512
L. Decrane, N. Plé and A. Turck
Vol. 42
2
-Bromo-3-(1-hydroxyethyl)pyrazine (8).
-1
1
49.1 (C ); 142.6 (C ,C ); 123.7 (C ). IR (cm ): 1529, 1494, 1421,
2 5 6 3
1
399, 1330, 1163, 1131, 1021, 857, 759.
Anal. Calcd. for C H BrIN (284.9): C, 16.86; H, 0.71; N,
Metalation of 2-bromopyrazine 1 (0.2 g, 1.26 mmol) following
the general procedure. V (THF) = 2 mL; T = -78 °C; LDA: n-
4
2
2
1
9
.83. Found: C, 16.89; H, 0.72; N, 9.62.
butyllithium 1.6 M (1.7 mL, 2.8 mmol, 2.2 equiv.), diiso-
propylamine (0.4 mL, 2.9 mmol, 2,3 equiv.), t = 15 min; t = 1
h; electrophile: acetaldehyde (1 mL). Dichloromethane was the
1
2
2,4-Dibromo-5-(1-hydroxyethyl)pyrimidine (12a).
Metalation of 2,4-dibromopyrimidine 2 (0,2 g, 0.84 mmol) fol-
eluent used for chromatography. Compound 8 was obtained as a
1
lowing the general procedure. V (THF) = 7 ml; T = -100 °C;
colorless oil (0.2 g, 78 %). H NMR (CDCl ): δ (ppm) = 8.50
1
3
LDA: n-butyllithium 1.6 M (1.7 mL, 2.7 mmol, 3.2 equiv.),
diisopropylamine (0.38 mL, 2.8 mmol, 3.8 equiv.). t = 30 min,
t2 = 1.5 h. Electrophile: acetaldehyde (1 mL). The eluent for
chromatography was a mixture of cyclohexane/ethyl acetate
(
d, 1H, J5-6 = 2.3 Hz, H ); 8.31 (d, 1H, J = 2.3 Hz, H ); 5.17 (q,
5 5,6 6
1
H, J = 8.3 Hz; J = 6.4 Hz, CH); 3.75 (d, 1H, J
= 8.3 Hz,
1
CHOH
1
3
OH); 1.52 (d, 3H, J = 6.4 Hz, CH3). C NMR: δ (ppm) = 159.1
(
C ); 143.9 (C ); 142.2 (C ); 139.8 (C ); 68 (CH); 23.6 (CH ). IR
3 6 5 2 3
-1
(90/10). Compound 12a was obtained as a colorless oil (56 mg,
(
cm ): 3401, 2977, 2929, 1518, 1442, 1401, 1364, 1320, 1183,
149, 1110, 1071, 1046, 1017.
Anal. Calcd. for C H BrN O (203,04): C, 35.49; H, 3.48; N,
1
2
0 %). H NMR (CDCl ): δ = 8.64 (s, 1H, H ); 5.16 (m, 1H,
1
3
6
1
3
CH); 2.69 (s, 1H, OH); 1.53 (d, 3H, JCH = 6.4 Hz CH3).
C
6
7
2
NMR: δ = 157.8 (C ); 152.3 (C ); 149.9 (C ); 139.1 (C ); 66.8
1
3.80. Found: C, 35.51; H, 3.52; N, 13.45.
6
4
2
5
-
1
(
CH); 23.7 (CH ). IR (cm ): 3399; 2977; 2928; 1548; 1514;
3
2
-Bromo-3-(1-hydroxyphenylmethyl)pyrazine (9).
Metalation of 2-bromopyrazine 1 (0.2 g, 1.26 mmol) following
1
370; 1225; 1154; 1117; 1068; 820; 764; 696. M.S. (EI) m/z: 284
+
+
+
(M + 2), 5); 282 ((M )), 10); 280 ((M – 2), 5); 269 (48); 267
(97); 265 (48); 187 (25); 185 (25).
the general procedure. V (THF) = 2 ml; T = -78 °C; LDA: n-butyl-
1
lithium 1.6 M (1.7 mL, 2.8 mmol, 2.2 equiv.), diisopropylamine (0.4
2
,4-Dibromo-6-(1-hydroxyethyl)pyrimidine (12b).
mL, 2.9 mmol, 2.3 equiv.). t1 = 15 min, t = 1 h. Electrophile:
2
Metalation of 2,4-dibromopyrimidine 2 (0,2 g, 0.84 mmol) fol-
benzaldehyde (0.31 ml, 2.8 mmol, 2.2 equiv.). Dichloromethane
lowing the general procedure. V (THF) = 7 ml; T = -100 °C;
LTMP: n-butyllithium 1.6 M (1.7 mL, 2.7 mmol, 3.2 equiv.),
was the eluent used for chromatography. 9 was obtained as a color-
1
1
less oil (0.23 g, 69 %). H NMR (CDCl ): δ (ppm) = 8.57 (d, 1H,
3
2
,2,6,6-tetramethylpiperidine (0.47 mL, 2.8 mmol, 3.3 equiv.).
J5-6 = 2,3 Hz); 8.34 (d, 1H, J5-6 = 2.3 Hz, H ); 7.34 (m, 5H, H );
6
Ph
t = 30 min, t = 1,5 h. Electrophile: acetaldehyde (1 mL). The
6
.04 (d, 1H, J
= 8.3 Hz, CH); 4.55 (d, 1H, JCHOH = 8.3
1
2
CHOH
13
eluent for chromatography was a mixture n-heptane/ethylacetate
Hz, OH). C NMR: δ (ppm) = 156.5 (C ); 143.7 (C ); 141.5 (C );
3
6
5
(80/20). Compound 12b was obtained as a colorless oil (59 mg,
1
40.4 (C + C ); 128.7 (C ); 128.4 (C ); 127.7 (C ); 73.2 (CH).
2 Ph Ph Ph Ph
1
-1
21 %). H NMR (CDCl ): δ (ppm) = 7.66 (s, 1H, H ); 4.84 (q,
IR (cm ): 3400; 3060; 3039; 2925; 1518; 1494; 1454; 1403; 1364;
186; 1144; 1083; 1037; 864; 758; 699.
Anal. Calcd. for C H BrN O (265.11): C, 49.84; H, 3.42; N,
3
5
1
H, J = 6.4 Hz, CH); 2.89 (s, 1H, OH); 1.53 (d, 3H, J = 6.4 Hz,
1
CH
1
3
CH3). C NMR: δ (ppm) = 176.5 (C ); 153.9 (C ); 151.2 (C );
6
4
2
1
1
9
2
-1
1
0.57. Found: C, 49.81; H, 3.57; N, 10.32.
120.5 (C5); 69.1 (CH); 23.6 (CH3). IR (cm ): 3377; 2971;
926; 1555; 1514; 1321; 1296; 1226;1075; 872; 837; 780; 658.
2
2
-Bromo-3-phenylsulfanylpyrazine (10).
+
+
+
M.S. (EI) m/z: 284 ((M + 2), 3); 282 ((M ), 6); 280 ((M – 2),
3); 269 (35); 267 (70); 265 (50); 187 (16); 159 (40); 157 (40).
Metalation of 2-bromopyrazine 1 (0.2 g, 1.26 mmol) following
the general procedure. V (THF) = 2 ml; T = -78 °C; LDA: n-
butyllithium (1.7 mL, 2.8 mmol, 2.2 equiv.), diisopropylamine
1
2
,4-Dibromo-5-(1-hydroxy-p-methoxyphenylmethyl)pyrimidine
(13a).
(
0.4 mL, 2.9 mol, 2.2 equiv.). t = 15 min, t = 1h. Electrophile:
1 2
diphenyl disulfide (0,6 g, 2.8 mmol, 2.3 equiv.).
Metalation of 2,4-dibromopyridine 2 (0.23 g, 0.96 mmol) fol-
A mixture dichloromethane/methylcyclohexane (1/1) was used
as the eluent for chromatography. Compound 10 was obtained as
lowing the general procedure. V1(THF) = 5 ml; T = -100 °C;
LDA: n-butyllithium 1.6 M (1.8 mL, 2.9 mmol, 3.2 equiv.),
diisopropylamine (0.45 mL, 3.2 mmol, 3.3 equiv.). t1 = 30
min, t2 = 1.5 h. Electrophile: p-methoxybenzaldehyde (0.38 mL,
2.9 mmol, 3.2 equiv.). The eluent for chromatography was a mix-
ture dichloromethane/ethylacetate (98/2). Compound 13a was
1
a white solid (0.18 g, 53 %). mp 108-10 °C. H NMR (CDCl ): δ
3
=
8.17 (d, 1H, J5,6 = 2,6 Hz, H5 or 6); 8.00 (d, 1H, J = 2.6 Hz,
5,6
1
3
H5or6); 7.55 (m, 2H, HPh); 7.46 (m, 3H, HPh). C NMR: δ (ppm)
159.2 (C ); 142.5 (C ); 139.5 (C ); 138.2 (C ); 135.8 (CPh);
=
3
5
6
2
-
1
obtained as a white solid (94 mg, 26 %). mp 112-4 °C. 1
1
1
29.8 (CPh); 129.6 (CPh), 128.7 (CPh). IR (cm ): 3056; 1475;
440; 1329; 1186; 1024; 859; 747; 688.
H
NMR: δ (ppm) = 8.75 (s, 1H, H ); 7.26 (d, 2H, J = 8.7, HPh);
6
Anal. Calcd. for C H BrN S (267.15): C, 44.96; H, 2.64; N,
0.49; S, 12.00. Found: C, 45.18; H, 2.68; N, 10.41; S, 11.84.
6.88 (d, 2H, J = 8.7, HPh); 5.92 (s, 1H, CH); 3.80 (s, 3H, OCH3);
1
0
7
2
1
3
1
2
2.65 (s, 1H, OH). C NMR: δ (ppm) = 160.0 (CPh, OMe); 158.1
C ); 153.2 (C ); 150.1 (C ); 137.1 (C ); 132 (C ); 128.8 (CPh);
(
1
6
4
2
5
Ph
-Bromo-3-iodopyrazine (11).
-
1
14.5 (CPh); 72.5 (CH); 55.8 (OCH ). IR (cm ): 3448, 2918,
3
Metalation of 2-bromopyrazine 1 (0.2 g, 1.26 mmol) following
2838, 1610, 1544, 1513, 1382, 1253, 1224, 1174, 1153, 1023,
+
+
the general procedure. V (THF) = 2 mL; T = -78 °C; LDA: n-
813, 776. M.S. (EI) m/z: 376 ((M + 2), 1); 374 ((M ), 2); 372
1
+
butyllithium 1.6 M (1.7 mL, 2.8 mmol, 2.3 equiv.), diisopropy-
((M – 2), 1); 360 (5); 358 (10); 356 (5); 345 (4); 348 (8); 341
lamine (0.4 mL, 2.9 mmol, 2.2 equiv.). t1 = 15 min, t = 1 h.
(4); 137 (100); 121 (40); 77 (29).
2
Electrophile: iodine (0.7 g, 2.8 mmol, 2.2 equiv.) dissolved in 5 mL
of THF. Purification by chromatography with a mixture
dichloromethane/methylcyclohexane (40/60). Compound 11 was
2
,4-Dibromo-6-(1-hydroxy-p-methoxyphenylmethyl)pyrimidine
(13b).
1
obtained as a white solid (0.18 g, 50 %), mp 75-77 °C; H NMR
Metalation of 2,4-dibromopyrimidine 2 (0.23 g, 0.96 mmol)
following the general procedure V (THF) = 5 ml; T = -100 °C.
13
(
CDCl ): δ (ppm) = 8.29 (m, 2H, H and H ); C NMR: δ (ppm) =
3 5 6
1