Recyclization on interaction of arylhydrazones of 2-aroylmethyl-1H-benzimidazoles with ethyl isothiocyanate

Abstract

Recyclizations are unique as a possibility for obtaining functionalized compounds but often have narrow preparative limits, since they are extremely sensitive to the stability of the initial rings and the effect of substituents [1][2][3][4][5][6]. For example, phenylhydrazones of 2-aroylmethyl-1H-benzimidazoles 1a-f are not inclined to remake the heterocyclic ring on acid catalysis, but undergo Fischer indolization [7]. However compounds of type 1 (and of the related type 2) are readily recyclized under the conditions of an acylation reaction, by the action of aroyl chlorides or anhydrides of carboxylic acids they give 5-(2-acylaminoanilino)-1,3-diarylpyrazoles [8-10]. According to our hypothesis and with data of quantum-chemical calculations [11], such a conversion is possibly caused by the direction of the acylation reaction to the benzimidazole nitrogen atom of the initial compounds, with the intermediate formation of the corresponding highly reactive acylbenzimidazolium derivative, which spontaneously undergoes rearrangement as a result of intramolecular nucleophilic attack at its position 2 of the hydrazone amino group. Initiation of an analogous recyclization by weak electrophiles of the isothiocyanate type remains unknown and was studied in the present work for this reason.We started from two series of compounds, the phenylhydrazones of 2-aroylmethylbenzimidazoles 1a-f and arylhydrazones of 2-phenacylbenzimidazole 2a-c. We used ethyl isothiocyanate as the second component of the reaction.It was found that the reactants interact at a molar ratio of 1:2 on boiling in pyridine. The isothiocyanate is probably added at the benzimidazole nitrogen atom with the intermediate formation of benzimidazolium derivatives 3, 4, the recyclization of which may proceed further through spiranes of structure 5, 6. However it does not stop at the stage of forming 5-(2-thioureidoanilino)pyrazoles 7, 8. Under the reaction conditions one further cyclocondensation readily occurs, which leads to the previously unknown 1-(1,3-diaryl-1H-pyrazol-5-yl)-1,3-dihydro-2H-benzimidazole-2-thiones 9a-f and 10a-c.