Untitled

2005

Self Cite

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.

mentioning

confidence: 79%

“…The reactions and the purity of the products were monitored by TLC on Silufol UV-254 plates in the 9:1 benzene-ethanol solvent system (with development in UV light). Compounds 1a,b and 3 were obtained by the methods in [7,8].…”

Section: Methodsmentioning

confidence: 99%

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

2005

Self Cite

“…The IR spectra of compounds 6a,b were recorded on a UR-20 instrument for KBr tablets. The starting materials were prepared by known methods: 1 [10], 5 [6], 7a-i [5, 11[, and 9 [12]. Before determination of elemental composition and spectroscopic properties the synthesized compounds were dried for 7 h in a water pump vacuum desiccator at 115°C.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and tautomerism of 2-[3(5)-aryl(methyl)pyrazol-4-yl]-1-benzimidazoles

2006

Self Cite

An efficient method has been developed for the synthesis of 2-[3(5)-aryl(methyl)pyrazol-4-yl]-1H-benzimidazoles by cyclocondensation of 2-acylmethyl-1H-benzimidazoles benzoylhydrazones with DMFdimethylacetal. The tautomerism of the compounds obtained via migrations of a proton between the pyrazole nitrogen atoms has been studied by 1 H NMR. The more stable tautomers have electron acceptor aryl substituents placed at position 3 of the pyrazole ring and electron donor aryl substituents or a methyl at position 5.The tautomerism of pyrazole compounds due to the migrations of a proton between the nitrogen ring atoms has been systematically studied [1-3] since it depends unpredictable of the nature and position of the ring substituent. It influences the selectivity of a series of chemical reactions and has to be taken into account when determining the structure and chemical purity of the corresponding substrates by spectroscopic methods. The effect on it of the electronic effects of the two aryl substituents at positions 3 (or 5) and 4 of the heterocycle has not been studied up to this time. It is possible that such a situation is due to the absence of samples and methods suitable for carrying out a reliable investigation. Thus, starting from 2-phenacylbenzimidazole 1 via its formylation product 2 and subsequent reaction with hydrazine, we have obtained the pyrazole 3a which, according to 1 H NMR data exists in solution in equilibrium with its tautomeric form 3'a [4]. The signals of the pyrazole ring aromatic proton for both tautomers are seen separately and would seem suitable and unproblematic for qualitative and quantitative determination of the composition of the equilibrium. However, the hoped for assignment of signals to a specific tautomer is complicated by the lack of a sample for comparison. In addition, the method itself is limited for the preparation of a broad series of compounds for a number of reasons, in particular the poor selectivity in the final stage reaction. Hence we set ourselves the task of overcoming the problem by preparing a series of compounds of type 3 and studying their tautomeric behaviour.Routes for an efficient synthetic method were not obvious and we therefore chose a method of trial and error in the reactions of 2-phenacylbenzimidazole 1 and its hydrazones. Hence we tried a possible synthetic route analogous to the known method of preparing 2-(4-pyrazolyl)benzimidazoles [5] based on the cyclocondensation of compound 1 with aroylhydrazines. However, the corresponding reaction with formylhydrazine occurs to give a mixture of products, from which we isolated only 1-(3-pyrazolyl)-benzimidazole 4. The result of the reaction is unexpected. However, the structure of the product is not in doubt because we had obtained it before by refluxing 2-phenacylbenzimidazole hydrazone 5 in DMF [6].

“…It should be noted that the starting compound 1a exists in solutions in equilibrium with an enamino ketone tautomeric form [13] but the obtained products 6 and 7 do not show a similar tendency to isomerize to form 8. On the other hand, the reaction of 2-acetonyl-1H-benzimidazole 1b with the azlactones 2a and 3a occurs by the route revealed for compound 1a but is complicated by a prototropic isomerization.…”

mentioning

confidence: 96%

Cycloaddition of 2-acylmethyl-1H-benzimidazoles to 4-arylidene-1,3-oxazol-5-ones

2007

Self Cite

Pyrido[1,2-a]benzimidazoles possess a broad spectrum of biological activity [1][2][3][4][5][6], have fluorescence properties [7], and are a component of light sensitive materials [8,9]. We hoped to prepare previously unavailable derivatives on the basis of the reaction of 2-acylmethyl-1H-benzimidazoles of type 1 with 4-arylidene-1,3-oxazol-5-ones (azlactones) of type 2 and 3 for the following reasons. 2-Aminobenzimidazole reacts regioselectively with azlactones to give pyrimido[1,2-a]benzimidazoles, in such a way that the exocyclic amino group is acylated as a result of opening of the oxazole ring and the endocyclic by addition to the arylidene fragment [10]. It is advisable to use compounds of type 1 as the 1,3-dinucleophile component. In the first place 2-phenacyl-1H-bezimidazole 1a is acylated by carboxylic acid anhydrides at the active methylene group [11]. In the second, azlactones are analogs of cyclic anhydrides which react with active methylene compounds to form C-acylation products [12].We have found that the reaction of compound 1 with azlactones 2a-f, 3a-c indeed occurs efficiently via the cycloaddition of a 1,3-dinucleophile to a 1,3-dielectrophile. However, the products of the expected structure 4 or any kind of prototropic isomers were not formed. A contrary scheme of regioselective construction or the ring is achieved via acylation at a benzimidazole nitrogen atom (possible by the intermediate formation of compound 5) and Michael addition of the methylene group to the arylidene fragment to give the previously unknown N-(3-aryl-4-benzoyl-1-oxo-1,2,3,4-tetrahydropyridino[1,2-a]benzimidazol-2-yl)benz-and -acetamides 6a-f, 7a-c.The reaction was carried out by refluxing in pyridine and is complete after 1 h. The product yields were 70-95%.