Effect of Solvents on Crystal Growth

Another example of the crystallization of chemically related compounds is found in the commercial separation of fructose from the impurity difructose dianhydride (Chu et al. 1989). Fructose undergoes irreversible dehydration during the crystallization process to yield several forms of difructose dianhydride impurities. Since the difructose dianhydride molecule consists of two fructose moieties, it exhibits some of the chemical and structural features of the host fructose molecule. In an analogous fashion to a tailor-made additive, the difructose dianhydride impurities appear to incorporate into the crystal (at 1 wt% level), thus inhibiting the subsequent adsorption and growth of fructose molecules. The resulting fructose crystal growth rates are so low that the crystallization time in fructose manufacture is often on the order of days. 

The impact of solvent on product quality should be given early consideration in process development efforts since it can have a significant effect on crystal size, morphology, and purity. A poor initial choice of solvent may thermodynamically limit the effectiveness of the separation, irrespective of all other factors, including crystallizer design and cost. In Section 3.5.1, the thermodynamic considerations for minimizing impurity incorporation are outlined based on solvent selection. 

---

Lahav, M. and Leiserowitz, L., 2001. The effect of solvent on crystal growth and morphology. Chemical Engineering Science, 56(7), 2245-2254. 

Some of the difficulties encountered in establishing the effect of solvent on crystal growth may be circumvented by focusing on polar crystals. This is because the difference in the rates of growth of opposite faces (hid) and (hkl) along a polar direction must arise primarily from differences in their solvent-surface interactions. Thus, one generally does not have to be concerned with faces other than the hemihedral ones in question. We illustrate below an approach to understanding solvent-surface interactions in the polar crystals of resorcinol (102). 

Growth of Hexamethykne Tetramine (HMT) from Various Solvents. Detailed studies of the effect of solvents on crystal growth have been conducted using the crystalline material HMT (Bourne and Davey 1976 Bourne 1980 Davey 1986). An analysis of HMT solubility data through the use of Eq. (3.33) indicates that HMT forms an approximately ideal solution with ethanol. By contrast, large negative deviations from ideal behavior are observed in water. 

Garti N, Leci CL, and Sarig S. The Effect of Solvents on Crystal Habit of 1,4-Di-Tert-Butylbenzene (DTB ). J Cryst Growth 1981 54 227-231. 

Bhat, M.N., Dharmaprakash, S.M. Effect of solvents on the growth morphology and physical characteristics of nonlinear optical y-glycine crystals, J. Crystal Growth 242 (1-2) (2002) 245-252. 

One of the most important results of theoretical investigations of crystal growth has been the quantification of the effect of solvents on crystal interface structure. In particular, a key parameter, called the a-factor, has been developed from fundamental theories that allows identification of likely growth mechanisms based only on solute and solution properties. 

The surface entropy factor, a, can be considered a relative measure of the degree of smoothness of a crystal face on the atomic level. In Section 3.9.3 it is shown how a correlates the effect of solvents on both growth rate and growth mechanism. 

The effects of a solvent on growth rates have been attributed to two sets of factors (28) one has to do with the effects of solvent on mass transfer of the solute through adjustments in viscosity, density, and diffusivity the second is concerned with the stmcture of the interface between crystal and solvent. The analysis (28) concludes that a solute-solvent system that has a high solubiUty is likely to produce a rough interface and, concomitandy, large crystal growth rates. 

As discussed in section 2.4.4 the coordinating ability of a solvent will often affect the rate of nucleation and crystal growth differently between two polymorphs. This can be used as an effective means of process control and information on solvent effects can often be obtained from polymorph screening experiments. There are no theoretical methods available at the present time which accurately predict the effect of solvents on nucleation rates in the industrial environment. 

A benchmark study on the effect of solvent on growth of polar crystals was carried out by Wells (42) in 1949. He found that in aqueous solution at room temperature the ot-form of resorcinol (space group Pna2t), 12a, grows unidi-rectionally along the polar c axis. The crystal exhibits benzene-rich 011 faces Sit one end of the c axis and O(hydroxyl)-rich OlT faces at the other end... 

Kitamura, M., Furukawa, H. and Asaeda, M. (1994) Solvent effect of ethanol on crystallization and growth of L-histidine polymorphs. Journal of Crystal Growth, 141, 193-199. 

Boochatum and co-workers [41] studied the effect of solvent on the crystallisation growth behaviour of crystals of l,4- r s-polyisoprene. 

An increase in viscosity usually accompanies competition. Water molecules bound by the hydrocolloid are no longer effective as solvent molecules and the concentration of the solution is thereby increased. Increase in viscosity itself has a retarding effect on crystal growth. 

Recent experimental and theoretical studies on crystal growth, especially in the presence of tailor-made inhibitors, provide a link between macroscopic and microscopic chirality. We shall discuss these principles in some detail for chiral molecules. Furthermore, we shall examine whether it is indeed feasible today to establish the absolute configuration of a chiral crystal from an analysis of solvent-surface interactions. Since these analyses are based on understanding the interactions between a growing crystal and inhibitors present in solution, we shall first illustrate the general mechanism of this effect in various chiral and nonchiral systems. 

The use of tailor made additives holds great promise in the area of crystal growth and morphology control. The routine selection and use of these type of additives will require a fundamental understanding of the mechanism which the additives work on a molecular basis. At the same time, the effect of solvent molecules on the crystal growth process is another related and important problem. In both instances, the relationship between internal aystal structure, aystal growth rate, solvent and impurities are needed to predict the habit of a crystal and thus allow seleaion of the proper conditions and components required to obtain a desired habit... 

---