28 November 2009

Contactor Separator - Grinding Induced Attrition - Prior Art

I'm impressed by the deracemization procedure described in "Grinding Induced Attrition" (sarcastic comments aside) where a racemic mixture was converted from a slurry containing a racemization agent to a slurry where the solid consisted of one of the enantiomers in the original slurry. See the post and links for details.

Rather than using glass beads to to do the grinding, I would use a contactor-separator of the sort I discussed in the post, "Contactor-Separator".
As you can see the image is lifted from the reference in "Contactor-Separator" along with labels appropriate to that usage.

So that it could be used to effect the chiral crystallization described, I would slowly charge it with a racemic slurry containing the racemization agent, and the appropriate homochiral seed. It is anticipated that the inlet would need an Archimedean screw to force the slurry into the contactor whilst the annular mixing gap would also be small enough to cause the necessary attrition. Whether this would be successful would depend upon the friability, or otherwise, of the solid component of the slurry. As the mixture is forced through the apparatus, it is anticipated that the enriched-entrained solid would be formed by crystallisation in the internal centrifuge. Conditions (spin, flow-rate and temperature) would need to be sought where the slurry would still exist as a slurry such that separation could occur. The two streams would then be recombined and passed through the apparatus again: note that it would not be necessary to seed the mixture.

The recombination and recycling would be repeated until the solid consisted entirely of the appropriate enantiomer. At this point the outlet would be directed to a simple settling tank in order to remove the homochiral product; which would, of course, be replaced at the inlet by racemic mixture.

If the removal of enantiomeric product and the addition of racemic starting material were done at the same rate; a rate that was less than the rate of deracemization, the process would operate under continuous flow conditions.

If I had the capital to reduce this concept of invention to practice, I would do so. Unfortunately, I don't. Here it is if anyone wants to use it.
Update 29th November 2009. I realise that the above process doesn't have any Oswald ripening in it; perhaps a better process would use an oscillatory flow reactor as described in Baffled by Chirality.
Update 23rd June 2010. Rather than using a contact separator, this paper, Scaling Up Attrition-Enhanced Deracemization by Use of an Industrial Bead Mill in a Route to Clopidogrel (Plavix), used a bead mill; the paper is behind a pay wall so it isn't clear whether or not the process is batch or continuous flow.

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