Month 2015
Synthesis of Thiobarbiturate Analogues
2b: white solid, yield (56.3%). mp =314.3–314.9°C. 1H-NMR
Table 1
(Continued)
(400 MHz, DMSO-d6) δ: 12.17 (s, 2H), 2.04 (t, J = 7.2 Hz, 4H),
1.75–1.71 (m, 4H). 13C-NMR (100 MHz, DMSO-d6) δ: 180.0,
173.0, 57.0, 27.2. HRMS (ESI): m/z calcd for C8H10N2O2S [M-
H]-: 197.0390, found: 197.0395.
Entry
R
Product
Yield (%)
35
8
4-CF3-phenyl
1
2c: yellow solid, yield (90.8%). mp = 207.3–208.2°C. H-NMR
(400 MHz, DMSO-d6) δ: 11.16 (s, 2H); 13C-NMR (100 MHz,
DMSO-d6) δ: 175.3, 157.6, 115.7. HRMS (ESI): m/z calcd for
C4H3N3O4S [M-H]-: 187.9760, found: 187.9754.
2d:sandybrown solid, yield (80%). mp = 330.3–330.8°C. 1H-NMR
(400 MHz, DMSO-d6) δ: 11.11 (s, 2H), 8.53 (s, 3H). HRMS (ESI):
m/z calcd for C4H6ClN3O2S [M-H]-: 193.9785, found: 193.9788.
2e: white solid, yield (83.5%). mp = 277.3–278.2°C. 1H-NMR
(400 MHz, DMSO-d6) δ: 11.84 (s, 2H), 7.40 (d, J = 6.8 Hz, 2H),
7.31 (t, J = 7.2 Hz, 2H), 7.21 (d, J = 6.8 Hz, 1H); 13C-NMR
(100 MHz, DMSO-d6) δ: 173.5, 160.5, 132.5, 131.1, 128.0,
126.6, 96.8. HRMS (ESI): m/z calcd for C10H8N2O2S [M-H]-:
219.0224, found: 219.0230.
9
1-Naphthyl
71
14
65
2f: white solid, yield (91.6%). mp = 287.1–289.0°C. 1H-NMR
(400 MHz, DMSO-d6) δ: 11.79 (s, 2H), 7.32 (d, J = 8.0 Hz, 2H),
6.87 (d, J = 8.4Hz, 2H), 3.74 (s, 3H). 13C-NMR (100 MHz,
DMSO-d6) δ: 172.7, 160.5, 157.9, 124.7, 113.4, 55.5. HRMS (ESI):
m/z calcd for C11H10N2O3S [M-H]-: 249.0339, found: 249.0332.
10
11
4-Pyridyl
1
2g: white solid, yield (87.6%). mp = 285.4–287.0°C. H-NMR
(400 MHz, DMSO-d6) δ: 11.96 (s,2H), 7.43–7.40 (m, 2H), 7.16–
7.12 (m, 2H). 13C-NMR (100 MHz, DMSO-d6) δ: 173.7, 162.6,
160.3, 160.2, 133.2, 133.1, 128.2, 115.0, 114.8, 96.3. 19F-NMR
(376 MHz) 115.8. HRMS (ESI): m/z calcd for C10H7N2O2SF
[M-H]-: 237.0140, found: 237.0143.
Thiobarbiturate
2h: red solid, yield (50.3%). mp = 270.3-272.0°C. 1H-NMR
(400 MHz, DMSO-d6) δ: 11.51 (s,2H), 7.87 (d, J = 8.0Hz, 2H),
7.57 (d, J = 8.0Hz, 2H). 13C-NMR (100 MHz, DMSO-d6) δ: 175.5,
166.4, 162.5, 131.2, 126.4, 124.5, 124.3, 82.5. HRMS (ESI): m/z
calcd for C11H7N2O2SF3 [M-H]-: 287.0111, found: 287.0108.
2i: yellow solid, yield (81.2%). mp = 271.2–272.0°C. 1H-NMR
(400 MHz, DMSO-d6) δ: 12.14 (s, 2H), 7.92 (q, J = 7.6 Hz, 2H),
7.68 (d, J = 8.4 Hz, 2H), 7.54–7.44 (m, 3H), 7.35 (d, J = 6.4Hz,
2H).13C-NMR (100 MHz, DMSO-d6) δ: 174.4, 160.7, 133.9, 130.4,
129.6, 128.5, 128.3, 126.2, 126.1, 126.0, 95.2; HRMS (ESI): m/z
calcd for C14H10N2O2S [M-H]-: 269.0390, found: 269.0394.
2j: yellow solid, yield (43.5%). mp = 263.5–267.0°C. 1H-NMR (400
MHz, DMSO-d6) δ: 11.47 (s,1H), 9.89 (s, 1H), 8.90 (d,146;J = 4.8
Hz, 2H), 7.91 (d, J = 5.6 Hz, 2H); 13C-NMR (100MHz, DMSO-d6)
δ: 178.8, 166.9, 143.7, 127.9. HRMS (ESI): m/z calcd for
C9H7N3O2S [M-H]-: 220.0186, found: 220.0183.
sodium was added 25 mL anhydrous ethanol. When the sodium
disappeared, thiourea and the corresponding 5-mono-substituted
malonic diethyl ester were added and then the mixture was well
stirred under reflux. After the corresponding malonic diethyl
ester reacted completely, the mixture was acidified to pH = 1~2
with conc. HCl at room temperature. Compounds 2a, 2c, 2d,
2e, and 2h were obtained by filtrating and washing with water
and ethanol. Compounds 2b, 2f, 2g, 2i, and 2k were obtained
after silica gel chromatography.
1
1
2a: white solid, yield (73.7%). mp = 253.6–254.8°C. H-NMR
2k: yellow solid, yield (75.2%). mp = 265.7–266.0°C. H-NMR
(400 MHz, DMSO-d6) δ: 12.04 (s, 2H), 1.7 (s, 3H).13C-NMR
(100 MHz, DMSO-d6) δ: 173.2, 160.7, 90.7, 7.8. HRMS (ESI):
m/z calcd for C5H6N2O2S [M-H]-: 157.0066, found: 157.0063.
(400 MHz, DMSO-d6) δ: 11.83 (s, 4H). 13C-NMR (100 MHz,
DMSO-d6) δ: 173.6, 161.0, 88.4. HRMS (ESI): m/z calcd for
C8H6N4O4S2 [M-H]-: 284.9758, found: 284.9762.
Scheme 3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet