harutyunyan.arthur@yahoo.com
Received December 12, 2012
Abstract—New 2,4,6-trisubstituted 5-(2-alkylsulfanylethyl)pyrimidines were synthesized by condensation of
ethyl 2-(2-alkylsulfanylethyl)-3-oxobutanoates with various amidines and thiourea. Fusion of substituted
2,6-dimethylpyrimidin-4(3H)-ones with aromatic aldehydes gave the corresponding 6-styrylpyrimidines. Some
5-(2-alkylsulfanylethyl)pyrimidines were oxidized to sulfoxides, and amination of 5-[2-(butylsulfanyl)ethyl]-6-
methyl-2-propylsulfanylpyrimidin-4(3H)-one with 4-aminobenzoic acid afforded 4-{5-[2-(butylsulfanyl)ethyl]-
4-methyl-6-oxo-1,6-dihydropyrimidin-2-ylamino}benzoic acid.
DOI: 10.1134/S1070428013120087
Many pyrimidine derivatives, in particular substi-
tuted sulfur-containing pyrimidines, act as nucleic ex-
change antimetabolites and thus exhibit pronounced
antitumor, antibacterial, antiviral, antiprotozoa, and
antithyroid activity [1]. However, in most of the syn-
thesized sulfur-containing pyrimidines the sulfur atom
is linked directly to the pyrimidine ring, whereas
pyrimidines with a side-chain sulfur atom are few in
number though they are promising as potential chemo-
therapeutically active compounds.
covalent bonding with a number of cell targets via the
Pummerer reaction, as was proposed for the mecha-
nism of action of the natural pyrimidine antibiotic
sparsomycin which possesses a sulfoxide group [2].
In view of the above stated, in continuation of
studies on new biologically active substituted pyrimi-
dines [3], the present article reports on the synthesis of
2,4,6-trisubstituted 5-[2-(alkylsulfanyl)ethyl]pyrimi-
dines II–VII. Alkylation of ethyl acetoacetate with
1-(2-chloroethylsulfanyl)alkanes I gave ethyl 2-(2-al-
kylsulfanylethyl)-3-oxobutanoates which were sub-
jected (without isolation) to cyclization with amidines
and thiourea; as a result, substituted pyrimidines IIa–
Introduction of a reactive sulfoxide group into
molecules of pyrimidine derivatives also seems to be
reasonable. Such modification is believed to ensure
Scheme 1.
NH
O
SR
R'
NH2
HN
R'
N
Me
IIa–IIg
O
O
O
O
EtONa, EtOH
EtONa, EtOH
SR
+
Me
RS
OEt
Cl
S
O
Me
OEt
I
SR
H2N
NH2
HN
S
N
Me
H
IIIa–IIIc
II, R′= Me, R = Bu (a), i-Bu (b), C5H11 (c), 2-ClC6H4CH2 (d); R = C5H11, R′ = Ph (e), PhCH2 (f); R′= Ph, R = CH2=C(Me)CH2 (g);
III, R = Bu (a), C5H11 (b), 4-EtOC6H4CH2 (c).
1753

ARUTYUNYAN
1754
Scheme 2.
O
N
SR
HN
CHO
ZnCl2
+
IIa–IId
Me
R'
R'
IVa–IVe
IV, R′ = Br, R = Bu (a), i-Bu (b); R′ = O2N, R = C5H11 (c), 2-ClC6H4CH2 (d); R = 2-ClC6H4CH2, R′ = Me2N (e).
Scheme 3.
O
N
O
S
NaIO4, 50% aq. dioxane
HN
IId
Cl
Me
Me
V
O
O
S
HN
Bu
NaIO4, 50% aq. dioxane
IVa
Me
N
Br
VI
IIg and IIIa–IIIc were obtained in moderate yields
Compounds IIc–IIe, IIIb, IIIc, IVa, IVc, IVe, and
(Scheme 1).
V were tested for antibacterial activity against
S. aureus 209 p 1, Sh. dysenteriae Flexneri 6858, and
E. coli 0-55. All compounds, except for pyrimidines
IIc, IIe, and IIIe, showed a weak activity in all bac-
terial strains used.
2,6-Dimethylpyrimidines IIa–IId smoothly reacted
at the 6-methyl group with some aromatic aldehydes in
the presence of ZnCl2 to afford 6-styryl-substituted
derivatives IVa–IVe via a Claisen-type condensation
(Scheme 2). Sulfides IId and IVa were oxidized to the
corresponding sulfoxides V and VI with sodium
periodate in aqueous dioxane (Scheme 3). Compounds
V and VI were isolated as racemates. 2-Thioxopyrimi-
dine IIIa was treated with propyl bromide in the
presence of alkali to obtain sulfide VII, and fusion of
the latter with 4-aminobenzoic acid gave 2-(4-carboxy-
phenylamino)pyrimidine VIII (Scheme 4)
EXPERIMENTAL
Analytical thin-layer chromatography was per-
formed on Silufol UV-254 plates; spots were detected
by treatment with iodine vapor. The IR spectra were
recorded on a Nicolet Avatar 330 spectrometer from
samples dispersed in mineral oil. The 1H NMR spectra
were measured on a Varian Mercury-300 instrument at
300 MHz using tetramethylsilane as internal standard.
The mass spectra were obtained on an MKh-1321A
mass spectrometer with direct sample admission into
the ion source.
The structure of the newly synthesized compounds
was proved by their IR, NMR, and mass spectra and
elemental analyses, and their purity was checked by
analytical TLC.
Scheme 4.
O
N
O
O
N
S
S
4-H2NC6H4COOH
PrBr, NaOH, EtOH
HN
Bu
HO
HN
Bu
IIIa
PrS
Me
VII
N
Me
H
VIII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 12 2013

SYNTHESIS OF 2,4,6-TRISUBSTITUTED 5-(2-ALKYLSULFANYLETHYL)PYRIMIDINES
1755
1.29–1.43 m (4H, CH2CH2CH3), 1.58 m (2H,
SCH2CH2), 2.19 s (3H, CH3), 2.21 s (3H, CH3), 2.48–
2.56 m (4H, CH2), 2.58–2.65 m (2H, CH2), 12.14 br.s
(1H, NH). Found, %: N 11.24; S 12.31. C13H22N2OS.
Calculated, %: N 11.01; S 12.60.
5-(2-R-Sulfanylethyl)-2,6-dimethylpyrimidin-
4(3H)-ones IIa–IIg and 5-(2-R-sulfanylethyl)-6-
methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-ones
IIIa–IIIc (general procedure). Metallic sodium, 2.3 g
(0.1 mol), was dissolved in 100 mL of anhydrous
ethanol, 13.0 g (0.1 mol) of ethyl acetoacetate was
added, 0.1 mol of the corresponding 1-(2-chloroethyl-
sulfanyl)alkane was then added, the mixture was
stirred for 24 h, and 0.09 mol of amidine or thiourea
and a solution of 4.6 g (0.2 mol) of sodium in 100 mL
of anhydrous ethanol were added. The resulting sus-
pension was heated for 8 h under reflux with stirring
and evaporated to dryness, 100 mL of water was added
to the residue, and the mixture was neutralized with
acetic acid and left overnight in a refrigerator. The
precipitate was filtered off, dried, and recrystallized
from 80% ethanol.
5-[2-(2-Chlorobenzylsulfanyl)ethyl]-2,6-dimeth-
ylpyrimidin-4(3H)-one (IId) was synthesized from
ethyl acetoacetate, 1-chloro-2-(2-chloroethylsulfanyl-
methyl)benzene [7], and acetamidine hydrochloride.
Yield 38%, mp 164–165°C, Rf 0.61 (octane–ethyl
acetate, 1:1). IR spectrum, ν, cm–1: 1645 s (C=O),
1
1610. H NMR spectrum (DMSO-d6–CCl4, 1:3), δ,
ppm: 2.17 s and 2.21 s (3H each, 2-CH3, 6-CH3),
2.55 m (2H, SCH2CH2), 2.66 m (2H, SCH2CH2),
3.84 s (2H, SCH2); 7.15–7.24 m (2H), 7.34 m (1H),
and 7.47 m (1H) (C6H4); 12.17 br.s (1H, NH). Found,
%: N 8.62; S 10.63. C15H17ClN2OS. Calculated, %:
N 9.07; S 10.38.
5-(2-Butylsulfanylethyl)-2,6-dimethylpyrimidin-
4(3H)-one (IIa) was synthesized from ethyl aceto-
acetate, 1-(2-chloroethylsulfanyl)butane [4], and acet-
amidine hydrochloride. Yield 37%, mp 62–63°C,
Rf 0.43 (octane–ethyl acetate, 1:1). IR spectrum, ν,
6-Methyl-5-[2-(pentylsulfanyl)ethyl]-2-phenyl-
pyrimidine-4(3H)-one (IIe) was synthesized from
ethyl acetoacetate, 1-(2-chloroethylsulfanyl)pentane,
and benzamidine hydrochloride. Yield 48%, mp 128–
129°C, Rf 0.71 (octane–ethyl acetate, 1:1). IR spec-
trum, ν, cm–1: 1660 s (C=O), 1600. 1H NMR spectrum
(DMSO-d6–CCl4, 1:3), δ, ppm: 0.92 m (3H, CH3),
1.30–1.43 m (4H, CH2CH2CH3), 1.60 m (2H,
SCH2CH2CH2), 2.36 s (3H, 6-CH3), 2.55 m (2H,
SCH2CH2CH2), 2.63 m and 2.71 m (2H each,
5-CH2CH2S), 7.39–7.48 m (3H) and 8.15 m (2H)
(C6H5), 12.45 br.s (1H, NH). Found, %: N 9.05;
S 10.47. C18H24N2OS. Calculated, %: N 8.85; S 10.13.
1
cm–1: 1652 s (C=O), 1605. H NMR spectrum
(DMSO-d6–CCl4, 1:3), δ, ppm: 0.93 t (3H, CH3CH2,
J = 7.2 Hz), 1.36–1.48 m (2H, CH2CH3), 1.51–1.61 m
(2H, CH2CH2CH3), 2.19 s and 2.21 s (3H each, CH3),
2 . 4 9 – 2 . 5 6 m ( 4 H ) a n d 2 . 5 8 – 2 . 6 5 m ( 2 H )
(CH2CH2SCH2), 12.14 br.s (1H, NH). Found, %:
N 11.35; S 13.48. C12H20N2OS. Calculated, %:
N 11.65; S 13.34.
5-(2-Isobutylsulfanylethyl)-2,6-dimethylpyrimi-
din-4(3H)-one (IIb) was synthesized from ethyl aceto-
acetate, 2-methyl-1-(2-chloroethylsulfanyl)propane
[5], and acetamidine hydrochloride. Yield 30%,
mp 117–118°C, Rf 0.31 (octane–ethyl acetate, 1:1). IR
spectrum, ν, cm–1: 1634 s (C=O), 1605. 1H NMR spec-
trum (DMSO-d6–CCl4, 1:3), δ, ppm: 0.99 d [6H,
CH(CH3)2, J = 6.6 Hz], 1.80 t.sept (1H, CHMe2, J =
6.8, 6.6 Hz), 2.19 s and 2.21 s (3H each, 2-CH3,
6-CH3), 2.41 d (2H, SCH2CH, J = 6.8 Hz), 2.49–
2.55 m and 2.58–2.64 m (2H each, CH2CH2),
12.14 br.s (1H, NH). Found, %: N 11.42; S 13.50.
C12H20N2OS. Calculated, %: N 11.65; S 13.34.
2-Benzyl-4-methyl-5-[2-(pentylsulfanyl)ethyl]-
pyrimidin-4(3H)-one (IIf) was synthesized from ethyl
acetoacetate, 1-(2-chloroethylsulfanyl)pentane, and
phenylacetamidine hydrochloride. Yield 53%, mp 125–
126°C, Rf 0.57 (octane–ethyl acetate, 1:1). IR spec-
trum, ν, cm–1: 1636 s (C=O), 1605. 1H NMR spectrum
(DMSO-d6–CCl4, 1:3), δ, ppm: 0.91 m (3H, CH3),
1.28–1.40 m (4H, CH2CH2CH3), 1.57 m (2H,
SCH2CH2CH2), 2.23 s (3H, 6-CH3), 2.47–2.64 m (6H,
5-CH2CH2SCH2), 3.75 s (2H, CH2Ph), 7.14–7.28 m
(2H) and 7.34 m (3H) (C6H5), 12.33 br.s (1H, NH).
Found, %: N 8.25; S 9.98. C19H26N2OS. Calculated, %:
N 8.48; S 9.70.
2,6-Dimethyl-5-(2-pentylsulfanylethyl)pyrimi-
din-4(3H)-one (IIc) was synthesized from ethyl aceto-
acetate, 1-(2-chloroethylsulfanyl)pentane [6], and acet-
amidine hydrochloride. Yield 40%, mp 77–78°C,
Rf 0.41 (octane–ethyl acetate, 1:1). IR spectrum, ν,
6-Methyl-5-[2-(2-methylprop2-en-1-ylsulfanyl)-
ethyl]-2-phenylpyrimidin-4(3H)-one (IIg) was syn-
thesized from ethyl acetoacetate, 3-(2-chloroethylsul-
fanyl)-2-methylprop-1-ene [8], and benzamidine
hydrochloride. Yield 36%, mp 155–156°C, Rf 0.46
(octane–ethyl acetate, 1:1). IR spectrum: ν 1640 cm–1, s
1
cm–1: 1660 s (C=O), 1608. H NMR spectrum
(DMSO-d6–CCl4, 1:3), δ, ppm: 0.91 m (3H, CH2CH3),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 12 2013

ARUTYUNYAN
1756
1
(C=O). H NMR spectrum (DMSO-d6–CCl4, 1:3), δ,
ppm: 1.82 t (3H, CH3CCH2, J = 1.0 Hz), 2.35 s (3H,
CH3), 2.52–2.57 m and 2.69–2.75 m (2H each,
CH2CH2S), 3.14 s (2H, SCH2CCH), 4.81 br.s and
4.89 br.s (1H each, =CH2), 7.39–7.49 m (3H) and
8.12–8.16 m (2H, C6H5), 12.28 br.s (1H, NH). Found,
%: N 9.55; S 10.38. C17H20N2OS. Calculated, %:
N 9.32; S 10.67.
2 h at 150–160°C on a Wood’s metal bath. The mixture
was cooled, and the product was washed with water,
dried, and recrystallized from 2-ethoxyethanol.
6-[(E)-2-(4-Bromophenyl)ethenyl]-5-[2-(butyl-
sulfanyl)ethyl]-2-methylpyrimidin-4(3H)-one (IVa)
was synthesized from compound IIa and 4-bromo-
benzaldehyde. Yield 53%, mp 191–193°C, Rf 0.20
(octane–ethyl acetate, 1:1). IR spectrum: ν 1649 cm–1,
1
5-[2-(Butylsulfanyl)ethyl]-6-methyl-2-thioxo-2,3-
dihydropyrimidin-4(1H)-one (IIIa) was synthesized
from ethyl acetoacetate, 1-(2-chloroethylsulfanyl)-
butane, and thiourea. Yield 55%, mp 137–138°C,
Rf 0.56 (octane–ethyl acetate, 1:1). IR spectrum, ν,
s (C=O). H NMR spectrum (DMSO-d6–CCl4, 1:3), δ,
ppm: 0.94 t (3H, CH2CH3, J = 7.3 Hz), 1.43 m (2H,
CH2CH3), 1.58 m (2H, CH2CH2CH3), 2.30 s (3H,
2-CH3), 2.54 m (2H, SCH2CH2CH2CH3), 2.59 m (2H,
5-CH2), 2.67 m (2H, 5-CH2CH2S), 6.79 d (1H, =CH,
J = 16.1 Hz), 7.47 m and 7.52 m (2H each, C6H4),
7.77 d (1H, =CH, J = 16.1 Hz), 12.28 br.s (1H, NH).
Found, %: N 6.59; S 7.65. C19H23BrN2OS. Calculated,
%: N 6.88; S 7.87.
cm–1: 1636 s (C=O), 1564. H NMR spectrum
1
(DMSO-d6–CCl4, 1:3), δ, ppm: 0.92 t (3H, CH2CH3,
J = 7.3 Hz), 1.34–1.46 m (2H, CH2CH3), 1.49–1.59 m
(2H, SCH2CH2CH2), 2.15 s (3H, 6-CH3), 2.47–2.52 m
(6H, 5-CH2CH2SCH2), 11.93 br.s (2H, NH). Found, %:
N 10.61; S 24.70. C11H18N2OS2. Calculated, %:
N 10.84; S 24.81.
6-[(E)-2-(4-Bromophenyl)ethenyl]-5-[2-(isobutyl-
sulfanylethyl)-2-methylpyrimidin-4(3H)-one (IVb)
was synthesized from compound IIb and 4-bromo-
benzaldehyde. Yield 60%, mp 149–151°C, Rf 0.26
(octane–ethyl acetate, 1:1). IR spectrum, ν, cm–1: 1644
6-Methyl-5-[2-(pentylsulfanyl)ethyl]-2-thioxo-
2,3-dihydropyrimidin-4(1H)-one (IIIb) was synthe-
sized from ethyl acetoacetate, 1-(2-chloroethylsul-
fanyl)pentane, and thiourea. Yield 45%, mp 135–
136°C, Rf 0.58 (octane–ethyl acetate, 1:1). IR spec-
trum, ν, cm–1: 1636 s (C=O), 1572. 1H NMR spectrum
(DMSO-d6–CCl4, 1:3), δ, ppm: 0.91 m (3H, CH2CH3),
1.29–1.41 m (4H, CH2CH2CH3), 1.51–1.61 m (2H,
SCH2CH2CH2), 2.16 s (3H, 6-CH3), 2.47–2.52 m (6H,
5-CH2CH2SCH2), 11.92 br.s and 11.96 br.s (1H each,
NH). Found, %: N 10.40; S 23.22. C12H20N2OS2. Cal-
culated, %: N 10.28; S 23.54.
1
(C=O), 1572. H NMR spectrum (DMSO-d6–CCl4,
1:3), δ, ppm: 1.00 d [6H, (CH3)2CH, J = 6.6 Hz],
1.81 m (1H, CH), 2.30 s (3H, 2-CH3), 2.43 d (2H,
CHCH2, J = 6.8 Hz), 2.54–2.61 m and 2.64–2.71 m
(2H each, CH2CH2S), 6.79 d (1H, =CH, J = 16.1 Hz),
7.44–7.54 m (4H, C6H4), 7.77 d (1H, =CH, J =
16.1 Hz), 12.30 br.s (1H, NH). Found, %: N 6.70;
S 7.52. C19H23BrN2OS. Calculated, %: N 6.88; S 7.87.
2-Methyl-6-[(E)-2-(4-nitrophenyl)ethenyl]-5-
[2-(pentylsulfanyl)ethyl]pyrimidin-4(3H)-one (IVc)
was synthesized from compound IIc and 4-nitrobenz-
aldehyde. Yield 63%, mp 198–199°C, Rf 0.38 (octane–
ethyl acetate, 1:1). IR spectrum: ν 1649 cm–1 (C=O).
1H NMR spectrum (DMSO-d6–CCl4, 1:3), δ, ppm:
0 . 9 2 m ( 3 H , C H 2 C H 3 ) , 1 . 3 0 – 1 . 4 5 m ( 4 H,
CH2CH2CH3), 1.60 m (2H, SCH2CH2CH2), 2.32 s
(3H, 2-CH3), 2.52–2.74 m (6H, 5-CH2CH2SCH2),
6.98 d (1H, =CH, J = 16.1 Hz), 7.78 m and 8.24 m (2H
each, C6H4), 7.88 d (1H, =CH, J = 16.1 Hz), 12.40 br.s
(1H, NH). Found, %: N 10.61; S 8.45. C20H25N3O3S.
Calculated, %: N 10.84; S 8.27.
5-[2-(4-Ethoxybenzylsulfanyl)ethyl]-6-methyl-
2-thioxo-2,3-dihydropyrimidin-4(1H)-one (IIIc) was
synthesized from ethyl acetoacetate, 1-[2-(chloro-
ethyl)sulfanylmethyl]-4-ethoxybenzene [9], and
thiourea. Yield 40%, mp 177–178°C, Rf 0.59 (octane–
ethyl acetate, 1:1). IR spectrum, ν, cm–1: 1648 s
1
(C=O), 1564. H NMR spectrum (DMSO-d6–CCl4,
1:3), δ, ppm: 1.39 t (3H, CH2CH3, J = 7.0 Hz), 2.10 s
(3H, CH3), 2.40–2.46 m and 2.47–2.54 m (2H each,
CH2CH2S), 3.65 s (2H, SCH2C6H4), 3.99 q (2H,
OCH2, J = 7.0 Hz), 6.75 m and 7.18 m (2H each,
C6H4), 11.90 br.s and 11.95 br.s (1H each, NH). Found,
%: N 8.57; S 19.30. C16H20N2O2S2. Calculated, %:
N 8.33; S 19.06.
5-[2-(2-Chlorobenzylsulfanyl)ethyl]-2-methyl-6-
[(E)-2-(4-nitrophenyl)ethenyl]pyrimidin-4(3H)-one
(IVd) was synthesized from compound IId and
4-nitrobenzaldehyde. Yield 65%, mp 230–231°C,
Rf 0.26 (octane–ethyl acetate, 1:1). IR spectrum, ν,
6-Styrylpyrimidin-4(3H)-ones IVa–IVe (general
procedure). A mixture of 0.01 mol of pyrimidine IIa–
IId, 0.011 mol of the corresponding aromatic alde-
hyde, and 1.36 g (0.01 mol) of ZnCl2 was heated for
1
cm–1: 1644 (C=O), 1597. H NMR spectrum
(DMSO-d6–CCl4, 1:3), δ, ppm: 2.29 s (3H, 2-CH3),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 12 2013

SYNTHESIS OF 2,4,6-TRISUBSTITUTED 5-(2-ALKYLSULFANYLETHYL)PYRIMIDINES
1757
2.61 m and 2.73 m (2H each, CH2CH2), 3.86 s (2H,
SCH2Ar), 6.98 d (1H, =CH, J = 16.1 Hz); 7.16–7.25 m
(2H), 7.35 m (1H), and 7.48 m (1H) (C6H4Cl); 7.79 m
and 8.24 m (2H each, C6H4), 7.89 d (1H, =CH, J =
16.1 Hz), 12.05 br.s (1H, NH). Mass spectrum, m/z
(Irel, %): 443/441 (9.7/28.5) [M]+, 317 (40.3) [M –
C H 2 C 6 H 4 C l ] + . F o u n d , % : N 9 . 8 0 ; S 7 . 5 2.
C22H20ClN3O3S. Calculated, %: N 9.51; S 7.25.
M 441.09.
CCl4, 1:3), δ, ppm: 0.99 t (3H, CH2CH3, J = 7.3 Hz),
1.50 m (2H, CH2CH3), 1.70 m (2H, CH2CH2CH3),
2.35 s (3H, 2-CH3), 2.62–2.76 m (2H) and 2.78–
2.94 m (4H) [5-CH2CH2S(O)CH2], 6.81 d (1H, =CH,
J = 16.1 Hz), 7.47 m and 7.53 m (2H each, C6H4),
7.78 d (1H, =CH, J = 16.1 Hz), 12.37 br.s (1H, NH).
Found, %: N 6.85; S 7.30. C19H23BrN2OS. Calculated,
%: N 6.62; S 7.57.
5-[2-(Butylsulfanyl)ethyl]-6-methyl-2-(propylsul-
fanyl)pyrimidin-4(3H)-one (VII). Propyl bromide,
1.23 g (0.01 mol), was added to a solution of 2.58 g
(0.01 mol) of 2-thioxopyrimidine IIIa and 0.4 g
(0.01 mol) of sodium hydroxide in 80 mL of 80%
ethanol, the mixture was heated for 6 h under reflux
and evaporated to dryness, the residue was treated with
50 mL of water, and the precipitate was filtered off.
Yield 78%, mp 54–55°C (from 70% EtOH), Rf 0.88
(octane–ethyl acetate, 1:1). IR spectrum: ν 1648 cm–1
5-[2-(2-Chlorobenzylsulfanyl)ethyl]-6-[(E)-2-(4-
dimethylaminophenyl)ethenyl]-2-methylpyrimidin-
4(3H)-one (IVe) was synthesized from compound IId
and 4-dimethylaminobenzaldehyde. Yield 55%,
mp 201–202°C, Rf 0.50 (octane–ethyl acetate, 1:1).
1
IR spectrum, ν, cm–1: 1624 (C=O), 1604. H NMR
spectrum (DMSO-d6–CCl4, 1:3), δ, ppm: 2.25 s (3H,
2-CH3), 2.54–2.61 m and 2.68–2.74 m (2H, CH2CH2),
3.02 s [6H, N(CH3)2], 3.86 s (2H, SCH2Ar), 6.50 d
(1H, =CH, J = 15.8 Hz), 6.67 m and 7.38 m (2H,
C6H4NMe2); 7.16–7.24 m (2H), 7.32–7.36 m (1H), and
7.48–7.51 m (1H) (C6H4Cl); 7.71 d (1H, =CH, J =
15.8 Hz), 12.41 br.s (1H, NH). Mass spectrum, m/z
(Irel, %): 441/439 (6.2/16.6) [M]+, 314 (88.8) [M –
CH2C6H4Cl]+, 268 (100) [M – CH2SCH2C6H4Cl]+.
Found, %: N 9.28; S 7.42. C24H26ClN3OS. Calculated,
%: N 9.55; S 7.29. M 439.15.
1
(C=O), 1545. H NMR spectrum (DMSO-d6–CCl4,
1:3), δ, ppm: 0.93 t (3H, CH3, J = 7.2 Hz), 1.03 t (3H,
SCH2CH2CH3, J = 7.3 Hz), 1.41 m (2H, CH2), 1.55 m
(2H, CH2), 1.71 m (2H, CH2), 2.23 s (3H, 6-CH3),
2.48–2.63 m (6H, 5-CH2CH2SCH2), 3.06 t (2H,
2-SCH2, J = 7.1 Hz), 12.28 br.s (1H, NH). Found, %:
N 9.05; S 21.58. C14H24N2OS2. Calculated, %: N 9.32;
S 21.34.
Sulfoxides V and VI (general procedure). A mix-
ture of 0.01 mol of compound IId or IVa, 2.14 g
(0.01 mol) of NaIO4, 25 mL of dioxane, and 25 mL of
water was stirred for 8 h at room temperature. The
mixture was then left overnight in a refrigerator, and
the precipitate was filtered off, washed with water, and
dried.
4-{5-[2-(Butylsulfanyl)ethyl]-4-methyl-6-oxo-1,6-
dihydropyrimidin-2-ylamino}benzoic acid (VIII).
A mixture of 1.50 g (5 mmol) of pyrimidine VII and
0.69 g (5 mmol) of 4-aminobenzoic acid was fused for
4 h at 150–160°C on a Wood’s metal bath. The melt
was cooled and treated with 20 mL of ethanol, and the
precipitate was filtered off. Yield 82%, mp 268–269°C
(from 70% EtOH), Rf 0.28 (ethanol–dichloroethane,
1:10). IR spectrum, ν, cm–1: 3441 and 3410 (OH, NH),
5-[2-(2-Chlorobenzenesulfinyl)ethyl]-2,6-dimeth-
ylpyrimidin-4(3H)-one (V) was synthesized from
compound IId. Yield 82%, mp 200–202°C (from
EtOH), Rf 0.29 (octane–ethyl acetate, 1:1). IR spec-
1
1641 (C=O), 1582. H NMR spectrum (DMSO-d6–
CCl4, 1:3), δ, ppm: 0.94 t (3H, CH2CH3, J = 7.3 Hz),
1.37–1.49 m (2H, CH2CH3), 1.52–1.63 m (2H,
CH2CH2CH3), 2.26 s (3H, 4-CH3), 2.49–2.64 m (6H,
CH2CH2SCH2), 7.70 m and 7.86 m (2H each, C6H4),
8.64 br.s (1H) and 11.18 br.s (2H) (NH, COOH).
Found, %: N 11.42; S 8.59. C18H23N3O3S. Calculated,
%: N 11.63; S 8.87.
1
trum, ν, cm–1: 1657 (C=O), 1606. H NMR spectrum
(DMSO-d6–CCl4, 1:3), δ, ppm: 2.20 s and 2.22 s (3H
each, 2-CH3, 6-CH3), 2.69–2.88 m (3H) and 2.95–
3.04 m (1H) [CH2CH2S(O)], 4.12 d and 4.33 d [1H
2
each, S(O)CH2Ar, J = 12.8 Hz], 7.31–7.59 m (4H,
C6H4), 12.30 br.s (1H, NH). Found, %: N 8.39; S 9.55.
C15H17ClN2O2S. Calculated, %: N 8.62; S 9.87.
The author is grateful to G.M. Stepanyan for per-
forming biological tests.
4-[(E)-2-(4-Bromophenyl)ethenyl]-5-[2-(butane-
sulfinyl)ethyl]-2-methylpyrimidin-4(3H)-one (VI)
was synthesized from compound IIIa. Yield 74%,
mp 228–230°C (from 2-ethoxyethanol), Rf 0.46
(ethanol–dichloroethane, 1:10). IR spectrum, ν, cm–1:
REFERENCES
1. Lagoja, I.M., Chem. Biodiversity, 2005, vol. 2, p. 1;
1
1649 (C=O), 1540. H NMR spectrum (DMSO-d6–
Mahmoud, M.R., El-Ziaty, A.K., Ismail, M.F., and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 12 2013

ARUTYUNYAN
1758
Shiba, S.A., Eur. J. Chem., 2011, vol. 2, p. 347; Mad-
6. Guseinov, Kh.K., Gasanzade, G.R., and Mustafaev, N.P.,
dila, S. and Jonnalagadda, S.B., Arch. Pharm., 2012,
Zh. Org. Khim., 1973, vol. 9, p. 697.
vol. 345, p. 163.
2. Flynn, G.A. and Ash, R.J., Biochem. Biophys. Res.
Commun., 1983, vol. 114, p. 1.
7. Relyea, D.I., SAR Patent no. 68-00398, 1968; Chem.
Abstr., 1969, vol. 70, p. 48454u.
8. King, J.F. and Harding, D.R.K., J. Am. Chem. Soc., 1976,
3. Arutyunyan, A.A., Khim. Zh. Arm., 2012, vol. 65, p. 257.
vol. 98, p. 3312.
4. Whithner, T.C., Jr. and Reid, E.E., J. Am. Chem. Soc.,
9. Gyul’akhmedov, L.M., Akhmedov, Sh.T., and Vekilo-
va, T.M., Nauch. Trudy Azerb. Gos. Univ., Ser. Khim.
Nauk, 1979, no. 4, p. 32; Ref. Zh., Khim., 1980,
no. 17Zh184.
1921, vol. 43, p. 636.
5. Buckley, G.D., Charlish, J.L., and Rose, J.D., J. Chem.
Soc., 1947, p. 1514.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 12 2013