Synthesis and spectral correlation study of some 3-(3,4-dichlorophenyl)-5-(substituted phenyl)-4,5-dihydro- 1 H -pyrazole-1-yl-ethanones

Some N-acetyl pyrazoles including 3-(3,4-dichlorophenyl)-5-(substituted phenyl)-4,5-dihydro- 1 H -pyrazole-1-yl-ethanones have been synthesised by solvent free cyclization cum acetylation of chalcones including substituted styryl 3,4-dichlorophenyl ketones using hydrazine hydrate and acetic anhydride in presence of catalytic amount of fly-ash: H 2 SO 4 catalyst. The yield of these N-acetyl pyrazole derivatives are more than 75 %. The synthesised N-acetyl pyrazoline derivatives were characterized by their physical constants and spectral data. The infrared spectral νC=N and C=O (cm - 1 ) frequencies, NMR chemical shifts (δ, ppm) of H a , H b , H c , CH 3 protons, C=N, C=O and CH 3 carbons of 1-(3-(3,4-dichlorophenyl)-5-(substitutedphenyl)-4,5-dihydro- 1 H -pyrazole-1-yl) ethanones have been assigned and correlated with Hammett substituent constants and Swain-Lupton’s parameters using single and multi-regression analysis. From the results of statistical analyses the effect of substituents on the above group frequencies and chemical shifts of the acetylated pyrazoles were discussed.

These 1-acetyl pyrazoline derivatives possess important biological activities such as antibacterial [6,7,10,13], endogenous proteolysis [12], cytotoxicity [11], EGFR kinase [8] and anti-inflammatory activities [9]. Spectroscopic data are useful for studying the ground state equilibration of organic compounds. The ultraviolet spectroscopic data of absorption maxima (λ max, nm) is also applied for prediction of the effect of substituents [16]. In pyrazoline molecules ( 1 H pyrazoles), the infrared spectra is used for predicting the effects of substituents on the vibrations of C=N, C-H, N-H [17]. From NMR spectroscopy, the spatial arrangements of the protons H a , H b and H c or H a , H b , H c and H d of the types shown in Fig. 1 were predictable by their frequencies with multiplicities viz., doublet or triplet or doublet of doublets. Based on the geometry, the chemical shift of the protons of respective pyrazoles has been assigned and the effects of substituent will be studied. The effects of substituent on the 2-naphthyl based pyrazoline ring protons were studied first by Sakthinathan et. al., [17]. In their study, they assigned infrared νC=N (cm - substituents. In these correlations they observed satisfactory r values. Thirunarayanan et al. [18] have studied the solvent free synthesis, spectral correlations of some 1-phenyl-3-(5bromothiophen-2-yl)-5-(substituted phenyl)-2-pyrazolines. Recently Thirunarayanan and Sekar have studied the microwave assisted synthesis and spectral correlation of some substituted 1-thiocarbomyl pyrazolines including 3-(3,4-dichlorophenyl)-5-(substituted phenyl)-4,5-dihydro-1 H-pyrazole-1-carbothioamides [19]. The literature survey reveals that there is no information available for solvent-free synthesis of some N-acetyl pyrazolines including 3-(3,4-dichlorophenyl)-5 (substitutedphenyl)-4,5-dihydro-1 H-pyrazole) derivatives by cyclization of the respective chalcones and acetic anhydride in presence of solid fly-ash: H 2 SO 4 catalyst. Therefore the authors have taken efforts to synthesis some N-acetyl pyrazolines including 3-(3,4dichlorophenyl)-5-(substitutedphenyl)-4,5-dihydro-1 H-pyrazole) derivatives by solvent free microwave assisted cyclization of chalcones, hydrazine hydrate and acetic anhydride in presence of catalytic quantity of fly-ash: H 2 SO 4 .
The purities of these pyrazolines were checked by their physical constants and spectral data published earlier in literature. Also the authors have recorded the infrared and NMR spectra of these synthesised N-acetyl pyrazoline derivatives for studying the Hammett spectral correlations.

1. Materials and methods
All chemicals used were procured from Sigma-Aldrich and E-Merck. Melting points of all pyrazoles have been determined in open glass capillaries on Mettler FP51 melting point apparatus and are uncorrected. Infrared spectra (KBr, 4000-400 cm -1 ) have been recorded on BRUKER (Thermo Nicolet) Fourier transform spectrophotometer.
The NMR spectra of all pyrazolines have been recorded on Bruker AV400 spectrometer operating at 400 MHz for recording 1 H and 100 MHz for 13 C spectra in CDCl 3 solvent using TMS as internal standard. Mass spectra have been recorded on SHIMADZU spectrometer using chemical ionization technique.
The solid, on recrystallization from benzene-hexane mixture afforded glittering product. The insoluble catalyst has been recycled by washing with ethyl acetate (8 mL) followed by drying in an oven at 100 °C for 1h and reused for further reactions. The analytical, physical constants and mass fragments of the synthesised 1-acetylpyrazolines were presented in Table1.
Where ν is the carbonyl frequencies of substituted system and ν 0 is the corresponding quantity of unsubstitued system; σ is a Hammett substituent constant, which is characteristics of the substituent and ρ is a reaction constant which depends upon the nature of the reaction.
The νC=N and C=O stretching frequencies (cm -1 ) with Hammett σ, σ + , σ I constants and F parameters has shown satisfactory correlation excluding 4-Cl, 4-OCH 3 , 4-CH 3 and nitro substituents. If these substituents included in the correlations, they reduced the correlations considerably. All correlations gave positive ρ value. This means that the normal substituent effects operate in all systems. The Hammett σ R constant and R parameters were fail in correlation. This is due to the weak resonance effect of the substituents, unable to transmit their effects on the stretching frequencies and is associated with the resonance -conjugative structure shown in Fig. 2.
. In view of the inability of some of the Hammett  constants to produce individually satisfactory correlations, it was thought as worthwhile to seek multiple correlations involving either  I and  R constants or Swain-Lupton's [27] F and R parameters. The correlation equations for CN and CO are given in equations (2)(3)(4)(5). ILCPA Volume 19

1. 2. 1 H NMR spectral study
The 1 H NMR spectra of synthesized 1-(3-(3,4-dichlorophenyl)-5-(substituted phenyl)-4,5-dihydro-1 H-pyrazole-1-yl) ethanones were recorded in deuteriochloroform solutions employing tetramethylsilane (TMS) as internal standard. The signals of the pyrazoline ring protons have been assigned. They have been calculated as AB or AA' systems respectively. The chemical shifts (ppm) of H a are at higher fields than those of H b and H c in this series of 1-acetyl pyrazolines. This is due to the deshielding of H b and H c which are in different chemical as well as magnetic environment. These H a protons gave an AB pattern and the H b proton doublet of doublet in most cases was well separated from the signals H c and the aromatic protons. The assigned chemical shifts (ppm) of the pyrazoline ring H a , H b and H c protons are presented in Table 2.
In nuclear magnetic resonance spectra, the 1 H or the 13 C chemical shifts (δ) depends on the electronic environment of the nuclei concerned. The assigned vinyl proton chemical shifts (ppm) have been correlated with reactivity parameters using Hammett equation in the form of where δ 0 is the chemical shift of unsubstitued ketones.
The results of statistical analysis of H b proton chemical shifts (δ, ppm) with Hammett substituent constants, F and R parameters were shown in Table 3. The H b proton chemical shifts (δ, ppm) with Hammett substituent constants, F and R parameters gave satisfactory correlation excluding 4-F, 4-OCH 3 and 4-NO 2 substituents. Hammett σ R constant has shown poor correlation. All correlation gave positive ρ values. The poor correlation is due to the absence or incapability of transmittance of resonance effect of substituent on the H b proton chemical shifts and it is associated with the conjugative structure shown in Fig. 2.
The results of statistical analysis of H c proton chemical shifts (δ, ppm) with Hammett substituents are presented in Table 3. The H c proton chemical shifts with Hammett σ, σ + , σ I , constants and F parameters gave satisfactory correlation excluding 4-F, 3-CH 3  in correlation was the reasons stated earlier and associated with conjugative structure shown in Fig. 2.
In view of the inability of the Hammett σ constants to produce satisfactory correlation individually, the authors think that it is worthwhile to seek multiple correlations involving either σ I and σ R constants or Swain-Lupton's [27] F and R parameters. The correlation equations for H a-c proton chemical shifts (δ, ppm) are given in (7)(8)(9)(10)(11)(12)(13)(14).

1. 13 C NMR spectra
Chemists, physical organic chemists and spectral analysts [16][17][18][19][21][22][23][24][25][26] have made extensive study of 13 C NMR spectra for a large number of ketones, styrenes keto-epoxides and pyrazolines. In their study, they investigated the linear correlation of the chemical shifts (ppm) of vinyl, C=N and carbonyl carbons with Hammett  constants, F and R parameters. In the present study, the 13 C chemical shifts (δ, ppm) of C=N, C=O and CH 3 carbon of 1-(3-(3,4-Dichlorophenyl)-5-(substituted phenyl)-4,5-dihydro-1 H-pyrazole-1-yl) ethanones have been assigned and are presented in Table 2. Attempts have been made to correlate the above assigned carbon chemical shifts (δ, ppm) with Hammett substituent constants, field and 54 ILCPA Volume 19 resonance parameters with the help of single and multi-regression analyses to study the reactivity through the effect of substituents. The chemical shifts (δ,ppm) observed for the C=N, C=O and CH 3 have been correlated with Hammett substituent constants and the results of statistical analysis are presented in Table 3. The C=N chemical shifts (δ, ppm) has shown satisfactory correlation with Hammett σ, σ + , σ I constants and F parameters excluding H, 4-F and 4-OCH 3 substituents. The resonance components were fail in correlation. All correlations gave positive ρ values. The failure in the correlation is due to incapability of transmittance of resonance effects of the substituents on the C=N carbon chemical shifts (δ, ppm). The chemical shifts (δ, ppm) observed for the C=O carbon of the 1-(3-(3,4-dichlorophenyl)-5-(substituted phenyl)-4,5dihydro-1 H-pyrazole-1-yl) ethanones have been correlated satisfactorily with Hammett substituent constants, F and R parameters excluding H, 4-F, 3-CH 3 and 4-CH 3 substituents. All correlation produced positive ρ values. This implies that the normal substituent effect operates in all systems.
The assigned methyl carbon chemical shifts of the 1-(3-(3,4-dichlorophenyl)-5-(substituted phenyl)-4,5-dihydro-1 H-pyrazole-1-yl) ethanones have been correlated with Hammett substituent constants, F and R parameters and the results of statistical analyses were shown in Table 3. From the table, the Hammett σ, σ + , σ R constants and R parameters gave satisfactory correlations excluding 2-Cl. 4-Cl and 3-CH 3 substituents. The Hammett σI constant and F parameters were fail in correlation. All correlations gave positive ρ values. This means that the normal substituent effect operates in all systems. The failure in the correlation was due to the reason stated earlier and it is associated with the resonanceconjugative structure shown in Fig. 2.
In view of the inability of some of the σ constants to produce individually satisfactory correlation, the authors think that, it is worthwhile to seek multiple correlation involving all either σ I , σ R or F and R parameters [27]. The generated correlation equations are given in (15)(16)(17)(18)(19)(20).