Reaction of 6-Methyl-2-Thiouracil and 6-Phenyl-2-Thiouracil with Chloro-β-Dicarbonyl and Bromo-β-Dicarbonyl Compounds and Their Nitrile Analogs

Article abstract of DOI:10.1002/jhet.2525

Derivatives of 2-methylidene-1,3-dihydropyrimidin-4-ones 2a, 2b, 2c, 2d, 2e, 2f, 2g were synthesized by interaction of 6-methyl-2-thiouracil and 6-phenyl-2-thiouracil 1a, 1b with some activated halogenides: diethyl bromomalonate, ethyl 2-chloro-3-oxobutanoate, ethyl 2-bromocyanoacetate, 2-bromo-5,5-dimethylcyclohexan-1,3-dione, and bromomalononitrile. The boiling of 1a with ethyl 2-bromocyanoacetate in mixture of ethanol and EtONa results in intramolecular cyclization and formation of thiazolo[3,2-a]pyrimidin-5-one 3. Interaction of 1a with 3-chloropentane-2,4-dione and 2-bromo-1,3-diphenylpropane-1,3-dione yielded corresponding S-substituted thiopyrimidines 4a,4b. In general, the products of 1b S-alkylation are less prone to sulfur extrusion. Reaction of 1b with diethyl bromomalonate in the absence of EtONa stops at the S-alkylation step, while in the presence of EtONa in ethanol or PPh₃in dioxane 2-(ethoxycarbonylmethyl)thio-6-phenyl-1,3-dihydropyrimidin-4(1H)-one 6 is formed exclusively. Molecular structure and crystal structure of 2-(1,1-diethoxycarbonylmethyliden)-6-methyl-1,3-dihydropyrimidin-4(1H)-one 2a are discussed.

Full text of DOI:10.1002/jhet.2525

Month 2015
Reaction of 6-Methyl-2-Thiouracil and 6-Phenyl-2-Thiouracil with
Chloro-β-Dicarbonyl and Bromo-β-Dicarbonyl Compounds and Their
Nitrile Analogs
a
a
b
b
a
c
a
*
A. A. Yavolovskii, Yu. E. Ivanov, M. S. Fonari, L. Croitor, L. V. Grishchuk, R. Yu. Ivanova, and G. L. Kamalov
aNational Academy of Sciences of Ukraine, A. V. Bogatsky Physico-Chemical Institute, Lyustdorfskaya doroga 86,
Odessa, 65080, Ukraine
bInstitute of Applied Physics, Academy of Sciences of Moldova, Academy str. 5, Chisinau, MD2028, Moldova
cOdessa National Maritime University, Mechnykova Str. 34, Odessa, 65029, Ukraine
*
E-mail: fonari.xray@phys.asm.md
Received May 14, 2015
DOI 10.1002/jhet.2525
Published online in 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
Derivatives of 2-methylidene-1,3-dihydropyrimidin-4-ones 2a-g were synthesized by interaction of 6-
methyl-2-thiouracil and 6-phenyl-2-thiouracil 1a,b with some activated halogenides: diethyl bromomalonate,
ethyl 2-chloro-3-oxobutanoate, ethyl 2-bromocyanoacetate, 2-bromo-5,5-dimethylcyclohexan-1,3-dione,
and bromomalononitrile. The boiling of 1a with ethyl 2-bromocyanoacetate in mixture of ethanol and EtONa
results in intramolecular cyclization and formation of thiazolo[3,2-a]pyrimidin-5-one 3. Interaction of 1a with
3-chloropentane-2,4-dione and 2-bromo-1,3-diphenylpropane-1,3-dione yielded corresponding S-substituted
thiopyrimidines 4a,b. In general, the products of 1b S-alkylation are less prone to sulfur extrusion. Reaction
of 1b with diethyl bromomalonate in the absence of EtONa stops at the S-alkylation step, while in the
presence of EtONa in ethanol or PPh3 in dioxane 2-(ethoxycarbonylmethyl)thio-6-phenyl-1,3-
dihydropyrimidin-4(1H)-one 6 is formed exclusively. Molecular structure and crystal structure of
2-(1,1-diethoxycarbonylmethyliden)-6-methyl-1,3-dihydropyrimidin-4(1H)-one 2a are discussed.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
The present work aimed to search conditions for the C–C
bond formation in position “2” of the pyrimidine ring by
Eschenmoser reaction of “sulfide contraction” that in
generally results in sulfur elimination from α-azomethine-β-
oxoalkylsulfides [4]. This method has found application in
synthesis of some natural substances and heterocyclic com-
pounds, including preparation of 2-(2-oxo-2-arylethyliden)-
1,3-dihydropyrimidin-4(1H)-ones from 2-phenacylthiouracils
[5–7]. The required condition for the reaction of “sulfide con-
traction” is the ability of starting compounds to form the
episulfide intermediate, whose desulfurization is facilitated
by the high temperature in the presence of base or trivalent
phosphorous compounds [4–7].
Because of the intensive growth of the number of different
methods and successful search for available reagents to
synthesize new functionalized pyrimidines, a huge amount
of drugs based on pyrimidine derivatives with anti-
inflammatory, antibacterial, antiviral, and antitumor activi-
ties have been developed in recent years [1,2]. In this regard,
of particular interest are the pyrimidine derivatives bearing
alkyl substituents with several electron withdrawing groups
(e.g., carbonyl and nitrile) in position “2” of the cycle. Thus,
the well-known method for preparing such compounds is cy-
clization of diaminomethylidene derivatives of diben-
zoylmethane or acetoacetic ester by aroylketenes [3].
© 2015 HeteroCorporation

A. A. Yavolovskii, Yu. E. Ivanov, M. S. Fonari, L. Croitor,
L. V. Grishchuk, R. Yu. Ivanova, and G. L. Kamalov
Vol 000
Scheme 3. Reaction of 1a with halo-β-diketones.
RESULTS AND DISCUSSION
The interaction of 6-methyl-2-thiouracil 1a with diethyl
bromomalonate resulted in the corresponding 2-
methylidene-1,3-dihydropyrimidin-4-one 2a in one step
(Scheme 1). The reaction was carried out by refluxing of
equimolecular amounts of reactants in ethanol in the pres-
ence of sodium ethylate. Under similar conditions, pyrim-
idine derivatives 2b,c were obtained from reaction of 1a
with 3-oxo-2-chlorobutyrate and/or 2-bromodimedone, re-
spectively. Depending on the absence or presence of a
base, reaction of 2-thiouracils 1a,b with the nitrile contain-
ing bromides can occur in two pathways. First, 2-
methylidene-pyrimidines 2d-g containing nitrile groups
were obtained by continuous boiling of thiouracils 1a,b
with ethyl 2-bromocyanoacetate or bromomalononitrile in
ethanol (Scheme 1) in the absence of sodium ethoxide.
The other pathway, boiling of the thiouracil 1a with
ethyl 2-bromocyanoacetate in the mixture of ethanol and
sodium ethoxide, facilitates intramolecular cyclization that
affords thiazolo[3,2-a]pyrimidin-5-one 3 (Scheme 2).
At the same time, reaction of thiouracil 1a with 3-
chloropentane-2,4-dione and 2-bromo-1,3-diphenylpro-
pane-1,3-dione yielded pyrimidine 4a,b (Scheme 3).
The similar splitting of one of the C–C bonds has
been found previously in alkylation of 2-mercapto-3-
ureidopyridines and 5-amino-6-mercaptopyrimidines by
symmetric and asymmetric halo-β-diketones [8,9].
Scheme 4. Synthesis and splitting of 5.
analyses. The mass spectra for compounds 2a-g reveal in-
tense peaks of molecular ions whose fragmentation corre-
sponds to the expected structures. The resulting
pyrimidines 2a-g formed due to sulfur extrusion can exist
in two prototropic isomeric forms, enamine ea, and
iminoalkyl ia ones (Scheme 5).
The availability of two proton signals associated with the
amide and amine groups in the absence of the methine pro-
ton signal of exocyclic methine group in the 1H NMR spec-
tra of pyrimidines 2a-g allow assigning them the ea
structure. The single crystal X-ray structure of 2-(1,1-
diethoxycarbonylmethyliden)-6-methyl-1,3-dihydropyrimidin-
4(1H)-one 2a indicates in favor of the ea form that is
stabilized by two intramolecular NH…O¼C hydrogen
bonds, N(1)-H(1N)…O(2) 1.73(3), 2.546(3)Å, ∠ NHO=
140(3)°, and N(2)-H(2N)…O(4) 1.78(3), 2.553(3)Å;
∠NHO= 138(2)° (Fig. 1). Compound 2a crystallizes in the
monoclinic crystal system with P21/c space group. The
single molecule occupies general position in the asymmetric
unit. The principle bond distances and angles are summa-
rized in Table 1. Molecule 2a is almost flat that is indicated
by the deviation of non-hydrogen atoms from the mean plane
of the molecule skeleton not exceeding 0.071Å. The two
aforementioned intramolecular NH…O hydrogen bonds
additionally stabilize the planar skeleton.
In general, the products of thiouracil 1b S-alkylation
are less prone to sulfur extrusion. Reaction of thiouracil
1b with diethyl bromomalonate (Scheme 4) in the ab-
sence of sodium ethoxide stops at the alkylation step
(compound 5), while in the presence of base (sodium
ethoxide in ethanol or triphenylphosphine in dioxane)
2-(1-ethoxycarbonylmethyl)thio-6-phenyl-1,3-dihydropy
rimidin-4(1H)-one 6 is formed exclusively (Scheme 4).
Structures of novel compounds have been confirmed by
1
their spectra (MS, H NMR) together with the elemental
Scheme 1. Synthesis of 2-methylidene-1,3-dihydropyrimidin-4-one de-
rivatives 2.
In the crystal, the molecules are linked by the system of
weak hydrogen bonds. At the same time, the dimers typical
for uracil and thiouracil derivatives [10–12], which are
usually formed because of two centrosymmetric NH…O
Scheme 2. Reaction of 1a with ethyl 2-bromocyanoacetate in the pres-
Scheme 5. Prototropic isomeric forms of pyrimidines 2a-g.
ence of sodium ethoxide.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Reaction of 6-Methyl-2-Thiouracil and 6-Phenyl-2-Thiouracil with Chloro-β-
Dicarbonyl and Bromo-β-Dicarbonyl Compounds
Month 2015
antiparallel stacks along the crystallographic a direction
with big overlapping areas and interplanar separation of
3.458 Å.
CONCLUSION
Thus, we developed an efficient method for synthesis of 2-
methylidene-1,3-dihydropyrimidin-4-one derivatives from
corresponding 2-thiouracils. Depending on the absence or
presence of a base, reaction of studied 2-thiouracils with ethyl
2-bromocyanoacetate or bromomalononitrile can occur in
two synthetic pathways. In general, the products of 6-
phenylthiouracil S-alkylation are less prone to sulfur extrusion.
Figure 1. Molecular structure of 2-(1,1-diethoxycarbonylmethyliden)-6-
methyl-1,3-dihydropyrimidin-4(1H)-one (2a). Thermal ellipsoids are
shown with 50% probability level. Dashed lines show hydrogen bonds.
[Color figure can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]
EXPERIMENTAL
Table 1
The TLC analysis was carried out on the Silufol UV-
254-VIS plates using chloroform-acetonitrile 5:1 and 1:1
systems. Mass spectra were obtained on a mass-
spectrometer MX-1321 using the direct sample introduc-
tion system with ionizing radiation energy electrons of
70eV and ion source temperature 220°C. 1H NMR spectra
were recorded on a Varian WXP-300 spectrometer with
working frequency 299.95 MHz in DMSO-d6; chemical
shifts were measured relative to TMS as internal standard.
2-(1,1-Diethoxycarbonylmethylidene)-6-methyl-1,3-
dihydropyrimidin-4(1H)-one (2a). To a solution of so-
dium ethoxide obtained by dissolving sodium (0.23 g,
0.01 mol) in anhydrous ethanol (250 mL), 6-methyl-2-
thiouracil (1a) [13] (1.42 g, 0.01 mol) was added with
stirring. The mixture was stirred at 18–20°C for 30 min,
and a solution of diethyl bromomalonate [14] (2.39 g,
0.01 mol) in anhydrous ethanol (50 mL) was added
slowly. The resulting mixture was kept at room tempera-
ture for 30 min and refluxed for 4–6 h. The reaction
mixture evaporated in a rotary evaporator under water
pump vacuum. The residue washed with cold water and
crystallized from ethanol as white crystals, 1.53 g (57%),
mp 139–140°C; 1Н NMR δ12.62 (s, 1H, NH), 12.55
(s, 1H, NH), 5.79 (s, 1H, CH pyrimid.), 4.16 (q, J=6.0Hz,
4H, CH2 ester), 2.26 (s, 3H, CH3 pyrimid.), 1.25
(t, J=6.0Hz, 6H, CH3 ester); MS m/z (%) 268 (M+, 72),
222 (100), 196 (45), 177 (24), 124 (46), 109 (11). Anal.
Calcd. for C12H16N2O5: C, 53.73; H, 6.01; N, 10.44%.
Found: C, 53.71; H, 6.03; N, 10.43%.
Bond lengths (Å) and angles (deg) in compound 2а.
O(1)-C(5)
O(2)-C(7)
O(3)-C(7)
O(3)-C(8)
O(4)-C(10)
O(5)-C(10)
O(5)-C(11)
N(1)-C(1)
1.216(4)
1.227(4)
1.328(4)
1.450(4)
1.229(5)
1.328(4)
1.444(4)
1.344(4)
1.397(4)
1.352(4)
116.5(2)
117.3(2)
126.7(3)
123.9(3)
114.8(3)
123.2(3)
122.0(3)
119.6(3)
115.3(3)
125.1(3)
120.9(3)
N(2)-C(2)
C(1)-C(6)
C(2)-C(3)
C(2)-C(4)
C(3)-C(5)
C(6)-C(7)
C(6)-C(10)
C(8)-C(9)
C(11)-C(12)
1.377(4)
1.409(4)
1.333(4)
1.491(6)
1.428(6)
1.461(5)
1.451(4)
1.496(4)
1.492(5)
N(1)-C(5)
N(2)-C(1)
C(7)-O(3)-C(8)
C(10)-O(5)-C(11)
C(1)-N(1)-C(5)
C(1)-N(2)-C(2)
N(1)-C(1)-N(2)
N(1)-C(1)-C(6)
N(2)-C(1)-C(6)
N(2)-C(2)-C(3)
N(2)-C(2)-C(4)
C(3)-C(2)-C(4)
C(2)-C(3)-C(5)
O(1)-C(5)-N(1)
O(1)-C(5)-C(3)
N(1)-C(5)-C(3)
C(1)-C(6)-C(7)
C(1)-C(6)-C(10)
C(7)-C(6)-C(10)
O(2)-C(7)-O(3)
O(2)-C(7)-C(6)
O(3)-C(7)-C(6)
O(3)-C(8)-C(9)
119.1(3)
126.9(3)
114.0(3)
116.8(3)
118.1(3)
125.0(3)
120.1(3)
124.4(3)
115.5(3)
105.8(2)
2-(1-Acetyl-1-ethoxycarbonylmethylidene)-6-methyl-
1,3-dihydropyrimidin-4(1H)-one (2b) was synthesized
similar to 2a from 1a (1.42 g, 0.01 mol) and ethyl 2-
chloro-3-oxobutanoate [15] (1.64 g, 0.01 mol). White crys-
Figure 2. Crystal packing in 2a with stacks along the crystallographic a
direction. [Color figure can be viewed in the online issue, which is avail-
able at wileyonlinelibrary.com.]
1
tals (ethanol), 1.5 g (63%), mp 121–122°С; Н NMR δ
13.84 (br. s, 1H, NH), 13.39 (br. s, 1H, NH), 5.92 (s,
1H, CH pyrimid.), 4.24 (q, J = 7.5 Hz, 2H, CH2 ester),
2.42 (s, 3H, CH3CO), 2.27 (s, 3H, CH3 pyrimid.), 1.30
(t, J = 7.5 Hz, 3H, CH3 ester); MS m/z (%) 238 (M+, 100),
228(14), 223 (43), 195(6), 193(17), 192(23), 182(10),
hydrogen bonds are absent in 2a (Fig. 2), which is obvi-
ously explained by the preference of intramolecular inter-
actions. Instead, the molecules are packed in the
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. A. Yavolovskii, Yu. E. Ivanov, M. S. Fonari, L. Croitor,
L. V. Grishchuk, R. Yu. Ivanova, and G. L. Kamalov
Vol 000
177(57), 166(25). Anal. Calcd. for С13Н16N2O3: C, 55.46;
H, 5.92; N, 11.76%. Found: C, 55.44; H, 5.90; N, 11.74%.
2-(4,4-Dimethyl-2,6-dioxocyclohexylidene)-6-methyl-
1,3-dihydropyrimidin-4(1H)-one (2с) was synthesized
similar to 2a from 1a (1.42g, 0.01mmol) and 2-bromo-5,5-
dimethylcyclohexan-1,3-dione [16] (2.19g, 0.01mmol).
1H, CH pyrimid.), 2.20 (s, 3H, CH3 pyrimid.); MS m/z
(%) 174 (M+, 100), 148(7), 146(13), 145(23), 120(5), 119
(10), 92(7), 83(6), 68(24), 67(30). Anal. Calcd. for
C8H6N4O: C, 55.17; H, 3.47; N, 32.17%. Found: C,
55.23; H, 3.46; N, 32.14%.
2-(1,1-Dicyalomethylidene)-6-phenyl-1,3-dihydropyrimidin-
4(1H)-one (2g) was synthesized similar to 2e from 1b
(2.04g, 0.01 mol) and bromomalononitrile (1.45 g,
0.01 mol). White needles (C6H6), 1.1 g (46%), mp
1
White solid (ethanol), 1.42g (57%), mp 186°С; Н NMR
δ14.16 (br. s, 1H, NH), 13.84 (br. s, 1H, NH), 6.03 (s, 1H,
CH pyrimid.), 6.41 (s, 4H, CH2), 2.30 (s, 3H, CH3 pyrimid.),
1.00 (s, 6H, CH3); MS m/z (%) 248 (M+, 100), 233(5), 220
(10), 205(6), 192(9), 179(8), 164(27), 151(74). Anal. Calcd.
for С13Н16N2O3: С, 62.89; Н, 6.50; N, 11.28%. Found: С,
62.81; Н, 6.57; N, 11.21%.
1
>300°С subl.; Н NMR δ 11.35 (br. s, 2H, NH), 7.69–
7.55 (m, 5H phenyl), 6.12 (s, 1H, CH pyrimid.), 2.50 (s,
3H, CH3 pyrimid.); MS m/z (%) 236 (M+, 100), 210(20),
129(34), 117(12), 104(65), 89(7). Anal. Calcd. for
C13H8N4O: C, 66.10; H, 3.41; N, 23.72%. Found: C,
66.18; H, 3.40; N, 23.74%.
3-Amino-7-methyl-2-ethoxycarbonyl-thiazolo[3,2-
a]pyrimidin-5-one (3). To a solution of sodium ethoxide
obtained by dissolving sodium (0.23g, 0.01mol) in anhy-
drous ethanol (250mL), 6-methyl-2-thiouracil (1a) (1.42g,
0.01mol) was added with stirring. The mixture was stirred
2-(1-Cyano-1-ethoxycarbonylmethylidene)-6-methyl-1,3-
dihydropyrimidin-4(1H)-one (2d). To a solution of 6-methyl-
2-thiouracil (1a) (1.42 g, 0.01 mol) in anhydrous ethanol
(250 mL), a solution of ethyl 2-bromocyanoacetate [14]
(1.92 g, 0.01 mol) in anhydrous ethanol (50 mL) was
added slowly under stirring at 18–20°C. The resulting
mixture kept at room temperature for 30 min and refluxed
for 8 h. The reaction mixture evaporated in a rotary evap-
orator underwater pump vacuum. The residue washed
with cold water and crystallized from ethanol as white
at 18–20°C for 30min, and
a solution of ethyl
bromocyanoacetate (1.92 g, 0.01 mol) in anhydrous etha-
nol (50 mL) was added slowly. The resulting mixture
was kept at room temperature for 30 min and refluxed
for 3 h. The reaction mixture was evaporated in a rotary
evaporator under water pump vacuum. The residue was
washed with cold water and crystallized from isopropyl
alcohol as yellow needles, 1.52 g (60%), mp 134–
1
needles, 0.99 g (45%), mp 247–248°С; Н NMR δ11.97
(br. s, 1H, NH), 11.96 (br. s, 1H, NH), 5.77 (s, 1H, CH
pyrimid.), 4.18 (q, J = 7.5 Hz, 2H, CH2 ester), 2.22 s (3H,
CH3 pyrimid.), 1.24 (t, J = 7.5 Hz, 3H, CH3 ester); MS
m/z (%) 221(M+, 100), 193(21), 175(80), 149(44). Anal.
Calcd. for С13Н16N2O3: C, 54.30; H, 5.01; N, 18.99%.
Found: C, 54.28; H, 4.99; N, 18.97%.
1
135°С; Н NMR δ 8.13 (br. s, 2H, NH2), 6.11 (s, 1H,
CH pyrimidin.), 4.25 (q, J = 7.5 Hz, 2H, CH2 ester), 2.23
(s, 3H, CH3 pyrimid.), 1.27 (t, J = 7.5 Hz, 3H, CH3 ester);
ms m/z (%) 253 (M+, 100), 225(15), 207(14), 181(12),
154(15), 142(5), 121(7), 109(45). Anal. Calcd. for
C10H11N3O3S: C, 47.42; H, 4.38; N, 16.59%. Found: C,
47.38; H, 4.36; N, 16.57%.
2-(1-Cyano-1-ethoxycarbonylmethylidene)-6-phenyl-
1,3-dihydropyrimidin-4(1H)-one (2e). To a solution of
6-phenyl-2-thiouracil (1b) [17] (2.04 g, 0.01 mol) in
anhydrous ethanol (250 mL) a solution of ethyl 2-
bromocyanoacetate (1.92 g, 0.01 mol) in anhydrous
ethanol (50 mL) was gradually added under stirring at
18–20°C. The resulting mixture kept at room temperature
for 30min and refluxed for 16 h. The reaction mixture
evaporated in a rotary evaporator under water pump vac-
uum. The residue was washed with cold water and crystal-
lized from acetonitrile as white needles, 1.36 g (48%), mp.
239–240°C; 1Н NMR δ 12.97 (br. s, 1H, NH), 11.98 (br. s,
1H, NH), 7.78–7.50 (m, 5H phenyl), 6.41 (s, 1H, CH
pyrimid.), 4.22 (q, J=7.5Hz, 2H, CH2 ester), 1.26
(t, J=7.5Hz, 3H, CH3 ester); MS m/z (%) 283 (M+, 100),
255(28), 237(85), 211(85), 186(30), 181(15), 172(13),
155(6), 148(10), 141(14),129(24), 117(15), 104(52), 93(10),
89(11), 77(34). Anal. Calcd. for C15H13N3O3: C, 63.60; H,
4.63; N, 14.83%. Found: C, 63.65; H, 4.62; N, 14.84%.
2-(1,1-Dicyanomethylidene)-6-methyl-1,3-dihydro
pyrimidin-4(1H)-one (2f) was synthesized similar to 2d
from 1a (1.42 g, 0.01 mol) and bromomalononitrile [18]
(1.45 g, 0.01 mol). White solid (C6H6), 0.89 g (51%), mp
6-Methyl-2-[(2-oxopropyl)thio]pyrimidin-4(3H)-one
(4a). To a solution of sodium ethoxide obtained by dis-
solving sodium (0.23 g, 0.01 mol) in anhydrous ethanol
(250 mL), 6-methyl-2-thiouracil (1a) (1.42 g, 0.01 mol)
was added with stirring. The mixture was stirred at 18–
20°C for 30 min, and a solution of 3-chloropentane-2,4-
dione [19] (1.34 g, 0.01 mol) in anhydrous ethanol
(50 mL) was added slowly. The resulting mixture was
kept at room temperature for 30 min and refluxed for
3 h. The reaction mixture was evaporated in a rotary evap-
orator underwater pump vacuum. The residue was washed
with cold water and recrystallized from isopropyl alcohol
as white solid, 1.15 g (58%), mp 97–98°C (lit. 97°C [20]);
1Н NMR δ 12.52 (br. s, 1H, NH), 5.92 (s, 1H, CH
pyrimid.), 4.05 (s, 2H, CH2S), 2.10 (s, 3H, CH3CO),
1.91 (s, 3H, CH3 pyrimid.); MS m/z (%) 198 (M+, 17),
156(30), 155(29), 127(5), 107(18), 109(26). Anal. Calcd.
for C8H10N2O2S: C, 48.47; H, 5.08; N, 14.13%. Found:
C, 48.45; H, 5.06; N, 14.11%.
1
280°С subl.; Н NMR δ 11.80 (br. s, 2H, NH), 5.74 (s,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Reaction of 6-Methyl-2-Thiouracil and 6-Phenyl-2-Thiouracil with Chloro-β-
Dicarbonyl and Bromo-β-Dicarbonyl Compounds
Month 2015
6-Methyl-2-[(2-oxo-2-phenylethyl)thio]pyrimidin-
4(3H)-one (4b) was synthesized similar to 4a from 6-
methyl-2-thiouracil (1a) (1.42 g, 0.01 mol) and 2-bromo-
1,3-diphenylpropane-1,3-dione [21] (3.03 g, 0.01 mol).
White solid (isopropyl alcohol), 1.23 g (47%), mp 175–
from ethanol solution. Intensity data were collected on a small
crystal (0.24×0.08× 0.04 mm3) on an automatic four-circle
CCD diffractometer «Xcalibur-III», MoKα-radiation,
graphite monochromator, θ/2θ scan, 2θmax = 50.0°. The
crystal structure was solved by direct methods using
SHELX97 program package [22]. Non-H atoms were
first refined isotropically, followed by anisotropic
refinement by full-matrix least squares calculation
based on F2 using SHELX97. N-bound H-atoms were
found from the differential Fourier maps and refined
freely in isotropic approximation. C-bound hydrogen atoms
were positioned geometrically and allowed to ride on their
respective parent atoms. Figures were generated using
MERCURY [23]. Crystal data. Molecular formula
C12H16N2O5, M=268.27; monoclinic; a=8.2162(15),
b=21.567(2), c=8.992(3)Å; α=γ =90°, β =122.232(15)°,
V=1347.8(5)Å3; T=293(2)K; space group P21/c (no. 14);
Z=4; 4331 reflections measured, 2363 unique
(Rint =0.028), which were used in all calculations.
Refinement as described earlier with 183 parameters gave
GOF=0.968 and final R indices R1 =0.0570 [I> 2σ(I)],
wR1 =0. 0947 and R2 =0.1324, wR2 =0.1211 (all data).
Selected bond lengths and bond angles are shown in
Table 1. CCDC 1052298 contains the supplementary
crystallographic data for 2a. These data can be obtained
free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
1
176°С (lit. 179–181°C [5]); Н NMR δ 12.50 (br. s, 1H,
NH), 7.98–7.54 (m, 5H phenyl), 5.95 (s, 1H, CH
pyrimid.), 4.74 (s, 2H, CH2S), 1.96 (s, 3H, CH3 pyrimid.);
MS m/z (%) 260 (M+, 12), 227(5), 155(8), 134(8), 105
(100), 77(21). Anal. Calcd. for C13H12N2O2S: C, 59.98;
H, 4.65; N, 10.76%. Found: C, 59.96; H, 4.64; N, 10.75%.
2-(1,1-Diethoxycarbonylmethylene)thio-6-phenyl-
1,3-dihydro-pyrimidin-4(1H)-one (5). To a solution
of 6-phenyl-2-thiouracil (1b) (2.04 g, 0.01 mol) in anhy-
drous ethanol (250 mL),
a
solution of diethyl
bromomalonate (2.39 g, 0.01 mol) in anhydrous ethanol
(50 mL) was gradually added under stirring at 18–20°C.
The resulting mixture was kept at room temperature for
30 min and refluxed for 16 h. The reaction mixture was
evaporated in a rotary evaporator under water pump vac-
uum. The residue was washed with cold water and crystal-
lized from acetonitrile as white needles, 2.32 g (64%), mp
184–186°C dec.; ms m/z (%) 362(M+, 47), 316(43), 289
(88), 217(87), 204(100), 188(21), 171(77), 156(27), 146
(16), 129(47), 116(71), 103(96). Anal. Calcd. for
C17H18N2O5S: C, 56.34; H, 5.01; N, 7.73%. Found: C,
56.40; H, 5.00; N, 7.74%.
2-(1-Ethoxycarbonylmethylene)thio-6-phenyl-1,3-dihydro
pyrimidin-4(1H)-one (6). Method A: A mixture of 2-(1,1-
Acknowledgments. M. S. F. and L. C. are indebted to the CSSDT
15.817.02.06F project for support.
diethoxycarbonylmethylene)thio-6-phenyl-1,3-dihydropyrimidin-4
(1H)-one (5) (1.81 g, 0.005 mol) and triphenylphosphine
(1.31g, 0.005 mol) in anhydrous 1,4-dioxane (250mL)
was refluxed for 6 h. The reaction mixture was evaporated
in a rotary evaporator under water pump vacuum. The
residue was washed with cold benzene and crystallized
from ethanol as white needles, 0.83 g (57%).
Method B: To a solution of sodium ethoxide obtained by
dissolving sodium (0.115g, 0.005mol) in anhydrous ethanol
(100mL) was added 2-(1,1-diethoxycarbonylmethylene)
thio-6-phenyl-1,3-dihydropyrimidin-4 (1H)-one (5) (1.81g,
0.005mol) and refluxed for 24h. The reaction mixture was
evaporated in a rotary evaporator under water pump vacuum.
The residue was washed with cold water and crystallized
from ethanol as white needles, 0.9 g (62%), mp
226–227°C; 1Н NMR δ 12.81 (br. s, 1H, NH), 8.06–7.50
(m, 5H phenyl), 6.75 (s, 1H, CH pyrimidin.), 4.12
(s, 2Н, SCH2), 4.10 (q, J = 7.5 Hz, 2H, CH2 ester), 1.18
(t, J=7.53Hz, 3H, CH3 ester); MS m/z (%) 290 (M+, 37),
244(26), 217(100), 204(12), 171(20), 158(8), 129(7),
116(12), 103(23). Anal. Calcd. for C14H14N2O3S: C, 57.92;
H, 4.86; N, 9.65%. Found: C, 57.98; H, 4.81; N, 9.66%.
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