Influence of Some Thia- or Azasubstituted Butyric Acid Derivatives on the Chemical Shift of the Benzene Ring Carbon Atoms

Eight thia- or azasubstituted butyric acid derivatives were prepared and the influence of these substituents on the chemical shifts of the benzene ring carbon atoms was studied.


Introduction
For the synthesis of derivatives of (iso)thiochromanone and isoquinolone it was necessary to prepare eight appropriately substituted 4-phenyl-3-(or 4-)thia(or aza)butyric acids and derivatives 1.We now report a study of the influence of these substituents on the chemical shifts of the benzene ring carbon atoms of the compounds prepared (Table 1).

Results and Discussion
Chemical shifts of all of the compounds studied were assigned on the basis of comparisons between the experimental values acquired from recorded spectra and those calculated using the following programs: ACD / CNMR ver.1.1 [6], CS Chem Draw Pro, ver.4.5 [7] and ChemWindow3, ver.3.0.0with C13-module [8], respectively.We obtained a good agreement between the measured chemical shifts values and those calculated using all three programs.
Chemical shifts (δ) and the substituent chemical shift (∆ δ) of all of the compounds with heteroatoms in the β−position are in the same range for all compounds studied.The compounds with the heteroatom in the α-position (1b,d) have the ipso-carbon less shifted than the analogues having the heteroatom in the β-position (1a,1c,1e-1h).Substituent chemical shifts of meta-carbon atoms of the benzene ring of compounds 1a, 1b and 1d have positive values unlike all the other compounds: 1c, 1e-1h.
The influence of the studied substituents on the chemical shifts of the benzene ring carbon atoms of can be compared, for example with CH 2 SMe (1a, 1c), SMe (1b, 1d) or CH 2 NHCHMe 2 , CH 2 NMeCH 2 Ph substituents [9] which show good agreement with model compounds (see Table 2).Perhaps ∆δ for C ipso are slight reduced for all compounds by about 2 ppm and 1b, 1d have positive values for C ortho in comparison with the compounds bearing the SMe substituents, but this also depends on the solvents used [9].

General
The synthesis of thiabutyric acid derivatives was described long ago [1][2][3] but their 13 C NMR spectra have not been published until now.In the case of 3-azabutyronitrile derivatives, the modified Strecker method [4] was applied for the synthesis of the corresponding 2,2-tetramethylene analogs according to the lit.[5].NMR spectra were determined with a Bruker AC 200 FT-NMR spectrometer and are expressed in ppm downfield from tetramethylsilane (internal standard).