2- Bromo-4-phenylpyrimidine, ANRORC

The amino-debromination of 6-bromo-4-phenylpyrimidine (Scheme 1.3). The reaction has been proved to occur by the formation of an initial ct-adduct at C-2, which subsequently rearranges into the 6-amino product [Sn(ANRORC) mechanism]. 

As we have seen in Section II,A, 6-bromo-4-phenylpyrimidine reacts on treatment with potassium amide in liquid ammonia at -75°C into the corresponding 6-amino compound nearly quantitatively according to the Sn(ANRORC) mechanism (71RTC1239). Extensive investigations have been carried out on the scope and limitations of this mechanism and on the several factors that influence the occurrence of the Sn(ANRORC) mechanism in the aminodehalogenation of 4-substituted-6-halogenopyrimidines. 

To establish which percentage of the label is present on the ring nitrogen and which on the amino group, the amino compound was converted by acid hydrolysis into 4-phenylpyrimidin-6(l//)-one, which was subsequently converted into 6-bromo-4-phenylpyrimidine (18a) by treatment with phosphoryl bromide (Scheme 11.12). If the content of the bromo compound 18a contains y%, the percentage of the 6-halogeno compound that reacts according to the Sn(ANRORC) mechanism can be calculated, i.e., (y X 100%. 

Fluoro-5-phenyl-l,2,4-triazine (109, X = F) reacts much faster than the 3-chloro-, 3-bromo-, or 3-iodo-compound. Moreover, the reaction mixture obtained is cleaner than that from the corresponding 3-chloro- or 3-bromo compounds 3-amino-5-phenyl-l,2,4-triazine (110) is formed in good yield. This conversion takes place to only a small extent (18%) via the ANRORC process the main part of the aminodefluorination seems to involve the Sn(AE) mechanism. This result is consistent with the observation that the aminodefluorination of 4,6-diphenyl-2-fluoropyrimidine follows the Sn(AE) process, whereas 2-fluoro-4-phenylpyrimidine (position 6 is vacant for addition of the nucleophile) reacts for the most part according to the Sn(ANRORC) mechanism (see Section II,C,l,c). 

There are cine- and fe/e-amination reactions which proceed via a special multi-step pathway, known as the ANRORC mechanism (Addition of a Aucleophile, Ring Opening, Ring Closure) (for reviews on this topics, see [11, 23,128]). For instance, 2-bromo-4-phenylpyrimidine reacts with KNH2 in liquid ammonia to afford 2-amino derivative 93 (Scheme 60). Thorough investigation of this reaction has shown that it proceeds via the formation of cr -adduct 91 followed by opening of the... 

It has been established by experimental data that the Chichibabin amination of pyrimidine proceeds either by an Sn(AE) or Sn(ANRORC) mechanism. Each mechanism is favored according to substituents, substitution pattern and reaction conditions. In turn, the region-chemical outcome for the reaction depends on the mechanism course the reaction follows. 2-bromo-4-phenylpyrimidine (21) reaction with KNH2-NH3... 

SCHEME 11.50 Reaction of 2-bromo-4-phenylpyrimidine with KNH proceeds via ANRORC mechanism. 

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