Influence Of Substituent Effects On The ¹³C NMR Chemical Shift Of Some Aliphatic Compouds

The study of Quantitative Structure Activity / Property Relationship involves a fundamental question of chemistry,that is,from the composition and structure of the chemical compound to quantitative predict its chemical properties or biology activities.Quantitative Structure-Spectrum Relationship(QSSR) study as a branch studies of QSAR / QSPR has been widely used to predict and explain the spectrum properties of various organic compounds (such as nuclear magnetic resonance spectroscopy and chromatography,etc.),to assign the spectrum "peaks",etc.The simulation of 13C NMR spectrum was attracted more attention than others,owing to the ¹³C NMR spectrum contains more information and it plays unique role in the identification of organic compounds,conformational analysis,as well as the reaction mechanism.In this paper,we obtained the simulation model of the ¹³C NMR spectrum for some aliphatic compound(include alcohols,amines,ethers,halogenated hydrocarbons) after studied the influence of substituent effects on the ¹³C NMR chemical shifts of these compounds,according to the current research of quantitative structure-activity and the basic principles of NMR.The computed results are testified fully agree to the experimental values. This paper was completed the following woks:A new QSPR model was established to calculate the ¹³C NMR chemical shift values of aliphatic alcohols,involving the electronegativity effect,polarizability effect,the electrostatic field effect and the steric effect.Using the partial net charge Q_i,atomic polarizability,the electrostatic field E,the steric effect S_OH and S_H as parameters,the relationship between the ¹³C NMR chemical shift and the parameters of substituent effects for aliphatic alcohols was carried out based on the linear free energy method.By introducing the values of these parameters and the experimental ¹³C NMR chemical shift values of alcohols(944 carbon atoms come from 91 alcohols,29diols) into the proposed model,the regression analysis was finished successfully and a detailed correlation expression with 7 parameters was obtained, whose correlation coefficient r is 0.9985 and the average absolute error between the calculated and the experimental values is 1.14 ppm.The cross-correlation was tested by the Leave-One-Out(LOO) cross-validation method,and the correlation coefficient r_cv is 0.9980 with an average absolute error of 1.16 ppm between the predicted and the experimental values. The proposed model perhaps lays a good foundation for computing the ¹³C NMR chemical shift values in more complex molecules.The ¹³C NMR chemical shift for an given carbon atom in aliphatic amine molecules was related to the atomic electronegativity,polarizability and steric effects of the substituents.The correlation equation between 307 ¹³C NMR chemical shift values and the parameters was carried out for 75 aliphatic amines(54 amines and 21 diamines),whose correlation coefficient r is 0.9943 and the average absolute error between the calculated and the experimental values is 1.51 ppm.The stability and prediction capacity of the model were tested using leave one out (LOO) cross validation method(R_cv=0.9940,R_cv²=0.9881,S_cv=1.54),and conformed by predicting forexternal compounds(55 different carbon atoms in 11 compounds).With the same methods,the correlation between the samples of 153 ¹³C NMR chemical shift values and the above parameters was carded out for 23 aliphatic ethers,and the expression was obtained,whose correlation coefficient r is 0.9990 and the average absolute error between the calculated and the experimental values is 0.85 ppm.The stability and prediction capacity of the model were tested by using leave-one-out(LOO) cross-validation method(R_cv=0.9980 R_cv²=0.9977 S_cv=0.89),and confirmed by predicting the external samples of 43 different carbon atoms in 4 external compounds.The ¹³C NMR chemical shift in methyl halide molecules was related to the atomic electronegativity,polarizability and stedc effects of the substituents.The correlation between the samples of 45 ¹³C NMR chemical shift values and the above parameters was carried out for 45 methyl halide.Influence of electronic effects and stedc effects on the ¹³C NMR chemical shift of other halogenated hydrocarbons(fluohydrocarbons,Chlorinated hydrocarbons,brominated hydrocarbons,iodochydrocarbons) are also discussed,and the calculated results using by the models proposed by this paper are satisfied with the experimental values.Obviously,the above-mentioned models are of intuitive,less computational expense,few parameters,clear physical meaning,and can offer precise predictions at last which will play an important role to help one fast determine the shift assignments and give an accurate structure elucidation in usual and laborious chemical practice.