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

The resolution of (RS)-alpha-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 epsilon range, the less-soluble salt was (S)-1 center dot(S)-2, while (R)-1 center dot(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 center dot(S)-2 and (R)-1 center dot(S)-2 crystals form a hydrogen-bonding network: however, (R)-1 center dot(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. (C) 2008 Elsevier Ltd. All rights reserved.