Chichibabin amination reaction mechanisms

Carboxamidation of heteroaromatic compounds, promoted by fluorine, provides a convenient alternative to the well-known Chichibabin amination reaction (Fig. 86) [228]. The mechanism of this reaction was suggested to proceed via a carbene intermediate (Fig 87). 

The Chichibabin amination reaction can progress through two distinct mechanisms. Through extensive experimental and spectroscopic data, it was... 

Diphenyl-l,3,5-triazine undergoes a Chichibabin-type amination reaction, the first example of this reaction to be reported for the 1,3,5-triazines. The 2-methylthio derivative (37 X = MeS) reacts exclusively via an Sn(ANRORC) mechanism rather than the SNAE mechanism (Scheme 21) (76RTC113). 

The most striking example of these reactions is the Chichibabin amination performed in its classical variant under heterogeneous conditions. The reaction is accompanied by the evolution of hydrogen gas that is conveniently monitored. Presumably, on elimination, the hydride ion is combined with an acidic proton, likely from an amino group 4, to form a hydrogen molecule the reaction mechanism without details is shown in Scheme 3. 

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... 

Pyridine and other heterocyclic nitrogen compounds can be aminated with alkali metal amides in a process called the Chichibabin reaction The attack is always in the 2 position unless both such positions are filled, in which case the 4 position is attacked. Substituted alkali metal amides (e.g., RNH and R2N ) have also been used. The mechanism is probably similar to that of 13-15. The existence of intermediate ions such as 15... 

Purine and its derivatives undergo amination with potassium amide in liquid ammonia. Under these conditions, two different mechanisms may be followed (1) the Chichibabin reaction, and (2) the Sn(ATSIRORC) (Addition of Nucleophile, Ring Opening, Ring Closure) reaction. 

Simig, G., Van der Plas, H. C. The SN(ANRORC) mechanism. XVII. An SN(ANRORC) mechanism in the amination of phenyl-1,3,5-triazine with potassium amide in liquid ammonia. A novel mechanism for the Chichibabin reaction. Red. Trav. Chim. Pays-Bas 1976, 95,125-126. 

When 2-phenyl-l,3,5-triazine (8) is aminated with potassium amide in liquid ammonia at - 33 C a very slow Chichibabin reaction occurs, partly via the Sn(ANRORC) mechanism and partly via the SNAE process (ratio ca. 55 45). H NMR and l5N-labelling studies have demonstrated that in solution an equilibrium exists between the starting triazine, amine adducts, open-chain amidines and triazine product 9.53... 

The mechanism of the Chichibabin reaction is still not clear, mainly due to the difficulties to handle with highly reactive alkali amides and also to study reaction kinetics under such specific conditions. Nevertheless, several remarkable observations shed some light on the mechanistic features of the process. Indeed, it has been found that heterocycles with values of 5-6 are aminated easily, while aromatic substrates with a lower basicity exhibit a low reactivity or undergo decomposition. Dependence of the reaction on basic character of starting azaaromatics suggests that the formation of an adsorbtion complex of the type 1 (Scheme 3) with a weak coordination bond between the ring nitrogen atom and sodium ion may be... 

Scheme 8.7 Mechanism of the Chichibabin reaction, the amination of pyridine...

---