The influence of molecular structure and crystallization time on the efficiency of diastereoisomeric salt forming resolutions

Reciprocal resolutions between compounds (racemates and enantiomers) with similar structures have been examined. Amongst structurally similar compounds (so called relative structures) several N-acyl amino acids and amino acid esters were investigated. A part of the resolving agent or the racemic compound could be replaced by an achiral compound with a relative structure and an additive could occasionally improve significantly the efficiency of the resolution. Both the kinetic and the thermodynamic controls were observed as governing factors of the reciprocal resolutions.

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N-Acetyl phenylalanineC11H13NO3Ee >99.5% by chiral GC[α]D20=+35.6 (c 1, MeOH)Prepared from optically active materialAbsolute configuration: (S)

N-Acetyl phenylglycineC10H12NO3Ee >99.5% by chiral GC[α]D20=+74.2 (c 1, MeOH)Prepared from optically active materialAbsolute configuration: (S)

PhenylethylamineC8H12NEe >99.5% by chiral GC[α]D20=-10.5 (c 1, EtOH)Prepared from optically active materialAbsolute configuration: (R)