Experimental and theoretical study of the proton methoxy chemical shifts of substituted 3,4-dimethoxyphenethylamines and maleimide/phthalimide derivatives

Proton chemical shifts of the following substituted ortho-dimethoxyphenethylamine derivatives: N-2-(2-nitro-4,5-dimethoxyphenyl)ethylphthalimide (1); N-2-(2-nitro-4,5-dimethoxyphenyl)ethylmaleimide (2); 2-nitro-4,5-dimethoxyphenylethylamine (3); N-2-(2-bromo-4,5-dimethoxyphenyl)ethylphthalimide (4); N-2-(2,3-dinitro-4,5-dimethoxy-phenyl)ethylphthalimide (5); 3,4-dimethoxyphenylethylamine (6), N-2-(3,4-dimethoxyphenyl)ethylmaleimide (7), N-2-(3,4-dimethoxyphenyl)ethylphthalimide (8) were determined in the present work. Significant differences between chemical shifts of methoxy groups of N-2-(2-nitro-4,5-dimethoxyphenyl)ethylphthalimide (1) compared to those of the other studied compounds were found. It is attributed to the differential influence of the phthalimide group on the methoxy groups. Methoxy group (2) is closer to the phthalimide group, so it is shielded by the π system, resulting in a significant lower chemical shift than methoxy group (1).Calculated 1H chemical shifts for some of the above molecules showed that lower-energy conformers play a relevant role to achieve good agreement with experimental data. The inclusion of conformers lying about 2 kcal/mol above the lowest-energy conformer for each molecule reduced dramatically absolute errors in chemical shifts, and allowed the assignment and interpretation of experimental data.