Straightforward Pyrimidine Ring Construction
FULL PAPER
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1507 (m), 1481 (m), 1358 (s), 1086 (m) cm–1. H NMR (300 MHz, 0.70. IR (film): ν = 1620 (s), 1520 (s), 1508 (m), 1466 (m), 1340 (s),
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CDCl3): δ = 2.40 (s, 3 H, CH3), 3.13 [s, 3 H, N(CH3)2], 3.33 [s, 3 1304 (s) cm–1. 1H NMR (300 MHz, CDCl3): δ = 2.42 (s, 3 H, CH3),
H, N(CH3)2], 6.11 (d, J = 7.8 Hz, 1 H, 5-CH), 7.25 (m, 4 H, 5.03 (d, J = 6.0 Hz, 2 H, CH2), 5.37 (m, 2 H, CH2=), 6.04 (m, 1
4CHar), 7.43 (d, J = 7.8 Hz, 1 H, 6-CH) ppm. 13C NMR (75 MHz, H, CH=), 6.26 (d, J = 6.9 Hz, 1 H, 5-CH), 7.21 (d, J = 8.4 Hz, 2
CDCl3): δ = 21.2 (CH3), 37.8 [N(CH3)2], 38.0 [N(CH3)2], 94.7 (5- H, 2CHar), 7.31 (d, J = 8.4 Hz, 2 H, 2CHar), 7.61 (d, J = 6.9 Hz,
CH), 126.9 (2CHar), 130.0 (2CHar), 138.7 (Car), 141.9 (Car), 146.4
(6-CH), 158.7 (4-C), 181.5 (2-C) ppm. MS (EI, 70 eV): m/z (%) =
245 (49) [M]+, 244 (100), 201 (12), 139 (15), 91 (19).
1 H, 6-CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.3 (CH3),
68.6 (CH2), 99.9 (5-CH), 119.3 (CH2=), 126.5 (2CHar), 130.4
(2CHar), 131.6 (CH=), 139.4 (Car), 141.4 (Car), 148.3 (6-CH), 165.8
(4-C), 184.4 (2-C) ppm. MS (EI, 70 eV): m/z (%) = 258 (16) [M]+,
243 (100), 160 (11), 130 (12), 91 (13).
4-Piperidino-1-p-tolylpyrimidine-2(1H)-thione (37): White solid
(1.380 g, 97%). M.p. 229–231 °C. IR (KBr): ν = 2937 (w), 1629 (s),
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1547 (m), 1509 (m), 1445 (m), 1386 (m), 1358 (s), 1347 (s) cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.68 (m, 6 H, 3CH2), 2.39 (s, 3
H, CH3), 3.49 (br. s, 2 H, CH2), 4.06 (br. s, 2 H, CH2), 6.16 (d, J
= 7.8 Hz, 1 H, 5-CH), 7.24 (m, 4 H, 4CHar), 7.40 (d, J = 7.8 Hz,
1 H, 6-CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.2 (CH3),
24.3 (CH2), 25.7 (CH2), 25.9 (CH2), 44.9 (CH2), 46.8 (CH2), 94.5
(5-CH), 126.9 (2CHar), 130.0 (2CHar), 138.7 (Car), 141.9 (Car),
145.5 (6-CH), 157.2 (4-C), 181.6 (2-C) ppm. MS (EI, 70 eV): m/z
(%) = 285 (62) [M]+, 284 (100), 201 (15), 179 (17), 121 (15), 91 (12).
Pyrimidines 38–42: Sodium alkoxide R3ONa (1.5 mmol) was added
to a solution of pyrimidine 3 (248 mg, 1.0 mmol) in alcohol R3OH
(15 mL) or in dichloromethane (15 mL) for 38. The reaction mix-
ture was stirred at room temperature for 90 min. The solvent was
then removed and the residue was dissolved in dichloromethane
(20 mL), washed five times with water, dried with magnesium sul-
fate and concentrated under vacuum. The residue was purified by
chromatography on silica gel (dichloromethane/petroleum ether/tri-
ethylamine, 40:57:3) or was washed with diethyl ether (39).
4-(2-Methoxy)ethoxy-1-p-tolylpyrimidine-2(1H)-thione (42): Yellow
oil (224 mg, 81%). TLC (petroleum ether/dichloromethane, 6:4): Rf
= 0.68. IR (film): ν = 1621 (m), 1522 (m), 1510 (m), 1466 (m), 1342
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(s), 1305 (s) cm–1. H NMR (300 MHz, CDCl3): δ = 2.41 (s, 3 H,
CH3), 3.43 (s, 3 H, OCH3), 3.74 (m, 2 H, CH2), 4.68 (m, 2 H, CH2),
6.31 (d, J = 6.9 Hz, 1 H, 5-CH), 7.20 (d, J = 8.1 Hz, 2 H, 2CHar),
7.30 (d, J = 8.1 Hz, 2 H, 2CHar), 7.62 (d, J = 6.9 Hz, 1 H, 6-CH)
ppm. 13C NMR (75 MHz, CDCl3): δ = 21.3 (CH3), 59.0 (OCH3),
66.9 (CH2), 70.2 (CH2), 100.1 (5-CH), 126.4 (2CHar), 130.4
(2CHar), 139.4 (Car), 141.4 (Car), 148.3 (6-CH), 166.1 (4-C), 184.3
(2-C) ppm. MS (EI, 70 eV): m/z (%) = 276 (91) [M]+, 245 (53), 217
(100), 160 (41), 159 (99), 130 (35), 91 (34).
4-Methylsulfanyl-1-(2,3,4,6-tetrahydroxy-β-D-galactopyranosyl)pyr-
imidine-2(1H)-thione (45): A solution of peracetylated carbohydrate
44a[18] (244 mg, 0.5 mmol) in methanol (15 mL) was stirred at 0 °C
for 3 h. Then, dichloromethane (50 mL) was added to the reaction
mixture and the mixture was concentrated under reduced pressure
without heating. The resulting solid was washed with diethyl ether.
4-Benzoxy-1-p-tolylpyrimidine-2(1H)-thione (38): Yellow oil
(200 mg, 65%). TLC (petroleum ether/dichloromethane, 8:2): Rf =
Yellow solid (160 mg, 100%). M.p. 136–138 °C. IR (KBr): ν = 3381
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(s), 1608 (s), 1495 (m), 1408 (m), 1312 (m), 1088 (s) cm–1. 1H NMR
(300 MHz, [D6]DMSO): δ = 2.52 (s, 3 H, CH3), 3.43–3.63 (m, 4 H,
gal 6a-H, 6b-H, 5-H and 3-H), 3.73 (m, 2 H, gal 2-H and 4-H),
0.73. IR (film): ν = 1655 (s), 1508 (w), 1471 (s), 1347 (m) cm–1. 1H
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NMR (300 MHz, CDCl3): δ = 2.42 (s, 3 H, CH3), 5.56 (s, 2 H,
CH2), 6.27 (d, J = 7.2 Hz, 1 H, 5-CH), 7.34 (m, 9 H, 9CHar), 7.61 4.71, 5.06 and 5.22 (3 br. s, 4 H, 4OH), 6.60 (d, J = 9.0 Hz, 1 H,
(d, J = 7.2 Hz, 1 H, 6-CH) ppm. 13C NMR (75 MHz, CDCl3): δ = gal 1-H), 6.93 (d, J = 7.2 Hz, 1 H, pyr 5-CH), 7.98 (d, J = 7.2 Hz,
21.3 (CH3), 69.8 (CH2), 100.0 (5-CH), 126.5,128.7 and 130.4
(9CHar), 135.2 (Car), 139.5 (Car), 141.5 (Car), 148.3 (6-CH), 165.9
1 H, pyr 6-CH) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 12.4
(CH3), 60.3 (gal, 6-C), 68.4 (gal, 4-C), 69.9 (gal, 2-C), 73.6 (gal, 3-
(4-C), 184.4 (2-C) ppm. MS (EI, 70 eV): m/z (%) = 308 (31) [M]+, C), 79.0 (gal, 5-C), 89.2 (gal, 1-C), 108.0 (pyr, 5-CH), 142.6 (pyr,
181 (50), 159 (21), 130 (27), 91 (100), 65 (28).
6-CH), 171.7 (pyr, 4-C), 181.0 (pyr, 2-C) ppm. HRMS (ESI+):
calcd. for C11H16N2O5S2Na [M + Na]+ 343.0398; found 343.0406.
4-Methoxy-1-p-tolylpyrimidine-2(1H)-thione (39): Yellow solid
(150 mg, 65%). M.p. 153–155 °C. IR (KBr): ν = 1633 (s), 1526 (s),
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4-Methylsulfanyl-1-(2,3,5-trihydroxy-β-D-ribofuranosyl)pyrimidine-
1509 (m), 1477 (s), 1343 (s), 1313 (s) cm–1. 1H NMR (300 MHz,
CDCl3): δ = 2.40 (s, 3 H, CH3), 4.07 (s, 3 H, OCH3), 6.23 (d, J =
7.2 Hz, 1 H, 5-CH), 7.18 (d, J = 8.4 Hz, 2 H, 2CHar), 7.29 (d, J =
8.4 Hz, 2 H, 2CHar), 7.58 (d, J = 7.2 Hz, 1 H, 6-CH) ppm. 13C
NMR (75 MHz, CDCl3): δ = 21.3 (CH3), 55.2 (OCH3), 99.9 (5-
CH), 126.5 (2CHar), 130.4 (2CHar), 139.4 (Car), 141.4 (Car), 148.2
(6-CH), 166.5 (4-C), 184.5 (2-C) ppm. MS (EI, 70 eV): m/z (%) =
232 (37) [M]+, 231 (100), 91 (12).
2(1H)-thione (46): A solution of perbenzoylated carbohydrate
44b[18] (301 mg, 0.5 mmol), first dissolved in dichloromethane
(5 mL), and potassium carbonate (3.5 mg, 0.025 mmol) in meth-
anol (15 mL) was stirred at 0 °C for 7 h. Then, dichloromethane
(50 mL) was added to the reaction mixture and the mixture was
concentrated under reduced pressure without heating. The residue
was purified by chromatography on silica gel (dichloromethane/
methanol, 95:5). White solid (98 mg, 67%). M.p. 146–148 °C. IR
(KBr): ν = 3446 (s), 1653 (m), 1436 (m) cm–1. 1H NMR (300 MHz,
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4-Isopropoxy-1-p-tolylpyrimidine(1H)-2-thione (40): Yellow oil
(185 mg, 71%). TLC (petroleum ether/dichloromethane, 6:4): Rf =
[D6]DMSO): δ = 2.52 (s, 3 H, CH3), 3.64 (dd, J = 4.5, 12.6 Hz, 1
H, rib 5a-H), 3.83 (dd, J = 4.5, 12.6 Hz, 1 H, rib 5b-H), 3.97 (m,
2 H, rib 3-H and 4-H), 4.05 (m, 1 H, rib 2-H), 5.04 (d, J = 4.4 Hz,
1 H, OH), 5.35 (t, J = 4.5 Hz, 1 H, CH2OH), 5.56 (d, J = 4.8 Hz,
1 H, OH), 6.37 (s, 1 H, rib 1-H), 6.94 (d, J = 7.2 Hz, 1 H, pyr 5-
CH), 8.63 (d, J = 7.2 Hz, 1 H, pyr 6-CH) ppm. 13C NMR (75 MHz,
[D6]DMSO): δ = 12.4 (CH3), 58.6 (rib, 5-C), 67.3 (rib, 3-C), 74.8
(rib, 2-C), 83.9 (rib, 4-C), 94.7 (rib, 1-C), 107.4 (pyr, 5-CH), 141.3
(pyr, 6-CH), 171.7 (pyr, 4-C), 178.5 (pyr, 2-C) ppm. HRMS (ESI+):
calcd. for C10H14N2O4S2Na [M + Na]+ 313.0293; found 313.0290.
0.82. IR (film): ν = 1621 (m), 1518 (m), 1509 (m), 1448 (s), 1339
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(m), 1301 (s) cm–1. H NMR (300 MHz, CDCl3): δ = 1.38 [d, J =
6.3 Hz, 6 H, CH(CH3)2], 2.41 (s, 3 H, CH3), 5.70 [hept, J = 6.3 Hz,
1 H, CH(CH3)2], 6.17 (d, J = 7.2 Hz, 1 H, 5-CH), 7.21 (d, J =
8.1 Hz, 2 H, 2CHar), 7.30 (d, J = 8.1 Hz, 2 H, 2CHar), 7.57 (d, J
= 7.2 Hz, 1 H, 6-CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.3
(CH3), 21.8 [CH(CH3)2], 71.2 [CH(CH3)2], 100.5 (5-CH), 126.5
(2CHar), 130.3 (2CHar), 139.3 (Car), 141.6 (Car), 147.9 (6-CH),
165.8 (4-C), 184.4 (2-C) ppm. MS (EI, 70 eV): m/z (%) = 260 (59)
[M]+, 217 (100), 160 (92), 130 (31), 91 (26).
Nucleosides Analogues 47 and 48: A solution of pyrimidine 45
(320 mg, 1.0 mmol) or 46 (290 mg, 1.0 mmol) in ethanol (5 mL)
and aqueous potassium hydroxide (2 m, 5 mL) was refluxed for 4 h.
4-Allyloxy-1-p-tolylpyrimidine-2(1H)-thione (41): Yellow oil
(168 mg, 65%). TLC (petroleum ether/dichloromethane, 6:4): Rf =
Eur. J. Org. Chem. 2006, 634–643
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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