Resolution of α-methylbenzylamine via diastereomeric salt formation using the naturally based reagent N-tosyl-( S)-phenylalanine together with a solvent switch technique

Abstract

The resolution of ( RS)-α-methylbenzylamine 1 with the naturally based reagent N-tosyl-( S)-phenylalanine 2 via the diastereomeric salt formation method together with the solvent switch technique has been investigated. In various alcoholic solvents with a wide ε range, the less-soluble salt was ( S)- 1·( S)- 2, while ( R)- 1·( S)- 2 was obtained when dioxane was used as a resolving solvent system. The highest enantiomeric purities of ( S)- 1 and ( R)- 1 were obtained from 2-PrOH and dioxane/MeOH, respectively. The X-ray single-crystal analysis showed that both ( S)- 1·( S)- 2 and ( R)- 1·( S)- 2 crystals form a hydrogen-bonding network; however, ( R)- 1·( S)- 2 contains dioxane molecules without incorporation in the hydrogen-bonding network. The drastic effect of dioxane on the present system is interpreted as space filling.