Viedma Ripening of Conglomerate Crystals of Achiral Molecules Monitored Using Solid-State Circular Dichroism

Abstract

Viedma ripening is the attrition-induced spontaneous chiral amplification of a conglomerate crystal mixture. To demonstrate the general nature of this deracemization process, we have extended attrition-enhanced chiral amplification to 10 achiral organic molecules that form conglomerate chiral crystals: benzil (1), diphenyl disulfide (2), benzophenone (3), tetraphenylethylene (4), guanidine carbonate (5), butylated hydroxytoluene (6), hippuric acid (7), ninhydrin (8), cytosine (9), and adeninium dinitrate (10). In these experiments the time required to reach homochirality was as low as 3 h and typically ranged from 25 to 50 h. In most cases amplification to homochirality of both enantiomers was observed in repeat experiments, although often in a nonstochastic fashion, reflecting the scalemic nature of the starting material. We have also demonstrated the utility of quantitative circular dichroism (CD) to determine enantiomeric excess in systems where chirality exists only in the solid-state.

Spontaneous Generation of Chirality in Simple Diaryl Ethers

“…It has recently been reported that benzil, diphenyl sulfide, benzophenone, tetraphenylethylene, guanidine carbonate, 2,6-di-tert-butyl-4-methylphenol, hipuric acid, cytosine, and ninhydrin may be optically active in commercial bulk samples. 50 In addition to 3 and 4, we found another three examples of "achiral" compounds commercially available in an optically active form: 2,6-diphenylphenol, 2-benzoyl pyridine, and antracene-9-carboxaldehyde (two bottles were optically active, one was racemic). All attempts to react optically active 2-benzoyl pyridine or antracen-9-carboxaldehyde with solid dimethylmagnesium gave racemic products.…”

Transmission vs. Diffuse Transmission in Circular Dichroism: What to Choose for Probing Solid‐State Samples?

“…This creates a range of possibilities for comparing structures, in particular, to seek differences between the two stereoisomers of a substance . It also enables the study of compounds that have only solid‐state chirality, thus achiral crystallizing in the chiral space group . Consequently, such an extended stereochemical analysis enables an examination of a larger group of compounds, including active pharmaceutical ingredients (APIs) and supramolecular systems.…”

How to Use Pasteur’s Tweezers

“…12 The deracemisation of achiral molecules that form chiral crystals is by no means limited to NaClO 3 and NaBrO 3 . Cytosine, diphenyl disulphide, tetraphenylethylene and ninhydrin, just to give a limited number of examples, have been deracemised in the crystal by use of attrition [69].…”

“…Application to the Mannich reaction has been described by Tsogoeva et al [71,72] and to an aldol condensation by Bolm et al [73]. Cuccia et al have described a rather broad application of attrition-induced deracemisation to a remarkable range of conglomerate crystals of intrinsically achiral organic molecules [69]. Attempts by us to use various organometallic catalysts for racemisation on nonactivated alcohols and amines have been so far unsuccessful as have been attempts to deracemise conglomerate helicenes by thermal activation.…”