IR and 1H NMR Spectral Studies of some 2-Amino-4-Isopropyl-6-Methoxy-N-Phenylpyrimidine-5-Carboxamides: Assessment of Substituent Effects

A series of 2-Amino-4-isopropyl-6-methoxy-N-phenylpyrimidine-5-carboxamide compounds have been synthesized from various substituted dithioacetal and guanidine. The purities of these compounds were checked by their physical constants, UV, IR, NMR and MASS spectral data. The IR and 1 HNMR spectral data of these compounds have been correlated with Hammett sigma constants, F and R parameters using single and multi-linear regression analysis. From the results of statistical analysis, the effects of substituents on the spectral group frequencies have been discussed.

The effects of substituent on the infrared group frequencies (ν, cm -1 ) and NMR chemical shifts (δ, ppm) of 2-amino-4-isopropyl-6-methoxy-N-phenylpyrimidine-5-carboxamide compounds. In their studies, they observed satisfactory and good correlations for each spectral data with Hammett substituent constants, F and R parameters.

1 General
All chemicals used were purchased from Sigma-Aldrich and E-Merck chemical companies. Melting points of all chalcones were determined in open glass capillaries on Mettler FP51 melting point apparatus and are uncorrected. Infrared spectra (KBr, 4000-400 cm -1 ) were recorded AVATAR-300 Fourier transform spectrophotometer. Bruker AV400 NMR spectrometer was used for recording NMR spectra operating at 400 MHz for 1 H spectra and 125.46 MHz for 13 C spectra in CDCl 3 solvent using TMS as internal standard. Mass spectra of all chalcones were recorded on SHIMADZU spectrometer using chemical ionization technique.

Synthesis of substituted 2-amino-4-isopropyl-6-methoxy-N-phenylpyrimidine-5carboxamides
All substituted 2-Amino-4-isopropyl-6-methoxy-N-phenylpyrimidine-5-carboxamide were synthesized and their purities were examined by procedure published in literature [23]. An equi-molar quantities of substituted dithioacetal (2 mmol) and guanidine (2 mmol), in the presence of sodium methoxide were refluxed for 6h and the completion of the reaction was monitored by thin layer chromatography. After completion of the reaction, the solid product was separated by filtration. Further the product was purified by column chromatography using dichloromethane and ethyl acetate mixture as eluent. The general structure of the carboxamides was shown in Fig. 1.
The infrared frequencies for carbonyl absorption are assigned based on the assignments made by Hays and Timmons [24] for CO at 1640, C=N at 1580, NH 2 at 3400 and -O-C-O-at 1200 cm -1 , respectively. The assigned infrared frequencies have been correlated with Hammett substituent constants and Swain-Lupton's constants [25]. In this correlation the structure parameter Hammett equation employed is as shown in the following equation: Where ν is the carbonyl frequencies of substituted system and ν 0 is the corresponding quantity of unsubstituted system; σ is a Hammett substituent constant, which in principle is characteristics of the substituent and ρ is a reaction constant which is depend upon the nature of the reaction.
The Hammett substituent constants and F parameters gave satisfactory correlation with C=N stretches. The remaining Hammett substituent constant σ R and R parameter have given poor correlation. This is due to the reasons stated in earlier and associated with the resonance conjugative structure. And all the compounds have positive ρ values.
Except R parameter, the Hammett substituent constants and F parameters gave satisfactory correlation with NH 2 stretches. The reasons stated in earlier and associated with the resonance conjugative structure for the correlations fail with NH 2 stretches.
The Hammett substituent constants and F and R parameters gave satisfactory correlation with -C-O-C-stretches and all correlations gave positive ρ values.
From Table 2, the chemical shifts values of -NH 2 and -OCH 3 (δ, ppm) correlated with Hammett substituent constants and F parameter gave satisfactory correlation except R parameter.
From Table 2, the chemical shifts values of -CONH (δ, ppm) correlated with Hammett substituent constants and F and R parameter gave satisfactory correlation. The other correlations were fail. This is due to the reasons stated earlier and associated with the resonance conjugative structure as shown in Fig. 2.
Some of the single parameter correlations with Hammett substituent constants were not obeyed in the regression. While seeking these parameters in multi-regression, with F and R Swain-Lupton's [33] constants, they gave satisfactory correlations with the chemical shifts of (δ, ppm ) Hα and Hβ. The multi correlation equations are given in (10)(11)(12)(13)(14)(15).

CONCLUSIONS
Totally ten substituted 2-amino-4-isopropyl-6-methoxy-N-phenylpyrimidine-5carboxamide compounds have been synthesized and their purities were examined by literature method. The IR and 1 H NMR spectral data of these chalcones have been assigned and correlated with Hammett sigma constants, F and R parameters using single and multi-linear

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ILCPA Volume 38 regression analysis. From the results of statistical analysis, the effects of substituents on the spectral group frequencies have been discussed. Satisfactory correlations coefficients(r) obtained for many single and all multi parameter correlations.