5472
R. Ta-Shma et al. / Tetrahedron 62 (2006) 5469–5473
requires C 55.59; H 7.60; N 13.20%]; d (300 MHz, DMSO-
H
for 2 h. Then the product was filtered and washed with water,
methanol, and ether, and dried under vacuum at 100 C.
ꢁ
Yield (3.2 g, 84.4%), mp>300 C; [Found: C 33.53; H
d ) 1.23–2.03 (6H, m), 2.27 (3H, s), 3.23–4.04 (2H, m), 5.47
6
ꢀ
1
ꢁ
2.60; N 19.30; S 22.96. C H N O S requires C 33.33; H
(
1
1H, br s), 7.60 (1H, s), 10.73 (1H, br s); nmax/cm 1670,
610, 1385, 1310, 1205, 1190, 1120, 980, 910, 820, 775,
and 740; MS(EI): m/z (%) 210 (100, M , C H N O ),
4
4 2 2
+
2.78; N 19.44; S 22.22%]; d (300 MHz, DMSO-d ) 6.97
H 6
1
0
14
2
3
+
+
1
26 (M , –C H O), 125 (M , –C H ).
5
(1H, d, J
nmax/cm
¼6.0 Hz), 9.60 (1H, br s), 10.27 (1H, br s);
8
5
9
HNCH
ꢀ1
3240, 3100, 1660, 1580, 1400, 1290, 1230,
1170, 1140, 890, 820, 760, 750, and 690; MS(EI): m/z (%)
4
.1.2. 5-Hydroxy-2-methylpyrimidin-4(3H)-one 6a. A
+
few crystals of p-toluenesulfonic acid were added to a solu-
tion of 1a (6.57 g) in hot methanol. After cooling the mixture
in an ice bath, white crystals were formed. The crystals were
144 (100, C H N O S, M ).
4 4 2 2
4.1.7. 5-Hydroxy-2-methylsulfanyl-6-phenylazo-3H-
pyrimidin-4-one 7c. Compound 6c (2.9 g) was dissolved in
a solution of sodium hydroxide (1.8 g) in water (12 cm ) and
ꢁ
filtered and dried under vacuum at 100 C. Yield (2.5 g, 63%),
ꢁ
3
mp>300 C; d (300 MHz, DMSO-d ) 2.2 (3H, s), 7.27 (1H,
H
6
ꢀ1
ꢁ
s), 9.27 (1H, br s); nmax/cm 3300, 1670, 1620, 1420, 1380,
245, 1110, 1020, 875, and 780; MS(EI): m/z (%) 126 (100,
C H N O , M ), 108 (M , –H O), 100 (M , ꢀ26).
heated to 40 C. Dimethylsulfate (3.0 g) was added drop-
1
wise while vigorously stirring and then the mixture was
cooled in an ice bath and filtered. The filtrate was acidified
with concentrated hydrochloric acid and was left overnight
+
+
+
5
6
2
2
2
ꢁ
4
4
.1.3. 5-Hydroxy-2-methyl-6-phenylazo-3H-pyrimidin-
-one 7a. Diazotation of aniline (1.17 g) was done in hydro-
at 4 C. The formed crystals were filtered, successively
washed with water, methanol, and ether, and dried under
3
3
ꢁ
dine formed (1.4 g) was subjected to the same diazotization
chloric acid (3.9 cm ) and water (8 cm ) by addition of
vacuum at 100 C. The 2-methylthio-4,5-dihydroxypyrimi-
3
ꢁ
sodium nitrite (0.87 g) in water (6 cm ) at 0–5 C. Then
sodium acetate (3.1 g) was added slowly under continuous
stirring, followed by the addition of a solution of 6a
ꢁ
(300 MHz, DMSO-d ) 2.73 (3H, s); 6.97–7.83 (5H, m);
procedure as 3a. Yield (1.5 g, 74.0%), mp 213–215 C; dH
6
3
ꢀ1
(
for 30 min, the reaction mixture was left for overnight at
1.59 g) in 10% sodium hydroxide (10.4 cm ). After stirring
10.73 (1H, br s); nmax/cm 3480, 3200, 3100, 1710, 1660,
1590, 1510, 1450, 1250, 1150, 1030, 990, 770, 750, 690,
ꢁ
tered. The red crystals formed were washed and dried under
ꢁ
+
4
C. Then the reaction was warmed to 40 C for 1 h and fil-
and 640; MS(EI): m/z (%) 262 (10, C H N O S, M ),
1
1 10 4 2
+
+
+
6 5
105 (100, C H N ), 91 (C H N ), 77 (C H ).
6
5
2
6
5
ꢁ
Found: C 57.60; H 4.22. C H N O requires C 57.89; H
ꢁ
vacuum at 100 C. Yield (1.61 g, 56%), mp 243–245 C;
[
4.1.8. 6-Amino-5-hydroxy-2-(methylthio)pyrimidin-4-
(3H)-one 8c. Identical to the procedure for the synthesis of
8a, except for the use of 7c (1.0 g) instead of 7a. White crys-
1
1 10 4 2
4
.35%]; d (300 MHz, DMSO-d ) 1.95 (3H, s), 6.44–7.73
H 6
ꢀ
1
(
5H, m), 11.19 (1H, br s), 11.64 (1H, br s); nmax/cm
ꢁ
3
1
220, 3180, 1710, 1670, 1600, 1520, 1470, 1430, 1360,
280, 1250, 1050, 800, 775, 715, 700, and 660; MS(EI):
tals were obtained. Yield (0.43 g, 66%), mp 243–245 C;
[Found: C 34.27; H 4.08; N 24.21; S 19.00. C H N O S re-
5
7 3 2
+
+
m/z (%) 230 (25, C H N O , M ), 105 (100, C H N ).
5
quires C 34.38; H 4.05; N 24.28; S 18.50%); d (300 MHz,
H
1
1
10
4
2
6
2
DMSO-d ) 2.45 (3H, s); 5.87 (2H, br s), 7.90 (1H, br s); nmax/
6
ꢀ
1
4
8
.1.4. 6-Amino-5-hydroxy-2-methylpyrimidin-4(3H)-one
a. A solution of 7a (1.61 g) in water (15 cm ) was heated
cm 3250, 3380, 1640, 1600, 1570, 1410, 1330, 1240, 970,
830, and 760; MS(EI): m/z (%) 173 (100, C H N O S, M ).
25
3
+
5
7 3 2
ꢁ
to 60–70 C, an excess of sodium dithionite was added to the
solution in batches until a bright yellow color was obtained
and the solution was cooled in an ice bath. The white crystals
formed were washed with water and dried under vacuum
4.1.9. 5-Hydroxypyrimidin-4(3H)-one 6b. To a solution
of water (76 cm ) and concentrated aqueous ammonia
(7.6 cm ), 5c (11.0 g) was added followed by the addition
3
3
ꢁ
ꢁ
at 100 C. Yield (0.44 g, 44%), mp>300 C; [Found: C
of Raney nickel (40.0 g). The mixture was refluxed for 4 h
then it was cooled and filtered. All the volatile solvents
were removed by rotor-evaporator and the residue was redis-
solved in methanol. After addition of ether, pink crystals pre-
cipitated out of the solution, and were dried under vacuum at
4
4
5
3
9
2.53; H 4.98; N 29.46. C H N O requires C 42.55; H
5 7 3 2
.96; N 29.79%]; dH (300 MHz, DMSO-d ) 2.13 (3H, s),
6
.36 (2H, br s), 7.85 (1H, br s), 11.66 (1H, br s); nmax/cm
420, 3320, 3160, 1600, 1440, 1380, 1280, 1210, 1020,
90, 900, 790, and 770; MS(EI): m/z (%) 141 (100,
ꢀ
1
ꢁ
ꢁ
100 C. Yield (2.5 g, 46%), mp 265–267 C; d (300 MHz,
H
+
ꢀ1
C H N O , M ).
5
DMSO-d ) 7.40 (1H, s), 7.67 (1H, s); nmax/cm 1640, 1600,
6
7
3
2
1
360, 1300, 1270, 1100, 930, 880, 790, 780, and 615;
+
4
.1.5. 2-Mercapto-5-(tetrahydro-pyran-2-yloxy)-3H-
MS(EI): m/z (%) 112 (100, C H N O , M ).
4 4 2 2
pyrimidin-4-one 5c. Identical to the procedure for the syn-
thesis of 5a, except for the addition of thiourea (15.29 g)
instead of acetamidine. White crystals were obtained. Yield
4.1.10. 5-Hydroxy-6-phenylazo-3H-pyrimidine-4-one 7b.
Identical to the procedure for the synthesis of 7a except for
the addition of 6b (1.12 g) instead of 6a. White crystals were
ꢁ
(
1
25.0 g, 54.5%), mp>300 C; [Found: C 47.15; H 5.38; S
4.49. C H N O S requires C 47.37; H 5.26; S 14.00]; d
3
ꢁ
obtained. Yield (1.9 g, 88%), mp 244–245 C; d (300 MHz,
H
9
12
2
H
ꢀ
1
(
m), 5.27 (1H, br s), 7.16 (1H, d, J
br s), 11.3 (1H, br s); nmax/cm 3150, 3080, 1630, 1570,
300 MHz, DMSO-d ) 0.8–1.97 (6H, m), 3.23–3.80 (2H,
¼6.0 Hz), 10.8 (1H,
DMSO-d ) 6.83–7.76 (6H, m), 11.88 (1H, br s); nmax/cm
6
6
3490, 3290, 1700, 1650, 1615, 1600, 1590, 1500, 1450,
1300, 1240, 1170, 1120, 1015, 900, 875, 750, 730, 680, 660,
640, 660, and 640; MS(EI): m/z (%) 216 (15, C H N O ,
HNCH
ꢀ
1
1
8
250, 1200, 1180, 1150, 1110, 1020, 980, 940, 900, 870,
10, and 670; MS(EI): m/z (%) 147 (100, M ꢀ81).
1
0 8 4 2
+
+
+
+
+
M ), 105 (100, C H N ), 91 (C H N ), 77 (C H ).
6 5 2 6 5 6 5
4.1.6. 5-Hydroxy-2-mercapto-3H-pyrimidin-4-one 6c. A
suspension of 5c (6.0 g) in 1 M H SO (30 cm ) was stirred
4.1.11. 6-Amino-5-hydroxypyrimidin-4(3H)-one 8b. Iden-
tical to the procedure for the synthesis of 8a except for the
3
2
4