A Curious Case of Partial Spontaneous Resolution on Crystallization of a Racemate. The Crystal and Molecular Structures of N-Acetyl-DL-alanine Methylester and iV-Acetyl-L-alanine Methylester

Chirality, Racemate, Amino Acids /V-Acetyl-L-alanine methylester crystallizes in the orthorhombic space group P2\2\2\ with one molecule in the asymmetric unit (a = 7.768(1), b = 9.606(1), c = 10.215(2) A, Z = 4). The individual molecules are linked into infinite strands by intermolecular hydrogen bonds between the amide hydrogen atom as donor and the acetyl oxygen atom as acceptor. The strands run parallel to the crystallographic b axis. The respective racemate, /V-acetyl-DL-alanine methylester, crystallizes in the monoclinic space group P 2 i/n with three molecules in the asymmetric unit (,a = 14.442(3), b = 8.467(2), c = 19.336(5) Ä, ß = 93.68(1)°, Z = 12). Again, the individual molecules are linked into infinite strands by N-H” 0=C aCetyi hydrogen bonds which run along the crystallographic a axis. The individual strands are made up of molecules of opposite chirality in a 2:1 ratio. More specifically, one set of strands consists of molecules in the sequence [D, D, L,]oo while a second set has the sequence [l, l, Djoo as imposed by the centrosymmetry o f the space group. Thus, although crystals o f /V-acetyl-DL-alanine methylester contain equal amounts o f the molecules o f opposite chirality, the strand formation through intermolecular hydrogen bonds leads to an incomplete resolution o f the racemic mixture of molecules within one strand. The reason for the preference o f the observed structure o f /V-acetyl-DL-alanine methylester over spontaneous resolution is seen in the optimization o f hydrogen bonding within one strand versus the overall crystal packing energy. Some principles o f the crystallization o f achiral molecules, chiral m olecules, and racemates are briefly reviewed, as is the phenomenon o f spontaneous resolution.