Recyclization of methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1 H - pyrrole-2-carboxylates in reaction with monosubstituted hydrazines

Methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1 H -pyrrole-2-carboxylates react with phenyl-hydrazine or benzylhydrazine to give the corresponding methyl 1-(phenyl or benzyl)-5- (arylcarbamoyl)-4-cinnamoyl-1 H -pyrazole-3-carboxylates in good yields. The structures of the compounds obtained were proved by 1D 1 H, 13 C and 2D NMR experiments.


Introduction
6][7][8] Recyclization of 1H-pyrrole-2,3-diones by the action of monosubstituted hydrazines is a convenient method of synthesis of polyfunctional pyrazoles.These recyclization proceeds with the carbonyl group of acyl substituent at the С 4 of heterocycle 9,10 or ketone carbonyl group of dioxopyrrole. 11Reactions of methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1Hpyrrole-2-carboxylates with hydrazine derivatives were not studied.The molecular structures of compounds 3a-f were confirmed with by spectral and analytical data.For example, the IR spectra of 3a-f contain stretching bands of the amide NH-group as broadened bands in a range of 3253-3315 cm -1 , the stretching bands of the ester carbonyl group at 1717-1733 cm -1 , the stretching bands of the amide carbonyl group at 1667-1685 cm -1 , the stretching bands of the ketone carbonyl group at 1635-1655 cm -1 , the stretching bands of the cinnamoyl HC=CH group at 1615-1625 cm -1 , and amide II band was observed at 1553-1566 cm -1 .

Results and Discussion
Analysis of the 1 H NMR spectra (DMSO-d 6 ) of compounds 3a-f has show that besides the signals inherent to the protons of aromatic rings and the substituents attached thereto, the spectra exhibited a singlet from the methoxycarbonyl protons at δ 3.80-3.86ppm, doublets from protons at the double bond in the cinnamoyl fragment at δ 7.24-7.61ppm with a coupling constant 3 J of 15.8-16.1 Hz typical of trans-configured alkenes 12 and a signal from the amide NH proton at δ 10.72-10.95ppm.Methylene protons in the benzyl substituent of compounds 3b,d,f resonated as a singlet at δ 5.55-5.56ppm.
In the 13  However, the 1 H and 13 C NMR spectral data did not allow performing an unambiguous choice between two possible structures (type A or B) of the recyclization products 3a-f (Figure 1).In the absence of suitable crystals for X-ray analysis, we undertook a thorough analysis of the structures of pyrazoles 3 via NMR spectroscopy, including 2D 1 Н-13 С HSQC / HMBC and 1 Н-1 Н NOESY experiments of compounds 3d,e as an example (Figure 2).This made it possible to decide between two structures of pyrazoles 3 in favor of type B. The most downfield-shifted 13 C resonance in the 13 С spectra corresponds to the carbonyl carbon of cinnamoyl moiety ( C 185.8 and 185.9 ppm, respectively), as evidenced by correlations of these carbons with protons at the double bond H 2' , H 3' in the 2D 1 H-13 C HMBC spectra.
In the 2D HMBC spectrum of compound 3d, cross-peaks between protons of NCH 2 -group and carbons Ci, The proposed pyrazole structure of type B is also confirmed by the data of 2D 1 H-1 H NOESY experiment, which suggests that substituents at N 1 and C 5 in pyrazole are spatially close.In particular, the NH-proton of arylcarbamoyl substituent at C 5 in compound 3d gives the cross-peak with methylene protons of the benzyl substituent at N 1 ; and in compound 3e, with ortho-protons of phenyl substituent at N 1 (Figure 3).

Conclusions
We have succeeded in developing a method for synthesis of new functionalized pyrazole derivatives of potential synthetic and pharmacological interest from the recyclization of 1Hpyrrole-2,3-diones with phenylhydrazine or benzylhydrazine.Our work presents a very simple reaction performed under neutral conditions and in the absence of any catalyst.From a structural viewpoint, the products are polycarbonyl compounds suitable for further modification.High yields and the simple reaction and purification procedures are the key advantages of this approach.

Experimental Section
General.Melting points were obtained on a standard melting point apparatus in open capillary tubes.IR spectra (mineral oil) were recorded on a Perkin Elmer Spectrum Two spectrophotometer.
The 1 H and 13 C NMR spectra were recorded at 500.1 and 125.6 MHz respectively on a Bruker AVANCE III 500 spectrometer with DMSO-d 6 as solvent and TMS as internal standard.All signals in the 1 H and 13 C NMR spectra of compounds 3d,e were assigned on the basis of 2D 1 H- 13 C HSQC and HMBC experiments.All reactions monitored by TLC (silica gel, Silufol aluminum sheets, benzene-ethyl acetate 5:1).Elemental analyses for C, H and N were obtained using a LECO CHNS-932 analyzer.