Molecular Recognition in the Formation of Conglomerate Crystal. 2. The Role of Arenesulfonic Acid in the Conglomerate Crystals of Amino Acid Salts

Abstract

The structures of conglomerate crystals, p-chlorobenzenesulfonic acid salt of l-alanine, p-toluenesulfonic acid salt of l-serine, and benzenesulfonic acid salt of l-leucine, were determined by X-ray analysis. The crystals are built up of repeating units consisting of two amine components and two acid components to form a helical column by hydrogen bonds. The arrangements of the arenesulfonic acids are found to be similar to each other in these systems. Moreover, the arrangements have similarity to those of cinnamic acid in the crystals of cinnamic acid salts of (R)-1-phenylethylamine and of (R)-1-(4-isopropylphenyl)ethylamine, which are also conglomerates. These results suggest that our proposed criteria for the choice of an achiral derivatizing agent in the transformation of a racemic compound into a conglomerate crystal is appropriate.

Deracemization of a Racemic Compound via Its Conglomerate-Forming Salt Using Temperature Cycling

“…One way around this restriction is by converting a racemic compound into a conglomerate salt: For a series of chiral compounds it has been shown that the probability of forming a conglomerate salt is 2 to 3 times larger than of forming a single component conglomerate . Recently, Spix et al managed to apply Viedma Ripening to racemic amino acid compounds, e.g., dl -Phenylalanine (Phe), via the formation of its conglomerate salt with 2,5-xylenesulfonic acid (XSA). , Their results showed that using a conglomerate forming salt enables the utilization of Viedma Ripening to racemic compounds. This would expand the application range of Viedma Ripening by roughly 10 times, if such conglomerate forming salts exist.…”

“…13 Recently, Spix et al managed to apply Viedma Ripening to racemic amino acid compounds, e.g., DL-Phenylalanine (Phe), via the formation of its conglomerate salt with 2,5-xylenesulfonic acid (XSA). 14,15 Their results showed that using a conglomerate forming salt enables the utilization of Viedma Ripening to racemic compounds. This would expand the application range of Viedma Ripening by roughly 10 times, if such conglomerate forming salts exist.…”

Anion Effect on the Binary and Ternary Phase Diagrams of Chiral Medetomidine Salts and Conglomerate Crystal Formation

“…The effect of anions as conglomerators on the crystal structure of racemates was studied, mostly concerning racemic coordination complexes and limited types of organic racemates were investigated from this point of view …”

“…13 The effect of anions as conglomerators on the crystal structure of racemates was studied, mostly concerning racemic coordination complexes [14][15][16][17][18][19] and limited types of organic racemates were investigated from this point of view. [20][21][22][23][24][25][26] The structural and thermoanalytical investigations of the rac-α-phenylethylammonium salts have proved that the hydrogen phthalate and hydrogen malonate anions form racemic compounds, while the hydrogen succinate anion forms a conglomerate, the latter being the only one which could be resolved by preferential crystallization. 22 A comparison of the structures has revealed that the hydrogen bonding network in hydrogen phthalate and hydrogen malonate salts are very similar, while the hydrogen succinate salt is different.…”

Resolution of racemates with achiral reagents

“…These methods can be applied to the resolution of amino acids as salts with aromatic sulfonic acids, which are known to be conglomerates. 26 The idea of using a deficiency of the conglomerator (Scheme 1) was extended to crystallization with a deficiency of the achiral solubiliser promoting the solubility of the compound to be resolved. As mentioned above, Werner complexes 2 and 3 highly differ in solubility, therefore the Clanion can be considered as a solubiliser, and a spontaneous resolution can be expected when crystallising with its deficiency.…”