4- Phenylpyrimidine, Chichibabin amination

The application of the Chichibabin amination to effect a direct amination of quinazoline has been reported. It gives 4-aminoquinazoline (60MII) as well as 2,4-diaminoquinazoline (59GEP958197). No mechanistic details were discussed, but it can be expected (based on the experience with the amination with 4-phenyl- and 5-phenylpyrimidine) that amination of quinazoline would also involve, at least partly, participation of the Sn(ANRORC) mechanism. Amination with N-labeled potassium amide/liquid ammonia will certainly shed some light on the mechanism operative in this Chichibabin amination. 

The Chichibabin amination of phenylpyrazine with N-labeled potassium amide/liquid ammonia gave two products, 3-amino- and 5-amino-2-phenylpyrazine in both products the label is only present in the amino group, and no label was found to be incorporated into the pyrazine ring (82MI1). This result proves that in the aminodehydrogenation of phenylpyrazine, no Sn(ANRORC) mechanism is involved. This result is confirmed by the fact that amination of phenylpyrazine in the presence of the radical scavenger azobenzene, a compound that has been found to prevent the Sn(ANRORC) mechanism in the Chichibabin amination of 4-phenylpyrimidine, still yields both aminopyrazines. 

Furthermore, it was pointed out that, whereas the formation of the amino adduct is fast and the formation of the product slow, it is possible that an equilibrium exists among the starting materials, their 1 1 a-amino adducts, and their open-chain amidines (Scheme 11.54). When this is the case, one may expect that, if the amination of phenyl-1,3,5-triazine is stopped before complete conversion, the retrieved starting material should be N-labeled. This has indeed been found. This behavior is in agreement with that observed with the Chichibabin amination of 4- and 5-phenylpyrimidine. 

Chichibabin amination of 4-phenylpyrimidine gives both the 2-amino- and 6-amino-derivatives, in 60 and 15% yields, respectively N-labelling showed that, in contrast to the 6-amino-derivative, the 2-amino-compound is formed by an ANRORC route. 

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... 

Breuker K, Van der Plas HC. Occurrence of an S m(ANRORC) mechanism in the chichibabin amination of 4-phenylpyrimidine. J Org Chem. 1979 44 4677-4680. Francis RF, Davis W, Wisener JT. Reaction intermediates in the alkylation of pyridine... 

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