Dehydroxy-halogenation

Dehydroxy-halogenation of thiazolidinedione (1) with phosphorus oxybromide led to 2,4-dibromothiazole (2) [3], whereas the same reaction conducted in DMF resulted in 2,4-dibromo-5-formylthiazole (3) [4],... 

Another reliable method of halopyrimidine synthesis is dehydroxy-halogenation . Refluxing pyrimidinones 10 and 13 with phosphorus oxychloride was followed by treating the resulting chloropyrimidines with hydroiodic acid to afford iodopyrimidine 11 and 14, respectively [10, 11]. 4-Chloropyrimidinone 13, on the other hand, was prepared by direct halogenation of pyrimidone 12. 

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). 

Dehydroxy-halogenation of thiazolidinedione (1) with phosphorus oxybromide led to... 

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