Reactions of α -cyanochalcones with phenylhydrazine

α -Cyanochalcones react with phenylhydrazine in acetic acid, forming 5-cyano-1-phenyl-3,4,6-triaryl-1 H -pyrazolo[3,4-b ]pyridines, while retroaldol condensation takes place in ethanol under acidic catalysis. The structures of the compounds obtained were determined by elemental analysis, IR, 1 H NMR-spectroscopy and X-ray study


Introduction
1,3-Diarylpropenones (chalcones) and their derivatives are known to be suitable reagents for synthesis of various heterocyclic systems, building-blocks and biologically active compounds. 1or instance, a number of heterocyclic derivatives were obtained starting from chalcones. 2 Generally, the presence of a CN-group in an α-position to a CO-group in the molecule of α-cyanochalcone should extend it's activity towards 1,2-binucleophiles because of extrapolarization of C=C double bond.After preliminary Michael addition by C=C-bond, binucleophile can alternatively attack CN-group or CO-group; furthermore, the first step of interaction may occur by CO-group, which is also highly polarized.Hence, this issue remains open.
The reaction of α-cyanochalcones with phenylhydrazine was realized by two ways: 1) in refluxing ethanol using catalytic amounts of H 2 SO 4 ; 2) in refluxing glacial acetic acid.
It was found that in ethanol in the presence of catalytic amounts of H 2 SO 4 α-cyanochalcones 2a-d underwent retroaldol condensation, resulting in formation of the corresponding phenylhydrazones 3a and 3b, in accordance with data 3 (Scheme 1).
If the reaction was carried out in glacial acetic acid, its pathway changed.Thus, the corresponding pyrazolo [3,4- IR-spectra of compounds 4a-d did not contain C=O-group signals, but, in contrast, the signal of CN-group (2200 cm -1 ) was present.The signal of the vinyl proton disappeared in 1 H NMRspectra of the compounds 4a-d (comparing with starting chalcones 2a-d), besides, the signals of two nonequivalent Ar 2 -substituents and Ar 1 -substituent were present.
Interestingly, compounds 4a-d possessed intensive luminescence both in the solid state and in solutions in ethanol, acetonitrile or ethyl acetate.Luminescence weakened in the presence of acids.
The structure of compound 4a was finally determined by X-ray diffraction analysis (Figure 1).

Figure 1
We proposed the following scheme of the compounds 4 formation.At the first step the retroaldol condensation of cyanochalcone takes place and formation of the corresponding 5-aminopyrazole 5 occurs, which interacts with another molecule of α-cyanochalcone, giving cyclic compound 6, which at the next step easily undergoes an oxidizing aromatization to the compound type 4 (Scheme 2).

Scheme 2
Signals at 5.1 ppm and 9.6 ppm were observed in the 1 H NMR-spectra of crude product 4b.We associated them with CH-and NH-protons of the intermediate like 6.After crystallization from ethanol only pure compounds 4a-d were obtained, so this fact pointed on the slight aromatization of the compounds like 6 even under action of air.Besides, we confirmed the proposed scheme by alternative synthesis of compound 8 starting from the α-cyanochalcone 2c and the aminopyrazole 5b (Scheme 3).This way is close to what has been reported 6 that led to formation of 5-cyano-1,3,4,6-tetraaryl-1H-pyrazolo [3,4-b]pyridines with non-equivalent substituents in positions ( 3) and ( 6) of pyrazolo [3,4-b]pyridine cycle.The regioselectivity of interaction of 5-amino-3-arylpyrazoles to chalcones, as well to α-cyanochalcones, was shown earlier. 6,7 fluxing of compounds 2c and 5b in glacial acetic acid resulted in the formation of the 1,4-dihydroderivative 7.There were the singlets of 1,4-dihydroform CH-and NH-protons in 1 H NMR-spectra of compound 7, which were similar to those for non-purified product 4b.
The compound 7 (its suspension in ethanol, in the presence of piperidine) was easily oxidized by air bubbling (the conditions of recrystallization of crude products 4а-d), forming the fully aromatic system 8 (Scheme 3).Yields, melting points and spectroscopic data of compounds obtained are given below (see Table 1).
α-Cyanochalcones (2a-d).The solution of the corresponding 3-aryl-3-oxopropanenitrile 1 (0.01 mol), appropriate aromatic aldehyde (0.012 mol) and 3 drops of piperidine in 6 ml of n-AmOH was refluxed for 15 minutes.After cooling the precipitate formed was filtered off, washed with n-AmOH, hexane and air-dried.The air was bubbled during 8 h through the suspension of the compound 7 (0.2 g, 0.4 mmol), N-methylmorpholine (1 ml) and 30 ml of EtOH at r.t.During the bubbling dissolution of compound 7 occurred.The solvent was removed under reduced pressure, the residue was cooled to give the precipitate of compound 8, which was filtered off, washed by EtOH and dried.

Table 1 .
Yields, melting points, elemental analysis and spectroscopic data of compounds 1-8