Pyrimidines 5-bromo

Trans-halogenation processes are especially important for the preparation of iodo (except 5-iodo) pyrimidines. Chloro- and bromo-pyrimidines... 

Coupling 5-isopropyl-l-methylpyrazol-3-ol 333 with 2-bromothi-azole, 5-bromo-pyrimidine and 3-bromoquinoline under Buchwald-type amidation gave pyrazolones 334a-c, in modest yields (06BMCL3713) (Scheme 76). 

Further work has appeared on the palladium(ii)-catalysed alkenylation of halogeno-pyrimidines (see also p. 230). The scope of the reaction had appeared to be neatly delineated in that 5-iodo- or 5-bromo-pyrimidines undergo the reaction whereas 2- or 4-iodopyrimidines do not it has now been discovered that, if the 4-iodopyrimidine possesses a substituent in the 5-position, e.g. (227 Z = I, Br, Cl, or Et), then alkenylation will occur (Scheme 89). Particularly noteworthy is the selective reaction at position 4 of the 4,5-di-iodo-compound (227 Z = I). "... 

The preparation of 2-bromopyridine from 2-amiaopyridine was first reported by Chichibabin and Ryasanjev in 1915/ however, the yield was low/ In 1934, Craig reported a modified method for preparing 2-bromo-pyridine in high yield from 2-amino-pyridine, therefore, this reaction is called Craig 2-bromo-pyridine synthesis. In this reaction, aconcen-trated aqueous solution of sodium nitrite and 2-amino-pyridine was added to a concentrated hydrobromic acid saturated with bromine. It was found that 2 mole of bromine and at least 2.5 mol of sodium nitrite are necessary to obtain an optimal yield of 2-bromo-pyridine. This method has been used to prepare 2-bromo-pyrimidines. ... 

This reaction has been used for the preparation of 2-bromo-pyridine and 2-bromo-pyrimidine. 

Figure 21 Crystal structure of the MOF constructed through reaction of 2-amino-5-bromo-pyrimidine and Cu(II) with zeolitic BCT topology. Cu (green), Br (brown), N (blue), C (gray), and H (white). Disordered solvent guest molecules omitted for clarity.

As mentioned above (Section 2.13.2.1.3), bipyrimidine photoproducts can arise, probably by reaction between two radicals. Thus, irradiation of an aqueous solution of 5-bromouracil (ill R=Br) in the absence of oxygen produces a variety of products including uracil, barbituric acid, 5-carboxyuracil (111 R = CO2H), several non-pyrimidine compounds and, as a stable end-product, the biuracil (114 R = H). A similar product (114 R = Me) is formed from 5-bromo-l,3-dimethyluracil (ilS). When two such related uracil derivatives are irradiated together, a mixed bipyrimidine product is formed, inter alia (B-76MI21302). 

The ease of displacing a chloro, bromo or iodo substituent in comparable pyrimidines by aminolysis is disappointingly similar. Using 2-halogeno-4,6-dimethyl- and 4-halogeno-... 

Primary synthesis has limited application in making pyrimidine-carboxylic acids or even their esters. However, some pyrimidine-4(and 5)-carboxylic acids can be effectively so made. For example, bromomucic acid (785) reacts as an aidehydo ketone with S-methyl-thiourea to give 5-bromo-2-methylthiopyrimidine-4-carboxylic acid (786) directly (53JCS3129) while the Whitehead synthesis (Section 2.13.3.1.2<7) can give, for instance, 3-methylcytosine-5-carboxylic acid (787) (55MI21300). 

---