2- Phenylbenzimidazole, formation

Huisgen found that 2-amino-3H-azepines are unstable under normal acylating conditions. Schotten-Baumann benzoylation, for example, brings about aromatization and, ultimately, formation of 2-(benzamido)diphenylamine, whereas p-nitrobenzoyl chloride in cold pyridine yields 2-(p-nitrophenyl)-l-phenylbenzimidazole. Benzenesulfonylation, however, proceeds normally at the exocyclic nitrogen. The mechanistic rationale for these ring contractions is outlined in Scheme 8 (b-69MI516oo). 

According to the data obtained, such a reaction either does not proceed at all [4] or yields the corresponding f3-amino adduct 2 or 2-phenylbenzimidazole 4 [2], depending on the reaction conditions. These results were treated as a general feature of the interaction between 0-PDA and chalcones [2]. The impossibility of the formation of aromatic dihydrobenzodiazepine derivatives was explained by the essentially lower reactivity of the carbonyl group in chalcone molecules in comparison with that of the C = C bond. 

The mass spectra of nitro derivatives of 2-phenylbenzimidazoles show the dissociative ionization to be characterized by two trends involving the formation of [M-NO]+ and [M-N02]+ ions (Scheme 3.72) [1342] ... 

There are reports that benzimidazoles can be made by eyclization of N-arylimidoyl nitrencs generated by photolysis of sulfimides of 1-aryltetrazoles [3, 4]. These should be compared to the related imidazole synthesis in Section 6.1.2.3. Examples include the formation of 2-phenylbenzimidazole (42%) from 1,5-diphenyltetrazoIe [5], and 5-phenoxybenzimidazole (36%) from 5-phenoxy-l-phenyltetrazole [6]. These reactions have little apparent synthetic importance. 

The latter steps, essentially irreversible, control the overall reaction. Thus 2,4-dimethylbenzodiazepine gives acetone and 2-methylbenzimida-zole,2 5 23 while 2-methyl-4-phenylbenzodiazepine gives a mixture of acetone, acetophenone, and 2-methyl- and 2-phenylbenzimidazoles.2 The same ring contraction also ensues when aqueous solutions of benzodiazepines or their salts are kept at room temperature. It seems likely that with solutions of the salts, free base, present to some extent in equilibrium with the cation, may be the species involved in hydrolysis, since addition of traces of mineral acid greatly retards the rate of formation of benzimidazole.23 Solutions in methanol are much more stable and solutions in methanol containing small amounts of mineral acid apparently keep indefinitely.23... 

First example Ogg and Bergstrom (1931) published a series of papers designed to demonstrate possible analogies between heterocyclic systems and their acyclic and alicyclic counterparts. Quinoxaline, for example, was described as an ammono glyoxal and 2,3-diphenylquinoxaline 1 was considered to be the heterocyclic equivalent of benzyl. In an attempt to justify this hypothesis, the authors carried out the reaction of 2,3-diphenylquinoxaline 1 with potassium amide in liquid ammonia, anticipating a reaction similar to the benzyl —> benzilic rearrangement, which would lead to the formation of 2,2-diphenyl-3-aminoquinoxaline 2 (Scheme 6.1). The reaction did, in fact, lead to a new product-2-phenylbenzimidazole 3 in an approximately 30 % yield and the recovery of about 60 % of unchanged 2,3-diphenylquinoxaline 1 (Taylor and McKillop 1965). 

The formation of 2-phenylbenzimidazole 3 from 2,3-diphenylquinoxaline 1 and potassium amide must involve the initial addition of an amide ion at the C(2) carbon atom, as Ogg and Bergstrom (1931) had postulated, but with subsequent ring contraction, presumably with the elimination of benzylidenimine. This would result in the observed product 3, rather than the phenyl migration of the benzyl acid-rearrangement type (Scheme 6.2). 

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