Physicochemical and Crystallographic Evidence for Polymorphism of the Racemic Ethyl (2‐Chloromethyl‐2,3‐dihydro‐5H‐oxazolo [3,2‐a]pyrimidin‐5‐one)‐6‐carboxylate

Chaimbault, Corinne; Bosc, Jean-Jacques; Léger, J. M.; Négrier, Philippe; Capelle, F.; Jarry, Christian

doi:10.1002/1520-6017(200011)89:11<1496::aid-jps12>3.0.co;2-7

Cited by 4 publications

(1 citation statement)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a survey of the Cambridge Structural Database (CSD), only 181 kryptoracemates structures have been identified showing that they represent only 0.1% of structures deposited in CSD . This fact agrees with the rarity of reports involving racemate and kryptoracemates as polymorphs in the literature. ,,,− In these research articles, chirality and symmetry have been attributed to different structural features of these compounds. While the chiral space group of racemates generates only one enantiomer in the asymmetric unit (ASU), the kryptoracemates show Z ′ > 1, and in most of them (about 60%) they exhibit a pseudosymmetric relationship between the enantiomers. ,, In addition, the self-assembly of chiral molecules in racemic chains motifs and their supramolecular chirality are the main structural differences between these polymorphs. ,, The formation of such polymorphs of racemic systems is well recognized, but they remain relatively unexplored.…”

Section: Introductionsupporting

confidence: 87%

Rare Case of Polymorphism in a Racemic Fluoxetine Nitrate Salt: Phase Behavior and Relative Stability

Carvalho

Ellena

Yufit

et al. 2016

Crystal Growth & Design

View full text Add to dashboard Cite

Polymorphism in racemic pharmaceutical compounds is relatively unexplored. However, this phenomenon may provide an additional tool to crystal engineering, opening the doors to rational design of chiral resolution, chiral enrichment, and chiral purification of pharmaceutical compounds. In this work we report two racemic polymorphs occurring for the nitrate salt of the antidepressant drug fluoxetine (FLX): a racemate (P2 1 /n, Z = 4, Z′ = 1) and a kryptoracemate (Pca2 1 , Z = 4, Z′ = 2). The relative stability of these polymorphs was established through a combination of techniques, namely, differential scanning calorimetric (DSC), thermogravimetric analysis (TGA), hot stage microscopy (HSM), and solubility measurements. Though the two polymorphs share some structural features, the N + −H•••O − hydrogen bonds have created dissimilar racemic motifs in their packing, resulting in different enantiomer orientations. The racemate is more stable over the temperature ranges we studied and is monotropically related to kryptoracemate. In our experiments, the obtaining of non-centrosymmetric lattice of racemic fluoxetine nitrate was shown to be dependent on kinetic factors. The thermodynamic relationships between both polymorphs were further confirmed by measuring their water solubility at 20 and 37 °C.

show abstract