Mechanism of solid-solid resolution of pantolactone

Abstract

The enantioselective solid-solid clathration of (S)-pantolactone ( I ) into (R,R)-trans-2,3-bis(diphenylhydroxymethyl)-l,4-dioxaspiro[4~4]nonane (2) and -[4.5]decane (3) was studied preparatively and mechanistically using atomic force microscopy (AFM) measurements and crystal packing data. Shortdistance solid-to-solid sublimation mechanisms occur in both cases with initial formation of epitaxial floes along the b-axis in 2 and random craters in 3. The bulk control in the phase rebuilding stage is understood from the particular crystal packings. Bulk control was largely lost in the phase transformation stage when passivation of the surfaces occurred in both cases. The host lattices of 2 and 3 exhibit closed molecular double layers with all hydroxyl groups inside and lacking access for intercalation of I. The reaction has to start at isolated surface defects. Once started, new doors for further entrance of guest molecules (S)-I are opened in the double layer. For practical use, both the crystallographic difficulties and the passivation have to be overcome. A slurry technique involving addition of stoichiometric amounts of water to the solids provided useful conditions for the preparative resolution of (R/S)-I or further racemates exhibiting passivation, whereas heating alone speeded up the resolution of 2-methylpiperwine with 2.

Organic Solid-State Reactions

“…They became twice as high and random in the phase transformation stage, as imaged in Ref. [54] Numerous solid (also liquid) racemates have been resolved by selective inclusion in various chiral hosts and finally isolated by distillation [52]. Extensions of these procedures are asymmetric photosyntheses by enforcing chiral conformers of achiral molecules in chiral hosts followed by irradiation.…”

Organic Solid-State Reactions with 100% Yield

“…Furthermore, (+)-b-ionone oxide [(+)-80] has been quantitatively included by (R,R)-(-)-79 upon grinding at room temperature. The quantitative inclusion of (S)-(-)-82 by (R,R)-(-)-81 required heating of coground solid mixtures to 80°C [44] or comilling at 25-30°C [22]. For the latter case and in the solid-state inclusion of (S)-(-)-82 by (R,R)-(-)-79,AFM investigations [44] indicated lowdistance solid-to-solid sublimation on the double layers with surface passivation that has to be broken for quantitative conversions in both cases by the above means, or by addition of water which partly dissolves the guest, a slurry technique that was also used to separate the racemate of pantolactone 82 by enantioselective inclusion [45].…”

The photodimerisation of the chloro-, methoxy- and nitro-derivatives of trans-cinnamic acid: a study of single crystals by vibrational microspectroscopy

“…13 Atomic Force Microscopy has also been employed and while this allows the progress of a reaction to be monitored it gives no information regarding the structures of intermediates or products of the reactions. [14][15][16][17] Infrared and Raman microscopy overcome many of these problems because the methods yield structural information while, at the same time, allowing small fragments (down to area limits of approximately 20 µm × 20 µm for infrared; 2 µm × 2 µm for Raman) to be studied.…”