Pyrimidine halogenations

Pyrimidine, 5-acetyI-2,4-dimethyI-synthesis, 3, 125 Pyrimidine, acylamino-deaeylation, 3, 85 Pyrimidine, alkoxy-hydrolysis, 3, 91 Primary Synthesis, 3, 134 synthesis, 3, 132, 134 Pyrimidine, 2-alkoxy-aminolysis, 3, 92 rearrangement, 3, 92, 135 synthesis, 3, 134 transalkoxylation, 3, 92 Pyrimidine, 4-alkoxy-aminolysis, 3, 92 rearrangement, 3, 92, 135 synthesis, 3, 134 transalkoxylation, 3, 92 Pyrimidine, 6-alkoxy-aminolysis, 3, 92 rearrangement, 3, 92, 135 synthesis, 3, 134 transalkoxylation, 3, 92 Pyrimidine, alkyl-halogenation, 3, 76 nitration, 3, 77 oxidation, 3, 76 synthesis, 3, 124... 

The halogen atom in benz-chloro substituted quinazolines is very stable (as in chlorobenzene), whereas the halogen atoms in positions 2 and 4 show the enhanced reactivity observed with halogen atoms on carbon atoms placed a and y to heterocyclic ring nitrogens. The chlorine atom in position 4 is more reactive than in position 2, and this property has been used to introduce two different substituents in the pyrimidine ring. ... 

The versatility of pyrimidine substituted chloroquinazolines as intermediates is due to the ready replacement of the halogen atoms by hydrogen, alkyl, alkoxyl, amino, and mercapto groups (see Section VI, A). 

Halogenation of pyrimidine bases may be done with bromine or iodine. Bromination occurs at the C-5 of cytosine, yielding a reactive derivative, which can be used to couple diamine spacer molecules by nucleophilic substitution (Figure 1.48) (Traincard et al., 1983 Sakamoto et al., 1987 Keller et al., 1988). Other pyrimidine derivatives also are reactive to bromine compounds... 

For the halogen-metal exchange reaction of bulkier halopyrimidines, steric hindrance retards the nucleophilic attack at the azomethine bond. As a consequence, halogen-metal exchange of 5-bromo-2,4-di-r-butoxypyrimidine (43) with n-BuLi could be carried out at -75 °C [20]. The resulting lithiated pyrimidine was then treated with n-butylborate followed by basic hydrolysis and acidification to provide 2,4-di-f-butoxy-5-pyrimidineboronic acid (44). 5-Bromopyrimidine 43 was prepared from 5-bromouracil in two steps consisting of a dehydroxy-halogenation with phosphorus oxychloride and an SnAt displacement with sodium r-butoxide. 

Dehydroxy-halogenation of 89 using POCU led to dihalopyrimidine 92, which was subsequently coupled with phenylacetylene to give 4-chIoro-5-alkynyIpyrimidine 93 [63, 64], Subsequent treatment of 93 with sodium hydrosulfide in refluxing ethanol gave 2,4-dimethyl-6-phenylthieno[2,3-d]pyrimidine (94). 

---