Rotational isomers of N-(β-phenylpropionyl)alanine ethyl dithioester: a Raman spectroscopic and MO study

Raman spectra of N-(β-phenylpropionyl)alanine ethyl dithioester (C₆H₅CH₂CH₂C(O)NHCH(CH₃)C(S)SC₂H₅) in CCl₄ and CH₃CN solutions were measured as a function of temperature and the enthalpy differences (ΔH) between rotational isomers differing by internal rotation around the NHCH(CH₃) and CH(CH₃)C(S) bonds (forms A, B and C₅) were evaluated from relative band intensities. The spectroscopic results are consistent with a greater thermodynamical stability of the B-type conformer, where the N and S_(thiol) atoms are in close contact. In addition, a comparison of the measured ΔH_(A-B) for the present molecules with previously reported values for a series of similar glycine-based ethyl dithioesters shows that the presence of the extra CH₃ group at the α-carbon atom leads to a stabilization of the B-type conformer relative to the A-type form in the alanine-based dithioester. Semiempirical AM1 molecular orbital calculations were also performed on the title molecule and on its glycine analogue, N(β-phenylpropionyl)glycine ethyl dithioester. In general terms, the results of these calculations agree with the experimental findings, thus providing good theoretical support for the experimental data.