Thermodynamic stability studies of racemic and conglomerate enantiomeric crystals.
Date
2004
Authors
Marriott, Robert A.
Journal Title
Journal ISSN
Volume Title
Publisher
Dalhousie University
Abstract
Description
Enantiomeric compounds can form crystals of two main types: conglomerates (1:1 mechanical mixture of optically pure crystals) or racemic crystals (1:1 enantiomers within the same crystal lattice). Conglomerates are less common than racemic crystals, and compounds which form conglomerate crystals generally are easier to resolve. Thermodynamic studies of the relative stability of conglomerate and racemic crystals could aid in the understanding and control of enantiomeric resolutions.
In this thesis, the thermodynamic changes on forming racemic crystals from the corresponding conglomerates have been investigated with emphasis on mandelic acids. Using a thermodynamic cycle and the fusion values, the thermodynamic changes for this process have been shown to be uncertain due to the common assumption that the solid-liquid heat capacity differences at the fusion temperature are zero. Semi-empirical investigations of the correlation between intermolecular rotational symmetry and flexibility with ideal gas, solid and liquid heat capacities, have shown that the solid and liquid heat capacity difference for various organic compounds can be estimated. This estimation has been applied to thermodynamic calculations involving enantiomeric crystals, to improve cycle calculation methods.
Furthermore, the experimental heat capacities of enantiomeric mandelic acid, o-fluoromandelic acid and o-chloromandelic acid crystals have been measured and used to independently calculate entropy and enthalpy changes from T = 0 K to above the fusion temperatures. Rac-mandelic acid was found to be entropically stabilised relative to its conglomerate, and this is linked to less hindered phenyl ring motion. Rac-o-fluoromandelic acid was found to the enthalpically stabilised and entropically destabilised relative to its conglomerate, and this is correlated with a stronger hydrogen bond network.
Overall, both enthalpic and entropic factors have been found to be potentially important for the relative stability of racemic and conglomerate enantiomeric crystals. However, the enthalpic differences were found to be more general than the entropic differences. Thus it would seem that if one wants to choose molecules which are more likely to form conglomerates, soft flexible molecules with sterically demanding groups would be favourable.
Thesis (Ph.D.)--Dalhousie University (Canada), 2004.
In this thesis, the thermodynamic changes on forming racemic crystals from the corresponding conglomerates have been investigated with emphasis on mandelic acids. Using a thermodynamic cycle and the fusion values, the thermodynamic changes for this process have been shown to be uncertain due to the common assumption that the solid-liquid heat capacity differences at the fusion temperature are zero. Semi-empirical investigations of the correlation between intermolecular rotational symmetry and flexibility with ideal gas, solid and liquid heat capacities, have shown that the solid and liquid heat capacity difference for various organic compounds can be estimated. This estimation has been applied to thermodynamic calculations involving enantiomeric crystals, to improve cycle calculation methods.
Furthermore, the experimental heat capacities of enantiomeric mandelic acid, o-fluoromandelic acid and o-chloromandelic acid crystals have been measured and used to independently calculate entropy and enthalpy changes from T = 0 K to above the fusion temperatures. Rac-mandelic acid was found to be entropically stabilised relative to its conglomerate, and this is linked to less hindered phenyl ring motion. Rac-o-fluoromandelic acid was found to the enthalpically stabilised and entropically destabilised relative to its conglomerate, and this is correlated with a stronger hydrogen bond network.
Overall, both enthalpic and entropic factors have been found to be potentially important for the relative stability of racemic and conglomerate enantiomeric crystals. However, the enthalpic differences were found to be more general than the entropic differences. Thus it would seem that if one wants to choose molecules which are more likely to form conglomerates, soft flexible molecules with sterically demanding groups would be favourable.
Thesis (Ph.D.)--Dalhousie University (Canada), 2004.
Keywords
Chemistry, Physical.