Preheated fly-ash catalyzed cyclization of chalcones: Synthesis of some substituted pyrazole-1-carbothioamides and spectral correlations in 3-(3,4-dichlorophenyl)-5-(substituted phenyl)-4,5-dihydro-1 H -pyrazole-1-carbothioamides

Some substituted 1-thiocarbomyl pyrazolines including 3-(3,4-dichlorophenyl)-5-(substituted phenyl)-4,5-dihydro-1 H -pyrazole-1-carbothioamides using solvent-free preheated fly-ash catalyzed cyclization between chalcones and thiosemicarbazide microwave irradiation. The yields of these thiocarbomyl pyrazolines are more than 80 %. The purities of these synthesised pyrazoline derivatives are checked by their physical constants and spectral data earlier reported in the literature The spectral data of these 3-(3,4-dichlorophenyl)-5-(substituted phenyl)-4,5-dihydro-1 H -pyrazole-1-carbothioamides had been correlated, using single and multi-linear regression analysis.

Patil et al., [37] have synthesised 60-85 % yields of 1-thiocarbomyl-2-(2,4-dichloro-5fluorophenyl)-5-(substituted phenyl)-pyrazoline derivatives using microwave with alumina/K 2 CO 3 as catalyst. Spectroscopic data applied for predicting the ground state equilibrium of organic compounds. The uv absorption maxima (λ max, nm) is also applied for prediction of effect of substituents [31]. In pyrazoline molecules ( 1 H pyrazoles), the infrared spectra is utilized for predicting the effects of substituents on the vibrations of C=N, C-H, N-H [21]. 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 assigned from their frequencies with multiplicities viz., doublet or triplet or doublet of doublets. Based on the stereo chemical terms, the chemical shifts of the protons of respective pyrazoles have been assigned and the effects of substituent were studied. The effects of substituent on the 2-naphthyl based pyrazoline ring protons were studied first by Sakthinathan et. al., [21]. In their study, they assigned infrared νC=N (cm - [23] have synthesised some 1-phenyl-3-(5-bromothiophen-2-yl)-5-(substituted phenyl)-2-pyrazolines by solvent free method and investigated the effect of substituents using spectral data with Hammett substituent constants and F and R parameters. The literature survey reveals that there is no information available for solvent-free synthesis of some substituted thiocarbomyl pyrazolines including 1-thiocarbomyl-2-(3,4-dichlorophenyl)-5-(substituted phenyl)pyrazoline derivatives by cyclization of the respective chalcones and thiosemicarbazide in presence of solid pre heated fly-ash. Therefore the authors have taken efforts to prepared some thiocarbomyl pyrazolines including 1-thiocarbomyl-2-(3,4-dichlorophenyl)-5-(substituted phenyl)-pyrazoline derivatives by solvent free microwave assisted cyclization of chalcones and thiosemicarbazide in presence of preheated fly-ash. 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 3-(3,4-dichlorophenyl)-5-(substituted phenyl)-4,5-dihydro-1Hpyrazole-1-carbothioamides for studying the Hammett spectral correlations.

1. General
All chemicals used were procured from Sigma-Aldrich and E-Merck. Fly-ash was collected from the Thermal Power Plant II, Neyveli Lignite Corporation, Tamilnadu, India. Melting points of all pyrazole-1-carbothioamides 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.

Preparation of preheated fly-ash
The preheated fly-ash has been prepared by the procedure reported in the literature [38]. The fly-ash was heated on hot air oven at 110 °C for 2 h. During the heating demoisturising takes place. This preheating helps for avoiding colloidal formation during the reaction.

3. Synthesis of substituted pyrazole-1-carbothioamide derivatives
Appropriate equi-molar quantities of chalcones (2 mmol), thiosemicarbazide (2 mmol) and preheated fly-ash (0.5 g) were taken in a 50 mL borosil glass tubes. The mixture was subjected to microwave irradiation for 4-6 minutes in a microwave irradiation at 550 watts, 2540 MHz frequency, 140 °C and atmospheric pressure in a microwave oven (Scheme 1) (Samsung Grill, GW73BD Microwave oven, 230 V A/c, 50 Hz, 2450 Hz, 100-750 W (IEC-705). The completion of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to room temperature. The product was isolated by adding 10 mL of dichloromethane and evaporation. The solid, on recrystallization from benzene-hexane mixture afforded glittering product. The insoluble catalyst has been recycled by washing with 20 ILCPA Volume 15 ethyl acetate (8 mL) followed by drying in an oven at 100 °C for 1h and reused for further reactions.

RESULTS AND DISCUSSION
In our research laboratory, we attempts to synthesize substituted pyrazoline-1carbothioamides derivatives by cyclization of chalcones and thiosemicarbazide in the presence of preheated fly-ash catalyst in microwave irradiation. Hence the authors have synthesized the substituted 1-thiocarbomyl pyrazoline derivatives by the cyclization of 2 mmole of chalcone, 2 mmole of thiosemicarbazide in microwave irradiation with 0.5 g preheated fly-ash catalyst at 550W, 4-6 minutes (Samsung Grill, GW73BD Microwave oven, 230 V A/c, 50 Hz, 2450 Hz, 100-750 W (IEC-705), (Scheme 1). During the course of this reaction preheated fly-ash assisted for the cyclization between chalcones and thiosemicarbazide to elimination of water followed by proton transfer gave the 1thiocarbomyl pyrazolines. The yields of the pyrazolines in this reaction are more than 80 %.
The chalcones containing electron donating substituent (-OCH 3 ) gave higher yields than electron-withdrawing halogens and -NO 2 substituents. Further we have investigated this cyclization reaction with equimolar quantities of the styryl 3,4-dichlorophenyl ketone (entry 25 ) and thiosemicarbazide under the same condition as above. In this reaction the obtained yield was 85 %. The effect of catalyst on this reaction was studied by varying the catalyst quantity from 0.1 g to 1 g. As the catalyst quantity is increased from 0.1 g to 1 g, the percentage of yield of product is increased from 80 to 85 %. Further increase the catalyst amount beyond 0.4 g, there is no significant increasing the percentage of the product. The effect of catalyst loading is shown in (Fig. 2). The optimum quantity of catalyst loading was found to be 0.4 g. The results, analytical and mass spectral data are summarized in Table 1.
The reusability of this catalyst was studied for the cyclization of styryl 2,4dichlorophenyl ketone and thiosemicarbazide (entry 25) is presented in Table 2. From the Table 2, first two runs gave 85 % product. The third, fourth and fifth runs of reactions gave the yields 84.5 %, 84.5 % and 84 % of 1-thiocarbomyl pyrazolines. There was no appreciable loss in its effect of catalytic activity were observed up to fifth run. The effect of solvents on the yield also studied with methanol, ethanol, dichloromethane and tetrahydrofuran from each component of the catalyst (entry 25). The effect of solvents on the yields of 1-thiocarbomyl pyrazolines was presented in Table 3 International Letters of Chemistry, Physics and Astronomy Vol. 15 pyrazolines obtained from the cyclization of chalcone and thiosemicarbazide with the catalyst preheated fly-ash in microwave irradiation.

2. 1 H NMR spectral study
The 1 H NMR spectra of synthesised 3-(3,4-dichlorophenyl)-5-(substituted phenyl)-4,5dihydro-1H-pyrazole-1-carbothioamide derivatives (entries 25-34) under investigation have been recorded in deuteriochloroform solution employing tetramethylsilane (TMS) as internal standard. The signals of the 3-(2,4-dichlorophenyl)-5-(substituted phenyl)-4,5-dihydro-1Hpyrazole-1-carbothioamides 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 International Letters of Chemistry, Physics and Astronomy Vol. 15 those of H b and H c in this series of 1-thiocarbomyl 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 4.
In nuclear magnetic resonance spectra, the 1 H or the 13 C chemical shifts (δ, ppm) depend on the electronic environment of the nuclei concerned. These chemical shifts have been correlated with reactivity parameters. Thus the Hammett equation may be used in the form as shown in (8): Log δ= Log δ 0 + ρσ where δ 0 is the chemical shift of the corresponding parent compound.
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 [50] F and R parameters. The correlation equations for H a-c proton chemical shifts (δ, ppm) are given in (9)

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ILCPA Volume 15 (ppm) of vinyl and carbonyl carbons with Hammett  constants, F and R parameters in alkenes, alkynes, acid chlorides and styrenes.
In the present study, the chemical shifts (δ, ppm) of 3-(3,4-dichlorophenyl)-5-(substituted phenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamides C=N and C=S carbon have been assigned and are presented in Table 4. Attempts have been made to correlate the above assigned carbon chemical shifts (δ, ppm) with Hammett substituent constants, field and resonance parameters with the help of single and multi-regression analyses to study the reactivity through the effect of substituents.
The observed C=N and C=S chemical shifts (δ, ppm) of synthesised 3-(3,4dichlorophenyl)-5-(substituted phenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamides have been correlated with Hammett substituent constants and the results of statistical analysis are presented in Table 5. The C=N chemical shifts (δ, ppm) has shown satisfactory correlation with Hammett σ I , σ R constants and F parameters excluding 4-Br and 4-NO 2 substituents. The remaining Hammett substituent constants and R parameter were fail in correlation. The failure in the correlation is due to incapability of transmittance of the resonance effect of the substituents on the C=N carbon chemical shifts (δ, ppm). The chemical shifts (δ, ppm) observed for the C=S carbon of the 3-(3,4-dichlorophenyl)-5-(substituted phenyl)-4,5dihydro-1H-pyrazole-1-carbothioamides have been shown poor correlation with Hammett substituent constants, F and R parameters along with negative ρ values. The failure in the correlation was due to the reason stated earlier and it is associated with the resonanceconjugative structure shown in Fig. 3. 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 either σ I , σ R or F and R parameters [50]. The generated correlation equations are given in (15) to (18)
International Letters of Chemistry, Physics and Astronomy Vol. 15