Alkylations of heterocyclic ambident anions. III. 4-Hydroxypyrimidines

Abstract

Salts of 4-hydroxypyrimidine and several 2-substituted 4-hydroxypyrimidines were treated with alkyl halides under a variety of reaction conditions. In cation-solvating media, methylation occurred mainly at N-3. Increased N-l methylation was observed in hydrogen-bonding solvents and solvents of lower dielectric constant. Studies in dimethylf ormamide revealed significant steric influences. When the alkyl halide was varied from methyl to ethyl to isopropyl or when the group on the 2 position was varied from hydrogen to methyl to ethyl, alkylation at oxygen increased at the expense of alkylation at N-3. 2-Trifluoromethyl-4-hydroxypyrimidine in dimethylf ormamide reacted with alkyl halides to give mainly 4-alkoxy-2-trifluoromethylpyrimidines.

A new diversity oriented and metal-free approach to highly functionalized 3H-pyrimidin-4-ones

“…R f 0.37 (PE/Me 2 CO 9 : 1, a or b). n max (CHCl 3 )/cm -1 3008, 2868, 1709, 1218, 1140, 920. d (8.7), 102 (8.2), 92 (10), 91 (100), 87 (5.9), 69 (11), 65 (7.0), 57 (28), 43 (19), 41 (9.5)…”

“…R f 0.28 (PE/AcOEt/CH 2 Cl 2 90 : 5 : 5, a or b). n max (CHCl 3 )/cm -1 2920, 2852, 1709, 1662, 1612, 1247, 1122. d (8.3), 242 (28), 269 (18), 268 (100), 240 (23), 225 (8.4), 224 (13), 223 (5.5), 222 (31), 197 (10), 196 (79), 194 (16), 182 (5.7), 178 (6.8), 169 (12), 168 (14), 156 (14), 152 (5.1), 151 (22), 150 (16), 142 (9.8), 140 (6.2), 124 (12), 123 (6.5), 122 (21), 110 (8.2), 109 (9.1), 108 (5.3), 98 (6.9), 97 (14), 96 (49), 95 (12), 94 (9.2), 83 (6.9), 82 (6.6), 81 (17), 80 (5.4), 79 (6.2), 70 (19), 69 (16), 68 (10), 67 (12), 57 (10), 56 (5.0), 55 (39), 54 (7.2), 53 (10), 44 (7.3), 43 (35), 42 (44), 41 (40), 39 (8.0). m/z (ESI -) 340.2133 (M -H + .…”

“…a) GC-MS (21b): R t 6.84 min; m/z (EI) 269 (M + , 1.4%), 115 (7.0), 114 (100), 101 (10), 96 (14), 70 (5.8), 57 (8.5), 55 (7.2), 42 (7.6), 41 (8.3). b) Chromatography of crude 18b with PE/Et 2 O 8 : 2 → 75 : 25 gave a pale yellow oil (81% from 7b).…”

“…R f 0.28 (PE/AcOEt/CH 2 Cl 2 90 : 5 : 5, a or b). n max (CHCl 3 )/cm -1 2917, 2852, 1704, 1609, 1451, 1367, 1194, 1010. d (19), 212 (8.8), 197 (11), 196 (30), 151 (12), 140 (8.1), 128 (10), 124 (6.6), 122 (15), 118 (30), 114 (15), 110 (7.2), 109 (6.2), 97 (8.9), 96 (40), 95 (10), 94 (7.2), 83 (6.0), 81 (12), 70 (18), 69 (14), 68 (8.0), 67 (9.0), 58 (5.5), 57 (100), 56 (7.5), 55 (36), 53 (7.4), 44 (7.2), 43 (28), 42 (33) 6.7), 114 (100), 96 (22), 57 (7.0), 55 (8.5), 42 (16), 41 (9.0). b) Chromatography of crude 18c with PE/Et 2 O 95 : 5 → 8 : 2 gave a pale yellow oil (82% from 7c).…”

“…R f 0.35 (PE/Et 2 O 85 : 15, a). n max (CHCl 3 )/cm -1 3012, 2953, 2865, 1706, 1607, 1463, 1251, 1151, 1125. d (9.0), 240 (7.9), 215 (11), 214 (100), 212 (14), 197 (6.3), 196 (16), 184 (19), 166 (10), 156 (5.7), 140 (8.8), 122 (9.9), 114 (6.1), 97 (7.5), 96 (33), 95 (7.7), 70 (8.9), 57 (48), 55 (17), 53 (5.3), 43 (13), 42 (20), 41 (34), 39 (7.0). m/z (ESI -) 312.1809 (M -H + .…”