Synthesis and structural characterization of products condensation 4-carboxy-1-( 4-styrylcarbonylphenyl )-2-pyrrolidinones with hydrazines

The synthesis of some new chalcones is described. A series of the pyrazole and pyrazoline type derivatives were obtained by the condensation of the chalcones with hydrazine and phenylhydrazine. All compounds were characterized using NMR, IR, MS techniques. Computer molecular modeling assisted for NMR spectral analysis.

The starting product -1-(4-acetylphenyl)-4-carboxy-2-pyrrolidinone 2 was synthesized according to the known method by the refluxing 4-aminoacetophenone 1 with itaconic acid in water.The chalcones 3a-c were obtained in good yields by base (NaOH) catalyzed aldol condensation of the substituted acetophenone derivative 2 and the substituted benzaldehydes in ethanol (Scheme 1).Compounds 3a-c were tested as precursors in the synthesis of the pyrazole and the pyrazoline derivatives (Scheme 2) by reaction with hydrazine hydrate or phenylhydrazine.
The structure of the above mentioned compounds was confirmed by NMR, IR and MS spectral data.The most comprehensive analytical data were obtained by NMR studies.The assignment was made on the substituents additivity rules, spectral characteristics of structurally related compounds, signal intensities and multiplicities.An APT 13 C NMR experiment was used to prove the interpretation of the carbon resonances in some cases.The data on 1 H and 13 C NMR chemical shifts are presented in experimental part.The carbon atoms are marked arbitrary according to the numbering given in Scheme 1 and Scheme 2.
ARKAT USA, Inc.The studied compounds possess nonsubstituted (a), OCH 3 (b) and Br (c) aromatic derivatives.Due to the substituent OCH 3 13 C NMR chemical shift of C-2 atom in compound 3b is shielded 2.5 ppm, while the atoms C-1 and C-3 were much less shielded (0.2 ppm and 0.1 ppm).Due to the Br substitution observed the low shielding effect 1.0 ppm for the C-1, and deshielding 0.7 ppm.for the C-2 atom. 1 H NMR spectra showed a weak shielding for H-1 and H-2 protons, especially for the H-2 proton (0.17 ppm) due to the Br substitution.Values of 63.7 ppm, 40.6 ppm and 148.3 ppm in 13 C NMR spectra of compounds 4a-c confirmed formation of the pyrazoline fragment after the condensation of the compounds 3a-c with the hydrazine hydrate in ethanol.Substitution of the aromatic ring (OCH 3 , Br) caused a low shielding effect for all carbon atoms of the pyrazoline moiety, only C-3 was negligibly deshielded.In the 1 H NMR spectra the 5-membered heterocyclic derivatives are observed as ABX type spin system pattern.Observed downfield chemical shift values of all the pyrrolidinone carbon atoms and the 4''-COOH carbon were caused by the interactions of the unsubstituted NH hydrogen with CO groups.
The spectra of the 5-membered heterocycles in compounds 5a-c and 6a-c changed significantly when substituents COCH 3 and Ph are attached in position 5.The substituent COCH 3 influenced C-1, C-2 and C-3 atoms about -4.2 ppm, 1.4 ppm and 5.3 ppm respectively.By the ascendancy of the substituent Ph the atoms of 5-membered heterocycle C-1 and C-3 is shifted upfield about -0.6 ppm and 4.1 ppm, C-2 -downfield up to 2.8 ppm.
The 5-membered heterocycle pyrazole in compounds 7a,b is characteristically influenced by phenyl substituents.The C-3 atom is found about 144.0 ppm, as in case of compounds 6a-c, while C-1 and C-2 are observed at ∼ 150.5 ppm and ∼ 104.9 ppm.
The average increments of the pyrazoline and the pyrazole for aromatic carbon atoms in 1,3,5-positions (A, B, C benzene rings) as for monosubstituted benzene rings were determined after assignment of all carbons of the studied compounds (Table 1).Values of the influences of CH=CH-CO fragment for A and B monosubstituted aromatic rings found in literature were verified.The increments of the pyrrolidinone ring, used in this calculation were found in previous our work. [34] Investigation of molecular structure of the studied compounds by the computer molecular modeling showed that all molecules are near to planar.Calculated Hückel charges successfully followed the chemical shifts of the studied compounds in 13 C NMR spectra (Table 2).
The charge allocation obtained by MM2 method for the optimized molecules models of studied compounds afforded ground for calculating the π-bond orders other than 1, 1.5, 2. The analysis of this computation showed the formation of the wide-ranging extended π-system in the molecules of compounds 3a-c, 7a,b (Table 3).-c).General Procedure.A solution of 0.002 mol of the corresponding chalcones 3a-c, 0.3 g (0.006 mol) of hydrazine hydrate and 10 ml of acetic acid was refluxed for 5 hours, then catalytic amount of HCI (4-5 drops) was added and yet refluxed for 30 min.After cooling 30 ml water was added and the resulting precipitate was filtered, washed with water.,b).General Procedure.A solution of 0.003 mol of the corresponding chalcones 3a-c, 0.43 g (0.004 mol) of phenylhydrazine and 10 ml of acetic acid was refluxed for 4 hours, when catalytic amount of HCl (4-5 drops) was added and yet refluxed for 30 min.After cooling 50 ml water was added and the resulting precipitate was filtered, washed with water.Purified by the repeated twice precipitation from 10% Na 2 CO 3 solution with acetic acid.

Table 1 .
The average increments of pyrazoline and pyrazole for chemical shifts of monosubstituted benzene carbons of the studied compounds

Table 3
Mass spectra were obtained on a Waters (Micromass) ZQ 2000 spectrometer using chemical ionization (CI) mode.Elemental analyses were performed on a CE-440 elemental analyser.The molecular modeling of the study compounds was carried out using Chem 3D Ultra 9.0 (Licence Cambridge Software Package, Serial number: 031 406391 4800).Hz, 4H, H ar ), 12.86 (s, 1H, COOH).