Pyrimidines, alkyl-, reactivity nucleophilic substitution

Pyridine can become involved in nucleophilic substitution when very reactive trifiates are being synthesized. One approach to minimize this disadvantage is to replace it with sterically hindered bases, such as 2,6-di-f-butyl-4-methylpyridine, 2,4,6-trisubs-tituted pyrimidines, or nonnucleophilic aliphatic amines (usually W,W-diisobutyl-2,4-dimethyl-3-pentylamine). No salt formation appears to take place under these conditions. The triflic anhydride seems to be the direct triflating agent and the base only neutralizes the triflic acid formed. Numerous alkyl triflates have been prepared in the literature by the above method. Some recent examples of triflates prepared from alcohols are illustrated in eqs 2 and 3. As an exception, 2,6-dinitrobenzyl alcohol does not react with Tf20 although similar sulfonyl esters could be prepared. ... 

In an efficient microwave-assisted solution or solid-phase protocol (07Mn2) for 2-amino-4-arylpyrimidine-5-carboxylate derivatives (Scheme 27), 22 (X = S, R = H) was S-alkylated with methyl iodide to 2-methylthiodihydropyrimidines 34, which was sequentially oxidized first with manganese dioxide and then with Oxone to 2-methylsulfonyl-pyr-imidines 66 as precursors of 2-substituted pyrimidines 67 via displacement of the reactive sulfonyl group with N, O, S, and C nucleophiles (Scheme 27). However, direct displacement of the S-methyl group of 34 with nitrogen nucleophiles provided 2-amino-l,4-dihydropyrimidines 68. 

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