SYNTHESIS AND CHARACTERIZATION OF ?-AMINO-N-PHENYL SUCCINIMIDE AS PRECURSOR FOR CORRESPONDING THIONIMIDES

Ibrahim S Al-Adham, Zuhair Muhi-Eldeen*, Elham Al-Kaissi, Tawfik Arafat, Bahaa Shafiq

ABSTRACT

The synthesis and structural elucidation of α-amino-N-phenylsuccinimide through the IR, hNMR, ORD, and elemental analysis was described as precursor to thionimides, L-(S)-aspartic acid served as starting material and was utilized to investigate routes applicable to the synthesis of α-amino-N-phenylsuccinimide of known absolute configuration. Various functional groups such as benzyloxycarbonyl group (cbz), t-butyloxycarbonyl group (BOC) were investigated in the synthesis. α-amino group protection utilizing the t-butyloxycarbonyl function proved most applicable to the synthesis of the desired L-α-amino-N-phenylsuccinimide hydrochloride. The five-step synthesis to the α-amino-N-phenylsuccinimide hydrochloride having the known L-(S) absolute configuration involves reaction of L-aspartic acid with some protecting group Z, followed by anhydride formation, reaction with aniline to form the anilide and subsequently ring closer affording the imide. Hydrolysis under mild acid conditions yielded optically pure L-(S)-α-amino-N-phenylsuccinimide. However, all attempts to convert this compound to the desired thionimide were not successful. The five-step sequence of the reactions involving the described protecting group was studied utilizing optical rotatory dispersion as a mean of detecting racemization. The sign of the Cotton effect for various intermediates in the synthesis of the final imide was correlated with the absolute configuration of the asymmetric center. NMR analysis of the ABX type for alicyclic protons of the imide ring was discussed. In all cases NMR analysis of the relatively flat heterocyclic ring showed cis-coupling (8.74-11.90 Hz) to be larger than trans-coupling (4.74-6.79 Hz). As expected, the germinal coupling for the extended π- system was larger than either cis- or trans-coupling.

Keywords: ?-amino-N-phenylsuccinimide, ionizing radiation, Protective agent, Stereochemistry, Optical rotatory dispersion, Alicyclic H-NMR analysis.