In CA2677670, a monoglyceride ester is separated from other impurities by absorbing the mixture on silica gel and washing with hexanes/ethyl acetate 90:10 v/v. This was not a column chromatography as can be determined from the experimental details. The 90:10 mixture of hexanes/ethyl acetate (10 ml) was used to dissolve the approx. 16 g of ester and to this solution 40 g of silica gel was added. The slurry was put on a fritted funnel and eluted with 150 ml of the mixed solvents to remove the impurities. A second elution with 300 ml of ethyl acetate removed the monoglyceride which was concentrated in vacuo. This seems to show that diols seem to bind tenaciously to polar solid adsorbants.
It is well known that mono alcohols often form insoluble complexes with CaCl2, LiCl, LiBr, CaBr2 and MnCl2 for example. So it not surprising that diols would form strong complexes with such inorganic salts. As evidence of this there is a patent, US 3,846,450 titled Purification of Oxygenated Compounds that describes the removal of diols by passing a liquid comprising some of these through solid alkali earth halides. This would trivialize their separation from compounds without this substructure.
It has been reported that complex steroidal and prostaglandin structures can be purified by precipitating as LiBr complexes [GB2094795]. The prostaglandin structures typically contain more than one alcohol functionality. This should increase the likelihood that metal halide complexes with 1,2-diols are more likely to produce solid precipitates. Kilomentor has already published a note about using such metal complexes to separate alcohols from non-alcohols and some alcohol mixtures from each other.
I have not found work showing that substances containing two or more non-adjacent alcohol groups dependably form lithium bromide or calcium bromide precipitates even though the work with lithium bromide and prostaglandin intermediates is promising in this respect. What is clear is that neutral 1,2-diols can be separated from other functionalities ruggedly and dependably.The 1,2-diol functionality most probably can be covalently attached to a very wide variety of intermediates as a ‘phase-separating tag’.
Substrates containing the tag would, perchance, be precipitated by stirring with an inorganic salt in non-polar solvent. It might turn out that the 1,2-diol at the end of a hydrocarbon chain might be a substructure that could control precipitation in a wide variety of intermediates using a standard set of conditions ( a particular salt, precipitating solvent, ethanol catalyst and reaction conditions). It is already known for example that a primary alcohol is preferred to a secondary or tertiary one.
After the terminal 1,2-diol had served its purpose for intermediate isolation/ purification it could be selectively cleaved to an aldehyde or cleaved and reduced to a primary alcohol with one fewer carbons than the diol. The functional group would be expected to work as a phase-separating tag best when the other functional groups in the intermediate were not polar ones that could also interact strongly with the inorganic salt.
It seems that whether a solid complex is formed may depend upon both the crystal lattice energy of the complex and the energy of the crystal lattice of the salt itself. As Sharpless notes, [K.B. Sharpless, A.O. Chong, and J.A. Scott, Rapid Separation of Organic Mixtures by Formation of Metal Complexes, J. Org. Chem., 40, 1252 (1975)}, whether they form solid complexes or not the alcohols do cause the dissolution of the calcium chloride into the hexane. Another important observation provided by Sharpless et al. was that mixtures of alcohols often dissolved but did not even partially precipitate under the complex forming conditions even when the pure components of the mixture formed solid calcium chloride complexes when treated individually but separately.
Why some alcohols form solid complexes and others just dissolve the inorganic salt ,but do not precipitate, has been hanging unsolved for a long time. The Sharpless strategy has never become popular. This is because, according to a personal communication from Sharpless himself, the best conditions for forming and precipitating the complexes were unfortunately not those recommended in his article. Not a 2:1 molar alcohol inorganic salt ratio, but a large excess of inorganic salt works best taking into account more cases. Perhaps the alcohols and inorganic salt form oil-in-water or water in-oil emulsions which only occasionally break down to precipitated solid.
If the problem is emulsion formation it might be important to remove completely any residual water. Using aprotic solvents that have fewer degrees of freedom themselves might help. Cyclohexane and diisopropyl ether might be tried. Diisopropyl ether seems to be the solvent of choice when it is difficult to get regular crystallization. Patent GB1555968 suggests that methyl isobutyl ketone (MIBK)or methyl n-amylketone are preferred candidates to form insoluble complexes, at least when calcium bromide is used.
Clearly solvents must be used that do not themselves dissolve these divalent inorganic salts because such solvents present in so large an excess would easily out compete substrates. Hexanes, methylene chloride, MIBK and methyl n-amyl ketones would meet the criterion of not dissolving much salt alone.
Besides the equilibrium effect sometimes giving rise to useful precipitation there is probably also a kinetic effect upon whether the precipitation/crystallization provides purification. The limited data could be interpreted as suggesting that small alcohols exchange more rapidly than large alcohols and small alcohols, present catalytically, promote exchanges.
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