Solvent Effect on the Preparation of Ionic Cocrystals of dl -Amino Acids with Lithium Chloride: Conglomerate versus Racemate Formation

Oleksii Shemchuk, Enrico Spoletti, Dario Braga, Fabrizia Grepioni

Research output: Contribution to journalArticlepeer-review

Abstract

The hydrophobic dl-amino acids alanine, valine, leucine, and isoleucine have been cocrystallized with LiCl via solid-state and solution methods, and the effect of preparation conditions and solvent choice on the racemic versus conglomerate formation has been investigated. For the sake of comparison, enantiopure l-amino acids have also been reacted with LiCl in the same experimental conditions. With dl-alanine only, a racemic ionic cocrystal of formula dl-alanine·LiCl·H2O is obtained, irrespective of the preparation conditions, while the amino acids dl-valine and dl-leucine undergo spontaneous chiral resolution when MeOH is used in ball milling conditions, yielding monohydrated conglomerates, which at ambient conditions convert over time into the racemic ionic cocrystals dl-Val·LiCl·H2O and dl-Leu·LiCl·1.5H2O; these racemic ionic cocrystals (ICCs) are otherwise obtained in a single step if water is employed instead of MeOH, both in ball milling and solution conditions. dl-Isoleucine behaves differently, and product characterization is complicated by the presence of dl-alloisoleucine (dl-aIle) in the commercial starting material; solution crystallization in the presence of excess LiCl, however, unexpectedly results in the formation of the alloisoleucine conglomerate d-aIle·LiCl·H2O and l-aIle·LiCl·H2O, together with unreacted dl-isoleucine. Solid-state syntheses of the ionic cocrystals proceed in most cases via formation of intermediate metastable polymorphs; phase identification and structural characterization for all ICCs have been conducted via single crystal and/or powder X-ray diffraction.

Original languageEnglish
Pages (from-to)3438-3448
Number of pages11
JournalCrystal Growth and Design
Volume21
Issue number6
DOIs
Publication statusPublished - 2 Jun 2021
Externally publishedYes

Fingerprint

Dive into the research topics of 'Solvent Effect on the Preparation of Ionic Cocrystals of dl -Amino Acids with Lithium Chloride: Conglomerate versus Racemate Formation'. Together they form a unique fingerprint.

Cite this