Hammett spectral correlations in benzofuranyl flavonols

A series containing eleven benzofuranyl flavonols have been prepared by cyclization of 3-hydroxybenzofuranyl chalcones with 30 % hydrogen peroxide in the presence of sodium bicarbonate. The synthesized flavonols were characterized by their physical constants, analytical and spectroscopic data. The infrared spectral νOH, CO stretches(cm -1 ), NMR chemical shifts of OH, CO(δ, ppm) of these flavonols were assigned and correlated with Hammett substituent constants, F and R parameters using single and multi linear regression analysis. From the results of statistical analyses, the effects of substituents on the above group frequencies were discussed.


INTRODUCTION
Hammett spectral correlation is useful for predicting the ground state equilibration of organic molecules such as unsaturated carbonyl compounds [1], alkenes [2], polyenes [3], acyl halides and its esters [4]. Infrared spectra are a good tool for analyzing the structure of organic molecules, qualitative and quantitative measurements, s-cis and s-trans equilibration of unsaturated ketones, antiand gaucheform of acyl halides and esters [4,5]. The NMR spectroscopy was utilized for predicting spatial arrangements of the E or Z isomers and conformers in unsaturated ketones, pyrazolines and it derivatives [6,7]. The effect of substituents on the above molecular conformers and isomers also studied through Hammett substituent constants, F and R parameters [8]. Thirunarayanan have studied the effect of substituents on spectral frequencies in thiadiazole-2-amines [9].
Joseph et al have studied the effect of substituents on dimethyl phenyl chalcones by Hammett equation with spectral data [10]. Sekar and Thirunarayanan have studied the spectral correlation in pyrazoline derivatives [11]. The substituent effects on oxazine-2amines were studied using spectral data using single and multi-regression analysis [12]. Kamalakkannan et al have studied the substituent effects on 2-indolyl chalcones by electrochemical redox potential with Hammett equation [13].
Within the above view there is no report available for the study of effect of substituents on the 3-hydroxy-2-(substituted phenyl)-4H-pyrano [3,2-b][1]benzofuron-4-ones through spectral data using regression analysis. Therefore the authors have taken effort to prepare some 3-hydroxy-2-(substituted phenyl)-4H-pyrano [3,2-b][1]benzofuron-4-one derivatives and recorded the infrared and NMR spectra for studying the effect of substituents on the spectral frequencies.

1. General
All chemicals and solvents used in this present study were procured from Sigma-Aldrich and Merck companies. The infrared spectra of all oxazine imines have been recorded in SHIMADUZ Fourier Transform IR spectrophotometer using KBr disc. The NMR spectra of all compounds were recorded in BRUKER AV 400 type spectrometer, using CDCl 3 as a solvent, 400 MHz frequency was applied for recording 1 H, 100 MHz for 13 C NMR spectra, taking TMS as standard.

General procedure for synthesis of 3-hydroxy-2-(substituted phenyl)-4H-pyrano [3, 2-b][1]benzofuron-4-one derivatives
About 2 mmol of 3-hydroxybenzofuranyl chalcones, 5 mL of 5 % sodium bicarbonate, 10 mL of ethanol were vigorously stirred in the three necked flask under cooling condition (Scheme 1). To this reaction mixture, added drop-wise 5 mL 30 % hydrogen peroxide through dropping funnel for half an hour duration and continued the stirring to one hour and it was kept overnight.
The mixture was diluted with 20 mL of water and acidified with concentrated H 2 SO 4 (5-7 mL). The obtained solid product was filtered at the pump washed with water, dried and recrystallized with ethanol. The analytical, physical constants and spectroscopic data of synthesized substituted flavonols were presented in Table 1.

1. Infrared spectral study
Infrared spectra of all synthesized 3-hydroxy-2-(substituted phenyl)-4H-pyrano[3,2b][1]benzofuron-4-ones were recorded in KBr disc technique. From the spectra, the authors have expected the doublet for the carbonyl stretches (cm -1 ) due to presence of cyclic α, βunsaturated moiety. But the doublet was not observed. It may happened by the suppression of hydroxyl group attached in α-position. The assigned νCO and OH stretches (cm -1 ) were presented in Table 1. These data are correlated with Hammett substituent constants, F and R parameters by linear regression analysis. In the infrared spectral correlation, the Hammett equation was taken in the form as: where ν o is the frequency for the parent member of the series, ν is the frequency for the substituted member of the series, ρ is the reaction constants and it depends on reaction conditions such as temperature and concentration, σ is the substituent constants.

International Letters of Chemistry, Physics and Astronomy Vol. 25
operates in all systems. Similarly the multi-regression analysis gave good correlation with Swain-Lupton's [20] σ I , σ R substituent constants, F and R parameters. The generated multiregression analysis equations are given in (2)  This supports that the normal substituent effects operates in all systems. The failure in correlation for R parameters is due to the inability of transmittance of substituent effects of substituents on the νCO stretches and associated with the resonance conjugative structure as shown in Fig. 1. The R parameter was failed in single regression analysis. This is worthwhile, when seeking in the multi-regression analysis with Swain-Lupton's [20] σ I , σ R substituent constants, F and R parameters. The generated multi-regression analysis equations are given in (4) and (5).

2. NMR spectral study
The NMR chemical shifts (δ, ppm) of OH and CO protons and carbons of 3-hydroxy-2-(substituted phenyl)-4H-pyrano [3, 2-b][1]benzofuron-4-ones were assigned and presented in Table 1. These chemical shifts (δ, ppm) were correlated with Hammett substituent constants, F and R parameters using single and multi-parameter correlations. In this NMR spectral correlation, the Hammett equation was employed as, δ = ρσ + δ o … (6) where δ o is the chemical shift (δ, ppm) for the parent member of the series, δ is the chemical shift (δ, ppm) for the substituted member of the series, ρ is the reaction constants and it depends on reaction conditions such as temperature and concentration, σ is the substituent constants.
The results of statistical analyses were presented in Table 2. From the Table 2, the correlation of OH and CO protons and carbon chemical shifts (δ, ppm) of 3-hydroxy-2-(substituted phenyl)-4H-pyrano [3,2-b][1]benzofuron-4-ones were failed with Hammett substituent constants, F and R parameters. All correlations gave positive ρ values. This supports that the normal substituent effects operates in all systems. The reason for failure of correlation was stated earlier and associated with resonance conjugative structure as shown in Fig. 1. In view of the inability of prediction of effect of substituents on the OH and CO protons and carbon chemical shifts (δ, ppm), they are worthwhile and produce satisfactory correlations when seeking in multi-regression analysis with Swain-Lupton's [20] σ I , σ R substituent constants, F and R parameters. The generated multi-regression analysis equations are given in (

CONCLUSION
Totally eleven benzofuranyl flavonols [3-hydroxy-2-(substituted phenyl)-4Hpyrano [3,2-b][1]benzofuron-4-ones] have been prepared by cyclization of 3hydroxybenzofuranyl chalcones with 30 % hydrogen peroxide in the presence of sodium bicarbonate. The synthesized flavonols were characterized by their physical constants, analytical and spectroscopic data. The infrared spectral νOH, CO stretches(cm -1 ), NMR chemical shifts of OH, CO(δ, ppm) proton and carbons of these flavonols were assigned and correlated with Hammett substituent constants, F and R parameters using single and multi International Letters of Chemistry, Physics and Astronomy Vol. 25 linear regression analysis. From the results of statistical analyses, νOH, CO stretches (cm -1 ), gave good and satisfactory correlation in single and multi-regression analysis.
The NMR chemical shifts of OH, CO (δ, ppm) proton and carbons of these flavonols were failed in single parameter correlation and satisfactory in multi-parameter correlation.