Benzimidazoles Chichibabin amination

A rate study of benzimidazoles with weak electron-donating groups showed that the rate of the Chichibabin amination decreased as the strength of the electron-donating character increased (i.e., 1,5-dimethyl > 5-methoxy-l-methyl > 1,5,6-trimethylbenzimidazole) (77CHE903). Because the substrates do not contain sterically hindered substituents, the rate decrease is a function of the increased electron density in the system, particularly the decreased effective positive charge at the 2-position. 

The Chichibabin reaction is exemplified by the amination of 2-methylpyridine (308) by sodium amide in toluene via intermediate 309 to yield 6-amino-2-methylpyridine (310). This reaction has been applied to pyridines, quinolines, isoquinolines, and naphthyridine as well as to benzimidazole, and was reviewed in great detail (66AHC229 78RCRI042 88AHC1). 

Since pyridine and benzimidazole derivatives both enter readily into the Chichibabin reaction, a study was undertaken with compounds that incorporated both types of nitrogen atoms into the same structure (72CHE1131). To determine the relative reactivities toward sodium amide, 1-pyridylbenzimidazoles such as 229 and 230 were synthesized. The pK, values of the parent compounds, benzimidazole and pyridine, are 5.53 and 5.21, respectively. These values are too close to predict the site of amination in the... 

The question of the rate-determining step in the Chichibabin reaction is still open. Clearly, it is difficult to expect that such a complex process can be controlled by any single parameter. On the basis of the rate of hydrogen gas evolution, the following sequence of the reactivity of aza-heterocyclic compounds has been established 1-R-benzimidazoles > isoquinoline > 1-R-perimidines > benzo[/]quinoline > pyridine acridine. Evidently, this raw indicates that sodamide amination depends on number of factors, involving electron deficiency of the substrate C(a)-atom, ease of the adduct aromatization, substrate basicity, etc. Evidently, acridine s position in this raw reflects the difficulty of the y-amination. 

---