2-Ethylthio-6-methylpyrimidin-4(3H)-one (3) was obtained analogously to compound 2 from
compound 1 (1.5 g, 10.6 mmol), NaOH (0.42 g, 10.6 mmol), and ethyl bromide (1.3 g, 11.6 mmol) in a yield of
1
1.5 g (84%); white crystals, mp 124-125°C. H NMR spectrum, δ, ppm: 1.15-1.22 (3H, t, J = 7 Hz, CH2CH3);
2.15 (3H, s, CH3); 2.95-3.05 (2H, q, J = 7 Hz, CH2CH3); 5.95 (1H, s, H-5); 12.5 (1H, s, NH). Found, %:
N 16.23. C7H10N2OS. Calculated, %: N 16.46.
6-Methyl-2-propylthiopyrimidin-4(3H)-one (4) was obtained analogously to compound 2 from
compound 1 (1.5 g, 10.6 mmol), NaOH (0.42 g, 10.6 mmol), and propyl iodide (1.8 g, 10.6 mmol). Yield was
1
1.7 g (88%); white crystals, mp 99-100°C. H NMR spectrum, δ, ppm: 0.85-0.95 (3H, m, CH2CH2CH3);
1.5-1.75 (2H, m, CH2CH2CH3); 2.1 (3H, s, CH3); 3.0-3.1 (2H, m, CH2CH2CH3); 5.95 (1H, s, H-5); 12.2 (1H, s,
NH). Found, %: N 15.04. C8H12N2OS. Calculated, %: N 15.20.
Synthesis of 2-Benzylthio-4-hydroxy-6-methylpyrimidine O-Sodium Salt. Sodium hydroxide
(0.16 g, 4 mmol) and compound 2 (1 g, 4 mmol) were dissolved in water (7 ml). The solution was evaporated,
and the obtained O-sodium salt of compound 2 was recrystallized from ethanol. 1H NMR spectrum, δ, ppm: 2.2
(3H, s, CH3); 4.3 (2H, s, SCH2); 5.95 (1H, s, H-5); 7.05-7.39 (5H, m, H arom.). Found, %: N 10.87.
C12H11N2NaOS. Calculated, 5: N 11.02.
Synthesis of S,O-Disubstituted Derivatives of Compound 1 (General Method).
4-Benzyloxy-2-benzylthio-6-methylpyrimidine (5). Sodium hydroxide (0.2 g, 5 mmol) and compound
2 (1 g, 4 mmol) were dissolved in water (9 ml). Dioxane (18 ml) and benzyl chloride (0.7 g, 5 mmol) were
added to the solution. The mixture was stirred at 50°C for 1 h. After cooling, the precipitated solid was filtered
off, washed with cold water, and recrystallized from benzene. The yield of compound 5 was 1.0 g (84%); white
crystals, mp 59-61°C. 1H NMR spectrum, δ, ppm: 1.85 (3H, s, CH3); 4.3 (2H, s, SCH2); 5.5 (2H, s, OCH2); 6.1
(1H, s, H-5); 7.05-7.39 (10H, m, H arom.). Found, %: N 8.54; C19H18N2OS. Calculated, %: N 8.60. The filtrate
was neutralized with 20% acetic acid acid solution, the precipitated solid was filtered off, washed with cold
water, dried, and recrystallized from ethanol. The yield of compound 2 was 0.3 g; white crystals, mp 173-174°C.
4-Ethoxy-2-ethylthio-6-methylpyrimidine (6) was obtained analogously to compound 5 from NaOH
(0.24 g, 6 mmol), compound 3 (1 g, 5.5 mmol), and ethyl bromide (1 g, 6 mmol) in water (8 ml) and dioxane (13
1
ml). Yield was 2.4 g (51%); white crystals, mp 124-125°C. H NMR spectrum, δ, ppm : 1.15-1.22 (3H, m,
SCH2CH3); 1.30-1.35 (3H, m, OCH2CH3); 2.15 (3H, s, CH3); 2.95-3.05 (2H, m, SCH2CH3); 3.40-3.60 (2H, m,
OCH2CH3); 5.95 (1H, s, H-5). Found, %: N 13.56. C9H14N2OS. Calculated, %: N 13.83.
6-Methyl-4-propoxy-2-propylthiopyrimidine (7) was obtained analogously to compound 5 from
NaOH (0.24 g, 6 mmol), compound 4 (1 g, 5.4 mmol), and propyl iodide (1 g, 6 mmol) in a yield of 1.1 g
(69%); white crystals, mp 83-85°C. 1H NMR spectrum, δ, ppm: 0.85-0.95 (6H, m, CH2CH2CH3); 1.5-1.75 (4H,
m, CH2CH2CH3); 2.1 (3H, s, CH3); 3.00-3.10 (2H, m, SCH2); 3.35-3.45 (2H, m, OCH2); 5.9 (1H, s, H-5). Found,
%: N 11.87. C11H12N2OS. Calculated, %: N 11.98.
Kinetic Investigations of Nucleophilic Substitution Reactions of Halogen in Pyrimidine Derivatives
by S-Anion. Reactions were carried out in a thermostatted three-necked reactor fitted with a stirrer,
thermometer, and a neck for removing samples.
The amount of compound 1 monosodium salt was determined after every 2 min, taking a test sample of
V = 1 ml from the reactor and transferring it to a small beaker containing distilled water (30 ml). The amount of
monosodium salt in the test sample (ω) was determined by potentiometric titration with 0.1 N H2SO4 solution in
a universal EV 74 ionomer instrument using a calomel reference electrode and a glass electrode as measuring
(indicator) electrode according to the following formula:
ω = Vк ·Vр ·0.1/1000,
where VK is the volume of H2SO4 consumed in the titration of 1 monosodium salt in ml; VP is the volume of the
reaction mass in ml.
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