How To Control Recognition: From Brucinium Double Salts to Racemic Resolution

Abstract

Studying the mechanisms of racemic resolution of the model compound N-(3-nitrobenzoyl)aspartic acid by formation and fractional crystallization of brucinium diastereomeric salts, we found that depending on the environment (solvents) the recognition leads to effective or ineffective racemic resolution. During successful racemic resolution, bis(brucinium)-N-(3-nitrobenzoyl)-L-aspartate hydrate methanol solvate precipitates as the first fraction. In turn, double salts and solid solution are formed in the fruitless racemic resolution. Formation of the double salt results from recognition of centrosymmetric anionic dimers on the common brucinium corrugated layer. The common brucinium corrugated layer together with its solvation sphere participates in recognition of the anions, leading to formation of the solid solution. Changing the solvent system according to its dielectric constant, more dispersive or more directional interactions gain importance. The racemic resolution and formation of bis(brucinium)-N-(3-nitrobenzoyl)-L-aspartate hydrate methanol solvate are related to three-point recognition of the anions by brucinium self-assembly.

Recognition in the Domain of Molecular Chirality: From Noncovalent Interactions to Separation of Enantiomers

“…884 Recently Białonśka et al studied the mechanisms of resolution of the N-(3-nitrobenzoyl)aspartic acid by formation and fractional crystallization of brucinium diastereomeric salts, finding that the recognition leads to effective or ineffective resolution depending on the nature of the solvent used in the process. 886 Double salts and solid solution were formed in the unsuccessful resolution, whereas during successful resolution, bis(brucinium)-N-(3-nitrobenzoyl)-L-aspartate hydrate MeOH solvate precipitates as the first fraction, owing to more dispersive or more directional interactions occurring as the solvent system changes according to its dielectric constant. On this basis, the racemic resolution and formation of bis(brucinium)-N-(3-nitrobenzoyl)-L-aspartate hydrate MeOH solvate was found related to three-point recognition of the anions by brucinium self-assembly.…”

“…In this regard, the ( R )- 52 ·(1 R ,2 S )-2-amino-1,2-diphenylethanol·2H 2 O crystal was arranged to form a sheet-like HB-network, together with two water molecules, rather than a columnar HB-network . Recently Białońska et al studied the mechanisms of resolution of the N -(3-nitrobenzoyl)­aspartic acid by formation and fractional crystallization of brucinium diastereomeric salts, finding that the recognition leads to effective or ineffective resolution depending on the nature of the solvent used in the process . Double salts and solid solution were formed in the unsuccessful resolution, whereas during successful resolution, bis­(brucinium)- N -(3-nitrobenzoyl)- l -aspartate hydrate MeOH solvate precipitates as the first fraction, owing to more dispersive or more directional interactions occurring as the solvent system changes according to its dielectric constant.…”

Spontaneous Resolution of RS-Fluoxetine to a Racemic Conglomerate upon Salt Formation with Oxalic Acid

“…A racemic conglomerate, as the outcome of the crystallization of a chiral racemate, termed spontaneous resolution, is much less probable than the formation of a racemic compound, reaching ∼5–10% of the cases. , The spontaneous resolution of racemic compounds is generally unpredictable. This context has driven the development of new crystallization-based resolution techniques. − …”

A bug in enantiomer separation: double salt formation – diastereomeric and double salt structures of 1-cyclohexylethylammonium 2- and 4-chloromandelate

“…In addition, by analogy of the above, there is also the possibility to obtain a crystalline salt that contains both enantiomers of the starting compound in 1 to 1 ratio and the resolving agent in optically pure form. Formation of such a so called double salt [6][7][8] is not so favoured by symmetry considerations, however other factors may promote its formation. The presence of the double salt during the optical resolution process practically sets the enantiomeric excess to zero in the product.…”