Molecular and Solid-State Modeling of the Crystal Purity and Morphology of ε-Caprolactam in the Presence of Synthesis Impurities and the Imino-Tautomeric Species Caprolactim

Abstract

A study of impurity incorporation into host crystal surfaces, using molecular modeling techniques, is presented for -caprolactam, illustrating a rapid method for predicting the effects of additives on the purity and shape of particles formed through crystallization. Optimum positions, in terms of calculated lattice energy, were located for the impurity molecules within the host crystal lattice. Differential binding energies and modified attachment energies were calculated using the program HABIT95 (Clydesdale, G.; Roberts, K. J; Docherty, R. Quantum Chemistry Program Exchange 1996, 16, 1) for each impurity molecule for all the important growth forms. From the differential binding energies, values were calculated for the equilibrium segregation coefficients. The impact of the impurities cyclohexane, cyclohexanol, cyclohexanone, and the imino-tautomeric form of -caprolactam (or caprolactim) was considered in the study. Excellent agreement was found between calculated equilibrium segregation coefficients for the impurity cyclohexanone in the {110} and {111 h} forms of -caprolactam and reported experimental values for crystals grown from the melt in the presence of a wide range of cyclohexanone impurity concentrations, 0.1-30 mol %, for supersaturations of the melt, 2 × 10 -3 to 6 × 10 -3 (van den Berg, E. P. G.; Bögels, G.; Arkenbout, G. J. J. Cryst. Growth 1998, 191, 169-177). It was calculated that the incorporation of cyclohexanol into -caprolactam would be most significant for the {110} form and that the extent of partitioning of cyclohexane into the most important growth forms is 10-100 times smaller than those in the cases of cyclohexanol and cyclohexanone. The effect of impurity incorporation on the habit of -caprolactam crystals was calculated from the modified attachment energies.

Nucleation mechanism and kinetics from the analysis of polythermal crystallisation data: methyl stearate from kerosene solutions

“…This is the case for many industrial materials such as fuels, confectionery products, pharmaceuticals and fine chemicals. In this regard, the shape of the particle needs further quantification, in a manner which draws down on the now comparatively routine application of the molecular modelling of dimers [32,33] , clusters [34][35][36][37][38] , surfaces [30,39,40] , point defects and additives [41][42][43][44][45] action on crystallisation. Such molecular scale modelling can be expected to have an impact e.g.…”

“…This is valuable given, its potential application through the use of the Gibb-Thompson expression, to calculate solubility enhancement as a function of reduced crystal size [40] . Such an approach can also be integrated with morphology prediction, with the potential to provide a more rigorous implementation of the model presented here, particularly in terms of defining a methodology for predicting the influence of crystallisation environment on the crystal growth rate [39,[41][42][43][44] .…”

“…40 Such an approach can also be integrated with morphology prediction, with the potential to provide a more rigorous implementation of the model presented here, particularly in terms of defining a methodology for predicting the influence of crystallisation environment on the crystal growth rate. 39,[41][42][43][44] Molecular cluster modelling also provide a useful predictive way for modelling the stability of different polymorphs as a function of their crystal size. Linking this approach to the prediction of cluster size through the study presented in this paper, is potentially valuable in terms of being able to predict the correct crystallisation supersaturation needed to generate the required cluster size and thus, through this, to design the crystallisation processes needed to direct the polymorphic form desired.…”

Molecular modelling of the incorporation of habit modifying additives: α-glycine in the presence of l-alanine

“…This methodology has been applied successfully for example, to study caprolactam in the absence and presence of synthesis impurities. 26 Having selected the S absolute configuration for the additive molecule, the calculations were performed specifically for each of the (020), (011), (110), (0 20), (0 1 1) and ( 1 10) crystal surfaces.…”

An examination of binding motifs associated with inter-particle interactions between facetted nano-crystals of acetylsalicylic acid and ascorbic acid through the application of molecular grid-based search methods

“…Systematic searching has also been applied successfully in the modelling of heterospecies binding both within the 3‐D crystalline bulk‐lattice, associated with impurity segregation, and on 2‐D crystal habit surfaces associated with solvent binding. In the 3‐D case, studies of impurity segregation in aromatic hydrocarbons,19 and ε‐caprolactam,20, 21 have evaluated the preferred orientation and location of impurity molecules within a host crystal lattice. Restricting the search strategy to crystal surfaces, the preferential sites for solvent binding on crystal surfaces of acetylsalicylic acid have been evaluated 22.…”