Substituent effects on 1H and 13C NMR chemical shifts in α-monosubstituted ethyl acetates:: principal component analysis and 1H chemical shift calculations

A principal component analysis is applied to a-monosubstituted ethyl acetates (YCH2CO2Et), where the observed chemical shifts for the a-carbon atom, the carbonyl carbon, and the a-hydrogen atoms are correlated with theoretically derived molecular properties, i.e. the partial charges on the same atoms and the electronegativity and hardness. The effects on H-1 and C-13 NMR chemical shifts of 12 alpha-substituents: F, Cl, Br, I, OMe, OEt, SMe, SEt, NMe2, NEt2, Me, and Et were investigated. A strong grouping of the same heteroatom substituents is observed, showing the chemical shift dependence on the type of substituent. Halogenated compounds represent a heterogeneous group, where the large effect of the fluorine substituent is similar to that of the oxygen derivatives (OMe and OEt). Theoretical calculations show that fluorine and oxygen derivatives exhibit similar energy curves with respect to the Y-C-C=O dihedral angle and the same conformational equilibrium between cis and trans rotamers. Sulfur, neutral substituents and halogen derivatives (Cl, Br and I) give an equilibrium between cis and gauche rotamers, with a predominance of the gauche conformers. The rotational equilibrium in solution was confirmed by H-1 chemical shift calculations utilizing the CHARGE 7H program. The calculated a-hydrogen atom chemical shifts are in very good agreement with the measured values. Copyright (C) 2002 John Wiley Sons, Ltd.