Example crystallization dimethyl sulfoxide

Another illustrative example of a solvent-dependent keto/enol tautomerism of a monocarbonyl compound is given by 4-[(pent-l-ylthio)acetyl]-A-(4 -chlorobenzyl)-pyridinium chloride. In the HBA solvent dimethyl sulfoxide, the enol predominates (84 cmol/mol), while in the HBD solvent water it exists as the ketone (47 cmol/mol) and its hydrate (40 cmol/mol) [250]. Recrystallization of this pyridinium salt from a DMSO/ ethyl acetate mixture yields the pure enoUc form, with one molecule of DMSO per molecule of enol present in the crystal lattice. 

Other crystallization techniques that are less frequently applied in the pharmaceutical industry, such as melt and freeze crystallization, may be applicable for some processes. In Example 11-4, purification of dimethyl sulfoxide (DMSO) is presented. In this case, low-level impurities, primarily dimethyl sulfide, are removed by controlled fractional crystallization from the melt (DMSO is a liquid above 18.45°C), in combination with adsorption of impurities from the unfrozen liquid. In the feed DMSO prior to the crystallization step, the impurities, while unacceptable, are at too low a level to be removable by adsorption alone. 

First examples of second-sphere coordination adduct between a CD and such organometallic complexes were observed with the ferrocene and its derivatives. Thus, Breslow was the first to report in 1975 that ferrocene forms a 1 1 adduct with the /3-CD in both A/T-dimethylformamide and dimethyl sulfoxide. Nevertheless, the first crystalline inclusion complexes of ferrocene and its derivatives were prepared by Harada and Takahashi in 1984. The inclusion complexes were obtained by direct addition of crystals of ferrocene or its derivatives into aqueous solutions of CD. The stoichiometry of the inclusion complexes was found to be dependent on the sizes of the CD. The /3-CD and y-CD formed 1 1 stoichiometric inclusion complexes whereas a-CD formed a 2 1 (CD guest) complex with ferrocene. From induced circular dichroism experiments, three structures were proposed for these adducts as shown in Figure... 

As a mle of thumb, addition of the analyte solution should not noticeably change the crystallization behavior of the neat matrix an unchanged morphology already indicates that the solution excess of the matrix with respect to the analyte is maintained in the crystals, and that the contaminant level is low. Any solute component which already at low concentrations dramatically changes the morphology of the subsequently crystallized matrix or prevents crystallization altogether - for example, low-volatility solvents such as dimethyl sulfoxide or common detergents -will prohibit a successful MALDI analysis. 

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