Crystal engineering: a novel strategy for the resolution of chiral compounds

The chemical industry often deals with chiral molecules, also called enantiomers. These are two molecules with the same chemical formula but that are mirror-like due to the different orientation of some functional groups. Enantiomers of the same molecule are often indicated with D and L or with R and S. Both enantiomers of the same molecule have the same physical-chemistry properties, but they might differ in pharmacological active and bioavailability. In fact, one enantiomer might provide the desired effect while the other might be ineffective or, even worse, toxic. For this reason, chirality is an important issue in the pharmaceutical industry, where enantiomers of Active Pharmaceutical Ingredients (APIs) need to be carefully differentiated and separated. To overcome this challenge, crystallization comes might be a suitable selective separation strategy. In fact, by creating a diastereomers salts of one specific enantiomer it is possible to separate two chiral components without the use of expensive techniques, such as chromatography. This separation process, also called resolution of a racemic mixture, occurs by “Resolving agent” to the solution. The resolving agent can preferentially precipitate with a specific enantiomer, allowing the separation from the other. In this work different amines with a chiral centre were tested as resolving agents for a model compound, Malic Acid. The natural enantiomer of the molecule is the L form; hence the use of resolving agents can allow the isolation of the D form. A screening of different compound was carried out through slurry crystallization. Afterward, a complete characterization of the crystal is done extrapolating all the necessary information. Result show that (1S,2R)-2-Amino-1,2-diphenylethanol, (R)-1-Phenylethylamine, (S)- 1-Phenylethylamine, (R)-1-(1-napthyl)ethylamine and (S)-1-(1-napthyl)ethylamine have formed diastereomer salts and a common features was noticed in all of them, a Benzyl group.