Spectral QSAR and QPR study of some ( E )-4-(((2-hydroxy-6-(substituted phenyl)-1,6-dihydropyrimidin-4-yl)methyl)diazenyl)benzoic acid derivatives

A series of titled compounds were synthesized and recorded the infrared and NMR spectra. The assigned spectral group frequencies were correlated with Hammett substituent constants, F and R parameter. From the statistical analysis results, the effect of substituents on the spectral group frequencies has been studied

Kalyanasundaram and his coworkers have studied the spectral correlation analysis of Hammett substituent constants and biological activities of some (E)-1-(4-phenoxyphenyl)-3phenylprop-2-en-1-ones [21]. Within the above view there is no report available in the literature for the study of effect of substituents through Hammett equation with spectral data for the titled compounds. In the present study, the authors have taken effort for studying the QSAR and QPR of spectral data of the titled compounds by synthesis and recorded their infrared and NMR spectra.

1. General
The infrared spectra of all compounds were recorded in SHIMADUZ Fourier Transform IR spectrophotometer using KBr disc technique. 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.

RESULTS AND DISCUSSION
In the present investigations, the authors have evaluated the effect of substituents on the assigned spectral frequencies using Hammett equation with Hammett substituent constants and Swain-Lupton's [23] constants by single and multi-linear regression analysis.

1. IR spectral study
In infrared spectral study, the Hammett equation is employed for evaluation of effect of substituents on the CO, N=N, CN, OH and NH stretches with Hammett substituent constants. In this correlation, the Hammett equation was utilized as, where ν is the frequency for the substituted system, ρ is the reaction constants in terms of intercept, σ is the substituent constants and ν o is the frequency for the parent member of the series.
The assigned CO, N=N, CN, OH and NH stretches (ν, cm -1 ) of all (E)-4-(((2-hydroxy-6-(substituted phenyl)-1,6-dihydropyrimidin-4-yl)methyl)diazenyl)benzoic acid derivatives are presented in Table 1. The results of statistical analysis [11][12][13][14][15][16][18][19][20][21] are shown in Table 2. From the table 2, the correlation of νCO stretches of all compounds gave satisfactory correlation for Hammett σ, σ + , and σ I constants. The Hammett σ I constants, F and R parameters were fail in correlations. This due to the inability of effect of substituents on the carbonyl group and associated with the resonance-conjugative structure as shown in Fig. 2. All correlations gave positive ρ values. This may mean that the normal substituent effects operated in all system. The N=N stretches (ν, cm -1 ) of pyrimidine derivatives were produced satisfactory correlation coefficient with Hammett substituent constants and F and R parameters along with positive ρ values.

International Letters of Chemistry, Physics and Astronomy Vol. 36
The C=N stretches (ν, cm -1 ) of pyrimidine derivatives were produced poor correlation coefficient with Hammett substituent constants and F and R parameters along with positive ρ values. The reasons for the poor correlation of this stretches are stated earlier and associated with resonance-conjugated structure as shown in Fig. 2.
The OH stretches (ν, cm -1 ) of pyrimidine derivatives were produced poor correlation coefficient with Hammett σ, σ + , σ I constants and F parameters. The resonance components of the substitutes were fail in correlation. All correlation gave positive ρ values. The reasons for the failure correlation of this stretches were stated earlier and associated with resonanceconjugated structure as shown in Fig. 2.
The NH stretches (ν, cm -1 ) of pyrimidine derivatives were produced satisfactory correlation coefficient with Hammett substituent constants and F and R parameters along with positive ρ values.
Among these correlations some of the correlation gave poor coefficients. They are worthwhile when they are subjected to multi-regression analysis. In multi parameter correlation with Swain-Lupton's [18] parameters, these stretches produced satisfactory correlations. The generated multi-regression analysis equations are shown in (2-11).

2. 1 H NMR Spectral study
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 of hydrazide have been correlated with reactivity parameters. Thus the Hammett equation was used in the form as shown in (12).
A satisfactory correlation were obtained for CH 2 proton chemical shifts (δ, ppm) of pyridines with Hammett σ R constant and R parameter. The remaining Hammett sigma constants and F parameters were fail in correlation.
The correlation of CH-N proton chemical shifts (δ, ppm) of pyridines gave satisfactory coefficients with Hammett σ, σ + , σ I constant and F parameter. The resonance components of the substituents were fail in correlation.
A poor correlation were observed for the correlation of CH=C proton chemical shifts (δ, ppm) of pyridines with Hammett substituent constants F and R parameters. All correlations gave positive ρ values. This is implies that the normal substituent effect operates in all system. The reason for failure in correlations of assigned proton chemical shifts were already stated earlier and is associated with the resonance-conjugative structure as shown in Fig. 2.
Some of the chemical shifts of assigned NH 2 , CH 2 , CH-NH and CH=C proton chemical shifts (δ, ppm) of pyrimidines have shown poor correlation in single parameter analysis. While seeking these chemical shifts are worthwhile, they are indulged in multi-parameter correlation. They produced satisfactory correlation either inductive and resonance International Letters of Chemistry, Physics and Astronomy Vol. 36 components or field and resonance components combined. The generated multi-regression equations are shown in (13)(14)(15)(16)(17)(18)(19)(20).
The results of statistical analysis are shown in Table 2. From Table 2, the correlation of CO carbon chemical shifts (δ, ppm) of hydrazides with Hammett substituent constants and F and R parameters were satisfactory. The correlation of CH 2 carbon chemical shifts (δ, ppm) were fail in correlation with Hammett substituent constants and F and R parameters. The CN carbon chemical shifts (δ, ppm) pyrimidines were shows satisfactory correlation with Hammett substituent constants and f and R parameters. The failure in correlation is due to the reasons stated earlier and was associated with the resonance-conjugative structure as shown in Figure 2.
The chemical shifts (δ, ppm) of CH 2 pyrimidines have shown poor correlation in single parameter analysis. While seeking these chemical shifts (δ, ppm) CO, CH 2 , and CN are worthwhile, they are indulged in multi-parameter correlation. They produced satisfactory correlation either inductive and resonance components or field and resonance components combined. The generated multi-regression equations are shown in (21-

CONCLUSIONS
A series of dihydropyimidine methyl diazenyl benzoic acid derivatives have been prepared and recorded their IR and NMR spectra. The assigned spectral group frequencies were correlated with Hammett substituent constants, F and R parameters. From the results of statistical analysis, almost all frequencies were shown satisfactorily correlations in both single and multi-parameter correlation analysis. There is a normal substituent effect operates in all systems evident with positive ρ values.