Isomerization of 2-Phenacyl-1H-benzimidazole Arylhydrazones to 1-Aryl-5-(o-aminoanilino)-3-phenylpyrazoles by Trifluoroacetylation and Hydrazinolysis

Abstract

Recyclization is particularly attractive on account of the possibility of obtaining functionalized compounds with a mutual arrangement of structural fragments that is difficult to obtained by other methods of preparative organic chemistry [1][2][3][4][5]. It was interesting from this standpoint to develop a method for recyclization of 2-phenacyl-1H-benzimidazole arylhydrazones 1a-e to the isomeric previously unknown 1-aryl-5-phenyl(oaminophenyl)-3-phenylpyrazoles 2a-e. Solution of this problem may increase the prospects for the synthesis of new pyrazole-containing compounds (Scheme 1).It should be noted that the direct recyclization of compounds 1 to the required products is essentially intramolecular transamination, which must be subject to substantial steric and energetic hindrances. The process requires intramolecular nucleophilic attack by the not very reactive arylhydrazone fragment at position 2 of the extremely reactive benzimidazole system followed by opening of the imidazole ring on account of cleavage of the nitrogen-carbon bond. We were unable to find conditions for such direct isomerization. On heating and with acid catalysis phenylhydrazones of type 1 are transformed in a different direction and undergo Fischer indolization [6]. As we found earlier [7], the recyclization of 2-phenacyl-1H-benzimidazole phenylhydrazone (1a) can be initiated during acylation with benzoyl chloride, leading to the production of the N-benzoylsubstituted compound 3, which is not however transformed into the required product when heated with hydrazine hydrate for 12 h.We were unable to synthesize compounds 2 by using trifluoroacetic anhydride, which contains an easily removed acyl group.The reaction of compounds 1a-e with trifluoroacetic anhydride is accompanied by recyclization with the formation of 1-aryl-3-phenyl-5-(o-trifluoroacetylaminoanilino)pyrazoles 4a-e, the hydrazinolysis of which leads to the required anilinopyrazoles 2a-e.

Recyclization on acylation of 1-methyl-2-phenacyl-1H-benzimidazole phenylhydrazone

“…For the first compound in KBr intermolecular hydrogen bonds were displayed noticeably, but for the second they were less significant. It is also notable that the absorption band of the trifluoroacetyl group is displayed in KBr for compound 3b at 1700 [2], and for compound 3d at 1750 cm -1 . Nevertheless the structure of compound 3d is not in doubt, it was unequivocally established by us by the X-ray structural method.…”

Comprehensive DFT and MP2 Level Investigations of Reaction of 2,3-Dihydro-1,5-benzodiazepine-2-thiones with Hydrazine

“…The recyclization of heterocyclic compounds in reactions with hydrazine and its derivatives has been extensively studied experimentally and has been shown to be very important in organic synthesis. − Despite numerous predictions of the possible mechanisms of the recyclization processes, theoretical verification for the proposed mechanisms by quantum mechanical calculations has not been yet accomplished. In a recent paper, we reported the theoretical investigation on hydrazinolysis of 4-methyl-2,3-dihydro-1,5-benzodiazepin-2-one leading to 3-methylpyrazolone-5.…”

Facile Synthesis of Amine-Terminated Aromatic Polyamide Dendrimers via a Divergent Method

“…Therefore, we selected a trifluoroacetyl group due to its high stability toward an acid, good affinity to common organic solvents, and outstanding ability as a leaving group. It was found that trifluoroacetanilide was completely converted into aniline without producing any byproducts during the transamidation reaction with 2 equiv of hydrazine in N -methyl-2-pyrrolidone (NMP) at room temperature for 4 h, as shown in Figure . On the contrary, benzanilidea model compound of the dendrimer backbonefailed to react with hydrazine even at 80 °C for 1 day.…”